Meta-analysis: Risk of dry mouth with second generation antidepressants.

Science.gov (United States)

Cappetta, Kiley; Beyer, Chad; Johnson, Jessica A; Bloch, Michael H

2018-06-08

The goal of this meta-analysis was to quantify the risk of dry mouth associated with commonly prescribed antidepressant agents and examine the potential implications of medication class, dose, and pharmacodynamics and dose on risk of treatment-induced dry mouth. A PubMed search was conducted to identify double-blind, randomized, placebo-controlled trials examining the efficacy and tolerability of second generation antidepressant medications for adults with depressive disorders, anxiety disorders, and OCD. A random-effects meta-analysis was used to quantify the pooled risk ratio of treatment-emergent dry mouth with second generation antidepressants compared to placebo. Stratified subgroup analysis and meta-regression was utilized to further examine the effects antidepressant agent, class, dosage, indication, and receptor affinity profile on the measured risk of dry mouth. 99 trials involving 20,868 adults. SNRIs (Relative Risk (RR)=2.24, 95% Confidence Interval (CI): 1.95-2.58, z=11.2, pz=5.8, pz=10.32, pz=5.85, pz=3.26, p=0.001) and Alpha-2 (PE=0.49, 95% CI: 0.22-0.75, z=3.64, pz=2.10, p<0.05) was significantly associated with increased risk of dry mouth. The current meta-analysis suggests that SSRIs, SNRIs, and atypical antidepressants are all associated with varying degrees of increased risk of dry mouth. SNRIs were associated with a significantly greater risk of dry mouth compared to SSRIs. Copyright © 2017 Elsevier Inc. All rights reserved.

New anti-trypanosomal active tetracyclic iridoid isolated from Morinda lucida Benth.

Science.gov (United States)

Suzuki, Mitsuko; Tung, Nguyen Huu; Kwofie, Kofi D; Adegle, Richard; Amoa-Bosompem, Michael; Sakyiamah, Maxwell; Ayertey, Frederick; Owusu, Kofi Baffour-Awuah; Tuffour, Isaac; Atchoglo, Philip; Frempong, Kwadwo Kyereme; Anyan, William K; Uto, Takuhiro; Morinaga, Osamu; Yamashita, Taizo; Aboagye, Frederic; Appiah, Alfred Ampomah; Appiah-Opong, Regina; Nyarko, Alexander K; Yamaoka, Shoji; Yamaguchi, Yasuchika; Edoh, Dominic; Koram, Kwadwo; Ohta, Nobuo; Boakye, Daniel A; Ayi, Irene; Shoyama, Yukihiro

2015-08-01

Human African trypanosomiasis (HAT), commonly known as sleeping sickness has remained a serious health problem in many African countries with thousands of new infected cases annually. Chemotherapy, which is the main form of control against HAT has been characterized lately by the viewpoints of toxicity and drug resistance issues. Recently, there have been a lot of emphases on the use of medicinal plants world-wide. Morinda lucida Benth. is one of the most popular medicinal plants widely distributed in Africa and several groups have reported on its anti-protozoa activities. In this study, we have isolated one novel tetracyclic iridoid, named as molucidin, from the CHCl3 fraction of the M. lucida leaves by bioassay-guided fractionation and purification. Molucidin was structurally elucidated by (1)H and (13)C NMR including HMQC, HMBC, H-H COSY and NOESY resulting in tetracyclic iridoid skeleton, and its absolute configuration was determined. We have further demonstrated that molucidin presented a strong anti-trypanosomal activity, indicating an IC50 value of 1.27 μM. The cytotoxicity study using human normal and cancer cell lines indicated that molucidin exhibited selectivity index (SI) against two normal fibroblasts greater than 4.73. Furthermore, structure-activity relationship (SAR) study was undertaken with molucidin and oregonin, which is identical to anti-trypanosomal active components of Alnus japonica. Overlapping analysis of the lowest energy conformation of molucidin with oregonin suggested a certain similarities of aromatic rings of both oregonin and molucidin. These results contribute to the future drug design studies for HAT. Copyright © 2015 Elsevier Ltd. All rights reserved.

3-aminopyridazine derivatives with atypical antidepressant, serotonergic, and dopaminergic activities.

Science.gov (United States)

Wermuth, C G; Schlewer, G; Bourguignon, J J; Maghioros, G; Bouchet, M J; Moire, C; Kan, J P; Worms, P; Biziere, K

1989-03-01

Minaprine [3-[(beta-morpholinoethyl)amino]-4-methyl-6-phenylpyridazine dihydrochloride] is active in most animal models of depression and exhibits in vivo a dual dopaminomimetic and serotoninomimetic activity profile. In an attempt to dissociate these two effects and to characterize the responsible structural requirements, a series of 47 diversely substituted analogues of minaprine were synthesized and tested for their potential antidepressant, serotonergic, and dopaminergic activities. The structure-activity relationships show that dopaminergic and serotonergic activities can be dissociated. Serotonergic activity appears to be correlated mainly with the substituent in the 4-position of the pyridazine ring whereas the dopaminergic activity appears to be dependent on the presence, or in the formation, of a para-hydroxylated aryl ring in the 6-position of the pyridazine ring.

Switching antidepressants

African Journals Online (AJOL)

Antidepressants are widely prescribed for depression in primary care,1 but a lack ... all antidepressants are capable of causing discontinuation .... antidepressant, or maintaining an antidepressant, in elderly, medically compromised (e.g. renal.

Atypicality of Atypical Antipsychotics

OpenAIRE

Farah, Andrew

2005-01-01

Objective: To review the current definition of atypicality, discuss the unique features of each atypical antipsychotic, and determine whether the available drugs in this class really meet the classical definition of atypicality.

Evaluation of antidepressant like property of amisulpride per se and its comparison with fluoxetine and olanzapine using forced swimming test in albino mice.

Science.gov (United States)

Pawar, Ganesh R; Agrawal, Rajendra P; Phadnis, Pradeep; Paliwal, Abhay; Vyas, Savita; Solanki, Pooja

2009-01-01

Amisulpride, an atypical antipsychotic was evaluated for antidepressant like activity in forced swimming test in Swiss albino mice. The effect of amisulpride was compared with that of fluoxetine, the standard antidepressant and olanzapine, another atypical antipsychotic claimed to have antidepressant like activity. Both acute and chronic studies were carried out. In both the studies, animals were divided into four groups (n = 8 each) and subjected to oral drug interventions as follows -- Group 1- control (distilled water, 1 mL/kg); Group 2- fluoxetine in a dose of 10 mg/kg 23.5, 5 and 1 h before the test; Group 3-amisulpride in a dose of 70 mg/kg 23.5, 5 and 1 h before the test; Group 4- olanzapine in a dose of 2 mg/kg 23.5, 5 and 1 h before the study. In the chronic study, the treatment was given daily for 28 days with last dose being given 2 h prior to the test. A time sampling method was used to score the behavioral activity in each group. Results of both the studies indicated that animals given amisulpride displayed significant improvement in swimming behavior (p Fluoxetine also showed significant difference in activity as compared to amisulpride and olanzapine (p swimming phases in albino mice (p > 0.05). We conclude that amisulpride per se has an antidepressant like activity comparable to that of olanzapine though the activity was significantly less than that of fluoxetine.

Antidepressants and dementia

DEFF Research Database (Denmark)

Kessing, Lars Vedel; Søndergård, Lars; Forman, Julie Lyng

2009-01-01

BACKGROUND: It has been suggested that antidepressants may have neuroprotective abilities but it has newer been investigated lately whether treatment with antidepressants reduces the risk of dementia. METHOD: Linkage of registers of all prescribed antidepressants and diagnoses of dementia...... in Denmark during a period from 1995 to 2005. RESULTS: Persons who purchased antidepressants once (N=687,552) had an increased rate of dementia compared to persons unexposed to antidepressants (N=779,831). Nevertheless, the rate of dementia changed over time; thus during the initial prescription periods...... the rate increased with the number of prescriptions but continued long-term antidepressants treatment was associated with a reduction in the rate of dementia, however, not to the same level as the rate for the general population. This pattern was found for all classes of antidepressants (SSRIs, newer non...

Antidepressant-Resistant Depression and Antidepressant-Associated Suicidal Behaviour: The Role of Underlying Bipolarity

Directory of Open Access Journals (Sweden)

Zoltan Rihmer

2011-01-01

Full Text Available The complex relationship between the use of antidepressants and suicidal behaviour is one of the hottest topics of our contemporary psychiatry. Based on the literature, this paper summarizes the author's view on antidepressant-resistant depression and antidepressant-associated suicidal behaviour. Antidepressant-resistance, antidepressant-induced worsening of depression, antidepressant-associated (hypomanic switches, mixed depressive episode, and antidepressant-associated suicidality among depressed patients are relatively most frequent in bipolar/bipolar spectrum depression and in children and adolescents. As early age at onset of major depressive episode and mixed depression are powerful clinical markers of bipolarity and the manic component of bipolar disorder (and possible its biological background shows a declining tendency with age antidepressant-resistance/worsening, antidepressant-induced (hypomanic switches and “suicide-inducing” potential of antidepressants seem to be related to the underlying bipolarity.

Antidepressant effects of ketamine: mechanisms underlying fast-acting novel antidepressants

Directory of Open Access Journals (Sweden)

Caroline Ann Browne

2013-12-01

Full Text Available Newer antidepressants are needed for the many individuals with major depressive disorder that do not respond adequately to treatment and because of a delay of weeks before the emergence of therapeutic effects. Recent evidence from clinical trials shows that the NMDA antagonist ketamine is a revolutionary novel antidepressant because it acts rapidly and is effective for treatment-resistant patients. A single infusion of ketamine alleviates depressive symptoms in treatment-resistant depressed patients within hours and these effects may be sustained for up to 2 weeks. Although the discovery of ketamine’s effects has reshaped drug discovery for antidepressants, the psychotomimetic properties of this compound limit the use of this therapy to the most severely ill patients. In order to develop additional antidepressants like ketamine, adequate preclinical behavioral screening paradigms for fast-acting antidepressants need to be established and used to identify the underlying neural mechanisms. This review examines the preclinical literature attempting to model the antidepressant-like effects of ketamine. Acute administration of ketamine has produced effects in behavioral screens for antidepressants like the forced swim test, novelty suppression of feeding and in rodent models for depression. Protracted behavioral effects of ketamine have been reported to appear after a single treatment that last for days. This temporal pattern is similar to its clinical effects and may serve as a new animal paradigm for rapid antidepressant effects in humans. In addition, protracted changes in molecules mediating synaptic plasticity have been implicated in mediating the antidepressant-like behavioral effects of ketamine. Current preclinical studies are examining compounds with more specific pharmacological effects at glutamate receptors and synapses in order to develop additional rapidly acting antidepressants without the hallucinogenic side effects or abuse

Diverse antidepressants increase CDP-diacylglycerol production and phosphatidylinositide resynthesis in depression-relevant regions of the rat brain

Directory of Open Access Journals (Sweden)

Undieh Ashiwel S

2008-01-01

Full Text Available Abstract Background Major depression is a serious mood disorder affecting millions of adults and children worldwide. While the etiopathology of depression remains obscure, antidepressant medications increase synaptic levels of monoamine neurotransmitters in brain regions associated with the disease. Monoamine transmitters activate multiple signaling cascades some of which have been investigated as potential mediators of depression or antidepressant drug action. However, the diacylglycerol arm of phosphoinositide signaling cascades has not been systematically investigated, even though downstream targets of this cascade have been implicated in depression. With the ultimate goal of uncovering the primary postsynaptic actions that may initiate cellular antidepressive signaling, we have examined the antidepressant-induced production of CDP-diacylglycerol which is both a product of diacylglycerol phosphorylation and a precursor for the synthesis of physiologically critical glycerophospholipids such as the phosphatidylinositides. For this, drug effects on [3H]cytidine-labeled CDP-diacylglycerol and [3H]inositol-labeled phosphatidylinositides were measured in response to the tricyclics desipramine and imipramine, the selective serotonin reuptake inhibitors fluoxetine and paroxetine, the atypical antidepressants maprotiline and nomifensine, and several monoamine oxidase inhibitors. Results Multiple compounds from each antidepressant category significantly stimulated [3H]CDP-diacylglycerol accumulation in cerebrocortical, hippocampal, and striatal tissues, and also enhanced the resynthesis of inositol phospholipids. Conversely, various antipsychotics, anxiolytics, and non-antidepressant psychotropic agents failed to significantly induce CDP-diacylglycerol or phosphoinositide synthesis. Drug-induced CDP-diacylglycerol accumulation was independent of lithium and only partially dependent on phosphoinositide hydrolysis, thus indicating that antidepressants

The effect of combined treatment with risperidone and antidepressants on the MK-801-induced deficits in the social interaction test in rats.

Science.gov (United States)

Kamińska, Katarzyna; Rogóż, Zofia

2015-12-01

Several clinical reports have suggested that augmentation of atypical antipsychotics' activity by antidepressants may efficiently improve the treatment of negative and some cognitive symptoms of schizophrenia. The aim of the present study was to investigate the effect of antidepressant mirtazapine or escitalopram and risperidone (an atypical antipsychotic), given separately or jointly, on the MK-801-induced deficits in the social interaction test in rats. Antidepressants and risperidone were given 60 and 30 min before the test, respectively. The social interaction of male Wistar rats was measured for 10 min, starting 4 h after MK-801 (0.1 mg/kg) administration. In the social interaction test, MK-801-induced deficits in the parameters studied, i.e. the number of episodes and the time of interactions. Risperidone at a higher dose (0.1 mg/kg) reversed that effect. Co-treatment with an ineffective dose of risperidone (0.01 mg/kg) and mirtazapine (2.5 or 5 mg/kg) or escitalopram only at a dose of 5 mg/kg (but not 2.5 and 10 mg/kg) abolished the deficits evoked by MK-801. The obtained results suggest that especially mirtazapine, and to a smaller degree escitalopram may enhance the antipsychotic-like effect of risperidone in the animal test modeling some negative symptoms of schizophrenia. Copyright © 2015 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

Antidepressants, antimicrobials or both? Gut microbiota dysbiosis in depression and possible implications of the antimicrobial effects of antidepressant drugs for antidepressant effectiveness.

Science.gov (United States)

Macedo, Danielle; Filho, Adriano José Maia Chaves; Soares de Sousa, Caren Nádia; Quevedo, João; Barichello, Tatiana; Júnior, Hélio Vitoriano Nobre; Freitas de Lucena, David

2017-01-15

The first drug repurposed for the treatment of depression was the tuberculostatic iproniazid. At present, drugs belonging to new classes of antidepressants still have antimicrobial effects. Dysbiosis of gut microbiota was implicated in the development or exacerbation of mental disorders, such as major depressive disorder (MDD). Based on the current interest in the gut-brain axis, the focus of this narrative review is to compile the available studies regarding the influences of gut microbiota in behavior and depression and to show the antimicrobial effect of antidepressant drugs. A discussion regarding the possible contribution of the antimicrobial effect of antidepressant drugs to its effectiveness/resistance is included. The search included relevant articles from PubMed, SciELO, LILACS, PsycINFO, and ISI Web of Knowledge. MDD is associated with changes in gut permeability and microbiota composition. In this respect, antidepressant drugs present antimicrobial effects that could also be related to the effectiveness of these drugs for MDD treatment. Conversely, some antimicrobials present antidepressant effects. Both antidepressants and antimicrobials present neuroprotective/antidepressant and antimicrobial effects. Further studies are needed to evaluate the participation of antimicrobial mechanisms of antidepressants in MDD treatment as well as to determine the contribution of this effect to antidepressant resistance. Copyright © 2016 Elsevier B.V. All rights reserved.

The antidepressant- and anxiolytic-like effects following co-treatment with escitalopram and risperidone in rats.

Science.gov (United States)

Kaminska, K; Rogoz, Z

2016-06-01

Several clinical reports have documented a beneficial effect of the addition of a low dose of risperidone to the ongoing treatment with antidepressants, in particular selective serotonin reuptake inhibitors (SSRI), in the treatment of drug-resistant depression and treatment-resistant anxiety disorders. In the present study, we investigated the effect of treatment with the antidepressant escitalopram (SSRI) given separately or jointly with a low dose of risperidone (an atypical antipsychotic) in the forced swim test and in the elevated plus-maze test in rats. The obtained results showed that escitalopram at doses of 2.5 or 5 mg/kg evoked antidepressant-like effect in the forced swim test. Moreover, risperidone at low doses (0.05 or 0.1 mg/kg) enhanced the antidepressant-like activity of escitalopram (1 mg/kg) in this test by increasing the swimming time and decreasing the immobility time in those animals. WAY 100635 (a serotonin 5-HT1A receptor antagonist) at a dose of 0.1 mg/kg abolished the antidepressant-like effect induced by co-administration of escitalopram and risperidone. The active behavior in that test did not reflect an increase in general activity, since the combined treatment with escitalopram and risperidone failed to enhance the exploratory activity of rats. In the following experiment, we showed that escitalopram (5 mg/kg) and mirtazapine (5 or 10 mg/kg) or risperidone (0.1 mg/kg) induced an anxiolytic-like effect in the elevated plus-maze test, and the combined treatment with an ineffective dose of risperidone (0.05 mg/kg) enhanced the anxiolytic-like effects of escitalopram (2.5 mg/kg) or mirtazapine (1 and 2.5 mg/kg) in this test. The obtained results suggest that risperidone applied at a low dose enhances the antidepressant-like activity of escitalopram in the forced swim test, and that 5-HT1A receptors may play some role in these effects. Moreover, a low dose of risperidone may also enhance the anxiolytic-like action of the studied

Seizures during antidepressant treatment in psychiatric inpatients--results from the transnational pharmacovigilance project "Arzneimittelsicherheit in der Psychiatrie" (AMSP) 1993-2008.

Science.gov (United States)

Köster, M; Grohmann, R; Engel, R R; Nitsche, M A; Rüther, E; Degner, D

2013-11-01

There is little clinical data available about seizure rates in psychiatric inpatients, and there are no studies with reference data to the frequencies of antidepressant (AD) use for this important clinical population. This study investigates seizure rates during AD treatment in psychiatric inpatient settings, drawn from the transnational pharmacovigilance programme Arzneimittelsicherheit in der Psychiatrie (AMSP) in relation to the known frequencies of ADs used in the participating clinics. Comparisons are made to former publications and their limitations. Seventy-seven cases were identified with grand mal seizures (GMS) during AD treatment between 1993 and 2008, with a total number of 142,090 inpatients under surveillance treated with ADs in the participating hospitals. The calculated overall rate of reported seizures of patients during AD treatment in this collective is 0.05 % for ADs imputed alone or in combination with other psychotropic drug groups and 0.02 % when only ADs were given and held responsible for GMS. The patients receiving tri- or tetracyclic ADs (TCAs) had a 2-fold risk to develop a seizure as compared to the overall average rate in this sample. In 11 cases, there was only one AD imputed--the majority of these cases (9/11) were TCA. Monotherapy with selective serotonin reuptake inhibitors (SSRI) or dual serotonin and noradrenaline reuptake inhibitors (SNRI) were never imputed alone in this sample. The results of the study favour the assumption that SSRIs, noradrenergic and specific serotonergic antidepressants (NaSSA) and dual SNRI might be more appropriate than TCAs for the treatment of psychiatric patients with an enhanced seizure risk.

Antidepressants and Valvular Heart Disease

Science.gov (United States)

Lin, Chia-Hui; Hsiao, Fei-Yuan; Liu, Yen-Bin; Gau, Susan Shur-Fen; Wang, Chi-Chuan; Shen, Li-Jiuan

2016-01-01

Abstract Empirical evidence regarding the association between antidepressants and valvular heart disease (VHD) is scarce. Using Taiwan's National Health Insurance Research database, this nested case-control study assessed the association between antidepressants and VHD in a Chinese population. Among a cohort of patients who used at least 3 prescription antidepressants, 874 cases with VHD and 3496 matched controls (1:4 ratio) were identified. Conditional logistic regression models were used to examine the timing, duration, dose and type of antidepressants use, and the risk of VHD. Current use of antidepressants was associated with a 1.4-fold increase in the risk of VHD (adjusted odds ratio [aOR] 1.44; 95% confidence interval [CI] 1.17–1.77). Among current users, a dose–response association was observed in terms of the cumulative duration and the cumulative antidepressant dose. Significantly higher risks of VHD were observed among the current users of tricyclic antidepressants (aOR 1.40 [1.05–1.87]). We found that the use of antidepressants was associated with a greater risk of VHD and that the risks varied according to different antidepressants. PMID:27057841

Preferential reduction of binding of 125I-iodopindolol to beta-1 adrenoceptors in the amygdala of rat after antidepressant treatments

International Nuclear Information System (INIS)

Ordway, G.A.; Gambarana, C.; Tejani-Butt, S.M.; Areso, P.; Hauptmann, M.; Frazer, A.

1991-01-01

This study utilized quantitative receptor autoradiography to examine the effects of repeated administration of antidepressants to rats on the binding of the beta adrenoceptor antagonist, 125 I-iodopindolol ( 125 I-IPIN) to either beta-1 or beta-2 adrenoceptors in various regions of brain. Antidepressants were selected to represent various chemical and pharmacological classes including tricyclic compounds (desipramine and protriptyline), monoamine oxidase inhibitors (clorgyline, phenelzine and tranylcypromine), atypical antidepressants (mianserin and trazodone) and selective inhibitors of the uptake of serotonin (citalopram and sertraline). Additionally, rats were treated with various psychotropic drugs that lack antidepressant efficacy (cocaine, deprenyl, diazepam and haloperidol). Repeated treatment of rats with desipramine, protriptyline, clorgyline, phenelzine, tranylcypromine or mianserin reduced the binding of 125 I-IPIN to beta-1 adrenoceptors in many brain areas. Only in the basolateral and lateral nuclei of the amygdala did all six of these antidepressants significantly reduce 125 I-IPIN binding to beta-1 adrenoceptors. In these amygdaloid nuclei, the magnitude of the reduction in the binding of 125 I-IPIN caused by each of these drugs was comparable to or greater than the reduction in binding produced in any other region of brain. Reductions of binding of 125 I-IPIN after antidepressant treatments were not consistently observed in the cortex, the area of brain examined most often in homogenate binding studies. Only the monoamine oxidase inhibitors caused reductions in the binding of 125 I-IPIN to beta-2 adrenoceptors, and this effect was generally localized to the amygdala and hypothalamus

Agmatine enhances antidepressant potency of MK-801 and conventional antidepressants in mice.

Science.gov (United States)

Neis, Vivian Binder; Moretti, Morgana; Manosso, Luana Meller; Lopes, Mark W; Leal, Rodrigo Bainy; Rodrigues, Ana Lúcia S

2015-03-01

Agmatine, an endogenous guanidine amine, has been shown to produce antidepressant-like effects in animal studies. This study investigated the effects of the combined administration of agmatine with either conventional monoaminergic antidepressants or the N-methyl-D-aspartate (NMDA) receptor antagonist MK-801 in the tail suspension test (TST) in mice. The aim was to evaluate the extent of the antidepressant synergism by examining the ability of a fixed dose of agmatine to shift the antidepressant potency of fluoxetine, imipramine, bupropion and MK-801. A sub-effective dose of agmatine (0.0001 mg/kg, p.o.) significantly increased the potency by which fluoxetine, imipramine, bupropion and MK-801 decreased immobility time in the TST by 2-fold (fluoxetine), 10-fold (imipramine and bupropion) and 100-fold (MK-801). Combined with previous evidence indicating a role of monoaminergic systems in the effect of agmatine, the current data suggest that agmatine may modulate monoaminergic neurotransmission and augment the activity of conventional antidepressants. Moreover, this study found that agmatine substantially augmented the antidepressant-like effect of MK-801, reinforcing the notion that this compound modulates NMDA receptor activation. These preclinical data may stimulate future clinical studies testing the effects of augmentation therapy with agmatine for the management of depressive disorders. Copyright © 2014 Elsevier Inc. All rights reserved.

Metabolic mapping of the effects of the antidepressant fluoxetine on the brains of congenitally helpless rats.

Science.gov (United States)

Shumake, Jason; Colorado, Rene A; Barrett, Douglas W; Gonzalez-Lima, F

2010-07-09

Antidepressants require adaptive brain changes before efficacy is achieved, and they may impact the affectively disordered brain differently than the normal brain. We previously demonstrated metabolic disturbances in limbic and cortical regions of the congenitally helpless rat, a model of susceptibility to affective disorder, and we wished to test whether administration of fluoxetine would normalize these metabolic differences. Fluoxetine was chosen because it has become a first-line drug for the treatment of affective disorders. We hypothesized that fluoxetine antidepressant effects may be mediated by decreasing metabolism in the habenula and increasing metabolism in the ventral tegmental area. We measured the effects of fluoxetine on forced swim behavior and regional brain cytochrome oxidase activity in congenitally helpless rats treated for 2 weeks with fluoxetine (5mg/kg, i.p., daily). Fluoxetine reduced immobility in the forced swim test as anticipated, but congenitally helpless rats responded in an atypical manner, i.e., increasing climbing without affecting swimming. As hypothesized, fluoxetine reduced metabolism in the habenula and increased metabolism in the ventral tegmental area. In addition, fluoxetine reduced the metabolism of the hippocampal dentate gyrus and dorsomedial prefrontal cortex. This study provided the first detailed mapping of the regional brain effects of an antidepressant drug in congenitally helpless rats. All of the effects were consistent with previous studies that have metabolically mapped the effects of serotonergic antidepressants in the normal rat brain, and were in the predicted direction of metabolic normalization of the congenitally helpless rat for all affected brain regions except the prefrontal cortex. Copyright (c) 2010 Elsevier B.V. All rights reserved.

Structure-based hybridization, synthesis and biological evaluation of novel tetracyclic heterocyclic azathioxanthone analogues as potential antitumor agents.

Science.gov (United States)

Chen, Tsung-Chih; Wu, Chia-Lun; Lee, Chia-Chung; Chen, Chun-Liang; Yu, Dah-Shyong; Huang, Hsu-Shan

2015-10-20

A series of tetracyclic heterocyclic azathioxanthones were synthesized and evaluated for cell proliferations, topoisomerase inhibitions, and NCI-60 cell panel assay, respectively. Compounds 5, 7, 8, 16, and 19 were selected for topoisomerase assay after MTT assay. 7 not only showed cytotoxic effect (IC50 = 2.84 ± 0.64 μM) in PC-3 cells but also revealed topoisomerases inhibition with IC50 (10-25 μM) and increased apoptotic cleavage of PARP and caspase 3 activity. The overall of novel azathioxanthones with different cytostatic and cytotoxic activities should be further developed as new potential candidates for anticancer drugs. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Lurasidone-β-cyclodextrin complexes: Physicochemical characterization and comparison of their antidepressant, antipsychotic activities against that of self microemulsifying formulation

Science.gov (United States)

Londhe, Vaishali Y.; Deshmane, Aishwarya B.; Singh, Sarita R.; Kulkarni, Yogesh A.

2018-04-01

Lurasidone hydrochloride (LHD) is an atypical antipsychotic drug has poor aqueous solubility and low bioavailability (9-19%). This study describes effect of different methods of complex formation with β-cyclodextrin (BCD) on enhancement of dissolution and on antidepressant, antipsychotic effects of LHD. Other purpose of this study is to compare pharmacodynamic effects of complexes with that of self microemulsifying drug delivery system of LHD (SMEDDS). Inclusion complexes (IC) of LHD and BCD were prepared by physical mixing (PM), kneading (KN) and spray drying (SD) in a 1:1 M ratio. These complexes were characterized by different techniques. KN and SD showing enhancement in dissolution, were compared with SMEDDS using Forced swim test (FST) and Tail suspension test (TST) for antidepressant action and Paw test for antipsychotic activity. Characterization of complexes confirmed interaction between LHD and BCD. Enhancement in dissolution is seen in following order SD > KN > PM > LHD. In all three animal models, SD, KN and SMEDDS showed statistically significant effect (p LHD.

Enhancement of the anti-immobility action of antidepressants by risperidone in the forced swimming test in mice.

Science.gov (United States)

Rogóż, Zofia; Kabziński, Marcin

2011-01-01

The aim of the present study was to examine the effect of antidepressants (ADs) belonging to different pharmacological groups and risperidone (an atypical antipsychotic drug), given separately or jointly, on immobility time in the forced swimming test in male C57BL/6J mice. The antidepressants: citalopram, fluvoxamine, sertraline, reboxetine, milnacipran (5 and 10 mg/kg), or risperidone in low doses (0.05 and 0.1 mg/kg) given alone did not change the immobility time of mice in the forced swimming test. Co-treatment with reboxetine or milnacipran (10 mg/kg) and risperidone in a lower dose of 0.05 mg/kg or with sertraline, reboxetine (5 and 10 mg/kg), citalopram, fluvoxamine, milnacipran (10 mg/kg) and risperidone in a higher dose of 0.1 mg/kg produced antidepressant-like effect in the forced swimming test. WAY100635 (a 5-HT(1A) receptor antagonist) inhibited the effects induced by co-administration of ADs and risperidone. Active behavior in the forced swimming test was not a consequence of an increased general activity, since the combined treatment with ADs and risperidone failed to enhance the locomotor activity of mice. The obtained results indicate that a low dose of risperidone enhances the activity of ADs in an animal model of depression, and that, among other mechanisms, 5-HT(1A) receptors may play a role in these effects.

[Apropos of atypical melancholia with Sustiva (efavirenz)].

Science.gov (United States)

Lang, J P; Halleguen, O; Picard, A; Lang, J M; Danion, J M

2001-01-01

The treatment of HIV infection has changed dramatically in recent years as a result of the development of new drugs which allows a variety of multitherapy combinations more adapted to patients' needs and thereby improving compliance. Efavirenz is a non-nucleoside reverse transcriptase inhibitor. In addition to a potent antiretroviral activity, efavirenz is an easy-to-take drug with once-daily dosing and is usually well tolerated. Efavirenz, however, may induce psychic alterations which are variable and atypical in both their clinical presentation and severity. As early as the first days of treatment, efavirenz may provoke surprising phenomena such as nightmares, vivid dreams, hallucinations or illusions, and twilight states. Depersonalization and derealization episodes, personality alterations, stream of thought troubles and unusual thought contents, atypical depression and cognitive disorders have also been observed. These phenomena may occur either early or later on treatment. The prevalence of severe psychic disorders is less than 5%, but they are often responsible for harmful treatment discontinuations. Psychiatric side effects are heterogeneous and probably not related to pre-existing psychologic weakness. We do not have enough data to evaluate these side effects and their etiopathogeny. The drug could act directly on the central nervous system since it crosses the blood-brain barrier, on the serotoninergic and dopaminergic systems. Some authors have compared efavirenz-induced psychic effects to those associated with LSD and found structural similarities between the two molecules. However, the heterogeneity and low prevalence of the psychiatric side effects of efavirenz suggest and individual sensitivity. In order to improve patient care, a better clinical approach, neuropsychological evaluation, and functional brain imagery should be used to progress in the analysis and comprehension of these disorders. We discuss in this paper the case of Mister H. This HIV

Potentiation of omega-3 fatty acid antidepressant-like effects with low non-antidepressant doses of fluoxetine and mirtazapine.

Science.gov (United States)

Laino, Carlos Horacio; Fonseca, Cristina; Sterin-Speziale, Norma; Slobodianik, Nora; Reinés, Analía

2010-12-01

Despite the advances in psychopharmacology, the treatment of depressive disorders is still not satisfactory. Side effects and resistance to antidepressant drugs are the greatest complications during treatment. Based on recent evidence, omega-3 fatty acids may influence vulnerability and outcome in depressive disorders. The aim of this study was to further characterize the omega-3 antidepressant-like effect in rats in terms of its behavioral features in the depression model forced swimming test either alone or in combination with antidepressants fluoxetine or mirtazapine. Ultimately, we prompted to determine the lowest dose at which omega-3 fatty acids and antidepressant drugs may still represent a pharmacological advantage when employed in combined treatments. Chronic diet supplementation with omega-3 fatty acids produced concentration-dependent antidepressant-like effects in the forced swimming test displaying a behavioral profile similar to fluoxetine but different from mirtazapine. Fluoxetine or mirtazapine at antidepressant doses (10 and 20 mg/kg/day, respectively) rendered additive effects in combination with omega-3 fatty acid supplementation (720 mg/kg/day). Beneficial effects of combined treatment were also observed at sub-effective doses (1 mg/kg/day) of fluoxetine or mirtazapine, since in combination with omega-3 fatty acids (720 mg/kg/day), antidepressants potentiated omega-3 antidepressant-like effects. The antidepressant-like effects occurred in the absence of changes in brain phospholipid classes. The therapeutic approach of combining omega-3 fatty acids with low ineffective doses of antidepressants might represent benefits in the treatment of depression, especially in patients with depression resistant to conventional treatments and even may contribute to patient compliance by decreasing the magnitude of some antidepressant dose-dependent side effects. Copyright © 2010 Elsevier B.V. All rights reserved.

Study of antinociceptive activity of SSRI (fluoxetine and escitalopram and atypical antidepressants (venlafaxine and mirtazepine and their interaction with morphine and naloxone in mice

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Pranav Sikka

2011-01-01

Full Text Available Objective : to study the probable site of antinociceptive action of SSRI (fluoxetine, escitalopram and atypical antidepressants (mirtazapine, venlafaxine and their interaction with morphine and naloxone. Materials and Methods : the study was conducted on albino mice (25-35 grams of either sex. Different doses of morphine (0.5 and 1 mg/kg, fluoxetine (2, 5 and 10 mg/kg, venlafaxine (30, 40 and 50 mg/kg, mirtazapine (3, 5 and 7 mg/kg and escitalopram (2.5, 5 and 10 mg/kg were administered subcutaneously to obtain their subanalgesic doses using tail flick analgesiometer. Tail flick latencies were obtained at 15, 30, 60 and 120 min. after drug administration. Naloxone (1 mg/kg was administered 10 minutes prior to test drug for testing antagonism. Observations : fluoxetine (5 and 10 mg/kg, mirtazapine (5 and 7 mg/kg and venlafaxine (40 and 50 mg/kg were found to have antinociceptive activity but not at lower doses. Escitalopram failed to show any antinociceptive activity at any of the doses used. The antinociceptive effect of all the drugs was antagonized by naloxone (1 mg/kg. Further, subanalgesic doses of fluoxetine, mirtazapine and venlafaxine showed analgesic activity with suboptimal dose of morphine (0.5 mg/kg. Result and conclusion : fluoxetine, mirtazapine and venlafaxine have antinociceptive activity whereas escitalopram doesn′t; their site of action seems to be the same as that of opioid analgesics (′mue′ receptors. However, other pathways (cholinergic, histaminic, noradrenergic, GABAergic may be involved in mediation of their analgesic activity, deserving further elucidation. Results apparently show that these drugs may be useful in the management of pain as monotherapy or in combination with other opioids.

Effects of BDNF polymorphisms on antidepressant action.

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Tsai, Shih-Jen; Hong, Chen-Jee; Liou, Ying-Jay

2010-12-01

Evidence suggests that the down-regulation of the signaling pathway involving brain-derived neurotrophic factor (BDNF), a molecular element known to regulate neuronal plasticity and survival, plays an important role in the pathogenesis of major depression. The restoration of BDNF activity induced by antidepressant treatment has been implicated in the antidepressant therapeutic mechanism. Because there is variability among patients with major depressive disorder in terms of response to antidepressant treatment and since genetic factors may contribute to this inter-individual variability in antidepressant response, pharmacogenetic studies have tested the associations between genetic polymorphisms in candidate genes related to antidepressant therapeutic action. In human BDNF gene, there is a common functional polymorphism (Val66Met) in the pro-region of BDNF, which affects the intracellular trafficking of proBDNF. Because of the potentially important role of BDNF in the antidepressant mechanism, many pharmacogenetic studies have tested the association between this polymorphism and the antidepressant therapeutic response, but they have produced inconsistent results. A recent meta-analysis of eight studies, which included data from 1,115 subjects, suggested that the Val/Met carriers have increased antidepressant response in comparison to Val/Val homozygotes, particularly in the Asian population. The positive molecular heterosis effect (subjects heterozygous for a specific genetic polymorphism show a significantly greater effect) is compatible with animal studies showing that, although BDNF exerts an antidepressant effect, too much BDNF may have a detrimental effect on mood. Several recommendations are proposed for future antidepressant pharmacogenetic studies of BDNF, including the consideration of multiple polymorphisms and a haplotype approach, gene-gene interaction, a single antidepressant regimen, controlling for age and gender interactions, and pharmacogenetic

Adherence to antidepressants

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Abimbola Farinde

2013-01-01

Full Text Available While major depression is considered a frequent mental illness there are ongoing reports of high non-adherence to antidepressant medications which places suffers at high risk for relapse, recurrence, or greater impairment,. The World Health Organization (WHO defines adherence as the extent to which a person′s behavior (e.g. taking medications can align with the agreed recommendations of a health care provider. Unfortunately while patient may recognize the importance of adherence to antidepressant medications the majority of patients do not adhere to their prescribed antidepressants. Some of the factors that may contribute to or lead to non-adherence include knowingly or unknowingly missing doses, taking extra doses, delaying administration times, or taking drug holidays. Pharmacists have the unique ability to deter non-adherence through the performance of continuous assessment and monitoring of adherence in this population given these accessibility. Additionally, pharmacists are able to develop therapeutic alliances with patients that can help to increase the likelihood of achieving positive patient outcomes. Antidepressant non-adherence can be viewed as a significant public health concern so it is important for patients to be educated about the importance of adherence, and health care professionals should be aware of factors or patient characteristics that can serve as barriers to non-adherence.

Relabeling the Medications We Call Antidepressants

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David Antonuccio

2012-01-01

Full Text Available This paper raises the question about whether the data on the medications we call antidepressants justify the label of antidepressant. The authors argue that a true antidepressant should be clearly superior to placebo, should offer a risk/benefit balance that exceeds that of alternative treatments, should not increase suicidality, should not increase anxiety and agitation, should not interfere with sexual functioning, and should not increase depression chronicity. Unfortunately, these medications appear to fall short on all of these dimensions. Many of the “side effects” of these medications have larger effect sizes than the antidepressant effect size. To call these medications antidepressants may make sense from a marketing standpoint but may be misleading from a scientific perspective. Consumers deserve a label that more accurately reflects the data on the largest effects and helps them understand the range of effects from these medications. In other words, it may make just as much sense to call these medications antiaphrodisiacs as antidepressants because the negative effects on libido and sexual functioning are so common. It can be argued that a misleading label may interfere with our commitment to informed consent. Therefore, it may be time to stop calling these medications antidepressants.

Antidepressants: Can They Lose Effectiveness?

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... t seem to be having the same effect. Can antidepressants lose effectiveness? Answers from Daniel K. Hall- ... some people and not in others. There also can be other reasons an antidepressant is no longer ...

Ketamine: A New Antidepressant?

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Feride Karacaer

2015-03-01

Full Text Available Standart antidepressants are needed for the many individuals with major depressive disorder. However they do not respond adequately to treatment and because of a delay of weeks before the emergence of therapeutic effects. Recent studies show that subanesthetic dose of ketamine is efficacy and safety for the treatment of depression. Antidepressant effects of ketamine have been found to be short-lived and its psychotomimetic properties may limit the use of ketamine to depressive patients. Future research studies should focus on identifying predictors of response (pharmalogical and clinical , investigating application of different doses and routes of administration and maintaining antidepressant effect. [Psikiyatride Guncel Yaklasimlar - Current Approaches in Psychiatry 2015; 7(1: 30-40

Factors influencing the choice of antidepressants: A study of antidepressant prescribing practice at University psychiatric clinic in Belgrade

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Marić Nađa P.

2012-01-01

Full Text Available Background/Aim. Antidepressants are a widely used class of drugs. The aim of this study was to investigate different aspects of antidepressant prescribing practice at University Psychiatric Clinic in Belgrade. Methods. This cross-sectional study was carried out by retrospective analysis of the patient's medical charts. The study included all patients with antidepressant prescribed at discharge during 2009 (n = 296. The evaluation was focused on patient- related factors (socio-demographic and illness related, psychiatrist-related factors (sex and duration of working experience and drug related factors (type of antidepressant, dose, polypharmacy and reimbursement by national health insurance. Results. Antidepressants were prescribed for unipolar depression (F32-34, ICD X either without comorbidity (46.2% or with comorbidity (24.7%, mostly as a monotherapy (91% had one antidepressant, to the patients who were 65% female, aged 50.1 ± 8.9, most of them with 12 years of education (52.6%, married (69.3% and employed (55.9%. The majority of patients had a history of two hospitalizations (Med 2; 25th-75th perc. 1-4 during nine years (Med 9; 25th-75th perc. 2-15 after the first episode of depression. Among them, 19% were found to be suicidal in a lifetime. The single most prescribed antidepressant was sertraline (20.4%, followed by fluoxetine (13.3% and maprotiline (11.7%. Utilization of antidepressants was positively correlated with the rate of reimbursement (p < 0.01. The most prescribed antidepressant group was selective serotonin reuptake inhibitors (SSRI (47.8%, followed by tricyclic antidepresants (TCA (25.3% and new antidepressants - venlafaxine, tianeptine, mirtazapine, bupropion, trazodone (15.1%. Most of the drugs were prescribed in doses which are at the lower end of the recommended dose-range. Regarding severity of the actual depressive episode, TCA were prescribed for severe depression with psychotic features, while SSRI were choice for

Antidepressants for Children and Teens

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... et al. Antidepressant drugs and the risk of suicide in children and adolescents. Pediatric Drugs. 2014;16:115. Gibbons RD, et al. Antidepressant treatment and suicide attempts and self-inflicted injury in children and adolescents. Pharmacoepidemiology and Drug Safety. 2015;24: ...

Depression, antidepressants and driving safety.

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Hill, Linda L; Lauzon, Vanessa L; Winbrock, Elise L; Li, Guohua; Chihuri, Stanford; Lee, Kelly C

2017-12-01

The purpose of this study was to review to review the reported associations of depression and antidepressants with motor vehicle crashes. A literature search for material published in the English language between January, 1995, and October, 2015, in bibliographic databases was combined with a search for other relevant material referenced in the retrieved articles. Retrieved articles were systematically reviewed for inclusion criteria: 19 epidemiological studies (17 case-control and 2 cohort studies) fulfilled the inclusion criteria by estimating the crash risk associated with depression and/or psychotropic medications in naturalistic settings. The estimates of the odds ratio (OR) of crash involvement associated with depression ranged from 1.78 to 3.99. All classes of antidepressants were reported to have side effects with the potential to affect driving safety. The majority of studies of antidepressant effects on driving reported an elevated crash risk, and ORs ranged from 1.19 to 2.03 for all crashes, and 3.19 for fatal crashes. In meta-analysis, depression was associated with approximately 2-fold increased crash risk (summary OR = 1.90; 95% CI, 1.06 to 3.39), and antidepressants were associated with approximately 40% increased crash risk (summary OR = 1.40; 95%CI, 1.18 to 1.66). Based on the findings of the studies reviewed, depression, antidepressants or the combination of depression and antidepressants may pose a potential hazard to driving safety. More research is needed to understand the individual contributions of depression and the medications used to treat depression.

Pharmacogenetics of antidepressant response: An update

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Drago Antonio

2009-04-01

Full Text Available Abstract The past few decades have witnessed much progress in the field of pharmacogenetics. The identification of the genetic background that regulates the antidepressant response has benefited from these advances. This review focuses on the pharmacogenetics of the antidepressant response through the analysis and discussion of the most compelling evidence in this line of research. Online databases (Medline and PsycINFO have been searched and the most replicated association findings relating to the genetics of the antidepressant response have been reported and discussed. Some replicated findings in the literature have suggested the serotonin transporter promoter (5-HTTLPR, serotonin receptor 1A (HTR1A, serotonin receptor 2A (HTR2A, brain derived neurotrophic factor (BDNF, corticotropin releasing hormone receptor 1 (CRHR1 and FK506 binding protein 5 (FKBP5 as putative regulators of the antidepressant response. A high rate of failure of replication has also been reported. Pharmacogenetics will hopefully provide the basis for personalised antidepressant treatment that is able to maximise the probability of a good response and to minimise side effects; however, this goal is not achievable at the moment. The extent of the validity of the replicated findings and the reasons for the poor results obtained from studies of the pharmacogenetics of the antidepressant response are discussed.

Antidepressants in the treatment of neuropathic pain

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Sindrup, Søren H.; Otto, Marit; Finnerup, Nanna Brix

2005-01-01

Neuropathic pain is due to lesion or dysfunction of the peripheral or central nervous system. Tricyclic antidepressants and anticonvulsants have long been the mainstay of treatment of this type of pain. Tricyclic antidepressants may relieve neuropathic pain by their unique ability to inhibit...... presynaptic reuptake of the biogenic amines serotonin and noradrenaline, but other mechanisms such as N-methyl-D-aspartate receptor and ion channel blockade probably also play a role in their pain-relieving effect. The effect of tricyclic antidepressants in neuropathic pain in man has been demonstrated...... in numerous randomised, controlled trials, and a few trials have shown that serotonin noradrenaline and selective serotonin reuptake inhibitor antidepressants also relieve neuropathic pain although with lower efficacy. Tricyclic antidepressants will relieve one in every 2-3 patients with peripheral...

The efficacy of primary care chaplaincy compared with antidepressants: a retrospective study comparing chaplaincy with antidepressants.

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Macdonald, Gordon

2017-07-01

Aim To determine the effectiveness of primary care chaplaincy (PCC) when used as the sole intervention, with outcomes being compared directly with those of antidepressants. This was to be carried out in a homogenous study population reflective of certain demographics in the United Kingdom. Increasing numbers of patients are living with long-term conditions and 'modern maladies' and are experiencing loss of well-being and depression. There is an increasing move to utilise non-pharmacological interventions such as 'talking therapies' within this context. Chaplaincy is one such 'talking therapy' but within primary care its evidence base is sparse with only one quantitative study to date. There is therefore a need to evaluate PCC excluding those co-prescribed antidepressants, as this is not evidenced in the literature as yet. PCC also needs to be directly compared with the use of antidepressants to justify its use as a valid alternative treatment for loss of well-being and depression. This was a retrospective observational study based on routinely collected data. There were 107 patients in the PCC group and 106 in the antidepressant group. Socio-demographic data were collected. Their pre- and post-intervention (either chaplaincy or antidepressant) well-being was assessed, by the Warwick-Edinburgh Mental Well-being Scale (WEMWBS) which is a validated Likert scale. Findings The majority of both groups were female with both groups showing marked ethnic homogeneity. PCC was associated with a significant and clinically meaningful improvement in well-being at a mean follow-up of 80 days. This treatment effect was maintained after those co-prescribed antidepressants were removed. PCC was associated with an improvement in well-being similar to that of antidepressants with no significant difference between the two groups.

Placental transfer of antidepressant medications: implications for postnatal adaptation syndrome.

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Ewing, Grace; Tatarchuk, Yekaterina; Appleby, Dina; Schwartz, Nadav; Kim, Deborah

2015-04-01

Seven to thirteen percent of women are either prescribed or taking (depending on the study) an antidepressant during pregnancy. Because antidepressants freely cross into the intrauterine environment, we aim to summarize the current findings on placental transfer of antidepressants. Although generally low risk, antidepressants have been associated with postnatal adaptation syndrome (PNAS). Specifically, we explore whether the antidepressants most closely associated with PNAS (paroxetine, fluoxetine, venlafaxine) cross the placenta to a greater extent than other antidepressants. We review research on antidepressants in the context of placental anatomy, placental transport mechanisms, placental metabolism, pharmacokinetics, as well as non-placental maternal and fetal factors. This provides insight into the complexity involved in understanding how placental transfer of antidepressants may relate to adverse perinatal outcomes. Ultimately, from this data there is no pattern in which PNAS is related to placental transfer of antidepressant medications. In general, there is large interindividual variability for each type of antidepressant. To make the most clinically informed decisions about the use of antidepressants in pregnancy, studies that link maternal, placental and fetal genetic polymorphisms, placental transfer rates and infant outcomes are needed.

[Tricyclic antidepressant therapy in headache].

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Magyar, Máté; Csépány, Éva; Gyüre, Tamás; Bozsik, György; Bereczki, Dániel; Ertsey, Csaba

2015-12-01

The two most important representatives of the primary headaches are migraine and tension-type headache. More than 10% of the population suffer from migraine and even a greater part, approximately 30-40% from tension-type headache. These two headache types have a great effect both on the individual and on the society. There are two types of therapeutic approaches to headaches: the abortive and the prophylactic therapy. Prophylactic treatment is used for frequent and/or difficult-to-treat headache attacks. Although both migraine and tension-type headache are often associated with depression, for their treatment - in contrast to the widespread medical opinion - not all antidepressants were found to be effective. Amitriptyline, which is a tricyclic antidepressant, is used as a prophylactic therapy for headache since 1968. Its efficacy has been demonstrated in several double-blind, placebo-controlled studies. Although the newer types of antidepressant, such as selective serotonin reuptake inhibitors and selective serotonin-norepinephrine reuptake inhibitor, have a more favorable side-effect profile than tricyclic antidepressants, their headache prophylactic effect has not been proven yet.

Sexual dysfunction, depression, and the impact of antidepressants.

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Kennedy, Sidney H; Rizvi, Sakina

2009-04-01

Sexual dysfunction is a common symptom of depression. Although decreased libido is most often reported, difficulties with arousal, resulting in vaginal dryness in women and erectile dysfunction in men, and absent or delayed orgasm are also prevalent. Sexual dysfunction is also a frequent adverse effect of treatment with most antidepressants and is one of the predominant reasons for premature drug discontinuation. Selective serotonin reuptake inhibitors are the most widely prescribed antidepressants and have significant effects on arousal and orgasm compared with antidepressants that target norepinephrine, dopamine, and melatonin systems. The availability of an antidepressant that does not cause or exacerbate sexual dysfunction represents an advance in pharmacotherapy for mood disorders and should reduce treatment noncompliance and decrease the need for switching antidepressants or adding antidotes. The purpose of this review was to provide an update on the prevalence, psychobiology, and relative adverse effect burden of sexual dysfunction associated with different antidepressants.

Sertraline: a new antidepressant.

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Auster, R

1993-08-01

Sertraline is a serotonin reuptake inhibitor that has been approved for use in the treatment of depression. Its side-effect profile is similar to that of fluoxetine, a drug of the same class. The side effects of these drugs most often affect the gastrointestinal tract. Serotonin reuptake inhibitors are nonsedating and free of cardiac effects; they do not cause hypotension, urinary retention or blurred vision. Sertraline, like fluoxetine, appears to be safer than tricyclic antidepressants in overdose. However, no clinical studies comparing sertraline and fluoxetine have been published. The wholesale cost of a month's supply of sertraline is about $50, compared with about $5 for a generic tricyclic antidepressant. Despite their cost, serotonin uptake inhibitors may be the initial drugs of choice in depressed elderly patients, because these patients are at increased risk for suicide and have a low tolerance for the side effects of tricyclic antidepressants.

Location of the Antidepressant Binding Site in the Serotonin Transporter IMPORTANCE OF SER-438 IN RECOGNITION OF CITALOPRAM AND TRICYCLIC ANTIDEPRESSANTS

DEFF Research Database (Denmark)

Andersen, Jacob; Taboureau, Olivier; Hansen, Kasper B.

2009-01-01

antidepressants, including the selective serotonin reuptake inhibitor citalopram and the tricyclic antidepressants imipramine, clomipramine, and amitriptyline. A conservative mutation of Ser-438 to threonine (S438T) selectively increased the K-i values for these antidepressants up to 175-fold. The effects...

NMDAR inhibition-independent antidepressant actions of ketamine metabolites

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Zanos, Panos; Moaddel, Ruin; Morris, Patrick J.; Georgiou, Polymnia; Fischell, Jonathan; Elmer, Greg I.; Alkondon, Manickavasagom; Yuan, Peixiong; Pribut, Heather J.; Singh, Nagendra S.; Dossou, Katina S.S.; Fang, Yuhong; Huang, Xi-Ping; Mayo, Cheryl L.; Wainer, Irving W.; Albuquerque, Edson X.; Thompson, Scott M.; Thomas, Craig J.; Zarate, Carlos A.; Gould, Todd D.

2016-01-01

Major depressive disorder afflicts ~16 percent of the world population at some point in their lives. Despite a number of available monoaminergic-based antidepressants, most patients require many weeks, if not months, to respond to these treatments, and many patients never attain sustained remission of their symptoms. The non-competitive glutamatergic N-methyl-D-aspartate receptor (NMDAR) antagonist, (R,S)-ketamine (ketamine), exerts rapid and sustained antidepressant effects following a single dose in depressed patients. Here we show that the metabolism of ketamine to (2S,6S;2R,6R)-hydroxynorketamine (HNK) is essential for its antidepressant effects, and that the (2R,6R)-HNK enantiomer exerts behavioural, electroencephalographic, electrophysiological and cellular antidepressant actions in vivo. Notably, we demonstrate that these antidepressant actions are NMDAR inhibition-independent but they involve early and sustained α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor activation. We also establish that (2R,6R)-HNK lacks ketamine-related side-effects. Our results indicate a novel mechanism underlying ketamine’s unique antidepressant properties, which involves the required activity of a distinct metabolite and is independent of NMDAR inhibition. These findings have relevance for the development of next generation, rapid-acting antidepressants. PMID:27144355

New generation of antidepressants in pregnant women

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Ladan Kashani

2007-03-01

Full Text Available Although pregnancy was once thought to protect against psychiatric disorders, gravid and non gravid women have similar risks for major depression, at 10% to 15%. Both depression and antidepressant treatment during pregnancy have been associated with risks. Few medications have been proved unequivocally safe during pregnancy. Although certain antidepressants have not been linked with an increased risk of birth defects or impaired development including bupropion, citalopram, escitalopram and venlafaxine, the latest studies aren't necessarily reassuring. As researchers continue to learn more about antidepressants, the risks and benefits of taking the drugs during pregnancy must be weighed carefully on a case-by-case basis. This review discusses about the use of new generation of antidepressants in pregnancy

Racial and ethnic disparities in antidepressant drug use.

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Chen, Jie; Rizzo, John A

2008-12-01

Little is known about racial and ethnic disparities in health care utilization, expenditures and drug choice in the antidepressant market. This study investigates factors associated with the racial and ethnic disparities in antidepressant drug use. We seek to determine the extent to which disparities reflect differences in observable population characteristics versus heterogeneity across racial and ethnic groups. Among the population characteristics, we are interested in identifying which factors are most important in accounting for racial and ethnic disparities in antidepressant drug use. Using Medical Expenditure Panel Survey (MEPS) data from 1996-2003, we have an available sample of 10,416 Caucasian, 1,089 African American and 1,539 Hispanic antidepressant drug users aged 18 to 64 years. We estimate individual out-of-pocket payments, total prescription drug expenditures, drug utilization, the probability of taking generic versus brand name antidepressants, and the share of drugs that are older types of antidepressants (e.g., TCAs and MAOIs) for these individuals during a calendar year. Blinder-Oaxaca decomposition techniques are employed to determine the extent to which disparities reflect differences in observable population characteristics versus unobserved heterogeneity across racial and ethnic groups. Caucasians have the highest antidepressant drug expenditures and utilization. African-Americans have the lowest drug expenditures and Hispanics have the lowest drug utilization. Relative to Caucasians and Hispanics, African-Americans are more likely to purchase generics and use a higher share of older drugs (e.g., TCAs and MAOIs). Differences in observable characteristics explain most of the racial/ethnic differences in these outcomes, with the exception of drug utilization. Differences in health insurance and education levels are particularly important factors in explaining disparities. In contrast, differences in drug utilization largely reflect unobserved

IC Treatment: Antidepressants

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... Federal Campaign ICA Resources for Donors Corporate Contributions Social Media ... depression. Did you know that antidepressants are also effective in treating symptoms of people with interstitial cystitis ( ...

GPs motivations of prescribing antidepressants and their practical relevance.

NARCIS (Netherlands)

Volkers, A.; Jong, A. de; Braspenning, J.C.C.; Bakker, D. de; Dijk, L. van

2004-01-01

Background: Insight in the motivations of prescribing antidepressants may contribute to advance the efficiency of the current, large antidepressant prescription rate. Less is known about why general practitioners (GPs) treat patients with antidepressants or not and choose modern SSRIs instead of the

Antidepressants: Selecting One That's Right for You

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Antidepressants: Selecting one that's right for you Confused by the choice in antidepressants? With persistence, you and your doctor should find one that works so ... Foundation for Medical Education and Research (MFMER). All rights reserved.

Migraine Medications and Antidepressants: A Risky Mix?

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... What are the health risks associated with taking migraine medications and antidepressants at the same time? Answers ... W. Swanson, M.D. Reports suggest that combining migraine medications called triptans with certain antidepressants — including selective ...

Antidepressant Medication Management among Older Patients Receiving Home Health Care

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Bao, Yuhua; Shao, Huibo; Bruce, Martha L.; Press, Matthew J.

2014-01-01

Objective Antidepressant management for older patients receiving home health care (HHC) may occur through two pathways: nurse-physician collaboration (without patient visits to the physician) and physician management through office visits. This study examines the relative contribution of the two pathways and how they interplay. Methods Retrospective analysis was conducted using Medicare claims of 7,389 depressed patients 65 or older who received HHC in 2006–7 and who possessed antidepressants at the start of HHC. A change in antidepressant therapy (vs. discontinuation or refill) was the main study outcome and could take the form of a change in dose, switch to a different antidepressant, or augmentation (addition of a new antidepressant). Logistic regressions were estimated to examine how use of home health nursing care, patient visits to physicians, and their interactions predict a change in antidepressant therapy. Results About 30% of patients experienced a change in antidepressants versus 51% who refilled and 18% who discontinued. Receipt of mental health specialty care was associated with a statistically significant, 10–20 percentage-point increase in the probability of antidepressant change; receipt of primary care was associated with a small and statistically significant increase in the probability of antidepressant change among patients with no mental health specialty care and above-average utilization of nursing care. Increased home health nursing care in absence of physician visits was not associated with increased antidepressant change. Conclusions Active antidepressant management resulting in a change in medication occurred on a limited scale among older patients receiving HHC. Addressing knowledge and practice gaps in antidepressant management by primary care providers and home health nurses and improving nurse-physician collaboration will be promising areas for future interventions. PMID:25158915

A prospective naturalistic study of antidepressant-induced jitteriness/anxiety syndrome

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Harada T

2014-11-01

Full Text Available Tsuyoto Harada, Ken Inada, Kazuo Yamada, Kaoru Sakamoto, Jun Ishigooka Department of Psychiatry, Tokyo Women’s Medical University School of Medicine, Tokyo, Japan Objective: Patients often develop neuropsychiatric symptoms such as anxiety and agitation after they have started taking an antidepressant, and this is thought to be associated with a potentially increased risk of suicide. However, the incidence of antidepressant-induced jitteriness/anxiety syndrome has not been fully investigated, and little has been reported on its predictors. The aim of this study was to survey the incidence of antidepressant-induced jitteriness/anxiety syndrome and clarify its predictors in a natural clinical setting.Materials and methods: Between January 2009 and July 2012, we prospectively surveyed 301 patients who had not taken any antidepressants for 1 month before presentation, and who were prescribed antidepressants for 1 month after their initial visit. Patients were classified as developing antidepressant-induced jitteriness/anxiety syndrome if they experienced any symptoms of anxiety, agitation, panic attacks, insomnia, irritability, hostility, aggressiveness, impulsivity, akathisia, hypomania, or mania during the first month.Results: Among the 301 patients, 21 (7.0% developed antidepressant-induced jitteriness/anxiety syndrome. Major depressive disorder and a diagnosis of mood disorder in first-degree relatives of patients were significantly associated with induction of antidepressant-induced jitteriness/anxiety syndrome (odds ratio 10.2, P=0.001; odds ratio 4.65, P=0.02; respectively. However, there was no such relationship for sex, age, class of antidepressant, combined use of benzodiazepines, or diagnosis of anxiety disorder.Conclusion: The findings of this study suggest that major depressive disorder and a diagnosis of mood disorder in first-degree relatives may be clinical predictors of antidepressant-induced jitteriness/anxiety syndrome

Chirality of Modern Antidepressants: An Overview

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Monica Budău

2017-12-01

Full Text Available The majority of modern antidepressants (selective serotonin reuptake inhibitors and selective serotonin and norepinephrine reuptake inhibitors have one or two centers of asymmetry in their structure; resulting in the formation of enantiomers which may exhibit different pharmacodynamic and pharmacokinetic properties. Recent developments in drug stereochemistry has led to understanding the role of chirality in modern therapy correlated with increased knowledge regarding the molecular structure of specific drug targets and towards the possible advantages of using pure enantiomers instead of racemic mixtures. The current review deals with chiral antidepressant drugs; presenting examples of stereoselectivity in the pharmacological actions of certain antidepressants and their metabolites and emphasizing the differences between pharmacological actions of the racemates and pure enantiomers.

SSRI antidepressants: altered psychomotor development following exposure in utero?

Science.gov (United States)

2013-02-01

Selective serotonin reuptake inhibitor antidepressants (SSRIs) are sometimes prescribed to pregnant women. The potential consequences for the unborn child are gradually becoming clearer. In a case-control study of 298 children with autism and 1507 controls, 6.7% of mothers of autistic children had been prescribed an antidepressant during the year before delivery, compared to 3.3% of control mothers. The antidepressant was usually an SSRI. A dozen other small epidemiological studies of neurological development in children exposed to antidepressants in utero have provided mixed results. Two of these studies suggested a risk of psychomotor retardation. In practice, SSRI antidepressants should only be considered for pregnant women when non-drug measures fail and when symptoms are sufficiently serious to warrant drug therapy.

Peripheral administration of lactate produces antidepressant-like effects

KAUST Repository

Carrard, A; Elsayed, M; Margineanu, Michael B.; Boury-Jamot, B; Fragniè re, L; Meylan, E M; Petit, J-M; Fiumelli, Hubert; Magistretti, Pierre J.; Martin, J-L

2016-01-01

In addition to its role as metabolic substrate that can sustain neuronal function and viability, emerging evidence supports a role for l-lactate as an intercellular signaling molecule involved in synaptic plasticity. Clinical and basic research studies have shown that major depression and chronic stress are associated with alterations in structural and functional plasticity. These findings led us to investigate the role of l-lactate as a potential novel antidepressant. Here we show that peripheral administration of l-lactate produces antidepressant-like effects in different animal models of depression that respond to acute and chronic antidepressant treatment. The antidepressant-like effects of l-lactate are associated with increases in hippocampal lactate levels and with changes in the expression of target genes involved in serotonin receptor trafficking, astrocyte functions, neurogenesis, nitric oxide synthesis and cAMP signaling. Further elucidation of the mechanisms underlying the antidepressant effects of l-lactate may help to identify novel therapeutic targets for the treatment of depression.

Peripheral administration of lactate produces antidepressant-like effects

KAUST Repository

Carrard, A

2016-10-18

In addition to its role as metabolic substrate that can sustain neuronal function and viability, emerging evidence supports a role for l-lactate as an intercellular signaling molecule involved in synaptic plasticity. Clinical and basic research studies have shown that major depression and chronic stress are associated with alterations in structural and functional plasticity. These findings led us to investigate the role of l-lactate as a potential novel antidepressant. Here we show that peripheral administration of l-lactate produces antidepressant-like effects in different animal models of depression that respond to acute and chronic antidepressant treatment. The antidepressant-like effects of l-lactate are associated with increases in hippocampal lactate levels and with changes in the expression of target genes involved in serotonin receptor trafficking, astrocyte functions, neurogenesis, nitric oxide synthesis and cAMP signaling. Further elucidation of the mechanisms underlying the antidepressant effects of l-lactate may help to identify novel therapeutic targets for the treatment of depression.

Potentials of Curcumin as an Antidepressant

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S.K. Kulkarni

2009-01-01

Full Text Available Major depression, a debilitating psychiatric disorder, is predicted to be the second most prevalent human illness by the year 2020. Various antidepressants, ranging from monoamine oxidase inhibitors to recently developed dual reuptake inhibitors, are prescribed for alleviating the symptoms of depression. Despite the availability of these blockbuster molecules, approximately 30% of depressed patients do not respond to the existing drug therapies and the remaining 70% fails to achieve complete remission. Moreover, antidepressants are associated with a plethora of side effects and drug-drug/drug-food interactions. In this context, novel approaches are being tried to find more efficacious and safer drugs for the treatment of major depression. Curcumin is one such molecule that has shown promising efficacy in various animal models of major depression. Although the mechanism of the antidepressant effect of curcumin is not fully understood, it is hypothesized to act through inhibiting the monoamine oxidase enzyme and modulating the release of serotonin and dopamine. Moreover, evidences have shown that curcumin enhances neurogenesis, notably in the frontal cortex and hippocampal regions of the brain. The use of curcumin in clinics for the treatment of major depression is limited due to its poor gastrointestinal absorption. The present review attempts to discuss the pharmacological profile along with molecular mechanisms of the antidepressant effect of curcumin in animal models of depression. A need for clinical trials in order to explore the antidepressant efficacy and safety profile of curcumin is emphasized.

Deuterated (d6)-dextromethorphan elicits antidepressant-like effects in mice.

Science.gov (United States)

Nguyen, Linda; Scandinaro, Anna L; Matsumoto, Rae R

2017-10-01

The over-the-counter antitussive dextromethorphan (DM) may have rapid antidepressant actions based on its overlapping pharmacology with ketamine, which has shown fast antidepressant effects but whose widespread use remains limited by problematic side effects. We have previously shown that DM produces antidepressant-like effects in the forced swim test (FST) and tail suspension test (TST) that are mediated in part through α-amino-3-hydroxy-5-methyl-4-isoxazole propionic (AMPA) and sigma-1 receptors, two protein targets associated with a faster onset of antidepressant efficacy. To utilize DM clinically, however, a major challenge that must be addressed is its rapid first-pass metabolism. Two strategies to inhibit metabolism of DM and maintain stable therapeutic blood levels are 1) chemically modifying DM and 2) adding quinidine, an inhibitor of the primary metabolizer of DM, the cytochrome P450 (CYP) 2D6 enzyme. The purpose of this study was to determine if modified DM (deuterated (d6)-DM) elicits antidepressant-like effects and if AMPA and sigma-1 receptors are involved. Furthermore, d6-DM was tested in conjunction with quinidine to determine if further slowing the metabolism of d6-DM affects its antidepressant-like actions. In the FST and TST, d6-DM produced antidepressant-like effects. Upon further investigation in the FST, the most validated animal model for predicting antidepressant efficacy, d6-DM produced antidepressant-like effects both in the absence and presence of quinidine. However, pretreatment with neither an AMPA receptor antagonist (NBQX) nor sigma-1 receptor antagonists (BD1063, BD1047) significantly attenuated the antidepressant-like effects. The data suggest d6-DM has antidepressant-like effects, though it may be recruiting different molecular targets and/or acting through a different mix or ratio of metabolites from regular DM. Copyright © 2017 Elsevier Inc. All rights reserved.

Placebo and antidepressant treatment for major depression

DEFF Research Database (Denmark)

Hougaard, Esben

2010-01-01

Antidepressant medication is generally considered the primary treatment for major depressive disorders (MDD), but antidepressant treatment has recently approached a crisis with shrinking specific effects and growing placebo responses in current trials. The aim of the paper is to review the placebo...

Antidepressants and gastrointestinal symptoms in the general Dutch adult population

NARCIS (Netherlands)

Schurink, B.; Tielemans, M.M.; Aaldering, B.R.; Eikendal, T.; Jaspers Focks, J.; Laheij, R.J.F.; Jansen, J.B.M.J.; Rossum, L.G.M. van; Oijen, M.G.H. van

2014-01-01

BACKGROUND: Gastrointestinal symptoms are frequently reported adverse effects of antidepressants, but antidepressants are also a treatment modality in functional gastrointestinal disorders. We aimed to assess the association between antidepressant use and gastrointestinal symptoms in the general

Milnacipran: a unique antidepressant?

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Siegfried Kasper

2010-08-01

Full Text Available Siegfried Kasper, Gerald PailDepartment of Psychiatry and Psychotherapy, Medical University of Vienna, AustriaAbstract: Tricyclic antidepressants (TCAs are among the most effective antidepressants available, although their poor tolerance at usual recommended doses and toxicity in ­overdose make them difficult to use. While selective serotonin reuptake inhibitors (SSRIs are ­better tolerated than TCAs, they have their own specific problems, such as the aggravation of sexual dysfunction, interaction with coadministered drugs, and for many, a discontinuation syndrome. In addition, some of them appear to be less effective than TCAs in more severely depressed patients. Increasing evidence of the importance of norepinephrine in the etiology of depression has led to the development of a new generation of antidepressants, the serotonin and ­norepinephrine reuptake inhibitors (SNRIs. Milnacipran, one of the pioneer SNRIs, was designed from theoretic considerations to be more effective than SSRIs and better tolerated than TCAs, and with a simple pharmacokinetic profile. Milnacipran has the most balanced potency ratio for reuptake inhibition of the two neurotransmitters compared with other SNRIs (1:1.6 for milnacipran, 1:10 for duloxetine, and 1:30 for venlafaxine, and in some studies milnacipran has been shown to inhibit norepinephrine uptake with greater potency than serotonin (2.2:1. Clinical studies have shown that milnacipran has efficacy comparable with the TCAs and is superior to SSRIs in severe depression. In addition, milnacipran is well tolerated, with a low potential for pharmacokinetic drug–drug interactions. Milnacipran is a first-line therapy suitable for most depressed patients. It is frequently successful when other treatments fail for reasons of efficacy or tolerability.Keywords: milnacipran, SNRI, antidepressant efficacy, tolerability

Antidepressants for non-specific low back pain

NARCIS (Netherlands)

Urquhart, D. M.; Hoving, J. L.; Assendelft, W. W. J. J.; Roland, M.; van Tulder, M. W.

