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

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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

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

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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.

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.

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 ( ...

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.

Physiological Bases of Bulimia, and Antidepressant Treatment.

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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…

Race, Genetic Ancestry and Response to Antidepressant Treatment for Major Depression

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Murphy, Eleanor; Hou, Liping; Maher, Brion S; Woldehawariat, Girma; Kassem, Layla; Akula, Nirmala; Laje, Gonzalo; McMahon, Francis J

2013-01-01

The Sequenced Treatment Alternatives to Relieve Depression (STAR*D) Study revealed poorer antidepressant treatment response among black compared with white participants. This racial disparity persisted even after socioeconomic and baseline clinical factors were taken into account. Some studies have suggested genetic contributions to this disparity, but none have attempted to disentangle race and genetic ancestry. Here we used genome-wide single-nucleotide polymorphism (SNP) data to examine independent contributions of race and genetic ancestry to citalopram response. Secondary data analyses included 1877 STAR*D participants who completed an average of 10 weeks of citalopram treatment and provided DNA samples. Participants reported their race as White (n=1464), black (n=299) or other/mixed (n=114). Genetic ancestry was estimated by multidimensional scaling (MDS) analyses of about 500 000 SNPs. Ancestry proportions were estimated by STRUCTURE. Structural equation modeling was used to examine the direct and indirect effects of observed and latent predictors of response, defined as change in the Quick Inventory of Depressive Symptomatology (QIDS) score from baseline to exit. Socioeconomic and baseline clinical factors, race, and anxiety significantly predicted response, as previously reported. However, direct effects of race disappeared in all models that included genetic ancestry. Genetic African ancestry predicted lower treatment response in all models. Although socioeconomic and baseline clinical factors drive racial differences in antidepressant response, genetic ancestry, rather than self-reported race, explains a significant fraction of the residual differences. Larger samples would be needed to identify the specific genetic mechanisms that may be involved, but these findings underscore the importance of including more African-American patients in drug trials. PMID:23827886

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...

Antidepressant treatment outcomes of psychogenic movement disorder.

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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.

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

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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...

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

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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-

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

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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.

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

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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.

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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.

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.

Mind the Gap: Gaps in Antidepressant Treatment, Treatment Adjustments, and Outcomes among Patients in Routine HIV Care in a Multisite U.S. Clinical Cohort.

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Rushina Cholera

Full Text Available Depression affects 20-30% of HIV-infected patients and is associated with worse HIV outcomes. Although effective depression treatment is available, depression is largely untreated or undertreated in this population.We quantified gaps in antidepressant treatment, treatment adjustments, and outcomes among US patients in routine HIV care in the nationally distributed CNICS observational clinical cohort. This cohort combines detailed clinical data with regular, self-reported depressive severity assessments (Patient Health Questionnaire-9, PHQ-9. We considered whether participants with likely depression received antidepressants, whether participants on antidepressants with persistently high depressive symptoms received timely dose adjustments, and whether participants achieved depression remission. We considered a cross-sectional analysis (6,219 participants in care in 2011-2012 and a prospective analysis (2,936 participants newly initiating CNICS care when PHQ-9 screening was active.The cross-sectional sample was 87% male, 53% Caucasian, 25% African American, and 18% Hispanic; the prospective sample was similar. In both samples, 39-44% had likely depression, with 44-60% of those receiving antidepressants. Of participants receiving antidepressants, 20-26% experienced persistently high depressive symptoms; only a small minority of those received antidepressant dose adjustments. Overall, 35-40% of participants on antidepressants achieved full depression remission. Remission among participants with persistently high depressive symptoms was rare regardless of dose adjustments.In this large, diverse cohort of US patients engaged in routine HIV care, we observed large gaps in antidepressant treatment, timely dose adjustment to address persistently high depressive symptoms, and antidepressant treatment outcomes. These results highlight the importance of more effective pharmacologic depression treatment models for HIV-infected patients.

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

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

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

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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

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.

The effects of drugs on human models of emotional processing: an account of antidepressant drug treatment.

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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.

Extracorporeal treatment for tricyclic antidepressant poisoning

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Yates, Christopher; Galvao, Tais; Sowinski, Kevin M

2014-01-01

The Extracorporeal Treatments In Poisoning (EXTRIP) workgroup was formed to provide recommendations on the use of extracorporeal treatments (ECTR) in poisoning. Here, the workgroup presents its results for tricyclic antidepressants (TCAs). After an extensive literature search, using a predefined...... methodology, the subgroup responsible for this poison reviewed the articles, extracted the data, summarized findings, and proposed structured voting statements following a predetermined format. A two-round modified Delphi method was chosen to reach a consensus on voting statements and RAND...... yielding a very low quality of evidence for all recommendations. Data on 108 patients, including 12 fatalities, were abstracted. The workgroup concluded that TCAs are not dialyzable and made the following recommendation: ECTR is not recommended in severe TCA poisoning (1D). The workgroup considers...

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

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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.

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

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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.

Role of AC-cAMP-PKA Cascade in Antidepressant Action of Electroacupuncture Treatment in Rats

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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.

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

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Xie, Chen; Tang, Yurong; 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...

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.

Randomised controlled trial of counseling sessions, antidepressant medication, and combined treatment for major depression in primary care setting

International Nuclear Information System (INIS)

Mossa, Samir Y.; Al-Sayed, H.; Malik, Mariam A.; Al-Hageri, S.; Al-Shaar, I.

2006-01-01

The study was made to determine whether counseling sessions using Egan's model combined with antidepressant medication is more effective than either treatment alone in the management of major depression in primary care. Patient aged 18 years and above with major depression on the research diagnostic criteria - a score of 13 or more on the 17 items. Hamilton rating scale for depression and a minimum duration of 4 weeks. Counseling sessions based on Egan's Model by research family physician or antidepressant medication or combination of both was performed. Hamilton rating scale for depression, Beck depression inventory, clinical interview schedule, and modified social adjustment schedule were used and assessed at 6 , 12 and 52 weeks. Patients in all groups showed a clear improvement after 12 weeks. The combination of counseling sessions and antidepressant medication is more effective than either treatment alone. Counseling sessions used by a trained family physician is an effective treatment for depressive disorders in primary care. The combination of this treatment with antidepressant medication is more effective than either treatment alone. (author)

Effectiveness and cost-effectiveness of mindfulness-based cognitive therapy compared with maintenance antidepressant treatment in the prevention of depressive relapse or recurrence (PREVENT): a randomised controlled trial.

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Kuyken, Willem; Hayes, Rachel; Barrett, Barbara; Byng, Richard; Dalgleish, Tim; Kessler, David; Lewis, Glyn; Watkins, Edward; Brejcha, Claire; Cardy, Jessica; Causley, Aaron; Cowderoy, Suzanne; Evans, Alison; Gradinger, Felix; Kaur, Surinder; Lanham, Paul; Morant, Nicola; Richards, Jonathan; Shah, Pooja; Sutton, Harry; Vicary, Rachael; Weaver, Alice; Wilks, Jenny; Williams, Matthew; Taylor, Rod S; Byford, Sarah

2015-07-04

Individuals with a history of recurrent depression have a high risk of repeated depressive relapse or recurrence. Maintenance antidepressants for at least 2 years is the current recommended treatment, but many individuals are interested in alternatives to medication. Mindfulness-based cognitive therapy (MBCT) has been shown to reduce risk of relapse or recurrence compared with usual care, but has not yet been compared with maintenance antidepressant treatment in a definitive trial. We aimed to see whether MBCT with support to taper or discontinue antidepressant treatment (MBCT-TS) was superior to maintenance antidepressants for prevention of depressive relapse or recurrence over 24 months. In this single-blind, parallel, group randomised controlled trial (PREVENT), we recruited adult patients with three or more previous major depressive episodes and on a therapeutic dose of maintenance antidepressants, from primary care general practices in urban and rural settings in the UK. Participants were randomly assigned to either MBCT-TS or maintenance antidepressants (in a 1:1 ratio) with a computer-generated random number sequence with stratification by centre and symptomatic status. Participants were aware of treatment allocation and research assessors were masked to treatment allocation. The primary outcome was time to relapse or recurrence of depression, with patients followed up at five separate intervals during the 24-month study period. The primary analysis was based on the principle of intention to treat. The trial is registered with Current Controlled Trials, ISRCTN26666654. Between March 23, 2010, and Oct 21, 2011, we assessed 2188 participants for eligibility and recruited 424 patients from 95 general practices. 212 patients were randomly assigned to MBCT-TS and 212 to maintenance antidepressants. The time to relapse or recurrence of depression did not differ between MBCT-TS and maintenance antidepressants over 24 months (hazard ratio 0·89, 95% CI 0·67-1·18

No interactions between genetic polymorphisms and stressful life events on outcome of antidepressant treatment

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Bukh, Jens Drachmann; Bock, Camilla; Vinberg, Maj

2009-01-01

Genetic polymorphisms seem to influence the response on antidepressant treatment and moderate the impact of stress on depression. The present study aimed to assess, whether allelic variants and stressful life events interact on the clinical outcome of depression. In a sample of 290 systematically...... recruited patients diagnosed with a single depressive episode according to ICD-10, we assessed the outcome of antidepressant treatment and the presence of stressful life events in a 6-month period preceding onset of depression by means of structured interviews. Further, we genotyped nine polymorphisms...... dependent on stressful life events experienced by the individual prior to onset of depression....

Risk factors for non-adherence to antidepressant treatment in patients with mood disorders.

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De las Cuevas, Carlos; Peñate, Wenceslao; Sanz, Emilio J

2014-01-01

Adherence to antidepressant therapy by patients with depressive disorders is essential not only to achieve a positive patient outcome but also to prevent a relapse. The aim of this study was to identify potential modelling factors influencing adherence to antidepressant treatment by patients with mood disorders in the community mental health care setting A total of 160 consecutive psychiatric outpatients attending two Community Mental Health Centres on Tenerife Island between September 2011 and May 2012 were asked to participate in the study; of these, 145 accepted. The Morisky self-report scale was used to assess adherence. The potential predictors examined included socio-demographic, clinical and therapeutic variables. The Clinical Global Impression-Severity and -Improvement scales and the Beck Depression Inventory were used for clinical assessment. Drug treatment side-effects were assessed using the "Self-report Antidepressant Side-Effect Checklist." All participants were also asked to complete the "Drug Attitude Inventory" (DAI), "Beliefs about Medicine Questionnaire" (BMQ), and "Leeds Attitude towards concordance Scale". Discriminant analyses were performed to predict non-adherence. There was no clear correlation between adherence and the socio-demographic variables examined, but adherence was related to a positive attitude of the patients towards his/her treatment (DAI) and low scores in the BMQ-Harm and -Concern subscales. Non-adherence was also related to an increasing severity of depression and to the presence and severity of side-effects. Among our study cohort, the profiles of adherent patients to antidepressant treatment were more closely associated with each patient's attitudes and beliefs than to objective socio-demographic variables. The severity of depression played a relevant role in adherence, but whether this role is direct or an interaction with several concurrent factors is not yet clear. Side-effects were also closely related to adherence, as

Mitochondrial dynamics in the hippocampus is influenced by antidepressant treatment in a genetic rat model of depression

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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...

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

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.

Subchronic treatment with fluoxetine and ketanserin increases hippocampal brain-derived neurotrophic factor, β-catenin and antidepressant-like effects.

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Pilar-Cuéllar, F; Vidal, R; Pazos, A

2012-02-01

5-HT(2A) receptor antagonists improve antidepressant responses when added to 5-HT-selective reuptake inhibitors (SSRIs) or tricyclic antidepressants. Here, we have studied the involvement of neuroplasticity pathways and/or the 5-hydroxytryptaminergic system in the antidepressant-like effect of this combined treatment, given subchronically. Expression of brain-derived neurotrophic factor (BDNF) and its receptor (TrkB), 5-bromo-2'-deoxyuridine (BrdU) incorporation, and β-catenin protein expression in different cellular fractions, as well as 5-HT(1A) receptor function were measured in the hippocampus of rats treated with fluoxetine, ketanserin and fluoxetine + ketanserin for 7 days, followed by a forced swimming test (FST) to analyse antidepressant efficacy. mRNA for BDNF was increased in the CA3 field and dentate gyrus of the hippocampus by combined treatment with fluoxetine + ketanserin. Expression of β-catenin was increased in total hippocampal homogenate and in the membrane fraction, but unchanged in the nuclear fraction after combined treatment with fluoxetine + ketanserin. These effects were paralleled by a decreased immobility time in the FST. There were no changes in BrdU incorporation, TrkB expression and 5-HT(1A) receptor function in any of the groups studied. The antidepressant-like effect induced by subchronic co-treatment with a SSRI and a 5-HT(2A) receptor antagonist may mainly be because of modifications in hippocampal neuroplasticity (BDNF and membrane-associated β-catenin), without a significant role for other mechanisms involved in chronic antidepressant response, such as hippocampal neuroproliferation or 5-HT(1A) receptor desensitization in the dorsal raphe nucleus. © 2011 The Authors. British Journal of Pharmacology © 2011 The British Pharmacological Society.

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: ...

Differential behavioral effects of the antidepressants reboxetine, fluoxetine, and moclobemide in a modified forced swim test following chronic treatment.

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Cryan, John F; Page, Michelle E; Lucki, Irwin

2005-11-01

The forced swim test (FST) is the most widely used model for assessing potential antidepressant activity in rodents following acute or short-term treatment. However, few studies have compared the effects of short- and long-term antidepressant treatment on behaviors in the test, despite the need to treat patients chronically to produce clinical effects. The current studies examined whether antidepressants from different classes produce different behavioral effects following short-term treatment and whether such effects change following administration for a longer duration. The effects of administering short-term (3 days) and long-term (14 days) treatments of antidepressants from three different chemical classes with distinct mechanisms of action via osmotic minipump were examined: the selective norepinephrine reuptake inhibitor reboxetine (10 and 60 mg kg(-1) day(-1)), the selective serotonin reuptake inhibitor fluoxetine (2.5 and 15 mg kg(-1) day(-1)), and the reversible inhibitor of monoamine oxidase moclobemide (2.5 and 15 mg kg(-1) day(-1)). All testing was carried out in a 15-min test with no preswim session in order to negate any confounding aspect of an induction procedure. The majority of antidepressant-sensitive behavioral changes were observed in the first 5 min of the test. The low dose of reboxetine failed to alter behavior in the test after 3 days but significantly decreased immobility and increased climbing behavior following administration for 14 days, whereas the high dose of reboxetine was equally effective following 3 and 14 days of treatment. In a similar fashion, the low dose of fluoxetine failed to alter behavior in the test following 3 days, but showed an augmented response on immobility and increased swimming following administration for 14 days. The high dose of fluoxetine was slightly more effective at reducing immobility following administration for 14 days than 3 days. The low dose of moclobemide decreased immobility and increased climbing

Increased rate of treatment with antidepressants in patients with multiple sclerosis

DEFF Research Database (Denmark)

Kessing, Lars Vedel; Harhoff, Mette; Andersen, Per Kragh

2008-01-01

The prevalence of depression and anxiety is increased in patients with multiple sclerosis, but it has not been investigated whether these conditions are treated in clinical practice. The objective of this study was to investigate whether the rate of treatment with antidepressants is increased...... in patients with multiple sclerosis compared with patients with other chronic illnesses and compared with the general population. By linkage of nationwide case registers, all patients were identified, who had received a main diagnosis of multiple sclerosis or osteoarthritis at first admission or during...... outpatient contact in the period 1995-2000 in Denmark. Rates of subsequent purchase of antidepressants for these patients were calculated. In total, 417 patients with a main diagnosis of multiple sclerosis and 12 127 patients with a main diagnosis of osteoarthritis, at first discharge from hospital...

Antidepressant therapy in complex treatment of painful diabetic polyneuropathy

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Lidia Grigor'evna Turbina

2012-09-01

Full Text Available Aims. Comparative efficiency and safety analysis of antidepressant agents from different pharmacological classes (pipofezine and venlafaxinein combination with carbamazepine for treatment of neuropathic pain (NP in patients with diabetic polyneuropathy (DP. Materials and methods. We examined 21 male and 27 female patients with painful DP (mean age 54.3?14.2 years; mean duration ofdiabetes mellitus (DM 8.9?5.1 years; mean duration of DP - 3.8?2.1 years. DP was diagnosed clinically and by electromyographymethod. Pain syndrome was assessed with DN4 questionnaire, visual analogue scale (VAS and McGill Pain Questionnaire. Psycho-vegetative status was evaluated by Spielberger test with reactive and personal anxiety (RA and PA assessment and Beck depressioninventory. All patients received symptomatic pharmacotherapy with anticonvulsant and antidepressant agent. First group (DP-1included 23 patients on carbamazepin and pipofezine. Second group (DP-2 included 25 patients on carbamazepin and venlafaxine. Results. Following treatment, pain syndrome was completely compensated in 8.7% of patients from DP-1 group and 12.5% from DP-2.Decrease in pain intensity?50% from initial level was achieved in 73.9% (DP-1 and 75% (DP-2 of cases. Mean pain intensityaccording to VAS reduced from 5.2?2.1 points to 2.3?1.4 points (DP-1 and from 5.8?2.3 points (DP-2 with equal statistical significance(p

Radioactive cDNA microarray (II): Gene expression profiling of antidepressant treatment by human cDNA microarray

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Lee, Ji Hye; Kang, Rhee Hun; Ham, Byung Joo; Lee, Min Su; Shin, Kyung Ho; Choe, Jae Gol; Kim, Meyoung Kon [College of Medicine, Univ. of Korea, Seoul (Korea, Republic of)

2003-07-01

Major depressive disorder is a prevalent psychiatric disorder in primary care, associated with impaired patient functioning and well-being. Fluoxetine is a selective serotonin-reuptake inhibitors (SSRIs) and is a commonly prescribed antidepressant compound. Its action is primarily attributed to selective inhibition of the reuptake of serotonin (5-hydroxytryptamine) in the central nervous system. Objectives ; the aims of this study were two-fold: (1) to determine the usefulness for investigation of the transcription profiles in depression patients, and (2) to assess the differences in gene expression profiles between positive response group and negative response groups by fluoxetine treatment. This study included 53 patients with major depression (26 in positive response group with antidepressant treatment, 27 in negative response group with antidepressant treatment), and 53 healthy controls. To examine the difference of gene expression profile in depression patients, radioactive complementary DNA microarrays were used to evaluate changes in the expression of 1,152 genes in total. Using 33p-labeled probes, this method provided highly sensitive gene expression profiles including brain receptors, drug metabolism, and cellular signaling. Gene transcription profiles were classified into several categories in accordance with the antidepressant gene-regulation. The gene profiles were significantly up-(22 genes) and down-(16 genes) regulated in the positive response group when compared to the control group. Also, in the negative response group, 35 genes were up-regulated and 8 genes were down-regulated when compared to the control group. 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.

Radioactive cDNA microarray (II): Gene expression profiling of antidepressant treatment by human cDNA microarray

International Nuclear Information System (INIS)

Lee, Ji Hye; Kang, Rhee Hun; Ham, Byung Joo; Lee, Min Su; Shin, Kyung Ho; Choe, Jae Gol; Kim, Meyoung Kon

2003-01-01

Major depressive disorder is a prevalent psychiatric disorder in primary care, associated with impaired patient functioning and well-being. Fluoxetine is a selective serotonin-reuptake inhibitors (SSRIs) and is a commonly prescribed antidepressant compound. Its action is primarily attributed to selective inhibition of the reuptake of serotonin (5-hydroxytryptamine) in the central nervous system. Objectives ; the aims of this study were two-fold: (1) to determine the usefulness for investigation of the transcription profiles in depression patients, and (2) to assess the differences in gene expression profiles between positive response group and negative response groups by fluoxetine treatment. This study included 53 patients with major depression (26 in positive response group with antidepressant treatment, 27 in negative response group with antidepressant treatment), and 53 healthy controls. To examine the difference of gene expression profile in depression patients, radioactive complementary DNA microarrays were used to evaluate changes in the expression of 1,152 genes in total. Using 33p-labeled probes, this method provided highly sensitive gene expression profiles including brain receptors, drug metabolism, and cellular signaling. Gene transcription profiles were classified into several categories in accordance with the antidepressant gene-regulation. The gene profiles were significantly up-(22 genes) and down-(16 genes) regulated in the positive response group when compared to the control group. Also, in the negative response group, 35 genes were up-regulated and 8 genes were down-regulated when compared to the control group. 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

Systems genetics analysis of pharmacogenomics variation during antidepressant treatment

DEFF Research Database (Denmark)

Madsen, Majbritt Busk; Kogelman, L J A; Kadarmideen, H N

2016-01-01

Selective serotonin reuptake inhibitors (SSRIs) are the most widely used antidepressants, but the efficacy of the treatment varies significantly among individuals. It is believed that complex genetic mechanisms play a part in this variation. We have used a network based approach to unravel the in...... genes involved in calcium homeostasis. In conclusion, we suggest a difference in genetic interaction networks between initial and subsequent SSRI response.The Pharmacogenomics Journal advance online publication, 18 October 2016; doi:10.1038/tpj.2016.68....

Anticonvulsants or Antidepressants in Combination Pharmacotherapy for Treatment of Neuropathic Pain in Cancer Patients: A Systematic Review and Meta-analysis.

Science.gov (United States)

Guan, Jia; Tanaka, Shiro; Kawakami, Koji

2016-08-01

To investigate the efficacy of anticonvulsants or antidepressants in combination pharmacotherapy for treatment of neuropathic pain in cancer patients. We systematically searched the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, and the metaRegister of Controlled Trials for randomized controlled trials that compared anticonvulsants or antidepressants in combination pharmacotherapy (experimental group) with treatments without anticonvulsants or antidepressants (control group) for neuropathic pain in cancer patients. Risk of bias was evaluated in accordance with the Cochrane Handbook for Systematic Reviews of Interventions. The primary outcome was a mean difference (MD) in change in global pain analyzed by a random-effects model. Eight trials met the inclusion criteria with a total of 1359 participants of whom 698 received an experimental intervention. The MD in change in global pain suggested a favorable association with anticonvulsants or antidepressants in combination pharmacotherapy compared with control groups (MD, -0.41; 95% confidence interval, -0.70 to -0.12) with no heterogeneity across trials (I=0%). The MD in change estimated in all sensitivity analyses ranged from -0.36 to -0.47, suggesting that these effects were consistent across different study designs and statistical assumptions. Anticonvulsants or antidepressants in combination pharmacotherapy reduce neuropathic pain in cancer patients compared with treatments without anticonvulsants or antidepressants. Limited evidence precludes a recommendation on specific adjuvants in combination pharmacotherapy.

Antidepressants in Parkinson's disease. Recommendations by the movement disorder study group of the Neurological Association of Madrid.

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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.

Telephone-administered psychotherapy in combination with antidepressant medication for the acute treatment of major depressive disorder.

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Corruble, Emmanuelle; Swartz, Holly A; Bottai, Thierry; Vaiva, Guillaume; Bayle, Frank; Llorca, Pierre-Michel; Courtet, Philippe; Frank, Ellen; Gorwood, Philip

2016-01-15

Telephone-administered psychotherapies (T-P) provided as an adjunct to antidepressant medication may improve response rates in major depressive disorder (MDD). The goal of this study was to compare telephone-administered social rhythm therapy (T-SRT) and telephone-administered intensive clinical management (T-ICM) as adjuncts to antidepressant medication for MDD. A secondary goal was to compare T-P with Treatment as Usual (TAU) as adjunctive treatment to medication for MDD. 221 adult out-patients with MDD, currently depressed, were randomly assigned to 8 sessions of weekly T-SRT (n=110) or T-ICM (n=111), administered as an adjunct to agomelatine. Both psychotherapies were administered entirely by telephone, by trained psychologists who were blind to other aspects of treatment. The 221 patients were a posteriori matched with 221 depressed outpatients receiving TAU (controls). The primary outcome measure was the percentage of responders at 8 weeks post-treatment. No significant differences were found between T-SRT and T-ICM. But T-P was associated with higher response rates (65.4% vs 54.8%, p=0.02) and a trend toward higher remission rates (33.2% vs 25.1%; p=0.06) compared to TAU. Short term study. This study is the first assessing the short-term effects of an add-on, brief, telephone-administered psychotherapy in depressed patients treated with antidepressant medication. Eight sessions of weekly telephone-delivered psychotherapy as an adjunct to antidepressant medication resulted in improved response rates relative to medication alone. Copyright © 2015 Elsevier B.V. All rights reserved.