2008-01-01

BACKGROUND: Antidepressants are commonly used in the management of low-back pain. However, their use is controversial. OBJECTIVES: The aim of this review was to determine whether antidepressants are more effective than placebo for the treatment of non-specific low-back pain. SEARCH STRATEGY:

Escitalopram versus other antidepressive agents for depression

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Cipriani, Andrea; Santilli, Claudio; Furukawa, Toshi A; Signoretti, Alessandra; Nakagawa, Atsuo; McGuire, Hugh; Churchill, Rachel; Barbui, Corrado

2014-01-01

Background Although pharmacological and psychological interventions are both effective for major depression, antidepressant drugs remain the mainstay of treatment in primary and secondary care settings. During the last 20 years, antidepressant prescribing has risen dramatically in western countries, mainly because of the increasing consumption of selective serotonin reuptake inhibitors (SSRIs) and newer antidepressants, which have progressively become the most commonly prescribed antidepressants. Escitalopram is the pure S-enantiomer of the racemic citalopram. Objectives To assess the evidence for the efficacy, acceptability and tolerability of escitalopram in comparison with tricyclics, other SSRIs, heterocyclics and newer agents in the acute-phase treatment of major depression. Search methods Electronic databases were searched up to July 2008. Trial databases of drug-approving agencies were hand-searched for published, unpublished and ongoing controlled trials. Selection criteria All randomised controlled trials comparing escitalopram against any other antidepressant (including non-conventional agents such as hypericum) for patients with major depressive disorder (regardless of the diagnostic criteria used). Data collection and analysis Data were entered by two review authors (double data entry). Responders and remitters to treatment were calculated on an intention-to-treat basis. For dichotomous data, odds ratios (ORs) were calculated with 95% confidence intervals (CI). Continuous data were analysed using standardised mean differences (with 95% CI) using the random effects model. Main results Fourteen trials compared escitalopram with another SSRI and eight compared escitalopram with a newer antidepressive agent (venlafaxine, bupropion and duloxetine). Escitalopram was shown to be significantly more effective than citalopram in achieving acute response (OR 0.67, 95% CI 0.50 to 0.87). Escitalopram was also more effective than citalopram in terms of remission (OR

Is the antidepressive effect of second-generation antidepressants a myth?

DEFF Research Database (Denmark)

Bech, P

2010-01-01

Two recent meta-analyses on second-generation antidepressants versus placebo in mild to moderate forms of major depression, based on data on all randomized clinical trials using the Hamilton Depression Scale (HAMD) submitted to FDA, have shown an effect size of approximately 0.30 in favour...

Pharmacogenetics and Imaging-Pharmacogenetics of Antidepressant Response: Towards Translational Strategies.

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Lett, Tristram A; Walter, Henrik; Brandl, Eva J

2016-12-01

Genetic variation underlies both the response to antidepressant treatment and the occurrence of side effects. Over the past two decades, a number of pharmacogenetic variants, among these the SCL6A4, BDNF, FKBP5, GNB3, GRIK4, and ABCB1 genes, have come to the forefront in this regard. However, small effects sizes, mixed results in independent samples, and conflicting meta-analyses results led to inherent difficulties in the field of pharmacogenetics translating these findings into clinical practice. Nearly all antidepressant pharmacogenetic variants have potentially pleiotropic effects in which they are associated with major depressive disorder, intermediate phenotypes involved in emotional processes, and brain areas affected by antidepressant treatment. The purpose of this article is to provide a comprehensive review of the advances made in the field of pharmacogenetics of antidepressant efficacy and side effects, imaging findings of antidepressant response, and the latest results in the expanding field of imaging-pharmacogenetics studies. We suggest there is mounting evidence that genetic factors exert their impact on treatment response by influencing brain structural and functional changes during antidepressant treatment, and combining neuroimaging and genetic methods may be a more powerful way to detect biological mechanisms of response than either method alone. The most promising imaging-pharmacogenetics findings exist for the SCL6A4 gene, with converging associations with antidepressant response, frontolimbic predictors of affective symptoms, and normalization of frontolimbic activity following antidepressant treatment. More research is required before imaging-pharmacogenetics informed personalized medicine can be applied to antidepressant treatment; nevertheless, inroads have been made towards assessing genetic and neuroanatomical liability and potential clinical application.

Progress and prospects in pharmacogenetics of antidepressant drugs.

Science.gov (United States)

Fabbri, Chiara; Crisafulli, Concetta; Calabrò, Marco; Spina, Edoardo; Serretti, Alessandro

2016-10-01

Depression is responsible for the most part of the personal and socio-economic burden due to psychiatric disorders. Since antidepressant response clusters in families, pharmacogenetics represents a meaningful tool to provide tailored treatments and improve the prognosis of depression. This review aims to summarize and discuss the pharmacogenetics of antidepressant drugs in major depressive disorder, with a focus on the most replicated genes, genome-wide association studies (GWAS), but also on the findings provided by new and promising analysis methods. In particular, multimarker tests such as pathway analysis and polygenic risk scores increase the power of detecting associations compared to the analysis of individual polymorphisms. Since genetic variants are not necessarily associated with a change in protein level, gene expression studies may provide complementary information to genetic studies. Finally, the pharmacogenetic tests that have been investigated for clinical application are discussed. Despite the lack of widespread clinical applications, preliminary results suggest that pharmacogenetics may be useful to guide antidepressant treatment. The US Food and Drug Administration included pharmacogenetic indications in the labeling of several antidepressants. This represented an important official recognition of the clinical relevance of genetic polymorphisms in antidepressant treatment.

Computational Model of Antidepressant Response Heterogeneity as Multi-pathway Neuroadaptation

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Mariam B. Camacho

2017-12-01

Full Text Available Current hypotheses cannot fully explain the clinically observed heterogeneity in antidepressant response. The therapeutic latency of antidepressants suggests that therapeutic outcomes are achieved not by the acute effects of the drugs, but rather by the homeostatic changes that occur as the brain adapts to their chronic administration. We present a computational model that represents the known interactions between the monoaminergic neurotransmitter-producing brain regions and associated non-monoaminergic neurotransmitter systems, and use the model to explore the possible ways in which the brain can homeostatically adjust to chronic antidepressant administration. The model also represents the neuron-specific neurotransmitter receptors that are known to adjust their strengths (expressions or sensitivities in response to chronic antidepressant administration, and neuroadaptation in the model occurs through sequential adjustments in these receptor strengths. The main result is that the model can reach similar levels of adaptation to chronic administration of the same antidepressant drug or combination along many different pathways, arriving correspondingly at many different receptor strength configurations, but not all of those adapted configurations are also associated with therapeutic elevations in monoamine levels. When expressed as the percentage of adapted configurations that are also associated with elevations in one or more of the monoamines, our modeling results largely agree with the percentage efficacy rates of antidepressants and antidepressant combinations observed in clinical trials. Our neuroadaptation model provides an explanation for the clinical reports of heterogeneous outcomes among patients chronically administered the same antidepressant drug regimen.

Involvement of AMPA receptors in the antidepressant-like effects of dextromethorphan in mice.

Science.gov (United States)

Nguyen, Linda; Matsumoto, Rae R

2015-12-15

Dextromethorphan (DM) is an antitussive with rapid acting antidepressant potential based on pharmacodynamic similarities to ketamine. Building upon our previous finding that DM produces antidepressant-like effects in the mouse forced swim test (FST), the present study aimed to establish the antidepressant-like actions of DM in the tail suspension test (TST), another well-established model predictive of antidepressant efficacy. Additionally, using the TST and FST, we investigated the role of α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors in the antidepressant-like properties of DM because accumulating evidence suggests that AMPA receptors play an important role in the pathophysiology of depression and may contribute to the efficacy of antidepressant medications, including that of ketamine. We found that DM displays antidepressant-like effects in the TST similar to the conventional and fast acting antidepressants characterized by imipramine and ketamine, respectively. Moreover, decreasing the first-pass metabolism of DM by concomitant administration of quinidine (CYP2D6 inhibitor) potentiated antidepressant-like actions, implying DM itself has antidepressant efficacy. Finally, in both the TST and FST, pretreatment with the AMPA receptor antagonist NBQX (2,3-dioxo-6-nitro-1,2,3,4-tetrahydrobenzo[f]quinoxaline-7-sulfonamide) significantly attenuated the antidepressant-like behavior elicited by DM. Together, the data show that DM exerts antidepressant-like actions through AMPA receptors, further suggesting DM may act as a safe and effective fast acting antidepressant drug. Copyright © 2015 Elsevier B.V. All rights reserved.

Tianeptine: an antidepressant with memory-protective properties.

Science.gov (United States)

Zoladz, Phillip R; Park, Collin R; Muñoz, Carmen; Fleshner, Monika; Diamond, David M

2008-12-01

The development of effective pharmacotherapy for major depression is important because it is such a widespread and debilitating mental disorder. Here, we have reviewed preclinical and clinical studies on tianeptine, an atypical antidepressant which ameliorates the adverse effects of stress on brain and memory. In animal studies, tianeptine has been shown to prevent stress-induced morphological sequelae in the hippocampus and amygdala, as well as to prevent stress from impairing synaptic plasticity in the prefrontal cortex and hippocampus. Tianeptine also has memory-protective characteristics, as it blocks the adverse effects of stress on hippocampus-dependent learning and memory. We have further extended the findings on stress, memory and tianeptine here with two novel observations: 1) stress impairs spatial memory in adrenalectomized (ADX), thereby corticosterone-depleted, rats; and 2) the stress-induced impairment of memory in ADX rats is blocked by tianeptine. These findings are consistent with previous research which indicates that tianeptine produces anti-stress and memory-protective properties without altering the response of the hypothalamic-pituitary-adrenal axis to stress. We conclude with a discussion of findings which indicate that tianeptine accomplishes its anti-stress effects by normalizing stress-induced increases in glutamate in the hippocampus and amygdala. This finding is potentially relevant to recent research which indicates that abnormalities in glutamatergic neurotransmission are involved in the pathogenesis of depression. Ultimately, tianeptine's prevention of depression-induced sequelae in the brain is likely to be a primary factor in its effectiveness as a pharmacological treatment for depression.

Influence of psychotherapist density and antidepressant sales on suicide rates.

Science.gov (United States)

Kapusta, N D; Niederkrotenthaler, T; Etzersdorfer, E; Voracek, M; Dervic, K; Jandl-Jager, E; Sonneck, G

2009-03-01

Antidepressant sales and suicide rates have been shown to be correlated in industrialized countries. The aim was to study the possible effects of psychotherapy utilization on suicide rates. We assessed the impact of antidepressant sales and psychotherapist density on suicide rates between 1991 and 2005. To adjust for serial correlation in time series, three first-order autoregressive models adjusted for per capita alcohol consumption and unemployment rates were employed. Antidepressant sales and the density of psychotherapists in the population were negatively associated with suicide rates. This study provides evidence that decreasing suicide rates were associated with both increasing antidepressant sales and an increasing density of psychotherapists. The decrease of suicide rates could reflect a general improvement in mental health care rather than being caused by antidepressant sales or psychotherapist density alone.

Antidepressants during pregnancy, risks for mother and child

NARCIS (Netherlands)

Ververs, F.F.T.

2009-01-01

The use of antidepressant drugs during pregnancy is increasing without firm evidence on safety or efficacy. When managing depression and anxiety with antidepressants, the expected benefits must outweigh the risks. For health care processionals it is difficult to balance the benefits against the

Duloxetine versus other anti-depressive agents for depression

Science.gov (United States)

Cipriani, Andrea; Koesters, Markus; Furukawa, Toshi A; Nosè, Michela; Purgato, Marianna; Omori, Ichiro M; Trespidi, Carlotta; Barbui, Corrado

2014-01-01

Background Although pharmacological and psychological interventions are both effective for major depression, in primary and secondary care settings antidepressant drugs remain the mainstay of treatment. Amongst antidepressants many different agents are available. Duloxetine hydrochloride is a dual reuptake inhibitor of serotonin and norepinephrine and has been licensed by the Food and Drug Administration in the US for major depressive disorder (MDD), generalised anxiety disorder, diabetic peripheral neuropathic pain, fibromyalgia and chronic musculoskeletal pain. Objectives To assess the evidence for the efficacy, acceptability and tolerability of duloxetine in comparison with all other antidepressant agents in the acute-phase treatment of major depression. Search methods MEDLINE (1966 to 2012), EMBASE (1974 to 2012), the Cochrane Collaboration Depression, Anxiety and Neurosis Controlled Trials Register and the Cochrane Central Register of Controlled Trials up to March 2012. No language restriction was applied. Reference lists of relevant papers and previous systematic reviews were hand-searched. Pharmaceutical company marketing duloxetine and experts in this field were contacted for supplemental data. Selection criteria Randomised controlled trials allocating patients with major depression to duloxetine versus any other antidepressive agent. Data collection and analysis Two review authors independently extracted data and a double-entry procedure was employed. Information extracted included study characteristics, participant characteristics, intervention details and outcome measures in terms of efficacy, acceptability and tolerability. Main results A total of 16 randomised controlled trials (overall 5735 participants) were included in this systematic review. Of these, three trials were unpublished. We found 11 studies (overall 3304 participants) comparing duloxetine with one selective serotonin reuptake inhibitor (SSRI) (six studies versus paroxetine, three studies

Atypical idiopathic inflammatory demyelinating lesions

DEFF Research Database (Denmark)

Wallner-Blazek, Mirja; Rovira, Alex; Fillipp, Massimo

2013-01-01

Atypical lesions of a presumably idiopathic inflammatory demyelinating origin present quite variably and may pose diagnostic problems. The subsequent clinical course is also uncertain. We, therefore, wanted to clarify if atypical idiopathic inflammatory demyelinating lesions (AIIDLs) can be class......Atypical lesions of a presumably idiopathic inflammatory demyelinating origin present quite variably and may pose diagnostic problems. The subsequent clinical course is also uncertain. We, therefore, wanted to clarify if atypical idiopathic inflammatory demyelinating lesions (AIIDLs) can...... be classified according to previously suggested radiologic characteristics and how this classification relates to prognosis. Searching the databases of eight tertiary referral centres we identified 90 adult patients (61 women, 29 men; mean age 34 years) with ≥1 AIIDL. We collected their demographic, clinical...

Poor guideline adherence in the initiation of antidepressant treatment in children and adolescents in the Netherlands : choice of antidepressant and dose

NARCIS (Netherlands)

de Vries, Ymkje Anna; de Jonge, Peter; Kalverdijk, Luuk; Bos, Jens H. J.; Schuiling-Veninga, Catharina C. M.; Hak, Eelko

2016-01-01

The Dutch guideline for the treatment of depression in young people recommends initiating antidepressant treatment with fluoxetine, as the evidence for its efficacy is strongest and the risk of suicidality may be lower than with other antidepressants. Furthermore, low starting doses are recommended.

Generic penetration in the retail antidepressant market.

Science.gov (United States)

Ventimiglia, Jeffrey; Kalali, Amir H

2010-06-01

In this article, we explore the accelerated penetration of generic antidepressants in the United States market following the availability of generic citalopram and sertraline. Analysis suggests that overall, generic penetration into the antidepressant market has grown from approximately 41 percent in January 2004 to over 73 percent in January 2010. Similar trends are uncovered when branded and generic prescriptions are analyzed by specialty.

Mechanisms Underlying the Antidepressant Response and Treatment Resistance

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Marjorie Rose Levinstein

2014-06-01

Full Text Available Depression is a complex and heterogeneous disorder affecting millions of Americans. There are several different medications and other treatments that are available and effective for many patients with depression. However, a substantial percentage of patients fail to achieve remission with these currently available interventions, and relapse rates are high. Therefore, it is necessary to determine both the mechanisms underlying the antidepressant response and the differences between responders and non-responders to treatment. Delineation of these mechanisms largely relies on experiments that utilize animal models. Therefore, this review provides an overview of the various mouse models that are currently used to assess the antidepressant response, such as chronic mild stress, social defeat, and chronic corticosterone. We discuss how these mouse models can be used to advance our understanding of the differences between responders and non-responders to antidepressant treatment. We also provide an overview of experimental treatment modalities that are used for treatment-resistant depression, such as deep brain stimulation and ketamine administration. We will then review the various genetic polymorphisms and transgenic mice that display resistance to antidepressant treatment. Finally, we synthesize the published data to describe a potential neural circuit underlying the antidepressant response and treatment resistance.

Acute antidepressant drug administration and autobiographical memory recall

DEFF Research Database (Denmark)

Papadatou-Pastou, Marietta; Miskowiak, Kamilla W; Williams, J Mark G

2012-01-01

Antidepressants affect memory and neural responses to emotionally valenced stimuli in healthy volunteers. However, it is unclear whether this extends to autobiographical memory for personally experienced events. The current study investigated the effects of acute administration of the antidepress...... of reboxetine on emotional memory extends to recall of personally experienced events. Such effects may be relevant to the cognitive improvements found with recovery from depression and with the mechanism of action of contemporary antidepressant drugs.......Antidepressants affect memory and neural responses to emotionally valenced stimuli in healthy volunteers. However, it is unclear whether this extends to autobiographical memory for personally experienced events. The current study investigated the effects of acute administration...... in the processing of positive versus negative memories was reduced following reboxetine compared with placebo in the left frontal lobe (extending into the insula) and the right superior temporal gyrus. This was paired with increased memory speed in volunteers given reboxetine versus placebo. The effect...

Effects of Calcium Channel Blockers on Antidepressant Action of Alprazolam and Imipramine

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Gorash ZM

2007-01-01

Full Text Available Alprazolam is effective as an anxiolytic and in the adjunct treatment of depression. In this study, the effects of calcium channel antagonists on the antidepressant action of alprazolam and imipramine were investigated. A forced swimming maze was used to study behavioral despair in albino mice. Mice were divided into nine groups (n = 7 per group. One group received a single dose of 1% Tween 80; two groups each received a single dose of the antidepressant alone (alprazolam or imipramine; two groups each received a single dose of the calcium channel blocker (nifedipine or verapamil; four groups each received a single dose of the calcium channel blocker followed by a single dose of the antidepressant (with same doses used for either in the previous four groups. Drug administration was performed concurrently on the nine groups. Our data confirmed the antidepressant action of alprazolam and imipramine. Both nifedipine and verapamil produced a significant antidepressant effect (delay the onset of immobility when administered separately. Verapamil augmented the antidepressant effects of alprazolam and imipramine (additive antidepressant effect. This may be due to the possibility that verapamil might have antidepressant-like effect through different mechanism. Nifedipine and imipramine combined led to a delay in the onset of immobility greater than their single use but less than the sum of their independent administration. This may be due to the fact that nifedipine on its own might act as an antidepressant but blocks one imipramine mechanism that depends on L-type calcium channel activation. Combining nifedipine with alprazolam produced additional antidepressant effects, which indicates that they exert antidepressant effects through different mechanisms.

Optimal antidepressant dosing. Practical framework for selection, titration, and duration of therapy.

Science.gov (United States)

Nielsen, J W; Witek, M W; Hurwitz, S

2000-10-01

Appropriate antidepressant dosing and trial duration are crucial for successful treatment of depression. Before prescribing an antidepressant, primary care physicians should take into account each patient's history, responses to previous antidepressants, depressive symptoms, coexisting illnesses, and current prescriptions. Physicians must be able to help patients manage side effects and know when to discontinue treatment, switch antidepressants, or refer patients to a psychiatrist.

Is Customization in Antidepressant Prescribing Associated with Acute-Phase Treatment Adherence?

Science.gov (United States)

Merrick, Elizabeth L; Hodgkin, Dominic; Panas, Lee; Soumerai, Stephen B; Ritter, Grant

2012-03-01

OBJECTIVES: The objective was to explore whether prescribing variation is associated with duration of antidepressant use during the acute phase of treatment. Improving quality of care and increasing the extent to which treatment is patient-centered and customized are interrelated goals. Prescribing variation may be considered a marker of customization, and could be associated with better antidepressant treatment adherence. METHODS: A cross-sectional secondary data analysis examining the association between providers' antidepressant prescribing variation and patient continuity of antidepressant treatment. The data source was two states' Medicaid claims for dual-eligible Medicaid/Medicare patients. The sample included 383 patients with new episodes of antidepressant treatment, representing 70 providers with at least four patients in the sample. We tested two alternate measures of prescribing concentration: 1) share of prescriber's initial antidepressant prescribing accounted for by the two most common regimens, and 2) Herfindahl index. The HEDIS performance measure of effective acute-phase treatment (at least 84 out of 114 days with antidepressant) was the dependent variable. KEY FINDINGS: In multivariate analyses, the concentration measure based on the top two regimens was significant and inversely related to duration adequacy (p customized care.

Stimulation of entorhinal cortex-dentate gyrus circuitry is antidepressive.

Science.gov (United States)

Yun, Sanghee; Reynolds, Ryan P; Petrof, Iraklis; White, Alicia; Rivera, Phillip D; Segev, Amir; Gibson, Adam D; Suarez, Maiko; DeSalle, Matthew J; Ito, Naoki; Mukherjee, Shibani; Richardson, Devon R; Kang, Catherine E; Ahrens-Nicklas, Rebecca C; Soler, Ivan; Chetkovich, Dane M; Kourrich, Saïd; Coulter, Douglas A; Eisch, Amelia J

2018-04-16

Major depressive disorder (MDD) is considered a 'circuitopathy', and brain stimulation therapies hold promise for ameliorating MDD symptoms, including hippocampal dysfunction. It is unknown whether stimulation of upstream hippocampal circuitry, such as the entorhinal cortex (Ent), is antidepressive, although Ent stimulation improves learning and memory in mice and humans. Here we show that molecular targeting (Ent-specific knockdown of a psychosocial stress-induced protein) and chemogenetic stimulation of Ent neurons induce antidepressive-like effects in mice. Mechanistically, we show that Ent-stimulation-induced antidepressive-like behavior relies on the generation of new hippocampal neurons. Thus, controlled stimulation of Ent hippocampal afferents is antidepressive via increased hippocampal neurogenesis. These findings emphasize the power and potential of Ent glutamatergic afferent stimulation-previously well-known for its ability to influence learning and memory-for MDD treatment.

Continued antidepressant treatment and suicide in patients with depressive disorder

DEFF Research Database (Denmark)

Søndergård, Lars; Lopez, Ana Garcia; Andersen, Per Kragh

2007-01-01

1995 to 2000, we investigated the relation between continued treatment with antidepressants and suicide in a population of all patients discharged from hospital psychiatry with a diagnosis of depressive disorder. Patients discharged from hospital psychiatry with a diagnosis of depressive disorder had...... of prescriptions. On individualized data from a cohort of patients with a known history of depressive disorder, continued antidepressant treatment was associated with reduced risk of suicide.......Antidepressant use in Denmark, as in many developed countries, has substantially increased during recent years, coinciding with a decreasing suicide rate. In a nationwide observational cohort study with linkage of registers of all prescribed antidepressants and recorded suicides in Denmark from...

Hippocampal Neurogenesis, Depressive Disorders, and Antidepressant Therapy

Directory of Open Access Journals (Sweden)

Eleni Paizanis

2007-01-01

Full Text Available There is a growing body of evidence that neural stem cells reside in the adult central nervous system where neurogenesis occurs throughout lifespan. Neurogenesis concerns mainly two areas in the brain: the subgranular zone of the dentate gyrus in the hippocampus and the subventricular zone, where it is controlled by several trophic factors and neuroactive molecules. Neurogenesis is involved in processes such as learning and memory and accumulating evidence implicates hippocampal neurogenesis in the physiopathology of depression. We herein review experimental and clinical data demonstrating that stress and antidepressant treatments affect neurogenesis in opposite direction in rodents. In particular, the stimulation of hippocampal neurogenesis by all types of antidepressant drugs supports the view that neuroplastic phenomena are involved in the physiopathology of depression and underlie—at least partly—antidepressant therapy.

Antidepressant therapy in epilepsy: can treating the comorbidities affect the underlying disorder?

Science.gov (United States)

Cardamone, L; Salzberg, MR; O'Brien, TJ; Jones, NC

2013-01-01

There is a high incidence of psychiatric comorbidity in people with epilepsy (PWE), particularly depression. The manifold adverse consequences of comorbid depression have been more clearly mapped in recent years. Accordingly, considerable efforts have been made to improve detection and diagnosis, with the result that many PWE are treated with antidepressant drugs, medications with the potential to influence both epilepsy and depression. Exposure to older generations of antidepressants (notably tricyclic antidepressants and bupropion) can increase seizure frequency. However, a growing body of evidence suggests that newer (‘second generation’) antidepressants, such as selective serotonin reuptake inhibitors or serotonin-noradrenaline reuptake inhibitors, have markedly less effect on excitability and may lead to improvements in epilepsy severity. Although a great deal is known about how antidepressants affect excitability on short time scales in experimental models, little is known about the effects of chronic antidepressant exposure on the underlying processes subsumed under the term ‘epileptogenesis’: the progressive neurobiological processes by which the non-epileptic brain changes so that it generates spontaneous, recurrent seizures. This paper reviews the literature concerning the influences of antidepressants in PWE and in animal models. The second section describes neurobiological mechanisms implicated in both antidepressant actions and in epileptogenesis, highlighting potential substrates that may mediate any effects of antidepressants on the development and progression of epilepsy. Although much indirect evidence suggests the overall clinical effects of antidepressants on epilepsy itself are beneficial, there are reasons for caution and the need for further research, discussed in the concluding section. PMID:23146067

Studies on polynuclear furoquinones. Part 1: Synthesis of tri- and tetra-cyclic furoquinones simulating BCD/ABCD ring system of furoquinone diterpenoids

Directory of Open Access Journals (Sweden)

Faruk H. Shaik

2009-09-01

Full Text Available Synthesis of phenanthro[1,2-b]furan-10,11-dione, the core nucleus present in Tanshinone-I is described in 8–10 steps starting from 2-bromo-3,4-dihydro-1-naphthaldehyde. The bromoaldehyde was converted to methyl 2-(2-bromo-1-naphthylacetate or 2-(2-bromo-1-naphthylacetonitrile following the protocol of functional group transformations. Subsequent Suzuki coupling of this ester/nitrile derivative with furan-2-boronic acid produced [2-(2-furyl-1-naphthyl]acetic ester/nitrile which on hydrolysis furnished the corresponding acid derivative. Cyclization of the acid followed by oxidation of the phenol, with Fremy’s salt, produced the tetra-cyclic furoquinone, phenanthro[1,2-b]furan-10,11-dione. This method has also been extended for the synthesis of the tricyclic furoquinone, naphtho[1,2-b]furan-4,5-dione.

Antidepressants and Weight Gain

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... 2015;37:46. Blumenthal SR, et al. An electronic health records study of long-term weight gain following antidepressant ... your agreement to the Terms and Conditions and Privacy Policy linked below. Terms and Conditions Privacy Policy ...

Use of antidepressants in dentistry: A systematic review.

Science.gov (United States)

Lino, P A; Martins, C C; Miranda, Gfpc; de Souza E Silva, M E; de Abreu, Mhng

2017-08-24

Previous research has suggested that antidepressants can be used in oral health care. The aim of this systematic review was to search for scientific evidence of the efficacy of the use of antidepressants in dentistry. The clinical question was as follows (PICO question): dentistry patients (Patients); antidepressants (Intervention); no use or placebo or other drug (Comparison); and efficacy in oral health problems (Outcome). An electronic search was conducted in seven databases, as well as a manual search without restriction regarding language and date of publication. Two independent reviewers selected studies based on eligibility criteria, extracted data and assessed methodological quality based on the PEDro scale. The PROSPERO record is number CRD42016037442. A total of 15 randomized controlled trials were associated with the use of antidepressants to control chronic or acute pain in dentistry, among other conditions such as bruxism and burning mouth syndrome. The most commonly used drug in clinical trials was amitriptyline (more than 50% of studies). Antidepressants may be effective in dentistry for acute and chronic pain, but there is a large amount of methodological heterogeneity among the evaluated studies. In summary, there is rationality for the indication of this class of medicine in dentistry in specific clinical situations. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd. All rights reserved.

Antidepressant medication and the risk of pregnancy-induced hypertension

NARCIS (Netherlands)

Ter Heijne, Loes F.; Zakiyah, Neily; Bos, Jens H.J.; Hak, Eelko; Schuiling-Veninga, Catharina C.M.

2016-01-01

Background: Increased activity of the sympatic nervous system could possibly cause pregnancy-induced hypertension (PIH). Previous studies have suggested that antidepressants could contribute to this increased activity. Objectives: To examine whether the use of antidepressants during pregnancy

Antidepressant use during pregnancy and asthma in the offspring

DEFF Research Database (Denmark)

Liu, Xiaoqin; Olsen, Jørn; Pedersen, Lars Henning

2015-01-01

in the offspring. METHODS: A cohort study was performed among all live singletons born in Denmark between 1996 and 2007. Mothers who had a diagnosis of depressive disorder and/or who used antidepressants 1 year before or during the index pregnancy were identified. Using a Cox proportional hazards regression model...... or use of antidepressants 1 year before or during pregnancy). Prenatal maternal depression was associated with childhood asthma (HR: 1.25 [95% confidence interval (CI): 1.20–1.30]). Overall, 8895 children were exposed to antidepressants in utero. Compared with children born to mothers with prenatal......BACKGROUND AND OBJECTIVES: It has been suggested that maternal depression during pregnancy is abstract associated with asthma in the offspring, but the role of medical treatment of depression is not known. Our goal was to examine whether prenatal antidepressant use increases the risk of asthma...

nfluence of antidepressants on glucose homeostasis : effects and mechanisms

NARCIS (Netherlands)

Derijks, H.J.

2009-01-01

Depression has shown to be a common morbidity in patients with diabetes mellitus and comorbid depression in diabetes mellitus patients is frequently treated with antidepressants. It has been postulated that antidepressants may interfere with glucose homeostasis and that the interference of

Depression, Antidepressants, and Neurogenesis: A Critical Reappraisal

Science.gov (United States)

Hanson, Nicola D; Owens, Michael J; Nemeroff, Charles B

2011-01-01

The neurogenesis hypothesis of depression posits (1) that neurogenesis in the subgranular zone of the dentate gyrus is regulated negatively by stressful experiences and positively by treatment with antidepressant drugs and (2) that alterations in the rate of neurogenesis play a fundamental role in the pathology and treatment of major depression. This hypothesis is supported by important experimental observations, but is challenged by equally compelling contradictory reports. This review summarizes the phenomenon of adult hippocampal neurogenesis, the initial and continued evidence leading to the development of the neurogenesis hypothesis of depression, and the recent studies that have disputed and/or qualified those findings, to conclude that it can be affected by stress and antidepressants under certain conditions, but that these effects do not appear in all cases of psychological stress, depression, and antidepressant treatment. PMID:21937982

Warfarin: pharmacological profile and drug interactions with antidepressants

Directory of Open Access Journals (Sweden)

Juliana Souto Teles

2012-03-01

Full Text Available Oral anticoagulants are among the drugs with the greatest numberof drug interactions. The concomitant use of several medications isa common practice in patients with cardiovascular problems, whooften also present with depression; therefore, the probability of aninteraction occurring between warfarin and the antidepressants ishigh, and may result in increased or decreased anticoagulant activity.Since the possible interactions between these two classes of drugshave been poorly explored in literature, with a risk to the patients who use them, we reviewed the pharmacology of warfarin and its possible interactions with antidepressants. Of the antidepressants analyzed, those that showed relevant effects on the interaction with warfarin were, in decreasing order: paroxetine, venlafaxine, fluoxetine, and duloxetine.

Antidepressant exposure during early pregnancy and congenital malformations

DEFF Research Database (Denmark)

Pedersen, Lars Henning

are reassuring, however, an association with heart malformations has been suggested for e.g. paroxetine. A potential biological explanation will be reviewed. The potential teratogenic potential of antidepressants needs to be balanced against the obvious problems associated with under-treated maternal depression......Pharmacological treatment of pregnant women with depression is hampered by concerns for the developing fetus. The presentation will summarize existing knowledge on the potential association between antidepressants and congenital malformations, elaborate on the scientific background, and discuss...... the clinical significance. Most information on malformations in humans is derived from epidemiological studies. The strengths and limitations of the different designs need careful consideration, including issues of confounding by indication, recall bias, and power. For most antidepressants existing data...

Antidepressant Use and Risk of Out-of-Hospital Cardiac Arrest

DEFF Research Database (Denmark)

Weeke, P; Jensen, Aksel Karl Georg; Folke, F

2012-01-01

being the most frequently used type of antidepressant (50.8%). Tricyclic antidepressants (TCAs; odds ratio (OR) = 1.69, confidence interval (CI): 1.14-2.50) and selective serotonin reuptake inhibitors (SSRIs; OR = 1.21, CI: 1.00-1.47) were both associated with comparable increases in risk of OHCA.......17-12.2). An association between cardiac arrest and antidepressant use could be documented in both the SSRI and TCA classes of drugs....

Perianal atypical leiomyoma: A case report.

Science.gov (United States)

Sun, Pingliang; Ou, Hailing; Huang, Shen; Wei, Longxiang; Zhang, Sen; Liu, Jiali; Geng, Shuguang; Yang, Kun

2017-12-01

Reports on perianal atypical leiomyoma, a perianal tumor, are rare. We confirmed a perianal atypical leiomyoma by its clinical presentation, magnetic resonance imaging findings, and immunohistochemistry. A 28-year-old female with a perianal mass found more than 4 years ago. The 5cm_4cm_4cm sized mass was located on the left side of the anus and vagina; The magnetic resonance imaging (MRI) scan revealed: A 4.1cm × 5.2cm × 4.9cm sized round mass was observed on the left side of the circumference. Perianal atypical leiomyoma. anal peripheral mass resection was performed under lumbar anesthesia. The postoperative course was uneventful, healing, the patient was discharged. Perianal atypical leiomyomas are benign tumors, but with the clinically atypical leiomyoma, it is sometimes difficult to distinguish between potential malignant smooth muscle tumors,and there may be malignant changes. Surgery should ensure complete resection, and to avoid postoperative recurrence, there should be a regular follow-up.

Increase in antidepressant medication in the US adult population between 1990 and 2003.

Science.gov (United States)

Mojtabai, Ramin

2008-01-01

The rate of antidepressant treatment in the US has significantly increased in the past decade. There are, however, concerns about undertreatment among traditionally underserved groups and overtreatment in less severely ill individuals. This study examines trends in the prevalence of antidepressant drug treatment in two US general population surveys. The prevalence of antidepressant treatment within a 12-month period was compared in the US National Comorbidity Survey (1990-1992) and the National Comorbidity Survey-Replication (2001-2003). Variations in trends across groups were examined using bivariate and multivariate logistic regression models. The rate of antidepressant drug treatment increased more than four times between early 1990s and early 2000s. The trend was similar across sociodemographic groups. Younger adults, men and racial/ethnic minorities continued to receive antidepressant treatment at a lower rate compared to middle-aged adults, women and non-Hispanic whites, respectively. The rate of antidepressant treatment increased more in the group of less severely ill individuals than in those with more severe psychopathology. Sociodemographic disparities in antidepressant treatment persisted over the last decade in the US, lending support to concerns about undertreatment among traditionally underserved groups, whereas the greater increase in the rate of antidepressant treatment in the less severely ill group lends support to concerns about antidepressant overtreatment in this population.

Risks for oral health with the use of antidepressants

NARCIS (Netherlands)

Peeters, FPML; deVries, MW; Vissink, A

In this article, attention is focused on ornl pathology, particularly dental caries, caused by hyposalivation as a consequence of (long-term) use of antidepressants. Changes in clinical psychiatric practice and increasing numbers of presciptions of antidepressants in primary care and specialty care

Increased use of antidepressants at the end of life

DEFF Research Database (Denmark)

Hansen, Dorte Gilså; Rosholm, Jens-Ulrik; Gichangi, Anthony

2007-01-01

of antidepressants increases steadily over time in all age groups. Among the 65+ year-olds it also increases with age and differs substantially between the youngest and the oldest. Very high prevalences are observed: 26.8% among females 85-89 years old and 17.5% among males 85 years and above in 2004. In all age......BACKGROUND: The new antidepressants are generally effective and safe for older people, but may have serious side-effects. The use has been rapidly increasing, but focus on upper age groups has been limited. The pattern of antidepressant use as death approaches has never been analysed. OBJECTIVE......: To analyse the use of antidepressants among individuals aged 65 years and above with respect to time trends, age and proximity to death. DESIGN: Population-based prescription study. SETTING: The County of Funen, Denmark, 1992-2004 (approximately 470,000 inhabitants). RESULTS: The 1-year prevalence...

Antidepressant treatment of depression in rural nursing home residents.

Science.gov (United States)

Kerber, Cindy Sullivan; Dyck, Mary J; Culp, Kennith R; Buckwalter, Kathleen

2008-09-01

Under-diagnosis and under-treatment of depression are major problems in nursing home residents. The purpose of this study was to determine antidepressant use among nursing home residents who were diagnosed with depression using three different methods: (1) the Geriatric Depression Scale, (2) Minimum Data Set, and (3) primary care provider assessments. As one would expect, the odds of being treated with an antidepressant were about eight times higher for those diagnosed as depressed by the primary care provider compared to the Geriatric Depression Scale or the Minimum Data Set. Men were less likely to be diagnosed and treated with antidepressants by their primary care provider than women. Depression detected by nurses through the Minimum Data Set was treated at a lower rate with antidepressants, which generates issues related to interprofessional communication, nursing staff communication, and the need for geropsychiatric role models in nursing homes.

Antidepressant induced excessive yawning and indifference

Directory of Open Access Journals (Sweden)

Bruno Palazzo Nazar

2015-03-01

Full Text Available Introduction Antidepressant induced excessive yawning has been described as a possible side effect of pharmacotherapy. A syndrome of indifference has also been described as another possible side effect. The frequency of those phenomena and their physiopathology are unknown. They are both considered benign and reversible after antidepressant discontinuation but severe cases with complications as temporomandibular lesions, have been described. Methods We report two unprecedented cases in which excessive yawning and indifference occurred simultaneously as side effects of antidepressant therapy, discussing possible physiopathological mechanisms for this co-occurrence. Case 1: A male patient presented excessive yawning (approximately 80/day and apathy after venlafaxine XR treatment. Symptoms reduced after a switch to escitalopram, with a reduction to 50 yawns/day. Case 2: A female patient presented excessive yawning (approximately 25/day and inability to react to environmental stressors with desvenlafaxine. Conclusion Induction of indifference and excessive yawning may be modulated by serotonergic and noradrenergic mechanisms. One proposal to unify these side effects would be enhancement of serotonin in midbrain, especially paraventricular and raphe nucleus.

The role of dopamine and norepinephrine in depression and antidepressant treatment.

Science.gov (United States)

Nutt, David J

2006-01-01

Most antidepressants in use today are descendants of the monoamine oxidase inhibitor iproniazid and the tricyclic agent imipramine. These agents were both originally developed for other indications but then were serendipitously determined to have antidepressant effects. Elucidation of the mechanisms of action of these first antidepressants, along with those of reserpine and amphetamine, led to the monoamine theories of depression. Through the past several decades, approaches undertaken to clarify the roles of the neurotransmitters norepinephrine, dopamine, and serotonin in depression have included animal studies, human biological and postmortem studies, inferences drawn from antidepressant drug actions, and challenge or depletion studies; most recently, brain imaging studies have proved to be especially informative. This research has identified novel potential targets, with the goal of developing new antidepressant drugs with better efficacy and faster onset of action than current "gold-standard" treatments.

Efficacy of antidepressants on orofacial pain: a systematic review

NARCIS (Netherlands)

Martin, W.J.J.M.; Perez, R.S.G.M.; Tuinzing, D.B.; Forouzanfar, T.

2012-01-01

Orofacial pain is a common complaint with multiple diagnoses. There is controversy about the effectiveness of antidepressants for the management of orofacial pain disorders. In order to be able to make a best evidence choice between available antidepressants for the treatment of orofacial pain, a

Harmane induces anxiolysis and antidepressant-like effects in rats.

Science.gov (United States)

Aricioglu, Feyza; Altunbas, Hale

2003-12-01

A forced swim test (FST) and an elevated plus maze (EPM) were used to determine antidepressant and anxiolytic effects of harmane in rats in comparison with a known antidepressant, imipramine (30 mg/kg i.p.). Harmane (2.5, 5.0, or 10 mg/kg, i.p.), saline, or imipramine were given 30 minutes before the tests. Administration of harmane decreased the time of immobility in the FST dose-dependently and increased the time spent in open arms in the EPM, as compared with the saline group. As an endogenous substance, harmane therefore has anti-anxiety and antidepressant effects.

Citalopram versus other anti-depressive agents for depression

Science.gov (United States)

Cipriani, Andrea; Purgato, Marianna; Furukawa, Toshi A; Trespidi, Carlotta; Imperadore, Giuseppe; Signoretti, Alessandra; Churchill, Rachel; Watanabe, Norio; Barbui, Corrado

2014-01-01

Background Recent US and UK clinical practice guidelines recommend that second-generation antidepressants should be considered amongst the best first-line options when drug therapy is indicated for a depressive episode. Systematic reviews have already highlighted some differences in efficacy between second-generation antidepressants. Citalopram, one of the first selective serotonin reuptake inhibitors (SSRI) introduced in the market, is one of these antidepressant drugs that clinicians use for routine depression care. Objectives To assess the evidence for the efficacy, acceptability and tolerability of citalopram in comparison with tricyclics, heterocyclics, other SSRIs and other conventional and non-conventional antidepressants in the acute-phase treatment of major depression. Search methods We searched The Cochrane Collaboration Depression, Anxiety and Neurosis Controlled Trials Register and the Cochrane Central Register of Controlled Trials up to February 2012. No language restriction was applied. We contacted pharmaceutical companies and experts in this field for supplemental data. Selection criteria Randomised controlled trials allocating patients with major depression to citalopram versus any other antidepressants. Data collection and analysis Two reviewers independently extracted data. Information extracted included study characteristics, participant characteristics, intervention details and outcome measures in terms of efficacy (the number of patients who responded or remitted), patient acceptability (the number of patients who failed to complete the study) and tolerability (side-effects). Main results Thirty-seven trials compared citalopram with other antidepressants (such as tricyclics, heterocyclics, SSRIs and other antidepressants, either conventional ones, such as mirtazapine, venlafaxine and reboxetine, or non-conventional, like hypericum). Citalopram was shown to be significantly less effective than escitalopram in achieving acute response (odds

Antidepressants during pregnancy and autism in offspring: population based cohort study.

Science.gov (United States)

Rai, Dheeraj; Lee, Brian K; Dalman, Christina; Newschaffer, Craig; Lewis, Glyn; Magnusson, Cecilia

2017-07-19

Objectives  To study the association between maternal use of antidepressants during pregnancy and autism spectrum disorder (ASD) in offspring. Design  Observational prospective cohort study with regression methods, propensity score matching, sibling controls, and negative control comparison. Setting  Stockholm County, Sweden. Participants  254 610 individuals aged 4-17, including 5378 with autism, living in Stockholm County in 2001-11 who were born to mothers who did not take antidepressants and did not have any psychiatric disorder, mothers who took antidepressants during pregnancy, or mothers with psychiatric disorders who did not take antidepressants during pregnancy. Maternal antidepressant use was recorded during first antenatal interview or determined from prescription records. Main outcome measure  Offspring diagnosis of autism spectrum disorder, with and without intellectual disability. Results  Of the 3342 children exposed to antidepressants during pregnancy, 4.1% (n=136) had a diagnosis of autism compared with a 2.9% prevalence (n=353) in 12 325 children not exposed to antidepressants whose mothers had a history of a psychiatric disorder (adjusted odds ratio 1.45, 95% confidence interval 1.13 to 1.85). Propensity score analysis led to similar results. The results of a sibling control analysis were in the same direction, although with wider confidence intervals. In a negative control comparison, there was no evidence of any increased risk of autism in children whose fathers were prescribed antidepressants during the mothers' pregnancy (1.13, 0.68 to 1.88). In all analyses, the risk increase concerned only autism without intellectual disability. Conclusions  The association between antidepressant use during pregnancy and autism, particularly autism without intellectual disability, might not solely be a byproduct of confounding. Study of the potential underlying biological mechanisms could help the understanding of modifiable mechanisms in the

Computerized tomography in atypical Pott's disease

International Nuclear Information System (INIS)

Cabrera, M.N.B.; Wang, E.H.M.

1993-01-01

Classical Pott's disease is described as a two-vertebrae disease with the destruction of the intervening invertebral disc. Computerized tomography has been used in the differential diagnosis of spine infections and neoplasms. We reviewed CT scans of patients seen at the Philippine General Hospital over a two-year period with atypical presentations of atypical tuberculous spondylitis. We used the computerized tomography findings described as characteristic of classical Pott's disease as criteria in evaluating the CT scans of patients diagnosed to have Atypical Pott's Disease. Although the number of patients prevented sensitivity and specificity studies to be done, our results strongly suggest that the same CT criteria used to diagnose Classical Pott's Disease may also be used to diagnose Pott's disease in its atypical form. (Author.). 13 refs

Tracing the associations between sex, the atypical and the combined atypical-melancholic depression subtypes: A path analysis.

Science.gov (United States)

Rodgers, Stephanie; Vandeleur, Caroline L; Ajdacic-Gross, Vladeta; Aleksandrowicz, Aleksandra A; Strippoli, Marie-Pierre F; Castelao, Enrique; Glaus, Jennifer; Lasserre, Aurélie M; Müller, Mario; Rössler, Wulf; Angst, Jules; Preisig, Martin

2016-01-15

Numerous studies have examined determinants leading to preponderance of women in major depressive disorder (MDD), which is particularly accentuated for the atypical depression subtype. It is thus of interest to explore the specific indirect effects influencing the association between sex and established depression subtypes. The data of 1624 subjects with a lifetime diagnosis of MDD derived from the population-based PsyCoLaus data were used. An atypical (n=256), a melancholic (n=422), a combined atypical and melancholic features subtype (n=198), and an unspecified MDD group (n=748) were constructed according to the DSM-IV specifiers. Path models with direct and indirect effects were applied to the data. Partial mediation of the female-related atypical and combined atypical-melancholic depression subtypes was found. Early anxiety disorders and high emotion-orientated coping acted as mediating variables between sex and the atypical depression subtype. In contrast, high Body Mass Index (BMI) served as a suppression variable, also concerning the association between sex and the combined atypical-melancholic subtype. The latter association was additionally mediated by an early age of MDD onset and early/late anxiety disorders. The use of cross-sectional data does not allow causal conclusions. This is the first study that provides evidence for a differentiation of the general mechanisms explaining sex differences of overall MDD by depression subtypes. Determinants affecting the pathways begin early in life. Since some of them are primarily of behavioral nature, the present findings could be a valuable target in mental health care. Copyright © 2015 Elsevier B.V. All rights reserved.

Antidepressant-Like Effect of Isorhynchophylline in Mice.

Science.gov (United States)

Xian, Yan-Fang; Fan, Ding; Ip, Siu-Po; Mao, Qing-Qiu; Lin, Zhi-Xiu

2017-02-01

Isorhynchophylline (IRN), an oxindole alkaloid, has been identified as the main active ingredient responsible for the biological activities of Uncaria rhynchophylla (Miq) Miq ex Havil. (Rubiaceae). Previous studies in our laboratory have revealed that IRN possesses potent neuroprotective effects in different models of Alzheimer's disease. However, the antidepressant-like effects of IRN are remained unclear. The present study aims to evaluate the antidepressant-like effects of IRN. The antidepressant-like effects of IRN was determined by using animal models of depression including forced swimming and tail suspension tests. The acting mechanism was explored by determining the effect of IRN on the levels of monoamine neurotransmitters and the activities of monoamine oxidases. Intragastric administration of IRN at 10, 20 and 40 mg/kg for 7 days caused a significant reduction of immobility time in both forced swimming and tail suspension tests, while IRN did not stimulate locomotor activity in the open-field test. In addition, IRN treatment antagonized reserpine-induced ptosis and significantly enhanced the levels of monoamine neurotransmitters including norepinephrine (NE) and 5-hydroxytryptamine (5-HT), and the activity of monoamine oxidase A (MAO-A) in the hippocampus and frontal cortex of mice. These results suggest that the antidepressant-like effects of IRN are mediated, at least in part, by the inhibition of monoamine oxidases.

Antidepressant medications and osteoporosis

DEFF Research Database (Denmark)

Rizzoli, R; Cooper, C; Reginster, J-Y

2012-01-01

Use of antidepressant medications that act on the serotonin system has been linked to detrimental impacts on bone mineral density (BMD), and to osteoporosis. This article reviews current evidence for such effects, and identifies themes for future research. Serotonin receptors are found in all major...

Antidepressants for bipolar disorder A meta-analysis of randomized, double-blind, controlled trials

Institute of Scientific and Technical Information of China (English)

Yingli Zhang; Huan Yang; Shichang Yang; Wei Liang; Ping Dai; Changhong Wang; Yalin Zhang

2013-01-01

OBJECTIVE: To examine the efficacy and safety of short-term and long-term use of antidepres-sants in the treatment of bipolar disorder. DATA SOURCES:A literature search of randomized, double-blind, control ed trials published until December 2012 was performed using the PubMed, ISI Web of Science, Medline and Cochrane Central Register of Control ed Trials databases. The keywords“bipolar disorder, bipolar I disorder, bipolar II disorder, bipolar mania, bipolar depression, cyclothymia, mixed mania and depression, rapid cycling and bipolar disorder”, AND “antidepressant agent, antidepressive agents second-generation, antidepressive agents tricyclic, monoamine oxidase inhibitor, noradrenaline uptake in-hibitor, serotonin uptake inhibitor, and tricyclic antidepressant agent” were used. The studies that were listed in the reference list of the published papers but were not retrieved in the above-mentioned databases were supplemented. STUDY SELECTION: Studies selected were double-blind randomized control ed trials assessing the efficacy and safety of antidepressants in patients with bipolar disorder. Al participants were aged 18 years or older, and were diagnosed as having primary bipolar disorder. Antidepressants or antidepressants combined with mood stabilizers were used in experimental interventions. Placebos, mood stabilizers, antipsychotics and other antide pressants were used in the control interventions. Studies that were quasi-randomized studies, or used antidepressants in combination with antipsy-chotics in the experimental group were excluded. Al analyses were conducted using Review Man-ager 5.1 provided by the Cochrane Col aboration. MAIN OUTCOME MEASURES:The primary outcome was the response and switching to mania. The secondary outcomes included remission, discontinuation rate, and suicidality. RESULTS: Among 5 001 treatment studies published, 14 double-blind randomized control ed trials involving 1 244 patients were included in the meta

Involvement of sigma-1 receptors in the antidepressant-like effects of dextromethorphan.

Science.gov (United States)

Nguyen, Linda; Robson, Matthew J; Healy, Jason R; Scandinaro, Anna L; Matsumoto, Rae R

2014-01-01

Dextromethorphan is an antitussive with a high margin of safety that has been hypothesized to display rapid-acting antidepressant activity based on pharmacodynamic similarities to the N-methyl-D-aspartate (NMDA) receptor antagonist ketamine. In addition to binding to NMDA receptors, dextromethorphan binds to sigma-1 (σ1) receptors, which are believed to be protein targets for a potential new class of antidepressant medications. The purpose of this study was to determine whether dextromethorphan elicits antidepressant-like effects and the involvement of σ1 receptors in mediating its antidepressant-like actions. The antidepressant-like effects of dextromethorphan were assessed in male, Swiss Webster mice using the forced swim test. Next, σ1 receptor antagonists (BD1063 and BD1047) were evaluated in conjunction with dextromethorphan to determine the involvement of σ receptors in its antidepressant-like effects. Quinidine, a cytochrome P450 (CYP) 2D6 inhibitor, was also evaluated in conjunction with dextromethorphan to increase the bioavailability of dextromethorphan and reduce exposure to additional metabolites. Finally, saturation binding assays were performed to assess the manner in which dextromethorphan interacts at the σ1 receptor. Our results revealed dextromethorphan displays antidepressant-like effects in the forced swim test that can be attenuated by pretreatment with σ1 receptor antagonists, with BD1063 causing a shift to the right in the dextromethorphan dose response curve. Concomitant administration of quinidine potentiated the antidepressant-like effects of dextromethorphan. Saturation binding assays revealed that a Ki concentration of dextromethorphan reduces both the Kd and the Bmax of [(3)H](+)-pentazocine binding to σ1 receptors. Taken together, these data suggest that dextromethorphan exerts some of its antidepressant actions through σ1 receptors.

Pregnancy and postpartum antidepressant use moderates the effects of sleep on depression.

Science.gov (United States)

Stone, Kristen C; Salisbury, Amy L; Miller-Loncar, Cynthia L; Mattera, Jennifer A; Battle, Cynthia L; Johnsen, Dawn M; O'Grady, Kevin E

2017-10-01

This study examined the course of antidepressant use, sleep quality, and depression severity from pregnancy through 6-month postpartum in women with and without a depressive disorder during pregnancy. Women (N = 215) were interviewed during pregnancy, 1- and 6-month postpartum. Mixed linear models were used to examine the longitudinal course and inter-relationships for the time-varying variables of antidepressant use, subjective sleep quality, and depression severity. Pregnant women with a depressive disorder who did not use antidepressants had more variable depression severity over time with improvements in depression severity by 6-month postpartum. In contrast, the depression severity of their medicated counterparts remained stable and high throughout. Pregnant women without a depressive disorder had worse sleep quality when using antidepressants compared with when they were not. Antidepressant use significantly strengthened the magnitude of the effect of sleep quality on depression severity in women with a depressive disorder during pregnancy. When prenatally depressed women use antidepressants, their sleep disturbance is more highly linked to depression severity than when they do not. Furthermore, antidepressants are not adequately treating the sleep disturbance of these women or their remitted counterparts, leaving both groups vulnerable to significant negative mental and physical health outcomes.

Body weight as a predictor of antidepressant efficacy in the GENDEP project

DEFF Research Database (Denmark)

Uher, Rudolf; Mors, Ole; Hauser, Joanna

2009-01-01

Background: Being overweight or obese may be associated with poor response to antidepressants. The present report explores the moderation of antidepressant response by body weight to establish the specificity to antidepressant mode of action, type of depressive symptoms and gender. Methods: Height....... The relationship between body weight and change in neurovegetative symptoms was moderated by gender with obese men responding less to nortriptyline and obese women having poorer response to both antidepressants. Limitations: As no placebo arm was included, the specificity of findings to antidepressants is relative...... and weight were measured in 797 men and women with major depression treated with escitalopram or nortriptyline for twelve weeks as part of the Genome Based Therapeutic Drugs for Depression (GENDEP) project. Body mass index (BMI) and obesity (BMI > 30) were tested as predictors of change in depressive...

FKBP5/FKBP51 enhances autophagy to synergize with antidepressant action

Science.gov (United States)

Gassen, Nils C; Hartmann, Jakob; Schmidt, Mathias V; Rein, Theo

2015-01-01

Levels of autophagy markers rise upon treatment of cells with antidepressants. However, it was not known whether this phenomenon might be linked to other antidepressant pathways or to any physiological effect. In this punctum, we summarize and discuss our recent findings that provide evidence for a role of the cochaperone FKBP5/FKBP51 (FK506 binding protein 5) in autophagy as a prerequisite for antidepressant action in cells, mice, and humans. FKBP5 associates with BECN1, changes its phosphorylation and protein levels and enhances markers of autophagy and autophagic flux. The effects of antidepressants on autophagy as well as their physiological effects in mice and human depend on FKBP5. PMID:25714272

Effect of antidepressants and neuroleptics on phosphoinositide turnover in human platelets

Energy Technology Data Exchange (ETDEWEB)

Pandey, S.C.; Davis, J.M.; Schwertz, D.; Pandey, G.N. (Illinois State Psychiatric Inst., Chicago (United States))

1990-02-26

The authors previously reported that tricyclic antidepressants and iprindole inhibit thrombin-stimulated formation of inositol-1, 4 bisphosphate (IP2) and inositol-1,4,5 triphosphate (IP3) but do not cause any change in inositol-1 phosphate (IP1). In order to examine if this decrease in IP2 and IP3 formation by antidepressants is related to the inhibition of the enzyme phospholipase C (PLC), the authors determined the effects of antidepressants and neuroleptics on the levels of 3(H) phosphotidylinositol (PI), 3(H) PI-4 phosphate (PIP), 3(H) PI-4, 5 bisphosphate (PIP2) in human platelets. The implications of the findings and their relevance to the mode of action of antidepressants are discussed.

The effects of antenatal depression and antidepressant treatment on placental gene expression

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Jocelien DA Olivier

2015-01-01

Full Text Available The effects of antenatal depression and antidepressant treatment during pregnancy on both mother and child are vigorously studied, but the underlying biology for these effects is largely unknown. The placenta plays a crucial role in the growth and development of the fetus. We performed a gene expression study on the fetal side of the placenta to investigate gene expression patterns in mothers with antenatal depression and in mothers using antidepressant treatment during pregnancy.Placental samples from mothers with normal pregnancies, from mothers with antenatal depression, and from mothers using antidepressants were collected. We performed a pilot microarray study to investigate alterations in the gene expression and selected several genes from the microarray for biological validation with qPCR in a larger sample.In mothers with antenatal depression 108 genes were differentially expressed, whereas 109 genes were differentially expressed in those using antidepressants. Validation of the microarray revealed more robust gene expression differences in the seven genes picked for confirmation in antidepressant-treated women than in depressed women. Among the genes that were validated ROCK2 and C12orf39 were differentially expressed in both depressed and antidepressant-treated women, whereas ROCK1, GCC2, KTN1, and DNM1L were only differentially expressed in the antidepressant-treated women. In conclusion, antenatal depression and antidepressant exposure during pregnancy are associated with altered gene expression in the placenta. Findings on those genes picked for validation were more robust among antidepressant-treated women than in depressed women, possibly due to the fact that depression is a multifactorial condition with varying degrees of endocrine disruption. It remains to be established whether the alterations found in the gene expression of the placenta are found in the fetus as well.

Involvement of sigma-1 receptors in the antidepressant-like effects of dextromethorphan.

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Linda Nguyen

Full Text Available Dextromethorphan is an antitussive with a high margin of safety that has been hypothesized to display rapid-acting antidepressant activity based on pharmacodynamic similarities to the N-methyl-D-aspartate (NMDA receptor antagonist ketamine. In addition to binding to NMDA receptors, dextromethorphan binds to sigma-1 (σ1 receptors, which are believed to be protein targets for a potential new class of antidepressant medications. The purpose of this study was to determine whether dextromethorphan elicits antidepressant-like effects and the involvement of σ1 receptors in mediating its antidepressant-like actions. The antidepressant-like effects of dextromethorphan were assessed in male, Swiss Webster mice using the forced swim test. Next, σ1 receptor antagonists (BD1063 and BD1047 were evaluated in conjunction with dextromethorphan to determine the involvement of σ receptors in its antidepressant-like effects. Quinidine, a cytochrome P450 (CYP 2D6 inhibitor, was also evaluated in conjunction with dextromethorphan to increase the bioavailability of dextromethorphan and reduce exposure to additional metabolites. Finally, saturation binding assays were performed to assess the manner in which dextromethorphan interacts at the σ1 receptor. Our results revealed dextromethorphan displays antidepressant-like effects in the forced swim test that can be attenuated by pretreatment with σ1 receptor antagonists, with BD1063 causing a shift to the right in the dextromethorphan dose response curve. Concomitant administration of quinidine potentiated the antidepressant-like effects of dextromethorphan. Saturation binding assays revealed that a Ki concentration of dextromethorphan reduces both the Kd and the Bmax of [(3H](+-pentazocine binding to σ1 receptors. Taken together, these data suggest that dextromethorphan exerts some of its antidepressant actions through σ1 receptors.

Mechanisms of action of antidepressants: from neurotransmitter systems to signaling pathways

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Taylor, Chirisse; Fricker, Ashwana D.; Devi, Lakshmi A.; Gomes, Ivone

2005-01-01

Antidepressants are commonly used in the treatment of anxiety and depression, medical conditions that affect ~17–20% of the population. The clinical effects of antidepressants take several weeks to manifest, suggesting that these drugs induce adaptive changes in brain structures affected by anxiety and depression. In order to develop shorter-acting and more effective drugs for the treatment of anxiety and depression, it is important to understand how antidepressants bring about their benefici...

The Effect of Sympathetic Antagonists on the Antidepressant Action of Alprazolam

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Gorash ZM

2008-01-01

Full Text Available Alprazolam is an anti-anxiety drug shown to be effective in the treatment of depression. In this study, the effect of sympathetic receptor antagonists on alprazolam–induced antidepressant action was studied using a mouse model of forced swimming behavioral despair. The interaction of three sympathetic receptor antagonists with benzodiazepines, which may impact the clinical use of alprazolam, was also studied. Behavioral despair was examined in six groups of albino mice. Drugs were administered intraperitoneally. The control group received only a single dose of 1% Tween 80. The second group received a single dose of alprazolam, and the third group received an antagonist followed by alprazolam. The fourth group was treated with imipramine, and the fifth group received an antagonist followed by imipramine. The sixth group was treated with a single dose of an antagonist alone (atenolol, a β1-selective adrenoceptor antagonist; propranolol, a non selective β-adrenoceptor antagonist; and prazocin, an α1-adrenoceptor antagonist. Results confirmed the antidepressant action of alprazolam and imipramine. Prazocin treatment alone produced depression, but it significantly potentiated the antidepressant actions of imipramine and alprazolam. Atenolol alone produced an antidepressant effect and potentiated the antidepressant action of alprazolam. Propranolol treatment alone produced depression, and antagonized the effects of alprazolam and imipramine, even producing depression in combined treatments. In conclusion, our results reveal that alprazolam may produce antidepressant effects through the release of noradrenaline, which stimulates β2 receptors to produce an antidepressant action. Imipramine may act by activating β2 receptors by blocking or down-regulating β1 receptors.

Antidepressant-Like Effects of Central BDNF Administration in Mice of Antidepressant Sensitive Catalepsy (ASC) Strain.

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Tikhonova, Maria; Kulikov, Alexander V

2012-08-31

Although numerous data evidence the implication of brain-derived neurotrophic factor (BDNF) in the pathophysiology of depression, the potential for BDNF to correct genetically defined depressive-like states is poorly studied. This study was aimed to reveal antidepressant-like effects of BDNF (300 ng, 2×, i.c.v.) on behavior and mRNA expression of genes associated with depression-like state in the brain in mice of antidepressant sensitive catalepsy (ASC) strain characterized by high hereditary predisposition to catalepsy and depressive-like features. Behavioral tests were held on the 7th-16th days after the first (4th-13th after the second) BDNF injection. Results showed that BDNF normalized impaired sexual motivation in the ASC males, and this BDNF effect differed, with advantageous effects, from that of widely used antidepressants. The anticataleptic effect of two BDNF injections was enhanced compared with a single administration. A tendency to decrease the immobility duration in tail-suspension test was observed in BDNF-treated ASC mice. The effects on catalepsy and sexual motivation were specific since BDNF did not alter locomotor and exploratory activity or social interest in the ASC mice. Along with behavioral antidepressant-like effects on the ASC mice, BDNF increased hippocampal mRNA levels of Bdnf and Creb1 (cAMP response element-binding protein gene). BDNF also augmented mRNA levels of Arc gene encoding Arc (Activity-regulated cytoskeleton-associated) protein involved in BDNF-induced processes of neuronal and synaptic plasticity in hippocampus and prefrontal cortex. The data suggest that: [1] BDNF is effective in the treatment of some genetically defined behavioral disturbances; [2] BDNF influences sexually-motivated behavior; [3] Arc mRNA levels may serve as a molecular marker of BDNF physiological activity associated with its long-lasting behavioral effects; [4] ASC mouse strain can be used as a suitable model to study mechanisms of BDNF effects on

Atypical disease phenotypes in pediatric ulcerative colitis

DEFF Research Database (Denmark)

Levine, Arie; de Bie, Charlotte I; Turner, Dan

2013-01-01

Definitive diagnosis of pediatric ulcerative colitis (UC) may be particularly challenging since isolated colitis with overlapping features is common in pediatric Crohn's disease (CD), while atypical phenotypes of UC are not uncommon. The Paris classification allows more accurate phenotyping...... of atypical inflammatory bowel disease (IBD) patients. Our aim was to identify the prevalence of atypical disease patterns in new-onset pediatric UC using the Paris classification....

Antidepressant-like effect of peony glycosides in mice.

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Mao, Qing-Qiu; Ip, Siu-Po; Tsai, Sam-Hip; Che, Chun-Tao

2008-09-26

The root part of Paeonia lactiflora Pall. (Ranunculaceae), known as peony, is often used in Chinese herbal formulae for the treatment of depression-like disorders. Previous studies in our laboratory have shown that an ethanol extract of peony produced antidepressive effects in mouse models of depression. It is well known that peony contains glycosides such as paeoniflorin and albiflorin, yet it remains unclear whether the total glycosides of peony (TGP) are effective. The present study aims to evaluate the antidepressant-like effects of TGP. The antidepressant-like effects of TGP was determined by using animal models of depression including forced swim and tail suspension tests. The acting mechanism was explored by determining the effect of TGP on the activities of monoamine oxidases. Intragastric administration of TGP at 80 and 160 mg/kg for seven days caused a significant reduction of immobility time in both forced swim and tail suspension tests, yet TGP did not stimulate locomotor activity in the open-field test. In addition, TGP treatment antagonized reserpine-induced ptosis and inhibited the activities of monoamine oxidases in mouse cerebrum. These results suggest that the antidepressive effects of TGP are mediated, at least in part, by the inhibition of monoamine oxidases.

Effect of antidepressant medication use on emotional information processing in major depression.

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Wells, Tony T; Clerkin, Elise M; Ellis, Alissa J; Beevers, Christopher G

2014-02-01

Acute administration of antidepressant medication increases emotional information processing for positive information in both depressed and healthy persons. This effect is likely relevant to the therapeutic actions of these medications, but it has not been studied in patients with major depressive disorder taking antidepressants as typically prescribed in the community. The authors used eye tracking to examine the effects of antidepressant medication on selective attention for emotional stimuli in a sample of 47 patients with major depressive disorder (21 medicated and 26 unmedicated) and 47 matched comparison subjects without depression. Participants completed a passive-viewing eye-tracking task assessing selective attention for positive, dysphoric, threatening, and neutral stimuli in addition to providing medication information and self-report measures of depression and anxiety severity. Depressed participants currently taking antidepressants and nondepressed comparison subjects demonstrated greater total gaze duration and more fixations for positive stimuli compared with unmedicated depressed participants. Depressed participants on medication also had fewer fixations for dysphoric stimuli compared with depressed participants not on medication. Antidepressants, as prescribed in the community to patients with depression, appear to modify emotional information processing in the absence of differences in depression severity. These results are consistent with previous work and indicate a robust effect for antidepressants on positive information processing. They also provide further evidence for modification of information processing as a potential mechanism of action for antidepressant medication.

Effects of antidepressant drugs on different receptors in the brain

International Nuclear Information System (INIS)

Hall, H.; Oegren, S.-O.

1981-01-01

Radioligand receptor binding techniques were used to characterize the effects of different structural types of antidepressant drugs on neurotransmitter receptors. The tricyclic antidepressants more or less potently inhibited the binding to rat brain preparations of several different radiolabelled ligands ([ 3 H]WB4101, [ 3 H]QNB, [ 3 H]d-LSD, [ 3 H]mepyramine). The potency of the nontricyclic antidepressants varied greatly. Mianserin, potently displaced [ 3 H]mepyramine, [ 3 H]d-LSD and [ 3 H]WB4101 while it was very weak on [ 3 H]QNB-binding. Nomifensine and the specific 5-HT uptake inhibitors zimelidine and alaproclate had very low affinity for these receptors. All the antidepressants tested were practically devoid of activity on [ 3 H]DHA binding, [ 3 H]spiroperidol binding, [ 3 H]flunitrazepam binding, [ 3 H]muscimol binding and [ 3 H]naloxone binding. The implications of these findings for biogenic amine theories of affective disorders are discussed. (Auth.)

Increase in depression diagnoses and prescribed antidepressants among young girls

DEFF Research Database (Denmark)

Skovlund, Charlotte Wessel; Kessing, Lars Vedel; Mørch, Lina Steinrud

2017-01-01

AIMS: To analyse trends in depression diagnoses and antidepressant use according to age and gender. METHODS: Nationwide cohort study including all women and men of 10-49 years living in Denmark during 2000-2013. The Psychiatric Registry and Prescription Registry provided data on depression...... diagnoses and antidepressant medication, respectively. Incidence rates as well as 1-year prevalence rates were calculated. RESULTS: The incidence and 1-year prevalence rates of depression diagnoses increased during 2000-2013. The women/men rates were 2.0 for both 1-year prevalence of depressions diagnoses...... and antidepressant use. For adolescent girls, the absolute increase was 3 per 1000 for depression diagnoses and 8 per 1000 for first use of antidepressants, compared to boys who had an increase of 1.1 and 3 per 1000, respectively. Before puberty, boys and girls had almost the same incidence rates of both depression...

A naturally occurring cowpox virus with an ectromelia virus A-type inclusion protein gene displays atypical A-type inclusions.

Science.gov (United States)

Okeke, Malachy Ifeanyi; Hansen, Hilde; Traavik, Terje

2012-01-01

Human orthopoxvirus (OPV) infections in Europe are usually caused by cowpox virus (CPXV). The genetic heterogeneity of CPXVs may in part be due to recombination with other OPV species. We describe the characterization of an atypical CPXV (CPXV-No-H2) isolated from a human patient in Norway. CPXV-No-H2 was characterized on the basis of A-type inclusion (ATI) phenotype as well as the DNA region containing the p4c and atip open reading frames. CPXV-No-H2 produced atypical V(+/) ATI, in which virions are on the surface of ATI but not within the ATI matrix. Phylogenetic analysis showed that the atip gene of CPXV-No-H2 clustered closely with that of ectromelia virus (ECTV) with a bootstrap support of 100% whereas its p4c gene is diverged compared to homologues in other OPV species. By recombination analysis we identified a putative crossover event at nucleotide 147, downstream the start of the atip gene. Our results suggest that CPXV-No-H2 originated from a recombination between CPXV and ECTV. Our findings are relevant to the evolution of OPVs. Copyright © 2011 Elsevier B.V. All rights reserved.

Risk of drug interaction: combination of antidepressants and other drugs

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Miyasaka Lincoln Sakiara

2003-01-01

Full Text Available OBJECTIVE: To assess the frequency of combination of antidepressants with other drugs and risk of drug interactions in the setting public hospital units in Brazil. METHODS: Prescriptions of all patients admitted to a public hospital from November 1996 to February 1997 were surveyed from the hospital's data processing center in São Paulo, Brazil. A manual search of case notes of all patients admitted to the psychiatric unit from January 1993 to December 1995 and all patients registered in the affective disorders outpatient clinic in December 1996 was carried out. Patients taking any antidepressant were identified and concomitant use of drugs was checked. By means of a software program (Micromedex® drug interactions were identified. RESULTS: Out of 6,844 patients admitted to the hospital, 63 (0.9% used antidepressants and 16 (25.3% were at risk of drug interaction. Out of 311 patients in the psychiatric unit, 63 (20.2% used antidepressants and 13 of them (20.6% were at risk. Out of 87 patients in the affective disorders outpatient clinic, 43 (49.4% took antidepressants and 7 (16.2% were at risk. In general, the use of antidepressants was recorded in 169 patients and 36 (21.3% were at risk of drug interactions. Twenty different forms of combinations at risk of drug interactions were identified: four were classified as mild, 15 moderate and one severe interaction. CONCLUSION: In the hospital general units the number of drug interactions per patient was higher than in the psychiatric unit; and prescription for depression was lower than expected.