Personality traits predict treatment outcome with an antidepressant in patients with functional gastrointestinal disorder.

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Tanum, L; Malt, U F

2000-09-01

We investigated the relationship between personality traits and response to treatment with the tetracyclic antidepressant mianserin or placebo in patients with functional gastrointestinal disorder (FGD) without psychopathology. Forty-eight patients completed the Buss-Durkee Hostility Inventory, Neuroticism Extroversion Openness -Personality Inventory (NEO-PI), and Eysenck Personality Questionnaire (EPQ), neuroticism + lie subscales, before they were consecutively allocated to a 7-week double-blind treatment study with mianserin or placebo. Treatment response to pain and target symptoms were recorded daily with the Visual Analogue Scale and Clinical Global Improvement Scale at every visit. A low level of neuroticism and little concealed aggressiveness predicted treatment outcome with the antidepressant drug mianserin in non-psychiatric patients with FGD. Inversely, moderate to high neuroticism and marked concealed aggressiveness predicted poor response to treatment. These findings were most prominent in women. Personality traits were better predictors of treatment outcome than serotonergic sensitivity assessed with the fenfluramine test. Assessment of the personality traits negativism, irritability, aggression, and neuroticism may predict response to drug treatment of FGD even when serotonergic sensitivity is controlled for. If confirmed in future studies, the findings point towards a more differential psychopharmacologic treatment of FGD.

Combining clinical variables to optimize prediction of antidepressant treatment outcomes.

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Iniesta, Raquel; Malki, Karim; Maier, Wolfgang; Rietschel, Marcella; Mors, Ole; Hauser, Joanna; Henigsberg, Neven; Dernovsek, Mojca Zvezdana; Souery, Daniel; Stahl, Daniel; Dobson, Richard; Aitchison, Katherine J; Farmer, Anne; Lewis, Cathryn M; McGuffin, Peter; Uher, Rudolf

2016-07-01

The outcome of treatment with antidepressants varies markedly across people with the same diagnosis. A clinically significant prediction of outcomes could spare the frustration of trial and error approach and improve the outcomes of major depressive disorder through individualized treatment selection. It is likely that a combination of multiple predictors is needed to achieve such prediction. We used elastic net regularized regression to optimize prediction of symptom improvement and remission during treatment with escitalopram or nortriptyline and to identify contributing predictors from a range of demographic and clinical variables in 793 adults with major depressive disorder. A combination of demographic and clinical variables, with strong contributions from symptoms of depressed mood, reduced interest, decreased activity, indecisiveness, pessimism and anxiety significantly predicted treatment outcomes, explaining 5-10% of variance in symptom improvement with escitalopram. Similar combinations of variables predicted remission with area under the curve 0.72, explaining approximately 15% of variance (pseudo R(2)) in who achieves remission, with strong contributions from body mass index, appetite, interest-activity symptom dimension and anxious-somatizing depression subtype. Escitalopram-specific outcome prediction was more accurate than generic outcome prediction, and reached effect sizes that were near or above a previously established benchmark for clinical significance. Outcome prediction on the nortriptyline arm did not significantly differ from chance. These results suggest that easily obtained demographic and clinical variables can predict therapeutic response to escitalopram with clinically meaningful accuracy, suggesting a potential for individualized prescription of this antidepressant drug. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Effects of BDNF polymorphisms on antidepressant action.

Science.gov (United States)

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

Sexual dysfunction, depression, and the impact of antidepressants.

Science.gov (United States)

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.

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

Science.gov (United States)

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.

Escitalopram versus other antidepressive agents for depression

Science.gov (United States)

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

[Tricyclic antidepressant therapy in headache].

Science.gov (United States)

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.

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.

Antidepressants for the treatment of abdominal pain-related functional gastrointestinal disorders in children and adolescents.

Science.gov (United States)

Kaminski, Angela; Kamper, Adrian; Thaler, Kylie; Chapman, Andrea; Gartlehner, Gerald

2011-07-06

Abdominal pain-related functional gastrointestinal disorders (FGIDs) are among the most common medical problems in paediatric medicine. Frequently, physicians prescribe antidepressants as a second-line treatment for children and adolescents with FGIDs. To date, the evidence on the benefits and harms of antidepressants for the treatment of abdominal pain-related FGIDs has not been assessed systematically. The primary objectives were to conduct a systematic review to evaluate the efficacy and safety of antidepressants for the treatment of abdominal pain-related FGIDs in children and adolescents. We searched The Cochrane Library, PubMed, EMBASE, IPA, CINAHL, PsycINFO, ISI Web of Science, Biosis Previews and the International Clinical Trials Registry Platform of the World Health Organization with appropriate filters (from inception to January 31, 2011). For efficacy we included double-blind, randomised controlled trials (RCTs) of antidepressants for treatment of abdominal pain-related FGIDs in children and adolescents 18 years or younger. Open-label and uncontrolled experimental studies, as well as observational studies were eligible for the assessment of harms. The minimum study duration was 4 weeks. The minimum study size was 30 participants. Two authors independently assessed all abstracts and full text articles, and rated the risk of bias for included studies. Data were extracted independently by one author and checked for accuracy by another author. Data were analysed using RevMan 5. Two RCTs (123 participants), both using amitriptyline, met the pre-specified inclusion criteria. These studies provided mixed findings on the efficacy of amitriptyline for the treatment of abdominal pain-related FGIDs. The larger, publicly-funded study reported no statistically significant difference in efficacy between amitriptyline and placebo in 90 children and adolescents with FGIDs after 4 weeks of treatment. On intention-to-treat (ITT)- analysis, 59% of the children reported

Testosterone levels and sexual function disorders in depressive female patients: effects of antidepressant treatment.

Science.gov (United States)

Kumsar, Şükrü; Kumsar, Neslihan Akkişi; Sağlam, Hasan Salih; Köse, Osman; Budak, Salih; Adsan, Öztuğ

2014-02-01

Women suffer from depression more frequently than men, which indicates that sex hormones might be involved in the etiology of this disease. The purpose of this study was to assess the relationship between testosterone and depression pathophysiology in depressive women along with sexual function. We also investigated whether antidepressant treatment causes any change in levels of this hormone or in sexual function. Premenopausal female patients aged 25-46 years (n = 52) with diagnosed major depression were included in this study as the patient group, and 25- to 46-year-old premenopausal women without depression (n = 30) were included as the control group. Serum testosterone and sex hormone-binding globulin (SHBG) levels were measured twice, before and after the antidepressant treatment. Bioavailable testosterone (cBT) levels were calculated using the assay results for total testosterone (TT), SHBG, and albumin according to the formulas of Vermeulen et al. Depression severity was measured using the 17-item Hamilton Depression Rating Scale, and sexual function was evaluated with the Arizona Sexual Experience Scale. The mean TT and cBT levels significantly increased in the patient group after the antidepressant treatment (P treatment TT and cBT levels were significantly lower in the patient group than in the control group (P treatment serum TT and cBT levels in the patient and control groups (P > 0.05). There were no significant differences among the groups in terms of SHBG level. The low testosterone levels in depressed women compared with women in the control group and the elevated levels post-pharmacotherapy suggest that testosterone may be involved in depression. © 2013 International Society for Sexual Medicine.

Reevaluating Antidepressant Selection in Patients With Bruxism and Temporomandibular Joint Disorder.

Science.gov (United States)

Rajan, Royce; Sun, Ye-Ming

2017-05-01

Temporomandibular joint disorder (TMD) is a broad pain disorder that refers to several conditions affecting the temporomandibular joint of the jaw and the muscles of mastication. As with most pain disorders, a high prevalence of depression and anxiety is associated with TMD. Research has shown that selective serotonin reuptake inhibitors (SSRIs), the first-line drug therapy for major depressive disorder, may not be suitable for TMD patients because SSRIs can induce teeth-grinding, otherwise known as bruxism. This is problematic because bruxism is believed to further exacerbate TMD. Therefore, the purpose of this literature review is to better understand the mechanism of SSRI-induced bruxism, as well as discuss alternative antidepressant options for treating depression and anxiety in patients with bruxism and TMD. Alternative classes of antidepressants reviewed include serotonin-norepinephrine reuptake inhibitors, tricyclic antidepressants, atypical antidepressants, and monoamine oxidase inhibitors. Findings indicate that dopamine agonists and buspirone are currently the most effective medications to treat the side effects of SSRI-induced bruxism, but results regarding the effectiveness of specific antidepressants that avoid bruxism altogether remain inconclusive.

Impact of a Student Pharmacist Driven Medication Reconciliation and Antidepressant Treatment History Project at a Depression Clinic: A Pilot Study

Science.gov (United States)

Tang, Stella S.; Jaward, Leanna; Ward, Kristen; Parikh, Sagar V.; Bostwick, Jolene R.

2017-01-01

Objectives To improve treatment of patients with depression, a new pilot service project involving student pharmacists who would conduct medication reconciliation and review of antidepressant treatment history was created and evaluated. Experimental design A prospective study conducted at the University of Michigan Depression Center. Principal observations From an initial sample of 78 referrals, 41 subjects were reached by phone, with 34 completing medication reconciliation and antidepressant treatment history. Of the 34 patients, 25 (73.5%) had at least one discrepancy identified in their medication list, resulting in 164 medication changes in the electronic medical record (EMR). A total of 105 past antidepressant trials were documented in the 34 individuals, with 34 (32.4%) trials found to be inadequate. Thirteen (38.2%) patients reported failure to respond to two different antidepressants from different classes. All 34 patients participated well in the phone calls and were willing to consult a pharmacist at their upcoming clinic visit. Conclusions A student pharmacist pilot was feasible, identified many discrepancies in the medication record, and identified important medication treatment history in patients with depression in advance of the clinic visit. The project provides support for a specialized role for student pharmacists and demonstrates that interprofessional care can contribute to improved treatment of depression. PMID:28626270

Use of antidepressants in the treatment of depression in Asia: guidelines, clinical evidence, and experience revisited.

Science.gov (United States)

Treuer, Tamás; Liu, Chia-Yih; Salazar, Gerardo; Kongsakon, Ronnachai; Jia, Fujun; Habil, Hussain; Lee, Min-Soo; Lowry, Amanda; Dueñas, Héctor

2013-12-01

Major depressive disorder is prevalent worldwide, and only about half of those affected will experience no further episodes or symptoms. Additionally, depressive symptoms can be challenging to identify, with many patients going undiagnosed despite a wide variety of available treatment options. Antidepressants are the cornerstone of depression treatment; however, a large number of factors must be considered in selecting the treatment best suited to the individual. To help support physicians in this process, international and national treatment guidelines have been developed. This review evaluates the current use of antidepressant treatment for major depressive disorder in six Asian countries (China, Korea, Malaysia, Philippines, Taiwan, and Thailand). No remarkable differences were noted between Asian and international treatment guidelines or among those from within Asia as these are adapted from western guidelines, although there were some local variations. Importantly, a shortage of evidence-based information at a country level is the primary problem in developing guidelines appropriate for Asia, so most of the guidelines are consensus opinions derived from western research data utilized in western guidelines. Treatment guidelines need to evolve from being consensus based to evidence based when evidence is available, taking into consideration cost/effectiveness or cost/benefit with an evidence-based approach that more accurately reflects clinical experience as well as the attributes of each antidepressant. In everyday practice, physicians must tailor their treatment to the patient's clinical needs while considering associated external factors; better tools are needed to help them reach the best possible prescribing decisions which are of maximum benefit to patients. Copyright © 2013 Wiley Publishing Asia Pty Ltd.

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.

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.

Hippocampal astrocytes are necessary for antidepressant treatment of learned helplessness rats.

Science.gov (United States)

Iwata, Masaaki; Shirayama, Yukihiko; Ishida, Hisahito; Hazama, Gen-i; Nakagome, Kazuyuki

2011-08-01

The astrocyte is a major component of the neural network and plays a role in brain function. Previous studies demonstrated changes in the number of astrocytes in depression. In this study, we examined alterations in the number of astrocytes in the learned helplessness (LH) rat, an animal model of depression. The numbers of activated and nonactivated astrocytes in the dentate gyrus (molecular layer, subgranular zone, and hilus), and CA1 and CA3 regions of the hippocampus were significantly increased 2 and 8 days after attainment of LH. Subchronic treatment with imipramine showed a tendency (although not statistically significant) to decrease the LH-induced increment of activated astrocytes in the CA3 region and dentate gyrus. Furthermore, subchronic treatment of naïve rats with imipramine did not alter the numbers of activated and nonactivated astrocytes. However, the antidepressant-like effects of imipramine in the LH paradigm were blocked when fluorocitrate (a reversible inhibitor of astrocyte function) was injected into the dentate gyrus or CA3 region. Injection of fluorocitrate into naive rats failed to induce behavioral deficits in the conditioned avoidance test. These results indicate that astrocytes are responsive to the antidepressant-like effect of imipramine in the dentate gyrus and CA3 region of the hippocampus. Copyright © 2010 Wiley-Liss, Inc.

The effect of flexible cognitive-behavioural therapy and medical treatment, including antidepressants on post-traumatic stress disorder and depression in traumatised refugees

DEFF Research Database (Denmark)

Buhmann, Caecilie Böck; Nordentoft, Merete; Ekstrøm, Morten

2016-01-01

design (registered with Clinicaltrials.gov, NCT00917397, EUDRACT no. 2008-006714-15). Participants were refugees with war-related traumatic experiences, post-traumatic stress disorder (PTSD) and without psychotic disorder. Treatment was weekly sessions with a physician and/or psychologist over 6 months....... RESULTS: A total of 217 of 280 patients completed treatment (78%). There was no effect on PTSD symptoms, no effect of psychotherapy and no interaction between psychotherapy and medicine. A small but significant effect of treatment with antidepressants was found on depression. CONCLUSIONS: In a pragmatic...... clinical setting, there was no effect of flexible CBT and antidepressants on PTSD, and there was a small-to-moderate effect of antidepressants and psychoeducation on depression in traumatised refugees....

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

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.

Association of FKBP51 with priming of autophagy pathways and mediation of antidepressant treatment response: evidence in cells, mice, and humans.

Directory of Open Access Journals (Sweden)

Nils C Gassen

2014-11-01

Full Text Available FK506 binding protein 51 (FKBP51 is an Hsp90 co-chaperone and regulator of the glucocorticoid receptor, and consequently of stress physiology. Clinical studies suggest a genetic link between FKBP51 and antidepressant response in mood disorders; however, the underlying mechanisms remain elusive. The objective of this study was to elucidate the role of FKBP51 in the actions of antidepressants, with a particular focus on pathways of autophagy.Established cell lines, primary neural cells, human blood cells of healthy individuals and patients with depression, and mice were treated with antidepressants. Mice were tested for several neuroendocrine and behavioral parameters. Protein interactions and autophagic pathway activity were mainly evaluated by co-immunoprecipitation and Western blots. We first show that the effects of acute antidepressant treatment on behavior are abolished in FKBP51 knockout (51KO mice. Autophagic markers, such as the autophagy initiator Beclin1, were increased following acute antidepressant treatment in brains from wild-type, but not 51KO, animals. FKBP51 binds to Beclin1, changes decisive protein interactions and phosphorylation of Beclin1, and triggers autophagic pathways. Antidepressants and FKBP51 exhibited synergistic effects on these pathways. Using chronic social defeat as a depression-relevant stress model in combination with chronic paroxetine (PAR treatment revealed that the stress response, as well as the effects of antidepressants on behavior and autophagic markers, depends on FKBP51. In human blood cells of healthy individuals, FKBP51 levels correlated with the potential of antidepressants to induce autophagic pathways. Importantly, the clinical antidepressant response of patients with depression (n = 51 could be predicted by the antidepressant response of autophagic markers in patient-derived peripheral blood lymphocytes cultivated and treated ex vivo (Beclin1/amitriptyline: r = 0.572, p = 0.003; Beclin1/PAR: r

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.

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:

Agomelatine Treatment with Adolescents with ADHD

Science.gov (United States)

Niederhofer, Helmut

2012-01-01

Objective: Antidepressants, in particular Atomextine, along with stimulants have demonstrated benefit in the treatment of ADHD. Agomelatine is a new antidepressant with additional affinities to the melatonergic system. As ADHD has been associated with sleep disorders, it is assumed that Agomelatiine might serve as a therapeutic alternative to…

Antidepressant-Like Effects of Lindera obtusiloba Extracts on the Immobility Behavior of Rats in the Forced Swim Test

Directory of Open Access Journals (Sweden)

Dong Wook Lim

2016-02-01

Full Text Available Lindera obtusiloba extracts are commonly used as an alternative medicine due to its numerous health benefits in Korea. However, the antidepressant-like effects of L. obtusiloba extracts have not been fully elucidated. In this study, we aimed to determine whether L. obtusiloba extracts exhibited antidepressant-like activity in rats subjected to forced swim test (FST-induced depression. Acute treatment of rats with L. obtusiloba extracts (200 mg/kg, p.o. significantly reduced immobility time and increased swimming time without any significant change in climbing. Rats treated with L. obtusiloba extracts also exhibited a decrease in the limbic hypothalamic-pituitary-adrenal (HPA axis response to the FST, as indicated by attenuation of the corticosterone response and decreased c-Fos immunoreactivity in the hippocampus CA3 region. In addition, L. obtusiloba extracts, at concentrations that were not affected by cell viability, significantly decreased luciferase activity in response to cortisol in a concentration-dependent manner by the glucocorticoid binding assay in HeLa cells. Our findings suggested that the antidepressant-like effects of L. obtusiloba extracts were likely mediated via the glucocorticoid receptor (GR. Further studies are needed to evaluate the potential of L. obtusiloba extracts as an alternative therapeutic approach for the treatment of depression.

Antidepressant-Like Effects of Sanggenon G, Isolated from the Root Bark of Morus alba, in Rats: Involvement of the Serotonergic System.

Science.gov (United States)

Lim, Dong Wook; Jung, Jae-Woo; Park, Ji-Hae; Baek, Nam-In; Kim, Yun Tai; Kim, In-Ho; Han, Daeseok

2015-01-01

The root bark of Morus alba is commonly used as an alternative medicine due to its numerous health benefits in humans. However, the antidepressant effects of various active components from M. alba have not been fully elucidated. In this study, we aimed to determine whether sanggenon G, an active compound isolated from the root bark of M. alba, exhibited antidepressant-like activity in rats subjected to forced swim test (FST)-induced depression. Acute treatment of rats with sanggenon G (30 mg/kg, intraperitoneally (i.p.)) significantly reduced immobility time and increased swimming time without any significant change in climbing. Rats treated with sanggenon G also exhibited a decrease in the limbic hypothalamic-pituitary-adrenal (HPA) axis response to the FST, as indicated by attenuation of the corticosterone response and decreased c-Fos immunoreactivity in the hypothalamic paraventricular nucleus (PVN). In addition, the antidepressant-like effects of sanggenon G were significantly inhibited by WAY100635 (1 mg/kg, i.p.; a selective 5-hydroxytryptamine1A (5-HT1A) receptor antagonist), but not SCH23390 (0.05 mg/kg, i.p.; a dopamine D1 receptor antagonist). Our findings suggested that the antidepressant-like effects of sanggenon G were mediated by an interaction with the serotonergic system. Further studies are needed to evaluate the potential of sanggenon G as an alternative therapeutic approach for the treatment of depression.

Rapid improvement of depressive symptoms in suicide attempters following treatment with milnacipran and tricyclic antidepressants – a case series

Directory of Open Access Journals (Sweden)

Kirino E

2011-12-01

Full Text Available Eiji Kirino, Masao GitohDepartment of Psychiatry, Juntendo University, School of Medicine, Shizuoka, JapanAbstract: Suicide is a serious social problem in many countries, including Japan. The majority of people who commit suicide suffer from depression. Suicide attempt patients suffering from serious physical injuries are initially treated in hospital emergency departments. The present post hoc analysis examined data from patients admitted to an emergency hospital for treatment of physical injuries, resulting from a suicide attempt, and initial psychiatric treatment for depression and prevention of future suicide attempts. The effects on depressive symptoms were studied in two groups of patients using the 17-item Hamilton depression scale (HAMD. One group (n = 6 had received intravenous tricyclic antidepressants (TCA (amitriptyline or clomipramine while the other group (n = 7 had been treated orally with milnacipran, a serotonin and norepinephrine reuptake inhibitor antidepressant. Prior to treatment the four highest scoring items on the HAMD scale were the same in both groups namely, item 1 (depressed mood, item 3 (suicidality, item 7 (interest in work and activities, and item 10 (psychic anxiety. After 1 week of treatment, mean global HAMD scores were significantly reduced in both groups. Treatment resulted in a significant reduction of five HAMD items in the TCA group, whereas in the milnacipran group 12 HAMD items were significantly reduced. Suicidality (item 3 was significantly improved by 1 week treatment with milnacipran, but not by TCAs. Milnacipran rapidly improved a wide range of depressive symptoms, including suicidality within the first week. The improvement with milnacipran would appear to be, at least, equivalent to that achieved with TCAs, possibly affecting a wider range of symptoms. Since milnacipran has been shown in comparative studies to be better tolerated than TCAs, this antidepressant offers an interesting option for the

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

Rapid and Longer-Term Antidepressant Effects of Repeated Ketamine Infusions in Treatment-Resistant Major Depression

NARCIS (Netherlands)

Murrough, James W.; Perez, Andrew M.; Pillemer, Sarah; Stern, Jessica; Parides, Michael K.; aan het Rot, Marije; Collins, Katherine A.; Mathew, Sanjay J.; Charney, Dennis S.; Iosifescu, Dan V.

2013-01-01

Background: Ketamine is reported to have rapid antidepressant effects; however, there is limited understanding of the time-course of ketamine effects beyond a single infusion. A previous report including 10 participants with treatment-resistant major depression (TRD) found that six ketamine

The influence of patients' preference/attitude towards psychotherapy and antidepressant medication on the treatment of major depressive disorder.

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Moradveisi, Latif; Huibers, Marcus; Renner, Fritz; Arntz, Arnoud

2014-03-01

Preferences and attitudes patients hold towards treatment are important, as these can influence treatment outcome. In depression research, the influence of patients' preference/attitudes on outcome and dropout has mainly been studied for antidepressant medication, and less for psychological treatments. We investigated the effects of patients' preference and attitudes towards psychological treatment and antidepressant medication on treatment outcome and dropout, and tested specificity of effects. Data are based on a randomized trial testing the effectiveness of behavioural activation (BA) vs antidepressant medication (ADM) for major depression (MDD) in Iran. Patients with MDD (N = 100) were randomized to BA (N = 50) or ADM (N = 50). Patients' preference/attitudes towards psychotherapy and ADM were assessed at baseline and associated with dropout and treatment outcome using logistic regression and multilevel analysis. High scores on psychotherapy preference/attitude and low scores on ADM preference/attitude predicted dropout from ADM, while no association between dropout and preference/attitude was found in BA. Psychotherapy preference/attitude moderated the differential effect of BA and ADM on one outcome measure, but the association disappeared after one year. Because in Iran most patients have only access to ADM, offering a psychological treatment for depression could attract especially those patients that prefer this newly available treatment. Patients' preferences and attitudes towards depression treatments influence dropout from ADM, and moderate the short-term difference in effectiveness between BA and ADM. The fact that dropout from BA was not affected by preference/attitude speaks for its acceptability among patients. Copyright © 2013 Elsevier Ltd. 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.

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

Advanced oxidation treatment and photochemical fate of selected antidepressant pharmaceuticals in solutions of Suwannee River humic acid

Energy Technology Data Exchange (ETDEWEB)

Santoke, Hanoz, E-mail: hsantoke@uci.edu [Urban Water Research Center, Department of Civil and Environmental Engineering, University of California, Irvine, Irvine, CA 92697-2175 (United States); Song, Weihua, E-mail: wsong@uci.edu [Urban Water Research Center, Department of Civil and Environmental Engineering, University of California, Irvine, Irvine, CA 92697-2175 (United States); Department of Environmental Science and Engineering, Fudan University, Shanghai, 200433 (China); Cooper, William J., E-mail: wcooper@uci.edu [Urban Water Research Center, Department of Civil and Environmental Engineering, University of California, Irvine, Irvine, CA 92697-2175 (United States); Peake, Barrie M., E-mail: bpeake@chemistry.otago.ac.nz [Chemistry Department, University of Otago, P.O. Box 56, Dunedin 9054 (New Zealand)

2012-05-30

Highlights: Black-Right-Pointing-Pointer We elucidate the photochemical degradation of three antidepressant pharmaceuticals. Black-Right-Pointing-Pointer Hydroxyl radical is the most significant contributor to the degradation. Black-Right-Pointing-Pointer Excited state dissolved organic matter also plays a significant role for duloxetine. Black-Right-Pointing-Pointer Tentative reaction byproducts are identified. - Abstract: Antidepressant pharmaceuticals have recently been detected at low concentrations in wastewater and surface water. This work reports studies of the direct and indirect photochemical fate and treatment by advanced oxidation of three antidepressant compounds (duloxetine, venlafaxine and bupropion) in solutions of humic acid in order to elucidate their behavior in the natural environment prior to reaching a water treatment facility and potentially entering a potable water supply. Humic acid solution was prepared by adding to distilled water a known amount of organic matter as a photosensitizer. All three antidepressants react very rapidly with hydroxyl radicals ({center_dot}OH) and hydrated electrons (e{sup -}{sub aq}) with rate constants of {approx}10{sup 8} to 10{sup 10} M{sup -1} s{sup -1}, but significantly slower with singlet oxygen ({sup 1}{Delta}O{sub 2}) ({approx}10{sup 3} to 10{sup 5} M{sup -1} s{sup -1}). The steady-state concentrations of {center_dot}OH and {sup 1}{Delta}O{sub 2}, in a sample of humic acid solution were measured and used with the second order rate constants to show that the hydroxyl radical was an order of magnitude more effective than the singlet oxygen in the solar-induced photochemical degradation of the antidepressants. Excited state dissolved organic matter also accounted for a substantial portion of degradation of duloxetine, decreasing its half-life by 27% under solar irradiation. Several reaction pathways and by-products arising from the photodegradation were identified using gamma-irradiation followed by LC

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.

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.

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

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.

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

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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.

Neural Plasticity Is Involved in Physiological Sleep, Depressive Sleep Disturbances, and Antidepressant Treatments

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Meng-Qi Zhang

2017-01-01

Full Text Available Depression, which is characterized by a pervasive and persistent low mood and anhedonia, greatly impacts patients, their families, and society. The associated and recurring sleep disturbances further reduce patient’s quality of life. However, therapeutic sleep deprivation has been regarded as a rapid and robust antidepressant treatment for several decades, which suggests a complicated role of sleep in development of depression. Changes in neural plasticity are observed during physiological sleep, therapeutic sleep deprivation, and depression. This correlation might help us to understand better the mechanism underlying development of depression and the role of sleep. In this review, we first introduce the structure of sleep and the facilitated neural plasticity caused by physiological sleep. Then, we introduce sleep disturbances and changes in plasticity in patients with depression. Finally, the effects and mechanisms of antidepressants and therapeutic sleep deprivation on neural plasticity are discussed.

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...

Effects of antidepressants on alternations in serum cytokines and depressive-like behavior in mice after lipopolysaccharide administration.

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Ohgi, Yuta; Futamura, Takashi; Kikuchi, Tetsuro; Hashimoto, Kenji

2013-02-01

Accumulating evidence suggests that inflammation may play a role in the pathophysiology of major depressive disorder (MDD). Antidepressants, including selective serotonin reuptake inhibitors (SSRIs) and serotonin and norepinephrine reuptake inhibitors (SNRIs), possess anti-inflammatory effects in vitro. Here, we examined the effects of SSRIs and SNRIs on lipopolysaccharide (LPS)-induced inflammation and depressive-like behavior in male mice. A single administration of LPS (0.5mg/kg, i.p.) increased serum levels of the pro-inflammatory cytokine, tumor necrosis factor-α (TNFα) and the anti-inflammatory cytokine, interleukin-10 (IL-10) in mice. Pretreatment with SSRIs (fluoxetine and paroxetine), SNRIs (venlafaxine and duloxetine), or 5-hydroxytryptophan (5-HTP), a precursor of serotonin, attenuated LPS-induced increases in TNFα, whereas it increased serum levels of IL-10, in mice treated with LPS. In the tail suspension test (TST), LPS increased the immobility time without affecting spontaneous locomotor activity, suggesting that LPS induced depressive-like behavior in mice. Treatment with fluoxetine (30 mg/kg) or paroxetine (10mg/kg) significantly shortened LPS-induced increases of immobility time. These results suggested that antidepressants exert anti-inflammatory effects in vivo, and that the serotonergic system may partially mediate these effects. In addition, the anti-inflammatory effects of antidepressants may help alleviate the symptoms of LPS-induced depression in mice. Copyright © 2012 Elsevier Inc. All rights reserved.

Ozone oxidation of antidepressants in wastewater –Treatment evaluation and characterization of new by-products by LC-QToFMS

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Lajeunesse André

2013-01-01

Full Text Available Abstract Background The fate of 14 antidepressants along with their respective N-desmethyl metabolites and the anticonvulsive drug carbamazepine was examined in a primary sewage treatment plant (STP and following advanced treatments with ozone (O3. The concentrations of each pharmaceutical compound were determined in raw sewage, effluent and sewage sludge samples by LC-MS/MS analysis. The occurrence of antidepressant by-products formed in treated effluent after ozonation was also investigated. Results Current primary treatments using physical and chemical processes removed little of the compounds (mean removal efficiency: 19%. Experimental sorption coefficients (Kd of each studied compounds were also calculated. Sorption of venlafaxine, desmethylvenlafaxine, and carbamazepine on sludge was assumed to be negligible (log Kd ≤ 2, but higher sorption behavior can be expected for sertraline (log Kd ≥ 4. Ozonation treatment with O3 (5 mg/L led to a satisfactory mean removal efficiency of 88% of the compounds. Screening of the final ozone-treated effluent samples by high resolution-mass spectrometry (LC-QqToFMS did confirm the presence of related N-oxide by-products. Conclusion Effluent ozonation led to higher mean removal efficiencies than current primary treatment, and therefore represented a promising strategy for the elimination of antidepressants in urban wastewaters. However, the use of O3 produced by-products with unknown toxicity.

Effectiveness and cost-effectiveness of antidepressants in primary care: a multiple treatment comparison meta-analysis and cost-effectiveness model.

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Joakim Ramsberg

Full Text Available OBJECTIVE: To determine effectiveness and cost-effectiveness over a one-year time horizon of pharmacological first line treatment in primary care for patients with moderate to severe depression. DESIGN: A multiple treatment comparison meta-analysis was employed to determine the relative efficacy in terms of remission of 10 antidepressants (citalopram, duloxetine escitalopram, fluoxetine, fluvoxamine mirtazapine, paroxetine, reboxetine, sertraline and venlafaxine. The estimated remission rates were then applied in a decision-analytic model in order to estimate costs and quality of life with different treatments at one year. DATA SOURCES: Meta-analyses of remission rates from randomised controlled trials, and cost and quality-of-life data from published sources. RESULTS: The most favourable pharmacological treatment in terms of remission was escitalopram with an 8- to 12-week probability of remission of 0.47. Despite a high acquisition cost, this clinical effectiveness translated into escitalopram being both more effective and having a lower total cost than all other comparators from a societal perspective. From a healthcare perspective, the cost per QALY of escitalopram was €3732 compared with venlafaxine. CONCLUSION: Of the investigated antidepressants, escitalopram has the highest probability of remission and is the most effective and cost-effective pharmacological treatment in a primary care setting, when evaluated over a one year time-horizon. Small differences in remission rates may be important when assessing costs and cost-effectiveness of antidepressants.

The effect of flexible cognitive-behavioural therapy and medical treatment, including antidepressants on post-traumatic stress disorder and depression in traumatised refugees: pragmatic randomised controlled clinical trial.

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Buhmann, Caecilie Böck; Nordentoft, Merete; Ekstroem, Morten; Carlsson, Jessica; Mortensen, Erik Lykke

2016-03-01

Little evidence exists on the treatment of traumatised refugees. To estimate treatment effects of flexible cognitive-behavioural therapy (CBT) and antidepressants (sertraline and mianserin) in traumatised refugees. Randomised controlled clinical trial with 2 × 2 factorial design (registered with Clinicaltrials.gov, NCT00917397, EUDRACT no. 2008-006714-15). Participants were refugees with war-related traumatic experiences, post-traumatic stress disorder (PTSD) and without psychotic disorder. Treatment was weekly sessions with a physician and/or psychologist over 6 months. A total of 217 of 280 patients completed treatment (78%). There was no effect on PTSD symptoms, no effect of psychotherapy and no interaction between psychotherapy and medicine. A small but significant effect of treatment with antidepressants was found on depression. In a pragmatic clinical setting, there was no effect of flexible CBT and antidepressants on PTSD, and there was a small-to-moderate effect of antidepressants and psychoeducation on depression in traumatised refugees. © The Royal College of Psychiatrists 2016.

Disrupting the rhythm of depression: design and protocol of a randomized controlled trial on preventing relapse using brief cognitive therapy with or without antidepressants

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Huibers Marcus JH

2011-01-01

Full Text Available Abstract Background Maintenance treatment with antidepressants is the leading strategy to prevent relapse and recurrence in patients with recurrent major depressive disorder (MDD who have responded to acute treatment with antidepressants (AD. However, in clinical practice most patients (up to 70-80% are not willing to take this medication after remission or take too low dosages. Moreover, as patients need to take medication for several years, it may not be the most cost-effective strategy. The best established effective and available alternative is brief cognitive therapy (CT. However, it is unclear whether brief CT while tapering antidepressants (AD is an effective alternative for long term use of AD in recurrent depression. In addition, it is unclear whether the combination of AD to brief CT is beneficial. Methods/design Therefore, we will compare the effectiveness and cost-effectiveness of brief CT while tapering AD to maintenance AD and the combination of CT with maintenance AD. In addition, we examine whether the prophylactic effect of CT was due to CT tackling illness related risk factors for recurrence such as residual symptoms or to its efficacy to modify presumed vulnerability factors of recurrence (e.g. rigid explicit and/or implicit dysfunctional attitudes. This is a multicenter RCT comparing the above treatment scenarios. Remitted patients on AD with at least two previous depressive episodes in the past five years (n = 276 will be recruited. The primary outcome is time related proportion of depression relapse/recurrence during minimal 15 months using DSM-IV-R criteria as assessed by the Structural Clinical Interview for Depression. Secondary outcome: economic evaluation (using a societal perspective and number, duration and severity of relapses/recurrences. Discussion This will be the first trial to investigate whether CT is effective in preventing relapse to depression in recurrent depression while tapering antidepressant treatment

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

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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.

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.

Duloxetine versus other anti-depressive agents for depression

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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

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.

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

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

Brain functional changes in facial expression recognition in patients with major depressive disorder before and after antidepressant treatment

OpenAIRE

Jiang, Wenyan; Yin, Zhongmin; Pang, Yixin; Wu, Feng; Kong, Lingtao; Xu, Ke

2012-01-01

Functional magnetic resonance imaging was used during emotion recognition to identify changes in functional brain activation in 21 first-episode, treatment-naive major depressive disorder patients before and after antidepressant treatment. Following escitalopram oxalate treatment, patients exhibited decreased activation in bilateral precentral gyrus, bilateral middle frontal gyrus, left middle temporal gyrus, bilateral postcentral gyrus, left cingulate and right parahippocampal gyrus, and inc...

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

The effects of antidepressants on gastric ulcer

Directory of Open Access Journals (Sweden)

Mehmet Latif Güneş

2013-12-01

Full Text Available In their daily practice, psychiatrists often experience gastriccomplaints in patients beside psychiatric disorders.Peptic ulcer is one of the diseases, which accompanyto psychiatric disorders including mainly depression. Itis shown that antidepressants can inflame the bleedingsincluding gastrointestinal (GI bleedings, while they havepositive effect on ulcer healing. In this review, studies,which conducted about the positive or negative effects ofantidepressant drugs on ulcer treatment were examined.Accordingly; it was found that opipramol, amitriptyline,imipramine that of tricyclic antidepressants was found tobe helpful in healing of the ulcer. It was stated that SelectiveSerotonin Reuptake Inhibitors generally inflamedulcers, exceptionally fluvoxamine and fluoxetine reducedulcer; moclobemide that of monoamine-oxidase inhibitorand tianeptine and mirtazapine that of atypical antidepressantshad positive effect in ulcer healing. To be carefulin choosing the appropriate antidepressant in psychiatricpatients with gastric ulcer is important in the prognosisof both ulcer and depression.Key words: peptic ulcer; depression; antidepressant drugs

An extension of hypotheses regarding rapid-acting, treatment-refractory, and conventional antidepressant activity of dextromethorphan and dextrorphan.

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Lauterbach, Edward C

2012-06-01

It was previously hypothesized that dextromethorphan (DM) and dextrorphan (DX) may possess antidepressant properties, including rapid and conventional onsets of action and utility in treatment-refractory depression, based on pharmacodynamic similarities to ketamine. These similarities included sigma-1 (σ(1)) agonist and NMDA antagonist properties, calcium channel blockade, muscarinic binding, serotonin transporter (5HTT) inhibition, and μ receptor potentiation. Here, six specific hypotheses are developed in light of additional mechanisms and evidence. Comparable potencies to ketamine for DM and DX are detailed for σ(1) (DX>DM>ketamine), NMDA PCP site (DX>ketamine>DM), and muscarinic (DX>ketamine>DM) receptors, 5HTT (DM>DX≫ketamine), and NMDA antagonist potentiation of μ receptor stimulation (DM>ketamine). Rapid acting antidepressant properties of DM include NMDA high-affinity site, NMDR-2A, and functional NMDR-2B receptor antagonism, σ(1) stimulation, putative mTOR activation (by σ(1) stimulation, μ potentiation, and 5HTT inhibition), putative AMPA receptor trafficking (by mTOR activation, PCP antagonism, σ(1) stimulation, μ potentiation, and 5HTT inhibition), and dendritogenesis, spinogenesis, synaptogenesis, and neuronal survival by NMDA antagonism and σ(1) and mTOR signaling. Those for dextrorphan include NMDA high-affinity site and NMDR-2A antagonism, σ(1) stimulation, putative mTOR activation (by σ(1) stimulation and ß adrenoreceptor stimulation), putative AMPA receptor trafficking (by mTOR activation, PCP antagonism, σ(1) stimulation, ß stimulation, and μ antagonism), and dendritogenesis, spinogenesis, synaptogenesis, and neuronal survival by NMDA antagonism and σ(1) and mTOR signaling. Conventional antidepressant properties for dextromethorphan and dextrorphan include 5HTT and norepinephrine transporter inhibition, σ(1) stimulation, NMDA and PCP antagonism, and possible serotonin 5HT1b/d receptor stimulation. Additional properties for

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

2011-11-01

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

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...

Consensus statement and research needs: the role of dopamine and norepinephrine in depression and antidepressant treatment.

Science.gov (United States)

Nutt, David J; Baldwin, David S; Clayton, Anita H; Elgie, Rodney; Lecrubier, Yves; Montejo, Angel L; Papakostas, George I; Souery, Daniel; Trivedi, Madhukar H; Tylee, Andre

2006-01-01

During a special session, the faculty identified several specific areas related to the role of dopamine and norepinephrine in depression and antidepressant treatment that either warrant the clinician's attention or are in need of more research. Areas of interest include fatigue and lethargy in depression, treatment strategies for treatment-resistant depression, the somatic presentation of depression, neurobiology of fatigue and its role in determining treatment, symptom rating scales, and sexual side effects. In addition, the faculty discussed the importance of patient psychoeducation and self-management as well as the ways in which disease models of depression affect treatment.

Antidepressant-like activity of resveratrol treatment in the forced swim test and tail suspension test in mice: the HPA axis, BDNF expression and phosphorylation of ERK.

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Wang, Zhen; Gu, Jianhua; Wang, Xueer; Xie, Kai; Luan, Qinsong; Wan, Nianqing; Zhang, Qun; Jiang, Hong; Liu, Dexiang

2013-11-01

Resveratrol is a natural polyphenol enriched in Polygonum cuspidatum and has diverse biological activities. There is only limited information about the antidepressant-like effect of resveratrol. The present study assessed whether resveratrol treatment (20, 40 and 80mg/kg, i.p., 21days) has an antidepressant-like effect on the forced swim test (FST) and tail suspension test (TST) in mice and examined what its molecular targets might be. The results showed that resveratrol administration produced antidepressant-like effects in mice, evidenced by the reduced immobility time in the FST and TST, while it had no effect on the locomotor activity in the open field test. Resveratrol treatment significantly reduced serum corticosterone levels, which had been elevated by the FST and TST. Moreover, resveratrol increased brain-derived neurotrophic factor (BDNF) protein and extracellular signal-regulated kinase (ERK) phosphorylation levels in the prefrontal cortex and hippocampus. All of these antidepressant-like effects of resveratrol were essentially similar to those observed with the clinical antidepressant, fluoxetine. These results suggest that the antidepressant-like effects of resveratrol in the FST and TST are mediated, at least in part, by modulating hypothalamic-pituitary-adrenal axis, BDNF and ERK phosphorylation expression in the brain region of mice. © 2013.

Atypical Antidepressants

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... health-medications/index.shtml. Accessed May 16, 2016. Hirsch M, et al. Atypical antidepressants: Pharmacology, admininstration, and ... www.uptodate.com/home. Accessed May 23, 2016. Hirsch M, et al. Discontinuing antidepressant medications in adults. ...

Systematic Review of Clinical Practice Guidelines for Failed Antidepressant Treatment Response in Major Depressive Disorder, Dysthymia, and Subthreshold Depression in Adults.

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MacQueen, Glenda; Santaguida, Pasqualina; Keshavarz, Homa; Jaworska, Natalia; Levine, Mitchell; Beyene, Joseph; Raina, Parminder

2017-01-01

This systematic review critically evaluated clinical practice guidelines (CPGs) for treating adults with major depressive disorder, dysthymia, or subthreshold or minor depression for recommendations following inadequate response to first-line treatment with selective serotonin reuptake inhibitors (SSRIs). Searches for CPGs (January 2004 to November 2014) in English included 7 bibliographic databases and grey literature sources using CPG and depression as the keywords. Two raters selected CPGs on depression with a national scope. Data extraction included definitions of adequate response and recommended treatment options. Two raters assessed quality using the Appraisal of Guidelines for Research and Evaluation II (AGREE II) instrument. From 46,908 citations, 3167 were screened at full text. From these 21 CPG were applicable to adults in primary care and outpatient settings. Five CPGs consider patients with dysthymia or subthreshold or minor depression. None provides recommendations for those who do not respond to first-line SSRI treatment. For adults with MDD, most CPGs do not define an "inadequate response" or provide specific suggestions regarding how to choose alternative medications when switching to an alternative antidepressant. There is variability between CPGs in recommending combination strategies. AGREE II ratings for stakeholder involvement in CPG development, editorial independence, and rigor of development are domains in which depression guidelines are often less robust. About half of patients with depression require second-line treatment to achieve remission. Consistency and clarity in guidelines for second-line treatment of depression are therefore important for clinicians but lacking in most current guidelines. This may reflect a paucity of primary studies upon which to base conclusions.

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

Science.gov (United States)

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.

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

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

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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.

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.

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

DEFF Research Database (Denmark)

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...

Antidepressant-like effect of peony glycosides in mice.

Science.gov (United States)

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.

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...

Comparative Benefits and Harms of Complementary and Alternative Medicine Therapies for Initial Treatment of Major Depressive Disorder: Systematic Review and Meta-Analysis.

Science.gov (United States)

Asher, Gary N; Gartlehner, Gerald; Gaynes, Bradley N; Amick, Halle R; Forneris, Catherine; Morgan, Laura C; Coker-Schwimmer, Emmanuel; Boland, Erin; Lux, Linda J; Gaylord, Susan; Bann, Carla; Pierl, Christiane Barbara; Lohr, Kathleen N

2017-12-01

To report the comparative benefits and harms of exercise and complementary and alternative medicine (CAM) treatments with second-generation antidepressants (SGA) for major depressive disorder (MDD). Systematic review and meta-analysis. Outpatient clinics. Adults, aged 18 years and older, with MDD receiving an initial treatment attempt with SGA. Any CAM or exercise intervention compared with an SGA. Treatment response, remission, change in depression rating, adverse events, treatment discontinuation, and treatment discontinuation due to adverse events. We found 22 randomized controlled trials for direct comparisons and 127 trials for network meta-analyses, including trials of acupuncture, omega-3 fatty acids, S-adenosyl methionine, St. John's wort, and exercise. For most treatment comparisons, we found no differences between treatment groups for response and remission. However, the risk of bias of these studies led us to conclude that the strength of evidence for these findings was either low or insufficient. The risk of treatment harms and treatment discontinuation attributed to adverse events was higher for selective serotonin receptor inhibitors than for St. John's wort. Although we found little difference in the comparative efficacy of most CAM therapies or exercise and SGAs, the overall poor quality of the available evidence base tempers any conclusions that we might draw from those trials. Future trials should incorporate patient-oriented outcomes, treatment expectancy, depressive severity, and harms assessments into their designs; antidepressants should be administered over their full dosage ranges; and larger trials using methods to reduce sampling bias are needed.

Cordance derived from REM sleep EEG as a biomarker for treatment response in depression--a naturalistic study after antidepressant medication.

Science.gov (United States)

Adamczyk, Marek; Gazea, Mary; Wollweber, Bastian; Holsboer, Florian; Dresler, Martin; Steiger, Axel; Pawlowski, Marcel

2015-04-01

To evaluate whether prefrontal cordance in theta frequency band derived from REM sleep EEG after the first week of antidepressant medication could characterize the treatment response after 4 weeks of therapy in depressed patients. 20 in-patients (15 females, 5 males) with a depressive episode and 20 healthy matched controls were recruited into 4-week, open label, case-control study. Patients were treated with various antidepressants. No significant differences in age (responders (mean ± SD): 45 ± 22) years; non-responders: 49 ± 12 years), medication or Hamilton Depression Rating Scale (HAM-D) score (responders: 23.8 ± 4.5; non-responders 24.5 ± 7.6) at inclusion into the study were found between responders and non-responders. Response to treatment was defined as a ≥50% reduction of HAM-D score at the end of four weeks of active medication. Sleep EEG of patients was recorded after the first and the fourth week of medication. Cordance was computed for prefrontal EEG channels in theta frequency band during tonic REM sleep. The group of 8 responders had significantly higher prefrontal theta cordance in relation to the group of 12 non-responders after the first week of antidepressant medication. This finding was significant also when controlling for age, gender and number of previous depressive episodes (F1,15 = 6.025, P = .027). Furthermore, prefrontal cordance of all patients showed significant positive correlation (r = 0.52; P = .019) with the improvement of HAM-D score between the inclusion week and fourth week of medication. The results suggest that prefrontal cordance derived from REM sleep EEG could provide a biomarker for the response to antidepressant treatment in depressed patients. Copyright © 2015 Elsevier Ltd. All rights reserved.