Atypical Cutaneous Manifestations in Syphilis.

Science.gov (United States)

Ivars Lleó, M; Clavo Escribano, P; Menéndez Prieto, B

2016-05-01

Although the diversity of the clinical manifestations of syphilis is well-known, atypical presentations can also occur. Such atypical presentations are associated with a high risk of transmission as a result of diagnostic confusion and treatment delays owing to the disease's ability to mimic other common skin diseases, deviate from classic clinical presentations, and adopt unique forms. Cases of atypical syphilis have been described most frequently in patients with concomitant human immunodeficiency virus (HIV) infection. Because the incidence of syphilis has been growing over recent years -particularly in patients with HIV co-infection- dermatologists need to be familiar with the less well-known clinical presentations of this venereal disease. Copyright © 2015 AEDV. Published by Elsevier España, S.L.U. All rights reserved.

Antidepressant use in 27 European countries: associations with sociodemographic, cultural and economic factors.

Science.gov (United States)

Lewer, Dan; O'Reilly, Claire; Mojtabai, Ramin; Evans-Lacko, Sara

2015-09-01

Prescribing of antidepressants varies widely between European countries despite no evidence of difference in the prevalence of affective disorders. To investigate associations between the use of antidepressants, country-level spending on healthcare and country-level attitudes towards mental health problems. We used Eurobarometer 2010, a large general population survey from 27 European countries, to measure antidepressant use and regularity of use. We then analysed the associations with country-level spending on healthcare and country-level attitudes towards mental health problems. Higher country spending on healthcare was strongly associated with regular use of antidepressants. Beliefs that mentally ill people are 'dangerous' were associated with higher use, and beliefs that they 'never recover' or 'have themselves to blame' were associated with lower and less regular use of antidepressants. Contextual factors, such as healthcare spending and public attitudes towards mental illness, may partly explain variations in antidepressant use and regular use of these medications. © The Royal College of Psychiatrists 2015.

Age-related response to redeemed antidepressants measured by completed suicide in older adults

DEFF Research Database (Denmark)

Erlangsen, Annette; Conwell, Yeates

2014-01-01

OBJECTIVE: To examine if the suicide rate of older adults prescribed antidepressants varies with age and to assess the proportion of older adults who died by suicide that had recently been prescribed antidepressants. METHODS: A population-based cohort study using a nationwide linkage of individua...... between estimated prevalence of depression and antidepressant prescription rate in persons dying by suicide underscores the need for assessment of depression in the oldest old.......OBJECTIVE: To examine if the suicide rate of older adults prescribed antidepressants varies with age and to assess the proportion of older adults who died by suicide that had recently been prescribed antidepressants. METHODS: A population-based cohort study using a nationwide linkage of individual......-level records was conducted on all persons aged 50+ living in Denmark during 1996-2006 (1,215,524 men and 1,343,568 women). Suicide rates by treatment status were calculated using data on all antidepressant prescriptions redeemed at pharmacies. RESULTS: Individual-level data covered 9,354,620 and 10...

Differential Risk of Peptic Ulcer Among Users of Antidepressants Combined With Nonsteroidal Anti-inflammatory Drugs.

Science.gov (United States)

Shin, Ju-Young; Song, Inmyung; Lee, Jin-Ho; Yoon, Jong Lull; Kwon, Jun Soo; Park, Byung-Joo

2017-04-01

Selective serotonin reuptake inhibitors (SSRIs) have been reported to have an increased risk of gastrointestinal adverse events, and the risk may be further increased by combined use of nonsteroidal anti-inflammatory drugs (NSAIDs). However, little has been known about the risk of peptic ulcer associated with other classes of antidepressants or individual antidepressants combined with NSAIDs. We conducted a retrospective cohort study to define the risk of peptic ulcer associated with combined use of antidepressants and NSAIDs, as compared with use of antidepressants alone. Using the Korean Health Insurance Review and Assessment Service database, we identified a total of 1,127,622 patients who began receiving antidepressants between 2009 and 2012. Propensity-based matching and Cox proportional hazards models were used to compare the risk of peptic ulcer between antidepressant users with NSAIDs and those without NSAIDs matched in a 1:1 ratio, for a total of 768,850 patients. The risk of peptic ulcer did not increase with combined use of overall antidepressants and NSAIDs, as compared with antidepressant use alone (hazard ratio [HR], 1.02; 95% confidence interval [CI], 0.99-1.06). A slightly increased risk was observed for combined use of NSAIDs with tricyclic antidepressants (HR, 1.15; 95% CI, 1.09-1.21) and with SSRIs (HR, 1.08; 95% CI, 1.01-1.16). We found that although concomitant use of NSAIDs and antidepressants was not associated with an increased risk of peptic ulcer for antidepressants in general, it was so for some specific classes including tricyclic antidepressants and SSRIs. However, we cannot rule out the possibility that the increased risk was solely due to NSAID use.

Identification of the chelocardin biosynthetic gene cluster from Amycolatopsis sulphurea: a platform for producing novel tetracycline antibiotics.

Science.gov (United States)

Lukežič, Tadeja; Lešnik, Urška; Podgoršek, Ajda; Horvat, Jaka; Polak, Tomaž; Šala, Martin; Jenko, Branko; Raspor, Peter; Herron, Paul R; Hunter, Iain S; Petković, Hrvoje

2013-12-01

Tetracyclines (TCs) are medically important antibiotics from the polyketide family of natural products. Chelocardin (CHD), produced by Amycolatopsis sulphurea, is a broad-spectrum tetracyclic antibiotic with potent bacteriolytic activity against a number of Gram-positive and Gram-negative multi-resistant pathogens. CHD has an unknown mode of action that is different from TCs. It has some structural features that define it as 'atypical' and, notably, is active against tetracycline-resistant pathogens. Identification and characterization of the chelocardin biosynthetic gene cluster from A. sulphurea revealed 18 putative open reading frames including a type II polyketide synthase. Compared to typical TCs, the chd cluster contains a number of features that relate to its classification as 'atypical': an additional gene for a putative two-component cyclase/aromatase that may be responsible for the different aromatization pattern, a gene for a putative aminotransferase for C-4 with the opposite stereochemistry to TCs and a gene for a putative C-9 methylase that is a unique feature of this biosynthetic cluster within the TCs. Collectively, these enzymes deliver a molecule with different aromatization of ring C that results in an unusual planar structure of the TC backbone. This is a likely contributor to its different mode of action. In addition CHD biosynthesis is primed with acetate, unlike the TCs, which are primed with malonamate, and offers a biosynthetic engineering platform that represents a unique opportunity for efficient generation of novel tetracyclic backbones using combinatorial biosynthesis.

[Unpredictable chronic mild stress effects on antidepressants activities in forced swim test].

Science.gov (United States)

Kudryashov, N V; Kalinina, T S; Voronina, T A

2015-02-01

The experiments has been designed to study unpredictable chronic mild stress effect on anti-depressive activities of amitriptyline (10 mg/kg) and fluoxetine (20 mg/kg) in forced swim test in male outbred mice. It is shown that acute treatment with fluoxetine does not produce any antidepressant effects in mice following stress of 14 days while the sub-chronic injections of fluoxetine result in more deep depressive-like behavior. In 28 daily stressed mice, antidepressant effect of fluoxetine is observed independently of the injection rates. Amitriptyline demonstrates the antidepressant activity regardless of the duration of stress or administration scheduling, but at the same time the severity of anti-immobilization effect of amitriptyline in stressed mice is weaker in compare to non-stressed trails. Thus, the injection rates and duration of unpredictable mild chronic stress are the parameters that determine the efficiency of antidepressants in the mouse forced swimming test.

Do continued antidepressants protect against dementia in patients with severe depressive disorder?

Science.gov (United States)

Kessing, Lars Vedel; Forman, Julie Lyng; Andersen, Per Kragh

2011-11-01

Studies on humans show that depressive disorder is associated with an increased risk of developing cognitive dysfunction, and animal studies suggest that antidepressants may have neuroprotective abilities. On the basis of these observations, it was hypothesized that treatment with antidepressants may decrease the risk of developing dementia in patients with depression. We investigated whether continued treatment with antidepressants is associated with a decreased rate of dementia in a population of patients discharged from psychiatric healthcare service with a diagnosis of depression. We used register data on all prescribed antidepressants in all patients discharged from psychiatric healthcare service with a diagnosis of depression and with subsequent diagnoses of dementia in Denmark from 1995 to 2005. A total of 37 658 patients with a diagnosis of depression at their first psychiatric contact and who were exposed to antidepressants after discharge were included in the study. A total of 2007 patients (5.3%) were subsequently diagnosed with dementia of any kind. The rate of dementia decreased during periods of two or more prescriptions of older antidepressants compared with the period of only one prescription of older antidepressants [relative risk (RR)=0.83 (95% confidence interval (CI)=0.70-0.98)]. This finding was replicated with Alzheimer's disease as the outcome [RR=0.66 (95% CI=0.47-0.94)] but not with dementia of other kinds as the outcome [RR=0.88 (95% CI=0.73-1.06)]. In contrast, during periods of continued use of selective serotonin reuptake inhibitors or newer nonselective serotonin reuptake inhibitors, the rate of dementia was not decreased, regardless of the subtype of dementia. It was concluded that continued long-term treatment with older antidepressants is associated with a reduced rate of dementia in patients treated in psychiatric healthcare settings, whereas continued treatment with other kinds of antidepressants is not. Methodological reasons for

Antidepressant medications and osteoporosis.

Science.gov (United States)

Rizzoli, R; Cooper, C; Reginster, J-Y; Abrahamsen, B; Adachi, J D; Brandi, M L; Bruyère, O; Compston, J; Ducy, P; Ferrari, S; Harvey, N C; Kanis, J A; Karsenty, G; Laslop, A; Rabenda, V; Vestergaard, P

2012-09-01

Use of antidepressant medications that act on the serotonin system has been linked to detrimental impacts on bone mineral density (BMD), and to osteoporosis. This article reviews current evidence for such effects, and identifies themes for future research. Serotonin receptors are found in all major types of bone cell (osteoblasts, osteocytes, and osteoclasts), indicating an important role of the neuroendocrine system in bone. Observational studies indicate a complex relationship between depression, antidepressants, and fracture. First, the presence of depression itself increases fracture risk, in relation with decreased BMD and an increase in falls. A range of aspects of depression may operate, including behavioral factors (e.g., smoking and nutrition), biological changes, and confounders (e.g., comorbidities and concomitant medications). A substantial proportion of depressed patients receive antidepressants, mostly selective serotonin reuptake inhibitors (SSRIs). Some of these have been linked to decreased BMD (SSRIs) and increased fracture risk (SSRIs and tricyclic agents). Current use of SSRIs and tricyclics increases fracture risk by as much as twofold versus nonusers, even after adjustment for potential confounders. While there is a dose-response relationship for SSRIs, the effect does not appear to be homogeneous across the whole class of drugs and may be linked to affinity for the serotonin transporter system. The increase in risk is the greatest in the early stages of treatment, with a dramatic increase after initiation, reaching a peak within 1 month for tricyclics and 8 months for SSRIs. Treatment-associated increased risk diminishes towards baseline in the year following discontinuation. The body of evidence suggests that SSRIs should be considered in the list of medications that are risk factors for osteoporotic fractures. Copyright © 2012 Elsevier Inc. All rights reserved.

Antidepressant treatment outcomes of psychogenic movement disorder.

Science.gov (United States)

Voon, Valerie; Lang, Anthony E

2005-12-01

Psychogenic movement disorder (PMD) is a subtype of conversion disorder. We describe the outcomes of a series of PMD patients following antidepressant treatment. Twenty-three outpatients with chronic PMD, diagnosed using Fahn and Williams' criteria, underwent psychiatric assessment. The patients were referred for assessment and management from January 2003 to July 2004. Fifteen agreed to be treated with antidepressants. Patients received citalopram or paroxetine; those who did not respond after 4 weeks of taking an optimal dose were switched to venlafaxine. Concurrently, 3 had supportive psychotherapy, and 1 had family intervention. Assessments included the DSM-IV-based Mini-International Neuropsychiatric Interview and scales measuring depression, anxiety, and motor and global severity. Eighteen patients (78%) had at least 1 Axis I diagnosis in addition to the somatoform diagnosis, and 3 (13%) had somatization disorder. Five (22%) had previous psychiatric contact. Nine (39%) had previously been treated with antidepressants, but only 4 (17%) had adequate trials. No significant differences existed in patient characteristics between treated and untreated groups. Among treated patients, Montgomery-Asberg Depression Rating Scale scores improved from baseline (p hypochondriasis, somatization disorder, or probable factitious disorder/malingering, of whom none improved. All of the patients with primary conversion disorder had a current or previous depressive or anxiety disorder compared with 40% (N = 2) of the patients with additional somatoform diagnoses. Our preliminary findings suggest that chronic PMD with primary conversion symptoms and with recent or current depression or anxiety may respond to antidepressants. Further well-designed studies, now under way, are required to confirm these findings.

Use of anti-depressants and the risk of fracture of the hip or femur

OpenAIRE

van den Brand, M. W. M.; Samson, M. M.; Pouwels, S.; van Staa, T. P.; Thio, B.; Cooper, C.; Leufkens, H. G. M.; Egberts, A. C. G.; Verhaar, H. J. J.; de Vries, F.

2009-01-01

Summary Anti-depressants are used largely, but have serious side effects. We show that both selective serotonin re-uptake inhibitors (SSRIs) and tricyclic anti-depressants (TCAs) increase the risk of hip/femur fracture and that this risk is time related and depends on the degree of serotonin transporter inhibition. This should be considered when prescribing anti-depressants to patients. Introduction Anti-depressants are known to have serious side effects. We examined the association between t...

The Association of Antidepressant Medication and Body Weight Gain.

Directory of Open Access Journals (Sweden)

Sara Ranjbar

2013-04-01

Full Text Available Objective: To review the literature and discover which antidepressants are responsible for weight gain and then to discuss the areas with lack of adequate knowledge. Method: An electronic search was conducted through Medline, Pubmed, Cochrane library, and ScienceDirect. Forty nine empirical researches were identified and reviewed. Results: Amitriptyline, clomipramine, and mirtazapine have been associated with more weight gain induction in clinical studies, but not in animal-based studies. All TCAs have been reported to cause weight gain except protriptyline. MAOIs have been associated with weight gain. In SSRI group, citalopram and ecitalopram induce weight, yet mixed results exist for paroxetine and fluoxetine. Researches unanimously reported weight loss effect for bupropion. Some studies suggest contributing factors in the relationship of antidepressants with body weight changes including age, gender, base-line weights and treatment duration. Various results of different treatment durations have been reported in some cases but there are not continuous time-dependent studies for the influences of antidepressants on body weight changes. Conclusion: More studies are required to discover underlying mechanisms and the time-dependent effects of antidepressants on body weight changes.

Regulation of neurotrophic factors and energy metabolism by antidepressants in astrocytes

KAUST Repository

Martin, Jean Luc; Magistretti, Pierre J.; Allaman, Igor

2013-01-01

There is growing evidence that astrocytes are involved in the neuropathology of major depression. In particular, decreases in glial cell density observed in the cerebral cortex of individuals with major depressive disorder are accompanied by a reduction of several astrocytic markers suggesting that astrocyte dysfunction may contribute to the pathophysiology of major depression. In rodents, glial loss in the prefrontal cortex is sufficient to induce depressive-like behaviors and antidepressant treatment prevents the stress-induced reduction of astrocyte number in the hippocampus. Collectively, these data support the existence of a link between astrocyte loss or dysfunction, depressive-like behavior and antidepressant treatment. Astrocytes are increasingly recognized to play important roles in neuronal development, neurotransmission, synaptic plasticity and maintenance of brain homeostasis. It is also well established that astrocytes provide trophic, structural, and metabolic support to neurons. In this article, we review evidence that antidepressants regulate energy metabolism and neurotrophic factor expression with particular emphasis on studies in astrocytes. These observations support a role for astrocytes as new targets for antidepressants. The contribution of changes in astrocyte glucose metabolism and neurotrophic factor expression to the therapeutic effects of antidepressants remains to be established. © 2013 Bentham Science Publishers.

Regulation of neurotrophic factors and energy metabolism by antidepressants in astrocytes

KAUST Repository

Martin, Jean Luc

2013-09-01

There is growing evidence that astrocytes are involved in the neuropathology of major depression. In particular, decreases in glial cell density observed in the cerebral cortex of individuals with major depressive disorder are accompanied by a reduction of several astrocytic markers suggesting that astrocyte dysfunction may contribute to the pathophysiology of major depression. In rodents, glial loss in the prefrontal cortex is sufficient to induce depressive-like behaviors and antidepressant treatment prevents the stress-induced reduction of astrocyte number in the hippocampus. Collectively, these data support the existence of a link between astrocyte loss or dysfunction, depressive-like behavior and antidepressant treatment. Astrocytes are increasingly recognized to play important roles in neuronal development, neurotransmission, synaptic plasticity and maintenance of brain homeostasis. It is also well established that astrocytes provide trophic, structural, and metabolic support to neurons. In this article, we review evidence that antidepressants regulate energy metabolism and neurotrophic factor expression with particular emphasis on studies in astrocytes. These observations support a role for astrocytes as new targets for antidepressants. The contribution of changes in astrocyte glucose metabolism and neurotrophic factor expression to the therapeutic effects of antidepressants remains to be established. © 2013 Bentham Science Publishers.

The Nicotinic Acetylcholine Receptor as a Target for Antidepressant Drug Development

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Noah S. Philip

2012-01-01

Full Text Available An important new area of antidepressant drug development involves targeting the nicotinic acetylcholine receptor (nAChR. This receptor, which is distributed widely in regions of the brain associated with depression, is also implicated in other important processes that are relevant to depression, such as stress and inflammation. The two classes of drugs that target nAChRs can be broadly divided into mecamylamine- and cytisine-based compounds. These drugs probably exert their effects via antagonism at α4β2 nAChRs, and strong preclinical data support the antidepressant efficacy of both classes when used in conjunction with other primary antidepressants (e.g., monoamine reuptake inhibitors. Although clinical data remain limited, preliminary results in this area constitute a compelling argument for further evaluation of the nAChR as a target for future antidepressant drug development.

Decisional conflict among women considering antidepressant medication use in pregnancy.

Science.gov (United States)

Walton, Georgia D; Ross, Lori E; Stewart, Donna E; Grigoriadis, Sophie; Dennis, Cindy-Lee; Vigod, Simone

2014-12-01

The purpose of this study was to examine decision-making among women considering antidepressant medication use in pregnancy. Decisional conflict was assessed using the Decisional Conflict Scale (DCS) among pregnant women considering antidepressant medication treatment (N = 40). Overall DCS and subscale scores were compared between women who were antidepressant users and non-users. Semi-structured interviews (N = 10) explored barriers and facilitators of decision-making. Twenty-one women (52 %) had moderate or high decisional conflict (DCS ≥ 25). Overall DCS scores did not differ between groups, but antidepressant use was associated with feeling more adequately informed (subscale mean 17.5, SD 17.9 vs. 42.1, SD 23.8, p = 0.001) and clear about values (subscale mean 16.7, SD 15.1 vs. 29.8, SD 24.0, p = 0.043). Barriers to decision-making were (1) difficulty weighing maternal versus infant health, (2) lack of high quality information, (3) negative external influences, and (4) emotional reactions to decision-making. Facilitators were (1) interpersonal supports, (2) accessible subspecialty care, and (3) severe depressive symptoms. Many pregnant women facing decisions regarding antidepressant medication use experience decisional conflict. Interventions that provide accurate information, assistance with weighing risks and benefits of treatment, management of problematic external influences, and emotional support may reduce decisional conflict and facilitate the decision-making process.

Serotonin 5-HT4 receptors: A new strategy for developing fast acting antidepressants?

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Vidal, Rebeca; Castro, Elena; Pilar-Cuéllar, Fuencisla; Pascual-Brazo, Jesús; Díaz, Alvaro; Rojo, María Luisa; Linge, Raquel; Martín, Alicia; Valdizán, Elsa M; Pazos, Angel

2014-01-01

The regulation of the activity of brain monoaminergic systems has been the focus of attention of many studies since the first antidepressant drug emerged 50 years ago. The search for novel antidepressants is deeply linked to the search for fast-acting strategies, taking into account that 2-4 weeks of treatment with classical antidepressant are required before clinical remission of the symptoms becomes evident. In the recent years several hypotheses have been proposed on the basis of the existence of alterations in brain synaptic plasticity in major depression. Recent evidences support a role for 5-HT4 receptors in the pathogenesis of depression as well as in the mechanism of action of antidepressant drugs. In fact, chronic treatment with antidepressant drugs appears to modulate, at different levels, the signaling pathway associated to 5-HT4 receptors, as well as their levels of expression in the brain. Moreover, several experimental studies have identified this receptor subtype as a promising new target for fast-acting antidepressant strategy: the administration of partial agonists of this receptor induces a number of responses similar to those observed after chronic treatment with classical antidepressants, but with a rapid onset of action. They include efficacy in behavioral models of depression, rapid desensitization of 5-HT1A autoreceptors, and modifications in the expression of several molecular markers of brain neuroplasticity. Although much work remains to be done in order to clarify the real therapeutic potential of these drugs, the evidences reviewed below support the hypothesis that 5-HT4 receptor partial agonists could behave as rapid and effective antidepressants.

Flat epithelial atypia and atypical ductal hyperplasia: carcinoma underestimation rate.

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Ingegnoli, Anna; d'Aloia, Cecilia; Frattaruolo, Antonia; Pallavera, Lara; Martella, Eugenia; Crisi, Girolamo; Zompatori, Maurizio

2010-01-01

This study was carried out to determine the underestimation rate of carcinoma upon surgical biopsy after a diagnosis of flat epithelial atypia and atypical ductal hyperplasia and 11-gauge vacuum-assisted breast biopsy. A retrospective review was conducted of 476 vacuum-assisted breast biopsy performed from May 2005 to January 2007 and a total of 70 cases of atypia were identified. Fifty cases (71%) were categorized as pure atypical ductal hyperplasia, 18 (26%) as pure flat epithelial atypia and two (3%) as concomitant flat epithelial atypia and atypical ductal hyperplasia. Each group were compared with the subsequent open surgical specimens. Surgical biopsy was performed in 44 patients with atypical ductal hyperplasia, 15 patients with flat epithelial atypia, and two patients with flat epithelial atypia and atypical ductal hyperplasia. Five cases of atypical ductal hyperplasia were upgraded to ductal carcinoma in situ, three cases of flat epithelial atypia yielded one ductal carcinoma in situ and two cases of invasive ductal carcinoma, and one case of flat epithelial atypia/atypical ductal hyperplasia had invasive ductal carcinoma. The overall rate of malignancy was 16% for atypical ductal hyperplasia (including flat epithelial atypia/atypical ductal hyperplasia patients) and 20% for flat epithelial atypia. The presence of flat epithelial atypia and atypical ductal hyperplasia at biopsy requires careful consideration, and surgical excision should be suggested.

Atypically presenting kaposiform hemangioendothelioma of the knee: ultrasound findings.

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Erdem Toslak, Iclal; Stegman, Matthew; Reiter, Michael P; Barkan, Güliz A; Borys, Dariusz; Lim-Dunham, Jennifer E

2018-04-10

Kaposiform hemangioendothelioma (KHE) is a rare vascular tumor of early childhood and infancy. Kasabach-Merritt phenomenon, a common complication of KHE, is characterized by life-threatening thrombocytopenia, hemolytic anemia, and consumption coagulopathy. There may be atypical cases that do not present with Kasabach-Merritt phenomenon and do have atypical imaging findings. Knowledge of atypical imaging features may assist radiologists in identifying KHE. In this report, we present a 4-year-old case of KHE with atypical ultrasound findings.

Imaging the neurobiological substrate of atypical depression by SPECT

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Pagani, Marco [Institute of Cognitive Sciences and Technologies, CNR, Rome (Italy); Karolinska University Hospital, Department of Nuclear Medicine, Stockholm (Sweden); Salmaso, Dario [Institute of Cognitive Sciences and Technologies, CNR, Rome (Italy); Nardo, Davide [University of Rome La Sapienza, Department of Psychology, Rome (Italy); Jonsson, Cathrine; Larsson, Stig A. [Karolinska University Hospital, Department of Nuclear Medicine, Stockholm (Sweden); Jacobsson, Hans [Karolinska University Hospital, Department of Radiology, Stockholm (Sweden); Gardner, Ann [Karolinska University Hospital Huddinge, Karolinska Institutet, Department of Clinical Neuroscience, Section of Psychiatry, Stockholm (Sweden)

2007-01-15

Neurobiological abnormalities underlying atypical depression have previously been suggested. The purpose of this study was to explore differences at functional brain imaging between depressed patients with and without atypical features and healthy controls. Twenty-three out-patients with chronic depressive disorder recruited from a service for patients with audiological symptoms were investigated. Eleven fulfilled the DSM-IV criteria for atypical depression (mood reactivity and at least two of the following: weight gain, hypersomnia, leaden paralysis and interpersonal rejection sensitivity). Twenty-three healthy subjects served as controls. Voxel-based analysis was applied to explore differences in {sup 99m}Tc-HMPAO uptake between groups. Patients in the atypical group had a higher prevalence of bilateral hearing impairment and higher depression and somatic distress ratings at the time of SPECT. Significantly higher tracer uptake was found bilaterally in the atypical group as compared with the non-atypicals in the sensorimotor (Brodmann areas, BA1-3) and premotor cortex in the superior frontal gyri (BA6), in the middle frontal cortex (BA8), in the parietal associative cortex (BA5, BA7) and in the inferior parietal lobule (BA40). Significantly lower tracer distribution was found in the right hemisphere in the non-atypicals compared with the controls in BA6, BA8, BA44, BA45 and BA46 in the frontal cortex, in the orbito-frontal cortex (BA11, BA47), in the postcentral parietal cortex (BA2) and in the multimodal association parietal cortex (BA40). The differences found between atypical and non-atypical depressed patients suggest different neurobiological substrates in these patient groups. The putative links with the clinical features of atypical depression are discussed. These findings encourage the use of functional neuroimaging in psychiatric disorders. (orig.)

Imaging the neurobiological substrate of atypical depression by SPECT

International Nuclear Information System (INIS)

Pagani, Marco; Salmaso, Dario; Nardo, Davide; Jonsson, Cathrine; Larsson, Stig A.; Jacobsson, Hans; Gardner, Ann

2007-01-01

Neurobiological abnormalities underlying atypical depression have previously been suggested. The purpose of this study was to explore differences at functional brain imaging between depressed patients with and without atypical features and healthy controls. Twenty-three out-patients with chronic depressive disorder recruited from a service for patients with audiological symptoms were investigated. Eleven fulfilled the DSM-IV criteria for atypical depression (mood reactivity and at least two of the following: weight gain, hypersomnia, leaden paralysis and interpersonal rejection sensitivity). Twenty-three healthy subjects served as controls. Voxel-based analysis was applied to explore differences in 99m Tc-HMPAO uptake between groups. Patients in the atypical group had a higher prevalence of bilateral hearing impairment and higher depression and somatic distress ratings at the time of SPECT. Significantly higher tracer uptake was found bilaterally in the atypical group as compared with the non-atypicals in the sensorimotor (Brodmann areas, BA1-3) and premotor cortex in the superior frontal gyri (BA6), in the middle frontal cortex (BA8), in the parietal associative cortex (BA5, BA7) and in the inferior parietal lobule (BA40). Significantly lower tracer distribution was found in the right hemisphere in the non-atypicals compared with the controls in BA6, BA8, BA44, BA45 and BA46 in the frontal cortex, in the orbito-frontal cortex (BA11, BA47), in the postcentral parietal cortex (BA2) and in the multimodal association parietal cortex (BA40). The differences found between atypical and non-atypical depressed patients suggest different neurobiological substrates in these patient groups. The putative links with the clinical features of atypical depression are discussed. These findings encourage the use of functional neuroimaging in psychiatric disorders. (orig.)

Atypical antipsychotics and glucose homeostasis.

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Bergman, Richard N; Ader, Marilyn

2005-04-01

Persistent reports have linked atypical antipsychotics with diabetes, yet causative mechanisms responsible for this linkage are unclear. Goals of this review are to outline the pathogenesis of nonimmune diabetes and to survey the available literature related to why antipsychotics may lead to this disease. We accessed the literature regarding atypical antipsychotics and glucose homeostasis using PubMed. The search included English-language publications from 1990 through October 2004. Keywords used included atypical antipsychotics plus one of the following: glucose, insulin, glucose tolerance, obesity, or diabetes. In addition, we culled information from published abstracts from several national and international scientific meetings for the years 2001 through 2004, including the American Diabetes Association, the International Congress on Schizophrenia Research, and the American College of Neuropsychopharmacology. The latter search was necessary because of the paucity of well-controlled prospective studies. We examined publications with significant new data or publications that contributed to the overall comprehension of the impact of atypical antipsychotics on glucose metabolism. We favored original peer-reviewed articles and were less likely to cite single case studies and/or anecdotal information. Approximately 75% of the fewer than 150 identified articles were examined and included in this review. Validity of data was evaluated using the existence of peer-review status as well as our own experience with methodology described in the specific articles. The metabolic profile caused by atypical antipsychotic treatment resembles type 2 diabetes. These agents cause weight gain in treated subjects and may induce obesity in both visceral and subcutaneous depots, as occurs in diabetes. Insulin resistance, usually associated with obesity, occurs to varying degrees with different antipsychotics, although more comparative studies with direct assessment of resistance are

Adherence to antidepressant treatment

DEFF Research Database (Denmark)

Hansen, Hanne Vibe; Kessing, Lars Vedel

2007-01-01

Depression is a common disorder with painful symptoms and, frequently, social impairment and decreased quality of life. The disorder has a tendency to be long lasting, often with frequent recurrence of symptoms. The risk of relapse and the severity of the symptoms may be reduced by correct...... of dependence of antidepressant medicine, have a great influence on adherence to treatment....

Poisoining with Tricyclic Antidepressants and Current Treatment

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Muge Gulen

2016-12-01

Full Text Available Poisoning with tricyclic antidepressants is one of the main causes of morbidity and mortality compared to all the antidepressants. Main toxic effects are on the cardiovascular system and central nervous system and manifests itself as anticholinergic symptoms. There is no antidote known to be used in the treatment. But sodium bicarbonate treatment is effective in preventing ventricular arrhythmias and hypotension, and resolving metabolic acidosis. There are some treatments that has been used for relief of symptoms and some of them still are in research stage. The drugs that are used can be customized according to the patients symptoms. [Archives Medical Review Journal 2016; 25(4.000: 608-621

Guidelines on treatment of perinatal depression with antidepressants: An international review.

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Molenaar, Nina M; Kamperman, Astrid M; Boyce, Philip; Bergink, Veerle

2018-04-01

Several countries have developed Clinical Practice Guidelines regarding treatment of perinatal depressive symptoms and perinatal use of antidepressant. We aimed to compare guidelines to guide clinicians in best clinical practice. An extensive search in guideline databases, MEDLINE and PsycINFO was performed. When no guidelines were (publicly) available online, we contacted psychiatric-, obstetric-, perinatal- and mood disorder societies of all first world countries and the five largest second world countries. Only Clinical Practice Guidelines adhering to quality criteria of the Appraisal of Guidelines for Research and Evaluation instrument and including a systematic review of evidence were included. Data extraction focussed on recommendations regarding continuation or withdrawal of antidepressants and preferred treatment in newly depressed patients. Our initial search resulted in 1094 articles. After first screening, 40 full-text articles were screened. Of these, 24 were excluded for not being an official Clinical Practice Guidelines. In total, 16 Clinical Practice Guidelines were included originating from 12 countries. Eight guidelines were perinatal specific and eight were general guidelines. During pregnancy, four guidelines advise to continue antidepressants, while there is a lack of evidence supporting this recommendation. Five guidelines do not specifically advise or discourage continuation. For new episodes, guidelines agree on psychotherapy (especially cognitive behavioural therapy) as initial treatment for mild to moderate depression and antidepressants for severe depression, with a preference for sertraline. Paroxetine is not preferred treatment for new episodes but switching antidepressants for ongoing treatment is discouraged (three guidelines). If mothers use antidepressants, observation of the neonate is generally recommended and breastfeeding encouraged.

A Pilot Study: Cardiac Parameters in Children Receiving New-Generation Antidepressants.

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Uchida, Mai; Spencer, Andrea E; Kenworthy, Tara; Chan, James; Fitzgerald, Maura; Rosales, Ana Maria; Kagan, Elana; Saunders, Alexandra; Biederman, Joseph

2017-06-01

Because of concerns about potential associations between high doses of citalopram and QTc prolongation in adults, this study examined whether such associations are operant in children. We hypothesized that therapeutic doses of nontricyclic antidepressant medications (non-TCAs) prescribed to children would be cardiovascularly safe. The sample consisted of 49 psychiatrically referred children and adolescents 6 to 17 years old of both sexes treated with a non-TCA (citalopram, escitalopram, fluoxetine, paroxetine, sertraline, bupropion, duloxetine, venlafaxine, mirtazapine). To standardize the doses of different antidepressants, we converted doses of individual medicines into "citalopram equivalent doses" (CEDs) based on dosing recommendation for individual antidepressants. Correlation analysis was carried out to compare the continuous and weight-based CED to variables of interest. A QTc grouping was defined as normal, borderline, or abnormal, and CED was compared across QTc groupings using linear regression. An antidepressant dosage group was defined as low or high dose, and a t test compared variables of interest across dosage groups. No significant associations were found between total or weight-corrected CEDs of any antidepressant examined and QTc or any other electrocardiogram or blood pressure parameters. In patients taking citalopram or escitalopram, a significant correlation was found between PR interval and total daily dose, which disappeared when weight-based doses were used or when corrected by age. Although limited by a relatively small sample size, these results suggest that therapeutic doses of non-TCA antidepressants when used in children do not seem to be associated with prolonged QTc interval or other adverse cardiovascular effects.

Evaluation of Overactive Bladder in Male Antidepressant Users: A Prospective Study

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Volkan Solmaz

2017-03-01

Full Text Available Purpose In this study, we investigated overactive bladder (OAB functions in male patients who used antidepressant drugs (ADs that were previously examined in female patients, based on conflicting data in literature regarding the effects of AD on OAB and the differences between male and female urinary system physiologies (anatomical and hormonal. Methods The study included 202 male patients (a control group of 90 healthy subjects, and an experimental group of 112 patients taking ADs for different disorders. All the patients completed the overactive bladder-validated 8 (OAB-V8 questionnaire, the International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF, and the Beck Depression Inventory (BDS. Results The OAB-V8, ICIQ-SF, and BDS scores for the antidepressant users were significantly higher than those of the control group. The highest prevalence of OAB symptoms was observed in patients taking venlafaxine (68.2%, and the lowest prevalence was in patients taking sertraline (28.0%. Moreover, the frequency of OAB between the antidepressant groups was statistically significant. The univariate logistic regression analyses showed a significant relationship between the presence of OAB, antidepressant usage, BDS score, and the age of a patient. In the multivariate logistic regression analyses, the association between the presence of OAB and antidepressant usage was statistically significant. Conclusions The present study showed that the incidence of OAB and the severity of OAB symptoms increased in males using antidepressants for various disorders. This may have been due to unique pharmacological effects, on a molecular or individual level, of serotonin-norepinephrine reuptake inhibitors.

Factors associated with the prescription of antidepressive medication to breast cancer patients

DEFF Research Database (Denmark)

Suppli, Nis P; Deltour, Isabelle; Damkjaer, Lars H

2011-01-01

We evaluated factors associated with use of antidepressant medication subsequent to a diagnosis of breast cancer. We also evaluated the effect of participation in a cancer rehabilitation program on use of antidepressants....

Antidepressants and Youth Suicide in New York City, 1999-2002

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Leon, Andrew C.; Marzuk, Peter M.; Tardiff, Kenneth; Bucciarelli, Angela; Piper, Tinka Markham; Galea, Sandro

2006-01-01

Objective: To determine the proportion of youth suicides in New York City from 1999 to 2002 in which antidepressants were detected at autopsy. Method: This is a medical examiner surveillance study of suicides in New York City among those younger than 18 years of age. The outcome measure is serum toxicology for antidepressants. Results: From 1999…

Economic impact of antidepressant treatment duration in naturalistic conditions.

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Tournier, M; Crott, R; Gaudron, Y; Verdoux, H

2013-05-01

To assess the economic impact of the duration of antidepressant drug treatment in a real-life setting. A historical fixed cohort study included 27 917 patients aged 18 and over with a new antidepressant treatment registered in the national insurance database. The economic impact concerned healthcare expenditure in the first 3 months after treatment discontinuation. Generalized linear models were used to compare two groups of treatment duration: adjustment for care costs before and during treatment episode, gender, age, chronic diseases, welfare and prescriber specialty, total healthcare costs (in log) [-0.06 (-0.14;0.01) P = 0.11] and psychiatric care costs (in square root) [-0.08 (-0.41;0.25) P = 0.6] were similar in both groups. Non-psychiatric care costs were significantly lower in the 'long treatment duration' group compared with the 'short treatment duration' group [-11.4 (-15.8; -7.0) P costs over the antidepressant treatment episode were larger in the 'long treatment duration' group compared with the 'short treatment duration' group. With regard to healthcare costs and global health, antidepressant drug treatments of short duration appear less effective than treatment of recommended duration. © 2012 John Wiley & Sons A/S. Published by Blackwell Publishing Ltd.

ATYPICAL ANTIPSYCHOTICS USE IN CHILDREN AND ADOLESCENTS

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Nataša Potočnik-Dajčman

2002-06-01

Full Text Available Background. Classical antipsychotics – neuroleptics are one of the most frequently prescribed psychotropic drugs in child psychiatry. Atypical antipsychotics are used for the same indications – psychotic (schizophrenia as well as unpsychotic disorders (pervasive developmental disorders, mood disorders, conduct disorders and tics disorders. It is surprising that the studies on their use with regard to this age group are rather rare. They are carried out on a small number of samples and only exceptionally double blind. This article summarizes published clinical experience with atypical antipsychotics in children and adolescents. A short overview of pharmacodynamics, pharmacokinetics and side effects is given. Schizophrenia and pervasive developmental disorders are major indications for use of atypical antipsychotics in children and adolescents, but they have also been successfully used for other disorders such as aggressive behaviour, tics and anorexia nervosa.Conclusions. With better side-effect profile, some of the atypical antipsychotics are expected to be doctrinally recognised as the first-line treatment for childhood schizophrenia and pervasive developmental disorders. However, more long-term studies carried out on a larger sample are needed. Atypical antipsychotics are already used in everyday practice as first-line treatment of childhood and adolescents schizophrenia.

Antidepressant-Induced Female Sexual Dysfunction.

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Lorenz, Tierney; Rullo, Jordan; Faubion, Stephanie

2016-09-01

Because 1 in 6 women in the United States takes antidepressants and a substantial proportion of patients report some disturbance of sexual function while taking these medications, it is a near certainty that the practicing clinician will need to know how to assess and manage antidepressant-related female sexual dysfunction. Adverse sexual effects can be complex because there are several potentially overlapping etiologies, including sexual dysfunction associated with the underlying mood disorder. As such, careful assessment of sexual function at the premedication visit followed by monitoring at subsequent visits is critical. Treatment of adverse sexual effects can be pharmacological (dose reduction, drug discontinuation or switching, augmentation, or using medications with lower adverse effect profiles), behavioral (exercising before sexual activity, scheduling sexual activity, vibratory stimulation, psychotherapy), complementary and integrative (acupuncture, nutraceuticals), or some combination of these modalities. Copyright © 2016 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.

[Development of an Atypical Response Scale.

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Mendelsohn, Mark; Linden, James

The development of an objective diagnostic scale to measure atypical behavior is discussed. The Atypical Response Scale (ARS) is a structured projective test consisting of 17 items, each weighted 1, 2, or 3, that were tested for convergence and reliability. ARS may be individually or group administered in 10-15 minutes; hand scoring requires 90…

Atypical chemokine receptors in cancer: friends or foes?

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Massara, Matteo; Bonavita, Ornella; Mantovani, Alberto; Locati, Massimo; Bonecchi, Raffaella

2016-06-01

The chemokine system is a fundamental component of cancer-related inflammation involved in all stages of cancer development. It controls not only leukocyte infiltration in primary tumors but also angiogenesis, cancer cell proliferation, and migration to metastatic sites. Atypical chemokine receptors are a new, emerging class of regulators of the chemokine system. They control chemokine bioavailability by scavenging, transporting, or storing chemokines. They can also regulate the activity of canonical chemokine receptors with which they share the ligands by forming heterodimers or by modulating their expression levels or signaling activity. Here, we summarize recent results about the role of these receptors (atypical chemokine receptor 1/Duffy antigen receptor for chemokine, atypical chemokine receptor 2/D6, atypical chemokine receptor 3/CXC-chemokine receptor 7, and atypical chemokine receptor 4/CC-chemokine receptor-like 1) on the tumorigenesis process, indicating that their effects are strictly dependent on the cell type on which they are expressed and on their coexpression with other chemokine receptors. Indeed, atypical chemokine receptors inhibit tumor growth and progression through their activity as negative regulators of chemokine bioavailability, whereas, on the contrary, they can promote tumorigenesis when they regulate the signaling of other chemokine receptors, such as CXC-chemokine receptor 4. Thus, atypical chemokine receptors are key components of the regulatory network of inflammation and immunity in cancer and may have a major effect on anti-inflammatory and immunotherapeutic strategies. © Society for Leukocyte Biology.

Exposure to antidepressants during pregnancy--prevalences and outcomes

DEFF Research Database (Denmark)

Jimenez-Solem, Espen

2014-01-01

conflicting. The main challenge is how to discern between the effects of the drug and the effect of the depression itself. We approached this dire problem conducting a nation-wide register based study analyzing the relation between use of antidepressants during pregnancy and the risk of congenital...... that the apparent risk associated with use of SSRIs during pregnancy is not related to the drug exposure, but to unknown characteristics associated with mothers redeeming a prescription for an antidepressant. We found no increased risk of stillbirths or neonatal mortality among off-spring exposed in utero...

Antidepressants Increase REM Sleep Muscle Tone in Patients with and without REM Sleep Behavior Disorder.

Science.gov (United States)

McCarter, Stuart J; St Louis, Erik K; Sandness, David J; Arndt, Katlyn; Erickson, Maia; Tabatabai, Grace; Boeve, Bradley F; Silber, Michael H

2015-06-01

REM sleep behavior disorder (RBD) is associated with antidepressant treatment, especially in younger patients; but quantitative REM sleep without atonia (RSWA) analyses of psychiatric RBD patients remain limited. We analyzed RSWA in adults receiving antidepressants, with and without RBD. We comparatively analyzed visual, manual, and automated RSWA between RBD and control groups. RSWA metrics were compared between groups, and regression was used to explore associations with clinical variables. Tertiary-care sleep center. Participants included traditional RBD without antidepressant treatment (n = 30, 15 Parkinson disease [PD-RBD] and 15 idiopathic); psychiatric RBD receiving antidepressants (n = 30); and adults without RBD, including antidepressant-treated psychiatric (n = 30), untreated psychiatric (n = 15), and OSA (n = 60) controls. N/A. RSWA was highest in traditional and psychiatric RBD, intermediate in treated psychiatric controls, and lowest in untreated psychiatric and OSA controls (P sleep without atonia (RSWA) even without REM sleep behavior disorder (RBD), suggesting that antidepressants, not depression, promote RSWA. Differences in RSWA distribution and type were also seen, with higher anterior tibialis RSWA in antidepressant-treated patients and higher tonic RSWA in Parkinson disease-RBD patients, which could aid distinction between RBD subtypes. These findings suggest that antidepressants may mediate different RSWA mechanisms or, alternatively, that RSWA type and distribution evolve during progressive neurodegeneration. Further prospective RSWA analyses are necessary to clarify the relationships between antidepressant treatment, psychiatric disease, and RBD. © 2015 Associated Professional Sleep Societies, LLC.

Adverse Effects of Antidepressants for Chronic Pain: A Systematic Review and Meta-analysis

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Carina Riediger

2017-07-01

Full Text Available BackgroundAntidepressants are widely used in the treatment of chronic pain. Applied doses are lower than those needed to unfold an antidepressive effect. While efficacy of antidepressants for chronic pain has been reported in large randomized-controlled trials (RCT, there is inconsistent data on adverse effects and tolerability. We aimed at synthesizing data from RCT to explore adverse effect profiles and tolerability of antidepressants for treatment of chronic pain.MethodsSystematic literature research and meta-analyses were performed regarding side effects and safety of different antidepressants in the treatment of chronic pain according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The National Center for Biotechnology Information library and MEDLINE were searched. Randomized placebo-controlled trials were included in quantitative data synthesis.ResultsOut of 1,975 screened articles, 33 papers published between 1995 and 2015 were included in our review and 23 studies were included in the meta-analyses. A higher risk for adverse effects compared to placebo was observed in all antidepressants included in our analyses, except nortriptyline. The most prevalent adverse effects were dry mouth, dizziness, nausea, headache, and constipation. Amitriptyline, mirtazapine, desipramine, venlafaxine, fluoxetine, and nortriptyline showed the highest placebo effect-adjusted risk of adverse effects. Risk for withdrawal due to adverse effects was highest in desipramine (risk ratio: 4.09, 95%-confidence interval [1.31; 12.82] followed by milnacipran, venlafaxine, and duloxetine. The most common adverse effects under treatment with antidepressants were dry mouth, dizziness, nausea, headache, and constipation followed by palpitations, sweating, and drowsiness. However, overall tolerability was high. Each antidepressant showed distinct risk profiles of adverse effects.ConclusionOur synthesized data analysis confirmed overall

Attitudes and beliefs of patients with chronic depression toward antidepressants and depression

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Jacob SA

2015-05-01

Full Text Available Sabrina Anne Jacob,1 Ab Fatah Ab Rahman,2 Mohamed Azmi Ahmad Hassali3 1School of Pharmacy, Monash University Malaysia, Sunway, 2Faculty of Health Sciences, Gong Badak Campus, Universiti Sultan Zainal Abidin (UniSZA, Kuala Terengganu, 3School of Pharmaceutical Sciences, University of Science Malaysia, Minden, Malaysia Background: Many patients have erroneous views with regard to depression and its management, and it was noted that these attitudes and beliefs significantly affected their adherence rates.Objectives: The primary aim of this study was to determine the attitudes and beliefs of patients with depression toward depression and antidepressants. A secondary aim was to assess the influence of ethnicity on patients’ attitudes and beliefs.Patients and methods: The study involved patients with chronic depression being followed up at an outpatient clinic at a government-run hospital in Malaysia. Patients’ attitudes and beliefs were assessed using the Antidepressant Compliance Questionnaire.Results: A total of 104 patients of Malay, Chinese, and Indian ethnic groups met the selection criteria. Chinese patients had significantly negative attitudes and beliefs toward depression and antidepressants compared to Malays and Indians (b=-8.96, t103=-3.22; P<0.05. Component analysis revealed that 59% of patients believed that antidepressants can cause a person to have less control over their thoughts and feelings, while 67% believed that antidepressants could alter one’s personality; 60% believed it was okay to take fewer tablets on days when they felt better, while 66% believed that antidepressants helped solve their emotional problems and helped them worry less.Conclusion: Patients had an overall positive view as to the benefits of antidepressants, but the majority had incorrect views as to the acceptable dosing of antidepressants and had concerns about the safety of the medication. Assessing patients’ attitudes and beliefs, as well as the

Genetics Home Reference: atypical hemolytic-uremic syndrome

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... Kidney Diseases: Kidney Failure: Choosing a Treatment That's Right for You Educational Resources (6 links) Disease InfoSearch: Hemolytic uremic syndrome, atypical MalaCards: genetic atypical hemolytic-uremic syndrome Merck Manual Consumer Version: Overview of Anemia Merck Manual Consumer Version: ...

[Influence of interleukin-1 beta gene polymorphism and childhood maltreatment on antidepressant treatment].

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Chen, Ying; Zhang, Zhijun; Xu, Zhi; Pu, Mengjia; Geng, Leiyu

2015-12-01

To explore the influence of interleukin-1 beta (IL1B) gene polymorphism and childhood maltreatment on antidepressant treatment. Two hundred and four patients with major depressive disorder (MDD) have received treatment with single antidepressant drugs and were followed up for 8 weeks. Hamilton depression scale-17 (HAMD-17) was used to evaluate the severity of depressive symptoms and therapeutic effect. Childhood maltreatment was assessed using Childhood Trauma Questionnaire, a 28-item Short Form (CTQ-SF). Single nucleotide polymorphism (SNP) of the IL1B gene was determined using a SNaPshot method. Correlation of rs16944 gene polymorphism with response to treatment was analyzed using Unphased 3.0.13 software. The main and interactive effects of SNP and childhood maltreatment on the antidepressant treatment were analyzed using Logistic regression analysis. No significant difference of gender, age, year of education, family history, episode time, and antidepressant agents was detected between the remitters and non-remitters. Association analysis has found that the SNP rs16944 in the IL1B AA genotype carriers antidepressant response was poorer (χ2=3.931, P=0.047). No significant difference was detected in the CTQ scores between the two groups. Genetic and environmental interaction analysis has demonstrated a significant correlation between rs16944 AA genotype and childhood maltreatment and poorer response to antidepressant treatment. The SNP rs16944 in the IL1B gene and its interaction with childhood maltreatment may influence the effect of antidepressant treatment for patients with MDD.

Do continued antidepressants protect against dementia in patients with severe depressive disorder?

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Kessing, Lars Vedel; Forman, Julie Lyng; Andersen, Per Kragh

2011-01-01

may decrease the risk of developing dementia in patients with depression. We investigated whether continued treatment with antidepressants is associated with a decreased rate of dementia in a population of patients discharged from psychiatric healthcare service with a diagnosis of depression. We used...... register data on all prescribed antidepressants in all patients discharged from psychiatric healthcare service with a diagnosis of depression and with subsequent diagnoses of dementia in Denmark from 1995 to 2005. A total of 37 658 patients with a diagnosis of depression at their first psychiatric contact......Studies on humans show that depressive disorder is associated with an increased risk of developing cognitive dysfunction, and animal studies suggest that antidepressants may have neuroprotective abilities. On the basis of these observations, it was hypothesized that treatment with antidepressants...

Age dependence of the rapid antidepressant and synaptic effects of acute NMDA receptor blockade

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Elena eNosyreva

2014-12-01

Full Text Available Ketamine is a NMDA receptor antagonist that produces rapid antidepressant responses in individuals with major depressive disorder. The antidepressant action of ketamine has been linked to blocking NMDA receptor activation at rest, which inhibits eukaryotic elongation factor2 kinase leading to desuppression of protein synthesis and synaptic potentiation in the CA1 region of the hippocampus. Here, we investigated ketamine mediated antidepressant response and the resulting synaptic potentiation in juvenile animals. We found that ketamine did not produce an antidepressant response in juvenile animals in the novelty suppressed feeding or the forced swim test. In addition ketamine application failed to trigger synaptic potentiation in hippocampal slices obtained from juvenile animals, unlike its action in slices from older animals (6-9 weeks old. The inability of ketamine to trigger an antidepressant response or subsequent synaptic plasticity processes suggests a developmental component to ketamine mediated antidepressant efficacy. We also show that the NMDAR antagonist AP5 triggers synaptic potentiation in mature hippocampus similar to the action of ketamine, demonstrating that global competitive blockade of NMDA receptors is sufficient to trigger this effect. These findings suggest that global blockade of NMDA receptors in developmentally mature hippocampal synapses are required for the antidepressant efficacy of ketamine.

Antidepressants use in children and adolescents and the risk of suicide

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Wohlfarth, Tamar D.; van Zwieten, Barbara J.; Lekkerkerker, Frits J.; Gispen-de Wied, Christine C.; Ruis, Jerry R.; Elferink, Andre J. A.; Storosum, Jitschak G.

2006-01-01

Antidepressants use in paediatric patients has been linked with risk of suicidal behaviours. The aim of this paper, therefore, is to examine whether all antidepressants are associated with such risk. All 22 paediatric short-term placebo-controlled trials of SSRIs and NSRIs that were submitted to

In utero exposure to antidepressants and the use of drugs for pulmonary diseases in children

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ter Horst, P. G. J.; Bos, H. J.; de Jong-van de Berg, L. T. W.; Wilffert, B.

Purpose The use of antidepressants during pregnancy is common. Some studies suggest an association between in utero exposure to antidepressants and the occurrence of pulmonary diseases like asthma later in life. Serotonin reuptake inhibitors (SSRIs) as well tricyclic antidepressants (TCAs) are

Efficacy of antidepressants for dysthymia: a meta-analysis of placebo-controlled randomized trials.

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Levkovitz, Yeciel; Tedeschini, Enrico; Papakostas, George I

2011-04-01

The authors sought to determine the efficacy of antidepressants in dysthymic disorder and to compare antidepressant and placebo response rates between major depressive disorder (MDD) and dysthymic disorder. PubMed/MEDLINE databases were searched for double-blind, randomized, placebo-controlled trials of antidepressants used as monotherapy for treatment of MDD or dysthymic disorder. We defined antidepressants as those with a letter of approval by the US, Canadian, or European Union drug regulatory agencies for treatment of MDD or dysthymic disorder, which included the following: amitriptyline, nortriptyline, imipramine, desipramine, clomipramine, trimipramine, protriptyline, dothiepin, doxepin, lofepramine, amoxapine, maprotiline, amineptine, nomifensine, bupropion, phenelzine, tranylcypromine, isocarboxazid, moclobemide, brofaromine, fluoxetine, sertraline, paroxetine, citalopram, escitalopram, fluvoxamine, zimelidine, tianeptine, ritanserin, trazodone, nefazodone, agomelatine, venlafaxine, desvenlafaxine, duloxetine, milnacipran, reboxetine, mirtazapine, and mianserin. Eligible studies were identified by cross-referencing the search term placebo with each of the above-mentioned agents. The search was limited to articles published between January 1, 1980, and November 20, 2009 (inclusive). To expand our database, we also reviewed the reference lists of the identified studies. We selected randomized, double-blind, placebo-controlled trials of antidepressants for either MDD or dysthymic disorder according to preset criteria relating to comorbidities, patient age, drug formulation, study duration, diagnostic criteria, choice of assessment scales, and whether or not the study reported original data. Final selection of articles was determined by consensus among the authors. A total of 194 studies were found that were eligible for inclusion in our analysis. Of these, 177 focused on the treatment of MDD and 17 on the treatment of dysthymic disorder. We found that

Antidepressants for depression in adults with HIV infection.

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Eshun-Wilson, Ingrid; Siegfried, Nandi; Akena, Dickens H; Stein, Dan J; Obuku, Ekwaro A; Joska, John A

2018-01-22

Rates of major depression among people living with HIV (PLWH) are substantially higher than those seen in the general population and this may adversely affect antiretroviral treatment outcomes. Several unique clinical and psychosocial factors may contribute to the development and persistence of depression in PLWH. Given these influences, it is unclear if antidepressant therapy is as effective for PLWH as the general population. To assess the efficacy of antidepressant therapy for treatment of depression in PLWH. We searched The Cochrane Common Mental Disorders Group's specialised register (CCMD-CTR), the Cochrane Library, PubMed, Embase and ran a cited reference search on the Web of Science for reports of all included studies. We conducted additional searches of the international trial registers including; ClinicalTrials.gov, World Health Organization Trials Portal (ICTRP), and the HIV and AIDS - Clinical trials register. We searched grey literature and reference lists to identify additional studies and contacted authors to obtain missing data. We applied no restrictions on date, language or publication status to the searches, which included studies conducted between 1 January 1980 and 18 April 2017. We included randomized controlled trials of antidepressant drug therapy compared to placebo or another antidepressant drug class. Participants eligible for inclusion had to be aged 18 years and older, from any setting, and have both HIV and depression. Depression was defined according to Diagnostic and Statistical Manual of Mental Disorders or International Statistical Classification of Diseases criteria. Two review authors independently applied the inclusion criteria and extracted data. We presented categorical outcomes as risk ratios (RR) with 95% confidence intervals (CIs). Continuous outcomes were presented mean (MD) or standardized mean differences (SMD) with standard deviations (SD). We assessed quality of evidence using the GRADE approach. We included 10 studies

Drug-drug interactions involving antidepressants: focus on desvenlafaxine.

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Low, Yvette; Setia, Sajita; Lima, Graca

2018-01-01

Psychiatric and physical conditions often coexist, and there is robust evidence that associates the frequency of depression with single and multiple physical conditions. More than half of patients with depression may have at least one chronic physical condition. Therefore, antidepressants are often used in cotherapy with other medications for the management of both psychiatric and chronic physical illnesses. The risk of drug-drug interactions (DDIs) is augmented by complex polypharmacy regimens and extended periods of treatment required, of which possible outcomes range from tolerability issues to lack of efficacy and serious adverse events. Optimal patient outcomes may be achieved through drug selection with minimal potential for DDIs. Desvenlafaxine is a serotonin-norepinephrine reuptake inhibitor approved for the treatment of adults with major depressive disorder. Pharmacokinetic studies of desvenlafaxine have shown a simple metabolic profile unique among antidepressants. This review examines the DDI profiles of antidepressants, particularly desvenlafaxine, in relation to drugs of different therapeutic areas. The summary and comparison of information available is meant to help clinicians in making informed decisions when using desvenlafaxine in patients with depression and comorbid chronic conditions.

Is the efficacy of antidepressants in panic disorder mediated by adverse events? A mediational analysis.

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Irene Bighelli

Full Text Available It has been hypothesised that the perception of adverse events in placebo-controlled antidepressant clinical trials may induce patients to conclude that they have been randomized to the active arm of the trial, leading to the breaking of blind. This may enhance the expectancies for improvement and the therapeutic response. The main objective of this study is to test the hypothesis that the efficacy of antidepressants in panic disorder is mediated by the perception of adverse events. The present analysis is based on a systematic review of published and unpublished randomised trials comparing antidepressants with placebo for panic disorder. The Baron and Kenny approach was applied to investigate the mediational role of adverse events in the relationship between antidepressants treatment and efficacy. Fourteen placebo-controlled antidepressants trials were included in the analysis. We found that: (a antidepressants treatment was significantly associated with better treatment response (ß = 0.127, 95% CI 0.04 to 0.21, p = 0.003; (b antidepressants treatment was not associated with adverse events (ß = 0.094, 95% CI -0.05 to 0.24, p = 0.221; (c adverse events were negatively associated with treatment response (ß = 0.035, 95% CI -0.06 to -0.05, p = 0.022. Finally, after adjustment for adverse events, the relationship between antidepressants treatment and treatment response remained statistically significant (ß = 0.122, 95% CI 0.01 to 0.23, p = 0.039. These findings do not support the hypothesis that the perception of adverse events in placebo-controlled antidepressant clinical trials may lead to the breaking of blind and to an artificial inflation of the efficacy measures. Based on these results, we argue that the moderate therapeutic effect of antidepressants in individuals with panic disorder is not an artefact, therefore reflecting a genuine effect that doctors can expect to replicate under real-world conditions.

Antidepressant drugs specifically inhibiting noradrenaline reuptake enhance recognition memory in rats.

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Feltmann, Kristin; Konradsson-Geuken, Åsa; De Bundel, Dimitri; Lindskog, Maria; Schilström, Björn

2015-12-01

Patients suffering from major depression often experience memory deficits even after the remission of mood symptoms, and many antidepressant drugs do not affect, or impair, memory in animals and humans. However, some antidepressant drugs, after a single dose, enhance cognition in humans (Harmer et al., 2009). To compare different classes of antidepressant drugs for their potential as memory enhancers, we used a version of the novel object recognition task in which rats spontaneously forget objects 24 hr after their presentation. Antidepressant drugs were injected systemically 30 min before or directly after the training phase (Session 1 [S1]). Post-S1 injections were used to test for specific memory-consolidation effects. The noradrenaline reuptake inhibitors reboxetine and atomoxetine, as well as the serotonin noradrenaline reuptake inhibitor duloxetine, injected prior to S1 significantly enhanced recognition memory. In contrast, the serotonin reuptake inhibitors citalopram and paroxetine and the cyclic antidepressant drugs desipramine and mianserin did not enhance recognition memory. Post-S1 injection of either reboxetine or citalopram significantly enhanced recognition memory, indicating an effect on memory consolidation. The fact that citalopram had an effect only when injected after S1 suggests that it may counteract its own consolidation-enhancing effect by interfering with memory acquisition. However, pretreatment with citalopram did not attenuate reboxetine's memory-enhancing effect. The D1/5-receptor antagonist SCH23390 blunted reboxetine's memory-enhancing effect, indicating a role of dopaminergic transmission in reboxetine-induced recognition memory enhancement. Our results suggest that antidepressant drugs specifically inhibiting noradrenaline reuptake enhance cognition and may be beneficial in the treatment of cognitive symptoms of depression. (c) 2015 APA, all rights reserved).

Antidepressants for depression in patients with dementia: a review of the literature.

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Leong, Christine

2014-04-01

To evaluate the literature investigating the efficacy and safety of antidepressants for treating depression in individuals with dementia. A literature search was conducted using MEDLINE, PUBMED, EMBASE, and Cochrane databases from inception to May 2013 for studies in English that evaluated the treatment of depression in patients with dementia. All relevant randomized controlled trials (RCTs) and meta-analyses were identified using the search terms "dementia" or "Alzheimer's disease," and "depression" or "major depressive disorder." Reference lists from retrieved articles and practice guidelines were also searched for relevant literature. Only randomized, placebo-controlled trials and meta-analyses that compared an antidepressant with placebo for the treatment of depression in patients with dementia were included. In this systematic review, 10 RCTs and 3 meta-analyses were identified that examined the efficacy and safety of antidepressants compared with placebo in treating depression in patients with dementia. The majority of the RCTs consisted of a small sample size, and the antidepressants studied were not routinely used in practice. The evidence for antidepressants in the treatment of depression in patients with dementia is inconclusive. The accumulation of evidence suggests nonpharmacologic approaches and watchful waiting be attempted for the first 8 to 12 weeks in a patient who presents with both mild-to-moderate depression and dementia. In cases of severe depression, or depression not managed through nonpharmacologic means, a trial of an antidepressant may be initiated. However, further well-designed trials are needed to support these recommendations.

Factors associated with the prescription of antidepressive medication to breast cancer patients

DEFF Research Database (Denmark)

Suppli, Nis P; Deltour, Isabelle; Damkjaer, Lars H

2011-01-01

We evaluated factors associated with use of antidepressant medication subsequent to a diagnosis of breast cancer. We also evaluated the effect of participation in a cancer rehabilitation program on use of antidepressants. Material and methods. We conducted a register-based cohort study of 1 247...... women with breast cancer diagnosed between 1998 and 2006 who attended a week-long rehabilitation program and a comparison group of 2 903 women who did not attend the program matched through the registers of the Danish Breast Cancer Cooperative Group. The associations between breast cancer......-related, treatment-related, and sociodemographic factors and use of antidepressants were evaluated in multivariate Cox proportional hazard models separated on use of antidepressants before diagnosis of breast cancer. Results. The mean follow-up for the 4 150 women in the study was 3.3 years (5-95% range, 0...

Neurogenesis and The Effect of Antidepressants

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Philippe Taupin

2006-01-01

Full Text Available The recent evidence that neurogenesis occurs throughout adulthood and neural stem cells (NSCs reside in the adult central nervous system (CNS suggests that the CNS has the potential for self-repair. Beside this potential, the function of newly generated neuronal cells in the adult brain remains the focus of intense research. The hippocampus of patients with depression show signs of atrophy and neuronal loss. This suggests that adult neurogenesis may contribute to the biology of depression. The observations that antidepressants, like fluoxetine, increase neurogenesis in the dentate gyrus (DG and neurogenesis is required for the behavioral effect of antidepressants, lead to a new theory for depression and the design of new strategies and drugs for the treatment of depression. However, the role of adult neurogenesis in the etiology of depression remains the source of controversies and debates.

Neurogenesis and the Effect of Antidepressants

Directory of Open Access Journals (Sweden)

Philippe Taupin

2006-01-01

Full Text Available The recent evidence that neurogenesis occurs throughout adulthood and neural stem cells (NSCs reside in the adult central nervous system (CNS suggests that the CNS has the potential for self-repair. Beside this potential, the function of newly generated neuronal cells in the adult brain remains the focus of intense research. The hippocampus of patients with depression show signs of atrophy and neuronal loss. This suggests that adult neurogenesis may contribute to the biology of depression. The observations that antidepressants, like fluoxetine, increase neurogenesis in the dentate gyrus (DG and neurogenesis is required for the behavioral effect of antidepressants, lead to a new theory for depression and the design of new strategies and drugs for the treatment of depression. However, the role of adult neurogenesis in the etiology of depression remains the source of controversies and debates.

Beliefs about medications predict adherence to antidepressants in older adults.

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Fawzi, Waleed; Abdel Mohsen, Mohamed Yousry; Hashem, Abdel Hamid; Moussa, Suaad; Coker, Elizabeth; Wilson, Kenneth C M

2012-01-01

Adherence to treatment is a complex and poorly understood phenomenon. This study investigates the relationship between older depressed patients' adherence to antidepressants and their beliefs about and knowledge of the medication. Assessment was undertaken of 108 outpatients over the age of 55 years diagnosed with depressive disorder and treated for at least four weeks with antidepressants. Adherence was assessed using two self-report measures: the Medication Adherence Rating Scale (MARS) and a Global Adherence Measure (GAM). Potential predictors of adherence investigated included sociodemographic, medication and illness variables. In addition, 33 carers were interviewed regarding general medication beliefs. 56% of patients reported 80% or higher adherence on the GAM. Sociodemographic variables were not associated with adherence on the MARS. Specific beliefs about medicines, such as "my health depends on antidepressants" (necessity) and being less worried about becoming dependant on antidepressants (concern) were highly correlated with adherence. General beliefs about medicines causing harm or being overprescribed, experiencing medication side-effects and severity of depression also correlated with poor adherence. Linear regression with the MARS as the dependent variable explained 44.3% of the variance and showed adherence to be higher in subjects with healthy specific beliefs who received more information about antidepressants and worse with depression severity and autonomic side-effects. Our findings strongly support a role for specific beliefs about medicines in adherence. Challenging patients' beliefs, providing information about treatment and discussing side-effects could improve adherence. Poor response to treatment and medication side-effects can indicate poor adherence and should be considered before switching medications.

Depression, antidepressants, and bone mineral density in a population-based cohort.

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Mezuk, Briana; Eaton, William W; Golden, Sherita Hill; Wand, Gary; Lee, Hochang Benjamin

2008-12-01

It is uncertain whether depression and antidepressant use are associated with decreased bone mineral density (BMD) and whether these relationships differ for men and women. The study used a case-cohort design within the Baltimore Epidemiologic Catchment Area Study, a population-based sample of adults that recently completed its 23-year follow-up. Depression was measured at four time points during the follow-up period by the Diagnostic Interview Schedule. Lower spine BMD was measured at the fourth wave by dual-energy x-ray absorptiometry. The association of BMD with lifetime history of depression and antidepressant medication use was studied using linear regression with bootstrap standard errors. A history of depression was associated with lower spine BMD after controlling for age, sex, race, calcium intake, alcohol use, smoking status, level of physical activity, percent body fat, and antidepressant medication use (-0.140 g/cm(2); p history of depression predicted decreased lumbar spine BMD in men and women, and antidepressant use predicted decreased BMD in women even after controlling for depression. The magnitude of the effect of depression on BMD was approximately equivalent to 1 standard deviation in BMD and was therefore clinically significant. Providers should be aware of the physiologic consequences of depression as well as the possible risks to bone strength associated with antidepressant use in older patients.

Antidepressant Use is Associated with Increased Energy Intake and Similar Levels of Physical Activity

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Elsbeth Jensen-Otsu

2015-11-01

Full Text Available Antidepressants have been associated with weight gain, but the causes are unclear. The aims of this study were to assess the association of antidepressant use with energy intake, macronutrient diet composition, and physical activity. We used data on medication use, energy intake, diet composition, and physical activity for 3073 eligible adults from the 2005–2006 National Health and Nutrition Examination Survey (NHANES. Potential confounding variables, including depression symptoms, were included in the models assessing energy intake, physical activity, and sedentary behavior. Antidepressant users reported consuming an additional (mean ± S.E. 215 ± 73 kcal/day compared to non-users (p = 0.01. There were no differences in percent calories from sugar, fat, or alcohol between the two groups. Antidepressant users had similar frequencies of walking or biking, engaging in muscle-strengthening activities, and engaging in moderate or vigorous physical activity. Antidepressant users were more likely to use a computer for ≥2 h/day (OR 1.77; 95% CI: 1.09–2.90, but TV watching was similar between the two groups. These results suggest increased energy intake and sedentary behavior may contribute to weight gain associated with antidepressant use. Focusing on limiting food intake and sedentary behaviors may be important in mitigating the weight gain associated with antidepressant use.

Emotional blunting with antidepressant treatments: A survey among depressed patients.