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 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...

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

Science.gov (United States)

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

Increased risk of treatment with antidepressants in stroke compared with other chronic illness

DEFF Research Database (Denmark)

Dam, Henrik; Harhoff, Mette; Andersen, Per Kragh

2007-01-01

The prevalence of depression and anxiety is higher in patients with stroke than in the general population but it is unclear whether patients with stroke are at an increased risk of being treated for depression and anxiety compared with patients with other chronic illness. The objective...... of the present study was to investigate whether the rate of treatment with antidepressants is increased in patients with stroke compared with patients with other chronic illness and compared with the general population. By linkage of nationwide case registers, all patients who received a main diagnosis of stroke...

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

Science.gov (United States)

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.

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

Experiences of antidepressant medication and cognitive-behavioural therapy for depression: a grounded theory study.

Science.gov (United States)

Bayliss, Paul; Holttum, Sue

2015-09-01

To develop a preliminary model of the experiences of people undergoing combined treatment with antidepressant medication and cognitive-behavioural therapy (CBT) for depression. The study used a qualitative methodology informed by grounded theory. Participants were 12 adults who had received treatment with antidepressant medication and CBT for depression. Participants engaged in a semistructured interview about their experiences. Interviews were transcribed and analysed using components of grounded theory methodology. Medication was often seen as an initial aid to surviving a crisis. Staying on medication longer term resulted in some participants feeling caught in a 'drug loop'. Feeling that medication was unhelpful or actively harmful could contribute to participants seeking CBT. Medics also offered information on CBT and acted as gatekeepers, meaning that negotiation was sometimes necessary. CBT was described as a process of being guided towards skilled self-management. Occasionally, participants felt that medication had facilitated CBT at one or more stages. Conversely, developing skilled self-management through CBT could reduce feelings of dependency on medication and affect several of the other elements maintaining the 'drug loop'. Antidepressant medication and CBT are perceived and experienced differently, with CBT often being seen as an alternative to medication, or even as a means to discontinue medication. Service users' experiences and beliefs about medication may thus affect their engagement and goals in CBT, and it may be important for therapists to consider this. Practitioners who prescribe medication should ensure that they also provide information on the availability and appropriateness of CBT, and engage in an open dialogue about treatment options. CBT practitioners should explore aspects of clients' experiences and beliefs about medication. This would particularly include clients' experiences of the effects of medication, their beliefs about

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.

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

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

Science.gov (United States)

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.

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.

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.

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...

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

Directory of Open Access Journals (Sweden)

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.

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.

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 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.

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

Beliefs about medications predict adherence to antidepressants in older adults.

Science.gov (United States)

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.

Milnacipran: a unique antidepressant?

Directory of Open Access Journals (Sweden)

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

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.

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.

Science.gov (United States)

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.

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.

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

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.

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.

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.

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

Science.gov (United States)

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

Platelet alpha 2-adrenergic receptors in major depressive disorder. Binding of tritiated clonidine before and after tricyclic antidepressant drug treatment

International Nuclear Information System (INIS)

Garcia-Sevilla, J.A.; Zis, A.P.; Hollingsworth, P.J.; Greden, J.F.; Smith, C.B.

1981-01-01

The specific binding of tritiated (3H)-clonidine, an alpha 2-adrenergic receptor agonist, to platelet membranes was measured in normal subjects and in patients with major depressive disorder. The number of platelet alpha 2-adrenergic receptors from the depressed group was significantly higher than that found in platelets obtained from the control population. Treatment with tricyclic antidepressant drugs led to significant decreases in the number of platelet alpha 2-adrenergic receptors. These results support the hypothesis that the depressive syndrome is related to an alpha 2-adrenergic receptor supersensitivity and that the clinical effectiveness of tricyclic antidepressant drugs is associated with a decrease in the number of these receptors

Antidepressant efficacy of sertraline and imipramine for the treatment of major depression in elderly outpatients

Directory of Open Access Journals (Sweden)

Orestes Vicente Forlenza

2000-07-01

Full Text Available CONTEXT: Most double-blind studies of efficacy and tolerability of sertraline as compared to tricyclics in the treatment of late-life major depression have used amitriptyline as a standard, leading to the inevitable conclusion that the former drug is better tolerated than the latter, with both being equally efficacious. OBJECTIVE: To compare the antidepressant efficacy and tolerability of sertraline (50 mg/day and imipramine (150 mg/day in the first 6 weeks of the treatment of major depression in the elderly. DESIGN: A randomized double-blind parallel study with 6 weeks of follow-up. SETTING: The psychogeriatric clinic at the Institute of Psychiatry, Hospital das Clínicas, Faculty of Medicine of the University of São Paulo. PARTICIPANTS: 55 severe and moderately depressed non-demented outpatients aged 60 years or more. INTERVENTION: Patients were assigned to sertraline 50 mg/day or imipramine 150 mg/day. MAIN MEASUREMENTS: CAMDEX interview. Psychiatric diagnosis followed the guidelines for "Major Depressive Episode" according to DSM-IV criteria. Severity of symptoms was evaluated using the "CGI" and "MADRS" scales. Cognitive state was assessed using the Mini-Mental State Examination. Side effects were assessed using the "Safetee-Up" schedule. RESULTS: Both groups had a significant decrease in depressive symptoms according to the MADRS scores after 6 weeks of treatment (P = 0.01. No significant differences between groups were detected regarding treatment outcome (t = 0.4; P = 0.7. Although the dropout rate was greater in the imipramine group, the overall tolerability among patients who completed the 6-week trial was similar in both test groups. CONCLUSIONS: Both sertraline and imipramine exhibited good efficacy and an acceptable side-effect profile for elderly depressed patients after 6 weeks of antidepressant treatment.

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.

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

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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.

COMPLIANCE TO LONG-TERM TREATMENT OF CARDIOLOGIC PATIENTS WITH MILD TO MODERATE DEPRESSION: INEFFECTIVENESS OF ANTIDEPRESSIVE THERAPY WITH PIRLINDOL IN RANDOMIZED STUDY

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E. V. Strokova

2015-12-01

Full Text Available Aim. To evaluate the influence of antidepressant therapy with pirlindol on compliance to the long-term treatment and quality of life in patients with cardiovascular diseases and mild to moderate depression. Material and methods. 61 patients with cardiovascular diseases and mild to moderate depression (according to Beck depression scale were randomized into two groups. Patients of intervention group received pirlindol, while patients of control group did not receive this drug. Compliance to cardiovascular and antidepressant treatment were estimated in 3 and 6 months. Adverse reactions and patients self-assessment of their well-being and global satisfaction in treatmen were also registered.  Results. 24 (75%, 2 (6% and 0 patients of intervention group continue pirlindol treatment in 1, 3 and 6 months, respectively. In 3 months of observation patients of intervention group took drugs for cardiovascular diseases more often than these in control group (81% vs 72%, respectively , р<0.05, they also less frequently showed adverse reactions (56% vs 72%, respectively ,p=0.01 and more often — improvement of their well-being (65% vs 50%, respectively , р=0.03. Compliance to cardiovascular therapy did not differ significantly in patients of both groups by the end the study.  Conclusion. Antidepressant therapy with pirlindol did not influence compliance to long-term cardiovascular treatment in patients with cardiovascular diseases and mild to moderate depression, apparently because of low compliance to pirlindol therapy.

Antidepressant induced excessive yawning and indifference

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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.

Antidepressant medications and osteoporosis.

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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.

A meta-analysis of randomised placebo-controlled treatment trials for depression and anxiety in Parkinson's disease.

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Lakkhina Troeung

Full Text Available Psychopharmacotherapy currently constitutes the first-line treatment for depression and anxiety in Parkinson's disease (PD however the efficacy of antidepressant treatments in PD is unclear. Several alternative treatments have been suggested as potentially more viable alternatives including dopamine agonists, repetitive transcranial magnetic stimulation, and cognitive behavioural therapy (CBT.A meta-analysis of randomised placebo-controlled trials for depression and/or anxiety in PD was conducted to systematically examine the efficacy of current treatments for depression and anxiety in PD.Nine trials were included. There was only sufficient data to calculate a pooled effect for antidepressant therapies. The pooled effect of antidepressants for depression in PD was moderate but non-significant (d = .71, 95% CI = -1.33 to 3.08. The secondary effect of antidepressants on anxiety in PD was large but also non-significant (d = 1.13, 95% CI = -.67 to 2.94. Two single-trials of non-pharmacological treatments for depression in PD resulted in significant large effects; Omega-3 supplementation (d = .92, 95% CI = .15 to 1.69 and CBT (d = 1.57, 95% CI = 1.06 to 2.07, and warrant further exploration.There remains a lack of controlled trials for both pharmacological and non-pharmacological treatments for depression and anxiety in PD which limits the conclusions which can be drawn. While the pooled effects of antidepressant therapies in PD were non-significant, the moderate to large magnitude of each pooled effect is promising. Non-pharmacological approaches show potential for depression in PD however more research is required.

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.

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

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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.

Cordance derived from REM sleep EEG as a biomarker for treatment response in depression--a naturalistic study after antidepressant medication

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Adamczyk, M.; Gazea, M.; Wollweber, B.; Holsboer, F.; Dresler, M.; Steiger, A.; Pawlowski, M.

2015-01-01

OBJECTIVE: To evaluate whether prefrontal cordance in theta frequency band derived from REM sleep EEG after the first week of antidepressant medication could characterize the treatment response after 4 weeks of therapy in depressed patients. METHOD: 20 in-patients (15 females, 5 males) with a

Non-Antidepressant Long-term Treatment in Post-Traumatic Stress Disorder (PTSD).

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Kerbage, Hala; Richa, Sami

2015-01-01

Post-traumatic stress disorder (PTSD) is a frequent and disabling condition that occurs after exposure to a traumatic event, and Selective Serotonin Reuptake Inhibitors (SSRIs) are considered the first-line treatment approach for this disorder. However, a large proportion of patients remain symptomatic and other pharmacological agents have been investigated, based on the understanding of the underlying biological dysfunctions of PTSD. We conducted a review of the literature on the pharmacological options for PTSD other than the antidepressants, using MedLine and Web of Science databases, with search terms including the pharmacologic class of each agent plus PTSD, or pharmacotherapy, or fear conditioning. The literature review covered articles published until august 2012, including reviews and original articles. Agents like antipsychotics, anticonvulsants, benzodiazepines, anti-adrenergic agents, have been studied in randomized clinical trials (RCTs), with general positive results for antipsychotics, especially as adjunct therapy, and for prazosin for sleep-related disturbances. However, one important target for novel medications is the modulation of the fear conditioning process, through the alteration of retrieval/reconsolidation or enhancement of fear extinction. This is traditionally targeted in prolonged exposure therapy, but pre-clinical findings from studies investigating agents like propanolol, clonidine, N-Methyl-D-aspartic Acid Receptor (NMDAR) compounds, 3,4-methylenedioxy-N-methylamphetamine (MDMA) and cannabinoids, indicate promising results in affecting the fear conditioning process and thus improving PTSD core symptoms. Antipsychotics can be considered a reasonable alternative option to PTSD, with the largest body of evidence for risperidone, even though larger RCTs are warranted. Prazosin is also a promising agent, especially for sleep-related disturbances, while anticonvulsants and benzodiazepines lack empirical support. However, the most promising

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. PMID:29497300

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

"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.

Study On The Anti-Depressant Effect Of Chaihu Guizhi Decoction ...

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Study On The Anti-Depressant Effect Of Chaihu Guizhi Decoction And Its Mechinisims Of Actions. Y Liu, C Cao, H Ding. Abstract. Background: Chaihu Guizhi has the effects of treating exogenous wind-cold; alternating episodes of chills and fever; noisy nose and retching; strong headache; chest and rib-side pain, and ...

Depression during pregnancy: views on antidepressant use and information sources of general practitioners and pharmacists

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Schobben Fred

2009-07-01

Full Text Available Abstract Background The use of antidepressants during pregnancy has increased in recent years. In the Netherlands, almost 2% of all pregnant women are exposed to antidepressants. Although guidelines have been developed on considerations that should be taken into account, prescribing antidepressants during pregnancy is still a subject of debate. Physicians and pharmacists may have opposing views on using medication during pregnancy and may give contradictory advice on whether or not to take medication for depression and anxiety disorders during pregnancy. In this study, we investigated information sources used by general practitioners (GPs and pharmacists and their common practices. Methods A questionnaire on the use of information sources and the general approach when managing depression during pregnancy was sent out to 1400 health care professionals to assess information sources on drug safety during pregnancy and also the factors that influence decision-making. The questionnaires consisted predominantly of closed multiple-choice questions. Results A total of 130 GPs (19% and 144 pharmacists (21% responded. The most popular source of information on the safety of drug use during pregnancy is the Dutch National Health Insurance System Formulary, while a minority of respondents contacts the Dutch national Teratology Information Service (TIS. The majority of GPs contact the pharmacy with questions concerning drug use during pregnancy. There is no clear line with regard to treatment or consensus between GPs on the best therapeutic strategy, nor do practitioners agree upon the drug of first choice. GPs have different views on stopping or continuing antidepressants during pregnancy or applying alternative treatment options. The debate appears to be ongoing as to whether or not specialised care for mother and child is indicated in cases of gestational antidepressant use. Conclusion Primary health care workers are not univocal concerning therapy for

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.

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.

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

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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.

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...

Regulation of brain-derived neurotrophic factor (BDNF) in the chronic unpredictable stress rat model and the effects of chronic antidepressant treatment

DEFF Research Database (Denmark)

Larsen, Marianne H; Mikkelsen, Jens D; Hay-Schmidt, Anders

2010-01-01

Chronic unpredictable stress (CUS) is a widely used animal model of depression. The present study was undertaken to investigate behavioral, physiological and molecular effects of CUS and/or chronic antidepressant treatment (venlafaxine or imipramine) in the same set of animals. Anhedonia, a core ...

Alterations in leukocyte transcriptional control pathway activity associated with major depressive disorder and antidepressant treatment.

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Mellon, S H; Wolkowitz, O M; Schonemann, M D; Epel, E S; Rosser, R; Burke, H B; Mahan, L; Reus, V I; Stamatiou, D; Liew, C-C; Cole, S W

2016-05-24

Major depressive disorder (MDD) is associated with a significantly elevated risk of developing serious medical illnesses such as cardiovascular disease, immune impairments, infection, dementia and premature death. Previous work has demonstrated immune dysregulation in subjects with MDD. Using genome-wide transcriptional profiling and promoter-based bioinformatic strategies, we assessed leukocyte transcription factor (TF) activity in leukocytes from 20 unmedicated MDD subjects versus 20 age-, sex- and ethnicity-matched healthy controls, before initiation of antidepressant therapy, and in 17 of the MDD subjects after 8 weeks of sertraline treatment. In leukocytes from unmedicated MDD subjects, bioinformatic analysis of transcription control pathway activity indicated an increased transcriptional activity of cAMP response element-binding/activating TF (CREB/ATF) and increased activity of TFs associated with cellular responses to oxidative stress (nuclear factor erythroid-derived 2-like 2, NFE2l2 or NRF2). Eight weeks of antidepressant therapy was associated with significant reductions in Hamilton Depression Rating Scale scores and reduced activity of NRF2, but not in CREB/ATF activity. Several other transcriptional regulation pathways, including the glucocorticoid receptor (GR), nuclear factor kappa-B cells (NF-κB), early growth response proteins 1-4 (EGR1-4) and interferon-responsive TFs, showed either no significant differences as a function of disease or treatment, or activities that were opposite to those previously hypothesized to be involved in the etiology of MDD or effective treatment. Our results suggest that CREB/ATF and NRF2 signaling may contribute to MDD by activating immune cell transcriptome dynamics that ultimately influence central nervous system (CNS) motivational and affective processes via circulating mediators.

Use and costs of prescription medications and alternative treatments in patients with osteoarthritis and chronic low back pain in community-based settings.

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Gore, Mugdha; Tai, Kei-Sing; Sadosky, Alesia; Leslie, Douglas; Stacey, Brett R

2012-09-01

To evaluate the use and direct medical costs of pharmacologic and alternative treatments for patients with osteoarthritis (OA) and chronic low back pain (CLBP). The LifeLink™ Health Plan Claims Database was used to identify patients ≥18 years old, diagnosed with OA (N = 112,951) or CLBP (N = 101,294). Of these patients, 64,085 with OA and 47,386 with CLBP received pain-related treatments during CY2008 and were selected for inclusion. For patients in both cohorts, pharmacologic and alternative treatments, and direct medical costs were examined during CY2008. Opioids were the most frequently prescribed medication (>70%) in both groups, followed by nonselective nonsteroidal anti-inflammatory drugs (>50%). Over 30% received antidepressants, >20% received benzodiazepines, and 15% in each group received sedative hypnotics. Use of alternative treatments was as follows: chiropractor, OA 11%, CLBP 34%; physical therapy, 20% in both groups; transcutaneous electrical nerve stimulations (TENS), OA 14%, CLBP 22%; acupuncture, hydrotherapy, massage therapy, and biofeedback, patients were, OA: $15,638 ($22,595); CLBP: $11,829 ($20,035). Pharmacologic therapies accounted for approximately 20% of these costs, whereas alternative treatments accounted for only 3% to 4% of the total costs. Patients with OA and CLBP used a variety of pain-related and adjunctive medications. Although, alternative treatments are widely recommended, we found limited use of several of these in clinical practice, potentially due to the source of our data (commercial claims). Further research is needed to ascertain the extent to which such therapies contribute to the total costs of OA and CLBP management. © 2012 The Authors. Pain Practice © 2012 World Institute of Pain.

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.

Low- vs high- frequency Repetitive Transcranial Magnetic Stimulation as an add-on treatment for refractory depression

Directory of Open Access Journals (Sweden)

julien eeche

2012-03-01

Full Text Available Objectives: Repetitive transcranial magnetic stimulation (rTMS seems to be effective as an antidepressant treatment, however, some confusion remain about the best parameters to apply and the efficacy of its association with pharmacological antidepressant treatments.Method: In a single blind randomized study14 patients with unipolar resistant depression to one antidepressant treatment were enrolled to received, in combination with venlafaxine (150 mg, either 20 sessions of 10Hz rTMS (2 000 pulses per session applied over le left dorsolateral prefrontal cortex (DLPFC or 20 sessions of 1 Hz rTMS (120 stimulations per sessions applied over the right DLPFC. Results: A similar antidepressant effect was observed in both groups with a comparable antidepressant delay of action (2 weeks and a comparable number of patients in remission after 4 weeks of daily rTMS sessions (66 vs 50 %.Conclusion: Low- and high- frequency rTMS seem to be effective as an add-on treatment to venlafaxine in pharmacological refractory major depression. Due to its short duration and its safety, low frequency rTMS may be a useful alternative treatment for patients with refractory depression.

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.

Antidepressant-Like Effect of Isorhynchophylline in Mice.

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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.

Alternative Cancer Treatments: 10 Options to Consider

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Alternative cancer treatments: 10 options to consider Alternative cancer treatments can't cure your cancer, but they may provide some ... that may help them, including complementary and alternative cancer treatments. If cancer makes you feel as if you ...

Cost effectiveness analysis comparing repetitive transcranial magnetic stimulation to antidepressant medications after a first treatment failure for major depressive disorder in newly diagnosed patients - A lifetime analysis.

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Voigt, Jeffrey; Carpenter, Linda; Leuchter, Andrew

2017-01-01

Repetitive Transcranial Magnetic Stimulation (rTMS) commonly is used for the treatment of Major Depressive Disorder (MDD) after patients have failed to benefit from trials of multiple antidepressant medications. No analysis to date has examined the cost-effectiveness of rTMS used earlier in the course of treatment and over a patients' lifetime. We used lifetime Markov simulation modeling to compare the direct costs and quality adjusted life years (QALYs) of rTMS and medication therapy in patients with newly diagnosed MDD (ages 20-59) who had failed to benefit from one pharmacotherapy trial. Patients' life expectancies, rates of response and remission, and quality of life outcomes were derived from the literature, and treatment costs were based upon published Medicare reimbursement data. Baseline costs, aggregate per year quality of life assessments (QALYs), Monte Carlo simulation, tornado analysis, assessment of dominance, and one way sensitivity analysis were also performed. The discount rate applied was 3%. Lifetime direct treatment costs, and QALYs identified rTMS as the dominant therapy compared to antidepressant medications (i.e., lower costs with better outcomes) in all age ranges, with costs/improved QALYs ranging from $2,952/0.32 (older patients) to $11,140/0.43 (younger patients). One-way sensitivity analysis demonstrated that the model was most sensitive to the input variables of cost per rTMS session, monthly prescription drug cost, and the number of rTMS sessions per year. rTMS was identified as the dominant therapy compared to antidepressant medication trials over the life of the patient across the lifespan of adults with MDD, given current costs of treatment. These models support the use of rTMS after a single failed antidepressant medication trial versus further attempts at medication treatment in adults with MDD.

Cost effectiveness analysis comparing repetitive transcranial magnetic stimulation to antidepressant medications after a first treatment failure for major depressive disorder in newly diagnosed patients - A lifetime analysis.

Directory of Open Access Journals (Sweden)

Jeffrey Voigt

Full Text Available Repetitive Transcranial Magnetic Stimulation (rTMS commonly is used for the treatment of Major Depressive Disorder (MDD after patients have failed to benefit from trials of multiple antidepressant medications. No analysis to date has examined the cost-effectiveness of rTMS used earlier in the course of treatment and over a patients' lifetime.We used lifetime Markov simulation modeling to compare the direct costs and quality adjusted life years (QALYs of rTMS and medication therapy in patients with newly diagnosed MDD (ages 20-59 who had failed to benefit from one pharmacotherapy trial. Patients' life expectancies, rates of response and remission, and quality of life outcomes were derived from the literature, and treatment costs were based upon published Medicare reimbursement data. Baseline costs, aggregate per year quality of life assessments (QALYs, Monte Carlo simulation, tornado analysis, assessment of dominance, and one way sensitivity analysis were also performed. The discount rate applied was 3%.Lifetime direct treatment costs, and QALYs identified rTMS as the dominant therapy compared to antidepressant medications (i.e., lower costs with better outcomes in all age ranges, with costs/improved QALYs ranging from $2,952/0.32 (older patients to $11,140/0.43 (younger patients. One-way sensitivity analysis demonstrated that the model was most sensitive to the input variables of cost per rTMS session, monthly prescription drug cost, and the number of rTMS sessions per year.rTMS was identified as the dominant therapy compared to antidepressant medication trials over the life of the patient across the lifespan of adults with MDD, given current costs of treatment. These models support the use of rTMS after a single failed antidepressant medication trial versus further attempts at medication treatment in adults with MDD.

Long-term treatment effect of trauma-affected refugees with flexible cognitive behavioural therapy and antidepressants.

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Buhmann, Caecilie Böck; Nordentoft, Merete; Ekstroem, Morten; Carlsson, Jessica; Mortensen, Erik Lykke

2018-04-04

Few studies exist on the long-term effect of treatment of trauma-affected refugees. The purpose of this study was to estimate the long-term treatment effects of cognitive behavioural therapy and antidepressants (sertraline and mianserin) in trauma-affected refugees. Follow-ups were conducted 6 and 18 months after a randomised controlled clinical trial. The included patients were refugees with war-related traumatic experiences, PTSD and without psychotic disorders. We found a small improvement over time in PTSD, depression and anxiety symptoms and level of functioning, but the improvement was not associated with any specific treatment. Personality change after catastrophic experiences and life events influenced the symptom level at all follow-ups while depression at completion of treatment was associated with a steeper decline in symptom load at the follow-ups. In spite of the limited decline in symptom scores and treatment effects immediately after treatment, the condition of the treated trauma-affected refugees was significantly improved 6 and 18 months after treatment although the improvement was small. Copyright © 2018 Elsevier B.V. All rights reserved.

The International Society for Bipolar Disorders (ISBD) Task Force Report on Antidepressant Use in Bipolar Disorders

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Pacchiarotti, Isabella; Bond, David J.; Baldessarini, Ross J.; Nolen, Willem A.; Grunze, Heinz; Licht, Rasmus W.; Post, Robert M.; Berk, Michael; Goodwin, Guy M.; Sachs, Gary S.; Tondo, Leonardo; Findling, Robert L.; Youngstrom, Eric A.; Tohen, Mauricio; Undurraga, Juan; González-Pinto, Ana; Goldberg, Joseph F.; Yildiz, Ayşegül; Altshuler, Lori L.; Calabrese, Joseph R.; Mitchell, Philip B.; Thase, Michael E.; Koukopoulos, Athanasios; Colom, Francesc; Frye, Mark A.; Malhi, Gin S.; Fountoulakis, Konstantinos N.; Vázquez, Gustavo; Perlis, Roy H.; Ketter, Terence A.; Cassidy, Frederick; Akiskal, Hagop; Azorin, Jean-Michel; Valentí, Marc; Mazzei, Diego Hidalgo; Lafer, Beny; Kato, Tadafumi; Mazzarini, Lorenzo; Martínez-Aran, Anabel; Parker, Gordon; Souery, Daniel; Özerdem, Ayşegül; McElroy, Susan L.; Girardi, Paolo; Bauer, Michael; Yatham, Lakshmi N.; Zarate, Carlos A.; Nierenberg, Andrew A.; Birmaher, Boris; Kanba, Shigenobu; El-Mallakh, Rif S.; Serretti, Alessandro; Rihmer, Zoltan; Young, Allan H.; Kotzalidis, Georgios D.; MacQueen, Glenda M.; Bowden, Charles L.; Ghaemi, S. Nassir; Lopez-Jaramillo, Carlos; Rybakowski, Janusz; Ha, Kyooseob; Perugi, Giulio; Kasper, Siegfried; Amsterdam, Jay D.; Hirschfeld, Robert M.; Kapczinski, Flávio; Vieta, Eduard

2014-01-01

Objective The risk-benefit profile of antidepressant medications in bipolar disorder is controversial. When conclusive evidence is lacking, expert consensus can guide treatment decisions. The International Society for Bipolar Disorders (ISBD) convened a task force to seek consensus recommendations on the use of antidepressants in bipolar disorders. Method An expert task force iteratively developed consensus through serial consensus-based revisions using the Delphi method. Initial survey items were based on systematic review of the literature. Subsequent surveys included new or reworded items and items that needed to be rerated. This process resulted in the final ISBD Task Force clinical recommendations on antidepressant use in bipolar disorder. Results There is striking incongruity between the wide use of and the weak evidence base for the efficacy and safety of antidepressant drugs in bipolar disorder. Few well-designed, long-term trials of prophylactic benefits have been conducted, and there is insufficient evidence for treatment benefits with antidepressants combined with mood stabilizers. A major concern is the risk for mood switch to hypomania, mania, and mixed states. Integrating the evidence and the experience of the task force members, a consensus was reached on 12 statements on the use of antidepressants in bipolar disorder. Conclusions Because of limited data, the task force could not make broad statements endorsing antidepressant use but acknowledged that individual bipolar patients may benefit from antidepressants. Regarding safety, serotonin reuptake inhibitors and bupropion may have lower rates of manic switch than tricyclic and tetracyclic antidepressants and norepinephrine-serotonin reuptake inhibitors. The frequency and severity of antidepressant-associated mood elevations appear to be greater in bipolar I than bipolar II disorder. Hence, in bipolar I patients antidepressants should be prescribed only as an adjunct to mood-stabilizing medications

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

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

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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.

Increased use of antidepressants in Wuhan, China: a retrospective study from 2006 to 2012.

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Gao, Ping; Zhang, Huanian; Xu, Hua; Zhang, Chengliang; Liu, Dong

2013-01-01

The aim of this study was to investigate the trend of antidepressant use and analyze the daily cost of antidepressants in Wuhan, China. The data on the expenditure of antidepressants in Wuhan from 2006 to 2012 were retrospectively analyzed based on the defined daily dose (DDD) method recommended by the World Health Organization. In addition, the daily cost of antidepressants was calculated for the pharmacoeconomic evaluation. The overall sales of antidepressants increased by 566.7% over the 7-year period. The utilization of antidepressants increased annually from 1.067 DDDs per 1000 inhabitants per day in 2006 to 4.144 in 2012. This upward trend was mainly driven by an increase in the use of selective serotonin reuptake inhibitors (SSRIs), which accounted for about 60% of antidepressant use. Notably, the use of traditional Chinese patent medicines (TCMs) approved to treat depression in China in 2010 increased from 0.158 DDDs per 1000 inhabitants per day in 2010 to 0.305 in 2012. The daily drug cost analysis indicated that selective serotonin and norepinephrine reuptake inhibitors (SNRIs) and other new antidepressants were more expensive while tricyclic and tetracyclic antidepressants (TCAs) had a low-cost advantage. Antidepressants were increasingly used over the study period. Among them, SSRIs followed by SNRIs were the most commonly used. After the approval for the treatment of depression, TCMs were generally accepted by physicians and patients. The low-cost advantage allowed TCAs to be used in the antidepressant therapy.

Parallel-group placebo-controlled trial of testosterone gel in men with major depressive disorder displaying an incomplete response to standard antidepressant treatment.

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Pope, Harrison G; Amiaz, Revital; Brennan, Brian P; Orr, Guy; Weiser, Mark; Kelly, John F; Kanayama, Gen; Siegel, Arthur; Hudson, James I; Seidman, Stuart N

2010-04-01

Exogenous testosterone therapy has psychotropic effects and has been proposed as an antidepressant augmentation strategy for depressed men. We sought to assess the antidepressant effects of testosterone augmentation of a serotonergic antidepressant in depressed, hypogonadal men. For this study, we recruited 100 medically healthy adult men with major depressive disorder showing partial response or no response to an adequate serotonergic antidepressant trial during the current episode and a screening total testosterone level of 350 ng/dL or lower. We randomized these men to receive testosterone gel or placebo gel in addition to their existing antidepressant regimen. The primary outcome measure was the Hamilton Depression Rating Scale (HDRS) score. Secondary measures included the Montgomery-Asberg Depression Rating Scale, the Clinical Global Impression Scale, and the Quality of Life Scale. Our primary analysis, using a mixed effects linear regression model to compare rate of change of scores between groups on the outcome measures, failed to show a significant difference between groups (mean [95% confidence interval] 6-week change in HDRS for testosterone vs placebo, -0.4 [-2.6 to 1.8]). However, in one exploratory analysis of treatment responders, we found a possible trend in favor of testosterone on the HDRS. Our findings, combined with the conflicting data from earlier smaller studies, suggest that testosterone is not generally effective for depressed men. The possibility remains that testosterone might benefit a particular subgroup of depressed men, but if so, the characteristics of this subgroup would still need to be established.

Evaluation of the antidepressant- and anxiolytic-like effects of a hydrophilic extract from the green seaweed Ulva sp. in rats.

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Violle, Nicolas; Rozan, Pascale; Demais, Hervé; Nyvall Collen, Pi; Bisson, Jean-François

2018-05-01

The green seaweed Ulva sp. contains a large amount of ulvans, a family of sulphated polysaccharides. The present study was designed to investigate in rats the antidepressant- and anxiolytic-like effects of a hydrophilic extract of Ulva sp. (MSP) containing about 45% of ulvans. After a 14-day administration of MSP at doses of 10, 20 and 40 mg/kg/day, 48 and 60 male adult Wistar rats were respectively tested in the elevated plus-maze (EPM) and the forced swimming test (FST). In the FST, MSP effects were compared to the reference antidepressant drug imipramine (IMI) (10 mg/kg/day). Acute and sub-chronic toxicities of the extract were also assessed in male and female rats following OECD guidelines. MSP treatment did not modify anxiety-related behaviour in the EPM. In contrast, MSP induced a dose-dependent reduction of immobility behaviour in the FST. At the highest tested dose of 40 mg/kg, MSP displayed a significant antidepressant-like effect similar to IMI. MSP did not modify the exploratory behaviour of rats in the open field test and did not produce any toxic effect. MSP may potentially represent a good adjunct or alternative to existing antidepressant therapeutics. Further studies are necessary to confirm the mechanism of action of MSP and its modulation of brain functioning.

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.

Spadin, a sortilin-derived peptide, targeting rodent TREK-1 channels: a new concept in the antidepressant drug design.

Directory of Open Access Journals (Sweden)

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

Ghrelin Serum Concentrations Are Associated with Treatment Response During Lithium Augmentation of Antidepressants.

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Ricken, Roland; Bopp, Sandra; Schlattmann, Peter; Himmerich, Hubertus; Bschor, Tom; Richter, Christoph; Elstner, Samuel; Stamm, Thomas J; Schulz-Ratei, Brigitte; Lingesleben, Alexandra; Reischies, Friedel M; Sterzer, Philipp; Borgwardt, Stefan; Bauer, Michael; Heinz, Andreas; Hellweg, Rainer; Lang, Undine E; Adli, Mazda

2017-09-01

Lithium augmentation of antidepressants is an effective strategy in treatment-resistant depression. The proteohormone ghrelin is thought to be involved in the pathophysiology of depression. The purpose of this study was to investigate the association of treatment response with the course of ghrelin levels during lithium augmentation. Ghrelin serum concentrations and severity of depression were measured in 85 acute depressive patients before and after 4 weeks of lithium augmentation. In a linear mixed model analysis, we found a significant effect of response*time interaction (F1.81=9.48; P=.0028): under treatment, ghrelin levels increased in nonresponders and slightly decreased in responders to lithium augmentation. The covariate female gender had a significant positive effect (F1.83=4.69; P=.033), whereas time, response, appetite, and body mass index (kg/m2) did not show any significant effect on ghrelin levels (P>.05). This is the first study showing that the course of ghrelin levels separates responders and nonresponders to lithium augmentation. Present results support the hypothesis that ghrelin serum concentrations might be involved in response to pharmacological treatment of depression. © The Author 2017. Published by Oxford University Press on behalf of CINP.

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

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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.

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.

Alternative Menopause Treatments

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... menopausal symptoms. These include estrogen—still the most effective treatment for many menopausal symptoms—non-estrogen prescription drugs, and complementary and alternative medicine (CAM). What is CAM? CAM refers to practices ...

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

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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

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.

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...

Mouse Strain Affects Behavioral and Neuroendocrine Stress Responses Following Administration of Probiotic Lactobacillus rhamnosus JB-1 or Traditional Antidepressant Fluoxetine.

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McVey Neufeld, Karen-Anne; Kay, Sebastian; Bienenstock, John

2018-01-01

Currently, there is keen interest in the development of alternative therapies in the treatment of depression. Given the explosion of research focused on the microbiota-gut-brain axis, consideration has turned to the potential of certain probiotics to improve patient outcomes for those suffering from mood disorders. Here we examine the abilities of a known antidepressant, fluoxetine, and the probiotic Lactobacillus rhamnosus JB-1™, to attenuate responses to two established criteria for depressive-like behavior in animal models, the tail suspension test (TST) and the corticosterone response to an acute restraint stressor. We examine two different strains of mice known to differ in the extent to which they express both anxiety-like behavior and measures of despair-BALB/c and Swiss Webster-with respectively high and normal behavioral phenotypes for each. While adult male BALB/c mice responded with increased antidepressive-like behavior to both fluoxetine and L. rhamnosus JB-1 in both the TST and the corticosterone stress response, SW mice did not respond to either treatment as compared to controls. These findings highlight the importance of investigating putative antidepressants in mouse strains known to express face validity for some markers of depression. Clinical studies examining the activity of L. rhamnosus JB-1 in patients suffering from mood disorders are warranted, as well as further pre-clinical work examining how interactions between host genotype and intestinal microbial alterations may impact behavioral responses. This study adds to the literature supporting the possibility that modifying the intestinal microbiota via probiotics represents a promising potential therapeutic breakthrough in the treatment of psychiatric disease.

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

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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.

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.

New insights into the pharmacogenomics of antidepressant response from the GENDEP and STAR*D studies: rare variant analysis and high-density imputation.

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Fabbri, C; Tansey, K E; Perlis, R H; Hauser, J; Henigsberg, N; Maier, W; Mors, O; Placentino, A; Rietschel, M; Souery, D; Breen, G; Curtis, C; Sang-Hyuk, L; Newhouse, S; Patel, H; Guipponi, M; Perroud, N; Bondolfi, G; O'Donovan, M; Lewis, G; Biernacka, J M; Weinshilboum, R M; Farmer, A; Aitchison, K J; Craig, I; McGuffin, P; Uher, R; Lewis, C M

2017-11-21

Genome-wide association studies have generally failed to identify polymorphisms associated with antidepressant response. Possible reasons include limited coverage of genetic variants that this study tried to address by exome genotyping and dense imputation. A meta-analysis of Genome-Based Therapeutic Drugs for Depression (GENDEP) and Sequenced Treatment Alternatives to Relieve Depression (STAR*D) studies was performed at the single-nucleotide polymorphism (SNP), gene and pathway levels. Coverage of genetic variants was increased compared with previous studies by adding exome genotypes to previously available genome-wide data and using the Haplotype Reference Consortium panel for imputation. Standard quality control was applied. Phenotypes were symptom improvement and remission after 12 weeks of antidepressant treatment. Significant findings were investigated in NEWMEDS consortium samples and Pharmacogenomic Research Network Antidepressant Medication Pharmacogenomic Study (PGRN-AMPS) for replication. A total of 7062 950 SNPs were analyzed in GENDEP (n=738) and STAR*D (n=1409). rs116692768 (P=1.80e-08, ITGA9 (integrin α9)) and rs76191705 (P=2.59e-08, NRXN3 (neurexin 3)) were significantly associated with symptom improvement during citalopram/escitalopram treatment. At the gene level, no consistent effect was found. At the pathway level, the Gene Ontology (GO) terms GO: 0005694 (chromosome) and GO: 0044427 (chromosomal part) were associated with improvement (corrected P=0.007 and 0.045, respectively). The association between rs116692768 and symptom improvement was replicated in PGRN-AMPS (P=0.047), whereas rs76191705 was not. The two SNPs did not replicate in NEWMEDS. ITGA9 codes for a membrane receptor for neurotrophins and NRXN3 is a transmembrane neuronal adhesion receptor involved in synaptic differentiation. Despite their meaningful biological rationale for being involved in antidepressant effect, replication was partial. Further studies may help in clarifying

Mesoporous hydroxyapatite as a carrier of olanzapine for long-acting antidepression treatment in rats with induced depression.

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Shyong, Yan-Jye; Wang, Mao-Hsien; Kuo, Li-Wei; Su, Chang-Fu; Kuo, Wei-Ting; Chang, Kuo-Chi; Lin, Feng-Huei

2017-06-10

An antidepressant carrier, mesoporous hydroxyapatite olanzapine (mesoHAP-OLZ), was designed to maintain 3weeks of constant medication release. The carrier was intramuscularly (IM) injected, where cellular activity played a role in achieving the goal of constant release. The efficiency of the treatment was evaluated from 3 perspectives in in vivo studies: locomotor activities, biomarkers, and learning and memory ability. MesoHAP-OLZ can increase the locomotor activity in rats with induced depression determined by open field test (OFT) and forced swim test (FST). Serotonin (5-HT), one of the most important biomarker in depression can also be increased by mesoHAP-OLZ, leading to increased hippocampus activity as measured by functional magnetic resonance imaging (fMRI). MesoHAP-OLZ can also improve learning and memory ability in rats with induced depression during Morris water maze (MWM) test. Our findings further show that mesoHAP-OLZ can provide long-term drug release with a single IM injection, helping to solve the problem of non-adherent medication intake that often occurs in antidepressant therapy. Copyright © 2017 Elsevier B.V. All rights reserved.

Suicidality and aggression during antidepressant treatment

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Sharma, Tarang; Guski, Louise Schow; Freund, Nanna

2016-01-01

OBJECTIVE: To study serious harms associated with selective serotonin and serotonin-norepinephrine reuptake inhibitors.Design Systematic review and meta-analysis. MAIN OUTCOME MEASURES: Mortality and suicidality. Secondary outcomes were aggressive behaviour and akathisia. DATA SOURCES: Clinical...... for any of the trials. Differences in mortality (all deaths were in adults, odds ratio 1.28, 95% confidence interval 0.40 to 4.06), suicidality (1.21, 0.84 to 1.74), and akathisia (2.04, 0.93 to 4.48) were not significant, whereas patients taking antidepressants displayed more aggressive behaviour (1.......93, 1.26 to 2.95). For adults, the odds ratios were 0.81 (0.51 to 1.28) for suicidality, 1.09 (0.55 to 2.14) for aggression, and 2.00 (0.79 to 5.04) for akathisia. The corresponding values for children and adolescents were 2.39 (1.31 to 4.33), 2.79 (1.62 to 4.81), and 2.15 (0.48 to 9.65). In the summary...

Vortioxetine: A new alternative for the treatment of major depressive disorder.

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Salagre, Estela; Grande, Iria; Solé, Brisa; Sanchez-Moreno, Jose; Vieta, Eduard

Major Depressive Disorder (MDD) is a serious psychiatric condition. Its treatment remains a challenge nowadays. Vortioxetine is a novel antidepressant with a unique profile, as it acts as a multimodal serotoninergic agent. Its efficacy in MDD has been established in many short- and long-term studies, with 7 positive, 4 negative and 1 failed randomized controlled trials. Moreover, its ability to modulate a wide range of neurotransmitters (serotonin, dopamine, norepinephrine, histamine, glutamate or GABA) confers vortioxetine pro-cognitive effects. Side effects are also different from conventional antidepressants, according to its low incidence of sexual dysfunction, weight gain or cardiovascular alterations. The aim of this systematic review is to describe the pharmacology, clinical efficacy and safety profile of vortioxetine, as well as its potential effectiveness in improving cognitive symptoms. Copyright © 2017 SEP y SEPB. Publicado por Elsevier España, S.L.U. All rights reserved.

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.

Highly polygenic architecture of antidepressant treatment response: Comparative analysis of SSRI and NRI treatment in an animal model of depression.

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Malki, Karim; Tosto, Maria Grazia; Mouriño-Talín, Héctor; Rodríguez-Lorenzo, Sabela; Pain, Oliver; Jumhaboy, Irfan; Liu, Tina; Parpas, Panos; Newman, Stuart; Malykh, Artem; Carboni, Lucia; Uher, Rudolf; McGuffin, Peter; Schalkwyk, Leonard C; Bryson, Kevin; Herbster, Mark

2017-04-01

Response to antidepressant (AD) treatment may be a more polygenic trait than previously hypothesized, with many genetic variants interacting in yet unclear ways. In this study we used methods that can automatically learn to detect patterns of statistical regularity from a sparsely distributed signal across hippocampal transcriptome measurements in a large-scale animal pharmacogenomic study to uncover genomic variations associated with AD. The study used four inbred mouse strains of both sexes, two drug treatments, and a control group (escitalopram, nortriptyline, and saline). Multi-class and binary classification using Machine Learning (ML) and regularization algorithms using iterative and univariate feature selection methods, including InfoGain, mRMR, ANOVA, and Chi Square, were used to uncover genomic markers associated with AD response. Relevant genes were selected based on Jaccard distance and carried forward for gene-network analysis. Linear association methods uncovered only one gene associated with drug treatment response. The implementation of ML algorithms, together with feature reduction methods, revealed a set of 204 genes associated with SSRI and 241 genes associated with NRI response. Although only 10% of genes overlapped across the two drugs, network analysis shows that both drugs modulated the CREB pathway, through different molecular mechanisms. Through careful implementation and optimisations, the algorithms detected a weak signal used to predict whether an animal was treated with nortriptyline (77%) or escitalopram (67%) on an independent testing set. The results from this study indicate that the molecular signature of AD treatment may include a much broader range of genomic markers than previously hypothesized, suggesting that response to medication may be as complex as the pathology. The search for biomarkers of antidepressant treatment response could therefore consider a higher number of genetic markers and their interactions. Through

Drug–drug interactions involving antidepressants: focus on desvenlafaxine

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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

A marginal structural model to estimate the causal effect of antidepressant medication treatment on viral suppression among homeless and marginally housed persons with HIV.

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Tsai, Alexander C; Weiser, Sheri D; Petersen, Maya L; Ragland, Kathleen; Kushel, Margot B; Bangsberg, David R

2010-12-01

Depression strongly predicts nonadherence to human immunodeficiency virus (HIV) antiretroviral therapy, and adherence is essential to maintaining viral suppression. This suggests that pharmacologic treatment of depression may improve virologic outcomes. However, previous longitudinal observational analyses have inadequately adjusted for time-varying confounding by depression severity, which could yield biased estimates of treatment effect. Application of marginal structural modeling to longitudinal observation data can, under certain assumptions, approximate the findings of a randomized controlled trial. To determine whether antidepressant medication treatment increases the probability of HIV viral suppression. Community-based prospective cohort study with assessments conducted every 3 months. Community-based research field site in San Francisco, California. One hundred fifty-eight homeless and marginally housed persons with HIV who met baseline immunologic (CD4+ T-lymphocyte count, 13) inclusion criteria, observed from April 2002 through August 2007. Probability of achieving viral suppression to less than 50 copies/mL. Secondary outcomes of interest were probability of being on an antiretroviral therapy regimen, 7-day self-reported percentage adherence to antiretroviral therapy, and probability of reporting complete (100%) adherence. Marginal structural models estimated a 2.03 greater odds of achieving viral suppression (95% confidence interval [CI], 1.15-3.58; P = .02) resulting from antidepressant medication treatment. In addition, antidepressant medication use increased the probability of antiretroviral uptake (weighted odds ratio, 3.87; 95% CI, 1.98-7.58; P effect is likely attributable to improved adherence to a continuum of HIV care, including increased uptake and adherence to antiretroviral therapy.

Segregating the cerebral mechanisms of antidepressants and placebo in fibromyalgia.