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Goodwin, G M; Price, J; De Bodinat, C; Laredo, J

2017-10-15

Emotional blunting is regularly reported in depressed patients on antidepressant treatment but its actual frequency is poorly understood. We have previously used qualitative methods to develop an appropriate scale, the Oxford Questionnaire on the Emotional Side-Effects of Antidepressants (OQESA). Six hundred and sixty nine depressed patients on treatment and 150 recovered (formerly depressed) controls (aged ≥18 years) participated in this internet-based survey. The rate of emotional blunting in treated depressed patients was 46%, slightly more frequent in men than women (52% versus 44%) and in those with higher Hospital Anxiety and Depression (HAD) scale scores. There was no difference according to antidepressant agent, though it appeared less frequent with bupropion. Depressed patients with emotional blunting had much higher total blunting scores on OQESA than controls (42.83 ± 14.73 versus 25.73 ± 15.00, p 7 (n = 170) had a higher total questionnaire score, 49.23±12.03, than those with HAD-D score ≤7 (n = 140), 35.07 ± 13.98, and the difference between the two groups was highly significant. However, patients with HAD-D score ≤7 (n = 140) had a higher total score (35.07 ± 13.98) than the recovered controls (n = 150) (25.73 ± 15.00), and the difference between the two groups was significant. Among the patients with emotional blunting, 37% had a negative perception of their condition and 38% positive. Men reported a more negative perception than women (p=0.008), and patients with a negative perception were more likely to have higher HAD scores. Higher levels of emotional blunting are associated with a more negative perception of it by the patient (r = -0.423). Include self-evaluation and the modest size of the sample for detection of differences between antidepressants. Emotional blunting is reported by nearly half of depressed patients on antidepressants. It appears to be common to all monoaminergic antidepressants. The OQESA scores are highly

Use of antidepressants and risk of epithelial ovarian cancer

DEFF Research Database (Denmark)

Mørch, Lina S; Dehlendorff, Christian; Baandrup, Louise

2017-01-01

antidepressants, selective serotonin reuptake inhibitors, other antidepressants, and potential confounder drugs), medical and reproductive history and socioeconomic parameters, were obtained from nationwide registries. We used conditional logistic regression models to estimate adjusted odds ratios (ORs) and two.......80 (95% CI, 0.60-1.08). Among postmenopausal women, the inverse association was restricted to users of menopausal hormone therapy. In conclusion, use of selective serotonin reuptake inhibitors was associated with a decreased risk of epithelial ovarian cancer; thereby implying potential chemopreventive...

Antidepressant potential of nitrogen-containing heterocyclic moieties: An updated review

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Nadeem Siddiqui

2011-01-01

Full Text Available Depression is currently the fourth leading cause of disease or disability worldwide. Antidepressant is approved for the treatment of major depression (including paediatric depression, obsessive-compulsive disorder (in both adult and paediatric populations, bulimia nervosa, panic disorder and premenstrual dysphoric disorder. Antidepressant is a psychiatric medication used to alleviate mood disorders, such as major depression and dysthymia and anxiety disorders such as social anxiety disorder. Many drugs produce an antidepressant effect, but restrictions on their use have caused controversy and off-label prescription a risk, despite claims of superior efficacy. Our current understanding of its pathogenesis is limited and existing treatments are inadequate, providing relief to only a subset of people suffering from depression. Reviews of literature suggest that heterocyclic moieties and their derivatives has proven success in treating depression.

Psychosocial work environment and antidepressant medication: a prospective cohort study

DEFF Research Database (Denmark)

Bonde, Jens Peter; Munch-Hansen, T.; Wieclaw, J.

2009-01-01

BACKGROUND: Adverse psychosocial work environments may lead to impaired mental health, but it is still a matter of conjecture if demonstrated associations are causal or biased. We aimed at verifying whether poor psychosocial working climate is related to increase of redeemed subscription...... alone. None of the measured psychosocial work environment factors were consistently related to prescription of antidepressant drugs during the follow-up period. CONCLUSION: The study does not indicate that a poor psychosocial work environment among public service employees is related to prescription...... of antidepressant medication. METHODS: Information on all antidepressant drugs (AD) purchased at pharmacies from 1995 through 2006 was obtained for a cohort of 21,129 Danish public service workers that participated in work climate surveys carried out during the period 2002-2005. Individual self...

Efficacy and feasibility of antidepressants for the prevention of migraine in adults: a meta-analysis.

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Xu, X-M; Yang, C; Liu, Y; Dong, M-X; Zou, D-Z; Wei, Y-D

2017-08-01

Migraine has greatly impacted the quality of life for migraineurs and was ranked as the seventh highest specific cause of disability worldwide in 2012. Because of the role of serotonin in migraine mechanisms, antidepressants have been used in the prevention of migraine. However, the role of antidepressants for migraine prophylaxis in adults has not been completely established. Our aim was systematically to assess the efficacy and feasibility of antidepressants for the prevention of migraine in adults based on currently available literature. A comprehensive search of databases was conducted including the Cochrane, PubMed, Web of Science and Embase databases from inception to July 2016. Randomized controlled trials that assigned adults with a clinical diagnosis of migraine to antidepressant or placebo treatment were included. The primary outcome was the reduction of migraine frequency or index. Overall, 16 randomized controlled trials including 1082 participants were identified. Antidepressants had a significant advantage over placebo in reducing the migraine frequency or index of adults with a standardized mean difference of -0.79 [95% confidence interval (CI) -1.13 to -0.45, P < 0.00001]. Patients receiving antidepressant therapy were more likely to experience an at least 50% reduction of headache burden than those receiving placebo (28.9% vs. 20.2%; risk ratio 1.40; 95% CI 0.97-2.02; P = 0.07). However, antidepressants were less well tolerated than placebo because of some adverse events (risk ratio 1.74, 95% CI 1.05-2.89, P = 0.03). Antidepressants are effective in the prophylaxis of migraine in adults, but the level of evidence for antidepressants except for amitriptyline seems to be quite shaky. © 2017 EAN.

Malignant atypical cell in urine cytology: a diagnostic dilemma

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Kakkar Nandita

2006-01-01

Full Text Available Abstract Aims The aim of this study was to find out the characteristic morphology of malignant atypical cells which were missed on routine cytology of urine. Materials and methods In this retrospective study, we examined detailed cytomorphology of 18 cases of atypical urinary cytology which were missed on routine examination and were further proved on histopathology as transitional cell carcinoma (TCC of bladder. The cytological features of these cases were compared with 10 cases of benign urine samples. Results There were 11 cases of high grade TCC and 7 cases of low grade TCC on histopathology of the atypical urine samples. Necrosis in the background and necrosed papillae were mostly seen in malignant atypical cells. The comet cells and cells with India ink nuclei (single cells with deep black structure-less nuclei were only observed in malignant atypical cells. The most consistent features in malignant atypical cells were: i high nuclear and cytoplasmic (N/C ratio ii nuclear pleomorphism iii nuclear margin irregularity iv hyperchromasia and v chromatin abnormalities Conclusion The present study emphasizes that nuclear features such as high N/C ratio, hyperchromasia and chromatin abnormalities are particularly useful for assessing the malignant atypical cells. Other cytological features such as comet cells and cells with India ink nuclei are also helpful for diagnosis but have limited value because they are less frequently seen.

Maternal depression, antidepressant use in pregnancy and Apgar scores in infants

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Jensen, Hans Mørch; Grøn, Randi; Lidegaard, Øjvind

2013-01-01

Use of antidepressants during pregnancy has been associated with a low Apgar score in infants but a contribution from the underlying depressive disorder might influence this association.......Use of antidepressants during pregnancy has been associated with a low Apgar score in infants but a contribution from the underlying depressive disorder might influence this association....

Sensitivity to changes during antidepressant treatment: a comparison of unidimensional subscales of the Inventory of Depressive Symptomatology (IDS-C) and the Hamilton Depression Rating Scale (HAMD) in patients with mild major, minor or subsyndromal depression.

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Helmreich, Isabella; Wagner, Stefanie; Mergl, Roland; Allgaier, Antje-Kathrin; Hautzinger, Martin; Henkel, Verena; Hegerl, Ulrich; Tadić, André

2012-06-01

In the efficacy evaluation of antidepressant treatments, the total score of the Hamilton Depression Rating Scale (HAMD) is still regarded as the 'gold standard'. We previously had shown that the Inventory of Depressive Symptomatology (IDS) was more sensitive to detect depressive symptom changes than the HAMD17 (Helmreich et al. 2011). Furthermore, studies suggest that the unidimensional subscales of the HAMD, which capture the core depressive symptoms, outperform the full HAMD regarding the detection of antidepressant treatment effects. The aim of the present study was to compare several unidimensional subscales of the HAMD and the IDS regarding their sensitivity to changes in depression symptoms in a sample of patients with mild major, minor or subsyndromal depression (MIND). Biweekly IDS-C28 and HAMD17 data from 287 patients of a 10-week randomised, placebo-controlled trial comparing the effectiveness of sertraline and cognitive-behavioural group therapy in patients with MIND were converted to subscale scores and analysed during the antidepressant treatment course. We investigated sensitivity to depressive change for all scales from assessment-to-assessment, in relation to depression severity level and placebo-verum differences. The subscales performed similarly during the treatment course, with slight advantages for some subscales in detecting treatment effects depending on the treatment modality and on the items included. Most changes in depressive symptomatology were detected by the IDS short scale, but regarding the effect sizes, it performed worse than most subscales. Unidimensional subscales are a time- and cost-saving option in judging drug therapy outcomes, especially in antidepressant treatment efficacy studies. However, subscales do not cover all facets of depression (e.g. atypical symptoms, sleep disturbances), which might be important for comprehensively understanding the nature of the disease depression. Therefore, the cost-to-benefit ratio must be

Is nitric oxide signalling involved in the antidepressant action of ketamine?

DEFF Research Database (Denmark)

Liebenberg, Nico; Müller, Heidi Kaastrup; Elfving, Betina

2012-01-01

Background and Aim: Stress-induced excessive glutamate transmission at N-methyl-D-aspartate (NMDA) receptors may underlie a major mechanism in the pathophysiology that leads to depression, while ketamine, an NMDA receptor antagonist, has been shown to induce a rapid antidepressant effect in depre......Background and Aim: Stress-induced excessive glutamate transmission at N-methyl-D-aspartate (NMDA) receptors may underlie a major mechanism in the pathophysiology that leads to depression, while ketamine, an NMDA receptor antagonist, has been shown to induce a rapid antidepressant effect...... in depressed patients following a single intravenous administration that is sustained for ± 7 days. A number of downstream cellular mechanisms appear to mediate the antidepressant action of ketamine, and the majority of evidence point to a rapid activation of protein translation leading to increased synaptic...... receptors, while the uncoupling of the nNOS-NMDA receptor complex prevents NMDA-induced excitotoxicity. Thus, it is possible that the inhibition of nitric oxide (NO) signalling underlies a key upstream mechanism in the antidepressant action of ketamine. Methods: We used a genetic rat model of depression...

Antidepressant Drugs for Chronic Urological Pelvic Pain: An Evidence-Based Review

Directory of Open Access Journals (Sweden)

Christos Papandreou

2009-01-01

Full Text Available The use of antidepressant drugs for the management of chronic pelvic pain has been supported in the past. This study aimed to evaluate the available evidence for the efficacy and acceptability of antidepressant drugs in the management of urological chronic pelvic pain. Studies were selected through a comprehensive literature search. We included all types of study designs due to the limited evidence. Studies were classified into levels of evidence according to their design. Ten studies were included with a total of 360 patients. Amitriptyline, sertraline, duloxetine, nortriptyline, and citalopram are the antidepressants that have been reported in the literature. Only four randomized controlled trials (RCTs were identified (two for amitriptyline and two for sertraline with mixed results. We conclude that the use of antidepressants for the management of chronic urological pelvic pain is not adequately supported by methodologically sound RCTs. From the existing studies amitriptyline may be effective in interstitial cystitis but publication bias should be considered as an alternative explanation. All drugs were generally well tolerated with no serious events reported.

Atypical Food Packaging Affects The Persuasive Impact of Product Claims

NARCIS (Netherlands)

van Ooijen, M.L.; Fransen, P.W.J.; Verlegh, P.W.J.; Smit, E.G.

2016-01-01

Atypical food packaging draws attention in the retail environment, and therefore increases product salience. However, until now, no research has focused on how atypical packaging affects the persuasive impact of other food information. In the present study, we propose that atypical packaging

Atypical food packaging affects the persuasive impact of product claims

NARCIS (Netherlands)

van Ooijen, I.; Fransen, M.L.; Verlegh, P.W.J.; Smit, E.G.

Atypical food packaging draws attention in the retail environment, and therefore increases product sal- ience. However, until now, no research has focused on how atypical packaging affects the persuasive impact of other food information. In the present study, we propose that atypical packaging

Antidepressant effects of Mentha pulegium in mice

Directory of Open Access Journals (Sweden)

Zahra Rabiei

2016-09-01

Full Text Available The aim of this study is to investigate the antidepressant effects of Mentha pulegium essential oil in BALB/c mice. Six experimental groups (7 mice each were used. Forced swim test was performed 30 min after essential oil injection. In the groups receiving M. pulegium essential oil (50, 75 and 100 mg/kg, immobility duration significantly decreased compared to the control group. M. pulegium (50 and 75 mg/kg resulted in significant decrease in nitrate/nitrite content in serum compared to the control group. M. pulegium essential oil antidepressant effect that may be due to the inhibition of oxidative stress. The results showed that decrease in nitrate/nitrite content in serum and high anti-oxidant effects of M. pulegium essential oil.

Antidepressant-like responses in the forced swimming test elicited by glutathione and redox modulation.

Science.gov (United States)

Rosa, Juliana M; Dafre, Alcir Luiz; Rodrigues, Ana Lúcia S

2013-09-15

Glutathione (GSH) displays a broad range of functions, among them a role as a neuromodulator with some neuroprotective properties. Taking into account that oxidative stress has been associated with depressive disorders, this study investigated the possibility that GSH, a major cell antioxidant, elicits an antidepressant-like effect in mice. Thus, GSH was administered by i.c.v. route to mice that were tested in the forced swimming test and in the tail suspension test, two predictive tests for antidepressant drug activity. In addition, GSH metabolism and the redox environment were modulated in order to study the possible mechanisms underlying the effects of GSH in the forced swimming test. The administration of GSH decreased the immobility time in the forced swimming test (300-3000nmol/site) and tail suspension test (100-1000nmol/site), consistent with an antidepressant-like effect. GSH depletion elicited by l-buthionine sulfoximine (3.2μmol/site, i.c.v.) did not alter the antidepressant-like effect of GSH, whereas the inhibition of extracellular GSH catabolism by acivicin (100nmol/site, i.c.v.) prevented the antidepressant-like effect of GSH. Moreover, a sub-effective dose (0.01nmol/site, i.c.v.) of the oxidizing agent DTNB (5,5'-dithiobis(2-nitrobenzoic acid)) potentiated the effect of GSH (100nmol/site, i.c.v.), while the pretreatment (25-100mg/kg, i.p.) with the reducing agent DTT (dl-dithiothreitol) prevented the antidepressant-like effect of GSH (300nmol/site, i.c.v.). DTNB (0.1nmol/site, i.c.v.), produced an antidepressant-like effect, per se, which was abolished by DTT (25mg/kg, i.p.). The results show, for the first time, that centrally administered GSH produces an antidepressant-like effect in mice, which can be modulated by the GSH metabolism and the thiol/disulfide reagents. The redox environment may constitute a new venue for future antidepressant-drug development. Copyright © 2013 Elsevier B.V. All rights reserved.

Chronic antidepressant administration alleviates frontal and hippocampal BDNF deficits in CUMS rat.

Science.gov (United States)

Zhang, Yang; Gu, Fenghua; Chen, Jia; Dong, Wenxin

2010-12-17

Stress activates the hypothalamo-pituitary-adrenal (HPA) axis, regulates the expression of brain-derived neurotrophic factor (BDNF) in the brain, and mediates mood. Antidepressants alleviate stress and up-regulate BDNF gene expression. In this study, we investigated the effect of chronic unpredictable mild stress (CUMS) and the different kinds of antidepressant treatments on the HPA axis and the BDNF expression in the rat brain. Adult Wistar male rats were exposed to a six-week CUMS procedure and received different antidepressant treatments including venlafaxine, mirtazapine, and fluoxetine. Immunohistochemistry and real-time PCR were used to measure BDNF expression levels in the rat brain, and ELISAs were used to investigate the plasma corticosterone (CORT) and adrenocorticotropic hormone (ACTH) levels. CUMS significantly decreased the BDNF protein level in the DG, CA1, and CA3 of the hippocampus and increased plasma CORT level. Chronic antidepressant treatments all significantly increased BDNF protein levels in the hippocampus and the pre-frontal cortex. In addition, venlafaxine and mirtazapine inhibited the increase of plasma CORT level. These results suggested that an increase in the BDNF level in the brain could be a pivotal mechanism of various antidepressants to exert their therapeutic effects. Copyright © 2010 Elsevier B.V. All rights reserved.

Use of antipsychotics in the treatment of depressive disorders

Institute of Scientific and Technical Information of China (English)

Ping WANG; Tianmei SI

2013-01-01

There is a long history of using antipsychotic medications in the treatment of depressive disorders. Atypical antipsychotics, which have fewer side effects than traditional antipsychotics, have been used as monotherapy or adjunctively with antidepressants to treat depressive disorders with or without psychotic symptoms. The antidepressant effect of atypical antipsychotics involves regulation of monoamine, glutamate, gamma-aminobutyric acid (GABA), cortisol, and neurotrophic factors. To date, the United States Food and Drug Administration (USFDA) has approved aripiprazole and quetiapine slow-release tablets as adjunctive treatment for depressive disorders, and the combination of olanzapine and fluoxetine for the treatment of treatment-resistant depression. When using atypical antipsychotics in the treatment of depressed patients, clinicians need to monitor patients for the emergence of adverse effects including extrapyramidal symptoms (EPS), weight gain, and hyperglycemia.

Antidepressant activity of curcumin: involvement of serotonin and dopamine system.

Science.gov (United States)

Kulkarni, Shrinivas K; Bhutani, Mohit Kumar; Bishnoi, Mahendra

2008-12-01

Curcumin is a major active principle of Curcuma longa, one of the widely used preparations in the Indian system of medicine. It is known for its diverse biological actions. The present study was designed to investigate the involvement of monoaminergic system(s) in the antidepressant activity of curcumin and the effect of piperine, a bioavailability enhancer, on the bioavailability and biological effects of curcumin. Behavioral (forced swim test), biochemical (monoamine oxidase (MAO) enzyme inhibitory activity), and neurochemical (neurotransmitter levels estimation) tests were carried out. Curcumin (10-80 mg/kg, i.p.) dose dependently inhibited the immobility period, increased serotonin (5-hydroxytryptamine, 5-HT) as well as dopamine levels (at higher doses), and inhibited the monoamine oxidase enzymes (both MAO-A and MAO-B, higher doses) in mice. Curcumin (20 mg/kg, i.p.) enhanced the anti-immobility effect of subthreshold doses of various antidepressant drugs like fluoxetine, venlafaxine, or bupropion. However, no significant change in the anti-immobility effect of imipramine and desipramine was observed. Furthermore, combination of subthreshold dose of curcumin and various antidepressant drugs resulted in synergistic increase in serotonin (5-HT) levels as compared to their effect per se. There was no change in the norepinephrine levels. The coadministration of piperine (2.5 mg/kg, i.p.), a bioavailability enhancing agent, with curcumin (20 and 40 mg/kg, i.p.) resulted in potentiation of pharmacological, biochemical, and neurochemical activities. The study provides evidences for mechanism-based antidepressant actions of curcumin. The coadministration of curcumin along with piperine may prove to be a useful and potent natural antidepressant approach in the management of depression.

Differential effect of an anticholinergic antidepressant on sleep-dependent memory consolidation.

Science.gov (United States)

Goerke, Monique; Cohrs, Stefan; Rodenbeck, Andrea; Kunz, Dieter

2014-05-01

Rapid eye movement (REM) sleep is considered critical to the consolidation of procedural memory - the memory of skills and habits. Many antidepressants strongly suppress REM sleep, however, and procedural memory consolidation has been shown to be impaired in depressed patients on antidepressant therapy. As a result, it is important to determine whether antidepressive therapy can lead to amnestic impairment. We thus investigated the effects of the anticholinergic antidepressant amitriptyline on sleep-dependent memory consolidation. Double-blind, placebo-controlled, randomized, parallel-group study. Sleep laboratory. Twenty-five healthy men (mean age: 26.8 ± 5.6 y). 75 mg amitriptyline versus placebo. To test memory consolidation, a visual discrimination task, a finger-tapping task, the Rey-Osterrieth Complex Figure Test, and the Rey Auditory-Verbal Learning Test were performed. Sleep was measured using polysomnography. Our findings show that amitriptyline profoundly suppressed REM sleep and impaired perceptual skill learning, but not motor skill or declarative learning. Our study is the first to demonstrate that an antidepressant can affect procedural memory consolidation in healthy subjects. Moreover, considering the results of a recent study, in which selective serotonin reuptake inhibitors and serotonin-norepinephrine reuptake inhibitors were shown not to impair procedural memory consolidation, our findings suggest that procedural memory consolidation is not facilitated by the characteristics of REM sleep captured by visual sleep scoring, but rather by the high cholinergic tone associated with REM sleep. Our study contributes to the understanding of potentially undesirable behavioral effects of amitriptyline.

Antidepressant drugs and the risk of suicide in children and adolescents.

Science.gov (United States)

Isacsson, Göran; Rich, Charles L

2014-04-01

Government agencies have issued warnings about the use of antidepressant medications in children, adolescents, and young adults since 2003. The statements warn that such medications may cause de novo 'suicidality' in some people. This review explores the data on the treatment of depression that led to these warnings and subsequent data that are relevant to the warnings. It also addresses the effectiveness of antidepressant treatment in general and the relationship of suicide rates to antidepressant treatment. It concludes that the decisions for the 'black box' warnings were based on biased data and invalid assumptions. Furthermore, the decisions were unsupported by the observational data regarding suicide in young people that existed in 2003. The following recommendations would seem to follow from these observations. First, drug authorities should re-evaluate the basis for their imposed warnings on antidepressant medicines, and analyze the actual public health consequences the warnings have had. In the absence of substantial evidence supporting the warnings, they should be removed. Second, physicians and other providers with prescription privileges should continue to be educated regarding the importance of aggressively treating depression in young people, using antidepressants when indicated. Third, physicians and other professionals who treat depressed young people must always be aware of the risk of suicide (albeit quite low) and observe them closely for any signs of increased risk of suicide. This is necessary regardless of the type of treatment being provided.

Drug–drug interactions involving antidepressants: focus on desvenlafaxine

Science.gov (United States)

Low, Yvette; Setia, Sajita; Lima, Graca

2018-01-01

Psychiatric and physical conditions often coexist, and there is robust evidence that associates the frequency of depression with single and multiple physical conditions. More than half of patients with depression may have at least one chronic physical condition. Therefore, antidepressants are often used in cotherapy with other medications for the management of both psychiatric and chronic physical illnesses. The risk of drug–drug interactions (DDIs) is augmented by complex polypharmacy regimens and extended periods of treatment required, of which possible outcomes range from tolerability issues to lack of efficacy and serious adverse events. Optimal patient outcomes may be achieved through drug selection with minimal potential for DDIs. Desvenlafaxine is a serotonin–norepinephrine reuptake inhibitor approved for the treatment of adults with major depressive disorder. Pharmacokinetic studies of desvenlafaxine have shown a simple metabolic profile unique among antidepressants. This review examines the DDI profiles of antidepressants, particularly desvenlafaxine, in relation to drugs of different therapeutic areas. The summary and comparison of information available is meant to help clinicians in making informed decisions when using desvenlafaxine in patients with depression and comorbid chronic conditions. PMID:29497300

Trace analysis of antidepressant pharmaceuticals and their select degradates in aquatic matrixes by LC/ESI/MS/MS

Science.gov (United States)

Schultz, M.M.; Furlong, E.T.

2008-01-01

Treated wastewater effluent is a potential environmental point source for antidepressant pharmaceuticals. A quantitative method was developed for the determination of trace levels of antidepressants in environmental aquatic matrixes using solid-phase extraction coupled with liquid chromatography- electrospray ionization tandem mass spectrometry. Recoveries of parent antidepressants from matrix spiking experiments for the individual antidepressants ranged from 72 to 118% at low concentrations (0.5 ng/L) and 70 to 118% at high concentrations (100 ng/L) for the solid-phase extraction method. Method detection limits for the individual antidepressant compounds ranged from 0.19 to 0.45 ng/L. The method was applied to wastewater effluent and samples collected from a wastewater-dominated stream. Venlafaxine was the predominant antidepressant observed in wastewater and river water samples. Individual antidepressant concentrations found in the wastewater effluent ranged from 3 (duloxetine) to 2190 ng/L (venlafaxine), whereas individual concentrations in the waste-dominated stream ranged from 0.72 (norfluoxetine) to 1310 ng/L (venlafaxine). ?? 2008 American Chemical Society.

Oxidative/nitrosative stress and antidepressants: targets for novel antidepressants.

Science.gov (United States)

Lee, Seung-Yup; Lee, Soo-Jung; Han, Changsu; Patkar, Ashwin A; Masand, Prakash S; Pae, Chi-Un

2013-10-01

The brain is an organ predisposed to oxidative/nitrosative stress. This is especially true in the case of aging as well as several neurodegenerative diseases. Under such circumstances, a decline in the normal antioxidant defense mechanisms leads to an increase in the vulnerability of the brain to the deleterious effects of oxidative damage. Highly reactive oxygen/nitrogen species damage lipids, proteins, and mitochondrial and neuronal genes. Unless antioxidant defenses react appropriately to damage inflicted by radicals, neurons may experience microalteration, microdysfunction, and degeneration. We reviewed how oxidative and nitrosative stresses contribute to the pathogenesis of depressive disorders and reviewed the clinical implications of various antioxidants as future targets for antidepressant treatment. Copyright © 2012 Elsevier Inc. All rights reserved.

Potentially inappropriate medication: Association between the use of antidepressant drugs and the subsequent risk for dementia.

Science.gov (United States)

Heser, Kathrin; Luck, Tobias; Röhr, Susanne; Wiese, Birgitt; Kaduszkiewicz, Hanna; Oey, Anke; Bickel, Horst; Mösch, Edelgard; Weyerer, Siegfried; Werle, Jochen; Brettschneider, Christian; König, Hans-Helmut; Fuchs, Angela; Pentzek, Michael; van den Bussche, Hendrik; Scherer, Martin; Maier, Wolfgang; Riedel-Heller, Steffi G; Wagner, Michael

2018-01-15

Potentially inappropriate medication (PIM) is associated with an increased risk for detrimental health outcomes in elderly patients. Some antidepressant drugs are considered as PIM, but previous research on the association between antidepressants and subsequent dementia has been inconclusive. Therefore, we investigated whether the intake of antidepressants, particularly of those considered as PIM according to the Priscus list, would predict incident dementia. We used data of a prospective cohort study of non-demented primary care patients (n = 3239, mean age = 79.62) to compute Cox proportional hazards models. The risk for subsequent dementia was estimated over eight follow-ups up to 12 years depending on antidepressant intake and covariates. The intake of antidepressants was associated with an increased risk for subsequent dementia (HR = 1.53, 95% CI: 1.16-2.02, p = .003; age-, sex-, education-adjusted). PIM antidepressants (HR = 1.49, 95% CI: 1.06-2.10, p = .021), but not other antidepressants (HR = 1.04, 95% CI: 0.66-1.66, p = .863), were associated with an increased risk for subsequent dementia (in age-, sex-, education-, and depressive symptoms adjusted models). Significant associations disappeared after global cognition at baseline was controlled for. Methodological limitations such as selection biases and self-reported drug assessments might have influenced the results. Only antidepressants considered as PIM were associated with an increased subsequent dementia risk. Anticholinergic effects might explain this relationship. The association disappeared after the statistical control for global cognition at baseline. Nonetheless, physicians should avoid the prescription of PIM antidepressants in elderly patients whenever possible. Copyright © 2017 Elsevier B.V. All rights reserved.

Antidepressants and Suicide Risk: A Comprehensive Overview

Directory of Open Access Journals (Sweden)

Roberto Tatarelli

2010-08-01

Full Text Available The annual worldwide suicide rate currently averages approximately 13 per 100,000 individuals per year (0.013% per year, with higher average rates for men than for women in all but a few countries, very low rates in children, and relatively high rates in elderly men. Suicide rates vary markedly between countries, reflecting in part differences in case-identification and reporting procedures. Rates of attempted suicide in the general population average 20–30 times higher than rates of completed suicide, but are probably under-reported. Research on the relationship between pharmacotherapy and suicidal behavior was rare until a decade ago. Most ecological studies and large clinical studies have found that a general reduction in suicide rates is significantly correlated with higher rates of prescribing modern antidepressants. However, ecological, cohort and case-control studies and data from brief, randomized, controlled trials in patients with acute affective disorders have found increases, particularly in young patients and particularly for the risk of suicide attempts, as well as increases in suicidal ideation in young patients. whether antidepressants are associated with specific aspects of suicidality (e.g., higher rates of completed suicide, attempted suicide and suicidal ideation in younger patients with major affective disorders remains a highly controversial question. In light of this gap this paper analyzes research on the relationship between suicidality and antidepressant treatment.

Preclinical evidence of rapid-onset antidepressant-like effect in Radix Polygalae extract.

Directory of Open Access Journals (Sweden)

Im-Joon Shin

Full Text Available Radix Polygalae (the root of Polygala tenuifolia is a herb widely used in traditional Asian medicine that is thought to exert a variety of neuropsychiatric effects. Radix Polygalae extract can protect against N-methyl D-aspartate (NMDA neurotoxicity and induce brain-derived neurotrophic factor (BDNF expression, suggesting modulatory roles at glutamatergic synapses and possible antidepressant action. In accordance with this hypothesis, Radix Polygalae extract demonstrated antidepressant-like effects in 8-week-old male C57Bl/6 mice by decreasing behavioral despair in the forced swim and tail suspension tasks and increasing hedonic-like behavior in the female urine sniffing test 30 minutes after a single oral administration of 0.1 mg/kg. Reduced latency to acquire a food pellet in the novely suppressed feeding paradigm, without change in anxiety-like behaviors suggested a rapid-onset nature of the antidepressant-like effect. In addition, it decreased the number of failed escapes in the learned helplessness paradigm after two oral administrations 24 hours and 30 minutes before the first test. Finally, it reversed anhedonia as measured by saccharin preference in mice exposed to the chronic stress model after two administrations of 0.1 mg/kg, in contrast to the repeated administration generally needed for similar effect by monoamergic antidepressants. Immobility reduction in tail suspension task was blocked by the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA receptor antagonist NBQX, a pattern previously demonstrated by ketamine and other ketamine-like rapid-onset antidepressants. Also similarly to ketamine, Radix Polygalae appeared to acutely decrease phosphorylation of GluR1 serine-845 in the hippocampus while leaving the phosphorylation of hippocampal mTOR serine 2448 unchanged. These findings serve as preclinical evidence that Radix Polygalae extract exerts rapid-onset antidepressant effects by modulating glutamatergic synapses in

Antidepressant induced sexual dysfunction Part 1: epidemiology ...

African Journals Online (AJOL)

Adele

Abstract. Sexual dysfunction is a common side effect of treatment with antidepressants, particularly those with a predominantly .... free of serotonergic effects or have highly selective receptor .... received little attention in the current literature.

Atypical Presentations of Tularemia.

Science.gov (United States)

Odegaard, Karah; Boersma, Beth; Keegan, James

2017-05-01

Francisella tularensis is a gram-negative coccobacillus that causes a condition commonly referred to as tularemia. There has been a dramatic increase in tularemia cases reported in South Dakota, many of which were challenging to diagnose due to atypical clinical manifestations. We describe an interesting case of pneumonic tularemia and summarize six similar cases, several of which presented with lung nodules suggestive of malignancy. According to the literature, this is only the third outbreak of pneumonic tularemia reported in the U.S. We believe it is important for clinicians to be aware of the increased incidence of tularemia in the area and to be vigilant in the diagnosis and management of these atypically presenting cases. Copyright© South Dakota State Medical Association.

Using time-series intervention analysis to understand U.S. Medicaid expenditures on antidepressant agents.

Science.gov (United States)

Ferrand, Yann; Kelton, Christina M L; Guo, Jeff J; Levy, Martin S; Yu, Yan

2011-03-01

Medicaid programs' spending on antidepressants increased from $159 million in 1991 to $2 billion in 2005. The National Institute for Health Care Management attributed this expenditure growth to increases in drug utilization, entry of newer higher-priced antidepressants, and greater prescription drug insurance coverage. Rising enrollment in Medicaid has also contributed to this expenditure growth. This research examines the impact of specific events, including branded-drug and generic entry, a black box warning, direct-to-consumer advertising (DTCA), and new indication approval, on Medicaid spending on antidepressants. Using quarterly expenditure data for 1991-2005 from the national Medicaid pharmacy claims database maintained by the Centers for Medicare and Medicaid Services, a time-series autoregressive integrated moving average (ARIMA) intervention analysis was performed on 6 specific antidepressant drugs and on overall antidepressant spending. Twenty-nine potentially relevant interventions and their dates of occurrence were identified from the literature. Each was tested for an impact on the time series. Forecasts from the models were compared with a holdout sample of actual expenditure data. Interventions with significant impacts on Medicaid expenditures included the patent expiration of Prozac® (P0.05), implying that the expanding market for antidepressants overwhelmed the effect of generic competition. Copyright © 2011 Elsevier Inc. All rights reserved.

[Atypical cerebellar neurocytoma resembling a hemangioblastoma. A case report].

Science.gov (United States)

Lista Martínez, Olalla; Rivas López, Luis Alfredo; Pombo Otero, Jorge Francisco; Amaro Cendón, Santiago; Bravo García, Christian; Villa Fernández, Juan Manuel

2014-01-01

Through August 2013, 105 cases of intracranial extraventricular neurocytoma (EVN) had been described; 6% were located in cerebellum and 22% were atypical EVN. A rare morphologic form of neurocytoma, atypical EVN has had only 24 cases reported to date. Its prognosis is poorer than the typical central neurocytoma. This case report describes an atypical cerebellar EVN, a form that has not been reported yet, hence the interest of this article. We emphasise its cystic nature and mural nodule, in an infrequent presentation. EVN are low-incidence tumours that we need to take into consideration when making the differential diagnosis of cystic cerebellar lesions with mural nodule. Given that the prognosis of atypical EVNs depends on the atypical nature and on the grade of resection, medical follow up has to be more constant, due to the greater degree of recurrence. Copyright © 2013 Sociedad Española de Neurocirugía. Published by Elsevier España. All rights reserved.

Amide proton transfer imaging for differentiation of benign and atypical meningiomas

Energy Technology Data Exchange (ETDEWEB)

Joo, Bio [The Armed Forces Capital Hospital, Department of Radiology, Seongnam, Gyeonggi-do (Korea, Republic of); Han, Kyunghwa; Choi, Yoon Seong; Lee, Seung-Koo [Yonsei University College of Medicine, Department of Radiology and Research Institute of Radiological Science, College of Medicine, Seoul (Korea, Republic of); Ahn, Sung Soo [Yonsei University College of Medicine, Department of Radiology and Research Institute of Radiological Science, College of Medicine, Seoul (Korea, Republic of); Yonsei University, Department of Radiology, College of Medicine, Seoul (Korea, Republic of); Chang, Jong Hee; Kang, Seok-Gu [Yonsei University College of Medicine, Department of Neurosurgery, Seoul (Korea, Republic of); Kim, Se Hoon [Yonsei University College of Medicine, Department of Pathology, Seoul (Korea, Republic of); Zhou, Jinyuan [Johns Hopkins University School of Medicine, Division of MRI Research, Department of Radiology, Baltimore, MD (United States)

2018-01-15

To investigate the difference in amide proton transfer (APT)-weighted signals between benign and atypical meningiomas and determine the value of APT imaging for differentiating the two. Fifty-seven patients with pathologically diagnosed meningiomas (benign, 44; atypical, 13), who underwent preoperative MRI with APT imaging between December 2014 and August 2016 were included. We compared normalised magnetisation transfer ratio asymmetry (nMTR{sub asym}) values between benign and atypical meningiomas on APT-weighted images. Conventional MRI features were qualitatively assessed. Both imaging features were evaluated by multivariable logistic regression analysis. The discriminative value of MRI with and without nMTR{sub asym} was evaluated. The nMTR{sub asym} of atypical meningiomas was significantly greater than that of benign meningiomas (2.46% vs. 1.67%; P < 0.001). In conventional MR images, benign and atypical meningiomas exhibited significant differences in maximum tumour diameter, non-skull base location, and heterogeneous enhancement. On multivariable logistic regression analysis, high nMTR{sub asym} was an independent predictor of atypical meningiomas (adjusted OR, 11.227; P = 0.014). The diagnostic performance of MRI improved with nMTR{sub asym} for predicting atypical meningiomas. Atypical meningiomas exhibited significantly higher APT-weighted signal intensities than benign meningiomas. The discriminative value of conventional MRI improved significantly when combined with APT imaging for diagnosis of atypical meningioma. (orig.)

Elevated plasma fibrinogen, psychological distress, antidepressant use, and hospitalization with depression

DEFF Research Database (Denmark)

Wium-Andersen, Marie Kim; Ørsted, David Dynnes; Nordestgaard, Børge Grønne

2013-01-01

with depression in the general population. METHODS: We examined 73,367 20-100 year old men and women from two large population-based studies, the Copenhagen General Population Study and the Copenhagen City Heart Study. We measured plasma fibrinogen and recorded symptoms of psychological distress, use......OBJECTIVES: Low-grade systemic inflammation may contribute to the development of depression. We tested the hypothesis that elevated plasma levels of the inflammatory marker fibrinogen are associated with psychological distress, use of antidepressant medication, and with hospitalization...... of antidepressant medication, and hospitalization with depression in both cross-sectional and prospective studies. RESULTS: In cross-sectional analyses, a stepwise increase in fibrinogen percentile categories was associated with a stepwise increase in risk of psychological distress, use of antidepressant medication...

Treating depression with antidepressants: drug-placebo efficacy debates limit broader considerations.

Science.gov (United States)

Yapko, Michael D

2013-01-01

The core issue regarding antidepressants for many clinicians is whether they perform significantly better than placebos. However, this article suggests eight additional concerns beyond drug efficacy alone to consider regarding antidepressants including: (1) formulating only a one-dimensional, biological view of depression; (2) defining the client's role as passive in treatment; (3) economic corruption of the research and reporting; (4) false or misleading consumer advertising; (5) conflicting data that confuse practitioners and consumers alike; (6) over- and under-prescription of medications; (7) drug side-effects; and (8) harm to the environment. The enhanced effects of psychotherapy utilizing hypnosis offer a means of avoiding most, if not all, of the problems associated with the use of antidepressants as a primary form of treatment.

Atypical Pneumonia: Updates on Legionella, Chlamydophila, and Mycoplasma Pneumonia.

Science.gov (United States)

Sharma, Lokesh; Losier, Ashley; Tolbert, Thomas; Dela Cruz, Charles S; Marion, Chad R

2017-03-01

Community-acquired pneumonia (CAP) has multiple causes and is associated with illness that requires admission to the hospital and mortality. The causes of atypical CAP include Legionella species, Chlamydophila, and Mycoplasma. Atypical CAP remains a diagnostic challenge and, therefore, likely is undertreated. This article reviews the advancements in the evaluation and treatment of patients and discusses current conflicts and controversies of atypical CAP. Copyright © 2016 Elsevier Inc. All rights reserved.

Antidepressants induce autophagy dependent-NLRP3-inflammasome inhibition in Major depressive disorder.

Science.gov (United States)

Alcocer-Gómez, Elísabet; Casas-Barquero, Nieves; Williams, Matthew R; Romero-Guillena, Samuel L; Cañadas-Lozano, Diego; Bullón, Pedro; Sánchez-Alcazar, José Antonio; Navarro-Pando, José M; Cordero, Mario D

2017-07-01

Major Depressive Disorder (MDD, ICD-10: F-33) is a prevalent illness in which the pathogenic mechanism remains elusive. Recently an important role has been attributed to neuro-inflammation, and specifically the NLRP3-inflammasome complex, in the pathogenesis of MDD. This suggests a key role for immunomodulation as a key pathway in the treatment of this disorder. This study evaluates the involvement of nine common antidepressants in the NLRP3-inflammasome complex (fluoxetine, paroxetine, mianserin, mirtazapine, venlafaxine, desvenlafaxine, amitriptyline, imipramine and agomelatine), both in in vitro THP-1 cells stimulated by ATP, and in a stress-induced depressive animal or MDD patients. Antidepressant treatment induced inflammasome inhibition was observed by decreased serum levels of IL-1β and IL-18 and decrease of NLRP3 and IL-1β (p17) protein expression. This was also observed under stress-induced depressive behaviour and inflammasome activation in C57Bl/6 mice in vivo. Deletion of key autophagy mediator Atg5 in embryonic fibroblasts (MEF cells) showed an autophagy dependent-NLRP3-inflammasome inhibition by antidepressant treatment. These results suggest the NLRP3-inflammasome could be a biomarker for antidepressant treatment response in MDD patients, and therefore the monitoring of NLRP3 expression levels and/or IL-1β/IL-18 release may have clinical value in drug selection. Existing evidence suggests an anti-inflammatory effect of some antidepressants shown by IL-1β, IL-6 and TNF-α. Our data have shown that antidepressant-mediated autophagy may have a role in restoration of certain metabolic and immunological pathways in MDD patients. Copyright © 2017 Elsevier Ltd. All rights reserved.

Misleading advertising for antidepressants in Sweden: a failure of pharmaceutical industry self-regulation.

Science.gov (United States)

Zetterqvist, Anna V; Mulinari, Shai

2013-01-01

The alleged efficacy of pharmaceutical industry self-regulation has been used to repudiate increased government oversight over promotional activity. European politicians and industry have cited Sweden as an excellent example of self-regulation based on an ethical code. This paper considers antidepressant advertising in Sweden to uncover the strengths and weaknesses of self-regulation. We analyzed all antidepressant advertisements in the Swedish Medical Journal, 1994-2003. The regulation of these advertisements was analyzed using case reports from self-regulatory bodies. The authors independently reviewed this material to investigate: (1) extent of violative advertising; (2) pattern of code breaches; (3) rate at which the system reacted to violative advertising; (4) prevalence of and oversight over claims regarding antidepressant efficacy and disease causality, and (5) costs for manufactures associated with violative advertising. Self-regulatory bodies identified numerous code breaches. Nonetheless, they failed to protect doctors from unreliable information on antidepressants, since as many as 247 of 722 (34%) advertisements breached the industry code. Self-regulatory bodies repeatedly failed to challenge inflated claims of antidepressant efficacy, lending evidence of lax oversight. On average, 15 weeks elapsed between printing and censure of a wrongful claim, and in 25% of cases 47 weeks or more elapsed. Industry paid roughly €108000 in fines for violative advertising, adding an estimated additional average cost of 11% to each purchased violative advertisement, or amounting to as little as 0.009% of total antidepressant sales of around €1.2 billion. Lax oversight, combined with lags in the system and low fines for violations, may explain the Swedish system's failure to pressure companies into providing reliable antidepressants information. If these shortcomings prove to be consistent across self-regulatory settings, and if appropriate measures are not taken to

Antidepressant treatment and suicide attempts and self-inflicted injury in children and adolescents.

Science.gov (United States)

Gibbons, Robert D; Coca Perraillon, Marcelo; Hur, Kwan; Conti, Rena M; Valuck, Robert J; Brent, David A

2015-02-01

In the 2004, FDA placed a black box warning on antidepressants for risk of suicidal thoughts and behavior in children and adolescents. The purpose of this paper is to examine the risk of suicide attempt and self-inflicted injury in depressed children ages 5-17 treated with antidepressants in two large observational datasets taking account time-varying confounding. We analyzed two large US medical claims databases (MarketScan and LifeLink) containing 221,028 youth (ages 5-17) with new episodes of depression, with and without antidepressant treatment during the period of 2004-2009. Subjects were followed for up to 180 days. Marginal structural models were used to adjust for time-dependent confounding. For both datasets, significantly increased risk of suicide attempts and self-inflicted injury were seen during antidepressant treatment episodes in the unadjusted and simple covariate adjusted analyses. Marginal structural models revealed that the majority of the association is produced by dynamic confounding in the treatment selection process; estimated odds ratios were close to 1.0 consistent with the unadjusted and simple covariate adjusted association being a product of chance alone. Our analysis suggests antidepressant treatment selection is a product of both static and dynamic patient characteristics. Lack of adjustment for treatment selection based on dynamic patient characteristics can lead to the appearance of an association between antidepressant treatment and suicide attempts and self-inflicted injury among youths in unadjusted and simple covariate adjusted analyses. Marginal structural models can be used to adjust for static and dynamic treatment selection processes such as that likely encountered in observational studies of associations between antidepressant treatment selection, suicide and related behaviors in youth. Copyright © 2014 John Wiley & Sons, Ltd.

Antidepressant exposure in pregnancy and risk of autism spectrum disorders

Directory of Open Access Journals (Sweden)

Sørensen MJ

2013-11-01

Full Text Available Merete Juul Sørensen,1 Therese Koops Grønborg,2 Jakob Christensen,3,4 Erik Thorlund Parner,2 Mogens Vestergaard,5,6 Diana Schendel,7 Lars Henning Pedersen8,9 1Regional Centre of Child and Adolescent Psychiatry, Aarhus University Hospital, Risskov, Denmark; 2Department of Public Health, Section of Biostatistics, Aarhus University, Aarhus, Denmark; 3Department of Neurology, Aarhus University Hospital, Aarhus, Denmark; 4Department of Clinical Pharmacology, 5Department of Public Health, Section of General Practice, 6Research unit for General Practice, Aarhus University, Aarhus, Denmark; 7Centers for Disease Control and Prevention, Atlanta, GA, USA; 8Danish Epidemiological Science Centre, Institute of Public Health, 9Department of Obstetrics and Gynecology, Institute of Clinical Medicine, Aarhus University, Aarhus, Denmark Background: Both the use of antidepressant medication during pregnancy and the prevalence of autism spectrum disorder have increased during recent years. A causal link has recently been suggested, but the association may be confounded by the underlying indication for antidepressant use. We investigated the association between maternal use of antidepressant medication in pregnancy and autism, controlling for potential confounding factors. Methods: We identified all children born alive in Denmark 1996–2006 (n=668,468 and their parents in the Danish Civil Registration System. We obtained information on the mother's prescriptions filled during pregnancy from the Danish National Prescription Registry, and on diagnoses of autism spectrum disorders in the children and diagnoses of psychiatric disorders in the parents from the Danish Psychiatric Central Register. In a cohort analysis, we estimated hazard ratios of autism spectrum disorders in children exposed to antidepressant medication during pregnancy compared with children who were not exposed, using Cox proportional hazards regression analysis. Furthermore, we estimated the risk

Poor response to antidepressants predicts new suicidal ideas and behavior in depressed outpatients.

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Courtet, Philippe; Jaussent, Isabelle; Lopez-Castroman, Jorge; Gorwood, Philip

2014-10-01

Only a few studies have investigated the factors associated with suicidal behavior after antidepressant treatment onset in adults. We examined the specific predictors of de novo suicidal ideas or attempts among depressed patients in the community, including subjects potentially at risk of suicidal behaviors, who initiated a new antidepressant treatment. A large set of GPs and psychiatrists throughout France followed-up, for 6 weeks, 4357 outpatients for whom an antidepressant drug was prescribed. Dimensions related with antidepressant-induced suicidal events, such as depression, anxiety or hopelessness, were assessed longitudinally using univariate and multivariate approaches among subjects with treatment-emergent suicide ideation or attempts. New suicidal ideas were observed in 9% of patients with no suicidal ideation at baseline (n=81), while suicidal attempts were reported for 1.7% of the sample during the 6-week observation period (n=75). The onset of suicidal ideas and attempts was associated with the initial features of the patients (baseline level of anxiety, past history of suicide attempts and alcohol misuse) and the non-improvement of depression. Worsening of depressive symptoms during the follow-up increased the onset of new suicidal ideas (OR=5.67, pideas or attempts, the link between antidepressants and suicide risk might be more adequately explained by a poor response to antidepressant treatment rather than by a direct trigger-effect. This naturalistic study is limited by the use of non-structured diagnoses and self-report outcomes. Copyright © 2014 Elsevier B.V. and ECNP. All rights reserved.

Cyclodextrins improving the physicochemical and pharmacological properties of antidepressant drugs: a patent review.

Science.gov (United States)

Diniz, Tâmara Coimbra; Pinto, Tiago Coimbra Costa; Menezes, Paula Dos Passos; Silva, Juliane Cabral; Teles, Roxana Braga de Andrade; Ximenes, Rosana Christine Cavalcanti; Guimarães, Adriana Gibara; Serafini, Mairim Russo; Araújo, Adriano Antunes de Souza; Quintans Júnior, Lucindo José; Almeida, Jackson Roberto Guedes da Silva

2018-01-01

Depression is a serious mood disorder and is one of the most common mental illnesses. Despite the availability of several classes of antidepressants, a substantial percentage of patients are unresponsive to these drugs, which have a slow onset of action in addition to producing undesirable side effects. Some scientific evidence suggests that cyclodextrins (CDs) can improve the physicochemical and pharmacological profile of antidepressant drugs (ADDs). The purpose of this paper is to disclose current data technology prospects involving antidepressant drugs and cyclodextrins. Areas covered: We conducted a patent review to evaluate the antidepressive activity of the compounds complexed in CDs, and we analyzed whether these complexes improved their physicochemical properties and pharmacological action. The present review used 8 specialized patent databases for patent research, using the term 'cyclodextrin' combined with 'antidepressive agents' and its related terms. We found 608 patents. In the end, considering the inclusion criteria, 27 patents reporting the benefits of complexation of ADDs with CDs were included. Expert opinion: The use of CDs can be considered an important tool for the optimization of physicochemical and pharmacological properties of ADDs, such as stability, solubility and bioavailability.

New potential antitumoral fluorescent tetracyclic thieno[3,2-b]pyridine derivatives: interaction with DNA and nanosized liposomes

Directory of Open Access Journals (Sweden)

Calhelha Ricardo

2011-01-01

Full Text Available Abstract Fluorescence properties of two new potential antitumoral tetracyclic thieno[3,2-b]pyridine derivatives were studied in solution and in liposomes of DPPC (dipalmitoyl phosphatidylcholine, egg lecithin (phosphatidylcholine from egg yolk; Egg-PC and DODAB (dioctadecyldimethylammonium bromide. Compound 1, pyrido[2',3':3,2]thieno[4,5-d]pyrido[1,2-a]pyrimidin-6-one, exhibits reasonably high fluorescence quantum yields in all solvents studied (0.20 ≤ ΦF ≤ 0.30, while for compound 2, 3-[(p-methoxyphenylethynyl]pyrido[2',3':3,2]thieno[4,5-d]pyrido[1,2-a]pyrimidin-6-one, the values are much lower (0.01 ≤ ΦF ≤ 0.05. The interaction of these compounds with salmon sperm DNA was studied using spectroscopic methods, allowing the determination of intrinsic binding constants, K i = (8.7 ± 0.9 × 103 M-1 for compound 1 and K i = (5.9 ± 0.6 × 103 M-1 for 2, and binding site sizes of n = 11 ± 3 and n = 7 ± 2 base pairs, respectively. Compound 2 is the most intercalative compound in salmon sperm DNA (35%, while for compound 1 only 11% of the molecules are intercalated. Studies of incorporation of both compounds in liposomes of DPPC, Egg-PC and DODAB revealed that compound 2 is mainly located in the hydrophobic region of the lipid bilayer, while compound 1 prefers a hydrated and fluid environment.

Antidepressant screening and flavonoids isolation from ...

African Journals Online (AJOL)

Eremostachys laciniata (L) Bunge (Lamiaceae), a rich source of flavonoids, has been investigated for chemical constituents and in vivo antidepressant property using forced swim test (FST) model. Five important compounds were isolated, including luteolin (1), apigenin (2), 5,8-dihydroxy-6,7- dimethoxyflavone (3), 5 ...

Atypical pathogens and challenges in community-acquired pneumonia

African Journals Online (AJOL)

Atypical organisms such as Mycoplasma pneumoniae, Chlamydia pneumoniae, and Legionella pneumophila are implicated in up to 40 percent of cases of community-acquired pneumonia. Antibiotic treatment is empiric and includes coverage for both typical and atypical organisms. Doxycycline, a fluoroquinolone with ...

Interplay between the key proteins of serotonin system in SSRI antidepressants efficacy.

Science.gov (United States)

Kulikov, Alexander V; Gainetdinov, Raul R; Ponimaskin, Evgeni; Kalueff, Allan V; Naumenko, Vladimir S; Popova, Nina K

2018-04-01

Selective serotonin reuptake inhibitors (SSRIs) are the most effective and most used antidepressant drugs. Acting by inhibiting serotonin (5-HT) transporter, SSRIs display a typical 3-4-week delay in their therapeutic effects, with nearly 40% of depressed patients remaining treatment-resistant. Recent evidence suggests complex interplay between 5-HT receptors and key proteins of 5-HT metabolism in molecular mechanisms of such delay and resistance to SSRIs. Area covered: This paper concentrates on the interplay between 5-HT receptors in the delay of therapeutic effect of SSRIs, and the interaction between tryptophan hydroxylase 2 and 5-HT transporter in the SSRI resistance. Specifically, it discusses: (1) the data on the association between antidepressant drug efficacy and genetically defined characteristics of key proteins in the 5-HT signaling (TPH2, MAOA, SERT and 5-HT 1A receptor), (2) the effect of dimerization of 5-HT 7 and 5-HT 1A receptors on the internalization and functioning of 5-HT 1A presynaptic receptors, (3) the role of Tph2 deficiency in the resistance to SSRIs treatment. We shift the emphasis from individual proteins to their interactions in explaining antidepressant action of SSRI. Expert opinion: These interactions should be considered when developing more effective antidepressant drugs as well as for predicting and improving the efficacy of antidepressant therapies.

Patients' perceptions and illness severity at start of antidepressant treatment in general practice

NARCIS (Netherlands)

Van Geffen, Erica C.G.; Heerdink, Eiebert R.; Hugtenburg, Jacqueline G.; Siero, Frans W.; Egberts, Antoine C.G.; Van Hulten, Rolf

2010-01-01

Objectives Patients' perceptions are important to consider when trying to understand why patients often do not follow prescriptions for antidepressant treatment. This study aimed to investigate the influence of patients' perceptions and illness severity at the start on antidepressant-medication-

Selective uptake and biological consequences of environmentally relevant antidepressant pharmaceutical exposures on male fathead minnows

Science.gov (United States)

Schultz, Melissa M.; Painter, Meghan M.; Bartell, Stephen E.; Logue, Amanda; Furlong, Edward T.; Werner, Stephen L.; Schoenfuss, Heiko L.

2011-01-01

Antidepressant pharmaceuticals have been reported in wastewater effluent at the nanogram to low microgram-per-liter range, and include bupropion (BUP), fluoxetine (FLX), sertraline (SER), and venlafaxine (VEN). To assess the effects of antidepressants on reproductive anatomy, physiology, and behavior, adult male fathead minnows (Pimeplwles promelas) were exposed for 21 days either to a single concentration of the antidepressants FLX, SER, VEN, or BUP, or to an antidepressant mixture. The data demonstrated that exposure to VEN (305 ng/L and 1104 ng/L) and SER (5.2 ng/L) resulted in mortality. Anatomical alterations were noted within the testes of fish exposed to SER and FLX, both modulators of the neurotransmitter serotonin. Additionally, FLX at 28 ng/L induced vitellogenin in male fish—a common endpoint for estrogenic endocrine disruption. Significant alterations in male secondary sex characteristics were noted with single exposures. Effects of single compound exposures neither carried over, nor became additive in the antidepressant mixtures, and reproductive behavior was not affected. Analysis of brain tissues from the exposed fish suggested increased uptake of FLX, SER and BUP and minimal uptake of VEN when compared to exposure water concentrations. Furthermore, the only metabolite detected consistently in the brain tissues was norfluoxetine. Similar trends of uptake by brain tissue were observed when fish were exposed to antidepressant mixtures. The present study demonstrates that anatomy and physiology, but not reproductive behavior, can be disrupted by exposure to environmental concentrations of some antidepressants. The observation that antidepressant uptake into fish tissues is selective may have consequences on assessing the mode-of-action and effects of these compounds in future studies.

Computerized tomography findings on schizophrenia and atypical psychosis

International Nuclear Information System (INIS)

Hayashi, Takuji; Watanabe, Toyonobu; Kito, Hiroshi; Sekine, Takeo

1988-01-01

The brain CTs of 54 endogenous psychotics (27 males, 27 females) who were less than 40 years of age and were first adimitted in Aichi Medical University from 1982 to 1986, and 20 controls (10 males, 10 females) were examined. Using Mitsuda's classification, we devided all the cases into 29 schizophrenics (18 males, 11 females) and 25 atypical psychotics (9 males, 16 females). In order to investigate the differences of CT findings between the two patient groups, the 3rd ventricle index (the ratio of 3rd ventricle width to the internal diameter of the skull), Evans'ratio, lateral ventricle brain ratio (VBR), Sylvian fissure to brain ratio, 4th ventricle to cerebellum ratio were determined. Schizophrenics had larger 3rd and lateral ventricles as well as Sylvian fissures when compared to controls, but atypical psychotics had not. Moreover, schizophrenics had larger 3rd and lateral ventricle than atypical psychotics. But in widths of Sylvian fissures there was no statistical significant difference between the two groups. Ventricle enlargements of schizophrenics did not correlate with duration of illness as well as age, and were not results of prior psychiatric treatment such as medication and EST. Therefore the following is suggested that, this abnormal CT findings predate the onset of schizophrenic psychoses. In atypical psychotics the changes of Sylvian fissures correlated with duration of illness, but not with age. Such observations may possibly suggest that recurrence of the illness might finally attain irreversible changes even in atypical psychotics. Finally, the heterogeneity of schizophrenia and the independence of atypical psychosis were also discussed. (author) 53 refs

Tricyclic antidepressant overdose necessitating ICU admission ...

African Journals Online (AJOL)

Tricyclic antidepressant (TCA) overdose necessitating intensive care unit (ICU) admission remains a significant problem in the Western Cape. In this retrospective study, we reviewed the course of life-threatening TCA overdose in our centre to identify potential prognostic indicators. TCA levels >1 000 ng/ml were associated ...

The Use of Electroconvulsive Therapy in Atypical Psychotic Presentations

Science.gov (United States)

Vasu, Devi

2007-01-01

Convulsive therapy and its progeny, electroconvulsive therapy (ECT), were originally used for the treatment of catatonic schizophrenia, and there is little doubt that ECT remains an effective intervention for the treatment of schizophrenia. However, current practice tends to favor the use of ECT in severe or treatment refractory affective disorders, and its use in schizophrenia and other nonaffective (atypical) psychotic disorders has become controversial. Case reports have suggested a role for ECT in two specific atypical psychotic disorders: Cotard's syndrome and cycloid psychosis. In this article, we review the atypical psychotic disorders and report a series of five case examples that signify the role of ECT in atypical psychotic presentations, particularly when the symptoms resemble those found in Cotard's syndrome and cycloid psychosis. PMID:20428309

Pharmacological Management of Anxiety Disorders in the Elderly

Science.gov (United States)

Crocco, Elizabeth A.; Jaramillo, Sindy; Cruz-Ortiz, Caroline; Camfield, Katherine

2017-01-01

Opinion Statement Anxiety disorders are common in the elderly. Additionally, anxiety symptoms often accompany co-morbid psychiatric, medical, as well as neurodegenerative diseases in the older population. Anxiety in the elderly, often accompanied by depression, can lead to worsening physical, cognitive and functional impairments in this vulnerable population. Antidepressants are considered first line treatment. Both SSRIs and SNRIs are efficacious and well-tolerated in the elderly. Some SSRIs are strong inhibitors of the cytochrome P450 hepatic pathway whereas others have less potential for drug interaction. Those antidepressants with more favorable pharmacokinetic profiles should be considered first-line in the treatment of anxiety. Mirtazapine and vortioxetine are also considered safe treatment options. Buspirone may have benefit, but lacks studies in elderly populations. Although tricyclic/tetracyclic antidepressants (TCAs) and monoamine oxidase inhibitors (MAOIs) may be effective in the elderly, their side effect and safety profiles are suboptimal and thus are not recommended in late-life. Benzodiazepines and beta blockers should generally be avoided when treating anxiety in the elderly. There is not enough evidence to support the use of antipsychotics or mood stabilizers given their risk of problems in both the long and short term. In addition, antipsychotics have a black box warning for increased mortality in elderly patients with dementia. PMID:28948135

Risk of dementia in German patients treated with antidepressants in general or psychiatric practices
.

Science.gov (United States)

Jacob, Louis; Bohlken, Jens; Kostev, Karel

2017-04-01

To study the impact of the use of antidepressants on dementia in German patients with depression treated in general (GPs) or psychiatric practices (PPs). Patients with a first-time documentation of depression with known severity level between 2010 and 2013 (index date) were identified by 1,126 general practitioners and 176 psychiatrists in the IMS Disease Analyzer database. We included patients between the ages of 60 and 80 years who had not previously received prescriptions for antidepressant drugs and had not been diagnosed with all-cause dementia prior to or on the index date. The main outcome of the study was the risk of dementia depending on antidepressant therapy. Cox proportional hazards models (dependent variable: incident dementia) were used to adjust for confounders and to estimate the effect of antidepressant therapy. A total of 22,838 patients treated in GPs and 33,112 patients treated in PPs were included in this study. Of those, 9,570, 30,321, and 16,059 individuals suffered from mild, moderate, and severe depression, respectively. Antidepressant drug use was associated with a decreased risk of dementia in patients affected by moderate (HR = 0.86, 95% CI: 0.77 - 0.95) or severe depression (HR = 0.83, 95% CI: 0.73 - 0.94). The use of antidepressants decreased dementia risk in patients with moderate or severe depression.
.

Explanatory models of depression and treatment adherence to antidepressant medication

DEFF Research Database (Denmark)

Buus, Niels; Johannessen, Helle; Stage, Kurt Bjerregaard

2012-01-01

and medicine were not central. However, taking antidepressant medication was a meaningful part of being admitted to hospital, and the adoption of the rhetoric and practices of biomedicine strengthened patients' sense of control and hope for recovery. If medicine was ineffective, the explanatory models...... legitimised alternative strategies towards recovery, including non-adherence. CONCLUSIONS: The patients' reasons for adhering to antidepressants included a range of diverse psychosocial issues, and could be regarded as a central part of their common sense illness management....

Methodological Flaws, Conflicts of Interest, and Scientific Fallacies: Implications for the Evaluation of Antidepressants' Efficacy and Harm.

Science.gov (United States)

Hengartner, Michael P

2017-01-01

In current psychiatric practice, antidepressants are widely and with ever-increasing frequency prescribed to patients. However, several scientific biases obfuscate estimates of antidepressants' efficacy and harm, and these are barely recognized in treatment guidelines. The aim of this mini-review is to critically evaluate the efficacy and harm of antidepressants for acute and maintenance treatment with respect to systematic biases related to industry funding and trial methodology. Narrative review based on a comprehensive search of the literature. It is shown that the pooled efficacy of antidepressants is weak and below the threshold of a minimally clinically important change once publication and reporting biases are considered. Moreover, the small mean difference in symptom reductions relative to placebo is possibly attributable to observer effects in unblinded assessors and patient expectancies. With respect to trial dropout rates, a hard outcome not subjected to observer bias, no difference was observed between antidepressants and placebo. The discontinuation trials on the efficacy of antidepressants in maintenance therapy are systematically flawed, because in these studies, spontaneous remitters are excluded, whereas half of all patients who remitted on antidepressants are abruptly switched to placebo. This can cause a severe withdrawal syndrome that is easily misdiagnosed as a relapse when assessed on subjective symptom rating scales. In accordance, the findings of naturalistic long-term studies suggest that maintenance therapy has no clear benefit, and non-drug users do not show increased recurrence rates. Moreover, a growing body of evidence from hundreds of randomized controlled trials suggests that antidepressants cause suicidality, but this risk is underestimated because data from industry-funded trials are systematically flawed. Unselected, population-wide observational studies indicate that depressive patients who use antidepressants are at an increased

Sexual side effects of serotonergic antidepressants: mediated by inhibition of serotonin on central dopamine release?

Science.gov (United States)

Bijlsma, Elisabeth Y; Chan, Johnny S W; Olivier, Berend; Veening, Jan G; Millan, Mark J; Waldinger, Marcel D; Oosting, Ronald S

2014-06-01

Antidepressant-induced sexual dysfunction adversely affects the quality of life of antidepressant users and reduces compliance with treatment. Animal models provide an instructive approach for examining potential sexual side effects of novel drugs. This review discusses the stability and reproducibility of our standardized test procedure that assesses the acute, subchronic and chronic effects of psychoactive compounds in a 30 minute mating test. In addition, we present an overview of the effects of several different (putative) antidepressants on male rat sexual behavior, as tested in our standardized test procedure. By comparing the effects of these mechanistically distinct antidepressants (paroxetine, venlafaxine, bupropion, buspirone, DOV 216,303 and S32006), this review discusses the putative mechanism underlying sexual side effects of antidepressants and their normalization. This review shows that sexual behavior is mainly inhibited by antidepressants that increase serotonin neurotransmission via blockade of serotonin transporters, while those that mainly increase the levels of dopamine and noradrenaline are devoid of sexual side effects. Those sexual disturbances cannot be normalized by simultaneously increasing noradrenaline neurotransmission, but are normalized by increasing both noradrenaline and dopamine neurotransmission. Therefore, it is hypothesized that the sexual side effects of selective serotonin reuptake inhibitors may be mediated by their inhibitory effects on dopamine signaling in sex brain circuits. Clinical development of novel antidepressants should therefore focus on compounds that simultaneously increase both serotonin and dopamine signaling. © 2013 Elsevier Inc. All rights reserved.

Atypical relapse of hemolytic uremic syndrome after transplantation

NARCIS (Netherlands)

Olie, Karolien H.; Florquin, Sandrine; Groothoff, Jaap W.; Verlaak, René; Strain, Lisa; Goodship, Timothy H. J.; Weening, Jan J.; Davin, Jean-Claude

2004-01-01

Atypical hemolytic uremic syndrome (HUS) frequently leads to end-stage renal failure and can relapse after transplantation. A 12-year-old girl presenting with familial atypical HUS with a factor H mutation was successfully transplanted 6 years after a first transplant that had failed because of

Antidepressant Exposure and Risk of Dementia in Older Adults with Major Depressive Disorder.

Science.gov (United States)

Brodrick, Joy E; Mathys, Monica L

2016-12-01

To identify whether duration of antidepressant use in depressed elderly veterans differed between those who later developed dementia and those who did not. Single-center, retrospective, observational, electronic chart review. Medical charts from a Veterans Affairs Mental Health Clinic. Veterans aged 65 and older with history of depression. Information on sociodemographic characteristics; duration of antidepressant, antipsychotic, and benzodiazepine therapy; diagnosis of dementia; and comorbid disease states was collected. Medication use since August 1, 1998 was recorded. Of 1,547 charts reviewed, 605 met inclusion criteria; 128 were excluded on the basis of psychiatric comorbidities. Of the remaining 477, 41 developed incident dementia. Thirty-seven of those were matched to individuals with depression without dementia according to age, cardiovascular disease, cerebrovascular disease, diabetes mellitus, and substance use. There were no differences between the groups with (n = 37) and without (n = 37) dementia with respect to baseline characteristics, antidepressant types, or benzodiazepine or antipsychotic use. Median duration of antidepressant use was 891 days in the group with dementia and 1,979 days in the group without (P = .03, W = -260, z = -2.13). Significantly fewer participants with dementia received antidepressant treatment for at least 5 years [n = 8 with dementia, n = 20 without dementia, P = .004, odds ratio = 0.235, 95% confidence interval = 0.085-0.647). Older veterans with depression who developed dementia were treated with antidepressants for a significantly shorter duration than matched veterans who did not develop dementia. © 2016, Copyright the Authors Journal compilation © 2016, The American Geriatrics Society.

Typical and atypical presentations of aspergilloma

International Nuclear Information System (INIS)

Villajos, M.; Darnell, A.; Gallardo, X.; Castaner, E.; Mata, J. M.; Paedavila, E.

1999-01-01

To show the different forms of radiological presentations of aspergilloma, emphasizing the importance of recognizing the atypical forms. The explorations of 11 patients with aspergilloma were examined retrospectively between 1993 and 1997. These patients were studied using conventional X-rays and computed tomography (CT): Typical and atypical radiological findings were observed. In two patients, who presented recurrent hemoptysis, a percutaneous installation of amphotericin B was carried out with tomographic control. Out of the 11 patients, two were female and nine male. In eight of the cases the radiological findings showed an intercavity injury with different evolutionary forms, while in three of the cases there was a progressive pleural swelling. In the two patients treated pertinaciously, no significant radiological changes were observed, however, neither of them showed hemoptysis again. The pleural swelling adjacent to the cavity and/or the swelling of the cavity wall are atypical radiological presentations of the aspergilloma, that can accompany or precede the appearance of this illness. (Author) 7 refs

Antidepressant-like effects of methanol extract of Hibiscus tiliaceus flowers in mice

Science.gov (United States)

2012-01-01

Background Hibiscus tiliaceus L. (Malvaceae) is used in postpartum disorders. Our purpose was to examine the antidepressant, anxiolytic and sedative actions of the methanol extract of H. tiliaceus flowers using animal models. Methods Adult male Swiss albino mice were treated with saline, standard drugs or methanol extract of H. tiliaceus and then subjected to behavioral tests. The forced swimming and tail suspension tests were used as predictive animal models of antidepressant activity, where the time of immobility was considered. The animals were submitted to the elevated plus-maze and ketamine-induced sleeping time to assess anxiolytic and sedative activities, respectively. Results Methanol extract of H. tiliaceus significantly decreased the duration of immobility in both animal models of antidepressant activity, forced swimming and tail suspension tests. This extract did not potentiate the effect of ketamine-induced hypnosis, as determined by the time to onset and duration of sleeping time. Conclusion Our results indicate an antidepressant-like profile of action for the extract of Hibiscus tiliaceus without sedative side effect. PMID:22494845

Antidepressant-like effects of methanol extract of Hibiscus tiliaceus flowers in mice

Directory of Open Access Journals (Sweden)

Vanzella Cláudia

2012-04-01

Full Text Available Abstract Background Hibiscus tiliaceus L. (Malvaceae is used in postpartum disorders. Our purpose was to examine the antidepressant, anxiolytic and sedative actions of the methanol extract of H. tiliaceus flowers using animal models. Methods Adult male Swiss albino mice were treated with saline, standard drugs or methanol extract of H. tiliaceus and then subjected to behavioral tests. The forced swimming and tail suspension tests were used as predictive animal models of antidepressant activity, where the time of immobility was considered. The animals were submitted to the elevated plus-maze and ketamine-induced sleeping time to assess anxiolytic and sedative activities, respectively. Results Methanol extract of H. tiliaceus significantly decreased the duration of immobility in both animal models of antidepressant activity, forced swimming and tail suspension tests. This extract did not potentiate the effect of ketamine-induced hypnosis, as determined by the time to onset and duration of sleeping time. Conclusion Our results indicate an antidepressant-like profile of action for the extract of Hibiscus tiliaceus without sedative side effect.