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Jensen, Karin B; Petzke, Frank; Carville, Serena; Choy, Ernest; Fransson, Peter; Gracely, Richard H; Vitton, Olivier; Marcus, Hanke; Williams, Steven C R; Ingvar, Martin; Kosek, Eva

2014-12-01

Antidepressant drugs are commonly used to treat fibromyalgia, but there is little knowledge about their mechanisms of action. The aim of this study was to compare the cerebral and behavioral response to positive treatment effects of antidepressants or placebo. Ninety-two fibromyalgia patients participated in a 12-week, double-blind, placebo-controlled clinical trial with milnacipran, a serotonin-norepinephrine reuptake inhibitor. Before and after treatment, measures of cerebral pain processing were obtained using functional magnetic resonance imaging. Also, there were stimulus response assessments of pressure pain, measures of weekly pain, and fibromyalgia impact. Following treatment, milnacipran responders exhibited significantly higher activity in the posterior cingulum compared with placebo responders. The mere exposure to milnacipran did not explain our findings because milnacipran responders exhibited increased activity also in comparison to milnacipran nonresponders. Stimulus response assessments revealed specific antihyperalgesic effects in milnacipran responders, which was also correlated with reduced clinical pain and with increased activation of the posterior cingulum. A short history of pain predicted positive treatment response to milnacipran. We report segregated neural mechanisms for positive responses to treatment with milnacipran and placebo, reflected in the posterior cingulum. The increase of pain-evoked activation in the posterior cingulum may reflect a normalization of altered default mode network processing, an alteration implicated in fibromyalgia pathophysiology. This study presents neural and psychophysical correlates to positive treatment responses in patients with fibromyalgia, treated with either milnacipran or placebo. The comparison between placebo responders and milnacipran responders may shed light on the specific mechanisms involved in antidepressant treatment of chronic pain. Copyright © 2014 American Pain Society. Published by

Sex-specific antidepressant effects of dietary creatine with and without sub-acute fluoxetine in rats

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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

3’-Deoxyadenosine (Cordycepin) Produces a Rapid and Robust Antidepressant Effect via Enhancing Prefrontal AMPA Receptor Signaling Pathway

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Li, Bai; Hou, Yangyang; Zhu, Ming; Bao, Hongkun; Nie, Jun; Zhang, Grace Y.; Shan, Liping; Yao, Yao; Du, Kai; Yang, Hongju; Li, Meizhang; Zheng, Bingrong; Xu, Xiufeng; Xiao, Chunjie; Du, Jing

2016-01-01

Background: The development of rapid and safe antidepressants for the treatment of major depression is in urgent demand. Converging evidence suggests that glutamatergic signaling seems to play important roles in the pathophysiology of depression. Methods: We studied the antidepressant effects of 3’-deoxyadenosine (3’-dA, Cordycepin) and the critical role of the α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor in male CD-1 mice via behavioral and biochemical experiments. After 3’-dA treatment, the phosphorylation and synaptic localization of the AMPA receptors GluR1 and GluR2 were determined in the prefrontal cortex (PFC) and hippocampus (HIP). The traditional antidepressant imipramine was applied as a positive control. Results: We found that an injection of 3’-dA led to a rapid and robust antidepressant effect, which was significantly faster and stronger than imipramine, after 45min in tail suspension and forced swim tests. This antidepressant effect remained after 5 days of treatment with 3’-dA. Unlike the psycho-stimulants, 3’-dA did not show a hyperactive effect in the open field test. After 45min or 5 days of treatment, 3’-dA enhanced GluR1 S845 phosphorylation in both the PFC and HIP. In addition, after 45min of treatment, 3’-dA significantly up-regulated GluR1 S845 phosphorylation and GluR1, but not GluR2 levels, at the synapses in the PFC. After 5 days of treatment, 3’-dA significantly enhanced GluR1 S845 phosphorylation and GluR1, but not GluR2, at the synapses in the PFC and HIP. Moreover, the AMPA-specific antagonist GYKI 52466 was able to block the rapid antidepressant effects of 3’-dA. Conclusion: This study identified 3’-dA as a novel rapid antidepressant with clinical potential and multiple beneficial mechanisms, particularly in regulating the prefrontal AMPA receptor signaling pathway. PMID:26443809

Peripheral blood and neuropsychological markers for the onset of action of antidepressant drugs in patients with Major Depressive Disorder

Directory of Open Access Journals (Sweden)

Hiemke Christoph

2011-01-01

Full Text Available Abstract Background In Major Depressive Disorder (MDD, treatment outcomes with currently available strategies are often disappointing. Therefore, it is sensible to develop new strategies to increase remission rates in acutely depressed patients. Many studies reported that true drug response can be observed within 14 days (early improvement of antidepressant treatment. The identical time course of symptom amelioration after early improvement in patients treated with antidepressants of all classes or with placebo strongly suggests a common biological mechanism, which is not specific for a particular antidepressant medication. However, the biology underlying early improvement and final treatment response is not understood and there is no established biological marker as yet, which can predict treatment response for the individual patient before initiation or during the course of antidepressant treatment. Peripheral blood markers and executive functions are particularly promising candidates as markers for the onset of action and thus the prediction of final treatment outcome in MDD. Methods/Design The present paper presents the rationales, objectives and methods of a multi-centre study applying close-meshed repetitive measurements of peripheral blood and neuropsychological parameters in patients with MDD and healthy controls during a study period of eight weeks for the identification of biomarkers for the onset of antidepressants' action in patients with MDD. Peripheral blood parameters and depression severity are assessed in weekly intervals from baseline to week 8, executive performance in bi-weekly intervals. Patients are participating in a randomized controlled multi-level clinical trial, healthy controls are matched according to mean age, sex and general intelligence. Discussion This investigation will help to identify a biomarker or a set of biomarkers with decision-making quality in the treatment of MDD in order to increase the currently

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 ...

B vitamins to enhance treatment response to antidepressants in middle-aged and older adults: results from the B-VITAGE randomised, double-blind, placebo-controlled trial.

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Almeida, Osvaldo P; Ford, Andrew H; Hirani, Varsha; Singh, Vash; vanBockxmeer, Frank M; McCaul, Kieran; Flicker, Leon

2014-12-01

Depression is common and the efficacy of antidepressants is suboptimal. High plasma homocysteine has been consistently associated with depression, and treatment with certain B vitamins demonstrably reduces its concentration. To determine whether vitamins B6, B12 and folic acid enhance response to antidepressant treatment over 52 weeks. Randomised, double-blind, placebo-controlled trial of citalopram (20-40 g) together with 0.5 mg of vitamin B12, 2 mg of folic acid and 25 mg of vitamin B6 for 52 weeks (Australian and New Zealand Clinical Trials Registry: 12609000256279). Participants were community-dwelling adults aged 50 years or over with DSM-IV-TR major depression. We measured severity of symptoms with the Montgomery-Åsberg Depression Rating Scale (MADRS). The primary outcome was remission of the depressive episode after 12, 26 and 52 weeks. Secondary outcomes included reduction of MADRS scores over time and relapse of major depression after recovery by week 12. Results In total, 153 people were randomised (76 placebo, 77 vitamins). Remission of symptoms was achieved by 78.1 and 79.4% of participants treated with placebo and vitamins by week 12 (P = 0.840), by 76.5 and 85.3% at week 26 and 75.8 and 85.5% at week 52 (effect of intervention over 52 weeks: odds ratio (OR) = 2.49, 95% CI 1.12-5.51). Group differences in MADRS scores over time were not significant (P = 0.739). The risk of subsequent relapse among those who had achieved remission of symptoms at week 12 was lower in the vitamins than placebo group (OR = 0.33, 95% CI 0.12-0.94). B vitamins did not increase the 12-week efficacy of antidepressant treatment, but enhanced and sustained antidepressant response over 1 year. Replication of these findings would mandate that treatment guidelines adopt the adjunctive use of B vitamins as a safe and inexpensive strategy to manage major depression in middle-aged and older adults. Royal College of Psychiatrists.

Persistent antidepressant effect of low-dose ketamine and activation in the supplementary motor area and anterior cingulate cortex in treatment-resistant depression: A randomized control study.

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Chen, Mu-Hong; Li, Cheng-Ta; Lin, Wei-Chen; Hong, Chen-Jee; Tu, Pei-Chi; Bai, Ya-Mei; Cheng, Chih-Ming; Su, Tung-Ping

2018-01-01

A single low-dose ketamine infusion exhibited a rapid antidepressant effect within 1h. Despite its short biological half-life (approximately 3h), the antidepressant effect of ketamine has been demonstrated to persist for several days. However, changes in brain function responsible for the persistent antidepressant effect of a single low-dose ketamine infusion remain unclear METHODS: Twenty-four patients with treatment-resistant depression (TRD) were randomized into three groups according to the treatment received: 0.5mg/kg ketamine, 0.2mg/kg ketamine, and normal saline infusion. Standardized uptake values (SUVs) of glucose metabolism measured through 18 F-FDG positron-emission-tomography before infusion and 1day after a 40-min ketamine or normal saline infusion were used for subsequent whole-brain voxel-wise analysis and were correlated with depressive symptoms, as defined using the Hamilton Depression Rating Scale-17 (HDRS-17) score RESULTS: The voxel-wise analysis revealed that patients with TRD receiving the 0.5mg/kg ketamine infusion had significantly higher SUVs (corrected for family-wise errors, P = 0.014) in the supplementary motor area (SMA) and dorsal anterior cingulate cortex (dACC) than did those receiving the 0.2mg/kg ketamine infusion. The increase in the SUV in the dACC was negatively correlated with depressive symptoms at 1day after ketamine infusion DISCUSSION: The persistent antidepressant effect of a 0.5mg/kg ketamine infusion may be mediated by increased activation in the SMA and dACC. The higher increase in dACC activation was related to the reduction in depressive symptoms after ketamine infusion. A 0.5mg/kg ketamine infusion facilitated the glutamatergic neurotransmission in the SMA and dACC, which may be responsible for the persistent antidepressant effect of ketamine much beyond its half-life. Copyright © 2017 Elsevier B.V. All rights reserved.

Treatment alternatives for non-fuel-bearing hardware

International Nuclear Information System (INIS)

Ross, W.A.; Clark, L.L.; Oma, K.H.

1987-01-01

This evaluation compared four alternatives for the treatment or processing of non-fuel bearing hardware (NFBH) to reduce its volume and prepare it for disposal. These treatment alternatives are: shredding; shredding and low pressure compaction; shredding and supercompaction; and melting. These alternatives are compared on the basis of system costs, waste form characteristics, and process considerations. The study recommends that melting and supercompaction alternatives be further considered and that additional testing be conducted for these two alternatives

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

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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.

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.

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.

Stopping Antidepressants and Anxiolytics as Major Concerns Reported in Online Health Communities: A Text Mining Approach.

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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.

Antidepressant activity of nociceptin/orphanin FQ receptor antagonists in the mouse learned helplessness.

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Holanda, Victor A D; Medeiros, Iris U; Asth, Laila; Guerrini, Remo; Calo', Girolamo; Gavioli, Elaine C

2016-07-01

Pharmacological and genetic evidence support antidepressant-like effects elicited by the blockade of the NOP receptor. The learned helplessness (LH) model employs uncontrollable and unpredictable electric footshocks as a stressor stimulus to induce a depressive-like phenotype that can be reversed by classical antidepressants. The present study aimed to evaluate the action of NOP receptor antagonists in helpless mice. Male Swiss mice were subjected to the three steps of the LH paradigm (i.e., (1) induction, (2) screening, and (3) test). Only helpless animals were subjected to the test session. During the test session, animals were placed in the electrified chamber and the latency to escape after the footshock and the frequency of escape failures were recorded. The effect of the following treatments administered before the test session were evaluated: nortriptyline (30 mg/kg, ip, 60 min), fluoxetine (30 mg/kg, ip, four consecutive days of treatment), and NOP antagonists SB-612111 (1-10 mg/kg, ip, 30 min) and UFP-101 (1-10 nmol, icv, 5 min). To rule out possible biases, the effects of treatments on controllable stressful and non stressful situations were assessed. In helpless mice, nortriptyline, fluoxetine, UFP-101 (3-10 nmol), and SB-612111 (3-10 mg/kg) significantly reduced escape latencies and escape failures. No effects of drug treatments were observed in mice subjected to the controllable electric footshocks and non stressful situations. Acute treatment with NOP antagonists reversed helplessness similarly to the classical antidepressants. These findings support the proposal that NOP receptor antagonists are worthy of development as innovative antidepressant drugs.

Dopamine mediated antidepressant effect of Mucuna pruriens seeds in various experimental models of depression.

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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-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

Study protocol for a randomized controlled trial comparing mindfulness-based cognitive therapy with maintenance anti-depressant treatment in the prevention of depressive relapse/recurrence: the PREVENT trial

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Hayes Rachel

2010-10-01

Full Text Available Abstract Background Depression is a common and distressing mental health problem that is responsible for significant individual disability and cost to society. Medication and psychological therapies are effective for treating depression and maintenance anti-depressants (m-ADM can prevent relapse. However, individuals with depression often express a wish for psychological help that can help them recover from depression in the long-term. We need to develop psychological therapies that prevent depressive relapse/recurrence. A recently developed treatment, Mindfulness-based Cognitive Therapy (MBCT, see http://www.mbct.co.uk shows potential as a brief group programme for people with recurring depression. In two studies it has been shown to halve the rates of depression recurring compared to usual care. This trial asks the policy research question, is MBCT superior to m-ADM in terms of: a primary outcome of preventing depressive relapse/recurrence over 24 months; and, secondary outcomes of (a depression free days, (b residual depressive symptoms, (c antidepressant (ADM usage, (d psychiatric and medical co-morbidity, (e quality of life, and (f cost effectiveness? An explanatory research question asks is an increase in mindfulness skills the key mechanism of change? Methods/Design The design is a single blind, parallel RCT examining MBCT vs. m-ADM with an embedded process study. To answer the main policy research question the proposed trial compares MBCT plus ADM-tapering with m-ADM for patients with recurrent depression. Four hundred and twenty patients with recurrent major depressive disorder in full or partial remission will be recruited through primary care. Depressive relapse/recurrence over two years is the primary outcome variable. The explanatory question will be addressed in two mutually informative ways: quantitative measurement of potential mediating variables pre/post-treatment and a qualitative study of service users' views and experiences

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

Does good leadership buffer effects of high emotional demands at work on risk of antidepressant treatment?

DEFF Research Database (Denmark)

Madsen, Ida E H; Hanson, Linda L Magnusson; Rugulies, Reiner Ernst

2014-01-01

Emotionally demanding work has been associated with increased risk of common mental disorders. Because emotional demands may not be preventable in certain occupations, the identification of workplace factors that can modify this association is vital. This article examines whether effects of emoti...... of emotional demands on antidepressant treatment, as an indicator of common mental disorders, are buffered by good leadership.......Emotionally demanding work has been associated with increased risk of common mental disorders. Because emotional demands may not be preventable in certain occupations, the identification of workplace factors that can modify this association is vital. This article examines whether effects...

Mouse Strain Affects Behavioral and Neuroendocrine Stress Responses Following Administration of Probiotic Lactobacillus rhamnosus JB-1 or Traditional Antidepressant Fluoxetine

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Karen-Anne McVey Neufeld

2018-05-01

Full Text Available Currently, there is keen interest in the development of alternative therapies in the treatment of depression. Given the explosion of research focused on the microbiota-gut-brain axis, consideration has turned to the potential of certain probiotics to improve patient outcomes for those suffering from mood disorders. Here we examine the abilities of a known antidepressant, fluoxetine, and the probiotic Lactobacillus rhamnosus JB-1™, to attenuate responses to two established criteria for depressive-like behavior in animal models, the tail suspension test (TST and the corticosterone response to an acute restraint stressor. We examine two different strains of mice known to differ in the extent to which they express both anxiety-like behavior and measures of despair—BALB/c and Swiss Webster—with respectively high and normal behavioral phenotypes for each. While adult male BALB/c mice responded with increased antidepressive-like behavior to both fluoxetine and L. rhamnosus JB-1 in both the TST and the corticosterone stress response, SW mice did not respond to either treatment as compared to controls. These findings highlight the importance of investigating putative antidepressants in mouse strains known to express face validity for some markers of depression. Clinical studies examining the activity of L. rhamnosus JB-1 in patients suffering from mood disorders are warranted, as well as further pre-clinical work examining how interactions between host genotype and intestinal microbial alterations may impact behavioral responses. This study adds to the literature supporting the possibility that modifying the intestinal microbiota via probiotics represents a promising potential therapeutic breakthrough in the treatment of psychiatric disease.

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.

Neurobiological aspects of depressive disorder and antidepressant treatment: role of glia

Czech Academy of Sciences Publication Activity Database

Páv, M.; Kovářů, H.; Fišerová, Anna; Havrdová, E.; Lisá, Věra

2008-01-01

Roč. 57, č. 2 (2008), s. 151-164 ISSN 0862-8408 R&D Projects: GA ČR GA524/05/0267; GA AV ČR IAA500200620 Institutional research plan: CEZ:AV0Z50110509; CEZ:AV0Z50200510 Keywords : major depression * mood disorder * antidepressant Subject RIV: EC - Immunology Impact factor: 1.653, year: 2008

Relationship between depressive symptoms and miRNA expression level in monocytes of patients with depression before and after antidepressant treatment

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Qiao-li ZHANG

2015-04-01

Full Text Available Objective　To explore the correlation of depressive symptoms to the microRNA (miRNA expression level in monocytes of patients with depression before and after antidepressant treatment. Methods　Eighty-one patients with depression, admitted to the 102 Hospital of PLA from Aug. 2012 to Oct. 2013, having not received antidepressants treatment and meeting the criteria as listed in Diagnostic and Statistical Manual 4th edition (DSM-IV, were selected as case group. Eighty-one normal individuals served as control group. With Affymetrix Expression Array, 26 miRNAs were identified from 3 individuals from each group as candidate miRNA, and among them 9 miRNAs (miR-146b, miR-1972, miR-26b, miR-29b, miR-338, miR-4485, miR-4498, miR-4743 and miR-874 in monocytes were selected for quantitative real-time reverse transcription polymerase chain reaction (RTPCR assessment. Twenty patients from the case group were selected for the assessment of miRNA expression levels, and the clinical symptoms and treatment effect were evaluated using Hamilton Depression Scale (HAMD and Clinical Global Impression (CGI, before and 6 weeks after antidepressant (venlafaxine, sertraline, mirtazapine, etc. treatment. Results　Compared with the control group, the expression levels of miRNA-26b, miRNA-4743, miRNA-4498, miRNA-4485 and miRNA-1972 of the case group were significantly up-regulated (P<0.05. The variance of expression level of miRNA-4743, miRNA-4498, miRNA-4485 and miRNA-1972 was respectively positively correlated with improvement in retardation factors (P<0.05, meanwhile the variance of expression level of miRNA-26b was negatively correlated with the improvement of day and night change factors (P<0.05. Logistic regression analysis demonstrated that the alteration of miRNA-4485 expression may account 28.8% of retardation variance (P<0.05. Conclusion　 The miRNA-4743, miRNA-4498, miRNA-4485, miRNA-1972 and miRNA-26b in monocytes may serve as the biomarkers for the

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

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.

Antidepressant-like effects of Gan-Mai-Dazao-Tang via monoamine regulatory pathways on forced swimming test in rats.

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Huang, Hsiang-Ling; Lim, Swee-Ling; Lu, Kuan-Hung; Sheen, Lee-Yan

2018-01-01

Depression is a highly prevalent and recurrent mental disorder that impacts all aspects of human life. Undesirable effects of the antidepressant drugs led to the development of complementary and alternative therapies. Gan-Mai-Da-Zao-Tang (, gān mài dà zǎo tang) is a traditional herbal formula commonly used for the treatment of depression, but lack of scientific proof on its mechanism. It consisted of Glycyrrhiza uralensis Fisch. (licorice), Triticum aestivum L. (wheat) and Zizphus jujuba Mill. (jujube). The objective of this study is to investigate the antidepressant effects of Gan-Mai-Dazao-Tang and its ingredients in rats exposed to forced swimming test (FST). The 72 of male Nerl: Wistar rats (8 weeks old) were randomized into control (10 mL/kg bw H 2 O), licorice (0.4 g/kg bw), wheat (1.6 g/kg bw), jujube (0.5 g/kg bw), Gan-Mai-Da-Zao-Tang (2.5 g/kg bw of licorice: wheat: jujube in ratio of 5:20:6) and Prozac (18 mg/kg bw) groups. Samples were administered by oral gavage for 21 days. FST was performed on 21st day, with 15 min for pretest followed by 5 min for real test. Then, the animals were sacrificed and brain tissues were collected for monoamines analyses. The Gan-Mai-Da-Zao-Tang (LWJ) showed significantly down-regulation of immobility time, 3,4-dihydroxyphenylacetic acid (DOPAC) and DOPAC/dopamine (DA) turnover rates, and also enhanced the concentration of serotonin (5-HT) and DA in brain tissues, as compared with the control. The LWJ stated the potent antidepressant-like effect by modulating these monoamines concentration, while the licorice, wheat and jujube did not reported significant results as compared with control group. The positive control (Prozac) was noted with significantly reduction in body weight and appetite. In conclusion, the antidepressant-like effects of LWJ might be mediated by the regulation of monoamine neurotransmitters. Thus, it could beneficial in depression treatment as a complementary approach.

Tratamento de idosos com depressão utilizando tricíclicos, IMAO, ISRS e outros antidepressivos Depression treatment of elderly patients using tricyclics, MAOI, SSRI, and other antidepressants

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Mônica Z Scalco

2002-04-01

Full Text Available Antidepressivos são eficazes no tratamento da depressão em idosos. O sucesso do tratamento depende do tipo e da gravidade da depressão; das comorbidades com outras doenças psiquiátricas ou clínicas; da escolha adequada de antidepressivos, de sua eficácia e perfil de efeitos adversos; da orientação do paciente e de sua aderência ao tratamento. O manejo dos efeitos adversos em pacientes idosos, que usam muito mais medicações e apresentam mais doenças, é o ponto forte na escolha de antidepressivos. Em geral, os inibidores seletivos da recaptação de serotonina têm sido preferidos por apresentar menos riscos de complicações por efeitos adversos. Porém, diferentes antidepressivos podem ser preferíveis para diferentes pacientes. É indispensável que o médico conheça o paciente que irá tratar e o perfil de efeitos adversos e de possíveis interações medicamentosas dos antidepressivos para poder escolher o mais adequado para cada paciente. Neste artigo, são abordados os diferentes grupos de antidepressivos no tratamento agudo da depressão em idosos e o tratamento em populações especiais de idosos (idosos debilitados e idosos com demência.Antidepressants are effective in treating depression in the elderly. Treatment response depends on the type and severity of depression, comorbidities, efficacy and tolerability of antidepressants, patient education and treatment compliance. The aging process leads to physiological changes that, in association with concomitant diseases and use of several medications, render the elderly person more vulnerable to the adverse effects of antidepressants and an increased risk of drug interactions. It is very important that psychiatrists treating elderly patients be aware of possible adverse effects and drug interactions of different antidepressants. This paper reviews data on the efficacy and safety of antidepressant agents currently available for the treatment of the elderly, and includes

Investigation of miR-1202, miR-135a, and miR-16 in Major Depressive Disorder and Antidepressant Response.

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Fiori, Laura M; Lopez, Juan Pablo; Richard-Devantoy, Stéphane; Berlim, Marcelo; Chachamovich, Eduardo; Jollant, Fabrice; Foster, Jane; Rotzinger, Susan; Kennedy, Sidney H; Turecki, Gustavo

2017-08-01

Major depressive disorder is a debilitating illness, which is most commonly treated with antidepressant drugs. As the majority of patients do not respond on their first trial, there is great interest in identifying biological factors that indicate the most appropriate treatment for each patient. Studies suggest that microRNA represent excellent biomarkers to predict antidepressant response. We investigated the expression of miR-1202, miR-135a, and miR-16 in peripheral blood from 2 cohorts of depressed patients who received 8 weeks of antidepressant therapy. Expression was quantified at baseline and after treatment, and its relationship to treatment response and depressive symptoms was assessed. In both cohorts, responders displayed lower baseline miR-1202 levels compared with nonresponders, which increased following treatment. Ultimately, our results support the involvement of microRNA in antidepressant response and suggest that quantification of their levels in peripheral samples represents a valid approach to informing treatment decisions. © The Author 2017. Published by Oxford University Press on behalf of CINP.

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.

Chronic treatment with escitalopram but not R-citalopram translocates Galpha(s) from lipid raft domains and potentiates adenylyl cyclase: a 5-hydroxytryptamine transporter-independent action of this antidepressant compound.