Mechanistic Target of Rapamycin-Independent Antidepressant Effects of (R)-Ketamine in a Social Defeat Stress Model.

Science.gov (United States)

Yang, Chun; Ren, Qian; Qu, Youge; Zhang, Ji-Chun; Ma, Min; Dong, Chao; Hashimoto, Kenji

2018-01-01

The role of the mechanistic target of rapamycin (mTOR) signaling in the antidepressant effects of ketamine is controversial. In addition to mTOR, extracellular signal-regulated kinase (ERK) is a key signaling molecule in prominent pathways that regulate protein synthesis. (R)-Ketamine has a greater potency and longer-lasting antidepressant effects than (S)-ketamine. Here we investigated whether mTOR signaling and ERK signaling play a role in the antidepressant effects of two enantiomers. The effects of mTOR inhibitors (rapamycin and AZD8055) and an ERK inhibitor (SL327) on the antidepressant effects of ketamine enantiomers in the chronic social defeat stress (CSDS) model (n = 7 or 8) and on those of ketamine enantiomers in these signaling pathways in mouse brain regions were examined. The intracerebroventricular infusion of rapamycin or AZD8055 blocked the antidepressant effects of (S)-ketamine, but not (R)-ketamine, in the CSDS model. Furthermore, (S)-ketamine, but not (R)-ketamine, significantly attenuated the decreased phosphorylation of mTOR and its downstream effector, ribosomal protein S6 kinase, in the prefrontal cortex of susceptible mice after CSDS. Pretreatment with SL327 blocked the antidepressant effects of (R)-ketamine but not (S)-ketamine. Moreover, (R)-ketamine, but not (S)-ketamine, significantly attenuated the decreased phosphorylation of ERK and its upstream effector, mitogen-activated protein kinase/ERK kinase, in the prefrontal cortex and hippocampal dentate gyrus of susceptible mice after CSDS. This study suggests that mTOR plays a role in the antidepressant effects of (S)-ketamine, but not (R)-ketamine, and that ERK plays a role in (R)-ketamine's antidepressant effects. Thus, it is unlikely that the activation of mTOR signaling is necessary for antidepressant actions of (R)-ketamine. Copyright © 2017 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Antidepressants Accumulate in Lipid Rafts Independent of Monoamine Transporters to Modulate Redistribution of the G Protein, Gαs.

Science.gov (United States)

Erb, Samuel J; Schappi, Jeffrey M; Rasenick, Mark M

2016-09-16

Depression is a significant public health problem for which currently available medications, if effective, require weeks to months of treatment before patients respond. Previous studies have shown that the G protein responsible for increasing cAMP (Gαs) is increasingly localized to lipid rafts in depressed subjects and that chronic antidepressant treatment translocates Gαs from lipid rafts. Translocation of Gαs, which shows delayed onset after chronic antidepressant treatment of rats or of C6 glioma cells, tracks with the delayed onset of therapeutic action of antidepressants. Because antidepressants appear to specifically modify Gαs localized to lipid rafts, we sought to determine whether structurally diverse antidepressants accumulate in lipid rafts. Sustained treatment of C6 glioma cells, which lack 5-hydroxytryptamine transporters, showed marked concentration of several antidepressants in raft fractions, as revealed by increased absorbance and by mass fingerprint. Closely related molecules without antidepressant activity did not concentrate in raft fractions. Thus, at least two classes of antidepressants accumulate in lipid rafts and effect translocation of Gαs to the non-raft membrane fraction, where it activates the cAMP-signaling cascade. Analysis of the structural determinants of raft localization may both help to explain the hysteresis of antidepressant action and lead to design and development of novel substrates for depression therapeutics. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Genetically encoded photocrosslinkers locate the high-affinity binding site of antidepressant drugs in the human serotonin transporter

DEFF Research Database (Denmark)

Rannversson, Hafsteinn; Andersen, Jacob; Hall, Lena Sørensen

2016-01-01

with p-azido-L-phenylalanine (azF) at selected positions in hSERT to map the binding site of imipramine, a prototypical tricyclic antidepressant, and vortioxetine, a novel multimodal antidepressant. We find that the two antidepressants crosslink with azF incorporated at different positions within...

Atypical antipsychotics in bipolar disorder: systematic review of randomised trials

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Moore R Andrew

2007-08-01

Full Text Available Abstract Background Atypical antipsychotics are increasingly used for treatment of mental illnesses like schizophrenia and bipolar disorder, and considered to have fewer extrapyramidal effects than older antipsychotics. Methods We examined efficacy in randomised trials of bipolar disorder where the presenting episode was either depression, or manic/mixed, comparing atypical antipsychotic with placebo or active comparator, examined withdrawals for any cause, or due to lack of efficacy or adverse events, and combined all phases for adverse event analysis. Studies were found through systematic search (PubMed, EMBASE, Cochrane Library, and data combined for analysis where there was clinical homogeneity, with especial reference to trial duration. Results In five trials (2,206 patients participants presented with a depressive episode, and in 25 trials (6,174 patients the presenting episode was manic or mixed. In 8-week studies presenting with depression, quetiapine and olanzapine produced significantly better rates of response and symptomatic remission than placebo, with NNTs of 5–6, but more adverse event withdrawals (NNH 12. With mania or mixed presentation atypical antipsychotics produced significantly better rates of response and symptomatic remission than placebo, with NNTs of about 5 up to six weeks, and 4 at 6–12 weeks, but more adverse event withdrawals (NNH of about 22 in studies of 6–12 weeks. In comparisons with established treatments, atypical antipsychotics had similar efficacy, but significantly fewer adverse event withdrawals (NNT to prevent one withdrawal about 10. In maintenance trials atypical antipsychotics had significantly fewer relapses to depression or mania than placebo or active comparator. In placebo-controlled trials, atypical antipsychotics were associated with higher rates of weight gain of ≥7% (mainly olanzapine trials, somnolence, and extrapyramidal symptoms. In active controlled trials, atypical antipsychotics

Playing With Antidepressants: Perspectives From Indian Australians and Anglo-Australians Living With Depression.

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Brijnath, Bianca; Antoniades, Josefine

2017-11-01

Patient perspectives were explored on the meaning and experience of antidepressant use by applying Johan Huizinga's theory of play to interviews from Indian Australians and Anglo-Australians diagnosed with depression. Through the analysis, the centrality of Huizinga's "magic circle" emerged, that is, defining the boundaries within which one could safely play. Consumption of antidepressants involved learning, breaking, and modulating rules of the game of adherence, then forging a new "magic circle." In these games, there were playful elements including experimentation, improvisation, absorption, and experiential learning. This application of Huizinga's theory in relation to antidepressant use is a novel approach in the literature on medication non/adherence. This application not only opens a new theoretical line of inquiry but also shows that antidepressant non/adherence is not a static practice but dynamic and changing, revealing critical insights around participant's agency, capabilities, desires, and notions of selfhood with regard to managing their depression and conceptualizing their recovery.

Radiographic differentiation of atypical tuberculosis from mycobacterium tuberculosis

International Nuclear Information System (INIS)

Tarver, R.D.; Pearcy, E.A.; Conces, D.J. Jr.; Mathur, P.N.

1987-01-01

The chest radiographs of 95 patients with the new diagnosis of atypical turberculosis were reviewed to determine if any significant differences between atypical tuberculosis and that caused by Mycobacterium tuberculosis could be discerned. Findings included upper lobe involvement in B4 of the 95 patients and cavities in 76, with nearly equal groups having no, moderate, or extensive surrounding alveolar disease. Nodules were common; in six patients a nodule was the sole manifestation of disease. Adenopathy was seen in 12 of the 95 patients, atlectasis in 45, pleural thickening in 90, and effusions in three. These radiographic findings did not allow the radiographic differentiation of atypical tuberculosis from Mycobacterium tuberculosis infection

Using tests and models to assess antidepressant-like activity in rodents

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Kedzierska Ewa

2016-06-01

Full Text Available In today's world, depression is one of the more prevalent forms of mental illness. According to WHO, about 10%-30% of all women and 7%-15% of all men are afflicted by depression at least once in their life-times. Today, depression is assessed to be affecting 350 million people. Regarding this issue, an important challenge for current psychopharmacology is to develop new, more effective pharmacotherapy and to understand the mechanism of action of known antidepressants. Furthermore, there is the necessity to improve the effectiveness of anti-depression treatment by way of bringing about an understanding of the neurobiology of this illness. In achieving these objectives, animal models of depression can be useful. Yet, presently, all available animal models of depression rely on two principles: the actions of known antidepressants or the responses to stress. In this paper, we present an overview of the most widely used animal tests and models that are employed in assessing antidepressant-like activity in rodents. These include amphetamine potentiation, reversal of reserpine action, the forced swimming test, the tail suspension test, learned helplessness, chronic mild stress and social defeat stress. Moreover, the advantages and major drawbacks of each model are also discussed.

Gemfibrozil has antidepressant effects in mice: Involvement of the hippocampal brain-derived neurotrophic factor system.

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Ni, Yu-Fei; Wang, Hao; Gu, Qiu-Yan; Wang, Fei-Ying; Wang, Ying-Jie; Wang, Jin-Liang; Jiang, Bo

2018-04-01

Major depressive disorder has become one of the most serious neuropsychiatric disorders worldwide. However, currently available antidepressants used in clinical practice are ineffective for a substantial proportion of patients and always have side effects. Besides being a lipid-regulating agent, gemfibrozil is an agonist of peroxisome proliferator-activated receptor-α (PPAR-α). We investigated the antidepressant effects of gemfibrozil on C57BL/6J mice using the forced swim test (FST) and tail suspension test (TST), as well as the chronic unpredictable mild stress (CUMS) model of depression. The changes in brain-derived neurotrophic factor (BDNF) signaling cascade in the brain after CUMS and gemfibrozil treatment were further assessed. Pharmacological inhibitors and lentivirus-expressed short hairpin RNA (shRNA) were also used to clarify the antidepressant mechanisms of gemfibrozil. Gemfibrozil exhibited significant antidepressant actions in the FST and TST without affecting the locomotor activity of mice. Chronic gemfibrozil administration fully reversed CUMS-induced depressive-like behaviors in the FST, TST and sucrose preference test. Gemfibrozil treatment also restored CUMS-induced inhibition of the hippocampal BDNF signaling pathway. Blocking PPAR-α and BDNF but not the serotonergic system abolished the antidepressant effects of gemfibrozil on mice. Gemfibrozil produced antidepressant effects in mice by promoting the hippocampal BDNF system.

Increased use of antidepressants and decreasing suicide rates: a population-based study using Danish register data

DEFF Research Database (Denmark)

Erlangsen, Annette; Canudas-Romo, V.; Conwell, Yeates

2008-01-01

OBJECTIVE: The objective of the present study was to examine if the change in the suicide rate is associated with individuals' use of antidepressants as has been suggested by ecological studies. DESIGN: Decomposition of suicide rates by antidepressant treatment group. SETTING: Population......-based record linkage. PARTICIPANTS: All individuals aged 50 years and older living in Denmark between 1 January 1996 and 31 December 2000 (N = 2,100,808). MAIN OUTCOME MEASURES: Suicide rates are calculated according to current antidepressant treatment status (no treatment, tricyclic antidepressants (TCA......), selective serotonin reuptake inhibitors (SSRI), other antidepressants). The change in the suicide rate during 1996-2000 was decomposed by treatment group. RESULTS: Only one in five older adults dying by suicide was in treatment at the time of death. Whereas the male suicide rate declined by 9.7 suicides per...

Misleading advertising for antidepressants in Sweden: a failure of pharmaceutical industry self-regulation.

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Anna V Zetterqvist

Full Text Available BACKGROUND: The alleged efficacy of pharmaceutical industry self-regulation has been used to repudiate increased government oversight over promotional activity. European politicians and industry have cited Sweden as an excellent example of self-regulation based on an ethical code. This paper considers antidepressant advertising in Sweden to uncover the strengths and weaknesses of self-regulation. METHODOLOGY: We analyzed all antidepressant advertisements in the Swedish Medical Journal, 1994-2003. The regulation of these advertisements was analyzed using case reports from self-regulatory bodies. The authors independently reviewed this material to investigate: (1 extent of violative advertising; (2 pattern of code breaches; (3 rate at which the system reacted to violative advertising; (4 prevalence of and oversight over claims regarding antidepressant efficacy and disease causality, and (5 costs for manufactures associated with violative advertising. PRINCIPAL FINDINGS: Self-regulatory bodies identified numerous code breaches. Nonetheless, they failed to protect doctors from unreliable information on antidepressants, since as many as 247 of 722 (34% advertisements breached the industry code. Self-regulatory bodies repeatedly failed to challenge inflated claims of antidepressant efficacy, lending evidence of lax oversight. On average, 15 weeks elapsed between printing and censure of a wrongful claim, and in 25% of cases 47 weeks or more elapsed. Industry paid roughly €108000 in fines for violative advertising, adding an estimated additional average cost of 11% to each purchased violative advertisement, or amounting to as little as 0.009% of total antidepressant sales of around €1.2 billion. CONCLUSIONS: Lax oversight, combined with lags in the system and low fines for violations, may explain the Swedish system's failure to pressure companies into providing reliable antidepressants information. If these shortcomings prove to be consistent across

Misleading Advertising for Antidepressants in Sweden: A Failure of Pharmaceutical Industry Self-Regulation

Science.gov (United States)

Zetterqvist, Anna V.; Mulinari, Shai

2013-01-01

Background The alleged efficacy of pharmaceutical industry self-regulation has been used to repudiate increased government oversight over promotional activity. European politicians and industry have cited Sweden as an excellent example of self-regulation based on an ethical code. This paper considers antidepressant advertising in Sweden to uncover the strengths and weaknesses of self-regulation. Methodology We analyzed all antidepressant advertisements in the Swedish Medical Journal, 1994–2003. The regulation of these advertisements was analyzed using case reports from self-regulatory bodies. The authors independently reviewed this material to investigate: (1) extent of violative advertising; (2) pattern of code breaches; (3) rate at which the system reacted to violative advertising; (4) prevalence of and oversight over claims regarding antidepressant efficacy and disease causality, and (5) costs for manufactures associated with violative advertising. Principal Findings Self-regulatory bodies identified numerous code breaches. Nonetheless, they failed to protect doctors from unreliable information on antidepressants, since as many as 247 of 722 (34%) advertisements breached the industry code. Self-regulatory bodies repeatedly failed to challenge inflated claims of antidepressant efficacy, lending evidence of lax oversight. On average, 15 weeks elapsed between printing and censure of a wrongful claim, and in 25% of cases 47 weeks or more elapsed. Industry paid roughly €108000 in fines for violative advertising, adding an estimated additional average cost of 11% to each purchased violative advertisement, or amounting to as little as 0.009% of total antidepressant sales of around €1.2 billion. Conclusions Lax oversight, combined with lags in the system and low fines for violations, may explain the Swedish system’s failure to pressure companies into providing reliable antidepressants information. If these shortcomings prove to be consistent across self

Use of anti-depressants and the risk of fracture of the hip or femur.

Science.gov (United States)

van den Brand, M W M; Pouwels, S; Samson, M M; van Staa, T P; Thio, B; Cooper, C; Leufkens, H G M; Egberts, A C G; Verhaar, H J J; de Vries, F

2009-10-01

Anti-depressants are used largely, but have serious side effects. We show that both selective serotonin re-uptake inhibitors (SSRIs) and tricyclic anti-depressants (TCAs) increase the risk of hip/femur fracture and that this risk is time related and depends on the degree of serotonin transporter inhibition. This should be considered when prescribing anti-depressants to patients. Anti-depressants are known to have serious side effects. We examined the association between the use of anti-depressants and the risk of hip/femur fractures with a special focus on the relation with the degree of 5-hydroxytryptamine transporter (5-HTT) inhibition and the duration of use. A case-control study was conducted within the Dutch PHARMO-RLS database. Cases (n = 6,763) were adult patients with a first hip/femur fracture during the study period. For each case, four controls (n = 26341) were matched by age, gender and geographic region. The risk of hip/femur fracture increased with current use of SSRIs (adjusted odds ratio (OR(adj)) 2.35 [95% confidence interval (CI) 1.94-2.84]) and TCAs (ORadj 1.76 [95% CI 1.45-2.15]). The risk of hip/femur fracture declined rapidly after discontinuation of use. The risk of hip/femur fracture increased as the degree of 5-HTT inhibition of all anti-depressants increased from OR(adj) 1.64 [95% CI 1.14-2.35] for drugs with low 5-HTT inhibition to OR(adj) 2.31 [95% CI 1.94-2.76] for those with high 5-HTT inhibiting properties. Current use of both SSRIs and TCAs increase hip/femur fracture risk. Further studies are needed to elucidate the mechanistic pathways and the relation with the underlying pathophysiology. Until then, the elevated fracture risk should be considered when prescribing anti-depressants.

"My dirty little habit": Patient constructions of antidepressant use and the 'crisis' of legitimacy.

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Ridge, Damien; Kokanovic, Renata; Broom, Alex; Kirkpatrick, Susan; Anderson, Claire; Tanner, Claire

2015-12-01

Discontents surrounding depression are many, and include concerns about a creeping appropriation of everyday kinds of misery; divergent opinions on the diagnostic category(ies); and debates about causes and appropriate treatments. The somewhat mixed fortunes of antidepressants - including concerns about their efficacy, overuse and impacts on personhood - have contributed to a moral ambivalence around antidepressant use for people with mental health issues. Given this, we set out to critically examine how antidepressant users engage in the moral underpinnings of their use, especially how they ascribe legitimacy (or otherwise) to this usage. Using a modified constant comparative approach, we analyzed 107 narrative interviews (32 in UKa, 36 in UKb, 39 in Australia) collected in three research studies of experiences of depression in the UK (2003-4 UKa, and 2012 UKb) and in Australia (2010-11). We contend that with the precariousness of the legitimacy of the pharmaceutical treatment of depression, participants embark on their own legitimization work, often alone and while distressed. We posit that here, individuals with depression may be particularly susceptible to moral uncertainty about their illness and pharmaceutical interventions, including concerns about shameful antidepressant use and deviance (e.g. conceiving medication as pseudo-illicit). We conclude that while people's experiences of antidepressants (including successful treatments) involve challenges to illegitimacy narratives, it is difficult for participants to escape the influence of underlying moral concerns, and the legitimacy quandary powerfully shapes antidepressant use. Copyright © 2015 Elsevier Ltd. All rights reserved.

Neuroplasticity-related mechanisms underlying the antidepressant-like effects of traditional herbal medicines.

Science.gov (United States)

Hirshler, Yafit; Doron, Ravid

2017-10-01

Traditional herbal medicine can offer efficacious and safe alternative pharmacotherapies for depression. The ability of an herbal medicine to produce neuroadaptive processes, that enhance neuroplasticity and cellular resilience in response to chronic stress, may point to its antidepressant potential. We suggest that among many investigated herbal medicines, those that can enhance neuroplasticity may have stronger therapeutic potential. The current article presents a summary of traditional herbal medicines, which are thought to exert antidepressant-like effects in chronic stress models via neuroplasticity enhancement. Brain-derived neurotrophic factor (BDNF) is a biomarker for neuroplasticity-related mechanisms compromised in depression and recovered by conventional antidepressants, including synaptic plasticity, cell survival, neurogenesis and spine formation. We therefore presumed that if an herbal medicine up-regulates BDNF in the hippocampus and/or prefrontal cortex (PFC), its antidepressant-like effect is mediated, at least partially, via neuroplasticity-related mechanisms. Literature search was performed using the general terms depression, stress, neuroplasticity and herbal medicines. Screening of retrieved preclinical studies revealed 30 traditional herbal medicines: 8 single herbs, 15 bioactive constituents, and 7 herbal formulas. The antidepressant-like effects of these medicines were associated with reversal of chronic stress-induced impairment in neuroplasticity, most notably by BDNF up-regulation, activation of BDNF downstream signaling pathways and increase in neurogenesis in the hippocampus and/or PFC/frontal cortex. In light of the ability of these medicines to enhance neuroplasticity, we suggest that they may be suitable candidates for clinical investigation in depressed individuals. Once their efficacy, tolerability and safety will be substantiated, they may serve as natural alternatives to conventional antidepressants. Copyright © 2017 Elsevier B

Depression, antidepressants and driving safety

OpenAIRE

Hill, Linda L.; Lauzon, Vanessa L.; Winbrock, Elise L.; Li, Guohua; Chihuri, Stanford; Lee, Kelly C.

2017-01-01

Background The purpose of this study was to review the reported associations of depression and antidepressants with motor vehicle crashes. Purpose A literature search for material published in the English language between January, 1995, and October, 2015, in bibliographic databases was combined with a search for other relevant material referenced in the retrieved articles. Methods Retrieved articles were systematically reviewed for inclusion criteria: 19 epidemiological studies (17 case-contr...

Prediction of outcome of bright light treatment in patients with seasonal affective disorder: Discarding the early response, confirming a higher atypical balance, and uncovering a higher body mass index at baseline as predictors of endpoint outcome.

Science.gov (United States)

Dimitrova, Tzvetelina D; Reeves, Gloria M; Snitker, Soren; Lapidus, Manana; Sleemi, Aamar R; Balis, Theodora G; Manalai, Partam; Tariq, Muhammad M; Cabassa, Johanna A; Karim, Naila N; Johnson, Mary A; Langenberg, Patricia; Rohan, Kelly J; Miller, Michael; Stiller, John W; Postolache, Teodor T

2017-11-01

We tested the hypothesis that the early improvement in mood after the first hour of bright light treatment compared to control dim-red light would predict the outcome at six weeks of bright light treatment for depressed mood in patients with Seasonal Affective Disorder (SAD). We also analyzed the value of Body Mass Index (BMI) and atypical symptoms of depression at baseline in predicting treatment outcome. Seventy-eight adult participants were enrolled. The first treatment was controlled crossover, with randomized order, and included one hour of active bright light treatment and one hour of control dim-red light, with one-hour washout. Depression was measured on the Structured Interview Guide for the Hamilton Rating Scale for Depression-SAD version (SIGH-SAD). The predictive association of depression scores changes after the first session. BMI and atypical score balance with treatment outcomes at endpoint were assessed using multivariable linear and logistic regressions. No significant prediction by changes in depression scores after the first session was found. However, higher atypical balance scores and BMI positively predicted treatment outcome. Absence of a control intervention for the six-weeks of treatment (only the first session in the laboratory was controlled). Exclusion of patients with comorbid substance abuse, suicidality and bipolar I disorder, and patients on antidepressant medications, reducing the generalizability of the study. Prediction of outcome by early response to light treatment was not replicated, and the previously reported prediction of baseline atypical balance was confirmed. BMI, a parameter routinely calculated in primary care, was identified as a novel predictor, and calls for replication and then exploration of possible mediating mechanisms. Published by Elsevier B.V.

Are studies of psychotherapies for depression more or less generalizable than studies of antidepressants?

NARCIS (Netherlands)

Lorenzo-Luaces, Lorenzo; Zimmerman, Mark; Cuijpers, Pim

Background: The generalizability of findings from studies exploring the efficacy of psychotherapy and antidepressants has been called into question in part because studies exclude many patients. Despite this, the frequency with which psychotherapy and antidepressant studies use specific inclusion

Ichthyosiform mycosis fungoides with alopecia and atypical membranous nephropathy

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Qiang Zhou

2011-01-01

Full Text Available We describe here a rare case of variant of mycosis fungoides (MF: ichthyosiform MF with alopecia and atypical membranous nephropathy. The diagnosis was made based on the following findings: generalized ichthyosis-like eruption, alopecia, enlarged superficial lymph nodes, proteinuria, and hematuria, the histological features of the skin biopsy from both ichthyotic and alopecic lesions with immunohistochemical staining, and the renal biopsy examination with immunofluorescence. The histological examination of ichthyotic and alopecic lesions displayed a predominant infiltration of atypical lymphocytes in the upper dermis with the characteristics of epidermotropism and folliculotropism. Immunohistochemical studies demonstrated that most infiltrated atypical lymphocytes were CD3, CD4, and CD45RO positive, whereas negative for CD5, CD7, CD20, CD30, and CD56. A renal biopsy examination revealed atypical membranous nephropathy with deposition of immunoglobulin G (IgG, IgM, IgA, C1q, and C3. In this case atypical membranous nephropathy was involved, which is very uncommon and has never been presented in the literature to date. Although ichthyosiform MF usually features a relatively favorable course, diffuse alopecia and the renal involvement in this case might indicate aggressive disease and poor prognosis.

Jieyuanshen decoction exerts antidepressant effects on depressive ...

African Journals Online (AJOL)

Conclusion: JYAS-D had a significant antidepressant-like effect on rat model through regulating serum concentration of CORT, ACTH and CRH, increasing the content of hippocampus GR and regulating the equilibrium of amino acids neurotransmitter. Keywords: Hypothalamic-pituitary-adrenal (HPA) axis; Glucocorticoid/ ...

Increased use of antidepressants and decreasing suicide rates: a population-based study using Danish register data

DEFF Research Database (Denmark)

Erlangsen, Annette; Canudas-Romo, V.; Conwell, Yeates

2008-01-01

-based record linkage. PARTICIPANTS: All individuals aged 50 years and older living in Denmark between 1 January 1996 and 31 December 2000 (N = 2,100,808). MAIN OUTCOME MEASURES: Suicide rates are calculated according to current antidepressant treatment status (no treatment, tricyclic antidepressants (TCA...... 100,000, recipients of antidepressants contributed to the decline by 0.9 suicides. Women redeeming antidepressant prescriptions accounted for 0.4 suicides of the observed reduction of 3.3 per 100,000. The average suicide rates for men receiving TCA and SSRI were 153.3 and 169.0 per 100,000 person......-years, respectively. Among older women, both TCA and SSRI users had an average suicide rate of 68.8 per 100,000 over the period examined. CONCLUSIONS: Just a small proportion of older adults dying by suicide were found to be in treatment with antidepressants at the time of death. Individuals in active treatment...

Childhood Central Nervous System Atypical Teratoid/Rhabdoid Tumor Treatment

Science.gov (United States)

... teratoid/rhabdoid tumor. There is no standard staging system for central nervous system atypical teratoid/rhabdoid tumor. The extent or spread ... different types of treatment for patients with central nervous system atypical teratoid/rhabdoid tumor. Different types of treatment ...

Antidepressant treatment with tianeptine reduces apoptosis in the hippocampal dentate gyrus and temporal cortex

NARCIS (Netherlands)

Lucassen, P.J.; Fuchs, E.; Czeh, B.

2004-01-01

BACKGROUND: Recent clinical and preclinical studies suggest that major depression may be related to impairments of structural plasticity. Consequently, antidepressants may act by restoring altered rates of cell birth or death. Here, we investigated whether the antidepressant tianeptine would affect

Atypical centrioles during sexual reproduction.

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Avidor-Reiss, Tomer; Khire, Atul; Fishman, Emily L; Jo, Kyoung H

2015-01-01

Centrioles are conserved, self-replicating, microtubule-based, 9-fold symmetric subcellular organelles that are essential for proper cell division and function. Most cells have two centrioles and maintaining this number of centrioles is important for animal development and physiology. However, how animals gain their first two centrioles during reproduction is only partially understood. It is well established that in most animals, the centrioles are contributed to the zygote by the sperm. However, in humans and many animals, the sperm centrioles are modified in their structure and protein composition, or they appear to be missing altogether. In these animals, the origin of the first centrioles is not clear. Here, we review various hypotheses on how centrioles are gained during reproduction and describe specialized functions of the zygotic centrioles. In particular, we discuss a new and atypical centriole found in sperm and zygote, called the proximal centriole-like structure (PCL). We also discuss another type of atypical centriole, the "zombie" centriole, which is degenerated but functional. Together, the presence of centrioles, PCL, and zombie centrioles suggests a universal mechanism of centriole inheritance among animals and new causes of infertility. Since the atypical centrioles of sperm and zygote share similar functions with typical centrioles in somatic cells, they can provide unmatched insight into centriole biology.

Atypical Centrioles During Sexual Reproduction

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Tomer eAvidor-Reiss

2015-04-01

Full Text Available Centrioles are conserved, self-replicating, microtubule-based 9-fold symmetric subcellular organelles that are essential for proper cell division and function. Most cells have two centrioles and maintaining this number of centrioles is important for animal development and physiology. However, how animals gain their first two centrioles during reproduction is only partially understood. It is well established that in most animals, the centrioles are contributed to the zygote by the sperm. However, in humans and many animals, the sperm centrioles are modified in their structure and protein composition, or they appear to be missing altogether. In these animals, the origin of the first centrioles is not clear. Here, we review various hypotheses on how centrioles are gained during reproduction and describe specialized functions of the zygotic centrioles. In particular, we discuss a new and atypical centriole found in sperm and zygote, the proximal centriole-like structure (PCL. We also discuss another type of atypical centriole, the zombie centriole, which is degenerated but functional. Together, the presence of centrioles, PCL, and zombie centrioles suggests a universal mechanism of centriole inheritance among animals and new causes of infertility. Since the atypical centrioles of sperm and zygote share similar functions with typical centrioles in somatic cells, they can provide unmatched insight into centriole biology.

Phytochemistry and pharmacology of anti-depressant medicinal plants: A review.

Science.gov (United States)

Martins, Jeanette; S, Brijesh

2018-05-16

Stress renders an individual to experience mental pressure and exhaustion which brings about feelings of anxiety, depression, anger and/or other negative emotions. Depression affects a person's state of mind, behaviour, health and is often associated with suicide. The use of anti-depressant drugs as therapeutic agents is associated with symptoms such as, delayed onset of action, side-effects, drug-drug and dietary interactions, sexual dysfunction, cardiac toxicity, etc. Thus, there is need to target these issues and improve current treatment options. Medicinal plants have long been used in discovering novel treatment strategies and compounds with promising roles in treating various disease conditions. There has been an increase, worldwide, in the use of medicinal plants and herbs for developing nutraceuticals for treatment of depression and other psychiatric disorders. Medicinal plants in their natural forms are valuable as they are rich in various phytochemical compounds. These phytochemical compounds have pharmacological roles in treating various diseases conditions; apart from being widely available in nature and commercially beneficial. The phytochemical compounds in plants are constantly being explored through various experimental studies to determine the molecular basis of how medicinal plants work in relation to drugs and diseases and to develop neutraceuticals for improving conditions. This review summarizes 110 medicinal plants and their phytochemical constituents that have been shown to possess anti-depressant activity. This review also highlights the various mechanisms of anti-depressant action of some of these plants and their plant parts like roots, stem, leaves, flowers, fruit or whole plant; phytochemical compounds showing anti-depressant activity such flavanoids, steroids, saponins, sugars, lectins, alkaloids, etc.; and various anti-depressant screening models used such as tail suspension test, forced swim test, chronic unpredictable stress test

Drug–drug interactions involving antidepressants: focus on desvenlafaxine

Directory of Open Access Journals (Sweden)

Low Y

2018-02-01

Full Text Available Yvette Low,1 Sajita Setia,2 Graca Lima3 1Department of Pharmacy, National University of Singapore, Singapore; 2Medical Affairs, Pfizer Pte. Ltd., Singapore; 3Global Medical Affairs, Asia-Pacific Region, Pfizer, Hong Kong Abstract: Psychiatric and physical conditions often coexist, and there is robust evidence that associates the frequency of depression with single and multiple physical conditions. More than half of patients with depression may have at least one chronic physical condition. Therefore, antidepressants are often used in cotherapy with other medications for the management of both psychiatric and chronic physical illnesses. The risk of drug–drug interactions (DDIs is augmented by complex polypharmacy regimens and extended periods of treatment required, of which possible outcomes range from tolerability issues to lack of efficacy and serious adverse events. Optimal patient outcomes may be achieved through drug selection with minimal potential for DDIs. Desvenlafaxine is a serotonin–norepinephrine reuptake inhibitor approved for the treatment of adults with major depressive disorder. Pharmacokinetic studies of desvenlafaxine have shown a simple metabolic profile unique among antidepressants. This review examines the DDI profiles of antidepressants, particularly desvenlafaxine, in relation to drugs of different therapeutic areas. The summary and comparison of information available is meant to help clinicians in making informed decisions when using desvenlafaxine in patients with depression and comorbid chronic conditions. Keywords: desvenlafaxine, polypharmacy, comorbidities, depression, pharmacokinetics

Modifying 5-HT1A receptor gene expression as a new target for antidepressant therapy

Directory of Open Access Journals (Sweden)

Paul R Albert

2010-06-01

Full Text Available Major depression is the most common form of mental illness, and is treated with antidepressant compounds that increase serotonin (5-HT neurotransmission. Increased 5-HT1A autoreceptor levels in the raphe nuclei act as a “brake” to inhibit the 5-HT system, leading to depression and resistance to antidepressants. Several 5-HT1A receptor agonists (buspirone, flesinoxan, ipsapirone that preferentially desensitize 5-HT1A autoreceptors have been tested for augmentation of antidepressant drugs with mixed results. One explanation could be the presence of the C(-1019G 5-HT1A promoter polymorphism that prevents gene repression of the 5-HT1A autoreceptor. Furthermore, down-regulation of 5-HT1A autoreceptor expression, not simply desensitization of receptor signaling, appears to be required to enhance and accelerate antidepressant action. The current review focuses on the transcriptional regulators of 5-HT1A autoreceptor expression, their roles in permitting response to 5-HT1A-targeted treatments and their potential as targets for new antidepressant compounds for treatment-resistant depression.

Role of NMDA receptor GluN2D subunit in the antidepressant effects of enantiomers of ketamine

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Soichiro Ide

2017-11-01

Full Text Available We investigated the rapid and sustained antidepressant effects of enantiomers of ketamine in N-methyl-d-aspartate (NMDA receptor GluN2D subunit knockout (GluN2D-KO mice. Intraperitoneal administration of ketamine or its enantiomers 10 min before the tail-suspension test exerted significant antidepressant effects on restraint stress-induced depression in both wildtype and GluN2D-KO mice. The antidepressant effects of (RS-ketamine and (S-ketamine were sustained 96 h after the injection in both wildtype and GluN2D-KO mice, but such sustained antidepressant effects of (R-ketamine were only observed in wildtype mice. These data suggest that the GluN2D subunit is critical for the sustained antidepressant effects of (R-ketamine.

Chronic administration of anticonvulsants but not antidepressants impairs bone strength: clinical implications.

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Gold, P W; Pavlatou, M G; Michelson, D; Mouro, C M; Kling, M A; Wong, M-L; Licinio, J; Goldstein, S A

2015-06-02

Major depression and bipolar disorder are associated with decreased bone mineral density (BMD). Antidepressants such as imipramine (IMIP) and specific serotonin reuptake inhibitors (SSRIs) have been implicated in reduced BMD and/or fracture in older depressed patients. Moreover, anticonvulsants such as valproate (VAL) and carbamazepine (CBZ) are also known to increase fracture rates. Although BMD is a predictor of susceptibility to fracture, bone strength is a more sensitive predictor. We measured mechanical and geometrical properties of bone in 68 male Sprague Dawley rats on IMIP, fluoxetine (FLX), VAL, CBZ, CBZ vehicle and saline (SAL), given intraperitoneally daily for 8 weeks. Distinct regions were tested to failure by four-point bending, whereas load displacement was used to determine stiffness. The left femurs were scanned in a MicroCT system to calculate mid-diaphyseal moments of inertia. None of these parameters were affected by antidepressants. However, VAL resulted in a significant decrease in stiffness and a reduction in yield, and CBZ induced a decrease in stiffness. Only CBZ induced alterations in mechanical properties that were accompanied by significant geometrical changes. These data reveal that chronic antidepressant treatment does not reduce bone strength, in contrast to chronic anticonvulsant treatment. Thus, decreased BMD and increased fracture rates in older patients on antidepressants are more likely to represent factors intrinsic to depression that weaken bone rather than antidepressants per se. Patients with affective illness on anticonvulsants may be at particularly high risk for fracture, especially as they grow older, as bone strength falls progressively with age.

Monoamine involvement in the antidepressant-like effect induced by P2 blockade.

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Diniz, Cassiano R A F; Rodrigues, Murilo; Casarotto, Plínio C; Pereira, Vítor S; Crestani, Carlos C; Joca, Sâmia R L

2017-12-01

Depression is a common mental disorder that affects millions of individuals worldwide. Available monoaminergic antidepressants are far from ideal since they show delayed onset of action and are ineffective in approximately 40% of patients, thus indicating the need of new and more effective drugs. ATP signaling through P2 receptors seems to play an important role in neuropathological mechanisms involved in depression, since their pharmacological or genetic inactivation induce antidepressant-like effects in the forced swimming test (FST). However, the mechanisms involved in these effects are not completely understood. The present work investigated monoamine involvement in the antidepressant-like effect induced by non-specific P2 receptor antagonist (PPADS) administration. First, the effects of combining sub-effective doses of PPADS with sub-effective doses of fluoxetine (FLX, selective serotonin reuptake inhibitor) or reboxetine (RBX, selective noradrenaline reuptake inhibitor) were investigated in mice submitted to FST. Significant antidepressant-like effect was observed when subeffective doses of PPADS was combined with subeffective doses of either FLX or RBX, with no significant locomotor changes. Next, the effects of depleting serotonin and noradrenaline levels, by means of PCPA (p-Chlorophenylalanine) or DSP-4 (N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine hydrochloride) pretreatment, respectively, was investigated. Both, PCPA and DSP-4 pretreatment partially attenuated PPADS-induced effects in FST, without inducing relevant locomotor changes. Our results suggest that the antidepressant-like effect of PPADS involves modulation of serotonin and noradrenaline levels in the brain. Copyright © 2017 Elsevier B.V. All rights reserved.

Antidepressants Are Effective in Decreasing Neuropathic Pain After SCI: A Meta-Analysis.

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Mehta, Swati; Guy, Stacey; Lam, Tracey; Teasell, Robert; Loh, Eldon

2015-01-01

To systematically review and assess the effectiveness and safety of antidepressants for neuropathic pain among individuals with spinal cord injury (SCI). A systematic search was conducted using multiple databases for relevant articles published from 1980 to April 2014. Randomized controlled trials (RCTs) involving antidepressant treatment of neuropathic pain with ≥ 3 individuals and ≥ 50% of study population with SCI were included. Two independent reviewers selected studies based on inclusion criteria and then extracted data. Pooled analysis using Cohen's d to calculate standardized mean difference, standard error, and 95% confidence interval for primary (pain) and other secondary outcomes was conducted. Four RCTs met inclusion criteria. Of these, 2 studies assessed amitriptyline, 1 trazadone, and 1 duloxetine among individuals with neuropathic SCI pain. A small effect was seen in the effectiveness of antidepressants in decreasing pain among individuals with SCI (standardized mean difference = 0.34 ± 0.15; 95% CI, 0.05-0.62; P = .02). A number needed to treat of 3.4 for 30% or more pain relief was found by pooling 2 studies. Of these, significantly higher risk of experiencing constipation (risk ratio [RR] = 1.74; 95% CI, 1.09-2.78; P = .02) and dry mouth (RR = 1.39; 95% CI, 1.04-1.85; P = .02) was found amongst individuals receiving antidepressant treatment compared to those in the control group. The current meta-analysis demonstrates that antidepressants are effective in reducing neuropathic SCI pain. However, this should be interpreted with caution due to the limited number of studies. Further evaluation of long-term therapeutic options may be required.

Yueju Pill Rapidly Induces Antidepressant-Like Effects and Acutely Enhances BDNF Expression in Mouse Brain

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Wenda Xue

2013-01-01

Full Text Available The traditional antidepressants have a major disadvantage in delayed onset of efficacy, and the emerging fast-acting antidepressant ketamine has adverse behavioral and neurotoxic effects. Yueju pill, an herb medicine formulated eight hundred years ago by Doctor Zhu Danxi, has been popularly prescribed in China for alleviation of depression-like symptoms. Although several clinical outcome studies reported the relative short onset of antidepressant effects of Yueju, this has not been scientifically investigated. We, therefore, examined the rapid antidepressant effect of Yueju in mice and tested the underlying molecular mechanisms. We found that acute administration of ethanol extract of Yueju rapidly attenuated depressive-like symptoms in learned helpless paradigm, and the antidepressant-like effects were sustained for at least 24 hours in tail suspension test in ICR mice. Additionally, Yueju, like ketamine, rapidly increased the expression of brain-derived neurotrophic factor (BDNF in the hippocampus, whereas the BDNF mRNA expression remained unaltered. Yueju rapidly reduced the phosphorylation of eukaryotic elongation factor 2 (eEF2, leading to desuppression of BDNF synthesis. Unlike ketamine, both the BDNF expression and eEF2 phosphorylation were revered at 24 hours after Yueju administration. This study is the first to demonstrate the rapid antidepressant effects of an herb medicine, offering an opportunity to improve therapy of depression.

Reduced Treatment-Emergent Sexual Dysfunction as a Potential Target in the Development of New Antidepressants

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David S. Baldwin

2013-01-01

Full Text Available Pleasurable sexual activity is an essential component of many human relationships, providing a sense of physical, psychological, and social well-being. Epidemiological and clinical studies show that depressive symptoms and depressive illness are associated with impairments in sexual function and satisfaction, both in untreated and treated patients. The findings of randomized placebo-controlled trials demonstrate that most of the currently available antidepressant drugs are associated with the development or worsening of sexual dysfunction, in a substantial proportion of patients. Sexual difficulties during antidepressant treatment often resolve as depression lifts but can endure over long periods and may reduce self-esteem and affect mood and relationships adversely. Sexual dysfunction during antidepressant treatment is typically associated with many possible causes, but the risk and type of dysfunction vary with differing compounds and should be considered when making decisions about the relative merits and drawbacks of differing antidepressants. A range of interventions can be considered when managing patients with sexual dysfunction associated with antidepressants, including the prescription of phosphodiesterase-5 inhibitors, but none of these approaches can be considered “ideal.” As treatment-emergent sexual dysfunction is less frequent with certain drugs, presumably related to differences in their pharmacological properties, and because current management approaches are less than ideal, a reduced burden of treatment-emergent sexual dysfunction represents a tolerability target in the development of novel antidepressants.

Possible role of more positive social behaviour in the clinical effect of antidepressant drugs

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Young, Simon N.; Moskowitz, Debbie S.; aan Het Rot, Marije

Increasing serotonin decreases quarrelsome behaviours and enhances agreeable behaviours in humans. Antidepressants, even those whose primary action is not on serotonin, seem to increase serotonin function. We suggest that antidepressants act in part by effects on social behaviour, which leads to a

Fluoxetine potentiation of omega-3 fatty acid antidepressant effect: evaluating pharmacokinetic and brain fatty acid-related aspects in rodents.

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Laino, Carlos Horacio; Garcia, Pilar; Podestá, María Fernanda; Höcht, Christian; Slobodianik, Nora; Reinés, Analía

2014-10-01

We previously reported that combined fluoxetine administration at antidepressant doses renders additive antidepressant effects, whereas non-antidepressant doses potentiate the omega-3 fatty acid antidepressant effect. In the present study, we aimed to evaluate putative pharmacokinetic and brain omega-3 fatty acid-related aspects for fluoxetine potentiation of omega-3 fatty acid antidepressant effect in rats. Coadministration of omega-3 fatty acids with a non-antidepressant dose of fluoxetine (1 mg/kg day) failed to affect both brain fluoxetine concentration and norfluoxetine plasma concentration profile. Fluoxetine plasma concentrations remained below the sensitivity limit of the detection method. Either antidepressant (10 mg/kg day) or non-antidepressant (1 mg/kg day) doses of fluoxetine in combination with omega-3 fatty acids increased hippocampal docosapentaenoic acid (DPA, 22:5 omega-3) levels. Although individual treatments had no effects on DPA concentration, DPA increase was higher when omega-3 were combined with the non-antidepressant dose of fluoxetine. Chronic DPA administration exerted antidepressant-like effects in the forced swimming test while increasing hippocampal docosahexaenoic (22:6 omega-3) and DPA levels. Our results suggest no pharmacokinetic interaction and reveal specific hippocampal DPA changes after fluoxetine and omega-3 combined treatments in our experimental conditions. The DPA role in the synergistic effect of fluoxetine and omega-3 combined treatments will be for sure the focus of future studies. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 103:3316-3325, 2014. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.

Effectiveness of antidepressants: an evidence myth constructed from a thousand randomized trials?

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Ioannidis John PA

2008-05-01

Full Text Available Abstract Antidepressants, in particular newer agents, are among the most widely prescribed medications worldwide with annual sales of billions of dollars. The introduction of these agents in the market has passed through seemingly strict regulatory control. Over a thousand randomized trials have been conducted with antidepressants. Statistically significant benefits have been repeatedly demonstrated and the medical literature is flooded with several hundreds of "positive" trials (both pre-approval and post-approval. However, two recent meta-analyses question this picture. The first meta-analysis used data that were submitted to FDA for the approval of 12 antidepressant drugs. While only half of these trials had formally significant effectiveness, published reports almost ubiquitously claimed significant results. "Negative" trials were either left unpublished or were distorted to present "positive" results. The average benefit of these drugs based on the FDA data was of small magnitude, while the published literature suggested larger benefits. A second meta-analysis using also FDA-submitted data examined the relationship between treatment effect and baseline severity of depression. Drug-placebo differences increased with increasing baseline severity and the difference became large enough to be clinically important only in the very small minority of patient populations with severe major depression. In severe major depression, antidepressants did not become more effective, simply placebo lost effectiveness. These data suggest that antidepressants may be less effective than their wide marketing suggests. Short-term benefits are small and long-term balance of benefits and harms is understudied. I discuss how the use of many small randomized trials with clinically non-relevant outcomes, improper interpretation of statistical significance, manipulated study design, biased selection of study populations, short follow-up, and selective and distorted

Beliefs of people taking antidepressants about causes of depression and reasons for increased prescribing rates.

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Read, John; Cartwright, Claire; Gibson, Kerry; Shiels, Christopher; Haslam, Nicholas

2014-10-01

Public beliefs about the causes of mental health problems are related to desire for distance and pessimism about recovery, and are therefore frequently studied. The beliefs of people receiving treatment are researched less often. An online survey on causal beliefs about depression and experiences with antidepressants was completed by 1829 New Zealand adults prescribed anti-depressants in the preceding five years, 97.4% of whom proceeded to take antidepressants. The most frequently endorsed of 17 causal beliefs were family stress, relationship problems, loss of loved one, financial problems, isolation, and abuse or neglect in childhood. Factor analysis produced three factors: 'bio-genetic', 'adulthood stress' and 'childhood adversity'. The most strongly endorsed explanations for increases in antidepressant prescribing invoked improved identification, reduced stigma and drug company marketing. The least strongly endorsed was 'Anti-depressants are the best treatment'. Regression analyses revealed that self-reported efficacy of the antidepressants was positively associated with bio-genetic causal beliefs, negatively associated with childhood adversity beliefs and unrelated to adulthood stress beliefs. The belief that 'People cannot׳ get better by themselves even if they try' was positively associated with bio-genetic beliefs. The convenience sample may have been biased towards a favourable view of bio-genetic explanations, since 83% reported that the medication reduced their depression. Clinicians׳ should consider exploring patients׳ causal beliefs. The public, even when taking antidepressants, continues to hold a multi-factorial causal model of depression with a primary emphasis on psycho-social causes. A three factor model of those beliefs may lead to more sophisticated understandings of relationships with stigma variables. Copyright © 2014 Elsevier B.V. All rights reserved.

Physical and Psychological Morbidity in Adolescents With Atypical Anorexia Nervosa.

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Sawyer, Susan M; Whitelaw, Melissa; Le Grange, Daniel; Yeo, Michele; Hughes, Elizabeth K

2016-04-01

Adolescents with atypical anorexia nervosa (AN) have lost significant weight but are not underweight. This study aimed to describe the physical and psychological morbidity of adolescents diagnosed with atypical AN, and to compare them with underweight adolescents with AN. All first presentations of atypical AN (n = 42) and full-threshold AN (n = 118) to a specialist pediatric eating disorder program between July 2010 and June 2014 were examined. Diagnosis was assessed by using the Eating Disorder Examination and anthropometric measurement. Psychological morbidity measures included eating and weight concerns, bingeing, purging, compulsive exercise, and psychiatric comorbidity. Compared with AN, more adolescents with atypical AN were premorbidly overweight or obese (71% vs 12%). They had lost more weight (17.6 kg vs 11.0 kg) over a longer period (13.3 vs 10.2 months). There was no significant difference in the frequency of bradycardia (24% vs 33%;) or orthostatic instability (43% vs 38%). We found no evidence of a difference in frequency of psychiatric comorbidities (38% vs 45%) or suicidal ideation (43% vs 39%). Distress related to eating and body image was more severe in atypical AN. Atypical AN considerably affects physical and psychological functioning, despite adolescents presenting within or above the normal weight range. There was little evidence that the morbidity of adolescents with atypical AN was any less severe than that of adolescents with full-threshold AN. The findings support the need for vigilance around weight loss in adolescents, regardless of body size. Copyright © 2016 by the American Academy of Pediatrics.

Antidepressant-selective gynecomastia.

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Kaufman, Kenneth R; Podolsky, Dina; Greenman, Danielle; Madraswala, Rehman

2013-01-01

To describe what we believe is the first reported case of synergistic gynecomastia during treatment of depressive and anxiety disorders when sertraline was added to a stable medication regimen including duloxetine, rosuvastatin, and amlodipine. A 67-year-old male with major depression, dysthymia, obsessive-compulsive disorder, social anxiety, hypertension, diabetes, and hyperlipidemia presented with new-onset gynecomastia and breast tenderness. Mammography revealed bilateral gynecomastia (fibroglandular tissue posterior to the nipples bilaterally) without suspicious mass, calcification, or other abnormalities. These new symptoms developed after sertraline was added to his stable medication regimen (duloxetine, alprazolam, rosuvastatin, metoprolol, amlodipine, hydrochlorothiazide/triamterene, metformin, and sitagliptin). These symptoms were dose-dependent, with gynecomastia and breast tenderness more severe as sertraline was titrated from 25 mg/day to 50 mg/day and then to 75 mg/day. When sertraline was discontinued, gynecomastia and breast tenderness rapidly resolved. Mammoplasia and gynecomastia are associated with altered dopamine neurotransmission and/or perturbations in sexual hormones. These adverse effects may be medication induced. Selective serotonin reuptake inhibitors (sertraline), serotonin-norepinephrine reuptake inhibitors (duloxetine), rosuvastatin, and amlodipine have been reported to cause these adverse effects. This case was unique, since the patient had been on both sertraline and duloxetine previously as independent psychotropics without the development of gynecomastia. In the context of an additive drug adverse effect, the probability of sertraline as the precipitant drug was determined by both the Naranjo probability scale and the Horn drug interaction probability scale as probable. Gynecomastia is associated with antidepressants and other medications but is rarely addressed. Gynecomastia may be antidepressant selective or may be the result of

The impact of direct-to-consumer television and magazine advertising on antidepressant use.

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Avery, Rosemary J; Eisenberg, Matthew D; Simon, Kosali I

2012-09-01

We examine whether exposure to direct-to-consumer advertising (DTCA) for antidepressant drugs affects individual use of these medications among those suffering from depression. Prior studies have almost exclusively relied on making connections between national or market-level advertising volume/expenditures and national or individual-level usage of medications. This is the first study to: estimate the impact of individual-level exposure to DTCA on individual-level use of antidepressants; estimate the impact of individual-level exposure to television DTCA on individual-level use in any drug class; consider the relative and interactive impact of DTCA in two different media in any drug class; and, consider the heterogeneity of impact among different populations in an econometric framework in the antidepressant market. There are also important limitations to note. Unlike prior market level studies that use monthly data, we are limited to aggregated annual data. Our measures of potential advertising exposure are constructed assuming that media consumption patterns are stable during the year. We are also not able to study the impact of advertising on use of antidepressants for conditions other than depression, such as anxiety disorders. We find that: DTCA impacts antidepressant use in a statistically and economically significant manner; that these effects are present in both television and magazine advertising exposure but do not appear to have interactive effects; are stronger for women than for men in the magazine medium, but are about equally strong for men and women in the TV medium; and, are somewhat stronger for groups suffering from more severe forms of depression. The overall size of the effect is a 6-10 percentage point increase in antidepressant use from being exposed to television advertising; the corresponding magazine effects are between 3 and 4 percentage points. Copyright © 2012 Elsevier B.V. All rights reserved.

Antidepressant sales and the risk for alcohol-related and non-alcohol-related suicide in Finland--an individual-level population study.

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Moustgaard, Heta; Joutsenniemi, Kaisla; Myrskylä, Mikko; Martikainen, Pekka

2014-01-01

A marked decline in suicide rates has co-occurred with increased antidepressant sales in several countries but the causal connection between the trends remains debated. Most previous studies have focused on overall suicide rates and neglected differential effects in population subgroups. Our objective was to investigate whether increasing sales of non-tricyclic antidepressants have reduced alcohol- and non-alcohol-related suicide risk in different population subgroups. We followed a nationally representative sample of 950,158 Finnish adults in 1995-2007 for alcohol-related (n = 2,859) and non-alcohol-related (n = 8,632) suicides. We assessed suicide risk by gender and social group according to regional sales of non-tricyclic antidepressants, measured by sold doses per capita, prevalence of antidepressant users, and proportion of antidepressant users with doses reflecting minimally adequate treatment. Fixed-effects Poisson regression models controlled for regional differences and time trends that may influence suicide risk irrespective of antidepressant sales. The number of sold antidepressant doses per capita and the prevalence of antidepressant users were unrelated to male suicide risk. However, one percentage point increase in the proportion of antidepressant users receiving minimally adequate treatment reduced non-alcohol-related male suicide risk by one percent (relative risk 0.987, 95% confidence interval 0.976-0.998). This beneficial effect only emerged among men with high education, high income, and employment, among men without a partner, and men not owning their home. Alcohol-related suicides and female suicides were unrelated to all measures of antidepressant sales. We found little evidence that increase in overall sales or in the prevalence of non-tricyclic antidepressant users would have caused the fall in suicide rates in Finland in 1995-2007. However, the rise in the proportion of antidepressant users receiving minimally adequate treatment, possibly

Effect of antidepressants and psychological therapies, including hypnotherapy, in irritable bowel syndrome: systematic review and meta-analysis.

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Ford, Alexander C; Quigley, Eamonn M M; Lacy, Brian E; Lembo, Anthony J; Saito, Yuri A; Schiller, Lawrence R; Soffer, Edy E; Spiegel, Brennan M R; Moayyedi, Paul

2014-09-01

Irritable bowel syndrome (IBS) is a chronic functional gastrointestinal disorder. Evidence relating to the treatment of this condition with antidepressants and psychological therapies continues to accumulate. We performed an updated systematic review and meta-analysis of randomized controlled trials (RCTs). MEDLINE, EMBASE, and the Cochrane Controlled Trials Register were searched (up to December 2013). Trials recruiting adults with IBS, which compared antidepressants with placebo, or psychological therapies with control therapy or "usual management," were eligible. Dichotomous symptom data were pooled to obtain a relative risk (RR) of remaining symptomatic after therapy, with a 95% confidence interval (CI). The search strategy identified 3,788 citations. Forty-eight RCTs were eligible for inclusion: thirty-one compared psychological therapies with control therapy or "usual management," sixteen compared antidepressants with placebo, and one compared both psychological therapy and antidepressants with placebo. Ten of the trials of psychological therapies, and four of the RCTs of antidepressants, had been published since our previous meta-analysis. The RR of IBS symptom not improving with antidepressants vs. placebo was 0.67 (95% CI=0.58-0.77), with similar treatment effects for both tricyclic antidepressants and selective serotonin reuptake inhibitors. The RR of symptoms not improving with psychological therapies was 0.68 (95% CI=0.61-0.76). Cognitive behavioral therapy, hypnotherapy, multicomponent psychological therapy, and dynamic psychotherapy were all beneficial. Antidepressants and some psychological therapies are effective treatments for IBS. Despite the considerable number of studies published in the intervening 5 years since we last examined this issue, the overall summary estimates of treatment effect have remained remarkably stable.

Antidepressant activity of standardised extract of Marsilea minuta Linn.

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Bhattamisra, Subrat Kumar; Khanna, Vinay Kumar; Agrawal, Ashok Kumar; Singh, Paras Nath; Singh, Sushil Kumar

2008-04-17

Marsilea minuta Linn. (Marsileaceae) has been referred in Indian traditional medicine system (Ayurveda) for the treatment of insomnia and other mental disorders. Marsiline isolated from Marsilea minuta was reported to have sedative and anticonvulsant property. The ethanol extract of Marsilea minuta was standardised for marsiline (1.15%, w/w) and studied for its antidepressant activity. Antidepressant activity was studied using forced swimming test (FST), tail suspension test (TST), learned helplessness test (LHT) and 5-hydroxytryptophan (5-HTP) induced head twitches response in rodents. Standardised extract of Marsilea minuta in doses of 100, 200 and 400 mg/kg/day were administered orally for three consecutive days and evaluated on day 3, 1h after the last dose treatment. Imipramine (15 mg/kg/day, i.p.) was used as the standard drug. Neurochemical mechanism of antidepressant activity was elucidated by using radioligand receptor binding assays for 5-HT2A and benzodiazepine receptors in rat frontal cortex. Immobility time in FST and TST was significantly (P<0.05) reduced by ethanol extract of Marsilea minuta treated animals. A decrease in number of escape failures in LHT was also observed in Marsilea minuta treated rats. Head twitch response induced by 5-HTP was significantly attenuated by Marsilea minuta (400 mg/kg, p.o.) and imipramine showing the involvement of serotonergic system. This effect was corroborated with radioligand receptor binding study where Marsilea minuta (400 mg/kg, p.o.) significantly (P<0.05) down regulated 5-HT2A receptor in frontal cortex, whereas, no marked effect was observed for benzodiazepine receptor. The antidepressant effect exhibited by Marsilea minuta extract may be due to its effect on 5-HT2A density in rat frontal cortex.

Cardiotoxicity of tricyclic antidepressant treated by 2650 mEq sodium bicarbonate: A case report.

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Amiri, Hassan; Zamani, Nasim; Hassanian-Moghaddam, Hossein; Shadnia, Shahin

2016-01-01

Poisoning with tricyclic antidepressants is an important cause of drug-related self-poisoning in the developed world and a very common cause of poisoning and mortality in developing countries. Electrocardiographic manifestations of most tricyclic antidepressant-poisoned patients resolve by the administration of 1-2 mEq/kg of sodium bicarbonate. Some rare cases have been reported who have been resistant to the long-term or high doses of bicarbonate administration. We present a case of acute tricyclic antidepressant toxicity referring with status epilepticus, hypotension, and refractory QRS complex widening that resolved after the intravenous administration of 2650 mEq sodium bicarbonate.

'Atypical' bacteria are a common cause of community-acquired ...

African Journals Online (AJOL)

Objectives. To assess the proportion of cases of community· acquired pneumonia caused by 'atypical' bacteria, inclUding the recently discovered Chlamydia pneumoniae, and to compare the clinical, radiographic and laboratory features of patients with and without 'atypical' bacteria. Methods. A prospective serological ...

Atypical manifestations of early syphilis

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R V Koranne

1990-01-01

Full Text Available A study of 36 untreated patients with early syphilis revealed atypical variations namely; long incubation period of 101 days in I patient, more than 3 chancres in 1, undermined margin of the chancre along with tenderness in 1 and moderate to severe tenderness of the ulcers in 2 cases. In 3 patients there was no indurations of the ulcers. Three patients with primary syphilis had unilateral lymphadenitis, and in I case the lymph nodes were not only tender but showed tendency towardsmatingawell. Insecondarysyphilis, 11 out of 16 patients having condylomata lata had no other muco-cutaneous lesions. Concomitant presence of other venereal disease to account for the atypical manifestations was discounted- by appropriate laboratory tests, response to therapeutic agents and follow up.

Mind your state: Insights into antidepressant nonadherence

African Journals Online (AJOL)

Major depressive disorder (MDD) is a severe and debilitating condition1 that occurs in ... that long-term emotional learning processes may play a key role in ... contribute to antidepressants not being highly effective. ... positive outcome with continuous drug treatment.23, 26 Moreover, ... psychological and biological domains.

Antidepressant effect of Melissa officinalis in the forced swimming test

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M Emamghoreishi

2009-03-01

Full Text Available ABSTRACT Background: In Iranian and other traditional medicines, an antidepressant effect has been indicated for Melissa officinalis (Lamiaceae. However, studies showing its antidepressant effect is lacking. Therefore, the present study was undertaken to examine whether the aqueous extract and essential oil from leaves of Melissa officinalis have an antidepressant-like activity in mice.  Materials and Methods: The effect of subchronic administration of different doses of the aqueous extract (25, 75, 150, 300 mg/kg or water; n=9-10 and the essential oil (10, 25, 75, 150, 300 mg/kg or almond oil; n=9-10 on immobility, climbing, and swimming behaviors were evaluated in the forced swimming test. Fluoxetine (20mg/kg and imipramine (15 mg/kg were used as reference drugs. Additionally, the effect of both plant preparations on spontaneous activity was examined. Results: All doses of the aqueous extract, used in this study, produced a significant reduction in immobility along with an increase in climbing behavior which is similar to those which have been observed with imipramine. Essential oil caused a dose-dependent reduction in immobility and an increase in climbing at all studied doses, compared to control group. Only the highest dose (300mg/kg of essential oil showed a significant increase in swimming behavior. The aqueous extract, but not the essential oil, decreased spontaneous activity in a dose dependent manner. Conclusion: The results of this study suggests that the Melissa officinalis possess an antidepressant-like activity similar to imipramine which may have a potential clinical value for treatment of depression.

Role of NMDA receptor GluN2D subunit in the antidepressant effects of enantiomers of ketamine.

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Ide, Soichiro; Ikekubo, Yuiko; Mishina, Masayoshi; Hashimoto, Kenji; Ikeda, Kazutaka

2017-11-01

We investigated the rapid and sustained antidepressant effects of enantiomers of ketamine in N-methyl-d-aspartate (NMDA) receptor GluN2D subunit knockout (GluN2D-KO) mice. Intraperitoneal administration of ketamine or its enantiomers 10 min before the tail-suspension test exerted significant antidepressant effects on restraint stress-induced depression in both wildtype and GluN2D-KO mice. The antidepressant effects of (RS)-ketamine and (S)-ketamine were sustained 96 h after the injection in both wildtype and GluN2D-KO mice, but such sustained antidepressant effects of (R)-ketamine were only observed in wildtype mice. These data suggest that the GluN2D subunit is critical for the sustained antidepressant effects of (R)-ketamine. Copyright © 2017 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

The effects of ifenprodil on the activity of antidepressant drugs in the forced swim test in mice.

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Poleszak, Ewa; Wośko, Sylwia; Serefko, Anna; Wlaź, Aleksandra; Kasperek, Regina; Dudka, Jarosław; Wróbel, Andrzej; Nowak, Gabriel; Wlaź, Piotr

2014-12-01

According to reports in the literature, more than 30% of depressive patients fail to achieve remission. Therapy with the conventional antidepressant drugs may induce the serious adverse reactions. Moreover, its benefits may be seen at least 2-4 weeks after the first dose. Therefore, the alternative strategies for prevention and treatment of depression are sought. The main aim of our study was to assess the effects of ifenprodil given at a non-active dose (10mg/kg) on the activity of antidepressant agents from diverse pharmacological groups. The antidepressant-like effect was assessed by the forced swim test in mice. Ifenprodil potentiated the antidepressant-like effect of imipramine (15mg/kg) and fluoxetine (5mg/kg) while did not reduce the immobility time of animals which simultaneously received reboxetine (2.5mg/kg) or tianeptine (15mg/kg). The concomitant administration of certain commonly prescribed antidepressant drugs that affect the serotonergic neurotransmission (i.e., typical tricyclic antidepressants and selective serotonin reuptake inhibitors) with a negative modulator selectively binding to the GluN1/N2B subunits of the NMDA receptor complex (i.e., ifenprodil) may induce a more pronounced antidepressant-like effect than monotherapy. However, these findings still need to be confirmed in further experiments. Copyright © 2014 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

Involvement of NMDA receptors in the antidepressant-like effect of tramadol in the mouse forced swimming test.

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Ostadhadi, Sattar; Norouzi-Javidan, Abbas; Chamanara, Mohsen; Akbarian, Reyhaneh; Imran-Khan, Muhammad; Ghasemi, Mehdi; Dehpour, Ahmad-Reza

2017-09-01

Tramadol is an analgesic agent that is mainly used to treat moderate to severe pain. There is evidence that tramadol may have antidepressant property. However, the mechanisms underlying the antidepressant effects of tramadol have not been elucidated yet. Considering that fact that N-methyl-d-aspartate (NMDA) receptor signaling may play an important role in the pathophysiology of depression, the aim of the present study was to investigate the role of NMDA receptor signaling in the possible antidepressant-like effects of tramadol in the mouse forced swimming test (mFST). We found that tramadol exerted antidepressant-like effects at high dose (40mg/kg, intraperitoneally [i.p.]) in the mFST. Co-administration of non-effective doses of NMDA receptor antagonists (ketamine [1mg/kg, i.p.], MK-801 [0.05mg/kg, i.p.], or magnesium sulfate [10mg/kg, i.p.]) with sub-effective dose of tramadol (20mg/kg, i.p.) exerted significant antidepressant-like effects in the mFST. The antidepressant-like effects of tramadol (40mg/kg) was also inhibited by pre-treatment with non-effective dose of the NMDA receptor agonist NMDA (75mg/kg, i.p.). Our data suggest a role for NMDA receptor signaling in the antidepressant-like effects of tramadol in the mFST. Copyright © 2017 Elsevier Inc. All rights reserved.

The effect of anti-depressant Amitriptyline on the immune system

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Dukan J

1994-04-01

Full Text Available We have studied the effect of amitriptyline, a tricyclic anti-depressant drug on several immune parameters of the Balb/c mice in order to evaluate its immunomodulatory effects. Results showed that amitriptyline will potentiates all of the immunocytes functions except for the production of PGE2 by LPS stimulated monocytes. We have also showed that amitriptyline can normalize the immunosuppressive effect of dexamethasone on mice (experimental stress. These results suggest that one of the mechanisms of action of the tricyclic anti-depressant drugs might be through the modulation of the immune system which has been suppressed by stress or distress

Tricyclic antidepressant overdose: emergency department findings as predictors of clinical course.

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Foulke, G E; Albertson, T E; Walby, W F

1986-11-01

There is controversy regarding the appropriate utilization of health care resources in the management of tricyclic antidepressant overdosage. Antidepressant overdose patients presenting to the emergency department (ED) are routinely admitted to intensive care units, but only a small proportion develop cardiac arrhythmias or other complications requiring such an environment. The authors reviewed the findings in 165 patients presenting to an ED with antidepressant overdose. They found that major manifestations of toxicity on ED evaluation (altered mental status, seizures, arrhythmias, and conduction defects) were commonly associated with a complicated hospital course. Patients with the isolated findings of sinus tachycardia or QTc prolongation had no complications. No patient experienced a serious toxic event without major evidence of toxicity on ED evaluation and continued evidence of toxicity during the hospital course. These data support the concept that proper ED evaluation can identify a large body of patients with trivial ingestions who may not require hospital observation.

An HDAC-dependent epigenetic mechanism that enhances the efficacy of the antidepressant drug fluoxetine

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Schmauss, C.

2015-01-01

Depression is a prevalent and debilitating psychiatric illnesses. However, currently prescribed antidepressant drugs are only efficacious in a limited group of patients. Studies on Balb/c mice suggested that histone deacetylase (HDAC) inhibition may enhance the efficacy of the widely-prescribed antidepressant drug fluoxetine. This study shows that reducing HDAC activity in fluoxetine-treated Balb/c mice leads to robust antidepressant and anxiolytic effects. While reducing the activity of class I HDACs 1 and 3 led to antidepressant effects, additional class II HDAC inhibition was necessary to exert anxiolytic effects. In fluoxetine-treated mice, HDAC inhibitors increased enrichment of acetylated histone H4 protein and RNA polymerase II at promotor 3 of the brain-derived neurotrophic factor (Bdnf) gene and increased Bdnf transcription from this promotor. Reducing Bdnf-stimulated tropomyosin kinase B receptor activation in fluoxetine-treated mice with low HDAC activity abolished the behavioral effects of fluoxetine, suggesting that the HDAC-triggered epigenetic stimulation of Bdnf expression is critical for therapeutic efficacy. PMID:25639887

Evolution of the concepts of the molecular mechanism of the action of antidepressants (survey)

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Mashkovskii, M.D.; Andreeva, N.I.

1986-01-01

The authors discuss investigation devoted to the study of the mechanisms of the action of antidepressants. Under the conditions of an acute experiment, antidepressants exhibit high affinity for the binding sites of [ 3 H] WB 4101, [ 3 H] LSD, and [ 3 H] spiroperiodol (alpha 1 - and S 2 -receptors). Certain antidepressants also have a high affinity for the binding sites of [ 3 H] clonidine and [ 3 H] S (alpha 2 - and S 1 -receptors). When the method of binding of radioligands was used to study the receptors, it was found that stimulation of cAMP synthesis, induced by norepinephrine, is primarily a beta-adrenergic response. Investigations of the influence of antidepressants in the case of their acute action in vitro on serotonin receptors showed that they inhibit the binding of [ 3 H] LSD and [ 3 H] spiroperiodol in the rat brain with high affinity and the binding of [ 3 H] S with low affinity

Association between antidepressant side effects and functional impairment in patients with major depressive disorders.

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Kikuchi, Toshiaki; Suzuki, Takefumi; Uchida, Hiroyuki; Watanabe, Koichiro; Mimura, Masaru

2013-11-30

Patients with depression may not well be aware of antidepressant adverse events (AEs); however, no studies have assessed how these AEs affect their daily function. Therefore, to evaluate the relationship between the quality of AEs and functional impairment, we studied 482 outpatients with depressive disorders who were not receiving any antidepressant treatment prior to the baseline visit and started it thereafter in usual clinical settings. The Quick Inventory for Depressive Symptomatology Self-Report Japanese version and antidepressant AEs for subjective assessment (antiAS) were performed at baseline and 10 days after antidepressant initiation (i.e. second visit). Functional impairment was evaluated with the Sheehan Disability Scale (SDS) on the second visit. As a result, the SDS was positively associated with the number of AEs (β=0.089, p=0.022) in multiple linear regression analysis (adjusted R(2)=0.357, pfunctional impairment than those who did not. Additionally, the number of severe AEs (β=0.151, pfunction. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Synthesis of Some Novel Thiadiazole Derivative Compounds and Screening Their Antidepressant-Like Activities

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Nafiz Öncü Can

2018-03-01

Full Text Available Novel thiadiazole derivatives were synthesized through the reaction of acetylated 2-aminothiadiazole and piperazine derivatives. The chemical structures of the compounds were clarified by Infrared Spectroscopy (IR, 1H Nuclear Magnetic Resonance Spectroscopy (1H-NMR, 13C Nuclear Magnetic Resonance Spectroscopy (13C-NMR and Electronspray Ionisation Mass Spectroscopy (ESI-MS spectroscopic methods. Antidepressant-like activities were evaluated by the tail-suspension (TST and modified forced swimming (MFST methods. Besides, possible influence of the test compounds on motor activities of the animals were examined by activity cage tests. In the TST, administration of the compounds 2c, 2d, 2e, 2f, 2g and 2h significantly decreased the immobility time of mice regarding the control values. Further, in the MFST, the same compounds reduced the total number of immobility behaviors while increasing swimming performance. However, no change was observed in the total number of climbing behaviors. These data suggested that compounds 2c, 2d, 2e, 2f, 2g and 2h possess notable antidepressant-like activities. Reference drug fluoxetine (10 mg/kg was also exhibited its antidepressant activity, as expected. No significant difference was seen between the locomotor activity values of the test groups signifying that observed antidepressant-like activities are specific. Theoretical calculation of absorption, distribution, metabolism, excretion (ADME properties for the obtained compounds were performed and obtained data supported the antidepressant-like potential of these novel thiadiazole derivatives.

Non-tricyclic and Non-selective Serotonin Reuptake Inhibitor Antidepressants and Recurrent Falls in Frail Older Women.

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Naples, Jennifer G; Kotlarczyk, Mary P; Perera, Subashan; Greenspan, Susan L; Hanlon, Joseph T

2016-12-01

To determine the risk of recurrent falls associated with antidepressants other than tricyclics (TCAs) and selective serotonin reuptake inhibitors (SSRIs) among frail older women. This is a secondary analysis of the Zoledronic acid in frail Elders to STrengthen bone, or ZEST, trial data treated as a longitudinal cohort in 181 frail, osteoporotic women aged ≥65 years in long-term care. The primary exposure was individual non-TCA/non-SSRI antidepressants (i.e., serotonin norepinephrine reuptake inhibitors, mirtazapine, trazodone, and bupropion) at baseline and 6 months. The main outcome was recurrent (at least two) falls within 6 months after antidepressant exposure. Adjusted odds ratios (AORs) and 95% confidence intervals (CIs) were derived using a generalized estimating equations model. At least 15% of women experienced recurrent falls between 0-6 and 6-12 months. At baseline and 6 months, 18.2% and 6.9% had a non-TCA/non-SSRI antidepressant, respectively. Adjusting for demographics, health status, and other drugs that increase risk of falls, non-TCA/non-SSRI antidepressant exposure significantly increased the risk of recurrent falls (AOR: 2.14; 95% CI: 1.01-4.54). Fall risk further increased after removing bupropion from the non-TCA/non-SSRI antidepressant group in sensitivity analyses (AOR: 2.73; 95% CI: 1.24-6.01). Other antidepressant classes may not be safer than TCAs/SSRIs with respect to recurrent falls in frail older women. Copyright © 2016 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.

Two Phase III randomised double-blind studies of fixed-dose TC-5214 (dexmecamylamine) adjunct to ongoing antidepressant therapy in patients with major depressive disorder and an inadequate response to prior antidepressant therapy.

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Möller, Hans-Jürgen; Demyttenaere, Koen; Olausson, Bengt; Szamosi, Johan; Wilson, Ellis; Hosford, David; Dunbar, Geoffrey; Tummala, Raj; Eriksson, Hans

2015-10-01

To evaluate the neuronal nicotinic channel modulator TC-5214 (dexmecamylamine) as adjunct therapy in patients with major depressive disorder (MDD) and inadequate response to prior antidepressant treatment. Study 004 (D4130C00004) and Study 005 (D4130C00005) comprised an 8-week open-label antidepressant (SSRI/SNRI) treatment period followed by an 8-week randomised, active treatment with twice-daily TC-5214 (0.5, 2 or 4 mg in Study 004; 0.1, 1 or 4 mg in Study 005) or placebo, adjunct to ongoing SSRI/SNRI. Primary efficacy endpoint was change in MADRS total score from randomisation (Week 8) to treatment end (Week 16). Secondary endpoints included MADRS response and remission, and changes in SDS and HAM-D-17-item scores. Safety and tolerability were monitored throughout. Studies 004 and 005 randomised 640 and 696 patients, respectively, to TC-5214 or placebo. No statistically significant improvements in MADRS total score or any secondary endpoints were seen with TC-5214 versus placebo in either study at treatment end. The most commonly reported adverse events (> 10%) with TC-5214 were constipation, dizziness and dry mouth. TC-5214 adjunct to antidepressant was generally well tolerated. However, the studies were not supportive of an antidepressant effect for TC-5214 in patients with MDD and inadequate response to prior antidepressant therapy.

Complement Mutations in Diacylglycerol Kinase-ε–Associated Atypical Hemolytic Uremic Syndrome

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Sánchez Chinchilla, Daniel; Pinto, Sheila; Hoppe, Bernd; Adragna, Marta; Lopez, Laura; Justa Roldan, Maria Luisa; Peña, Antonia; Lopez Trascasa, Margarita; Sánchez-Corral, Pilar; Rodríguez de Córdoba, Santiago

2014-01-01

Background and objectives Atypical hemolytic uremic syndrome is characterized by vascular endothelial damage caused by complement dysregulation. Consistently, complement inhibition therapies are highly effective in most patients with atypical hemolytic uremic syndrome. Recently, it was shown that a significant percentage of patients with early-onset atypical hemolytic uremic syndrome carry mutations in diacylglycerol kinase-ε, an intracellular protein with no obvious role in complement. These data support an alternative, complement-independent mechanism leading to thrombotic microangiopathy that has implications for treatment of early-onset atypical hemolytic uremic syndrome. To get additional insights into this new form of atypical hemolytic uremic syndrome, the diacylglycerol kinase-ε gene in a cohort with atypical hemolytic uremic syndrome was analyzed. Design, setting, participants, & measurements Eighty-three patients with early-onset atypical hemolytic uremic syndrome (<2 years) enrolled in the Spanish atypical hemolytic uremic syndrome registry between 1999 and 2013 were screened for mutations in diacylglycerol kinase-ε. These patients were also fully characterized for mutations in the genes encoding factor H, membrane cofactor protein, factor I, C3, factor B, and thrombomodulin CFHRs copy number variations and rearrangements, and antifactor H antibodies. Results Four patients carried mutations in diacylglycerol kinase-ε, one p.H536Qfs*16 homozygote and three compound heterozygotes (p.W322*/p.P498R, two patients; p.Q248H/p.G484Gfs*10, one patient). Three patients also carried heterozygous mutations in thrombomodulin or C3. Extensive plasma infusions controlled atypical hemolytic uremic syndrome recurrences and prevented renal failure in the two patients with diacylglycerol kinase-ε and thrombomodulin mutations. A positive response to plasma infusions and complement inhibition treatment was also observed in the patient with concurrent diacylglycerol

Complement mutations in diacylglycerol kinase-ε-associated atypical hemolytic uremic syndrome.

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Sánchez Chinchilla, Daniel; Pinto, Sheila; Hoppe, Bernd; Adragna, Marta; Lopez, Laura; Justa Roldan, Maria Luisa; Peña, Antonia; Lopez Trascasa, Margarita; Sánchez-Corral, Pilar; Rodríguez de Córdoba, Santiago

2014-09-05

Atypical hemolytic uremic syndrome is characterized by vascular endothelial damage caused by complement dysregulation. Consistently, complement inhibition therapies are highly effective in most patients with atypical hemolytic uremic syndrome. Recently, it was shown that a significant percentage of patients with early-onset atypical hemolytic uremic syndrome carry mutations in diacylglycerol kinase-ε, an intracellular protein with no obvious role in complement. These data support an alternative, complement-independent mechanism leading to thrombotic microangiopathy that has implications for treatment of early-onset atypical hemolytic uremic syndrome. To get additional insights into this new form of atypical hemolytic uremic syndrome, the diacylglycerol kinase-ε gene in a cohort with atypical hemolytic uremic syndrome was analyzed. Eighty-three patients with early-onset atypical hemolytic uremic syndrome (<2 years) enrolled in the Spanish atypical hemolytic uremic syndrome registry between 1999 and 2013 were screened for mutations in diacylglycerol kinase-ε. These patients were also fully characterized for mutations in the genes encoding factor H, membrane cofactor protein, factor I, C3, factor B, and thrombomodulin CFHRs copy number variations and rearrangements, and antifactor H antibodies. Four patients carried mutations in diacylglycerol kinase-ε, one p.H536Qfs*16 homozygote and three compound heterozygotes (p.W322*/p.P498R, two patients; p.Q248H/p.G484Gfs*10, one patient). Three patients also carried heterozygous mutations in thrombomodulin or C3. Extensive plasma infusions controlled atypical hemolytic uremic syndrome recurrences and prevented renal failure in the two patients with diacylglycerol kinase-ε and thrombomodulin mutations. A positive response to plasma infusions and complement inhibition treatment was also observed in the patient with concurrent diacylglycerol kinase-ε and C3 mutations. Data suggest that complement dysregulation influences

Use of Sedatives, Antidepressants and Antipsychotic Medicine among Seventh-day Adventists and Baptists in Denmark.

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Rasmussen, Peter; Johansen, Christoffer; Hvidt, Niels Christian; Kørup, Alex Kappel; Søndergaard, Jens; Thygesen, Lau Caspar

2017-10-01

Earlier it has been found that female Seventh-day Adventists (SDA) and Baptists have an increased incidence of psychiatric affective disorders, in contrast to findings that religious practice is associated with better health. In this study, we examined whether the increase in incidence is due to less use of prescribed antidepressants, sedatives and antipsychotics by members of these religious societies than by the general population. In a cohort study, we examined records of all drugs redeemed by 3121 SDA and 2888 Baptists and 29,817 age- and gender-matched members of the general population between 1995 and 2010 in the Danish Prescription Register and compared the prevalence and incidence of use of antidepressants, sedatives and antipsychotics. The prevalence of antidepressant use by women was lower in 1998 but no different from that in controls in 2003 and 2008; the prevalence of antidepressant use by men was higher in both 1998 and 2008 than in the Danish population. The incidence of antidepressant use was lower for female members in 1996-2000, but no difference was observed in the other periods. The prevalence and incidence of use of sedatives and antipsychotics did not consistently differ from those of the general population. The prevalence and incidence of use of antidepressants, sedatives and antipsychotics by female SDA and Baptists were not consistently lower than in the general Danish population. Our findings hence do not explain the increased incidence of psychiatric disorders among female members of these Danish religious societies.

Antidepressant stimulation of CDP-diacylglycerol synthesis does not require monoamine reuptake inhibition

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Aboukhatwa Marwa A

2010-01-01

Full Text Available Abstract Background Recent studies demonstrate that diverse antidepressant agents increase the cellular production of the nucleolipid CDP-diacylglycerol and its synthetic derivative, phosphatidylinositol, in depression-relevant brain regions. Pharmacological blockade of downstream phosphatidylinositide signaling disrupted the behavioral antidepressant effects in rats. However, the nucleolipid responses were resistant to inhibition by serotonin receptor antagonists, even though antidepressant-facilitated inositol phosphate accumulation was blocked. Could the neurochemical effects be additional to the known effects of the drugs on monoamine transmitter transporters? To examine this question, we tested selected agents in serotonin-depleted brain tissues, in PC12 cells devoid of serotonin transporters, and on the enzymatic activity of brain CDP-diacylglycerol synthase - the enzyme that catalyzes the physiological synthesis of CDP-diacylglycerol. Results Imipramine, paroxetine, and maprotiline concentration-dependently increased the levels of CDP-diacylglycerol and phosphatidylinositides in PC12 cells. Rat forebrain tissues depleted of serotonin by pretreatment with p-chlorophenylalanine showed responses to imipramine or maprotiline that were comparable to respective responses from saline-injected controls. With fluoxetine, nucleolipid responses in the serotonin-depleted cortex or hippocampus were significantly reduced, but not abolished. Each drug significantly increased the enzymatic activity of CDP-diacylglycerol synthase following incubations with cortical or hippocampal brain tissues. Conclusion Antidepressants probably induce the activity of CDP-diacylglycerol synthase leading to increased production of CDP-diacylglycerol and facilitation of downstream phosphatidylinositol synthesis. Phosphatidylinositol-dependent signaling cascades exert diverse salutary effects in neural cells, including facilitation of BDNF signaling and neurogenesis. Hence

Treatment of antidepressant-associated sexual dysfunction with sildenafil: a randomized controlled trial.

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Nurnberg, H George; Hensley, Paula L; Gelenberg, Alan J; Fava, Maurizio; Lauriello, John; Paine, Susan

2003-01-01

Sexual dysfunction is a common adverse effect of antidepressants that frequently results in treatment noncompliance. To assess the efficacy of sildenafil citrate in men with sexual dysfunction associated with the use of selective and nonselective serotonin reuptake inhibitor (SRI) antidepressants. Prospective, parallel-group, randomized, double-blind, placebo-controlled trial conducted between November 1, 2000, and January 1, 2001, at 3 US university medical centers among 90 male outpatients (mean [SD] age, 45 [8] years) with major depression in remission and sexual dysfunction associated with SRI antidepressant treatment. Patients were randomly assigned to take sildenafil (n = 45) or placebo (n = 45) at a flexible dose starting at 50 mg and adjustable to 100 mg before sexual activity for 6 weeks. The primary outcome measure was score on the Clinical Global Impression-Sexual Function (CGI-SF); secondary measures were scores on the International Index of Erectile Function, Arizona Sexual Experience Scale, Massachusetts General Hospital-Sexual Functioning Questionnaire, and Hamilton Rating Scale for Depression (HAM-D). Among the 90 randomized patients, 93% (83/89) of patients treated per protocol took at least 1 dose of study drug and 85% (76/89) completed week 6 end-point assessments with last observation carried forward analyses. At a CGI-SF score of 2 or lower, 54.5% (24/44) of sildenafil compared with 4.4% (2/45) of placebo patients were much or very much improved (Psatisfaction domain measures improved significantly in sildenafil compared with placebo patients. Mean depression scores remained consistent with remission (HAM-D score sexual function in men with sexual dysfunction associated with the use of SRI antidepressants. These improvements may allow patients to maintain adherence with effective antidepressant treatment.

Antidepressant-like effects of erythropoietin: a focus on behavioural and hippocampal processes.

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Osborn, Meagan; Rustom, Nazneen; Clarke, Melanie; Litteljohn, Darcy; Rudyk, Chris; Anisman, Hymie; Hayley, Shawn

2013-01-01

Depression is a chronic and debilitating condition with a significant degree of relapse and treatment resistance that could stem, at least in part, from disturbances of neuroplasticity. This has led to an increased focus on treatment strategies that target brain derived neurotrophic factor (BDNF), synaptic plasticity and adult neurogenesis. In the current study we aimed to assess whether erythropoietin (EPO) would have antidepressant-like effects given its already established pro-trophic actions. In particular, we assessed whether EPO would diminish the deleterious effects of a social stressor in mice. Indeed, EPO induced anxiolytic and antidepressant-like responses in a forced swim test, open field, elevated-plus maze, and a novelty test, and appeared to blunt some of the negative behavioural effects of a social stressor. Furthermore, EPO promoted adult hippocampal neurogenesis, an important feature of effective antidepressants. Finally, a separate study using the mTOR inhibitor rapamycin revealed that antagonizing this pathway prevented the impact of EPO upon forced swim performance. These data are consistent with previous findings showing that the mTOR pathway and its neurogenic and synaptogenic effects might mediate the behavioral consequences of antidepressant agents. Our findings further highlight EPO as a possible adjunct treatment for affective disorders, as well as other stressor associated disorders of impaired neuroplasticity.

Neural Plasticity and Proliferation in the Generation of Antidepressant Effects: Hippocampal Implication

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Fuencisla Pilar-Cuéllar

2013-01-01

Full Text Available It is widely accepted that changes underlying depression and antidepressant-like effects involve not only alterations in the levels of neurotransmitters as monoamines and their receptors in the brain, but also structural and functional changes far beyond. During the last two decades, emerging theories are providing new explanations about the neurobiology of depression and the mechanism of action of antidepressant strategies based on cellular changes at the CNS level. The neurotrophic/plasticity hypothesis of depression, proposed more than a decade ago, is now supported by multiple basic and clinical studies focused on the role of intracellular-signalling cascades that govern neural proliferation and plasticity. Herein, we review the state-of-the-art of the changes in these signalling pathways which appear to underlie both depressive disorders and antidepressant actions. We will especially focus on the hippocampal cellularity and plasticity modulation by serotonin, trophic factors as brain-derived neurotrophic factor (BDNF, and vascular endothelial growth factor (VEGF through intracellular signalling pathways—cAMP, Wnt/β-catenin, and mTOR. Connecting the classic monoaminergic hypothesis with proliferation/neuroplasticity-related evidence is an appealing and comprehensive attempt for improving our knowledge about the neurobiological events leading to depression and associated to antidepressant therapies.

Evidence for Broadening Criteria for Atypical Depression Which May Define a Reactive Depressive Disorder.

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Silverstein, Brett; Angst, Jules

2015-01-01

Objective. Arguing that additional symptoms should be added to the criteria for atypical depression. Method. Published research articles on atypical depression are reviewed. Results. (1) The original studies upon which the criteria for atypical depression were based cited fatigue, insomnia, pain, and loss of weight as characteristic symptoms. (2) Several studies of DSM depressive criteria found patients with atypical depression to exhibit high levels of insomnia, fatigue, and loss of appetite/weight. (3) Several studies have found atypical depression to be comorbid with headaches, bulimia, and body image issues. (4) Most probands who report atypical depression meet criteria for "somatic depression," defined as depression associated with several of disordered eating, poor body image, headaches, fatigue, and insomnia. The gender difference in prevalence of atypical depression results from its overlap with somatic depression. Somatic depression is associated with psychosocial measures related to gender, linking it with the descriptions of atypical depression as "reactive" appearing in the studies upon which the original criteria for atypical depression were based. Conclusion. Insomnia, disordered eating, poor body image, and aches/pains should be added as criteria for atypical depression matching criteria for somatic depression defining a reactive depressive disorder possibly distinct from endogenous melancholic depression.

Evidence for Broadening Criteria for Atypical Depression Which May Define a Reactive Depressive Disorder

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Brett Silverstein

2015-01-01

Full Text Available Objective. Arguing that additional symptoms should be added to the criteria for atypical depression. Method. Published research articles on atypical depression are reviewed. Results. (1 The original studies upon which the criteria for atypical depression were based cited fatigue, insomnia, pain, and loss of weight as characteristic symptoms. (2 Several studies of DSM depressive criteria found patients with atypical depression to exhibit high levels of insomnia, fatigue, and loss of appetite/weight. (3 Several studies have found atypical depression to be comorbid with headaches, bulimia, and body image issues. (4 Most probands who report atypical depression meet criteria for “somatic depression,” defined as depression associated with several of disordered eating, poor body image, headaches, fatigue, and insomnia. The gender difference in prevalence of atypical depression results from its overlap with somatic depression. Somatic depression is associated with psychosocial measures related to gender, linking it with the descriptions of atypical depression as “reactive” appearing in the studies upon which the original criteria for atypical depression were based. Conclusion. Insomnia, disordered eating, poor body image, and aches/pains should be added as criteria for atypical depression matching criteria for somatic depression defining a reactive depressive disorder possibly distinct from endogenous melancholic depression.

Effort-reward imbalance at work and the risk of antidepressant treatment in the Danish workforce

DEFF Research Database (Denmark)

Nielsen, Maj Britt D.; Madsen, Ida E. H.; Aust, Birgit

2016-01-01

Background: Previous studies have shown that high effort-reward imbalance (ERI) at work is a risk factor for the onset of self-reported depressive symptoms. In this study, we examined whether ERI predicts risk of treatment with antidepressant medication in a representative sample of the Danish...... workforce. Methods: We linked survey data on ERI and covariates of 4541 participants from the Danish Work Environment Cohort Study 2000 with the Danish National Prescription Registry that includes all legally purchased prescription drugs at pharmacies in Denmark since 1995. Participants with a history....... Results: A total of 309 (6.8%) participants started antidepressant treatment during follow-up. Exposure to ERI at baseline was not related to risk of antidepressant treatment (hazard ratio: 0.91, 95% CI=0.81–1.03 after adjustment for potential confounders). Limitations: The use of antidepressant treatment...

Delayed Recurrence of Atypical Pulmonary Carcinoid Cluster: A Rare Occurrence

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Salim Surani

2014-01-01

Full Text Available Carcinoid is one of the most common tumors of the gastrointestinal tract followed by the tracheobronchial tree. Bronchial carcinoid compromises 20% of total carcinoid and accounts for 1–5% of pulmonary malignancies. Carcinoid can be typical or atypical, with atypical carcinoid compromises 10% of the carcinoid tumors. Carcinoid usually presents as peripheral lung lesion or solitary endobronchial abnormality. Rarely it can present as multiple endobronchial lesion. We hereby present a rare case of an elderly gentleman who had undergone resection of right middle and lower lobe of lung for atypical carcinoid. Seven years later he presented with cough. CT scan of chest revealed right hilar mass. Flexible bronchoscopy revealed numerous endobronchial polypoid lesions in the tracheobronchial tree. Recurrent atypical carcinoid was then confirmed on biopsy.

[Indications for antidepressive agents in relation to diseases of the cardiovascular system].

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Tikal, K; Hrabánková, M

1993-06-01

Antidepressants, in particular tricyclic ones (TCA), and inhibitors of monoaminooxidase (IMAO) exert a number of undesirable cardiovascular effects. TCA and IMAO frequently cause postural hypotension (PH). IMAO administration is associated with the risk of hypertensive crisis. TCA raises the heart rate and can cause abnormalities in the conduction of the cardiac excitation. TCA are contraindicated after myocardial infarction and are the cause of death after overdosage. When PH is undesirable, in hypertension and cardiac insufficiency the following safe antidepressants are recommended: nortriptyline, mianserine, trazodone and viloxazine. In abnormalities of conduction of the cardiac excitation and after myocardial infarction only mianserine, trazodione and viloxazine are recommended. With regard to cardiovascular toxicity, antidepressants from the series of selective inhibitors of serotonin reabsorption are very promising: fluvoxamine, fluoxetine, citalopram, paroxetine and sertraline. The same applies also to the reversible IMAO type A moclobemide.

Attitudes and beliefs of patients with chronic depression toward antidepressants and depression.

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Jacob, Sabrina Anne; Ab Rahman, Ab Fatah; Hassali, Mohamed Azmi Ahmad

2015-01-01

Many patients have erroneous views with regard to depression and its management, and it was noted that these attitudes and beliefs significantly affected their adherence rates. The primary aim of this study was to determine the attitudes and beliefs of patients with depression toward depression and antidepressants. A secondary aim was to assess the influence of ethnicity on patients' attitudes and beliefs. The study involved patients with chronic depression being followed up at an outpatient clinic at a government-run hospital in Malaysia. Patients' attitudes and beliefs were assessed using the Antidepressant Compliance Questionnaire. A total of 104 patients of Malay, Chinese, and Indian ethnic groups met the selection criteria. Chinese patients had significantly negative attitudes and beliefs toward depression and antidepressants compared to Malays and Indians (b=-8.96, t 103=-3.22; Pcultures, can be used in tailoring psychoeducation sessions accordingly.

Permanent relief from intermittent cold stress-induced fibromyalgia-like abnormal pain by repeated intrathecal administration of antidepressants

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Mukae Takehiro

2011-09-01

Full Text Available Abstract Background Fibromyalgia (FM is characterized by chronic widespread pain, which is often refractory to conventional painkillers. Numerous clinical studies have demonstrated that antidepressants are effective in treating FM pain. We previously established a mouse model of FM-like pain, induced by intermittent cold stress (ICS. Results In this study, we find that ICS exposure causes a transient increase in plasma corticosterone concentration, but not in anxiety or depression-like behaviors. A single intrathecal injection of an antidepressant, such as milnacipran, amitriptyline, mianserin or paroxetine, had an acute analgesic effect on ICS-induced thermal hyperalgesia at post-stress day 1 in a dose-dependent manner. In addition, repeated daily antidepressant treatments during post-stress days 1-5 gradually reversed the reduction in thermal pain threshold, and this recovery was maintained for at least 7 days after the final treatment. In addition, relief from mechanical allodynia, induced by ICS exposure, was also observed at day 9 after the cessation of antidepressant treatment. In contrast, the intravenous administration of these antidepressants at conventional doses failed to provide relief. Conclusions These results suggest that the repetitive intrathecal administration of antidepressants permanently cures ICS-induced FM pain in mice.

Extracutaneous atypical syphilis in HIV-infected patients.

Science.gov (United States)

Prieto, Paula; Imaz, Arkaitz; Calatayud, Laura; García, Olga; Saumoy, María; Podzamczer, Daniel

2017-12-07

We describe a series of cases of syphilis with atypical extracutaneous clinical presentation diagnosed in HIV-infected patients. Retrospective observational study. All cases of syphilis diagnosed in HIV-infected patients during the period between June 2013 and June 2016 in a tertiary hospital of the Barcelona metropolitan area were analysed. A total of 71 cases of syphilis were diagnosed, 32 of them presenting with clinical signs or symptoms. Seven of these cases (9.8% of the total and 21.8% of the symptomatic cases) had atypical presentations with extracutaneous involvement: ocular (4), gastric (1), multiple hepatic abscesses (1) and generalised adenopathies (1). Patients were treated with intramuscular or intravenous penicillin and the clinical and serological evolution was good in all of them. Extracutaneous atypical clinical presentations were observed in 21.8% of symptomatic cases of syphilis in HIV+ patients with ocular involvement being the most freqent. Copyright © 2017 Elsevier España, S.L.U. All rights reserved.

Globalization and deregulation: does flexicuritiy protect atypically employed?

OpenAIRE

Seifert, Hartmut; Tangian, Andranik S.

2006-01-01

"Hitherto, discussion of flexicurity has focused on normal employment (permanent full-time), with atypical work receiving only cursory attention. Nevertheless, the most affected are just atypically employed (= other than normally employed). To monitor effects of flexicurity policies in Europe, flexicurity indices are constructed from: (a) scores of the strictness of employment protection legislation provided by the OECD, (b) qualitative juridical data on social security benefits (unemployment...

The Efficacy of Acute Electroconvulsive Therapy in Atypical Depression

Science.gov (United States)

Husain, Mustafa M.; McClintock, Shawn M.; Rush, A. John; Knapp, Rebecca G.; Fink, Max; Rummans, Teresa A.; Rasmussen, Keith; Claassen, Cynthia; Petrides, Georgios; Biggs, Melanie M.; Mueller, Martina; Sampson, Shirlene; Bailine, Samuel H.; Lisanby, Sarah H.; Kellner, Charles H.

2013-01-01

Objective This study examined the characteristics and outcomes of patients with major depressive disorder (MDD), with or without atypical features, who were treated with acute bilateral electroconvulsive therapy (ECT). Method Analyses were conducted with 489 patients who met DSM-IV criteria for MDD. Subjects were identified as typical or atypical on the basis of the Structured Clinical Interview for DSM-IV obtained at baseline prior to ECT. Depression symptom severity was measured by the 24-item Hamilton Rating Scale for Depression (HAM-D24) and the 30-item Inventory of Depressive Symptomatology–Self-Report (IDS-SR30). Remission was defined as at least a 60% decrease from baseline in HAM-D24 score and a total score of 10 or below on the last 2 consecutive HAM-D24 ratings. The randomized controlled trial was performed from 1997 to 2004. Results The typical (N = 453) and atypical (N = 36) groups differed in several sociodemographic and clinical variables including gender (p = .0071), age (p = .0005), treatment resistance (p = .0014), and age at first illness onset (p < .0001) and onset of current episode (p = .0008). Following an acute course of bilateral ECT, a considerable portion of both the typical (67.1%) and the atypical (80.6%) groups reached remission. The atypical group was 2.6 (95% CI = 1.1 to 6.2) times more likely to remit than the typical group after adjustment for age, psychosis, gender, clinical site, and depression severity based on the HAM-D24. Conclusion Acute ECT is an efficacious treatment for depressed patients with typical or atypical symptom features. PMID:18278988

A review on antidepressant effect of medicinal plants

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Zahra Rabiei

2017-03-01

Full Text Available Depression is a life-threatening, debilitating, and common disease affecting different segments of community. Chemical and synthetic drugs available to treat this disease cause many adverse effects and may lead to complete recovery in only 50% of patients. At the same time, medicinal plants have been reported to exert optimal pharmacological effects in treating depression in different models. In this review, the relevant articles indexed in the reliable databases PubMed, PubMed central, Scopus and Web of Science were review-ed. The review indicated that most medicinal plants exerted antidepressant effects through synaptic regulation of serotonin, noradrenaline, and dopamine, regulating activity of hypothalamic-pituitary-adrenal axis, reinfor-cing anti-oxidant defense system, and decreasing inflammatory mediators. The medicinal plants and their active compounds can relieve depression through different pathways and hence are considered a new source to produce antidepressants.

Cardiotoxicity of tricyclic antidepressant treated by 2650 mEq sodium bicarbonate: A case report

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Hassan Amiri

2016-12-01

Full Text Available Poisoning with tricyclic antidepressants is an important cause of drug-related self-poisoning in the developed world and a very common cause of poisoning and mortality in developing countries. Electrocardiographic manifestations of most tricyclic antidepressant-poisoned patients resolve by the administration of 1–2 mEq/kg of sodium bicarbonate. Some rare cases have been reported who have been resistant to the long-term or high doses of bicarbonate administration. We present a case of acute tricyclic antidepressant toxicity referring with status epilepticus, hypotension, and refractory QRS complex widening that resolved after the intravenous administration of 2650 mEq sodium bicarbonate.

Atypical real estate objects: legal regime and control system

Directory of Open Access Journals (Sweden)

Voskresenskaya Elena

2017-01-01

Full Text Available The legal concept of immovable things raises controversy in legal practice. Determining and understanding the definition of real estate, the complexity and diversity of these objects, a growing appearance of so-called atypical properties (such as sport stadiums, roads, boreholes, analyzing legislation and judicial practice of this field – all these issues call for a deep study of this topic. There is a conflicting arbitration practice, the subject of which is the learning of the legal nature of atypical real estate (for instance, asphalt playgrounds, car parks, fences, wells. The object of the research is the learning of the legal status of atypical real estate.

Antidepressant Sales and the Risk for Alcohol-Related and Non-Alcohol-Related Suicide in Finland—An Individual-Level Population Study

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Moustgaard, Heta; Joutsenniemi, Kaisla; Myrskylä, Mikko; Martikainen, Pekka

2014-01-01

Objectives A marked decline in suicide rates has co-occurred with increased antidepressant sales in several countries but the causal connection between the trends remains debated. Most previous studies have focused on overall suicide rates and neglected differential effects in population subgroups. Our objective was to investigate whether increasing sales of non-tricyclic antidepressants have reduced alcohol- and non-alcohol-related suicide risk in different population subgroups. Methods We followed a nationally representative sample of 950,158 Finnish adults in 1995–2007 for alcohol-related (n = 2,859) and non-alcohol-related (n = 8,632) suicides. We assessed suicide risk by gender and social group according to regional sales of non-tricyclic antidepressants, measured by sold doses per capita, prevalence of antidepressant users, and proportion of antidepressant users with doses reflecting minimally adequate treatment. Fixed-effects Poisson regression models controlled for regional differences and time trends that may influence suicide risk irrespective of antidepressant sales. Results The number of sold antidepressant doses per capita and the prevalence of antidepressant users were unrelated to male suicide risk. However, one percentage point increase in the proportion of antidepressant users receiving minimally adequate treatment reduced non-alcohol-related male suicide risk by one percent (relative risk 0.987, 95% confidence interval 0.976–0.998). This beneficial effect only emerged among men with high education, high income, and employment, among men without a partner, and men not owning their home. Alcohol-related suicides and female suicides were unrelated to all measures of antidepressant sales. Conclusion We found little evidence that increase in overall sales or in the prevalence of non-tricyclic antidepressant users would have caused the fall in suicide rates in Finland in 1995–2007. However, the rise in the proportion of antidepressant

Atypical visual loss in giant cell arteritis

DEFF Research Database (Denmark)

Thystrup, Jan Deichmann; Knudsen, G M; Mogensen, A M

1994-01-01

Three patients with atypical ocular involvement due to histologically verified giant cell arteritis are reported. Prior to diagnosis, the first patient had periods of amaurosis fugax. He presented with normal vision. In spite of high-dose systemic corticosteroid therapy, he became blind in the te......Three patients with atypical ocular involvement due to histologically verified giant cell arteritis are reported. Prior to diagnosis, the first patient had periods of amaurosis fugax. He presented with normal vision. In spite of high-dose systemic corticosteroid therapy, he became blind...

Antidepressant Drug Treatment in Association with Multiple Sclerosis Disease-Modifying Therapy: Using Explorys in the MS Population.

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Mirsky, Matthew M; Marrie, Ruth Ann; Rae-Grant, Alexander

2016-01-01

Background: The Explorys Enterprise Performance Management (EPM) database contains de-identified clinical data for 50 million patients. Multiple sclerosis (MS) disease-modifying therapies (DMTs), specifically interferon beta (IFNβ) treatments, may potentiate depression. Conflicting data have emerged, and a large-scale claims-based study by Patten et al. did not support such an association. This study compares the results of Patten et al. with those using the EPM database. Methods: "Power searches" were built to test the relationship between antidepressant drug use and DMT in the MS population. Searches were built to produce a cohort of individuals diagnosed as having MS in the past 3 years taking a specific DMT who were then given any antidepressant drug. The antidepressant drug therapy prevalence was tested in the MS population on the following DMTs: IFNβ-1a, IFNβ-1b, combined IFNβ, glatiramer acetate, natalizumab, fingolimod, and dimethyl fumarate. Results: In patients with MS, the rate of antidepressant drug use in those receiving DMTs was 40.60% to 44.57%. The rate of antidepressant drug use for combined IFNβ DMTs was 41.61% (males: 31.25%-39.62%; females: 43.10%-47.33%). Antidepressant drug use peaked in the group aged 45 to 54 years for five of six DMTs. Conclusions: We found no association between IFNβ treatment and antidepressant drug use in the MS population compared with other DMTs. The EPM database has been validated against the Patten et al. data for future use in the MS population.

[Prevalence of Avoidable Potential Interactions Between Antidepressants and Other Drugs in Colombian Patients].

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Machado-Alba, Jorge E; Morales-Plaza, Cristhian David

2013-06-01

To determine the possible drugs interactions with antidepressive agents in data bases of patients in the Health Insurance System of Colombia. From data bases of about 4 million users in Colombia, a systematic review of drugs dispensation statistics was made to identify drug interactions between antidepressive agents, cholinergic antagonists and tramadol in 2010. We identified 114,465 monthly users of antidepressive agents. Of these, 5776 (5.0%) received two, and 178 (0.2%) received three antidepressive agents simultaneously. The most frequent combination was fluoxetine+trazodone (n=3235; 56.9% of cases). About 1127 (1.0%) patients were prescribed a cholinergic antagonist simultaneously; 2523 (2.1%) users were dispensed tramadol at the same time, while raising the risk of serotonin syndrome. Drug interactions represent a potential risk that is often underestimated by physicians. Pharmacovigilance is a useful tool to optimize resources and prevent negative outcomes associated with medication. It is recommended that systematic search is made to enhance surveillance programs for the rational use of medicines in this country. Copyright © 2013 Asociación Colombiana de Psiquiatría. Publicado por Elsevier España. All rights reserved.

Atypical sonographic patterns of fibroadenoma of the breast : pathologic correlation

Energy Technology Data Exchange (ETDEWEB)

Kook, Shin Ho; Kim, Myung Sook; Pae, Won Kil [Kangbuk Samsung Hospital, Sungkyunkwan Univ. College of Medicine, Seoul (Korea, Republic of)

1999-03-01

To correlate the atypical sonographic patterns of fibroadenoma of the breast with the pathologic findings. Among 203 surgically proven 43 which were sonographically atypical fibroadenomas, were retrospectively reviewed. The diagnostic criteria for atypical variety, as seen on sonography, were an ill-defined margin, microlobulated or irregular shape, heterogeneous internal echo-pattern, posterior shadowing, microcalcification, and clefts. The atypical sonographic patterns of these 43 fibroadenomas were analysed and compared with the pathologic findings. Among 43 lesions, ill-defined margins or irregular shapes were seen in 15 cases, heterogeneous internal echo-patterns in 27, posterior attenuation in nine, and clefts in seven. Thirty-seven (86%) of the 43 were predominantly ductal or had a mixed ductal and stromal component. Eleven (73.3%) of fifteen ill-defined margin or irregular shaped lesions were caused by interdigitation of surrounding normal breast parenchyma and mass. Twenty two (81.5%) of 27 heterogeneous internal echo-pat-terns were related to dilated ducts, phyllodes features, collagen bundles, adenosis, microcalcification, or fat vacuoles. Eight (88.9%) of nine posterior attenuations were caused by collagen bundles, microcalcification, ductal proliferation or dilatation. All seven cases showing clefts revealed phyllodes features and dilated ducts. Most atypical fibroadenomas had a predominantly ductal or mixed component. Ill-defined margin or irregular shape was mainly due to interdigitation of normal surrounding parenchyma. Variable histologic features were related to the heterogeneous internal echo-pattern, posterior shadowing, and the clefts revealed by atypical sonographic findings.

Atypical sonographic patterns of fibroadenoma of the breast : pathologic correlation

International Nuclear Information System (INIS)

Kook, Shin Ho; Kim, Myung Sook; Pae, Won Kil

1999-01-01

To correlate the atypical sonographic patterns of fibroadenoma of the breast with the pathologic findings. Among 203 surgically proven 43 which were sonographically atypical fibroadenomas, were retrospectively reviewed. The diagnostic criteria for atypical variety, as seen on sonography, were an ill-defined margin, microlobulated or irregular shape, heterogeneous internal echo-pattern, posterior shadowing, microcalcification, and clefts. The atypical sonographic patterns of these 43 fibroadenomas were analysed and compared with the pathologic findings. Among 43 lesions, ill-defined margins or irregular shapes were seen in 15 cases, heterogeneous internal echo-patterns in 27, posterior attenuation in nine, and clefts in seven. Thirty-seven (86%) of the 43 were predominantly ductal or had a mixed ductal and stromal component. Eleven (73.3%) of fifteen ill-defined margin or irregular shaped lesions were caused by interdigitation of surrounding normal breast parenchyma and mass. Twenty two (81.5%) of 27 heterogeneous internal echo-pat-terns were related to dilated ducts, phyllodes features, collagen bundles, adenosis, microcalcification, or fat vacuoles. Eight (88.9%) of nine posterior attenuations were caused by collagen bundles, microcalcification, ductal proliferation or dilatation. All seven cases showing clefts revealed phyllodes features and dilated ducts. Most atypical fibroadenomas had a predominantly ductal or mixed component. Ill-defined margin or irregular shape was mainly due to interdigitation of normal surrounding parenchyma. Variable histologic features were related to the heterogeneous internal echo-pattern, posterior shadowing, and the clefts revealed by atypical sonographic findings

Prognostic significance of atypical papillary urothelial hyperplasia.

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Swierczynski, Sharon L; Epstein, Jonathan I

2002-05-01

Typical papillary hyperplasia, a recently recognized precursor lesion to low-grade papillary urothelial neoplasms, consists of undulating folds of cytologically benign urothelium. Well-developed, branching fibrovascular cores of a papillary neoplasm are not evident. We have noted lesions with the architectural pattern of papillary hyperplasia; however, the overlying urothelium demonstrated varying degrees of cytologic atypia. We identified 15 cases of atypical papillary hyperplasia (13 males, 2 females, age 55 to 92) with overlying urothelium showing cytologic atypia. Of these cases, 8 (53%) were received in consultation. Of the 15 cases, 8 exhibited overlying flat carcinoma in situ (CIS), 4 had overlying dysplasia, and 3 were transitional between papillary hyperplasia with atypia and the earliest lesions of papillary neoplasia. Of these cases, 5 patients had multiple specimens with atypical papillary hyperplasia (range, 2 to 8) over time. Concurrent to the diagnosis of atypical papillary hyperplasia, there were 25 different urothelial lesions: CIS (n = 11), papilloma (n = 1), papillary neoplasm of low malignant potential with CIS (n = 1), high-grade papillary urothelial carcinoma (n = 10; 3 with CIS), small-cell carcinoma (n = 1), and infiltrating urothelial carcinoma (n = 1). Of 11 patients with known prior history, 2 had 12 prior urothelial neoplasms (9 low-grade papillary neoplasms, 2 papillary urothelial neoplasms of low malignant potential, and 1 high-grade papillary cancer). Of 10 patients with atypical papillary hyperplasia and a minimum of 1 year of follow-up, 9 had 19 recurrences: CIS (n = 4), papilloma (n = 1), papillary neoplasm of low malignant potential (n = 1), infiltrating urothelial carcinoma (n = 3; 1 with CIS), and high-grade papillary urothelial carcinoma (n = 10; 5 with invasion and 2 with CIS). Whether the papillary hyperplasia had overlying CIS or dysplasia did not affect the correlation with urothelial neoplasms. Immunohistochemical analysis

Generic penetration in the retail atypical antipsychotic market.

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Lenderts, Susan; Kalali, Amir H; Buckley, Peter

2010-03-01

In this article, we explore the penetration of generic atypical antipsychotics in the United States market before and after the availability of generic risperidone in July 2008. Analysis suggests that, overall, generic penetration into the atypical antipsychotic market has grown from approximately three percent in January 2008 to more than 25 percent in December 2009. Similar trends are uncovered when branded and generic prescriptions are analyzed by specialty.

Atypical Odontalgia (Phantom Tooth Pain)

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... atypical facial pain, phantom tooth pain, or neuropathic orofacial pain, is characterized by chronic pain in a tooth ... such as a specialist in oral medicine or orofacial pain. The information contained in this monograph is for ...

Cohort study of atypical pressure ulcers development.

Science.gov (United States)

Jaul, Efraim

2014-12-01

Atypical pressure ulcers (APU) are distinguished from common pressure ulcers (PU) with both unusual location and different aetiology. The occurrence and attempts to characterise APU remain unrecognised. The purpose of this cohort study was to analyse the occurrence of atypical location and the circumstances of the causation, and draw attention to the prevention and treatment by a multidisciplinary team. The cohort study spanned three and a half years totalling 174 patients. The unit incorporates two weekly combined staff meetings. One concentrates on wound assessment with treatment decisions made by the physician and nurse, and the other, a multidisciplinary team reviewing all patients and coordinating treatment. The main finding of this study identified APU occurrence rate of 21% within acquired PU over a three and a half year period. Severe spasticity constituted the largest group in this study and the most difficult to cure wounds, located in medial aspects of knees, elbows and palms. Medical devices caused the second largest occurrence of atypical wounds, located in the nape of the neck, penis and nostrils. Bony deformities were the third recognisable atypical wound group located in shoulder blades and upper spine. These three categories are definable and time observable. APU are important to be recognisable, and can be healed as well as being prevented. The prominent role of the multidisciplinary team is primary in identification, prevention and treatment. © 2013 The Authors. International Wound Journal © 2013 Medicalhelplines.com Inc and John Wiley & Sons Ltd.

Physiological Bases of Bulimia, and Antidepressant Treatment.

Science.gov (United States)

Getzfeld, Andrew R.

This paper reviews the literature on the physiological causes of bulimia and investigates the rationale behind the usage of antidepressant medication in the treatment of bulimia nervosa. No definite conclusions can be stated regarding the physiology of bulimia, but a number of hypotheses are suggested. It appears that the hypothalamus is involved…

Cyclic AMP-specific phosphodiesterase-4 as a target for the development of antidepressant drugs.

Science.gov (United States)

Zhang, Han-Ting

2009-01-01

Phosphodiesterase-4 (PDE4), one of eleven PDE enzyme families, specifically catalyzes hydrolysis of cyclic AMP (cAMP); it has four subtypes (PDE4A-D) with at least 25 splice variants. PDE4 plays a critical role in the control of intracellular cAMP concentrations. PDE4 inhibitors produce antidepressant actions in both animals and humans via enhancement of cAMP signaling in the brain. However, their clinical utility has been hampered by side effects, in particular nausea and emesis. While there is still a long way to go before PDE4 inhibitors with high therapeutic indices are available for treatment of depressive disorders, important advances have been made in the development of PDE4 inhibitors as antidepressants. First, limited, but significant studies point to PDE4D as the major PDE4 subtype responsible for antidepressant-like effects of PDE4 inhibitors, although the role of PDE4A cannot be excluded. Second, PDE4D may contribute to emesis, the major side effect of PDE4 inhibitors. For this reason, identification of roles of PDE4D splice variants in mediating antidepressant activity is particularly important. Recent studies using small interfering RNAs (siRNAs) have demonstrated the feasibility to identify cellular functions of individual PDE4 variants. Third, mixed inhibitors of PDE4 and PDE7 or PDE4 and serotonin reuptake have been developed and may be potential antidepressants with minimized side effects. Finally, relatively selective inhibitors of one or two PDE4 subtypes have been synthesized using structure- and scaffold-based design. This review also discusses the relationship between PDE4 and antidepressant activity based on structures, brain distributions, and pharmacological properties of PDE4 and its isoforms.

EXERCISE IMPROVES SEXUAL FUNCTION IN WOMEN TAKING ANTIDEPRESSANTS: RESULTS FROM A RANDOMIZED CROSSOVER TRIAL

Science.gov (United States)

Lorenz, Tierney Ahrold; Meston, Cindy May

2014-01-01

Background In laboratory studies, exercise immediately before sexual stimuli improved sexual arousal of women taking antidepressants [1]. We evaluated if exercise improves sexual desire, orgasm, and global sexual functioning in women experiencing antidepressant-induced sexual side effects. Methods Fifty-two women who were reporting antidepressant sexual side effects were followed for 3 weeks of sexual activity only. They were randomized to complete either three weeks of exercise immediately before sexual activity (3×/week) or 3 weeks of exercise separate from sexual activity (3×/week). At the end of the first exercise arm, participants crossed to the other. We measured sexual functioning, sexual satisfaction, depression, and physical health. Results Exercise immediately prior to sexual activity significantly improved sexual desire and, for women with sexual dysfunction at baseline, global sexual function. Scheduling regular sexual activity significantly improved orgasm function; exercise did not increase this benefit. Neither regular sexual activity nor exercise significantly changed sexual satisfaction. Conclusions Scheduling regular sexual activity and exercise may be an effective tool for the behavioral management of sexual side effects of antidepressants. PMID:24754044

Adult hippocampal neurogenesis: an important target associated with antidepressant effects of exercise.

Science.gov (United States)

Sun, Lina; Sun, Qingshan; Qi, Jinshun

2017-10-26

Depression is a prevalent devastating mental disorder that affects the normal life of patients and brings a heavy burden to whole society. Although many efforts have been made to attenuate depressive/anxiety symptoms, the current clinic antidepressants have limited effects. Scientists have long been making attempts to find some new strategies that can be applied as the alternative antidepressant therapy. Exercise, a widely recognized healthy lifestyle, has been suggested as a therapy that can relieve psychiatric stress. However, how exercise improves the brain functions and reaches the antidepressant target needs systematic summarization due to the complexity and heterogeneous feature of depression. Brain plasticity, especially adult neurogenesis in the hippocampus, is an important neurophysiology to facilitate animals for neurogenesis can occur in not only humans. Many studies indicated that an appropriate level of exercise can promote neurogenesis in the adult brains. In this article, we provide information about the antidepressant effects of exercise and its implications in adult neurogenesis. From the neurogenesis perspective, we summarize evidence about the effects of exercise in enhancing neurogenesis in the hippocampus through regulating growth factors, neurotrophins, neurotransmitters and metabolism as well as inflammations. Taken together, a large number of published works indicate the multiple benefits of exercise in the brain functions of animals, particularly brain plasticity like neurogenesis and synaptogenesis. Therefore, a new treatment method for depression therapy can be developed by regulating the exercise activity.

Radioactive cDNA microarrys for gene expression profiles in antidepressant therapy

International Nuclear Information System (INIS)

Lee, M. S.; Han, B. J.; Cha, J. H.; Ryu, Y. M.; Shin, E. K.; Park, J. H.; Park, Y. H.; Kim, M. K.

2002-01-01

Using radioactive cDNA microarray, we investigated a pattern of gene regulation under treatment of antidepressant on patients of depressive disoder. Basic microarray technology was performed as previously described in our research. The bioinformatic selection of human cDNAs, which is specifically designed for psychiatry, neurology, and signal transduction, were arrayed on nylon membranes. Using with 33P-labeled probes, this method provided highly sensitive gene expression profiles of our interest including brain receptors, drug metabolism, and cellular signalings. Gene expression profiles were also classified into several categories in accordance with the gene-regulation of antidepressant. The gene profiles of our interest were significantly up- (16 genes, >2.0 of Z-ratio) or down- (24 genes, <-2.0 of Z ratio) regulated when compared the good responsed group with the bad-responsed one. Consequently, we demonstrated that radioactive human cDNA microarray is highly likely to be an efficient technology for evaluating the gene regulation of antidepressants, such as selective serotonin-reuptake inhibitors (SSRIs), by using high-throughput biotechnology

Atypical Focal Osteomyelitis as Initial Manifestation of AIDS

OpenAIRE

A. Akiki; Y. Bilde

2011-01-01

Persistent pain development after a skeletal contusion rarely poses the diagnosis of osteomyelitis. We report the case of a fibular head contusion as an initial manifestation of a focal abscess development in a healthy young patient. The traditional treatment of surgical drainage revealed the presence of an atypical Mycobacterium haemophilum isolates in the abscess. This lead to further investigations that concluded and established the diagnosis of AIDS. Conclusion. Isolation of an atypical M...

Epigenetic Mechanisms of Depression and Antidepressants Action

Science.gov (United States)

Vialou, Vincent; Feng, Jian; Robison, Alfred J.; Nestler, Eric J.

2013-01-01

Epigenetic mechanisms, which control chromatin structure and function, mediate changes in gene expression that occur in response to diverse stimuli. Recent research has established that environmental events and behavioral experience induce epigenetic changes at particular gene loci that help shape neuronal plasticity and function, and hence behavior, and that some of these changes can be very stable and even persist for a lifetime. Increasing evidence supports the hypothesis that aberrations in chromatin remodeling and subsequent effects on gene expression within limbic brain regions contribute to the pathogenesis of depression and other stress-related disorders such as post-traumatic stress disorder and other anxiety syndromes. Likewise, the gradually developing but persistent therapeutic effects of antidepressant medications may be achieved in part via epigenetic mechanisms. This review discusses recent advances in understanding epigenetic regulation of stress-related disorders and focuses on three distinct aspects of stress-induced epigenetic pathology: the effects of stress and antidepressant treatment during adulthood, the life-long effects of early life stress on subsequent stress vulnerability, and the possible trans-generational transmission of stress-induced abnormalities. PMID:23020296

Efficacy and Safety of Antidepressants for the Treatment of Irritable Bowel Syndrome: A Meta-Analysis

Science.gov (United States)

Wang, Yunfeng; Yu, Ting; Wang, Yun; Jiang, Liuqin; Lin, Lin

2015-01-01

Aim The aim of this meta-analysis was to analyze the efficacy and safety of antidepressants for the treatment of irritable bowel syndrome. Methods We searched MEDLINE, EMBASE, Scopus and The Cochrane Library for randomized controlled trials investigating the efficacy and safety of antidepressants in the treatment of irritable bowel syndrome. Article quality was evaluated by Jadad score. RevMan 5.0 and Stata 12.0 were used for the meta-analysis. Results Twelve randomized controlled trials were included in this study and most of these trials were of high quality (Jadad score ≥4). Five articles focused on tricyclic antidepressants, six articles involved selective serotonin reuptake inhibitors, and one article investigated both types of treatment. The pooled risk ratio showed antidepressant treatment can improve global symptoms (RR = 1.38, 95% CI 1.08, 1.77). In the subgroup analysis, treatment with tricyclic antidepressants showed an improvement in global symptoms (RR = 1.36, 95% CI 1.07, 1.71), while treatment with selective serotonin reuptake inhibitors showed no statistically significant difference in global symptoms compared with the control groups (RR = 1.38, 95% CI 0.83, 2.28). The pooled risk ratio of dropout due to side effects following antidepressant treatment was 1.71 with 95% CI (0.98, 2.99). The subgroup analysis showed the pooled risk ratio of dropout in the tricyclic antidepressants group was 1.92 with 95% CI (0.89, 4.17). In the selective serotonin reuptake inhibitors group, the pooled risk ratio of dropout was 1.5 with 95% CI (0.67, 3.37). Selective serotonin reuptake inhibitors showed no benefit in alleviating abdominal pain and improving quality of life. There was no difference in the incidence of common adverse events between treatment and control groups. Conclusions TCAs can improve global symptoms of irritable bowel syndrome, while there was no strong evidence to confirm the effectiveness of SSRIs for the treatment of IBS. PMID:26252008

Efficacy and Safety of Antidepressants for the Treatment of Irritable Bowel Syndrome: A Meta-Analysis.

Directory of Open Access Journals (Sweden)

Chen Xie

Full Text Available The aim of this meta-analysis was to analyze the efficacy and safety of antidepressants for the treatment of irritable bowel syndrome.We searched MEDLINE, EMBASE, Scopus and The Cochrane Library for randomized controlled trials investigating the efficacy and safety of antidepressants in the treatment of irritable bowel syndrome. Article quality was evaluated by Jadad score. RevMan 5.0 and Stata 12.0 were used for the meta-analysis.Twelve randomized controlled trials were included in this study and most of these trials were of high quality (Jadad score ≥4. Five articles focused on tricyclic antidepressants, six articles involved selective serotonin reuptake inhibitors, and one article investigated both types of treatment. The pooled risk ratio showed antidepressant treatment can improve global symptoms (RR = 1.38, 95% CI 1.08, 1.77. In the subgroup analysis, treatment with tricyclic antidepressants showed an improvement in global symptoms (RR = 1.36, 95% CI 1.07, 1.71, while treatment with selective serotonin reuptake inhibitors showed no statistically significant difference in global symptoms compared with the control groups (RR = 1.38, 95% CI 0.83, 2.28. The pooled risk ratio of dropout due to side effects following antidepressant treatment was 1.71 with 95% CI (0.98, 2.99. The subgroup analysis showed the pooled risk ratio of dropout in the tricyclic antidepressants group was 1.92 with 95% CI (0.89, 4.17. In the selective serotonin reuptake inhibitors group, the pooled risk ratio of dropout was 1.5 with 95% CI (0.67, 3.37. Selective serotonin reuptake inhibitors showed no benefit in alleviating abdominal pain and improving quality of life. There was no difference in the incidence of common adverse events between treatment and control groups.TCAs can improve global symptoms of irritable bowel syndrome, while there was no strong evidence to confirm the effectiveness of SSRIs for the treatment of IBS.

Divorce and subsequent increase in uptake of antidepressant medication: a Finnish registry-based study on couple versus individual effects.

Science.gov (United States)

Monden, Christiaan W S; Metsä-Simola, Niina; Saarioja, Saska; Martikainen, Pekka

2015-02-19

There is an average negative mental health effect for individuals who experience divorce. Little is known whether the pattern of such divorce effects varies within couples. We study whether the husband and wife experience similar harmful effects of divorce, whether they experience opposite effects, or whether divorce effects are purely individual. We use Finnish registry data to compare changes over a period of 5 years in antidepressant use of husbands and wives from 4,558 divorcing couples to 108,637 continuously married pairs aged 40-64, all of whom were healthy at baseline. In the period three years before and after divorce antidepressant use increases substantially. However, the likelihood of uptake of antidepressant medication during this process of divorce by one partner appears to be independent of medication uptake in the other partner. In contrast, among continuously married couples there is a clear pattern of convergence: If one partner starts to use antidepressants this increases the likelihood of uptake of antidepressant medication in the other partner. Our findings suggest that divorce effects on antidepressant use are individual and show no pattern of either convergence or divergence at the level of the couple. The increased incidence of antidepressant use associated with divorce occurs in individuals independent of what happens to their ex-partner.

Regulation of proteolytic cleavage of brain-derived neurotrophic factor precursor by antidepressants in human neuroblastoma cells

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Lin PY

2015-10-01

Full Text Available Pao-Yen Lin1,2 1Department of Psychiatry, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, 2Center for Translational Research in Biomedical Sciences, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan Abstract: Evidence has supported the role of brain-derived neurotrophic factor (BDNF in antidepressant effect. The precursor of BDNF (proBDNF often exerts opposing biological effects on mature BDNF (mBDNF. Hence, the balance between proBDNF and mBDNF might be critical in total neurotrophic effects, leading to susceptibility to or recovery from depression. In the current study, we measured the protein expression levels of proBDNF, and its proteolytic products, truncated BDNF, and mBDNF, in human SH-SY5Y cells treated with different antidepressants. We found that the treatment significantly increased the production of mBDNF, but decreased the production of truncated BDNF and proBDNF. These results support that antidepressants can promote proBDNF cleavage. Further studies are needed to clarify whether proBDNF cleavage plays a role in antidepressant mechanisms. Keywords: antidepressant, mature BDNF, neurotrophic effect, proBDNF cleavage 

Distinct Neuropsychological Mechanisms May Explain Delayed- Versus Rapid-Onset Antidepressant Efficacy

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Stuart, Sarah A; Butler, Paul; Munafò, Marcus R; Nutt, David J; Robinson, Emma SJ

2015-01-01

The biochemical targets for antidepressants are relatively well established, but we lack a clear understanding of how actions at these proteins translate to clinical benefits. This study used a novel rodent assay to investigate how different antidepressant drugs act to modify affective biases that have been implicated in depression. In this bowl-digging task, rats encounter two equal value learning experiences on separate days (one during an affective manipulation and the other during control conditions). This induces an affective bias that is quantified using a preference test in which both digging substrates are presented together and the individual rats’ choices recorded. The assay can be used to measure affective biases associated with learning (when the treatment is given at the time of the experience) or examine the modification of previously acquired biases (when the treatment is administered before the preference test). The rapid-onset antidepressant ketamine, but not the delayed-onset antidepressant, venlafaxine, attenuated the previously acquired FG7142-induced negative bias following systemic administration. Venlafaxine but not ketamine induced a positive bias when administered before learning. We then used local drug infusions and excitotoxic lesions to localize the effects of ketamine to the medial prefrontal cortex and venlafaxine to the amygdala. Using a modified protocol we also showed that positive and negative biases amplified further when the numbers of substrate–reinforcer associations are increased. We propose that this pattern of results could explain the delayed onset of action of venlafaxine and the rapid onset of action but lack of long-term efficacy seen with ketamine. PMID:25740288

Disparities in Depressive Symptoms and Antidepressant Treatment by Gender and Race/Ethnicity among People Living with HIV in the United States.

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Bengtson, Angela M; Pence, Brian W; Crane, Heidi M; Christopoulos, Katerina; Fredericksen, Rob J; Gaynes, Bradley N; Heine, Amy; Mathews, W Christopher; Moore, Richard; Napravnik, Sonia; Safren, Steven; Mugavero, Michael J

2016-01-01

To describe disparities along the depression treatment cascade, from indication for antidepressant treatment to effective treatment, in HIV-infected individuals by gender and race/ethnicity. The Center for AIDS Research (CFAR) Network of Integrated Clinical Systems (CNICS) cohort includes 31,000 HIV-infected adults in routine clinical care at 8 sites. Individuals were included in the analysis if they had a depressive symptoms measure within one month of establishing HIV care at a CNICS site. Depressive symptoms were measured using the validated Patient Health Questionnaire-9 (PHQ-9). Indication for antidepressant treatment was defined as PHQ-9 ≥ 10 or a current antidepressant prescription. Antidepressant treatment was defined as a current antidepressant prescription. Evidence-based antidepressant treatment was considered treatment changes based on a person's most recent PHQ-9, in accordance with clinical guidelines. We calculated the cumulative probability of moving through the depression treatment cascade within 24 months of entering CNICS HIV care. We used multivariable Cox proportional hazards models to estimate associations between gender, race/ethnicity, and a range of depression outcomes. In our cohort of HIV-infected adults in routine care, 47% had an indication for antidepressant treatment. Significant drop-offs along the depression treatment cascade were seen for the entire study sample. However, important disparities existed. Women were more likely to have an indication for antidepressant treatment (HR 1.54; 95% CI 1.34, 1.78), receive antidepressant treatment (HR 2.03; 95% CI 1.53, 2.69) and receive evidence-based antidepressant treatment (HR 1.67; 95% CI 1.03, 2.74), even after accounting for race/ethnicity. Black non-Hispanics (HR 0.47, 95% CI 0.35, 0.65), Hispanics (HR 0.63, 95% CI 0.44, 0.89) and other race/ethnicities (HR 0.35, 95% CI 0.17, 0.73) were less likely to initiate antidepressant treatment, compared to white non-Hispanics. In our cohort

Pharmacological Experimental Study Of The Anti-Depressant Effect ...

African Journals Online (AJOL)

Pharmacological Experimental Study Of The Anti-Depressant Effect Of Total Saikosaponins. Y Liu, C Cao, H Ding. Abstract. Background: Chai Hu has the hepato-protective, choleretic, anti-tussive, analgesic, anti-inflammatory, anti-viral, hypotensive, hypolipidemic, and anti-tumor pharmacological effects. In this study, the ...

Psychosocial work environment and antidepressant medication: a prospective cohort study

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Westergaard-Nielsen Niels

2009-07-01

Full Text Available Abstract Background Adverse psychosocial work environments may lead to impaired mental health, but it is still a matter of conjecture if demonstrated associations are causal or biased. We aimed at verifying whether poor psychosocial working climate is related to increase of redeemed subscription of antidepressant medication. Methods Information on all antidepressant drugs (AD purchased at pharmacies from 1995 through 2006 was obtained for a cohort of 21,129 Danish public service workers that participated in work climate surveys carried out during the period 2002–2005. Individual self-reports of psychosocial factors at work including satisfaction with the work climate and dimensions of the job strain model were obtained by self-administered questionnaires (response rate 77,2%. Each employee was assigned the average score value for all employees at his/her managerial work unit [1094 units with an average of 18 employees (range 3–120]. The risk of first-time AD prescription during follow-up was examined according to level of satisfaction and psychosocial strain by Cox regression with adjustment for gender, age, marital status, occupational status and calendar year of the survey. Results The proportion of employees that received at least one prescription of ADs from 1995 through 2006 was 11.9% and prescriptions rose steadily from 1.50% in 1996 to the highest level 6.47% in 2006. ADs were prescribed more frequent among women, middle aged, employees with low occupational status and those living alone. None of the measured psychosocial work environment factors were consistently related to prescription of antidepressant drugs during the follow-up period. Conclusion The study does not indicate that a poor psychosocial work environment among public service employees is related to prescription of antidepressant pharmaceuticals. These findings need cautious interpretation because of lacking individual exposure assessments.

Oxidative stress in major depressive and anxiety disorders, and the association with antidepressant use; results from a large adult cohort.

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Black, C N; Bot, M; Scheffer, P G; Penninx, B W J H

2017-04-01

Oxidative stress has been implicated in the pathophysiology of major depressive disorder (MDD) and anxiety disorders and may be influenced by antidepressant use. This study investigated the association of oxidative stress, measured by plasma levels of F2-isoprostanes and 8-hydroxy-2'-deoxyguanosine (8-OHdG) reflecting oxidative lipid and DNA damage respectively, with MDD, anxiety disorders and antidepressant use in a large cohort. Data was derived from the Netherlands Study of Depression and Anxiety including patients with current (N = 1619) or remitted (N = 610) MDD and/or anxiety disorder(s) (of which N = 704 antidepressant users) and 612 controls. Diagnoses were established with the Composite International Diagnostic Interview. Plasma 8-OHdG and F2-isoprostanes were measured using LC-MS/MS. ANCOVA was performed adjusted for sampling, sociodemographic, health and lifestyle variables. F2-isoprostanes did not differ between controls and patients, or by antidepressant use. Patients with current disorders had lower 8-OHdG (mean 42.1 pmol/l, 95% CI 40.4-43.8) compared to controls (45.0 pmol/l, 95% CI 42.9-47.2; p anxiety disorders), and all antidepressant types (SSRIs, TCAs, other antidepressants). Contrary to previous findings this large-scale study found no increased oxidative stress in MDD and anxiety disorders. Antidepressant use was associated with lower oxidative DNA damage, suggesting antidepressants may have antioxidant effects.

A novel examination of atypical major depressive disorder based on attachment theory.

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Levitan, Robert D; Atkinson, Leslie; Pedersen, Rebecca; Buis, Tom; Kennedy, Sidney H; Chopra, Kevin; Leung, Eman M; Segal, Zindel V

2009-06-01

While a large body of descriptive work has thoroughly investigated the clinical correlates of atypical depression, little is known about its fundamental origins. This study examined atypical depression from an attachment theory framework. Our hypothesis was that, compared to adults with melancholic depression, those with atypical depression would report more anxious-ambivalent attachment and less secure attachment. As gender has been an important consideration in prior work on atypical depression, this same hypothesis was further tested in female subjects only. One hundred ninety-nine consecutive adults presenting to a tertiary mood disorders clinic with major depressive disorder with either atypical or melancholic features according to the Structured Clinical Interview for DSM-IV Axis-I Disorders were administered a self-report adult attachment questionnaire to assess the core dimensions of secure, anxious-ambivalent, and avoidant attachment. Attachment scores were compared across the 2 depressed groups defined by atypical and melancholic features using multivariate analysis of variance. The study was conducted between 1999 and 2004. When men and women were considered together, the multivariate test comparing attachment scores by depressive group was statistically significant at p depression was associated with significantly lower secure attachment scores, with a trend toward higher anxious-ambivalent attachment scores, than was melancholia. When women were analyzed separately, the multivariate test was statistically significant at p depressive groups. These preliminary findings suggest that attachment theory, and insecure and anxious-ambivalent attachment in particular, may be a useful framework from which to study the origins, clinical correlates, and treatment of atypical depression. Gender may be an important consideration when considering atypical depression from an attachment perspective. Copyright 2009 Physicians Postgraduate Press, Inc.

Potential antidepressant properties of IDN 5491 (hyperforin-trimethoxybenzoate), a semisynthetic ester of hyperforin.

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Cervo, Luigi; Mennini, Tiziana; Rozio, Marco; Ekalle-Soppo, Charlotte Blanche; Canetta, Alessandro; Burbassi, Silvia; Guiso, Giovanna; Pirona, Lorenza; Riva, Antonella; Morazzoni, Paolo; Caccia, Silvio; Gobbi, Marco

2005-03-01

Hyperforin is one of the possible active principles mediating the antidepressant activity of Hypericum perforatum L. extracts. The ester derivative IDN 5491 (hyperforin-trimethoxybenzoate) showed antidepressant-like properties in the forced swimming test (FST) in rats, with no effect on open-field activity, when given as three intraperitoneal injections in 24 h at 3.125 and 6.25 mg/kg. The plasma concentrations of IDN 5491 were 30-50 microM, and those of hyperforin much lower but still close to those after effective doses of hyperforin-dicyclohexylammonium and Hypericum extract. This suggests that hyperforin plays a role in the antidepressant-like effect of the ester and of Hypericum extract. In vitro binding and uptake data showed that IDN 5491 is inactive on a wide panel of CNS targets at a concentration (14 microM) much higher than that measured in the brain of treated rats (0.3 microM). Like the extract, the antidepressant-like effect of IDN 5491 was blocked by (-)-sulpiride, a selective D2 receptor antagonist and by BD-1047, a selective sigma1 antagonist. Ex-vivo binding studies showed that brain sigma1 receptors are occupied after in vivo treatment with IDN 5491, possibly by an unknown metabolite or by endogenous ligand induced by hyperforin.

Atypical pyoderma gangrenosum in a patient with osteomyelofibrosis

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Živanović Dubravka

2007-01-01

Full Text Available Background. Atypical forms of pyoderma gangrenosum generally appear on the upper extremities; most frequently they are associated with myeloproliferative disorders, including osteomyelofibrosis. A response to systemic steroids is more pronounced than in classical form. Sometimes it may be the first sign of an underlying malignancy. Case report. We reported a patient with atypical pyoderma gangrenosum developed during the course of a myeloid malignancy - osteomyelofibrosis. The lesions occurred after a minor trauma. Painful blistering plaques, with an elevated, bluish-gray border were located on the dorsal aspect of hands. No skin malignancy was found. The lesions resolved rapidly to systemic steroids. Conclusion. Considering the unusual clinical presentation which makes the diagnosis difficult, as well as the fact that atypical forms of pyoderma gangrenosum can be the first sign of malignancies, especially myeloproliferative ones, recognizing this entity enables timely guiding future investigations toward their prompt detection.

A meta-analysis of the effects of antidepressants on cognitive functioning in depressed and non-depressed samples.

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Prado, Catherine E; Watt, Stephanie; Crowe, Simon F

2018-03-01

A thorough understanding of the cognitive effects of antidepressant medications is essential given their frequency of use. This meta-analysis was conducted to investigate whether antidepressants differentially affect the various domains of cognitive functioning for depressed and non-depressed participants. An electronic search of PsycInfo, Medline and Google Scholar was conducted for all journal articles published between January 1998 and January 2017. Thirty-three studies were included enabling calculation of Hedges' g using a random effects model for the cognitive domains of divided attention, executive function, expressive language, immediate memory, perceptual motor skills, processing speed, recent memory, sustained attention, visuospatial-constructional skills and working memory. Results revealed that overall, antidepressants have a modest, positive effect on divided attention, executive function, immediate memory, processing speed, recent memory and sustained attention for depressed participants. Selective serotonin reuptake inhibitors (SSRI's) were found to have the greatest positive effect on cognition for depressed participants, as compared to the other classes of antidepressants analysed. Antidepressants did not significantly affect cognitive function in non-depressed participants.