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Zhang, Lanqiu; Rasenick, Mark M

2010-03-01

Chronic antidepressant treatment has been shown to increase adenylyl cyclase activity, in part, due to translocation of Galpha(s) from lipid rafts to a nonraft fraction of the plasma membrane where they engage in a more facile stimulation of adenylyl cyclase. This effect holds for multiple classes of antidepressants, and for serotonin uptake inhibitors, it occurs in the absence of the serotonin transporter. In the present study, we examined the change in the amount of Galpha(s) in lipid raft and whole cell lysate after exposing C6 cells to escitalopram. The results showed that chronic (but not acute) escitalopram decreased the content of Galpha(s) in lipid rafts, whereas there was no change in overall Galpha(s) content. These effects were drug dose- and exposure time-dependent. Although R-citalopram has been reported to antagonize some effects of escitalopram, this compound was without effect on Galpha(s) localization in lipid rafts, and R-citalopram did not inhibit these actions of escitalopram. Escitalopram treatment increased cAMP accumulation, and this seemed due to increased coupling between Galpha(s) and adenylyl cyclase. Thus, escitalopram is potent, rapid and efficacious in translocating Galpha(s) from lipid rafts, and this effect seems to occur independently of 5-hydroxytryptamine transporters. Our results suggest that, although antidepressants display distinct affinities for well identified targets (e.g., monoamine transporters), several presynaptic and postsynaptic molecules are probably modified during chronic antidepressant treatment, and these additional targets may be required for clinical efficacy of these drugs.

Chronic Treatment with Escitalopram but Not R-Citalopram Translocates Gαs from Lipid Raft Domains and Potentiates Adenylyl Cyclase: A 5-Hydroxytryptamine Transporter-Independent Action of This Antidepressant Compound

Science.gov (United States)

Zhang, Lanqiu

2010-01-01

Chronic antidepressant treatment has been shown to increase adenylyl cyclase activity, in part, due to translocation of Gαs from lipid rafts to a nonraft fraction of the plasma membrane where they engage in a more facile stimulation of adenylyl cyclase. This effect holds for multiple classes of antidepressants, and for serotonin uptake inhibitors, it occurs in the absence of the serotonin transporter. In the present study, we examined the change in the amount of Gαs in lipid raft and whole cell lysate after exposing C6 cells to escitalopram. The results showed that chronic (but not acute) escitalopram decreased the content of Gαs in lipid rafts, whereas there was no change in overall Gαs content. These effects were drug dose- and exposure time-dependent. Although R-citalopram has been reported to antagonize some effects of escitalopram, this compound was without effect on Gαs localization in lipid rafts, and R-citalopram did not inhibit these actions of escitalopram. Escitalopram treatment increased cAMP accumulation, and this seemed due to increased coupling between Gαs and adenylyl cyclase. Thus, escitalopram is potent, rapid and efficacious in translocating Gαs from lipid rafts, and this effect seems to occur independently of 5-hydroxytryptamine transporters. Our results suggest that, although antidepressants display distinct affinities for well identified targets (e.g., monoamine transporters), several presynaptic and postsynaptic molecules are probably modified during chronic antidepressant treatment, and these additional targets may be required for clinical efficacy of these drugs. PMID:19996298

Antidepressive-drug-induced bodyweight gain is associated with polymorphisms in genes coding for COMT and TPH1

DEFF Research Database (Denmark)

Secher, Anna; Bukh, Jens; Bock, Camilla

2009-01-01

of a single depressive episode and who were under antidepressive treatment. Weight gainers were identified based on rating with the Udvalg for Kliniske Undersøgelser Side Effect Rating Scale. Polymorphisms in catechol-O-methyltransferase, tryptophan hydroxylase (TPH1), serotonin receptor 2C (HTR2C...... and sex. These new findings may aid the understanding of susceptibility to side effects such as weight gain during clinical antidepressive treatment....

No change in N-acetyl aspartate in first episode of moderate depression after antidepressant treatment: 1H magnetic spectroscopy study of left amygdala and left dorsolateral prefrontal cortex

Directory of Open Access Journals (Sweden)

Bajs Janović M

2014-09-01

Full Text Available Maja Bajs Janović,1,3 Petra Kalember,2 Špiro Janović,1,3 Pero Hrabač,2 Petra Folnegović Grošić,1 Vladimir Grošić,4 Marko Radoš,5 Neven Henigsberg2,61University Department of Psychiatry, Clinical Hospital Center Zagreb, Zagreb, 2Polyclinic Neuron, Croatian Institute for Brain Research, School of Medicine, University of Zagreb, Zagreb, 3University North, Varaždin, 4Psychiatric Hospital Sveti Ivan, Zagreb, 5University Department of Radiology, Clinical Hospital Center Zagreb, Zagreb, 6Psychiatric Clinic Vrapče, Zagreb, CroatiaBackground: The role of brain metabolites as biological correlates of the intensity, symptoms, and course of major depression has not been determined. It has also been inconclusive whether the change in brain metabolites, measured with proton magnetic spectroscopy, could be correlated with the treatment outcome. Methods: Proton magnetic spectroscopy was performed in 29 participants with a first episode of moderate depression occurring in the left dorsolateral prefrontal cortex and left amygdala at baseline and after 8 weeks of antidepressant treatment with escitalopram. The Montgomery-Asberg Depression Rating Scale, the Hamilton Rating Scale for Depression, and the Beck Depression Inventory were used to assess the intensity of depression at baseline and at the endpoint of the study. At endpoint, the participants were identified as responders (n=17 or nonresponders (n=12 to the antidepressant therapy. Results: There was no significant change in the N-acetyl aspartate/creatine ratio (NAA/Cr after treatment with antidepressant medication. The baseline and endpoint NAA/Cr ratios were not significantly different between the responder and nonresponder groups. The correlation between NAA/Cr and changes in the scores of clinical scales were not significant in either group. Conclusion: This study could not confirm any significant changes in NAA after antidepressant treatment in the first episode of moderate depression, or in

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

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...

The Modulatory Properties of Chronic Antidepressant Drugs Treatment on the Brain Chemokine – Chemokine Receptor Network: A Molecular Study in an Animal Model of Depression

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Ewa Trojan

2017-11-01

Full Text Available An increasing number of studies indicate that the chemokine system may be the third major communication system of the brain. Therefore, the role of the chemokine system in the development of brain disorders, including depression, has been recently proposed. However, little is known about the impact of the administration of various antidepressant drugs on the brain chemokine – chemokine receptor axis. In the present study, we used an animal model of depression based on the prenatal stress procedure. We determined whether chronic treatment with tianeptine, venlafaxine, or fluoxetine influenced the evoked by prenatal stress procedure changes in the mRNA and protein levels of the homeostatic chemokines, CXCL12 (SDF-1α, CX3CL1 (fractalkine and their receptors, in the hippocampus and frontal cortex. Moreover, the impact of mentioned antidepressants on the TGF-β, a molecular pathway related to fractalkine receptor (CX3CR1, was explored. We found that prenatal stress caused anxiety and depressive-like disturbances in adult offspring rats, which were normalized by chronic antidepressant treatment. Furthermore, we showed the stress-evoked CXCL12 upregulation while CXCR4 downregulation in hippocampus and frontal cortex. CXCR7 expression was enhanced in frontal cortex but not hippocampus. Furthermore, the levels of CX3CL1 and CX3CR1 were diminished by prenatal stress in the both examined brain areas. The mentioned changes were normalized with various potency by chronic administration of tested antidepressants. All drugs in hippocampus, while tianeptine and venlafaxine in frontal cortex normalized the CXCL12 level in prenatally stressed offspring. Moreover, in hippocampus only fluoxetine enhanced CXCR4 level, while fluoxetine and tianeptine diminished CXCR7 level in frontal cortex. Additionally, the diminished by prenatal stress levels of CX3CL1 and CX3CR1 in the both examined brain areas were normalized by chronic tianeptine and partially fluoxetine

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 ...

Sequenced treatment alternatives to relieve depression (STAR*D): rationale and design.

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Rush, A John; Fava, Maurizio; Wisniewski, Stephen R; Lavori, Philip W; Trivedi, Madhukar H; Sackeim, Harold A; Thase, Michael E; Nierenberg, Andrew A; Quitkin, Frederic M; Kashner, T Michael; Kupfer, David J; Rosenbaum, Jerrold F; Alpert, Jonathan; Stewart, Jonathan W; McGrath, Patrick J; Biggs, Melanie M; Shores-Wilson, Kathy; Lebowitz, Barry D; Ritz, Louise; Niederehe, George

2004-02-01

STAR*D is a multisite, prospective, randomized, multistep clinical trial of outpatients with nonpsychotic major depressive disorder. The study compares various treatment options for those who do not attain a satisfactory response with citalopram, a selective serotonin reuptake inhibitor antidepressant. The study enrolls 4000 adults (ages 18-75) from both primary and specialty care practices who have not had either a prior inadequate response or clear-cut intolerance to a robust trial of protocol treatments during the current major depressive episode. After receiving citalopram (level 1), participants without sufficient symptomatic benefit are eligible for randomization to level 2 treatments, which entail four switch options (sertraline, bupropion, venlafaxine, cognitive therapy) and three citalopram augment options (bupropion, buspirone, cognitive therapy). Those who receive cognitive therapy (switch or augment options) at level 2 without sufficient improvement are eligible for randomization to one of two level 2A switch options (venlafaxine or bupropion). Level 2 and 2A participants are eligible for random assignment to two switch options (mirtazapine or nortriptyline) and to two augment options (lithium or thyroid hormone) added to the primary antidepressant (citalopram, bupropion, sertraline, or venlafaxine) (level 3). Those without sufficient improvement at level 3 are eligible for level 4 random assignment to one of two switch options (tranylcypromine or the combination of mirtazapine and venlafaxine). The primary outcome is the clinician-rated, 17-item Hamilton Rating Scale for Depression, administered at entry and exit from each treatment level through telephone interviews by assessors masked to treatment assignments. Secondary outcomes include self-reported depressive symptoms, physical and mental function, side-effect burden, client satisfaction, and health care utilization and cost. Participants with an adequate symptomatic response may enter the 12-month

The Strategy of Combining Antidepressants in the Treatment of Major Depression: Clinical Experience in Spanish Outpatients

Directory of Open Access Journals (Sweden)

Luis M. Martín-López

2011-01-01

The most frequent combinations are SSRIs and tricyclic antidepressants. The active principle most widely combined is fluoxetine. Conclusions. The prevalence of use of antidepressant combination therapy is 2.2% of the global sample and 8.3% of treated patients. Other than duration of the depressive episode, no clinical characteristics exclusive to patients who received combination rather than monotherapy were found. Our study found that the most frequent combination is SSRIs + TCAs, also being the most studied.

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

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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.

Common genetic variation in the indoleamine-2,3-dioxygenase genes and antidepressant treatment outcome in major depressive disorder.

Science.gov (United States)

Cutler, Jessica A; Rush, A John; McMahon, Francis J; Laje, Gonzalo

2012-03-01

The essential amino acid tryptophan is the precursor to serotonin, but it can also be metabolized into kynurenine through indoleamine-2,3-dioxygenase (IDO). Increased immune activation has long been associated with symptoms of depression and has been shown to upregulate the expression of IDO. The presence of additional IDO directs more tryptophan down the kynurenine pathway, leaving less available for synthesis of serotonin and its metabolites. Kynurenine can be metabolized through a series of enzymes to quinolinic acid, a potent N-methyl-D-aspartate receptor agonist with demonstrated neurotoxic effects. We tested the hypothesis that IDO plays a role in outcome of treatment with the selective serotonin reuptake inhibitor, citalopram. Patients consisted of 1953 participants enrolled in the Sequenced Treatment Alternatives to Relieve Depression study (STAR*D). Genotypes corresponding to 94 single nucleotide polymorphisms (SNPs) in the genes IDO1 and IDO2, which encode IDO and IDO2, were extracted from a larger genome-wide set and analyzed using single marker tests to look for association with previously defined response, remission and QIDS-C score change phenotypes, with adequate correction for racial stratification and multiple testing. One SNP, rs2929115, showed evidence of association with citalopram response (OR = 0.64, p = 0.0005) after experiment-wide correction for multiple testing. Another closely associated marker, rs2929116 (OR = 0.64, p = 0.0006) had an experiment-wide significant result. Both implicated SNPs are located between 26 kb and 28 kb downstream of IDO2. We conclude that common genetic variation in IDO1 and IDO2 may play a role in antidepressant treatment outcome. These results are modest in a genome-wide context and need to be replicated in an independent sample.

Genetic predictors of response to serotonergic and noradrenergic antidepressants in major depressive disorder: a genome-wide analysis of individual-level data and a meta-analysis.

Science.gov (United States)

Tansey, Katherine E; Guipponi, Michel; Perroud, Nader; Bondolfi, Guido; Domenici, Enrico; Evans, David; Hall, Stephanie K; Hauser, Joanna; Henigsberg, Neven; Hu, Xiaolan; Jerman, Borut; Maier, Wolfgang; Mors, Ole; O'Donovan, Michael; Peters, Tim J; Placentino, Anna; Rietschel, Marcella; Souery, Daniel; Aitchison, Katherine J; Craig, Ian; Farmer, Anne; Wendland, Jens R; Malafosse, Alain; Holmans, Peter; Lewis, Glyn; Lewis, Cathryn M; Stensbøl, Tine Bryan; Kapur, Shitij; McGuffin, Peter; Uher, Rudolf

2012-01-01

It has been suggested that outcomes of antidepressant treatment for major depressive disorder could be significantly improved if treatment choice is informed by genetic data. This study aims to test the hypothesis that common genetic variants can predict response to antidepressants in a clinically meaningful way. The NEWMEDS consortium, an academia-industry partnership, assembled a database of over 2,000 European-ancestry individuals with major depressive disorder, prospectively measured treatment outcomes with serotonin reuptake inhibiting or noradrenaline reuptake inhibiting antidepressants and available genetic samples from five studies (three randomized controlled trials, one part-randomized controlled trial, and one treatment cohort study). After quality control, a dataset of 1,790 individuals with high-quality genome-wide genotyping provided adequate power to test the hypotheses that antidepressant response or a clinically significant differential response to the two classes of antidepressants could be predicted from a single common genetic polymorphism. None of the more than half million genetic markers significantly predicted response to antidepressants overall, serotonin reuptake inhibitors, or noradrenaline reuptake inhibitors, or differential response to the two types of antidepressants (genome-wide significance panalysis of NEWMEDS and another large sample (STAR*D), with 2,897 individuals in total. Polygenic scoring found no convergence among multiple associations in NEWMEDS and STAR*D. No single common genetic variant was associated with antidepressant response at a clinically relevant level in a European-ancestry cohort. Effects specific to particular antidepressant drugs could not be investigated in the current study. Please see later in the article for the Editors' Summary.

Neuronal NOS inhibitor 1-(2-trifluoromethylphenyl)-imidazole augment the effects of antidepressants acting via serotonergic system in the forced swimming test in rats.

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Ulak, Güner; Mutlu, Oguz; Akar, Füruzan Yildiz; Komsuoğlu, F Ipek; Tanyeri, Pelin; Erden, B Faruk

2008-10-01

Treatment-resistant depression has necessitated new therapeutic strategies in augmenting the therapeutic actions of currently existing antidepressant drugs. The aim of this study was to investigate the possibility of synergistic interaction between 1-(2-trifluoromethylphenyl)-imidazole (TRIM), a novel neuronal nitric oxide synthase (nNOS) inhibitor and conventional antidepressants of different classes in the forced swimming test (FST) in rats. TRIM decreased the immobility time at 50 mg/kg doses in the FST in rats. Treatment with a behaviourally subeffective dose of TRIM (20 mg/kg) augmented the behavioural effect of tricyclic antidepressant imipramine, selective serotonin re-uptake inhibitor (SSRI) citalopram and fluoxetine or selective serotonin reuptake enhancer tianeptine but failed to augment the antidepressant effect of reboxetine, a noradrenaline re-uptake inhibitor, in this test. Therefore inhibition of NOS augments the effects of antidepressants acting on serotonergic system in the FST. Neither TRIM (10-50 mg/kg) nor other drug treatments affected the locomotor activity of animals. These findings are in agreement with the view that antidepressant effects or augmentation of these effects in the FST may be explained with inhibition of NOS activity and this may be a new approach in offering greater therapeutic efficacy of antidepressants acting via serotonergic system.

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.

Use of alternative treatment in pediatric oncology

NARCIS (Netherlands)

Grootenhuis, M. A.; Last, B. F.; de Graaf-Nijkerk, J. H.; van der Wel, M.

1998-01-01

The use of alternative treatment along with conventional cancer therapy is very popular. However, little is known about the use of alternative treatment in pediatric oncology. A study to determine which medical and demographic characteristics distinguish users from nonusers was conducted in a

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.

Growth Modeling with Non-Ignorable Dropout: Alternative Analyses of the STAR*D Antidepressant Trial

Science.gov (United States)

Muthén, Bengt; Asparouhov, Tihomir; Hunter, Aimee; Leuchter, Andrew

2011-01-01

This paper uses a general latent variable framework to study a series of models for non-ignorable missingness due to dropout. Non-ignorable missing data modeling acknowledges that missingness may depend on not only covariates and observed outcomes at previous time points as with the standard missing at random (MAR) assumption, but also on latent variables such as values that would have been observed (missing outcomes), developmental trends (growth factors), and qualitatively different types of development (latent trajectory classes). These alternative predictors of missing data can be explored in a general latent variable framework using the Mplus program. A flexible new model uses an extended pattern-mixture approach where missingness is a function of latent dropout classes in combination with growth mixture modeling using latent trajectory classes. A new selection model allows not only an influence of the outcomes on missingness, but allows this influence to vary across latent trajectory classes. Recommendations are given for choosing models. The missing data models are applied to longitudinal data from STAR*D, the largest antidepressant clinical trial in the U.S. to date. Despite the importance of this trial, STAR*D growth model analyses using non-ignorable missing data techniques have not been explored until now. The STAR*D data are shown to feature distinct trajectory classes, including a low class corresponding to substantial improvement in depression, a minority class with a U-shaped curve corresponding to transient improvement, and a high class corresponding to no improvement. The analyses provide a new way to assess drug efficiency in the presence of dropout. PMID:21381817

Antidepressants for depression in adults with HIV infection.

Science.gov (United States)

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

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

Science.gov (United States)

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).

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

Science.gov (United States)

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

The promise of ketamine for treatment-resistant depression: current evidence and future directions

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DeWilde, Kaitlin E.; Levitch, Cara F.; Murrough, James W.; Mathew, Sanjay J.; Iosifescu, Dan V.

2014-01-01

Major depressive disorder (MDD) is one of the most disabling diseases worldwide and is a significant public health threat. Current treatments for MDD primarily consist of monoamine-targeting agents and have limited efficacy. However, the glutamate neurotransmitter system has recently come into focus as a promising alternative for novel antidepressant treatments. We review the current data on the glutamate NMDA receptor antagonist ketamine, which has been shown in clinical trials to act as a rapid antidepressant in MDD. We also examine ketamine efficacy on dimensions of psychopathology, including anhedonia, cognition, and suicidality, consistent with the NIMH Research Domain Criteria (RDoC) initiative. Other aspects of ketamine reviewed in this paper include safety and efficacy, different administration methods, and the risks of misuse of ketamine outside of medical settings. Finally, we conclude with a discussion of other glutamatergic agents other than ketamine currently being tested as novel antidepressants. PMID:25649308

Antidepressants and Suicide Risk: A Comprehensive Overview

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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.

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.

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.

Antidepressant efficacy and side-effect burden: a quick guide for clinicians

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Daniel Santarsieri

2015-10-01

Full Text Available Prescribing of antidepressant treatment (ADT for major depressive disorder (MDD has increased in quantity and popularity over the last two decades. This is likely due to the approval of safer medications, better education of clinicians and their patients, direct-to-consumer marketing practices, and less stigma associated with those taking ADT. This trend has also been met with some controversy, however, as the ongoing safety and effectiveness of these treatments have at times been called into question. This paper discusses the differing levels of evidence that support the use of ADT based on (A Food and Drug Administration approvals, (B data from randomized controlled trials or meta-analyses and, where these are not available, the authors discuss and apply, (C theoretical pharmacodynamic principles to justify antidepressant choice in the treatment of MDD patients. The final section discusses standard psychopharmacology guideline approaches to better alert the reader as to which practices are commonplace compared with those which are more outside of the standard of care.

Modelling the cost effectiveness of antidepressant treatment in primary care.

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Revicki, D A; Brown, R E; Palmer, W; Bakish, D; Rosser, W W; Anton, S F; Feeny, D

1995-12-01

The aim of this study was to estimate the cost effectiveness of nefazodone compared with imipramine or fluoxetine in treating women with major depressive disorder. Clinical decision analysis and a Markov state-transition model were used to estimate the lifetime health outcomes and medical costs of 3 antidepressant treatments. The model, which represents ideal primary care practice, compares treatment with nefazodone to treatment with either imipramine or fluoxetine. The economic analysis was based on the healthcare system of the Canadian province of Ontario, and considered only direct medical costs. Health outcomes were expressed as quality-adjusted life years (QALYs) and costs were in 1993 Canadian dollars ($Can; $Can1 = $US0.75, September 1995). Incremental cost-utility ratios were calculated comparing the relative lifetime discounted medical costs and QALYs associated with nefazodone with those of imipramine or fluoxetine. Data for constructing the model and estimating necessary parameters were derived from the medical literature, clinical trial data, and physician judgement. Data included information on: Ontario primary care physicians' clinical management of major depression; medical resource use and costs; probabilities of recurrence of depression; suicide rates; compliance rates; and health utilities. Estimates of utilities for depression-related hypothetical health states were obtained from patients with major depression (n = 70). Medical costs and QALYs were discounted to present value using a 5% rate. Sensitivity analyses tested the assumptions of the model by varying the discount rate, depression recurrence rates, compliance rates, and the duration of the model. The base case analysis found that nefazodone treatment costs $Can1447 less per patient than imipramine treatment (discounted lifetime medical costs were $Can50,664 vs $Can52,111) and increases the number of QALYs by 0.72 (13.90 vs 13.18). Nefazodone treatment costs $Can14 less than fluoxetine

Behavioral and biochemical effects of ketamine and dextromethorphan relative to its antidepressant-like effects in Swiss Webster mice.

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Nguyen, Linda; Lucke-Wold, Brandon P; Logsdon, Aric F; Scandinaro, Anna L; Huber, Jason D; Matsumoto, Rae R

2016-09-28

Ketamine has been shown to produce rapid and robust antidepressant effects in depressed individuals; however, its abuse potential and adverse psychotomimetic effects limit its widespread use. Dextromethorphan (DM) may serve as a safer alternative on the basis of pharmacodynamic similarities to ketamine. In this proof-of-concept study, behavioral and biochemical analyses were carried out to evaluate the potential involvement of brain-derived neurotrophic factor (BDNF) in the antidepressant-like effects of DM in mice, with comparisons to ketamine and imipramine. Male Swiss, Webster mice were injected with DM, ketamine, or imipramine and their behaviors were evaluated in the forced-swim test and the open-field test. Western blots were used to measure BDNF and its precursor, pro-BDNF, protein expression in the hippocampus and the frontal cortex of these mice. Our results show that both DM and imipramine reduced immobility time in the forced-swim test without affecting locomotor activity, whereas ketamine reduced immobility time and increased locomotor activity. Ketamine also rapidly (within 40 min) increased pro-BDNF expression in an α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor-dependent manner in the hippocampus, whereas DM and imipramine did not alter pro-BDNF or BDNF levels in either the hippocampus or the frontal cortex within this timeframe. These data show that DM shares some features with both ketamine and imipramine. Additional studies examining DM may aid in the development of more rapid, safe, and efficacious antidepressant treatments.

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...

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.

Mitochondrial energy metabolism of rat hippocampus after treatment with the antidepressants desipramine and fluoxetine.