Compliance and persistence of antidepressants versus anticonvulsants in patients with neuropathic pain during the first year of therapy.

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Gharibian, Derenik; Polzin, Jennifer K; Rho, Jay P

2013-05-01

Neuropathic pain (NP) is a chronic condition that has human, social, and economic consequences. A variety of agents can be used for treatment; however, antidepressants and anticonvulsants are the 2 classes most widely studied and represent first-line agents in the management of NP. Little information is known about the adherence patterns of these medications during the first year of therapy in patients with NP. To examine the compliance and persistence of antidepressants versus anticonvulsants in patients with NP during the first year of therapy. Using electronic medical and pharmacy data for the Kaiser Permanente Southern California region, the adherence patterns for patients with a NP diagnosis prescribed an antidepressant or an anticonvulsant were studied. Compliance and persistence were measured using the medication possession ratio and the Refill-Sequence model, respectively. The study included 1817 patients with NP diagnosis taking either an antidepressant or an anticonvulsant. Within the antidepressant group, 42.9% were considered compliant, compared with 43.7% in the anticonvulsant group. Subanalysis of the 2 cohorts revealed that patients on venlafaxine were the most compliant (69.4%) compared with patients taking gabapentin (44.4%) and tricyclic antidepressants (41.8%) (Panticonvulsant group were considered persistent with their medication refills. Compliance and persistence rates were similar for patients with NP diagnosis taking antidepressants and anticonvulsants. Higher compliance was observed among patients taking venlafaxine; however, this population did have a small sample size.

Atypical antipsychotics: trends in analysis and sample preparation of various biological samples.

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Fragou, Domniki; Dotsika, Spyridoula; Sarafidou, Parthena; Samanidou, Victoria; Njau, Samuel; Kovatsi, Leda

2012-05-01

Atypical antipsychotics are increasingly popular and increasingly prescribed. In some countries, they can even be obtained over-the-counter, without a prescription, making their abuse quite easy. Although atypical antipsychotics are thought to be safer than typical antipsychotics, they still have severe side effects. Intoxications are not rare and some of them have a fatal outcome. Drug interactions involving atypical antipsychotics complicate patient management in clinical settings and the determination of the cause of death in fatalities. In view of the above, analytical strategies that can efficiently isolate atypical antipsychotics from a variety of biological samples and quantify them accurately, sensitively and reliably, are of utmost importance both for the clinical, as well as for the forensic toxicologist. In this review, we will present and discuss novel analytical strategies that have been developed from 2004 to the present day for the determination of atypical antipsychotics in various biological samples.

The analgesic effect of different antidepressants combined with ...

African Journals Online (AJOL)

Background: Combination analgesics provide more effective pain relief for a broader spectrum of pain. This research examines the possible potentiation of the analgesic effect of different classes of antidepressants when combined with aspirin in thermal model of pain using Albino mice. Methods: Different groups of six ...

Prescription and predictors of post-stroke antidepressant treatment: A population-based study

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Mortensen, Janne Kærgård; Johnsen, Søren Paaske; Andersen, Grethe

2018-01-01

OBJECTIVES: Post-stroke depression and pathological crying are common and potentially serious complications after stroke and should be diagnosed and treated accordingly. Diagnosis and treatment probably rely on clinical experience and may pose certain challenges. We aimed to examine prescription...... corresponding to 48.1% (95% CI: 45.8-50.5) of all treated patients, and the most widely prescribed group of antidepressants was selective serotonin reuptake inhibitors (86%). Increasing stroke severity was associated with higher odds of initiating treatment. CONCLUSION: Antidepressant treatment in this real...

Fluctuation theorems and atypical trajectories

International Nuclear Information System (INIS)

Sahoo, M; Lahiri, S; Jayannavar, A M

2011-01-01

In this work, we have studied simple models that can be solved analytically to illustrate various fluctuation theorems. These fluctuation theorems provide symmetries individually to the distributions of physical quantities such as the classical work (W c ), thermodynamic work (W), total entropy (Δs tot ) and dissipated heat (Q), when the system is driven arbitrarily out of equilibrium. All these quantities can be defined for individual trajectories. We have studied the number of trajectories which exhibit behaviour unexpected at the macroscopic level. As the time of observation increases, the fraction of such atypical trajectories decreases, as expected at the macroscale. The distributions for the thermodynamic work and entropy production in nonlinear models may exhibit a peak (most probable value) in the atypical regime without violating the expected average behaviour. However, dissipated heat and classical work exhibit a peak in the regime of typical behaviour only.

Early Freezing of Gait: Atypical versus Typical Parkinson Disorders

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Abraham Lieberman

2015-01-01

Full Text Available In 18 months, 850 patients were referred to Muhammad Ali Parkinson Center (MAPC. Among them, 810 patients had typical Parkinson disease (PD and 212 had PD for ≤5 years. Among the 212 patients with early PD, 27 (12.7% had freezing of gait (FOG. Forty of the 850 had atypical parkinsonism. Among these 40 patients, all of whom had symptoms for ≤5 years, 12 (30.0% had FOG. FOG improved with levodopa in 21/27 patients with typical PD but did not improve in the 12 patients with atypical parkinsonism. FOG was associated with falls in both groups of patients. We believe that FOG unresponsive to levodopa in typical PD resembles FOG in atypical parkinsonism. We thus compared the 6 typical PD patients with FOG unresponsive to levodopa plus the 12 patients with atypical parkinsonism with the 21 patients with typical PD responsive to levodopa. We compared them by tests of locomotion and postural stability. Among the patients with FOG unresponsive to levodopa, postural stability was more impaired than locomotion. This finding leads us to believe that, in these patients, postural stability, not locomotion, is the principal problem underlying FOG.

Childhood Atypical Teratoid/Rhabdoid Tumor Treatment (PDQ®)—Patient Version

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Atypical teratoid/rhabdoid tumor (AT/RT) is a fast-growing tumor of the brain or spinal cord. Treatment may include surgery, radiation therapy, and chemotherapy. Get information about the symptoms, diagnosis, prognosis, and treatment of newly diagnosed and recurrent childhood atypical teratoid/rhabdoid tumors in this expert-reviewed summary.

Typical and Atypical Dementia Family Caregivers: Systematic and Objective Comparisons

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Nichols, Linda O.; Martindale-Adams, Jennifer; Burns, Robert; Graney, Marshall J.; Zuber, Jeffrey

2011-01-01

This systematic, objective comparison of typical (spouse, children) and atypical (in-law, sibling, nephew/niece, grandchild) dementia family caregivers examined demographic, caregiving and clinical variables. Analysis was of 1,476 caregivers, of whom 125 were atypical, from the Resources for Enhancing Alzheimer's Caregivers Health (REACH I and II)…

The contribution of diffusion-weighted MR imaging to distinguishing typical from atypical meningiomas

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Hakyemez, Bahattin [Uludag University School of Medicine, Department of Radiology, Gorukle, Bursa (Turkey); Bursa State Hospital, Department of Radiology, Bursa (Turkey); Yildirim, Nalan; Gokalp, Gokhan; Erdogan, Cuneyt; Parlak, Mufit [Uludag University School of Medicine, Department of Radiology, Gorukle, Bursa (Turkey)

2006-08-15

Atypical/malignant meningiomas recur more frequently then typical meningiomas. In this study, the contribution of diffusion-weighted MR imaging to the differentiation of atypical/malignant and typical meningiomas and to the determination of histological subtypes of typical meningiomas was investigated. The study was performed prospectively on 39 patients. The signal intensity of the lesions was evaluated on trace and apparent diffusion coefficient (ADC) images. ADC values were measured in the lesions and peritumoral edema. Student's t-test was used for statistical analysis. P<0.05 was considered statistically significant. Mean ADC values in atypical/malignant and typical meningiomas were 0.75{+-}0.21 and 1.17{+-}0.21, respectively. Mean ADC values for subtypes of typical meningiomas were as follows: meningothelial, 1.09{+-}0.20; transitional, 1.19{+-}0.07; fibroblastic, 1.29{+-}0.28; and angiomatous, 1.48{+-}0.10. Normal white matter was 0.91{+-}0.10. ADC values of typical meningiomas and atypical/malignant meningiomas significantly differed (P<0.001). However, the difference between peritumoral edema ADC values was not significant (P>0.05). Furthermore, the difference between the subtypes of typical meningiomas and atypical/malignant meningiomas was significant (P<0.001). Diffusion-weighted MR imaging findings of atypical/malignant meningiomas and typical meningiomas differ. Atypical/malignant meningiomas have lower intratumoral ADC values than typical meningiomas. Mean ADC values for peritumoral edema do not differ between typical and atypical meningiomas. (orig.)

Closing the antidepressant efficacy gap between clinical trials and real patient populations.

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Wade, Alan G

2006-01-01

Overall, patient outcomes in the primary care of depression are seldom as good as those achieved in clinical trials - the "efficacy gap". Many factors contribute to this, including poor patient compliance, poor family and social support and negative media reporting of antidepressants. Indeed, negative media reporting has had far more impact on physicians' prescribing of antidepressants than have regulatory agencies, partly as a result of changing public attitudes. Negative media reports linking SSRIs to increased child suicide rates have also resulted in a decline in the prescribing of SSRIs to this age group, but with no concomitant increase in the prescribing of fluoxetine, the only antidepressant recommended for the treatment of children. There are also inadequacies in the guidelines available to primary care givers that might contribute to the efficacy gap. Guidelines can be too specific for clinical practice - especially where depression coexists with anxiety disorders - and too passive, resulting in delayed or inadequate intervention. Evidence suggests that many physicians prefer to be more proactive. In the recent AHEAD survey, physicians identified faster resolution of symptoms as the property most desirable for improving antidepressant therapy. There is recent evidence that structured long-term therapy and easily-implemented measurement-based care procedures can improve remission rates and help bridge the efficacy gap. If these can be allied with greater public/media understanding of depression and its treatment, along with improved guidelines, then significant progress can be anticipated in the management of mood disorders.

Low dose of caffeine enhances the efficacy of antidepressants in major depressive disorder and the underlying neural substrates.

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Liu, Qing-Shan; Deng, Ran; Fan, Yuyan; Li, Keqin; Meng, Fangang; Li, Xueli; Liu, Rui

2017-08-01

Caffeine is one of the most frequently used psychoactive substances ingested mainly via beverage or food products. Major depressive disorder is a serious and devastating psychiatric disorder. Emerging evidence indicates that caffeine enhances the antidepressant-like activity of common antidepressant drugs in rodents. However, whether joint administration of low dose of caffeine enhances the antidepressant actions in depressed patients remains unclear. A total of 95 male inpatients were assigned to three groups and were asked to take either caffeine (60, 120 mg) or placebo (soymilk powder) daily for 4 wk on the basis of their current antidepressant medications. Results showed that chronic supplementation with low dose of caffeine (60 mg) produced rapid antidepressant action by reduction of depressive scores. Furthermore, low dose of caffeine improved cognitive performance in depressed patients. However, caffeine did not affect sleep as measured by overnight polysomnography. Moreover, chronic caffeine consumption elicited inhibition of hypothalamic-pituitary-adrenal axis activation by normalization of salivary cortisol induced by Trier social stress test. These findings indicated the potential benefits of further implications of supplementary administration of caffeine to reverse the development of depression and enhance the outcome of antidepressants treatment in major depressive disorder. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

The Effect of Antidepressants on Mesenchymal Stem Cell Differentiation.

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Kruk, Jeffrey S; Bermeo, Sandra; Skarratt, Kristen K; Fuller, Stephen J; Duque, Gustavo

2018-02-01

Use of antidepressant medications has been linked to detrimental impacts on bone mineral density and osteoporosis; however, the cellular basis behind these observations remains poorly understood. The effect does not appear to be homogeneous across the whole class of drugs and may be linked to affinity for the serotonin transporter system. In this study, we hypothesized that antidepressants have a class- and dose-dependent effect on mesenchymal stem cell (MSC) differentiation, which may affect bone metabolism. Human MSCs (hMSCs) were committed to differentiate when either adipogenic or osteogenic media was added, supplemented with five increasing concentrations of amitriptyline (0.001-10 µM), venlafaxine (0.01-25 µM), or fluoxetine (0.001-10 µM). Alizarin red staining (mineralization), alkaline phosphatase (osteoblastogenesis), and oil red O (adipogenesis) assays were performed at timed intervals. In addition, cell viability was assessed using a MTT. We found that fluoxetine had a significant inhibitory effect on mineralization. Furthermore, adipogenic differentiation of hMSC was affected by the addition of amitriptyline, venlafaxine, and fluoxetine to the media. Finally, none of the tested medications significantly affected cell survival. This study showed a divergent effect of three antidepressants on hMSC differentiation, which appears to be independent of class and dose. As fluoxetine and amitriptyline, but not venlafaxine, affected both osteoblastogenesis and adipogenesis, this inhibitory effect could be associated to the high affinity of fluoxetine to the serotonin transporter system.

Systematic identification and quantification of tetracyclic monoterpenoid oxindole alkaloids in Uncaria rhynchophylla and their fragmentations in Q-TOF-MS spectra.

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Xie, Shuanglu; Shi, Yuanyuan; Wang, Yixiang; Wu, Chunyong; Liu, Wenyuan; Feng, Feng; Xie, Ning

2013-01-01

Uncaria rhynchophylla (UR) is a species of Uncaria that is distributed mainly in China and Japan. In this study, the chemical constituents, including alkaloids, flavonoids, and quinic acids, in UR have been systematically identified and quantified by a developed method of high-performance liquid chromatography coupled with diode-array detection and quadrupole time-of-flight mass spectrometry (Q-TOF-MS). Tetracyclic monoterpenoid oxindole alkaloids (TMOAs) are characteristic compounds in this herb, and their fragmentations in Q-TOF-MS have been investigated. Diagnostic fragmentation ions (DFIs) were first delineated for isorhynchophylline-type (7S, C20-ethyl) and corynoxeine-type (7R, C20-vinyl) TMOAs, and these were used for identification of these alkaloids in UR. In this study, a total of 29 compounds, comprising 18 alkaloids, six flavonoids, and five quinic acids, were identified. Among them, there are four novel TMOAs, named as 22-O-β-glucopyranosyl isorhynchophyllic acid (10), 22-O-β-glucopyranosyl rhynchophyllic acid (11), 9-hydroxy isocorynoxeine (16), and 9-hydroxy corynoxeine (20), which have not been reported previously. Furthermore, eight marker compounds, namely chlorogenic acid (3), catechin (8), epicatechin (9), isocorynoxeine (24), rhynchophylline (25), isorhynchophylline (27), vincoside lactam (28), and corynoxeine (29), have been simultaneously quantified. The developed method has been validated and successfully applied to analyze three samples of UR from Jiangxi Province. The contents of the marker compounds have been detected and compared. Copyright © 2013 Elsevier B.V. All rights reserved.

Gender-Atypical Mental Illness as Male Gender Threat.

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Michniewicz, Kenneth S; Bosson, Jennifer K; Lenes, Joshua G; Chen, Jason I

2016-07-01

The present study examined whether men view gender-atypical (i.e., feminine) psychological disorders as threats to their gender status. Men and women (N = 355) rated their expectations of gender status loss, feelings of distress, and help-seeking intentions in response to 10 different stereotypically masculine and feminine psychological disorders. Men as compared to women expected greater gender status loss for, and reported more distress to, gender-atypical versus gender-typical disorders. Expectations of gender status loss partially mediated the link between participant gender and distress at the thought of gender-atypical disorders. These findings suggest that feminine disorders pose more powerful gender status threats for men than masculine disorders do and that men's expectations of gender status loss for feminine disorders drive their negative reactions to these mental illnesses. The discussion emphasizes the importance of considering the gender-typicality of disorders, and the implications of these findings for clinical interventions. © The Author(s) 2015.

Atypical presentation of HELLP syndrome: clinical case report

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Juan Manuel Tobar Parra

2017-12-01

Full Text Available Objective: To describe a case of HELLP syndrome with atypical presentation form. Background: HELLP syndrome is a complication of preeclampsia, characterized by: haemolysis, elevation of liver enzymes and thrombocytopenia; Can present atypical, without hypertension or proteinuria, 10-20% of the cases. Case report: 38 year old female patient, with a pregnancy of 38.5 weeks of gestation, treated at the Hospital Universitario San José de Popayán (Colombia. Atypical HELLP syndrome is diagnosed in a pregnant woman with thrombocytopenia, impaired liver enzymes, but no evidence of proteinuria or hypertension. Gestation is terminated by cesarean section and magnesium sulfate is given for 24 hours, with adequate post-surgical evolution, clinical improvement of the symptomatology presented, normalization of liver enzymes and platelet elevation. Conclusion: Knowledge of this syndrome, although of rare occurrence, allows a fast action, an effective diagnosis and treatment, to avoid morbidity and greater maternal fetal mortality.

Preparation and cellular response of porous A-type carbonated hydroxyapatite nanoceramics

International Nuclear Information System (INIS)

Li Bo; Liao Xiaoling; Zheng Li; He Huawei; Wang Hong; Fan Hongsong; Zhang Xingdong

2012-01-01

Microwave sintering using the activated carbon as embedding material was applied in preparation of porous A-type carbonated hydroxyapatite ceramics with nano(nCHA) and submicron (mCHA) structure. By examining the linear shrinkages and the compressive strengths of samples at different temperatures, a suitable microwave sintering temperature was achieved. The microwave sintering method was successfully used to prepare A-type CHA with nano or submicron structure, and the mechanism of the formation of A-type carbonate groups was discussed also. Compared with the samples prepared by the conventional sintering method (mHA), the nCHA bioceramics synthesized by the microwave sintering approach had smaller grain size and more uniform microstructure, and showed a compressive strength similar to the conventional samples. In vitro dissolution test proved that nCHA exhibits better degradation property in comparison to pure HA. Rat osteoblasts were cultured with nCHA, mCHA and mHA to evaluate their biocompatibility, and nCHA showed significant enhancement of cells in attachment, proliferation and differentiation. In conclusion, carbonate groups can be easily introduced to HA crystal structure using the activated carbon as embedding material, and microwave sintering is an effective and simple method in preparing A-type CHA with a nanostructure. Results from this in vitro biological study suggest that porous A-type carbonated hydroxyapatite nanoceramics may be a much better candidate for clinical use in terms of bioactivity. - Highlights: ► We prepared porous A-type carbonated hydroxyapatite nanoceramics with microwave sintering. ► We examined physico-chemical characterization and osteoblast response. ► The nanoceramics have a comparable compressive strength to samples with conventional sintering method. ► The nanoceramics enhance degradation property, osteoblast proliferation and differentiation. ► The activated carbon is favorable for preheating samples and providing

Increased risk of antidepressant use in childhood cancer survivors

DEFF Research Database (Denmark)

Lund, Lasse Wegener; Winther, J.F.; Cederkvist, L

2015-01-01

to the National Prescription Drug Database, which worldwide is the oldest nationwide registry of prescription medication. Hazard ratios (HRs) for antidepressant use were estimated in a Cox proportional hazards model stratified on sex, with population comparisons as referents. RESULTS: Overall, childhood cancer......AIM: Childhood cancer survivors are at risk of both somatic and mental late effects, but large population-based studies of depression are lacking. METHODS: Risk of antidepressant use was evaluated in a population-based cohort of 5452 Danish children treated for cancer in 1975-2009 by linkage....... Increased HRs of 30-50% were seen for survivors of cancers of all main groups (haematological malignancies, central nervous system (CNS) and solid tumors); the highest risk was among children treated with haematopoietic stem cell transplantation (HR, 1.9; 95% CI, 1.2-3.1). Our data suggested that the risk...

Antidepressant-like effects of the xanthine oxidase enzyme inhibitor allopurinol in rats. A comparison with fluoxetine.

Science.gov (United States)

Gürbüz Özgür, Börte; Aksu, Hatice; Birincioğlu, Mustafa; Dost, Turhan

2015-11-01

Allopurinol is a xanthine oxidase enzyme inhibitor that is widely used for the treatment of hyperuricemia and gout. The activity of tryptophan 2,3-dioxygenase, which metabolizes tryptophan (TRP), is decreased by xanthine oxidase inhibitors, causing TRP levels in the body to be increased. Increases in TRP levels in the brain might have antidepressant effects. The purpose of this study is to evaluate the antidepressant effects of allopurinol compared to those of fluoxetine, which is a proven antidepressant. Thirty-two Wistar albino male rats were divided into four groups (control, 10mg/kg fluoxetine, 50mg/kg allopurinol, 50mg/kg allopurinol+10 mg/kg fluoxetine; n=8 per group), and forced swimming tests were performed before and after 14days of drug administration. Serotonin, 5-hydroxyindolacetic acid and uric acid levels were measured in blood samples after the final treatment. When allopurinol and fluoxetine were administered separately, a decrease in the duration of immobility and an increased duration of swimming were observed in the forced swimming test. The results showed similar antidepressant efficacies between allopurinol and fluoxetine. However, we found no statistically significant difference in the antidepressant effect of the combined therapy versus single drug therapy. Copyright © 2015 Elsevier Inc. All rights reserved.

The association between major depressive disorder, use of antidepressants and bone mineral density (BMD) in men.

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Rauma, P H; Pasco, J A; Berk, M; Stuart, A L; Koivumaa-Honkanen, H; Honkanen, R J; Hodge, J M; Williams, L J

2015-06-01

Both depression and use of antidepressants have been negatively associated with bone mineral density (BMD) but mainly in studies among postmenopausal women. Therefore, the aim of this study was to investigate these relationships in men. Between 2006 and 2011, 928 men (aged 24-98 years) from the Geelong Osteoporosis Study completed a comprehensive questionnaire, clinical measurements and had BMD assessments at the forearm, spine, total hip and total body. Major depressive disorder (MDD) was identified using a structured clinical interview (SCID-I/NP). The cross-sectional associations between BMD and both MDD and antidepressant use were analyzed using multivariable linear regression. Of the study population, 84 (9.1%) men had a single MDD episode, 50 (5.4%) had recurrent episodes and 65 (7.0%) were using antidepressants at the time of assessment. Following adjustments, recurrent MDD was associated with lower BMD at the forearm and total body (-6.5%, P=0.033 and -2.5%, P=0.033, respectively compared to men with no history of MDD), while single MDD episodes were associated with higher BMD at the total hip (+3.4%, P=0.030). Antidepressant use was associated with lower BMD only in lower-weight men (depression and use of antidepressants should be taken into account as possible risk factors for osteoporosis in men.

5-Hydroxytryptamine-Independent Antidepressant Actions of (R)-Ketamine in a Chronic Social Defeat Stress Model.

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Zhang, Kai; Dong, Chao; Fujita, Yuko; Fujita, Atsuhiro; Hashimoto, Kenji

2018-02-01

Previous reports suggest that 5-hydroxytryptamine might play a role in the antidepressant actions of (R,S)-ketamine. However, its role in the antidepressant actions of (R)-ketamine, which is more potent than (S)-ketamine, is unknown. This study was conducted to examine whether 5-hydroxytryptamine depletion affects the antidepressant actions of (R)-ketamine in a chronic social defeat stress model. An inhibitor of 5-hydroxytryptamine synthesis, para-chlorophenylalanine methyl ester hydrochloride (300 mg/kg, twice daily for 3 consecutive days), or vehicle was administered to control and chronic social defeat stress-susceptible mice. Levels of 5-hydroxytryptamine and its metabolite, 5-hydroxyindoleacetic acid, in mouse brain regions were measured using high-performance liquid chromatography. Furthermore, antidepressant effects of (R)-ketamine (10 mg/kg) in the vehicle- and para-chlorophenylalanine methyl ester hydrochloride-treated susceptible mice were assessed using tail suspension test and 1% sucrose preference test. para-Chlorophenylalanine methyl ester hydrochloride treatment caused marked reductions of 5-hydroxytryptamine and 5-hydroxyindoleacetic acid in the brain regions of control and chronic social defeat stress susceptible mice. In the tail suspension test, (R)-ketamine significantly attenuated the increased immobility time in the chronic social defeat stress-susceptible mice with or without 5-hydroxytryptamine depletion. In the sucrose preference test (2 and 5 days after a single dose), (R)-ketamine significantly enhanced reduced sucrose consumption in the chronic social defeat stress-susceptible mice with or without 5-hydroxytryptamine depletion. These findings show that 5-hydroxytryptamine depletion did not affect the antidepressant effects of (R)-ketamine in a chronic social defeat stress model. Therefore, it is unlikely that 5-hydroxytryptamine plays a major role in the antidepressant actions of (R)-ketamine. © The Author 2017. Published by Oxford

Modulation of attention network activation under antidepressant agents in healthy subjects.

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Graf, Heiko; Abler, Birgit; Hartmann, Antonie; Metzger, Coraline D; Walter, Martin

2013-07-01

While antidepressants are supposed to exert similar effects on mood and drive via various mechanisms of action, diverging effects are observed regarding side-effects and accordingly on neural correlates of motivation, emotion, reward and salient stimuli processing as a function of the drugs impact on neurotransmission. In the context of erotic stimulation, a unidirectional modulation of attentional functioning despite opposite effects on sexual arousal has been suggested for the selective serotonin reuptake-inhibitor (SSRI) paroxetine and the selective dopamine and noradrenaline reuptake-inhibitor (SDNRI) bupropion. To further elucidate the effects of antidepressant-related alterations of neural attention networks, we investigated 18 healthy males under subchronic administration (7 d) of paroxetine (20 mg), bupropion (150 mg) and placebo within a randomized placebo-controlled cross-over double-blind functional magnetic resonance imaging (fMRI) design during an established preceding attention task. Neuropsychological effects beyond the fMRI-paradigm were assessed by measuring alertness and divided attention. Comparing preceding attention periods of salient vs. neutral pictures, we revealed congruent effects of both drugs vs. placebo within the anterior midcingulate cortex, dorsolateral prefrontal cortex, anterior prefrontal cortex, superior temporal gyrus, anterior insula and the thalamus. Relatively decreased activation in this network was paralleled by slower reaction times in the divided attention task in both verum conditions compared to placebo. Our results suggest similar effects of antidepressant treatments on behavioural and neural attentional functioning by diverging neurochemical pathways. Concurrent alterations of brain regions within a fronto-parietal and cingulo-opercular attention network for top-down control could point to basic neural mechanisms of antidepressant action irrespective of receptor profiles.

[Driving under the influence of benzodiazepines and antidepressants: prescription and abuse].

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Coutinho, Daniel; Vieira, Duarte Nuno; Teixeira, Helena M

2011-01-01

Benzodiazepines are drugs usually used in anxiety disorders, dyssomnias, convulsions, muscle disorders, alcohol and other drugs detoxification, as well as in preoperative sedation/amnesia. Moreover, antidepressants are mainly indicated in depression and as co-therapeutic drugs in other psychiatric disorders. The use of benzodiazepines and antidepressants is associated with some health and public safety problems. Decreased of attention, concentration, reflexes, visual capacity, motor coordination and reasoning, associated with increased reaction time and lack of awareness of driving impairment among these drug users, contributes to the increased risk on traffic safety linked with these drugs. This risk may further increase with non-compliance of medical prescription, drug abuse or concomitant use of alcohol. The relationship between the use of psychoactive drugs and road traffic safety is, however, an extremely complex subject and has a primordial importance in the clarification of the role of benzodiazepine and antidepressant effects on driving skills. The prevention of driving under the influence of these drugs depends on the awareness, among doctors, of the risks associated with their use. Thus, the consciousness of medical prescription, as well as providing clear information to patients is extremely important.

Antidepressant monotherapy in pre-bipolar depression; predictive value and inherent risk.

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O'Donovan, Claire; Garnham, Julie S; Hajek, Tomas; Alda, Martin

2008-04-01

To identify specific treatment-emergent symptoms in response to antidepressant therapy in depression preceding bipolar disorder. Retrospective chart review of response to antidepressants in "pre-bipolar" depression, compared to a matched unipolar sample. Family history of completed suicide (p=0.0003) and bipolar disorder (p=0.004) were more common in the pre-bipolar subgroup. Earlier age of onset of diagnosed depression (p=0.005) as well as even earlier episodes of untreated retrospectively diagnosed major depression (p<0.0001) were associated with a future bipolar course. The pre-bipolar group was less likely to respond to antidepressant treatment (p=0.009). Treatment-emergent "mixed" symptoms (two or more symptoms of DSM IV mania, mood lability, irritability/rage with co-existing depression) and in particular, "serious symptoms" (treatment emergent or increased agitation, rage or suicidality) occurred more commonly in the bipolar group. The two variables that best accounted for the between-group differences in logistic regression, were early age at first symptoms of depression and treatment-emergent agitation. Family history of completed suicide and/or bipolar disorder, early onset of depressive symptoms as well as treatment-emergent "mixed" symptoms are common in depression preceding the diagnosis of bipolar disorder.

The effects of antidepressants and pilocarpine on rat parotid glands: an immunohistochemical study

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Tatiana Maria Folador Mattioli

2011-01-01

Full Text Available OBJECTIVES: To evaluate the effects of antidepressants and pilocarpine on the quantity of myoepithelial cells and on the proliferation index of the epithelial cells of rat parotid glands. INTRODUCTION: Hyposalivation, xerostomia, and alterations in saliva composition are important clinical side effects related to the use of antidepressants. METHODS: Ninety male Wistar rats were allocated to nine groups. The control groups received saline for 30 (group C30 or 60 days (group C60 or pilocarpine for 60 days (group Pilo. The experimental groups were administered fluoxetine (group F30 or venlafaxine for 30 days (group V30; fluoxetine (group FS60 or venlafaxine (group VS60 with saline for 60 days; or fluoxetine (group FP60 or venlafaxine (group VP60 with pilocarpine for 60 days. Parotid gland specimens were processed, and the immunohistochemical expression of calponin and proliferating cell nuclear anti-antigen on the myoepithelial and parenchymal cells, respectively, was evaluated. Analysis of variance (ANOVA, Tukey HSD and Games-Howell tests were applied to detect differences among groups (p<0.05. RESULTS: Compared with the controls, chronic exposure to antidepressants was associated with an increase in the number of positively stained cells for calponin. In addition, venlafaxine administration for 30 days was associated with an increase in the number of positively stained cells for proliferating cell nuclear anti-antigen. Fluoxetine and pilocarpine (group FP60 induced a significant decrease in the number of positively stained cells for calponin compared with all other groups. CONCLUSIONS: The number of positively stained cells for calponin increased after chronic administration of antidepressants. The proliferation index of the epithelial cells of rat parotid glands was not altered by the use of antidepressants for 60 days.

The antidepressant debate and the balanced placebo trial design: an ethical analysis.

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Waring, Duff R

2008-12-01

There is ongoing debate about whether randomized, placebo-controlled trials under a double-blind have reliably established the pharmacological efficacy of antidepressants. Numerous meta-analyses of antidepressant efficacy trials, e.g., Kirsch et al. [Kirsch, I., Moore, T. J., Scoboria, A., & Nicholls, S. (2002). The emperor's new drugs: An analysis of antidepressant medication data submitted to the U.S. food and drug administration. Prevention and Treatment, 5, Article 23. (Retrieved July 19, 2007 from http://journals.apa.org/prevention/volume5)], have shown a modest drug-placebo difference but methodological problems with standard trial design preclude a definitive conclusion that this difference results from specific biological effects of antidepressants or the nonspecific factors that have not been adequately excluded. Standard trial design assumes the additivity thesis of pharmacological efficacy, being the assumption that the specific or "true" magnitude of the pharmacological effect is limited to the difference between the drug and placebo responses in a standard trial. If the drug effects are as small as these meta-analyses suggest, then their clinical effectiveness is questionable. If the drug effects are actually larger but masked by placebo effects, then the additivity thesis is not valid and we risk false negative results with standard trial design. Kirsch et al. propose an alternative, four arm balanced placebo trial design (BPTD) that can accurately test the additivity thesis. The BPTD uses antidepressants, active placebos and the intentional deception of research subjects. My focal question is whether the BPTD is ethically defensible. I will explore two objections that can be raised against it: 1) lying to BPTD research subjects violates their autonomy and exploits their illness and 2) the BPTD may not enable us to test the additivity thesis with accuracy, i.e., it may contribute to the masking of drug effects that it aims to avoid. I argue that these

Antidepressant, psychostimulant, and nootropic effects of major and trace element composition.

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Afanasieva, O G; Suslov, N I; Shilova, I V

2013-06-01

The antidepressant, psychostimulant, and nootropic effects of a composition of major and trace elements including KCl, RbNO3, magnesium sulfate, and zinc sulfate were studied on the models of behavioural despair (Porsolt test) and conditioned passive avoidance test. The preparation was found to shorten the immobilization time in the Porsolt test and promote retention of the conditioned passive avoidance. The most pronounced psychostimulant effect of the substance was observed at a dose of 4.68 mg/kg and the most pronounced antidepressant effect was found at a dose of 18.72 mg/kg. Maximum nootropic activity of the preparation was found at a dose of 93.6 mg/kg.

Atypical imaging appearances of intracranial meningiomas

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O' Leary, S. [Radiology Department, Derriford Hospital, Plymouth (United Kingdom); Adams, W.M. [Radiology Department, Derriford Hospital, Plymouth (United Kingdom); Parrish, R.W. [Radiology Department, Derriford Hospital, Plymouth (United Kingdom); Mukonoweshuro, W. [Radiology Department, Derriford Hospital, Plymouth (United Kingdom)]. E-mail: William.mukonoweshuro@phnt.swest.nhs.uk

2007-01-15

Meningiomas are the commonest primary, non-glial intracranial tumours. The diagnosis is often correctly predicted from characteristic imaging appearances. This paper presents some examples of atypical imaging appearances that may cause diagnostic confusion.

[Auricular sporotrichosis. Atypical case report simulating bacterial cellulitis].

Science.gov (United States)

Ochoa-Reyes, Juan; Ramos-Martínez, Ernesto; Treviño-Rangel, Rogelio; González, Gloria M; Bonifaz, Alexandro

Sporotrichosis is the most common subcutaneous or implantation mycosis in Mexico. The case of a preauricular cutaneous-fixed sporotrichosis simulating atypical bacterial cellulitis is reported in an elderly patient with no history of trauma. The biopsy showed a suppurative granuloma with scarce yeast. Sporothrix schenckii was identified in the culture and confirmed by molecular biology. She was treated with itraconazole and a clinical and mycological cure was obtained. The case of atypical presentation is presented, coming from a semi-arid zone with extreme weather.

The role of atypical antipsychotics for treatment of Tourette's syndrome: an overview.

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Budman, Cathy L

2014-07-01

Tourette's syndrome (TS) is a neuropsychiatric disorder of childhood onset characterized by multiple motor and phonic tics that fluctuate over time. Tic symptoms often improve by late adolescence, but some children and adults with TS may experience significant tic-related morbidity, including social and family problems, academic difficulties, and pain. When more conservative interventions are not successful, and when certain psychiatric co-morbidities further complicate the clinical profile, treating TS with an atypical antipsychotic medication may be a reasonable second-tier approach. However, the evidence supporting efficacy and safety of the atypical antipsychotics for treatment of tics is still very limited. The objective of this paper is to provide an updated overview of the role of atypical antipsychotics for treatment of TS, with evidence-based guidance on their use. Evidence for efficacy of different typical and atypical antipsychotics for treatment of tics was examined by conducting a systematic, keyword-related search of 'atypical antipsychotics' and 'Tourette's syndrome' in PubMed (National Library of Medicine, Washington, DC, USA). Four recent treatment consensus publications were also reviewed. This review focused on literature published from 2000 to 2013 and on available randomized controlled trials in TS. Evidence supporting the use of atypical antipsychotics for treatment of TS is limited. There are few randomized medication treatment trials in TS (i.e. risperidone, aripiprazole, ziprasidone), which employed varying methodologies, thereby restricting meaningful comparisons among studies. Future collaborations among clinical sites with TS expertise employing high-quality study design may better elucidate the role of atypical antipsychotics for treatment of TS.

Antidepressants in Parkinson's disease. Recommendations by the movement disorder study group of the Neurological Association of Madrid.

Science.gov (United States)

Peña, E; Mata, M; López-Manzanares, L; Kurtis, M; Eimil, M; Martínez-Castrillo, J C; Navas, I; Posada, I J; Prieto, C; Ruíz-Huete, C; Vela, L; Venegas, B

2016-03-19

Although antidepressants are widely used in Parkinson's disease (PD), few well-designed studies to support their efficacy have been conducted. These clinical guidelines are based on a review of the literature and the results of an AMN movement disorder study group survey. Evidence suggests that nortriptyline, venlafaxine, paroxetine, and citalopram may be useful in treating depression in PD, although studies on paroxetine and citalopram yield conflicting results. In clinical practice, however, selective serotonin reuptake inhibitors are usually considered the treatment of choice. Duloxetine may be an alternative to venlafaxine, although the evidence for this is less, and venlafaxine plus mirtazapine may be useful in drug-resistant cases. Furthermore, citalopram may be indicated for the treatment of anxiety, atomoxetine for hypersomnia, trazodone and mirtazapine for insomnia and psychosis, and bupropion for apathy. In general, antidepressants are well tolerated in PD. However, clinicians should consider the anticholinergic effect of tricyclic antidepressants, the impact of serotonin-norepinephrine reuptake inhibitors on blood pressure, the extrapyramidal effects of antidepressants, and any potential interactions between monoamine oxidase B inhibitors and other antidepressants. Copyright © 2016 Sociedad Española de Neurología. Published by Elsevier España, S.L.U. All rights reserved.

Atypical Rulings of the Indonesian Constitutional Court

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Bisariyadi

2016-08-01

Full Text Available In deciding judicial review cases, the Court may issue rulings that is not in accordance to what is stipulated in the Constitutional Court Law (Law Number 8 Year 2011. Atypical rulings means that the court may reconstruct a provision, delay the legislation/rulings enactment or give instruction to lawmakers. In addition, the court also introduce the “conditionally (unconstitutional” concept. This essay attempts to identify and classify these atypical rulings, including conditionally (un constitutional rulings, by examined the constitutional court judicial review rulings from 2003 to 2015. This study will provide a ground work for advance research on typical rulings by the Indonesian constitutional court.

Spadin, a sortilin-derived peptide, targeting rodent TREK-1 channels: a new concept in the antidepressant drug design.

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Jean Mazella

2010-04-01

Full Text Available Current antidepressant treatments are inadequate for many individuals, and when they are effective, they require several weeks of administration before a therapeutic effect can be observed. Improving the treatment of depression is challenging. Recently, the two-pore domain potassium channel TREK-1 has been identified as a new target in depression, and its antagonists might become effective antidepressants. In mice, deletion of the TREK-1 gene results in a depression-resistant phenotype that mimics antidepressant treatments. Here, we validate in mice the antidepressant effects of spadin, a secreted peptide derived from the propeptide generated by the maturation of the neurotensin receptor 3 (NTSR3/Sortilin and acting through TREK-1 inhibition. NTSR3/Sortilin interacted with the TREK-1 channel, as shown by immunoprecipitation of TREK-1 and NTSR3/Sortilin from COS-7 cells and cortical neurons co-expressing both proteins. TREK-1 and NTSR3/Sortilin were colocalized in mouse cortical neurons. Spadin bound specifically to TREK-1 with an affinity of 10 nM. Electrophysiological studies showed that spadin efficiently blocked the TREK-1 activity in COS-7 cells, cultured hippocampal pyramidal neurons, and CA3 hippocampal neurons in brain slices. Spadin also induced in vivo an increase of the 5-HT neuron firing rate in the Dorsal Raphe Nucleus. In five behavioral tests predicting an antidepressant response, spadin-treated mice showed a resistance to depression as found in TREK-1 deficient mice. More importantly, an intravenous 4-d treatment with spadin not only induced a strong antidepressant effect but also enhanced hippocampal phosphorylation of CREB protein and neurogenesis, considered to be key markers of antidepressant action after chronic treatment with selective serotonin reuptake inhibitors. This work also shows the development of a reliable method for dosing the propeptide in serum of mice by using AlphaScreen technology. These findings point out

Antidepressant and neurocognitive effects of isoflurane anesthesia versus electroconvulsive therapy in refractory depression.

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Howard R Weeks

Full Text Available Many patients have serious depression that is nonresponsive to medications, but refuse electroconvulsive therapy (ECT. Early research suggested that isoflurane anesthesia may be an effective alternative to ECT. Subsequent studies altered drug, dose or number of treatments, and failed to replicate this success, halting research on isoflurane's antidepressant effects for a decade. Our aim was to re-examine whether isoflurane has antidepressant effects comparable to ECT, with less adverse effects on cognition.Patients with medication-refractory depression received an average of 10 treatments of bifrontal ECT (n = 20 or isoflurane (n = 8 over 3 weeks. Depression severity (Hamilton Rating Scale for Depression-24 and neurocognitive responses (anterograde and retrograde memory, processing speed and verbal fluency were assessed at Pretreatment, Post all treatments and 4-week Follow-up.Both treatments produced significant reductions in depression scores at Post-treatment and 4-week Follow-up; however, ECT had modestly better antidepressant effect at follow-up in severity-matched patients. Immediately Post-treatment, ECT (but not isoflurane patients showed declines in memory, fluency, and processing speed. At Follow-up, only autobiographical memory remained below Pretreatment level for ECT patients, but isoflurane patients had greater test-retest neurocognitive score improvement.Our data reconfirm that isoflurane has an antidepressant effect approaching ECT with less adverse neurocognitive effects, and reinforce the need for a larger clinical trial.

Lack of Antidepressant Effects of (2R,6R)-Hydroxynorketamine in a Rat Learned Helplessness Model: Comparison with (R)-Ketamine.

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Shirayama, Yukihiko; Hashimoto, Kenji

2018-01-01

(R)-Ketamine exhibits rapid and sustained antidepressant effects in animal models of depression. It is stereoselectively metabolized to (R)-norketamine and subsequently to (2R,6R)-hydroxynorketamine in the liver. The metabolism of ketamine to hydroxynorketamine was recently demonstrated to be essential for ketamine's antidepressant actions. However, no study has compared the antidepressant effects of these 3 compounds in animal models of depression. The effects of a single i.p. injection of (R)-ketamine, (R)-norketamine, and (2R,6R)-hydroxynorketamine in a rat learned helplessness model were examined. A single dose of (R)-ketamine (20 mg/kg) showed an antidepressant effect in the rat learned helplessness model. In contrast, neither (R)-norketamine (20 mg/kg) nor (2R,6R)-hydroxynorketamine (20 and 40 mg/kg) did so. Unlike (R)-ketamine, its metabolite (2R,6R)-hydroxynorketamine did not show antidepressant actions in the rat learned helplessness model. Therefore, it is unlikely that the metabolism of ketamine to hydroxynorketamine is essential for ketamine's antidepressant actions. © The Author 2017. Published by Oxford University Press on behalf of CINP.

Primary lateral sclerosis mimicking atypical parkinsonism

DEFF Research Database (Denmark)

Norlinah, Ibrahim M; Bhatia, Kailash P; Østergaard, Karen

2007-01-01

of the atypical parkinsonian syndromes. Here we describe five patients initially referred with a diagnosis of levodopa-unresponsive atypical parkinsonism (n = 4) or primary progressive multiple sclerosis (n = 1), but subsequently found to have features consistent with PLS instead. Onset age varied from 49 to 67......Primary lateral sclerosis (PLS), the upper motor neurone variant of motor neurone disease, is characterized by progressive spinal or bulbar spasticity with minimal motor weakness. Rarely, PLS may present with clinical features resembling parkinsonism resulting in occasional misdiagnosis as one...... in all patients. Anterior horn cell involvement developed in three cases. Early gait disturbances resulting in falls were seen in all patients and none of them responded to dopaminergic medications. Two patients underwent dopamine transporter (DaT) SPECT scanning with normal results. Other features...

The association between concomitant use of serotonergic antidepressants and lithium-induced polyuria. A multicenter medical chart review study.

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Wilting, I; Egberts, A C G; Movig, K L L; Laarhoven, J H M van; Heerdink, E R; Nolen, W A

2008-07-01

A previous study aimed at revealing the prevalence and determinants of lithium induced polyuria suggested an increased risk of polyuria (urine volume > or =3 L/24 h) in those using serotonergic antidepressants next to lithium. The objective of our study was to re-evaluate this secondary finding in another study population. We performed a multicenter medical chart review study in patients using lithium in whom a 24-hour urine volume had been determined. We included 116 patients, twelve (26%)of the 46 patients with polyuria used serotonergic antidepressants compared to ten (14%) of the 70 patients without polyuria. We found an increased risk of polyuria in lithium users concurrently using serotonergic antidepressants (oddsratio 2.86; 95% confidence interval 1.00-8.21), adjusted for age, gender, use of antiepileptics and thyreomimetics. Our results confirm the previous secondary finding of an increased risk of polyuria in patients using serotonergic antidepressants next to lithium. Physicians should take this into account when evaluating polyuria in patients using lithium and when choosing an antidepressant in patients using lithium.

Lipoma arborescens: Comparison of typical and atypical disease presentations

International Nuclear Information System (INIS)

Howe, B.M.; Wenger, D.E.

2013-01-01

Aim: To determine whether the aetiology differed between typical cases of lipoma arborescens with unilateral knee involvement and atypical cases involving joints other than the knee, polyarticular disease, and disease outside of the knee joint. Materials and methods: Cases of lipoma arborescens involving the knee joint were evaluated for the distribution of the disease and severity of degenerative arthritis. Joints other than the knee were evaluated for the presence and severity of degenerative arthritis, and the distribution was classified as either intra-articular, extra-articular, or both. Clinical history was reviewed for patient age at presentation, a history of inflammatory arthritis, diabetes mellitus, and known steroid use. Fisher's exact test was used to determine whether there was a statistically significant difference between typical and atypical presentations of the disease. Results: Lipoma arborescens was identified in 45 joints in 39 patients. Twenty-eight patients were classified as “typical” and 11 patients had “atypical” disease. There was no significant difference in age at presentation, presence of degenerative arthritis, or known inflammatory arthritis when comparing typical and atypical presentations of the disease. Conclusion: Twenty-eight percent of patients in the present study had atypical presentation of lipoma arborescens with multifocal lipoma arborescens or disease in joints other than the knee. There was no significant difference in age at presentation, presence of degenerative arthritis, or known inflammatory arthritis when comparing typical and atypical presentations of the disease. Of the 39 patients, only three had no evidence of degenerative arthritis, which suggests that many cases of lipoma arborescens are secondary to chronic reactive change in association with degenerative arthritis

The use of electroconvulsive therapy in atypical psychotic presentations: a case review.

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Montgomery, John H; Vasu, Devi

2007-10-01

Convulsive therapy and its progeny, electroconvulsive therapy (ECT), were originally used for the treatment of catatonic schizophrenia, and there is little doubt that ECT remains an effective intervention for the treatment of schizophrenia. However, current practice tends to favor the use of ECT in severe or treatment refractory affective disorders, and its use in schizophrenia and other nonaffective (atypical) psychotic disorders has become controversial.CASE REPORTS HAVE SUGGESTED A ROLE FOR ECT IN TWO SPECIFIC ATYPICAL PSYCHOTIC DISORDERS: Cotard's syndrome and cycloid psychosis. In this article, we review the atypical psychotic disorders and report a series of five case examples that signify the role of ECT in atypical psychotic presentations, particularly when the symptoms resemble those found in Cotard's syndrome and cycloid psychosis.

Association between depressive symptoms, use of antidepressant medication and the metabolic syndrome: the Maine-Syracuse Study

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Georgina E. Crichton

2016-06-01

Full Text Available Abstract Background Both depression and the metabolic syndrome (MetS are two major public health issues. The aim of this study was to examine associations between depressive symptoms, the use of antidepressant medications, and the prevalence of MetS. Methods Cross-sectional analyses were undertaken on 970 participants from the Maine-Syracuse Study. Depressive symptoms were measured using two self-reported depression scales, the Center for Epidemiological Studies Depression Scale (CES-D, and the Zung self-rating depression scale. Antidepressant medication use was also self-reported. MetS was defined according to the recent harmonized criteria. Results The risk of MetS were approximately 79 and 86 % higher for those in the highest quartile for the CESD and the Zung (CES-D: OR = 1.79, p = 0.003; Zung: OR = 1.71, p = 0.006, compared to those in the lowest quartile. With adjustment for socio-demographic variables, lifestyle factors and C-reactive protein (CRP, risk was attenuated, but remained statistically significant for the CES-D. In those who reported using antidepressant medication, the odds of having MetS were over 2-fold higher (OR = 2.22, p < 0.001, fully adjusted model, compared to those who did not use antidepressants. Both measures of depressed mood were also associated with low high density-lipoprotein (HDL cholesterol levels. Antidepressant use was associated with elevated fasting plasma glucose concentrations, hypertension, and low HDL-cholesterol. Conclusion Depressive symptoms and the use of antidepressant medications are associated with the prevalence of MetS, and with some of the individual components of the syndrome.

MANIFESTATIONS OF AGGRESSIVE ATYPICAL KAPOSI'S ...

African Journals Online (AJOL)

... weight loss (86.8%), skin nodules (86.4%) and diarrhoea (55.3%). Virtually, all occupational groups were affected, with students, civil servants and businessmen topping the list. Key Words: Atypical Aggressive Kaposi's sarcoma, HIV infection. African Journal Of Clinical And Experimental Microbiology Jan 2004 Vol.5 No.1 ...

Mitochondrial dynamics in the hippocampus is influenced by antidepressant treatment in a genetic rat model of depression

DEFF Research Database (Denmark)

Chen, F.; Wegener, Gregers; Madsen, T. M.

2013-01-01

Post-mortem, genetic, brain imaging, and peripheral cell studies showed that mitochondria may play an important role in the pathophysiology of depression and effects of antidepressant therapy. Here we investigated whether chronic antidepressant treatment on rats induce changes of the mitochondria...

Clinical features of Friedreich's ataxia: classical and atypical phenotypes.

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Parkinson, Michael H; Boesch, Sylvia; Nachbauer, Wolfgang; Mariotti, Caterina; Giunti, Paola

2013-08-01

One hundred and fifty years since Nikolaus Friedreich's first description of the degenerative ataxic syndrome which bears his name, his description remains at the core of the classical clinical phenotype of gait and limb ataxia, poor balance and coordination, leg weakness, sensory loss, areflexia, impaired walking, dysarthria, dysphagia, eye movement abnormalities, scoliosis, foot deformities, cardiomyopathy and diabetes. Onset is typically around puberty with slow progression and shortened life-span often related to cardiac complications. Inheritance is autosomal recessive with the vast majority of cases showing an unstable intronic GAA expansion in both alleles of the frataxin gene on chromosome 9q13. A small number of cases are caused by a compound heterozygous expansion with a point mutation or deletion. Understanding of the underlying molecular biology has enabled identification of atypical phenotypes with late onset, or atypical features such as retained reflexes. Late-onset cases tend to have slower progression and are associated with smaller GAA expansions. Early-onset cases tend to have more rapid progression and a higher frequency of non-neurological features such as diabetes, cardiomyopathy, scoliosis and pes cavus. Compound heterozygotes, including those with large deletions, often have atypical features. In this paper, we review the classical and atypical clinical phenotypes of Friedreich's ataxia. © 2013 International Society for Neurochemistry.

Antidepressant therapy with milnacipran and venlafaxine

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Lucilla Mansuy

2010-08-01

Full Text Available Lucilla MansuyPierre Fabre Médicament, Toulouse, FranceAbstract: Specific serotonin norepinephrine reuptake inhibitors (SNRIs have been described as “better tolerated tricyclic antidepressants” or as “boosted” selective serotonin reuptake inhibitors (SSRIs. Venlafaxine has become a therapeutic reference treatment for major depression. Although less widely studied, indirect comparisons with another SNRI, milnacipran, suggest an equivalent efficacy. This paper discusses these indirect comparisons and the recently published first double-blind, head-to-head comparison. Venlafaxine has potency at serotonin transporters which is about 30-fold greater than that at norepinephrine transporters while milnacipran has a similar potency at each transporter. Thus, at low doses, venlafaxine acts essentially as a SSRI, with significant noradrenergic activity only occurring at higher doses. To overcome the problem of the differing profile of venlafaxine at increasing doses, the first head-to-head study compared the therapeutic effects and tolerability of the two antidepressants when flexibly titrated to the high dose of 200 mg/day. The study showed that the two SNRIs have similar efficacy and safety profiles. Both drugs produced about 42% remissions at the end of the 20-week study. The most frequent adverse events in both groups were nausea, dizziness, headache, and sweating. Certain specific differences in tolerability are discussed.Keywords: milnacipran, venlafaxine, antidepressant efficacy, tolerability, dose-titration

Synthesis and Antidepressant Activity Profile of Some Novel Benzothiazole Derivatives

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Ümide Demir Özkay

2017-09-01

Full Text Available Within the scope of our new antidepressant drug development efforts, in this study, we synthesized eight novel benzothiazole derivatives 3a–3h. The chemical structures of the synthesized compounds were elucidated by spectroscopic methods. Test compounds were administered orally at a dose of 40 mg/kg to mice 24, 5 and 1 h before performing tail suspension, modified forced swimming, and activity cage tests. The obtained results showed that compounds 3c, 3d, 3f–3h reduced the immobility time of mice as assessed in the tail suspension test. Moreover, in the modified forced swimming tests, the same compounds significantly decreased the immobility, but increased the swimming frequencies of mice, without any alteration in the climbing frequencies. These results, similar to the results induced by the reference drug fluoxetine (20 mg/kg, po, indicated the antidepressant-like activities of the compounds 3c, 3d, 3f–3h. Owing to the fact that test compounds did not induce any significant alteration in the total number of spontaneous locomotor activities, the antidepressant-like effects of these derivatives seemed to be specific. In order to predict ADME parameters of the synthesized compounds 3a–3h, some physicochemical parameters were calculated. The ADME prediction study revealed that all synthesized compounds may possess good pharmacokinetic profiles.

Bullying, Physical Aggression, Gender-Atypicality, and Sexual Orientation in Samoan Males.

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Semenyna, Scott W; Vasey, Paul L

2017-07-01

Bullying is characterized by the repeated attempts of a group or individual to gain social advantage by the use of relational, verbal, or physical aggression against a target, especially when there is a perceived or actual power imbalance (Espelage & Swearer, 2003). One consistent finding is that gay (i.e., androphilic) males report higher rates of victimization due to bullying in adolescence than their heterosexual (i.e., gynephilic) counterparts. Western data indicate that gender-atypical behavior, regardless of sexual orientation, is a key predictor of victimization due to bullying. Androphilic males generally display childhood gender-atypicality, including reduced levels of physical aggression, which may cause bullies to perceive them as "easy" targets. In order to test the associations between sexual orientation, childhood gender-atypicality, and recalled victimization due to bullying, a sample of Samoan gynephilic men (n = 100) were compared to a group of Samoan transgender androphilic males (n = 103), known as fa'afafine. Although the fa'afafine reported far more childhood gender-atypicality, the two groups did not differ significantly on measures of physical aggression or their reported rates of victimization due to bullying. Additionally, greater physical aggression, not gender-atypicality, was the only significant predictor of being bullied in both men and fa'afafine. These results suggest that there is nothing inherent in sexual orientation or childhood gender-atypicality that would potentiate victimization from bullying. Instead, the cultural context in which a bully functions influences the extent to which these are "acceptable" reasons to target certain individuals.

GLYX-13, a NMDA receptor glycine-site functional partial agonist, induces antidepressant-like effects without ketamine-like side effects.

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Burgdorf, Jeffrey; Zhang, Xiao-lei; Nicholson, Katherine L; Balster, Robert L; Leander, J David; Stanton, Patric K; Gross, Amanda L; Kroes, Roger A; Moskal, Joseph R

2013-04-01

Recent human clinical studies with the NMDA receptor (NMDAR) antagonist ketamine have revealed profound and long-lasting antidepressant effects with rapid onset in several clinical trials, but antidepressant effects were preceded by dissociative side effects. Here we show that GLYX-13, a novel NMDAR glycine-site functional partial agonist, produces an antidepressant-like effect in the Porsolt, novelty induced hypophagia, and learned helplessness tests in rats without exhibiting substance abuse-related, gating, and sedative side effects of ketamine in the drug discrimination, conditioned place preference, pre-pulse inhibition and open-field tests. Like ketamine, the GLYX-13-induced antidepressant-like effects required AMPA/kainate receptor activation, as evidenced by the ability of NBQX to abolish the antidepressant-like effect. Both GLYX-13 and ketamine persistently (24 h) enhanced the induction of long-term potentiation of synaptic transmission and the magnitude of NMDAR-NR2B conductance at rat Schaffer collateral-CA1 synapses in vitro. Cell surface biotinylation studies showed that both GLYX-13 and ketamine led to increases in both NR2B and GluR1 protein levels, as measured by Western analysis, whereas no changes were seen in mRNA expression (microarray and qRT-PCR). GLYX-13, unlike ketamine, produced its antidepressant-like effect when injected directly into the medial prefrontal cortex (MPFC). These results suggest that GLYX-13 produces an antidepressant-like effect without the side effects seen with ketamine at least in part by directly modulating NR2B-containing NMDARs in the MPFC. Furthermore, the enhancement of 'metaplasticity' by both GLYX-13 and ketamine may help explain the long-lasting antidepressant effects of these NMDAR modulators. GLYX-13 is currently in a Phase II clinical development program for treatment-resistant depression.

Influence of enrichment on behavioral and neurogenic effects of antidepressants in Wistar rats submitted to repeated forced swim test.

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Possamai, Fernanda; dos Santos, Juliano; Walber, Thais; Marcon, Juliana C; dos Santos, Tiago Souza; Lino de Oliveira, Cilene

2015-04-03

Repeated forced swimming test (rFST) may detect gradual effects of antidepressants in adult rats. Antidepressants, as enrichment, affected behavior and neurogenesis in rats. However, the influence of enrichment on behavioral and neurogenic effects of antidepressants is unknown. Here, effects of antidepressants on rFST and hippocampal neurogenesis were investigated in rats under enriched conditions. Behaviors of male Wistar rats, housed from weaning in standard (SE) or enriched environment (EE), were registered during rFST. The rFST consisted of 15min of swimming (pretest) followed by 5min of swimming in the first (test), seventh (retest 1) and fourteenth (retest 2) days after pretest. One hour before the test, rats received an intraperitoneal injection of saline (1ml/kg), fluoxetine (2.5mg/kg) or imipramine (2.5 or 5mg/kg). These treatments were performed daily until the day of the retest 2. After retest 2, rats were euthanized for the identification of markers for neurogenesis in the hippocampus. Fluoxetine or imipramine decreased immobility in retests 1 and 2, as compared to saline. EE abolished these differences. In EE, fluoxetine or imipramine (5mg/kg) reduced immobility time in retest 2, as compared to the test. Independent of the housing conditions, fluoxetine and imipramine (5mg/kg) increased the ratio of immature neurons per progenitor cell in the hippocampus. In summary, antidepressants or enrichment counteracted the high immobility in rFST. Enrichment changed the effects of antidepressants in rFST depending on the type, and the dose of a substance but failed to change neurogenesis in control or antidepressant treated-rats. Effects of antidepressants and enrichment on rFST seemed neurogenesis-independent. Copyright © 2014 Elsevier Inc. All rights reserved.

The role of protein kinase-G in the antidepressant-like response of sildenafil in combination with muscarinic acetylcholine receptor antagonism

DEFF Research Database (Denmark)

Liebenberg, Nico; Wegener, Gregers; Brink, Christiaan

not affect swimming or climbing. Lastly, locomotor activity was unaltered by all treatment conditions. Conclusions These results confirm cholinergic-cGMP-PK-G interactions in the antidepressant-like effects of sildenafil, putatively acting via noradrenergic mechanisms, whereas direct PK-G activation induces...... the antidepressant-like activity of sildenafil + atropine is mediated via the activation of PK-G, a downstream effector for cGMP, and whether this may target known pathways in antidepressant action. Purpose We investigated whether the antidepressant-like response of sildenafil ± atropine could be reversed by Rp-8-Br.......c.v.) ± atropine (1 mg/kg, i.p.), Rp-8-Br-PET-cGMP or atropine. Antidepressant-like activity was scored in terms of a reduction of immobility (in seconds) relative to vehicle-treated controls. Swimming and climbing behaviours were scored as an indication of serotonergic and noradrenergic mechanisms, respectively...

Adverse Effects of Antidepressants Reported by 1,431 people from 38 Countries: Emotional Blunting, Suicidality, and Withdrawal Effects.

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Read, John; Williams, James

2018-06-04

Studies of the adverse effects of antidepressants tend to focus on biological symptoms. The prevalence of suicidality and withdrawal effects are currently a source of controversy. To directly ascertain the experiences of an international sample of antidepressant users. An online survey asked adult antidepressant users whether they had experienced 20 adverse effects 'as a result of taking the antidepressant', and if so, to what degree of severity. 1,431 people from 38 countries responded. 61% of the respondents reported at least ten of the 20 effects, most commonly: 'Feeling emotionally numb' (reported by 71%), 'Feeling foggy or detached' (70%); 'Feeling not like myself' (66%), 'Sexual difficulties' (66%), 'Drowsiness' (63%), and 'Reduction in positive feelings' (60%). 'Suicidality' as a result of the drugs was reported by 50%. Withdrawal effects were reported by 59%, and 'Addiction' by 40%. Rates of adverse effects were higher for those prescribed multiple antidepressants and those who also took antipsychotics. Younger age and longer use of ADs were positively related to total adverse effects. One third did not recall being told about any side effects by the prescriber. Less than 5% were told about suicidality, emotional numbing, withdrawal effects or addiction. Asking people directly reveals far higher rates of adverse responses to antidepressants than previously understood, especially in the emotional, psychological and interpersonal domains. Given recent findings that antidepressants are only marginally more effective than placebo, the findings of the current study imply a cost-benefit analysis that cannot justify the extremely high prescription rates for these drugs. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Inhibition of G protein-activated inwardly rectifying K+ channels by different classes of antidepressants.

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Toru Kobayashi

Full Text Available Various antidepressants are commonly used for the treatment of depression and several other neuropsychiatric disorders. In addition to their primary effects on serotonergic or noradrenergic neurotransmitter systems, antidepressants have been shown to interact with several receptors and ion channels. However, the molecular mechanisms that underlie the effects of antidepressants have not yet been sufficiently clarified. G protein-activated inwardly rectifying K(+ (GIRK, Kir3 channels play an important role in regulating neuronal excitability and heart rate, and GIRK channel modulation has been suggested to have therapeutic potential for several neuropsychiatric disorders and cardiac arrhythmias. In the present study, we investigated the effects of various classes of antidepressants on GIRK channels using the Xenopus oocyte expression assay. In oocytes injected with mRNA for GIRK1/GIRK2 or GIRK1/GIRK4 subunits, extracellular application of sertraline, duloxetine, and amoxapine effectively reduced GIRK currents, whereas nefazodone, venlafaxine, mianserin, and mirtazapine weakly inhibited GIRK currents even at toxic levels. The inhibitory effects were concentration-dependent, with various degrees of potency and effectiveness. Furthermore, the effects of sertraline were voltage-independent and time-independent during each voltage pulse, whereas the effects of duloxetine were voltage-dependent with weaker inhibition with negative membrane potentials and time-dependent with a gradual decrease in each voltage pulse. However, Kir2.1 channels were insensitive to all of the drugs. Moreover, the GIRK currents induced by ethanol were inhibited by sertraline but not by intracellularly applied sertraline. The present results suggest that GIRK channel inhibition may reveal a novel characteristic of the commonly used antidepressants, particularly sertraline, and contributes to some of the therapeutic effects and adverse effects.

Atypical E2f functions are critical for pancreas polyploidization.

Science.gov (United States)

Matondo, Ramadhan B; Moreno, Eva; Toussaint, Mathilda J M; Tooten, Peter C J; van Essen, Saskia C; van Liere, Elsbeth A; Youssef, Sameh A; Bongiovanni, Laura; de Bruin, Alain

2018-01-01

The presence of polyploid cells in the endocrine and exocrine pancreas has been reported for four decades. In rodents, pancreatic polyploidization is initiated after weaning and the number of polyploid cells increases with age. Surprisingly the molecular regulators and biological functions of polyploidization in the pancreas are still unknown. We discovered that atypical E2f activity is essential for polyploidization in the pancreas, using an inducible Cre/LoxP approach in new-born mice to delete ubiquitously the atypical E2f transcription factors, E2f7 and E2f8. In contrast to its critical role in embryonic survival, conditional deletion of both of both atypical E2fs in newborn mice had no impact on postnatal survival and mice lived until old age. However, deficiency of E2f7 or E2f8 alone was sufficient to suppress polyploidization in the pancreas and associated with only a minor decrease in blood serum levels of glucose, insulin, amylase and lipase under 4 hours starvation condition compared to wildtype littermates. In mice with fewer pancreatic polyploid cells that were fed ad libitum, no major impact on hormones or enzymes levels was observed. In summary, we identified atypical E2fs to be essential for polyploidization in the pancreas and discovered that postnatal induced loss of both atypical E2fs in many organs is compatible with life until old age.

Atypical forms of acute Epstein-Barr virus infection in children

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T.V. Sorokman

2018-03-01

Full Text Available Background. Today, there is a tendency to increase in Epstein-Barr virus infection (EBVI morbidity. The purpose of the study was to identify the incidence and features of atypical forms of acute EBVI in children. Material and methods. We have examined 28 children aged 6 months to 18 years with EBVI who were monitored in pediatric polyclinic. The activity of alanine aminotransferase and aspartate aminotransferase, levels of bilirubin, alkaline phosphatase, gamma-glutamyl transpeptidase, markers of viral hepatitis were evaluated. Enzyme-linked immunosorbent assay was performed with determination of blood markers of EBV (immunoglobulin (Ig M viral capsid antigen (VCA, IgG early antigen, IgG VCA, avidity and cytomegalovirus (CMV (IgM, IgG, avidity, EBV deoxyribonucleic acid (DNA, CMV DNA; polymerase chain reaction was used for serological diagnosis. The data were processed by statistical analysis using Statistica 6 program. Results. In 71.4 % of cases, EBVI had usual course and moderate severity. The atypical forms of acute EBVI were observed in 28.5 % of cases. Clinically atypical forms began mainly from signs of acute respiratory infections followed by lesions of the internal organs (liver and heart, in particular, in children under 1 year of age, and changes in liver functional tests. Conclusions. The incidence of atypical forms of EBVI is 28.5 %. Atypical forms of EBVI are more common in infants and adolescents and associated with the damage to the internal organs (liver and heart.

Atypical E2f functions are critical for pancreas polyploidization.

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Ramadhan B Matondo

Full Text Available The presence of polyploid cells in the endocrine and exocrine pancreas has been reported for four decades. In rodents, pancreatic polyploidization is initiated after weaning and the number of polyploid cells increases with age. Surprisingly the molecular regulators and biological functions of polyploidization in the pancreas are still unknown. We discovered that atypical E2f activity is essential for polyploidization in the pancreas, using an inducible Cre/LoxP approach in new-born mice to delete ubiquitously the atypical E2f transcription factors, E2f7 and E2f8. In contrast to its critical role in embryonic survival, conditional deletion of both of both atypical E2fs in newborn mice had no impact on postnatal survival and mice lived until old age. However, deficiency of E2f7 or E2f8 alone was sufficient to suppress polyploidization in the pancreas and associated with only a minor decrease in blood serum levels of glucose, insulin, amylase and lipase under 4 hours starvation condition compared to wildtype littermates. In mice with fewer pancreatic polyploid cells that were fed ad libitum, no major impact on hormones or enzymes levels was observed. In summary, we identified atypical E2fs to be essential for polyploidization in the pancreas and discovered that postnatal induced loss of both atypical E2fs in many organs is compatible with life until old age.

N,N-dimethylglycine differentially modulates psychotomimetic and antidepressant-like effects of ketamine in mice.

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Lin, Jen-Cheng; Chan, Ming-Huan; Lee, Mei-Yi; Chen, Yi-Chyan; Chen, Hwei-Hsien

2016-11-03

Ketamine, a dissociative anesthetic, produces rapid and sustained antidepressant effects at subanesthtic doses. However, it still inevitably induces psychotomimetic side effects. N,N-dimethylglycine (DMG) is a derivative of the amino acid glycine and is used as a dietary supplement. Recently, DMG has been found acting at glycine binding site of the N-methyl-d-aspartate receptor (NMDAR). As blockade of NMDARs is one of the main mechanisms responsible for the action of ketamine on central nervous system, DMG might modulate the behavioral responses to ketamine. The present study determined the effects of DMG on the ketamine-induced psychotomimetic, anesthetic and antidepressant-like effects in mice. DMG pretreatment reversed the ketamine-induced locomotor hyperactivity and impairment in the rotarod performance, novel location and novel object recognition tests, and prepulse inhibition. In addition, DMG alone exhibited antidepressant-like effects in the forced swim test and produced additive effects when combined with ketamine. However, DMG did not affect ketamine-induced anesthesia. These results reveal that DMG could antagonize ketamine's psychotomimetic effects, yet produce additive antidepressant-like effects with ketamine, suggesting that DMG might have antipsychotic potential and be suitable as an add-on therapy to ketamine for patients with treatment-resistant depression. Copyright © 2016 Elsevier Inc. All rights reserved.

Is the Risk of Preterm Birth and Low Birth Weight Affected by the Use of Antidepressant Agents during Pregnancy? A Population-Based Investigation.

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Anna Cantarutti

Full Text Available Untreated depression during pregnancy increases the risk of morbidity and mortality in the mother and child. Therefore, specific treatments are required for this population.The study aimed to investigating the effect of antidepressant medication used during pregnancy with reference to the risk of preterm birth (PTB and low birth weight (LBW.A population-based study was carried out with data provided by the healthcare utilization database of Lombardy, an Italian region with about ten million inhabitants. The study included 384,673 births from 2005 to 2010. Maternal use of antidepressants before and during pregnancy was investigated. Log-binomial regression was used to estimate the association between the use of antidepressants during pregnancy, compared to the non-use or use just before pregnancy, and the prevalence ratio of PTB and LBW.Women who used antidepressants during pregnancy had a 20% (95% CI: 10-40% increased prevalence of both PTB and LBW compared to those who never used antidepressants. There was no evidence that women who used antidepressants during pregnancy had a higher prevalence of the considered outcomes compared to women who used antidepressants before pregnancy, but stopped during pregnancy. Such findings were confirmed by considering separately the effects of SSRIs and other antidepressants together.Our findings suggest that depression in itself, rather than antidepressant medication, might be implicated in the causal pathway of PTB and LBW.

Stopping Antidepressants and Anxiolytics as Major Concerns Reported in Online Health Communities: A Text Mining Approach.

Science.gov (United States)

Abbe, Adeline; Falissard, Bruno

2017-10-23

Internet is a particularly dynamic way to quickly capture the perceptions of a population in real time. Complementary to traditional face-to-face communication, online social networks help patients to improve self-esteem and self-help. The aim of this study was to use text mining on material from an online forum exploring patients' concerns about treatment (antidepressants and anxiolytics). Concerns about treatment were collected from discussion titles in patients' online community related to antidepressants and anxiolytics. To examine the content of these titles automatically, we used text mining methods, such as word frequency in a document-term matrix and co-occurrence of words using a network analysis. It was thus possible to identify topics discussed on the forum. The forum included 2415 discussions on antidepressants and anxiolytics over a period of 3 years. After a preprocessing step, the text mining algorithm identified the 99 most frequently occurring words in titles, among which were escitalopram, withdrawal, antidepressant, venlafaxine, paroxetine, and effect. Patients' concerns were related to antidepressant withdrawal, the need to share experience about symptoms, effects, and questions on weight gain with some drugs. Patients' expression on the Internet is a potential additional resource in addressing patients' concerns about treatment. Patient profiles are close to that of patients treated in psychiatry. ©Adeline Abbe, Bruno Falissard. Originally published in JMIR Mental Health (http://mental.jmir.org), 23.10.2017.

[Consumption of antidepressants in Chile from 1992 to 2004].

Science.gov (United States)

Jirón, Marcela; Machado, Márcio; Ruiz, Inés

2008-09-01

Data from the Ministry of Health show that in Chile in 2004, 17% of the population had some form of depression, and mood disorders are the tenth cause of disability-adjusted life years (DALY) loss. To determine consumption of antidepressants (ADs) in Chile from 1992 to 2004. National sales data were obtained from the company IMS Health Chile and converted into defined daily doses (DDDs) per 1,000 inhabitants per day. Available ADs were classified in four pharmacological groups (i.e., serotonin-norepinephrine reuptake inhibitors, SNRLs; selective-serotonin reuptake inhibitors, SSRLs; tricyclic antidepressants, TCAs; and others). Total economic burden of ADs utilization and cost per DDDs were also calculated. Trends over time were analyzed using Pearson-R2. Total ADs consumption in Chile measured by DDDs per 1,000 inhabitants per day (DHD) increased linearly (y =0.901x + 1.9129; R2 =0.9296; p economic burden of ADs in Chile (total cost of DDDs consumed) increased from US$65.4 million in 2001 to US$74.6 million in 2004 (14% increase). Average cost per DDD of all AD increased linearly, however not significantly from US$ 0.94 in 2001 to US$ 1.04 in 2004 (y =0.0362x + 0.8784; R2 =0.7382; p =0,262). DDDs per 1,000 inhabitants per day increased linearly over 470% from 1992-2004. SSRLs were the most commonly consumed drugs in Chile. Future research should evaluate the cost-effectiveness of antidepressants in Chile, comparing the results with drug utilization, and determining if unnecessary expenditures have been paid out.

Suppressive immunoregulatory effects of three antidepressants via inhibition of the nuclear factor-κB activation assessed using primary macrophages of carp (Cyprinus carpio)

International Nuclear Information System (INIS)

Qiu, Wenhui; Wu, Minghong; Liu, Shuai; Chen, Bei; Pan, Chenyuan; Yang, Ming; Wang, Ke-Jian

2017-01-01

Antidepressants, having been applied for the treatment of major depressive disorder and other conditions for decades, are among the most commonly detected human pharmaceuticals in the aquatic environment. This study evaluated the immunotoxicity of acute exposure to environmentally relevant concentrations of amitriptyline, fluoxetine and mianserin using an in vitro primary macrophage model isolated from red common carp (Cyprinus carpio), and also explored their potential mechanisms of action. A potential suppressive immunoregulatory effect of antidepressant exposure was suggested based on the observed suppressive effects on oxidative stress parameters, bactericidal activity, NO production, and NO synthase activity, as well as pro-inflammatory cytokine gene expression, and a significant stimulatory effect on anti-inflammatory interleukin-10 and interferon cytokine gene expression and ATPase activities in macrophages after 6 h-exposure to three individual antidepressants and a combination thereof. Notably, we also found these effects were significantly associated with a corresponding decrease in nuclear factor-κB (NF-κB) activity after antidepressants exposure, and the NF-κB antagonist significantly restrained the effects of antidepressants on gene expression of cytokines, indicating that antidepressants could alter the response of various immune-associated components via the inhibition of NF-κB. Moreover, time-dependent lethal concentrations of three antidepressants on primary macrophages were firstly determined at mg/L levels, and the synergetic effects of antidepressant mixtures were suggested and in particular, for some parameters including total antioxidant capacity and cytokine genes expression, they could be significantly affected by antidepressants exposure at concentrations as low as 10 ng/L, which together thereby revealed the potential risk of antidepressants to aquatic life. - Highlights: • Three different antidepressants all have immunoregulatory

Suppressive immunoregulatory effects of three antidepressants via inhibition of the nuclear factor-κB activation assessed using primary macrophages of carp (Cyprinus carpio)

Energy Technology Data Exchange (ETDEWEB)

Qiu, Wenhui [School of Environmental and Chemical Engineering, Shanghai University, Shanghai 200444 (China); State Key Laboratory of Marine Environmental Science, Xiamen University, Xiamen, Fujian 361005 (China); School of Environmental Science & Engineering, Southern University of Science and Technology, Shenzhen, Guangdong 518055 (China); Wu, Minghong; Liu, Shuai [School of Environmental and Chemical Engineering, Shanghai University, Shanghai 200444 (China); Chen, Bei [State Key Laboratory of Marine Environmental Science, Xiamen University, Xiamen, Fujian 361005 (China); Pan, Chenyuan [School of Environmental and Chemical Engineering, Shanghai University, Shanghai 200444 (China); Yang, Ming, E-mail: mingyang@shu.edu.cn [School of Environmental and Chemical Engineering, Shanghai University, Shanghai 200444 (China); Wang, Ke-Jian, E-mail: wkjian@xmu.edu.cn [State Key Laboratory of Marine Environmental Science, Xiamen University, Xiamen, Fujian 361005 (China)

2017-05-01

Antidepressants, having been applied for the treatment of major depressive disorder and other conditions for decades, are among the most commonly detected human pharmaceuticals in the aquatic environment. This study evaluated the immunotoxicity of acute exposure to environmentally relevant concentrations of amitriptyline, fluoxetine and mianserin using an in vitro primary macrophage model isolated from red common carp (Cyprinus carpio), and also explored their potential mechanisms of action. A potential suppressive immunoregulatory effect of antidepressant exposure was suggested based on the observed suppressive effects on oxidative stress parameters, bactericidal activity, NO production, and NO synthase activity, as well as pro-inflammatory cytokine gene expression, and a significant stimulatory effect on anti-inflammatory interleukin-10 and interferon cytokine gene expression and ATPase activities in macrophages after 6 h-exposure to three individual antidepressants and a combination thereof. Notably, we also found these effects were significantly associated with a corresponding decrease in nuclear factor-κB (NF-κB) activity after antidepressants exposure, and the NF-κB antagonist significantly restrained the effects of antidepressants on gene expression of cytokines, indicating that antidepressants could alter the response of various immune-associated components via the inhibition of NF-κB. Moreover, time-dependent lethal concentrations of three antidepressants on primary macrophages were firstly determined at mg/L levels, and the synergetic effects of antidepressant mixtures were suggested and in particular, for some parameters including total antioxidant capacity and cytokine genes expression, they could be significantly affected by antidepressants exposure at concentrations as low as 10 ng/L, which together thereby revealed the potential risk of antidepressants to aquatic life. - Highlights: • Three different antidepressants all have immunoregulatory

Tramadol Pretreatment Enhances Ketamine-Induced Antidepressant Effects and Increases Mammalian Target of Rapamycin in Rat Hippocampus and Prefrontal Cortex

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Chun Yang

2012-01-01

Full Text Available Several lines of evidence have demonstrated that acute administration of ketamine elicits fast-acting antidepressant effects. Moreover, tramadol also has potential antidepressant effects. The aim of this study was to investigate the effects of pretreatment with tramadol on ketamine-induced antidepressant activity and was to determine the expression of mammalian target of rapamycin (mTOR in rat hippocampus and prefrontal cortex. Rats were intraperitoneally administrated with ketamine at the dose of 10 mg/kg or saline 1 h before the second episode of the forced swimming test (FST. Tramadol or saline was intraperitoneally pretreated 30 min before the former administration of ketamine or saline. The locomotor activity and the immobility time of FST were both measured. After that, rats were sacrificed to determine the expression of mTOR in hippocampus and prefrontal cortex. Tramadol at the dose of 5 mg/kg administrated alone did not elicit the antidepressant effects. More importantly, pretreatment with tramadol enhanced the ketamine-induced antidepressant effects and upregulated the expression of mTOR in rat hippocampus and prefrontal cortex. Pretreatment with tramadol enhances the ketamine-induced antidepressant effects, which is associated with the increased expression of mTOR in rat hippocampus and prefrontal cortex.

Does recent mania affect response to antidepressants in bipolar disorder? A re-analysis of STEP-BD data.

Science.gov (United States)

Mousavi, Zahra; Johnson, Sheri; Li, Descartes

2018-08-15

One previous study suggested that the presence of a manic episode before bipolar depression is related to worse response to antidepressants. To examine this effect in a larger sample, we used data from the large, multi-site STEP-BD study. We hypothesized that among persons treated with antidepressants for bipolar depression, manic or mixed episodes before depression onset (as compared to euthymia) would predict lower rate of recovery, more sustained depressive symptoms and higher rate of switching into mania/hypomania after antidepressant treatment of bipolar depression. 320 participants were available for analyses (140 male) diagnosed with bipolar I, bipolar II, cyclothymia, bipolar disorder not otherwise specified, or schizoaffective disorder bipolar subtype. Patients were randomly assigned to 3 treatment randomization strata (placebo, bupropion, and paroxetine) as adjuncts to mood stabilizers. Analyses were conducted to examine the effect of episode status before the depressive episode on the degree of change in depressive symptoms at 3 and 6 months, the likelihood of depression recovery and the likelihood of anti-depressant induced switching. Presence of a manic episode before depression in patients with bipolar disorder did not significantly predict response to antidepressants. The study was limited by a high rate of attrition, and consideration of only two antidepressant medications. Our findings are in agreement with other past studies suggesting that mania and depression may operate separately for those with bipolar disorder, with differential predictors of the onset and offset of mania versus depression. Future directions may consider vulnerability for these episodes separately. Copyright © 2018 Elsevier B.V. All rights reserved.

Evaluation of the antidepressant, anxiolytic and memory-improving efficacy of aripiprazole and fluoxetine in ethanol-treated rats.

Science.gov (United States)

Burda-Malarz, Kinga; Kus, Krzysztof; Ratajczak, Piotr; Czubak, Anna; Hardyk, Szymon; Nowakowska, Elżbieta

2014-07-01

Some study results indicate a positive effect of aripiprazole (ARI) on impaired cognitive functions caused by brain damage resulting from chronic EtOH abuse. However, other research shows that to manifest itself, an ARI antidepressant effect requires a combined therapy with another selective serotonin reuptake inhibitor antidepressant, namely, fluoxetine (FLX). The aim of this article was to assess antidepressant and anxiolytic effects of ARI as well as its effect on spatial memory in ethanol-treated (alcoholized) rats. On the basis of alcohol consumption pattern, groups of (1) ethanol-preferring rats, with mean ethanol intake above 50%, and (2) ethanol-nonpreferring rats (EtNPRs), with mean ethanol intake below 50% of total daily fluid intake, were formed. The group of EtNPRs was used for this study, subdivided further into three groups administered ARI, FLX and a combination of both, respectively. Behavioral tests such as Porsolt's forced swimming test, the Morris water maze test and the two-compartment exploratory test were employed. Behavioral test results demonstrated (1) no antidepressant effect of ARI in EtNPRs in subchronic treatment and (2) no procognitive effect of ARI and FLX in EtNPRs in combined single administration. Combined administration of both drugs led to an anxiogenic effect and spatial memory deterioration in study animals. ARI had no antidepressant effect and failed to improve spatial memory in rats. However, potential antidepressant, anxiolytic and procognitive properties of the drug resulting from its mechanism of action encourage further research aimed at developing a dose of both ARI and FLX that will prove such effects in alcoholized EtNPRs.

Genetic predictors of response to antidepressants in the GENDEP project

DEFF Research Database (Denmark)

Uher, Rudolf; Huezo-Diaz, Patricia; Perroud, Nader

2009-01-01

-reuptake-inhibiting and norepinephrine-reuptake-inhibiting antidepressants. A total of 116 single nucleotide polymorphisms in 10 candidate genes were genotyped in 760 adult patients with moderate-to-severe depression, treated with escitalopram (a serotonin reuptake inhibitor) or nortriptyline (a norepinephrine reuptake inhibitor......) for 12 weeks in an open-label part-randomized multicenter study. The effect of genetic variants on change in depressive symptoms was evaluated using mixed linear models. Several variants in a serotonin receptor gene (HTR2A) predicted response to escitalopram with one marker (rs9316233) explaining 1...... to the serotonin-reuptake-inhibiting escitalopram, genes encoding proteins in norepinephrine signaling influencing response to the norepinephrine-reuptake-inhibiting nortriptyline and a common pathway gene influencing response to both antidepressants. The single marker associations explained only a small...

[Suicide, antidepressant prescription and unemployment in Andalusia (Spain)].

Science.gov (United States)

Alameda-Palacios, José; Ruiz-Ramos, Miguel; García-Robredo, Beatriz

2014-01-01

To analyze the trend in suicide mortality in Andalusia from 1975 to 2012 and its relationship with unemployment and the use of antidepressants. Poisson's segmented regression models were used to estimate changes over time. The association between suicide and the factors examined was measured using Spearman's correlation coefficient. Suicide mortality patterns in men and women are rising. The largest increase was found in people aged from 15 to 44 years, with an annual percentage rate change of 1.21 (95%CI: 0.7-1.7) for men and 0.93 (95%CI: 0.4-1.4) for women. Mortality by suicide has increased in Andalusia since 1975 in all age and gender groups except for women aged 65 years or above. During the last few decades, an upward trend has been observed in young people and a stable or falling trend in the remaining population. Temporary variations in suicide rates are not associated with unemployment rates or with changes in antidepressant prescription. Copyright © 2013 SESPAS. Published by Elsevier Espana. All rights reserved.

The role of antidepressants in the management of inflammatory bowel disease (IBD): a short report on a clinical case-note audit.

Science.gov (United States)

Mikocka-Walus, Antonina A; Gordon, Andrea L; Stewart, Benjamin J; Andrews, Jane M

2012-02-01

This study sought to determine the frequency of use and types of antidepressants used in IBD patients and to collect data with respect to any effect of antidepressants on the course of IBD in a usual care setting. A case-note audit was conducted at an IBD Service in a public tertiary hospital. Included patients were those diagnosed with IBD by a gastroenterologist; and have had contact with the IBD Service in the last 6months. Descriptive statistics were used to summarise the data. Overall, 313 patients were eligible and 287 had complete data. Overall, 51 (17.8%) patients were currently taking antidepressants and 71 (24.7%) previously received antidepressants. Eighty-three (28.9%) patients had used an antidepressant at some time. In terms of disease activity while on antidepressants, the majority of patients had inactive disease but presented with what were thought by their clinicians to be functional symptoms. Antidepressants are commonly prescribed in IBD patients. In our cohort, they appear to be mostly used for functional symptoms. The current data do not allow us to judge whether they improve IBD disease activity. Targeted studies are needed to answer this question and to improve practice and patient outcomes. Copyright © 2011 Elsevier Inc. All rights reserved.

Atypical Rocky Mountain spotted fever with polyarticular arthritis.

Science.gov (United States)

Chaudhry, Muhammad A; Scofield, Robert Hal

2013-11-01

Rocky Mountain spotted fever (RMSF) is an acute, serious tick borne illness caused by Rickettsia rickettsi. Frequently, RMSF is manifested by headache, a typical rash and fever but atypical disease is common, making diagnosis difficult. Inflammatory arthritis as a manifestation is rare. The purpose of this study is to describe a patient with serologically proven RMSF who presented in an atypical manner with inflammatory arthritis of the small joints of the hands and to review the previously reported patients with rickettsial infection and inflammatory arthritis. An 18-year-old woman presented with a rash that began on the distal extremities and spread centrally, along with hand pain and swelling. She had tenderness and swelling of the metacarpophlangeal joints on examination in addition to an erythematosus macular rash and occasional fever. Acute and convalescent serology demonstrated R rickettsi infection. She was successfully treated with doxycycline. Inflammatory arthritis is a rare manifestation of RMSF or other rickettsial infection with 8 previously reported patients, only 1 of whom had RMSF. Physician must have a high index of suspicion for RMSF because of atypical presentations.

IPHAS A-TYPE STARS WITH MID-INFRARED EXCESSES IN SPITZER SURVEYS

International Nuclear Information System (INIS)

Hales, Antonio S.; Barlow, Michael J.; Drew, Janet E.; Unruh, Yvonne C.; Greimel, Robert; Irwin, Michael J.; Gonzalez-Solares, Eduardo

2009-01-01

We have identified 17 A-type stars in the Galactic Plane that have mid-infrared (mid-IR) excesses at 8 μm. From observed colors in the (r' - Hα) - (r' - i') plane, we first identified 23,050 early A-type main-sequence (MS) star candidates in the Isaac Newton Photometric H-Alpha Survey (IPHAS) point source database that are located in Spitzer Galactic Legacy Mid-Plane Survey Extraordinaire Galactic plane fields. Imposing the requirement that they be detected in all seven Two Micron All Sky Survey and Infrared Astronomical Satellite bands led to a sample of 2692 candidate A-type stars with fully sampled 0.6 to 8 μm spectral energy distributions (SEDs). Optical classification spectra of 18 of the IPHAS candidate A-type MS stars showed that all but one could be well fitted using MS A-type templates, with the other being an A-type supergiant. Out of the 2692 A-type candidates 17 (0.6%) were found to have 8 μm excesses above the expected photospheric values. Taking into account non-A-Type contamination estimates, the 8 μm excess fraction is adjusted to ∼0.7%. The distances to these sources range from 0.7 to 2.5 kpc. Only 10 out of the 17 excess stars had been covered by Spitzer MIPSGAL survey fields, of which five had detectable excesses at 24 μm. For sources with excesses detected in at least two mid-IR wavelength bands, blackbody fits to the excess SEDs yielded temperatures ranging from 270 to 650 K, and bolometric luminosity ratios L IR /L * from 2.2 x 10 -3 - 1.9 x 10 -2 , with a mean value of 7.9 x 10 -3 (these bolometric luminosities are lower limits as cold dust is not detectable by this survey). Both the presence of mid-IR excesses and the derived bolometric luminosity ratios are consistent with many of these systems being in the planet-building transition phase between the early protoplanetary disk phase and the later debris disk phase.

Preparation and cellular response of porous A-type carbonated hydroxyapatite nanoceramics

Energy Technology Data Exchange (ETDEWEB)

Li Bo, E-mail: Leewave@126.com [Institute of Biomaterials and Living Cell Imaging Technology, School of Metallurgy and Materials Engineering, Chongqing University of Science and Technology, Chongqing 401331 (China) and National Engineering Research Center for Biomaterials, Sichuan University, Chengdu 610064 (China); Liao Xiaoling [Institute of Biomaterials and Living Cell Imaging Technology, School of Metallurgy and Materials Engineering, Chongqing University of Science and Technology, Chongqing 401331 (China); Zheng Li [National Engineering Research Center for Biomaterials, Sichuan University, Chengdu 610064 (China); He Huawei [Department of Prosthodontics, Beijing Stomatological Hospital, Capital Medical University, Beijing, 100050 (China); Wang Hong [National Engineering Research Center for Biomaterials, Sichuan University, Chengdu 610064 (China); Fan Hongsong, E-mail: hsfan68@hotmail.com [National Engineering Research Center for Biomaterials, Sichuan University, Chengdu 610064 (China); Zhang Xingdong [National Engineering Research Center for Biomaterials, Sichuan University, Chengdu 610064 (China)

2012-05-01

Microwave sintering using the activated carbon as embedding material was applied in preparation of porous A-type carbonated hydroxyapatite ceramics with nano(nCHA) and submicron (mCHA) structure. By examining the linear shrinkages and the compressive strengths of samples at different temperatures, a suitable microwave sintering temperature was achieved. The microwave sintering method was successfully used to prepare A-type CHA with nano or submicron structure, and the mechanism of the formation of A-type carbonate groups was discussed also. Compared with the samples prepared by the conventional sintering method (mHA), the nCHA bioceramics synthesized by the microwave sintering approach had smaller grain size and more uniform microstructure, and showed a compressive strength similar to the conventional samples. In vitro dissolution test proved that nCHA exhibits better degradation property in comparison to pure HA. Rat osteoblasts were cultured with nCHA, mCHA and mHA to evaluate their biocompatibility, and nCHA showed significant enhancement of cells in attachment, proliferation and differentiation. In conclusion, carbonate groups can be easily introduced to HA crystal structure using the activated carbon as embedding material, and microwave sintering is an effective and simple method in preparing A-type CHA with a nanostructure. Results from this in vitro biological study suggest that porous A-type carbonated hydroxyapatite nanoceramics may be a much better candidate for clinical use in terms of bioactivity. - Highlights: Black-Right-Pointing-Pointer We prepared porous A-type carbonated hydroxyapatite nanoceramics with microwave sintering. Black-Right-Pointing-Pointer We examined physico-chemical characterization and osteoblast response. Black-Right-Pointing-Pointer The nanoceramics have a comparable compressive strength to samples with conventional sintering method. Black-Right-Pointing-Pointer The nanoceramics enhance degradation property, osteoblast

Conns' syndrome - atypical presentations

International Nuclear Information System (INIS)

Kumar, K V S Hari; Modi, K D; Jha, Sangeeta; Jha, Ratan

2009-01-01

Primary hyperaldosteronism (Conns' syndrome) commonly presents with a combination of clinical features of hypokalemia and hypertension. Atypical presentations like normotension, normokalemia and neurological ailments are described in few cases. We encountered two such cases, the first presenting with acute neurological complaint and second case having insignificant hypertension. Both the patients had a characteristic biochemical and imaging profile consistent with primary hyperaldosteronism and responded to surgical resection of adrenal adenoma. (author)

The anxieties of globalization: antidepressant sales and economic crisis in Argentina.

Science.gov (United States)

Lakoff, Andrew

2004-04-01

This paper describes the role of market research firms in shaping the actions of key players in the pharmaceutical arena. It focuses on strategies for marketing novel antidepressants (selective serotonin reuptake inhibitors, SSRIs) to doctors in Buenos Aires during the Argentine financial crisis of 2001, posing the question of whether increased antidepressant sales were due to the social situation or to promotional practices. This case demonstrates how 'pharmaceutical relations' - interactions between doctors and pharmaceutical companies - are structured by a gift economy whose effects are monitored through the sales numbers produced by database firms. It suggests that the use of these numbers takes on special importance given the distinctiveness of both the Argentine context and the antidepressant market. More generally, the case points to the interpretive flexibility of psychotropic medication. In the Argentine setting, doctors' prescription of SSRIs was dependent neither on a diagnosis of depression nor on a biological understanding of mental disorder. These drugs found a different means of entering the professionally mediated marketplace: doctors understood and used SSRIs as a treatment not for a lack of serotonin in the brain, but for the suffering caused by the social situation - the sense of insecurity and vulnerability that the economic and political crisis had wrought.

Association Between Serotonergic Antidepressant Use During Pregnancy and Autism Spectrum Disorder in Children.

Science.gov (United States)

Brown, Hilary K; Ray, Joel G; Wilton, Andrew S; Lunsky, Yona; Gomes, Tara; Vigod, Simone N

2017-04-18

Previous observations of a higher risk of child autism spectrum disorder with serotonergic antidepressant exposure during pregnancy may have been confounded. To evaluate the association between serotonergic antidepressant exposure during pregnancy and child autism spectrum disorder. Retrospective cohort study. Health administrative data sets were used to study children born to mothers who were receiving public prescription drug coverage during pregnancy in Ontario, Canada, from 2002-2010, reflecting 4.2% of births. Children were followed up until March 31, 2014. Serotonergic antidepressant exposure was defined as 2 or more consecutive maternal prescriptions for a selective serotonin or serotonin-norepinephrine reuptake inhibitor between conception and delivery. Child autism spectrum disorder identified after the age of 2 years. Exposure group differences were addressed by inverse probability of treatment weighting based on derived high-dimensional propensity scores (computerized algorithm used to select a large number of potential confounders) and by comparing exposed children with unexposed siblings. There were 35 906 singleton births at a mean gestational age of 38.7 weeks (50.4% were male, mean maternal age was 26.7 years, and mean duration of follow-up was 4.95 years). In the 2837 pregnancies (7.9%) exposed to antidepressants, 2.0% (95% CI, 1.6%-2.6%) of children were diagnosed with autism spectrum disorder. The incidence of autism spectrum disorder was 4.51 per 1000 person-years among children exposed to antidepressants vs 2.03 per 1000 person-years among unexposed children (between-group difference, 2.48 [95% CI, 2.33-2.62] per 1000 person-years; hazard ratio [HR], 2.16 [95% CI, 1.64-2.86]; adjusted HR, 1.59 [95% CI, 1.17-2.17]). After inverse probability of treatment weighting based on the high-dimensional propensity score, the association was not significant (HR, 1.61 [95% CI, 0.997-2.59]). The association was also not significant when exposed children

Kappa-opioid receptors mediate the antidepressant-like activity of hesperidin in the mouse forced swimming test.

Science.gov (United States)

Filho, Carlos B; Del Fabbro, Lucian; de Gomes, Marcelo G; Goes, André T R; Souza, Leandro C; Boeira, Silvana P; Jesse, Cristiano R

2013-01-05

The opioid system has been implicated as a contributing factor for major depression and is thought to play a role in the mechanism of action of antidepressants. This study investigated the involvement of the opioid system in the antidepressant-like effect of hesperidin in the mouse forced swimming test. Our results demonstrate that hesperidin (0.1, 0.3 and 1 mg/kg; intraperitoneal) decreased the immobility time in the forced swimming test without affecting locomotor activity in the open field test. The antidepressant-like effect of hesperidin (0.3 mg/kg) in the forced swimming test was prevented by pretreating mice with naloxone (1 mg/kg, a nonselective opioid receptor antagonist) and 2-(3,4-dichlorophenyl)-Nmethyl-N-[(1S)-1-(3-isothiocyanatophenyl)-2-(1-pyrrolidinyl)ethyl] acetamide (DIPPA (1 mg/kg), a selective κ-opioid receptor antagonist), but not with naloxone methiodide (1 mg/kg, a peripherally acting opioid receptor antagonist), naltrindole (3 mg/kg, a selective δ-opioid receptor antagonist), clocinnamox (1 mg/kg, a selective μ-opioid receptor antagonist) or caffeine (3 mg/kg, a nonselective adenosine receptor antagonist). In addition, a sub-effective dose of hesperidin (0.01 mg/kg) produced a synergistic antidepressant-like effect in the forced swimming test when combined with a sub-effective dose of morphine (1 mg/kg). The antidepressant-like effect of hesperidin in the forced swimming test on mice was dependent on its interaction with the κ-opioid receptor, but not with the δ-opioid, μ-opioid or adenosinergic receptors. Taken together, these results suggest that hesperidin possesses antidepressant-like properties and may be of interest as a therapeutic agent for the treatment of depressive disorders. Published by Elsevier B.V.

Atypical imaging of spinal tuberculosis: a case report and review of ...

African Journals Online (AJOL)

... is a rare imaging manifestation and diagnosis was confirmed by pathology after the surgery. Therefore atypical imaging is often appeared in clinical practice and it is meaningful and necessary for the diagnosis of atypical spinal tuberculosis combined with multiple organ tuberculosis. Pan African Medical Journal 2016; 24 ...

Antidepressant and antioxidant activities of Artemisia absinthium L ...

African Journals Online (AJOL)

STORAGESEVER

2009-12-15

Dec 15, 2009 ... Mora S, Millıan R, Lungenstrass H, Dııaz-Vıeliz G, Morıan JA, Herrera-. Ruiz M, Tortoriello J (2006). The hydroalcoholic extract of Salvia elegans induces anxiolytic- and antidepressant-like effects in rats. J. Ethnopharmacol. 106: 76-81. Morteza-Semnani K, Mahmoudi M, Riahi G (2007). Effects of essential.

Effect of cognitive therapy with antidepressant medications vs antidepressants alone on the rate of recovery in major depressive disorder a randomized clinical trial

NARCIS (Netherlands)

Hollon, S.D.; DeRubeis, R.J.; Fawcett, J.; Amsterdam, J.D.; Shelton, R.C.; Zajecka, J.; Young, P.R.; Gallop, R.

2014-01-01

IMPORTANCE Antidepressant medication (ADM) is efficacious in the treatment of depression, but not all patients achieve remission and fewer still achieve recovery with ADM alone. OBJECTIVE To determine the effects of combining cognitive therapy (CT) with ADM vs ADM alone on remission and recovery in

Endoscopic management of pancreatic pseudocysts at atypical locations.

Science.gov (United States)

Bhasin, Deepak Kumar; Rana, Surinder Singh; Nanda, Mohit; Chandail, Vijant Singh; Masoodi, Ibrahim; Kang, Mandeep; Kalra, Navin; Sinha, Saroj Kant; Nagi, Birinder; Singh, Kartar

2010-05-01

There is paucity of data on endoscopic management of pseudocysts at atypical locations. We evaluated the efficacy of endoscopic transpapillary nasopancreatic drain (NPD) placement in the management of pseudocysts of pancreas at atypical locations. Eleven patients with pseudocysts at atypical locations were treated with attempted endoscopic transpapillary nasopancreatic drainage. On endoscopic retrograde pancreatography (ERP), a 5-F NPD was placed across/near the site of duct disruption. Three patients each had mediastinal, intrahepatic, and intra/perisplenic pseudocysts and one patient each had renal and pelvic pseudocyst. Nine patients had chronic pancreatitis whereas two patients had acute pancreatitis. The size of the pseudocysts ranged from 2 to 15 cm. On ERP, the site of ductal disruption was in the body of pancreas in five patients (45.4%), and tail of pancreas in six patients (54.6%). All the patients had partial disruption of pancreatic duct. The NPD was successfully placed across the disruption in 10 of the 11 patients (90.9%) and pseudocysts resolved in 4-8 weeks. One of the patients developed fever, 5 days after the procedure, which was successfully treated by intravenous antibiotics. In another patient, NPD became blocked 12 days after the procedure and was successfully opened by aspiration. The NPD slipped out in one of the patient with splenic pseudocyst and was replaced with a stent. There was no recurrence of symptoms or pseudocysts during follow-up of 3-70 months. Pancreatic pseudocysts at atypical locations with ductal communication and partial ductal disruption that is bridged by NPD can also be effectively treated with endoscopic transpapillary NPD placement.

Investigating altered nitric oxide signalling as an up-stream mediator of the antidepressant action of ketamine

DEFF Research Database (Denmark)

Liebenberg, N.; Muller, H. K.; Elfving, B.

2012-01-01

Background and Aim: Stress-induced excessive glutamate transmission at N-methyl-D-aspartate (NMDA) receptors may underlie a major mechanism in the pathophysiology that leads to depression, while ketamine, an NMDA receptor antagonist, has been shown to induce a rapid antidepressant effect in depre......Background and Aim: Stress-induced excessive glutamate transmission at N-methyl-D-aspartate (NMDA) receptors may underlie a major mechanism in the pathophysiology that leads to depression, while ketamine, an NMDA receptor antagonist, has been shown to induce a rapid antidepressant effect...... in depressed patients following a single intravenous administration that is sustained for (plus or minus) 7 days. A number of downstream cellular mechanisms appear to mediate the antidepressant action of ketamine, and the majority of evidence point to a rapid activation of protein translation leading...... to and activated by NMDA receptors, while the uncoupling of the nNOS-NMDA receptor complex prevents NMDA-induced excitotoxicity. Thus, it is possible that the inhibition of nitric oxide (NO) signalling underlies a key upstream mechanism in the antidepressant action of ketamine. Methods: We used a genetic rat model...

Combined rasagiline and antidepressant use in Parkinson disease in the ADAGIO study: effects on nonmotor symptoms and tolerability.

Science.gov (United States)

Smith, Kara M; Eyal, Eli; Weintraub, Daniel

2015-01-01

Depression, cognitive impairment, and other nonmotor symptoms (NMSs) are common early in Parkinson disease (PD) and may be in part due to disease-related dopamine deficiency. Many patients with PD are treated with antidepressants for NMSs, and the effect of the combination of PD medications that enhance dopamine neurotransmission and antidepressants on NMSs has not been studied. We report the effects of the addition of a monoamine oxidase B inhibitor, rasagiline, to antidepressant treatment in PD. To evaluate the effect of rasagiline on depression, cognition, and other PD NMSs in patients taking an antidepressant in the Attenuation of Disease Progression With Azilect Given Once Daily (ADAGIO) study. The ADAGIO study was a double-blind, placebo-controlled, delayed-start trial of rasagiline in de novo PD. In this exploratory post hoc analysis, we analyzed patients taking an antidepressant during the 36-week phase 1 period, in which patients were randomized to rasagiline (1 or 2 mg/d) or placebo. We evaluated the change in NMSs in patients taking an antidepressant and rasagiline compared with those taking placebo. The NMSs were assessed by Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale Nonmotor Experiences of Daily Living, the original Unified Parkinson's Disease Rating Scale, and the Parkinson Fatigue Scale. A total of 191 of the 1174 patients (16.3%) were treated with antidepressants during phase 1 and provided efficacy data. Depression and cognition scores revealed significantly less worsening in the rasagiline group compared with the placebo group (differences in Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale item-adjusted means [SEs], -0.19 [0.10], P = .048, and -0.20 [0.05], P rasagiline group compared with placebo. There was a nonsignificant trend toward less worsening in apathy and no significant between-group differences in anxiety or sleep. The effect on

The relationship between tiredness prior to sleep deprivation and the antidepressant response to sleep deprivation in depression.

NARCIS (Netherlands)

Van den Burg, W.; Bouhuys, A.L; van den Hoofdakker, R.H

1995-01-01

Recently it was hypothesized that the antidepressant response to total sleep deprivation (SD) results from a disinhibition process induced by the increase of tiredness in the course of SD. In the present study, the role of tiredness in the antidepressant response to SD is further investigated,

The effects of drugs on human models of emotional processing: an account of antidepressant drug treatment.

Science.gov (United States)

Pringle, Abbie; Harmer, Catherine J

2015-12-01

Human models of emotional processing suggest that the direct effect of successful antidepressant drug treatment may be to modify biases in the processing of emotional information. Negative biases in emotional processing are documented in depression, and single or short-term dosing with conventional antidepressant drugs reverses these biases in depressed patients prior to any subjective change in mood. Antidepressant drug treatments also modulate emotional processing in healthy volunteers, which allows the consideration of the psychological effects of these drugs without the confound of changes in mood. As such, human models of emotional processing may prove to be useful for testing the efficacy of novel treatments and for matching treatments to individual patients or subgroups of patients.

The (Surprising) Impact of Televised Antidepressant Direct-to-Consumer Advertising on the Stigmatization of Mental Illness.

Science.gov (United States)

Rainone, Nicolette; Oodal, Reshma; Niederdeppe, Jeff

2018-04-01

This study tests the effect of pharmaceutical Direct-to-Consumer Advertising (DTCA) for antidepressants on perceived stigma surrounding mental disorders. We randomly assigned participants into one of three experimental conditions: antidepressant DTCA with portrayals of discrimination, cognitive separation, and stereotyping (DCSS), antidepressant DTCA without these representations, or a no-exposure control. Contrary to study hypotheses, participants who viewed ads containing portrayals of DCSS were significantly less likely to want to socially distance themselves from those with mental illnesses than those assigned to the no-exposure control condition, even when controlling for demographics and personal experience with mental illness. We discuss plausible explanations for the unexpected pattern of effects and resulting implications for future research on the topic.

The Effect of Sympathetic Antagonists on the Antidepressant Action ...

African Journals Online (AJOL)

Alprazolam is an anti-anxiety drug shown to be effective in the treatment of depression. In this study, the effect of sympathetic receptor antagonists on alprazolam–induced antidepressant action was studied using a mouse model of forced swimming behavioral despair. The interaction of three sympathetic receptor ...

Treatment with antidepressants and lithium is associated with increased risk of treatment with antiparkinson drugs: a pharmacoepidemiological study

DEFF Research Database (Denmark)

Brandt-Christensen, Anne Mette; Kvist, Tine Kajsa; Nielsen, F.M.

2006-01-01

OBJECTIVE: To estimate the risk for persons treated with antidepressants or lithium of subsequent treatment with antiparkinson drugs (APD). METHODS: The Danish national prescription database supplied data on all persons who received antidepressants, lithium, or antidiabetics (first control group......). A second control group was included comprising persons from the general population. Outcome was purchase of APD and the study period was 1995 to 1999. RESULTS: In total, 1 293 789 persons were included. The rate ratio of treatment with APD after treatment with antidepressants was 2.27 (95% CI 2.14 to 2.......42) for men and 1.50 (95% CI 1.43 to 1.58) for women. Figures for lithium were almost identical. CONCLUSION: Persons treated with antidepressants or lithium are at increased risk of subsequently treatment with APD, showing an association between anxiety/affective disorder and Parkinson's disease....

Antidepressant or Antipsychotic Overdose in the Intensive Care Unit - Identification of Patients at Risk

DEFF Research Database (Denmark)

Borg, Linda; Julkunen, Anna; Madsen, Kristian Rørbaek

2016-01-01

It is often advised that patients who have ingested an overdose of antidepressants (AD) or antipsychotics (AP) are monitored with continuous ECG for minimum of 12-24 hr. These patients are often observed in an ICU. Our aim was to identify the number of patients with AD and/or AP overdose without...... adverse signs at hospital admission that turned out to need intensive care treatment. The effect of the antidepressants overdose risk assessment (ADORA) system was evaluated in patients with antidepressant as well as antipsychotic overdose. Our hypothesis was that patients with low ADORA do not need...... intensive care treatment. This retrospective study was conducted in adult patients admitted to the ICU at Odense University Hospital after an overdose with AP and/or AD between 1 January 2009 and 1 September 2014. Patients with predefined adverse signs in the emergency department were excluded due...

Evaluation of Antidepressant-like Effect of Citrus Maxima Leaves in Animal Models of Depression.

Science.gov (United States)

Potdar, Vikram H; Kibile, Swati J

2011-09-01

This study planned to assess antidepressant like activity of aqueous extract from leaves of Citrus maxima Merr. (Rutaceae). Boiling was used for aqueous extraction. Acute toxicity study was performed in mice. Antidepressant activity was studied using locomotor activity test, modified forced swimming test (FST) and tail suspension test (TST). Three doses 100, 200 and 300 mg/kg of aqueous extract of leaves were selected for testing. Fluoxetine (20 mg/kg, i.p.) and imipramine (30 mg/kg, i.p.) were used as the standard drugs. Aqueous extract of Citrus maxima leaves significantly reduced immobility time in both TST and FST. In locomotor activity testing it showed psychostimulant effect. Extract increased the climbing behavior in FST, which is similar to effect observed with imipramine. The results of this study suggest that antidepressant like effect of Citrus maxima seems to be mediated by an increase in norepinephrine level in synapses.

Role of AC-cAMP-PKA Cascade in Antidepressant Action of Electroacupuncture Treatment in Rats

Directory of Open Access Journals (Sweden)

Jian-hua Liu

2012-01-01

Full Text Available Adenylyl cyclase (AC-cyclic adenosine monophosphate (cAMP-cAMP-dependent protein kinase A (PKA cascade is considered to be associated with the pathogenesis and treatment of depression. The present study was conducted to explore the role of the cAMP cascade in antidepressant action of electroacupuncture (EA treatment for chronic mild stress (CMS-induced depression model rats. The results showed that EA improved significantly behavior symptoms in depression and dysfunction of AC-cAMP-PKA signal transduction pathway induced by CMS, which was as effective as fluoxetine. Moreover, the antidepressant effects of EA rather than Fluoxetine were completely abolished by H89, a specific PKA inhibitor. Consequently, EA has a significant antidepressant treatment in CMS-induced depression model rats, and AC-cAMP-PKA signal transduction pathway is crucial for it.

Dopamine mediated antidepressant effect of Mucuna pruriens seeds in various experimental models of depression.

Science.gov (United States)

Rana, Digvijay G; Galani, Varsha J

2014-01-01

The effects of antidepressant treatments have traditionally been discussed primarily in terms of effects on noradrenergic and serotonergic systems. Multiple lines of investigation have also explored the role of dopaminergic systems in mental depression. Seed of Mucuna pruriens Linn. (DC) (Leguminoseae) is well-known with dopaminergic action and has several therapeutic applications in folk medicine in curing or managing a wide range of diseases including Parkinsonism. To elucidate the anti-depressent profile and possible dopaminergic modulating action of M. pruriens seeds in various experimental models of depression. In the present study, antidepressant effect of the hydroalcoholic extract of the M. pruriens seeds (MPE) (100 and 200 mg/kg, p.o.) was investigated in the Forced Swimming Test (FST), Tail Suspension Test (TST), and Chronic Unpredictable Mild Stress (CUMS) test in mice. Further, dopaminergic interaction of same doses of MPE in the FST and TST were checked by the administration of a haloperidol (0.1 mg/kg, i.p.) and bromocriptine (2 mg/kg, i.p.) on the 7(th) day of MPE treatment. Effect of MPE on locomotor activity was also checked using actophotometer. MPE produced a significant reduction of the immobility time in the FST and TST. Further, antidepressant action of MPE was significantly inhibited by haloperidol and potentiated by bromocriptine in the FST and TST. 21 days of MPE treatment produced protection in CUMS as indicated by a significant increase of sucrose intake of stressed mice. Locomotor activities of mice were not significantly changed after 1 h and 7(th) day of the MPE treatment. The results of this study indicate that hydroalcoholic extract of MPE have antidepressant action, which may be mediated by an interaction with the dopaminergic system.

Antidepressant sales and regional variations of suicide mortality in Germany

NARCIS (Netherlands)

Blüml, V; Helbich, M.; Mayr, M; Turnwald, R; Vyssoki, B; Lewitzka, U; Hartung, S; Plener, P; Fegert, J; Kapusta, N

2017-01-01

Suicides account for over one million deaths per year worldwide with depression among the most important risk factors. Epidemiological research into the relationship between antidepressant utilization and suicide mortality has shown heterogeneous and contradictory results. Different methodological

Genetic structure of typical and atypical populations of Candida albicans from Africa.

Science.gov (United States)

Forche, A; Schönian, G; Gräser, Y; Vilgalys, R; Mitchell, T G

1999-11-01

Atypical isolates of the pathogenic yeast Candida albicans have been reported with increasing frequency. To investigate the origin of a set of atypical isolates and their relationship to typical isolates, we employed a combination of molecular phylogenetic and population genetic analyses using rDNA sequencing, PCR fingerprinting, and analysis of co-dominant DNA nucleotide polymorphisms to characterize the population structure of one typical and two atypical populations of C. albicans from Angola and Madagascar. The extent of clonality and recombination was assessed in each population. The analyses revealed that the structure of all three populations of C. albicans was predominantly clonal but, as in previous studies, there was also evidence for recombination. Allele frequencies differed significantly between the typical and the atypical populations, suggesting very low levels of gene flow between them. However, allele frequencies were quite similar in the two atypical C. albicans populations, suggesting that they are closely related. Phylogenetic analysis of partial sequences encoding the nuclear 26S rDNA demonstrated that all three populations belong to a single monophyletic group, which includes the type strain of C. albicans. Copyright 1999 Academic Press.

Non-diabetic atypical necrobiosis lipoidica

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Mittal R

1994-01-01

Full Text Available One 8 year female child had asymptomatic, anaesthetic, hypohidrotic, atrophic, yellowish, waxy plaque on the front of left thigh since 2 months. No nerve thickening was observed clinically or histopathologically. Hyperkeratosis, follicular keratosis, epidermal atrophy, degeneration of collagen, mononuclear granulomas and perivascular mononuclear infiltrate confirmed the clinical diagnosis of atypical necrobiosis lipoidica.

Stereological estimation of nuclear volume in benign and atypical meningiomas

DEFF Research Database (Denmark)

Madsen, C; Schrøder, H D

1993-01-01

A stereological estimation of nuclear volume in benign and atypical meningiomas was made. The aim was to investigate whether this method could discriminate between these two meningeal neoplasms. The difference was significant and it was moreover seen that there was no overlap between the two groups....... The results demonstrate that atypical meningiomas can be distinguished from benign meningiomas by an objective stereological estimation of nuclear volume....

Beliefs of people taking antidepressants about the causes of their own depression.

Science.gov (United States)

Read, John; Cartwright, Claire; Gibson, Kerry; Shiels, Christopher; Magliano, Lorenza

2015-03-15

The beliefs of people receiving treatment about the causes of their own mental health problems are researched less often than the causal beliefs of the public, but have important implications for relationships with prescribers, treatment choices and recovery. An online survey on a range of beliefs about depression, and experiences with antidepressants, was completed by 1829 New Zealand adults prescribed anti-depressants in the preceding five years, 97.4% of whom proceeded to take antidepressants. Six of 17 beliefs about the causes of their own depression were endorsed by more than half the sample: chemical imbalance, family stress, work stress, heredity, relationship problems and distressing events in childhood. There were some marked differences in content, structure and level of conviction of beliefs about one׳s own depression and the sample׳s previously published beliefs about depression in general. There were also significant differences between the beliefs of demographic groupings. Regression analyses revealed that self-reported effectiveness of the antidepressants was positively associated with bio-genetic causal beliefs. The quality of the relationship with the prescribing doctor was positively related to a belief in chemical imbalance as a cause and negatively related to a belief in unemployment as a cause. The convenience sample may have been biased towards a favourable view of bio-genetic explanations, since 83% reported that the medication reduced their depression. People experiencing depression hold complex, multifactorial and idiosyncratic sets of beliefs about the causes of their own depression, apparently based at least in part on their own life experiences and circumstances. Exploring those beliefs may enhance the doctor-patient relationship and selection of appropriate treatment modality. Copyright © 2014 Elsevier B.V. All rights reserved.

R-ketamine: a rapid-onset and sustained antidepressant without psychotomimetic side effects

Science.gov (United States)

Yang, C; Shirayama, Y; Zhang, J-c; Ren, Q; Yao, W; Ma, M; Dong, C; Hashimoto, K

2015-01-01

Although the efficacy of racemate ketamine, a rapid onset and sustained antidepressant, for patients with treatment-resistant depression was a serendipitous finding, clinical use of ketamine is limited, due to psychotomimetic side effects and abuse liability. Behavioral and side-effect evaluation tests were applied to compare the two stereoisomers of ketamine. To elucidate their potential therapeutic mechanisms, we examined the effects of these stereoisomers on brain-derived neurotrophic factor (BDNF)–TrkB signaling, and synaptogenesis in selected brain regions. In the social defeat stress and learned helplessness models of depression, R-ketamine showed a greater potency and longer-lasting antidepressant effect than S-ketamine (esketamine). Furthermore, R-ketamine induced a more potent beneficial effect on decreased dendritic spine density, BDNF–TrkB signaling and synaptogenesis in the prefrontal cortex (PFC), CA3 and dentate gyrus (DG) of the hippocampus from depressed mice compared with S-ketamine. However, neither stereoisomer affected these alterations in the nucleus accumbens of depressed mice. In behavioral tests for side effects, S-ketamine, but not R-ketamine, precipitated behavioral abnormalities, such as hyperlocomotion, prepulse inhibition deficits and rewarding effects. In addition, a single dose of S-ketamine, but not R-ketamine, caused a loss of parvalbumin (PV)-positive cells in the prelimbic region of the medial PFC and DG. These findings suggest that, unlike S-ketamine, R-ketamine can elicit a sustained antidepressant effect, mediated by increased BDNF–TrkB signaling and synaptogenesis in the PFC, DG and CA3. R-ketamine appears to be a potent, long-lasting and safe antidepressant, relative to S-ketamine, as R-ketamine appears to be free of psychotomimetic side effects and abuse liability. PMID:26327690

Atypical Manifestation of Vestibular Schwannoma

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Webster, Guilherme

2013-09-01

Full Text Available Introduction: Vestibular schwannoma (also known as acoustic neuroma is a benign tumor whose cells are derived from Schwann sheaths, which commonly occurs from the vestibular portion of the eighth cranial nerve. Furthermore, vestibular schwannomas account for ∼8% of intracranial tumors in adults and 80 to 90% of tumors of the cerebellopontine angle. Its symptoms are varied, but what stands out most is a unilateral sensorineural hearing loss, with a low index of speech recognition. Objective: Describe an atypical manifestation of vestibular schwannoma. Case Report: The 46-year-old woman had vertigo and binaural hearing loss and fullness, with ear, nose, and throat examination suggestive of cochlear injury. After 6 months, the patient developed worsening of symptoms and onset of right unilateral tinnitus. In further exams the signs of cochlear damage remained, except for the vestibular test (hyporeflexia. Magnetic resonance imaging showed an expansive lesion in the right cerebellopontine angle. Discussion: This report warns about the atypical manifestations of vestibular schwannoma, which must always be remembered in investigating and diagnosing hearing loss.

Atypical meningococcal meningitis with rashless presentation：A case report

Institute of Scientific and Technical Information of China (English)

Sunita; Singh Manpreet; Kapoor Dheeraj

2012-01-01

Meningococcal disease is the major health problem in developing world. The clinical presentation is varied, ranging from transient fever and bacteraemia to fulminant disease with death ensuing within hours of the onset of clinical symptoms. The classical clinical manifestations of meningococcal disease have been well described, but atypical presentations if unrecognized, may lead to a delay in treatment and fatal outcome. We here report a case presented with atypical presentation of meningococcal meningitis without classical rash, which was diagnosed and managed successfully.

Atypical presentation of macrophagic myofasciitis 10 years post vaccination.

LENUS (Irish Health Repository)

Ryan, Aisling M

2012-02-03

Macrophagic myofasciitis (MMF) is an uncommon inflammatory disorder of muscle believed to be due to persistence of vaccine-derived aluminium hydroxide at the site of injection. The condition is characterised by diffuse myalgias, arthralgia and fatigue. We describe a patient with histologically confirmed MMF whose presentation was atypical with left chest and upper limb pain beginning more than 10 years post vaccination. Treatment with steroids led to symptomatic improvement. Although rare, clinicians should consider MMF in cases of atypical myalgia.

Antidepressant-like effects of Tagetes lucida Cav. in the forced swimming test.

Science.gov (United States)

Guadarrama-Cruz, G; Alarcon-Aguilar, F J; Lezama-Velasco, R; Vazquez-Palacios, G; Bonilla-Jaime, H

2008-11-20

Tagetes lucida (Asteraceae), has been referred in Mexican traditional medicine for the treatment of different central nervous system (CNS) diseases, mainly depression. Nevertheless, the available scientific information about this species is scarce and there are no reports related to its possible effect on the CNS. In this work, the antidepressant-like effect of extract of Tagetes lucida was evaluated in rats, as well as its potential adverse effects on male sexual behavior (MSB). Antidepressant activity was studied using forced swimming test (FST), motor activity in the open-field test and on MSB in sexually experienced male. The aqueous extract of Tagetes lucida in doses of 5, 10, 50, 100 and 200mg/(kgday)(-1) were administered orally for 14 consecutive days and evaluated on day 14, 2h after the last dose treatment. Fluoxetine (10mg/(kgday)(-1), p.o.) was used as the control positive. The aqueous extract (10, 50, 100mg/(kgday)(-1)) significantly reduced immobility and increased swimming without affecting climbing behavior in the FST. These same doses were not able to modify neither the motor activity nor the MSB. These data indicate that the extract of Tagetes lucida possesses antidepressant-like properties in rats.

Synthesis and Antidepressant Activity of Some New 5-(1H-Indol-3-yl-3-(substituted aryl-4,5-dihydroisoxazoline Derivatives

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Pravin O. Patil

2013-01-01

Full Text Available The present study refers to the synthesis of new antidepressant candidates using the indole scaffold. In an attempt to identify potential lead antidepressant agents, a number of indole molecules, incorporating isoxazoline, were synthesized by microwave-assisted synthesis. The antidepressant activity of the synthesized compounds (3a–3n was evaluated by forced swim test in mice and their locomotor activity was assessed using actophotometry. The present paper showed significant antidepressant activity for all compounds of the series and no significant change in locomotor activity of mice. Compounds 3d and 3j were found to be potent molecules of this series, when compared with the reference drugs imipramine and fluoxetine. It clearly demonstrated that replacement of aromatic core by appropriate heterocycles such as pyridine and pyrrole on the 5-(1H-Indol-3-yl-3-(Phenyl-4,5-dihydroisoxazoline (3a would generate more potent derivatives. Thus, these compounds can serve as potential leads for further antidepressant studies.

Self-limiting atypical antipsychotics-induced edema: Clinical cases and systematic review

OpenAIRE

Musa Usman Umar; Aminu Taura Abdullahi

2016-01-01

A number of atypical antipsychotics have been associated with peripheral edema. The exact cause is not known. We report two cases of olanzapine-induced edema and a brief review of atypical antipsychotic-induced edema, possible risk factors, etiology, and clinical features. The recommendation is given on different methods of managing this side effect.

Self-limiting Atypical Antipsychotics-induced Edema: Clinical Cases and Systematic Review.

Science.gov (United States)

Umar, Musa Usman; Abdullahi, Aminu Taura

2016-01-01

A number of atypical antipsychotics have been associated with peripheral edema. The exact cause is not known. We report two cases of olanzapine-induced edema and a brief review of atypical antipsychotic-induced edema, possible risk factors, etiology, and clinical features. The recommendation is given on different methods of managing this side effect.

Summary of the comparative effectiveness review on off-label use of atypical antipsychotics.

Science.gov (United States)

Maher, Alicia R; Theodore, George

2012-06-01

Conventional and atypical antipsychotic medications are approved by the FDA for treatment of schizophrenia and bipolar disorder. Over many decades, the widespread use of conventional antipsychotics produced various side effects requiring additional medications, such as the atypical antipsychotics. Beginning in 2006, 9 atypical antipsychotic drugs have been approved by the FDA for indications that were previously off-label uses: aripiprazole (as augmentation for major depressive disorder [MDD] and for autism spectrum disorders), asenapine, clozapine, iloperidone, olanzapine (in combination with fluoxetine for MDD and bipolar depression), paliperidone, quetiapine (quetiapine and quetiapine XR [extended release] as monotherapy in bipolar depression and quetiapine XR as augmentation for MDD), risperidone (for autism spectrum disorders), and ziprasidone. In 2006, the Agency for Healthcare Research and Quality (AHRQ) published a systematic review on the comparative effectiveness of off-label uses of atypical antipsychotics. Since that time, numerous studies have been published evaluating these therapies in various new off-label uses; new or increased adverse effects have been observed with off-label uses; new atypical antipsychotics have been approved; and previously off-label uses have been approved for some atypical antipsychotics. Hence, AHRQ published an updated review in September 2011 that summarized the benefits and harms of atypical antipsychotics in the treatment of attention-deficit hyperactivity disorder/attention deficit disorder (ADHD), anxiety, behavioral disturbances of dementia and severe geriatric agitation, depression, eating disorders, insomnia, obsessive-compulsive disorder (OCD), personality disorder, post-traumatic stress disorder (PTSD), substance use and dependence disorders, and Tourette's syndrome. The new report also investigated topics for which data in the previous report were found to be insufficient to make conclusions, including

Rapid Antidepressant Activity of Ethanol Extract of Gardenia jasminoides Ellis Is Associated with Upregulation of BDNF Expression in the Hippocampus

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Hailou Zhang

2015-01-01

Full Text Available Ethanol extract of Yueju pill, a Traditional Chinese Medicine herbal formula widely used to treat mood disorders, demonstrates rapid antidepressant effects similar to ketamine, likely via instant enhancement of brain-derived neurotrophic factor (BDNF expression in the hippocampus. Here we investigated ethanol extracts of the constituent herbs of Yueju responsible for rapid antidepressant effects. Screening with tail suspension test in Kunming mice at 24 hours after a single administration of five individual constituent herbs of Yueju, we found that only Gardenia jasminoides Ellis (GJ showed a significant effect. The antidepressant response started at 2 hours after GJ administration. Similar to Yueju and ketamine, a single administration of GJ significantly reduced the number of escape failures in the learned helplessness test. Furthermore, GJ decreased latency of food consumption in the novelty suppressed-feeding test. Additionally, starting from 2 hours and continuing for over 20 hours after GJ administration, BDNF expression in the hippocampus was upregulated, temporally linked with the antidepressant response. These findings suggest that GJ has rapid antidepressant effects, which are associated with the elevated expression of BDNF in the hippocampus. In Yueju formula, Yue represents GJ, as thus our study demonstrates the primary role of GJ in rapid antidepressant efficacy of Yueju.

Pharmacogenetics of antidepressant drugs: State of the art and clinical implementation - recommendations from the French National Network of Pharmacogenetics.

Science.gov (United States)

Quaranta, Sylvie; Dupouey, Julien; Colle, Romain; Verstuyft, Céline

2017-04-01

Tailoring antidepressant drug therapy to each individual patient is a complex process because these drugs have adverse effects leading to discontinuation. Pharmacogenetics may provide useful information in routine practice for optimizing antidepressant treatment by helping limit toxic effects while maintaining efficacy. This review presents the usefulness of pharmacogenetic tests for P450 cytochromes CYP2C19 and CYP2D6 in psychiatric patients taking antidepressants. Depending on the level of evidence, the French National Network of Pharmacogenetics (RNPGx) has issued recommendations stating that pharmacogenetic tests for CYP2D6 and CYP2C19 genes are potentially useful in psychiatric patients treated with antidepressant drugs. Copyright © 2017 Société française de pharmacologie et de thérapeutique. Published by Elsevier Masson SAS. All rights reserved.

Self-limiting Atypical Antipsychotics-induced Edema: Clinical Cases and Systematic Review

Science.gov (United States)

Umar, Musa Usman; Abdullahi, Aminu Taura

2016-01-01

A number of atypical antipsychotics have been associated with peripheral edema. The exact cause is not known. We report two cases of olanzapine-induced edema and a brief review of atypical antipsychotic-induced edema, possible risk factors, etiology, and clinical features. The recommendation is given on different methods of managing this side effect. PMID:27335511

The folic acid combined with 17-β estradiol produces antidepressant-like actions in ovariectomized rats forced to swim.

Science.gov (United States)

Molina-Hernández, Miguel; Téllez-Alcántara, N Patricia; Olivera-López, Jorge I; Jaramillo, M Teresa

2011-01-15

Folic acid or 17-β estradiol produces antidepressant effects, either alone or combined with several antidepressants. However, the antidepressant-like actions of folic acid combined with 17-β estradiol in the forced swimming test (FST) have not been tested before. Thus, in the present study, ovariectomized female rats received folic acid (5.0 nmol/i.c.v., Pfluoxetine (20.0mg/kg, Pswimming behavior when they were tested in the FST. Combination of subthreshold doses of folic acid (2.5 nmol/i.c.v.; or 25.0mg/kg, p.o.) with subthreshold doses of 17-β estradiol (5.0 μg/rat, Pfluoxetine (15.0mg/kg, Pfluoxetine in the FST reduced immobility in the FST. These antidepressant-like actions probably were due to modifications of the serotonergic system since swimming behavior was increased and these effects were cancelled by ketanserin. Copyright © 2010 Elsevier Inc. All rights reserved.

Antidepressants and the risk of hyponatremia

DEFF Research Database (Denmark)

Leth-Møller, Katja Biering; Hansen, Annette Højmann; Torstensson, Maia

2016-01-01

for the association with hyponatremia in the first p-sodium measured after initiation of treatment were for citalopram 7.8 (CI 7.42 to 8.20); clomipramine 4.93 (CI 2.72 to 8.94); duloxetine 2.05 (CI 1.44 to 292); venlafaxine 2.90 (CI 2.43 to 3.46); mirtazapine 2.95 (CI 2.71 to 3.21); and mianserin 0.90 (CI 0.71 to 1.......14). CONCLUSIONS: All antidepressants except mianserin are associated with hyponatremia. The association is strongest with citalopram and lowest with duloxetine, venlafaxine and mirtazapine....

Sex-specific antidepressant effects of dietary creatine with and without sub-acute fluoxetine in rats

Science.gov (United States)

Allen, Patricia J.; D'Anci, Kristen E.; Kanarek, Robin B.; Renshaw, Perry F.

2013-01-01

The potential role of metabolic impairments in the pathophysiology of depression is motivating researchers to evaluate the treatment efficacy of creatine, a naturally occurring energetic and neuroprotective compound found in brain and muscle tissues. Growing evidence is demonstrating the benefit of oral creatine supplements for reducing depressive symptoms in humans and animals. A novel question is whether dietary creatine, when combined with antidepressant drug therapy, would be more effective than either compound alone. To answer this question, four studies were conducted to investigate the behavioral effects of combined creatine and low-dose fluoxetine treatment using the forced swim test in male and female rats. Sprague-Dawley rats were fed powdered rodent chow supplemented with 0%, 2% or 4% w/w creatine monohydrate for 5 weeks. Rats were injected with fluoxetine (5.0 or 10.0 mg/kg) or saline according to a sub-acute dosing schedule. Female rats maintained on a 4% creatine diet displayed antidepressant-like effects compared to non-supplemented females prior to fluoxetine treatment. In contrast, creatine did not alter behavior reliably in males. Following drug treatment and a second forced swim trial, the antidepressant-like profile of creatine remained significant only in females co-administered 5.0 mg/kg fluoxetine. Moreover, in females only, supplementation with 4% creatine produced a more robust antidepressant-like behavioral profile compared to either dose of fluoxetine alone. Estrous cycle data indicated that ovarian hormones influenced the antidepressant-like effects of creatine. Addressing the issue of sex differences in response to treatment may affect our understanding of creatine, its relationship with depressive behavior, and may lead to sex-specific therapeutic strategies. PMID:22429992

Synthesis, potential anticonvulsant and antidepressant effects of 2-(5-methyl-2,3-dioxoindolin-1-ylacetamide derivatives

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Xinghua Zhen

2015-07-01

Full Text Available A new series of 2-(5-methyl-2,3-dioxoindolin-1-ylacetamide derivatives were synthesized and evaluated for their anticonvulsive activity in a pentylenetetrazole (PTZ-evoked convulsion model and antidepressant activity in the forced swimming test (FST model. Eleven synthesized compounds were found to be protective against PTZ-induced seizure and showed the anticonvulsant activity. In addition, four of the synthesized compounds (4l, 4m, 4p and 4q showed potent antidepressant-like activity. Among these compounds, compound 4l was found to have the most potent antidepressant-like activity, and significantly reduced the duration of immobility time at 100 mg/kg dose level when compared to the vehicle control, which is similar to the reference drug fluoxetine.

Antidepressant Potentials of Components from Trichilia monadelpha (Thonn. J.J. de Wilde in Murine Models

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Kennedy Kwami Edem Kukuia

2018-01-01

Full Text Available Trichilia monadelpha is a common medicinal plant used traditionally in treating central nervous system conditions such as epilepsy, depression, pain, and psychosis. In this study, the antidepressant-like effect of crude extracts of the stem bark of T. monadelpha was investigated using two classical murine models, forced swimming test (FST and tail suspension test (TST. The extracts, petroleum ether, ethyl acetate, and hydroethanolic extracts (30–300 mg/kg, p.o., standard drug (imipramine; fluoxetine, 3–30 mg/kg, p.o., and saline (vehicle were given to mice one hour prior to the acute study. In a separate experiment the components (flavonoids, saponins, alkaloids, tannins, and terpenoids; 30–300 mg/kg, p.o. from the most efficacious extract fraction were screened to ascertain which components possessed the antidepressant effect. All the extracts and components significantly induced a decline in immobility in the FST and TST, indicative of an antidepressant-like activity. The extracts and some components showed increase in swimming and climbing in the FST as well as a significant enhancement in swinging and/or curling scores in the TST, suggesting a possible involvement of monoaminergic and/or opioidergic activity. This study reveals the antidepressant-like potential of the stem bark extracts and components of T. monadelpha.

Ten years after the FDA black box warning for antidepressant drugs: a critical narrative review

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Juan Carlos Martínez-Aguayo

2016-06-01

Full Text Available ABSTRACT Background The United States Food and Drug Administration (FDA has warned about the increased suicidality risk associated with the use of selective serotonin reuptake inhibitors (SSRI and venlafaxine in children and adolescents. Objectives To critically appraise the available evidence supporting the FDA Black box warning concerning to the use of antidepressants in child and adolescents. Methods A critical review of articles in Medline/PubMed and SciELO databases regarding the FDA Black box warning for antidepressants, and the impact of FDA warnings on antidepressant prescriptions and suicide rates. Results The warning was based on surveys that did not report either cases of suicide nor a significant difference supporting an increased suicidality rate. The concept was defined in an ambiguous way and there is currently more available evidence to support such definition. The use of SSRI and venlafaxine has been associated to lower suicidality rates, but the prescription fall due to the warning increased suicide rates. Discussion Suicidality is an inherent feature of depressive disorders so it would be desirable to consider how much of the phenomenon may be attributed to antidepressants per se. It would be appropriate to consider that suicide rates might increase also as a consequence of the warning.

Antidepressant Effects of (+)-MK-801 and (-)-MK-801 in the Social Defeat Stress Model

Science.gov (United States)

Yang, Bangkun; Ren, Qian; Ma, Min; Chen, Qian-Xue

2016-01-01

Background: Current data on antidepressant action of the N-methyl-D-aspartate receptor antagonist, (+)-MK-801, is inconsistent. This study was conducted to examine the effects of (+)-MK-801 and its less potent stereoisomer, (-)-MK-801, in the social defeat stress model of depression. Methods: The antidepressant effects of (+)-MK-801 (0.1mg/kg) and (-)-MK-801 (0.1mg/kg) in the social defeat stress model were examined. Results: In the tail suspension and forced swimming tests, both stereoisomers significantly attenuated increased immobility time in susceptible mice. In the sucrose preference test, (+)-MK-801, but not (-)-MK-801, significantly enhanced reduced sucrose consumption 2 or 4 days after a single dose. However, no antianhedonia effects were detected 7 days after a single dose of either stereoisomer. Conclusions: Both stereoisomers of MK-801 induced rapid antidepressant effects in the social defeat stress model, although neither produced a long-lasting effect (7 days). PMID:27608811

The association of antidepressant drug usage with cognitive impairment or dementia, including Alzheimer disease: A systematic review and meta‐analysis

Science.gov (United States)

Moraros, John; Nwankwo, Chijioke; Patten, Scott B.

2016-01-01

1 Objective To determine if antidepressant drug usage is associated with cognitive impairment or dementia, including Alzheimer disease (AD). 2 Method We conducted a systematic search of Medline, PubMed, PsycINFO, Web of Science, Embase, CINAHL, and the Cochrane Library. An initial screen by abstracts and titles was performed, and relevant full articles were then reviewed and assessed for their methodologic quality. Crude effect estimates were extracted from the included articles and a pooled estimate was obtained using a random effects model. 3 Results Five articles were selected from an initial pool of 4,123 articles. Use of antidepressant drugs was associated with a significant twofold increase in the odds of some form of cognitive impairment or dementia (OR = 2.17). Age was identified as a likely modifier of the association between antidepressant use and some form of cognitive impairment or AD/dementia. Studies that included participants with an average age equal to or greater than 65 years showed an increased odds of some form of cognitive impairment with antidepressant drug usage (OR = 1.65), whereas those with participants less than age 65 revealed an even stronger association (OR = 3.25). 4 Conclusions Antidepressant drug usage is associated with AD/dementia and this is particularly evident if usage begins before age 65. This association may arise due to confounding by depression or depression severity. However, biological mechanisms potentially linking antidepressant exposure to dementia have been described, so an etiological effect of antidepressants is possible. With this confirmation that an association exists, clarification of underlying etiologic pathways requires urgent attention. PMID:28029715

A critical analysis of the new equal pay provisions relating to atypical ...

African Journals Online (AJOL)

Keywords: Equal pay; Labour Relations Act; equal pay for atypical employees; atypical employment; sections 198A-198D of the Labour Relations Act; Agency Workers Regulations 2010; Fixed-term Employees (Prevention of Less Favourable Treatment) Regulations 2002; Part-time Workers (Prevention of Less Favourable ...

Use of atypical antipsychotics in nursing homes and pharmaceutical marketing.

Science.gov (United States)

Pimentel, Camilla B; Donovan, Jennifer L; Field, Terry S; Gurwitz, Jerry H; Harrold, Leslie R; Kanaan, Abir O; Lemay, Celeste A; Mazor, Kathleen M; Tjia, Jennifer; Briesacher, Becky A

2015-02-01

To describe the current extent and type of pharmaceutical marketing in nursing homes (NHs) in one state and to provide preliminary evidence for the potential influence of pharmaceutical marketing on the use of atypical antipsychotics in NHs. Nested mixed-methods, cross-sectional study of NHs in a cluster randomized trial. Forty-one NHs in Connecticut. NH administrators, directors of nursing, and medical directors (n = 93, response rate 75.6%). Quantitative data, including prescription drug dispensing data (September 2009-August 2010) linked with Nursing Home Compare data (April 2011), were used to determine facility-level prevalence of atypical antipsychotic use, facility-level characteristics, NH staffing, and NH quality. Qualitative data, including semistructured interviews and surveys of NH leaders conducted in the first quarter of 2011, were used to determine encounters with pharmaceutical marketing. Leadership at 46.3% of NHs (n = 19) reported pharmaceutical marketing encounters, consisting of educational training, written and Internet-based materials, and sponsored training. No association was detected between level of atypical antipsychotic prescribing and reports of any pharmaceutical marketing by at least one NH leader. NH leaders frequently encounter pharmaceutical marketing through a variety of ways, although the impact on atypical antipsychotic prescribing is unclear. © 2015, Copyright the Authors Journal compilation © 2015, The American Geriatrics Society.