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Villa, Roberto Federico; Ferrari, Federica; Bagini, Laura; Gorini, Antonella; Brunello, Nicoletta; Tascedda, Fabio

2017-07-15

Alterations in mitochondrial functions have been hypothesized to participate in the pathogenesis of depression, because brain bioenergetic abnormalities have been detected in depressed patients by neuroimaging in vivo studies. However, this hypothesis is not clearly demonstrated in experimental studies: some suggest that antidepressants are inhibitors of mitochondrial metabolism, while others observe the opposite. In this study, the effects of 21-day treatment with desipramine (15 mg/kg) and fluoxetine (10 mg/kg) were examined on the energy metabolism of rat hippocampus, evaluating the catalytic activity of regulatory enzymes of mitochondrial energy-yielding metabolic pathways. Because of the micro-heterogeneity of brain mitochondria, we have distinguished between (a) non-synaptic mitochondria (FM) of neuronal perikaryon (post-synaptic compartment) and (b) intra-synaptic light (LM) and heavy (HM) mitochondria (pre-synaptic compartment). Desipramine and fluoxetine changed the catalytic activity of specific enzymes in the different types of mitochondria: (a) in FM, both drugs enhanced cytochrome oxidase and glutamate dehydrogenase, (b) in LM, the overall bioenergetics was unaffected and (c) in HM only desipramine increased malate dehydrogenase and decreased the activities of Electron Transport Chain Complexes. These results integrate the pharmacodynamic features of desipramine and fluoxetine at subcellular level, overcoming the previous conflicting data about the effects of antidepressants on brain energy metabolism, mainly referred to whole brain homogenates or to bulk of cerebral mitochondria. With the differentiation in non-synaptic and intra-synaptic mitochondria, this study demonstrates that desipramine and fluoxetine lead to adjustments in the mitochondrial bioenergetics respect to the energy requirements of pre- and post-synaptic compartments. Copyright © 2017 Elsevier Ltd. All rights reserved.

Antidepressant-like effects of Tagetes lucida Cav. in the forced swimming test.

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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.

Cost-effectiveness of collaborative care including PST and an antidepressant treatment algorithm for the treatment of major depressive disorder in primary care; a randomised clinical trial

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Beekman Aartjan TF

2007-03-01

Full Text Available Abstract Background Depressive disorder is currently one of the most burdensome disorders worldwide. Evidence-based treatments for depressive disorder are already available, but these are used insufficiently, and with less positive results than possible. Earlier research in the USA has shown good results in the treatment of depressive disorder based on a collaborative care approach with Problem Solving Treatment and an antidepressant treatment algorithm, and research in the UK has also shown good results with Problem Solving Treatment. These treatment strategies may also work very well in the Netherlands too, even though health care systems differ between countries. Methods/design This study is a two-armed randomised clinical trial, with randomization on patient-level. The aim of the trial is to evaluate the treatment of depressive disorder in primary care in the Netherlands by means of an adapted collaborative care framework, including contracting and adherence-improving strategies, combined with Problem Solving Treatment and antidepressant medication according to a treatment algorithm. Forty general practices will be randomised to either the intervention group or the control group. Included will be patients who are diagnosed with moderate to severe depression, based on DSM-IV criteria, and stratified according to comorbid chronic physical illness. Patients in the intervention group will receive treatment based on the collaborative care approach, and patients in the control group will receive care as usual. Baseline measurements and follow up measures (3, 6, 9 and 12 months are assessed using questionnaires and an interview. The primary outcome measure is severity of depressive symptoms, according to the PHQ9. Secondary outcome measures are remission as measured with the PHQ9 and the IDS-SR, and cost-effectiveness measured with the TiC-P, the EQ-5D and the SF-36. Discussion In this study, an American model to enhance care for patients with a

Use of antidepressants in the treatment of major depressive disorder in primary care during a period of economic crisis

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Sicras-Mainar A

2015-12-01

Full Text Available Antoni Sicras-Mainar,1 Ruth Navarro-Artieda2 1Research Unit, Badalona Serveis Assistencials SA, 2Medical Documentation Unit, Hospital Germans Trias i Pujol, Badalona, Barcelona, Spain Objective: To describe antidepressant (AD use in the treatment of major depressive disorder during a period of economic crisis.Patients and methods: This was a retrospective, observational study using population-based databases. Two periods were considered: 1 2008–2009, precrisis, and 2 2012–2013, economic crisis. Certain inclusion/exclusion criteria were taken into account for the study (initiation of AD treatment. Patients were followed up for 12 months. The main measures were use (defined daily doses, epidemiologic measures, strategies used and treatment persistence, referrals, and use of resources. Statistical significance was set at P<0.05.Results: In the precrisis period, 3,662 patients were enrolled, and 5,722 were enrolled in the period of economic crisis. Average age was 58.8 years and 65.4% were women. Comparing the two periods, major depressive disorder prevalence was 5.4% vs 8.1%, P<0.001. During the period of economic crisis, AD use rose by 35.2% and drug expenditures decreased by 38.7%. Defined daily dose per patient per day was 10.0 mg vs 13.5 mg, respectively, P<0.001. At 12-month follow-up, the majority of patients (60.8% discontinued the treatment or continued on the same medication as before, and in 23.3% a change of AD was made.Conclusion: Primary health care professionals are highly involved in the management of the illness; in addition, during the period of economic crisis, patients with major depressive disorder showed higher rates of prevalence of the illness, with increased use of AD drugs. Keywords: consumption, antidepressants, economic crisis

Declining efficacy in controlled trials of antidepressants: effects of placebo dropout

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Schalkwijk, S.J.; Undurraga, J.; Tondo, L.; Baldessarini, R.J.

2014-01-01

Drug-placebo differences (effect-sizes) in controlled trials of antidepressants for major depressive episodes have declined for several decades, in association with selectively increasing clinical improvement associated with placebo-treatment. As these trends require adequate explanation, we tested

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.

[Sequential prescriptions: Arguments for a change of therapeutic patterns in treatment resistant depressions].

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Allouche, G

2016-02-01

Among the therapeutic strategies in treatment of resistant depression, the use of sequential prescriptions is discussed here. A number of observations, initially quite isolated and few controlled studies, some large-scale, have been reported, which showed a definite therapeutic effect of certain requirements in sequential treatment of depression. The Sequenced Treatment Alternatives to Relieve Depression Study (STAR*D) is up to now the largest clinical trial exploring treatment strategies in non psychotic resistant depression in real-life conditions with an algorithm of sequential decision. The main conclusions of this study are the following: after two unsuccessful attempts, the chance of remission decreases considerably. A 12-months follow-up showed that the higher the use of the processing steps were high, the more common the relapses were during this period. The pharmacological differences between psychotropic did not cause clinically significant difference. The positive effect of lithium in combination with antidepressants has been known since the work of De Montigny. Antidepressants allow readjustment of physiological sequence involving different monoaminergic systems together. Studies with tricyclic antidepressant-thyroid hormone T3: in depression, decreased norepinephrine at the synaptic receptors believed to cause hypersensitivity of these receptors. Thyroid hormones modulate the activity of adrenergic receptors. There would be a balance of activity between alpha and beta-adrenergic receptors, depending on the bioavailability of thyroid hormones. ECT may in some cases promote pharmacological response in case of previous resistance, or be effective in preventing relapse. Cognitive therapy and antidepressant medications likely have an effect on different types of depression. We can consider the interest of cognitive therapy in a sequential pattern after effective treatment with an antidepressant effect for treatment of residual symptoms, preventing relapses

Mesolimbic effects of the antidepressant fluoxetine in Holtzman rats, a genetic strain with increased vulnerability to stress

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Padilla, Eimeira; Shumake, Jason; Barrett, Douglas W.; Sheridan, Eva C.; Gonzalez-Lima, F.

2011-01-01

This is the first metabolic mapping study of the effects of fluoxetine after learned helplessness training. Antidepressants are the most commonly prescribed medications, but the regions underlying treatment effects in affectively disordered brains are poorly understood. We hypothesized the antidepressant action of fluoxetine would produce adaptations in mesolimbic regions after two weeks of treatment. We used Holtzman rats, a genetic strain showing susceptibility to novelty-evoked hyperactivity and stress-evoked helplessness, to map regional brain metabolic effects caused by fluoxetine treatment. Animals underwent learned helplessness, and subsequently immobility time was scored in the forced swim test (FST). On the next day, animals began receiving two weeks of fluoxetine (5 mg/kg/day) or vehicle and were retested in the FST at the end of drug treatment. Antidepressant behavioral effects of fluoxetine were analyzed using a ratio of immobility during pre- and post-treatment FST sessions. Brains were analyzed for regional metabolic activity using quantitative cytochrome oxidase histochemistry as in our previous study using congenitally helpless rats. Fluoxetine exerted a protective effect against FST-induced immobility behavior in Holtzman rats. Fluoxetine also caused a significant reduction in the mean regional metabolism of the nucleus accumbens shell and the ventral hippocampus as compared to vehicle-treated subjects. Additional networks affected by fluoxetine treatment included the prefrontal-cingulate cortex and brainstem nuclei linked to depression (e.g. habenula, dorsal raphe and interpeduncular nucleus). We concluded that corticolimbic regions such as the prefrontal-cingulate cortex, nucleus accumbens, ventral hippocampus and key brainstem nuclei represent important contributors to the neural network mediating fluoxetine antidepressant action. PMID:21376019

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.

Genetic predictors of response to serotonergic and noradrenergic antidepressants in major depressive disorder: a genome-wide analysis of individual-level data and a meta-analysis.

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Katherine E Tansey

Full Text Available It has been suggested that outcomes of antidepressant treatment for major depressive disorder could be significantly improved if treatment choice is informed by genetic data. This study aims to test the hypothesis that common genetic variants can predict response to antidepressants in a clinically meaningful way.The NEWMEDS consortium, an academia-industry partnership, assembled a database of over 2,000 European-ancestry individuals with major depressive disorder, prospectively measured treatment outcomes with serotonin reuptake inhibiting or noradrenaline reuptake inhibiting antidepressants and available genetic samples from five studies (three randomized controlled trials, one part-randomized controlled trial, and one treatment cohort study. After quality control, a dataset of 1,790 individuals with high-quality genome-wide genotyping provided adequate power to test the hypotheses that antidepressant response or a clinically significant differential response to the two classes of antidepressants could be predicted from a single common genetic polymorphism. None of the more than half million genetic markers significantly predicted response to antidepressants overall, serotonin reuptake inhibitors, or noradrenaline reuptake inhibitors, or differential response to the two types of antidepressants (genome-wide significance p<5×10(-8. No biological pathways were significantly overrepresented in the results. No significant associations (genome-wide significance p<5×10(-8 were detected in a meta-analysis of NEWMEDS and another large sample (STAR*D, with 2,897 individuals in total. Polygenic scoring found no convergence among multiple associations in NEWMEDS and STAR*D.No single common genetic variant was associated with antidepressant response at a clinically relevant level in a European-ancestry cohort. Effects specific to particular antidepressant drugs could not be investigated in the current study. Please see later in the article for the

EMSAM (deprenyl patch: how a promising antidepressant was underutilized

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Asnis GM

2014-10-01

Full Text Available Gregory M Asnis,1,2 Margaret A Henderson2 1Department of Psychiatry and Behavioral Sciences, Albert Einstein College of Medicine, New York, NY, USA; 2Anxiety and Depression Clinic, Montefiore Medical Center, New York, NY, USA Abstract: The EMSAM patch is a unique monoamine oxidase inhibitor (MAOI being the only antidepressant utilizing a transdermal delivery system. This was welcomed by clinicians who hoped that EMSAM would be better tolerated than oral MAOIs and non-MAOI antidepressants, as well as being effective for treatment in a wide spectrum of depressed patients including atypical depression, bipolar depression, and refractory depression. Unfortunately, the clinical use of EMSAM has been underutilized and its potential usefulness overlooked. This article suggests that fear of possible side effects, particularly the “cheese reaction” and serotonin syndrome, are some of the main contributors to underutilization by clinicians. These risks have been significantly exaggerated with the 6 mg/day dose not even requiring a special diet. Other contributing factors leading to underutilization are reviewed such as: the lack of studies addressing many important clinical questions; inadequate data analyses; not evaluating the effect of EMSAM on comorbid psychiatric conditions, particularly anxiety disorders; lack of antidepressant comparators versus EMSAM; no dose–response relationship examined; various depressive subtypes and conditions are unexplored, eg, bipolar depression and refractory depression; poor insurance coverage for an expensive medication; as well as minimal marketing efforts and postmarketing studies. On the other hand, many potential advantages of EMSAM are not highlighted enough in the literature and by pharmaceutical companies which might have increased clinical interest and utilization of the antidepressant. For example, the advantages of EMSAM include: avoidance of swallowing issues, as can be seen with oral antidepressants

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

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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.

Right and left amygdalae activation in patients with major depression receiving antidepressant treatment, as revealed by fMRI.

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Chen, Yen-Ting; Huang, Min-Wei; Hung, I-Chung; Lane, Hsien-Yuan; Hou, Chun-Ju

2014-10-08

A differential contribution of the right and left amygdalae to affective information processing has been proposed. However, the direction of this lateralization has not been confirmed. In this study, we used a pre- and post-treatment (escitalopram) design to analyze the relative differences between neural activity in the right and left amygdalae during exposure to emotional stimuli in currently depressed patients. To the best of our knowledge, this study is to compare neural activity between the left and right amygdalae in people with depression. Our findings could lead to the development of parameters or biomarkers for depressive symptoms and treatment response. We used a pre-post-test design without a control group. Twenty currently depressed participants underwent an emotion processing task during fMRI. These participants were then treated with an antidepressant for 6 weeks. We used amygdala region-of-interest analysis to evaluate the hemodynamic response during exposure to colored emotional pictures. In total, thirteen of the 20 participants were placed into a separate group based on degree of response to antidepressants. The partial response group had an averaged HDRS score of 10.75 ± 2.25 and an averaged DBOLDLR signal of 189.18 ± 140.23 (m1 = 8), and the remitted group had an averaged HDRS score of 4.80 ± 1.64 and an averaged DBOLDLR signal of 421.26 ± 109.19 (m2 = 5). Each individual had lateralized amygdala activity, and the direction of asymmetry persisted following treatment. Amygdala responses to four types of emotional stimuli did not significantly change (p > 0.05) with treatment in either the right or the left amygdala. However, the difference in neural activity between the right and left amygdalae was greater after treatment, and the variation in neural activity was larger in the left amygdala. We found that the response between the right and left amygdala did not differ in terms of time series, although activity increased after pharmaceutical

Pain Relief in Depressive Disorders: A Meta-Analysis of the Effects of Antidepressants.

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Gebhardt, Stefan; Heinzel-Gutenbrunner, Monika; König, Udo

2016-12-01

Pain is a common symptom in patients with depressive disorders, which, if present, worsens the prognosis. However, there is little empirical knowledge of the therapeutic effects of antidepressants on painful physical symptoms of patients with depressive disorders. Furthermore, tricyclic/tetracyclic antidepressants (TCAs) have not yet been included in existing meta-analyses. A broad, systematic search of PubMed literature on antidepressant drug treatment of patients with depressive disorders with comorbid pain symptoms was carried out. A random-effects meta-analysis has been performed among 3 different groups of drugs for the 2 end points: pain and depression. Fourteen placebo-controlled studies with selective serotonin-noradrenaline reuptake inhibitors (SSNRIs) could be included, with 3 of them also investigating selective serotonin reuptake inhibitors (SSRIs). Three further placebo-controlled SSRI studies were identified, but only 2 placebo-controlled TCA studies.Both SSNRIs and SSRIs, but not TCAs, were significantly superior to placebo as regards their analgesic effects. However, all effects were small. For SSNRIs, there was a strong positive correlation between their effectiveness for pain relief and their positive effect on the mood of the patients. The analgesic effects of SSNRIs and SSRIs in patients with primary depressive disorders can be interpreted as largely equivalent. Because of a lack of placebo-controlled TCA studies, the results for TCAs would be comparable only to those of SSRIs and SSNRIs, if non-placebo-controlled TCA studies were included. The positive correlation found indicates a close relationship of pain relief and antidepressant treatment effects. These results refer merely to patients with primary depressive disorders, not to patients with primary pain disorders. Further studies comparing the effects of different types of antidepressant drugs on pain in depressive patients are warranted.

Electro-peroxone treatment of the antidepressant venlafaxine: Operational parameters and mechanism

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Li, Xiang; Wang, Yujue; Zhao, Jian; Wang, Huijiao; Wang, Bin; Huang, Jun; Deng, Shubo; Yu, Gang, E-mail: yg-den@mail.tsinghua.edu.cn

2015-12-30

Highlights: • E-peroxone is a novel electrocatalytic ozonation process that couples ozonation with electrolysis to enhance pollutant decay. • Carbon-based cathodes are used to electrocatalytically produce H{sub 2}O{sub 2} from O{sub 2} in sparged O{sub 2} and O{sub 3} mixture. • The in-situ generated H{sub 2}O{sub 2} reacts with O{sub 3} to yield ·OH for pollutant mineralization. • Venlafaxine is mineralized much faster by E-peroxone than by ozonation and electrolysis. - Abstract: Degradation of the antidepressant venlafaxine by a novel electrocatalytic ozonation process, electro-peroxone (E-peroxone), was studied. The E-peroxone treatment involves sparging ozone generator effluent (O{sub 2} and O{sub 3} gas mixture) into an electrolysis reactor that is equipped with a carbon-polytetrafluoroethylene cathode to electrocatalytically transform O{sub 2} in the bubbled gas to H{sub 2}O{sub 2}. The in-situ generate H{sub 2}O{sub 2} then reacts with the bubbled O{sub 3} to yield ·OH, which can non-selectively degrade organic compounds rapidly in the solution. Thanks to the significant ·OH production, the E-peroxone treatment greatly enhanced both venlafaxine degradation and total organic carbon (TOC) removal as compared to ozonation and electrolysis alone. Under optimal reaction conditions, complete venlafaxine degradation and TOC elimination could be achieved within 3 and 120 min of E-peroxone process, respectively. Based on the by-products (e.g., hydroxylated venlafaxine, phenolics, and carboxylic acids) identified by UPLC–UV and UPLC/Q-TOF-mass spectrometry, plausible reaction pathways were proposed for venlafaxine mineralization by the E-peroxone process. The results of this study suggest that the E-peroxone treatment may provide a promising way to treat venlafaxine contaminated water.

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

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

Antidepressant-like effects of Gan-Mai-Dazao-Tang via monoamine regulatory pathways on forced swimming test in rats

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Hsiang-Ling Huang

2018-01-01

Full Text Available Depression is a highly prevalent and recurrent mental disorder that impacts all aspects of human life. Undesirable effects of the antidepressant drugs led to the development of complementary and alternative therapies. Gan-Mai-Da-Zao-Tang (甘麥大棗湯, gān mài dà zǎo tang is a traditional herbal formula commonly used for the treatment of depression, but lack of scientific proof on its mechanism. It consisted of Glycyrrhiza uralensis Fisch. (licorice, Triticum aestivum L. (wheat and Zizphus jujuba Mill. (jujube. The objective of this study is to investigate the antidepressant effects of Gan-Mai-Dazao-Tang and its ingredients in rats exposed to forced swimming test (FST. The 72 of male Nerl: Wistar rats (8 weeks old were randomized into control (10 mL/kg bw H2O, licorice (0.4 g/kg bw, wheat (1.6 g/kg bw, jujube (0.5 g/kg bw, Gan-Mai-Da-Zao-Tang (2.5 g/kg bw of licorice: wheat: jujube in ratio of 5:20:6 and Prozac (18 mg/kg bw groups. Samples were administered by oral gavage for 21 days. FST was performed on 21st day, with 15 min for pretest followed by 5 min for real test. Then, the animals were sacrificed and brain tissues were collected for monoamines analyses. The Gan-Mai-Da-Zao-Tang (LWJ showed significantly down-regulation of immobility time, 3,4-dihydroxyphenylacetic acid (DOPAC and DOPAC/dopamine (DA turnover rates, and also enhanced the concentration of serotonin (5-HT and DA in brain tissues, as compared with the control. The LWJ stated the potent antidepressant-like effect by modulating these monoamines concentration, while the licorice, wheat and jujube did not reported significant results as compared with control group. The positive control (Prozac was noted with significantly reduction in body weight and appetite. In conclusion, the antidepressant-like effects of LWJ might be mediated by the regulation of monoamine neurotransmitters. Thus, it could beneficial in depression treatment as a complementary approach.

Does recent mania affect response to antidepressants in bipolar disorder? A re-analysis of STEP-BD data.

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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.

Triple Reuptake Inhibitors: The Next Generation of Antidepressants

OpenAIRE

Marks, David M; Pae, Chi-Un; Patkar, Ashwin A

2008-01-01

Depression has been associated with impaired neurotransmission of serotonergic, norepinephrinergic, and dopaminergic pathways, although most pharmacologic treatment strategies for depression enhance only serotonin and norepinephrine neurotransmission. Current drug development efforts are aimed at a new class of antidepressants which inhibit the reuptake of all three neurotransmitters in the hope of creating medications with broader efficacy and/or quicker onset of action. The current review e...

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

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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.

Novel Antidepressant-Like Activity of Caffeic Acid Phenethyl Ester Is Mediated by Enhanced Glucocorticoid Receptor Function in the Hippocampus

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Mi-Sook Lee

2014-01-01

Full Text Available Caffeic acid phenethyl ester (CAPE is an active component of propolis that has a variety of potential pharmacological effects. Although we previously demonstrated that propolis has antidepressant-like activity, the effect of CAPE on this activity remains unknown. The present study assessed whether treatment with CAPE (5, 10, and 20 µmol/kg for 21 days has an antidepressant-like effect in mice subjected to chronic unpredictable stress via tail suspension (TST and forced swim (FST tests. CAPE administration induced behaviors consistent with an antidepressant effect, evidenced by decreased immobility in the TST and FST independent of any effect on serum corticosterone secretion. Western blots, conducted subsequent to behavioral assessment, revealed that CAPE significantly decreased glucocorticoid receptor phosphorylation at S234 (pGR(S234, resulting in an increased pGR(S220/S234 ratio. We also observed negative correlations between pGR(S220/(S234 and p38 mitogen-activated protein kinase (p38MAPK phosphorylation, which was decreased by CAPE treatment. These findings suggest that CAPE treatment exerts an antidepressant-like effect via downregulation of p38MAPK phosphorylation, thereby contributing to enhanced GR function.

A retrospective study of predictive factors for effective aripiprazole augmentation of antidepressant therapy in treatment-resistant depression

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Sugawara H

2016-05-01

Full Text Available Hiroko Sugawara,1,2 Kaoru Sakamoto,1 Tsuyoto Harada,3 Satoru Shimizu,4 Jun Ishigooka1 1Department of Psychiatry, Tokyo Women’s Medical University, 2Support Center for Women Health Care Professionals and Researchers, Tokyo Women’s Medical University, Shinjuku-ku, 3Department of Psychiatry, Tokyo Women’s Medical University Medical Center East, Arakawa-ku, 4Department of Research, Medical Research Institute, Tokyo Women’s Medical University, Shinjuku-ku, Tokyo, Japan Background: Several studies have evaluated the efficacy and tolerability of aripiprazole for augmentation of antidepressant therapy for treatment-resistant depression (TRD. Here, we investigated the efficacy of aripiprazole augmentation for TRD including both major depressive disorder and bipolar disorder and the clinical predictors of treatment efficacy in a Japanese population.  Methods: Eighty-five depressed Japanese patients who underwent aripiprazole augmentation therapy after failing to respond satisfactorily to antidepressant monotherapy were included in the study. Treatment responses were evaluated based on Clinical Global Impression Improvement scores assessed 8 weeks after initiation of aripiprazole administration. We compared demographic and diagnostic variables, psychiatric medication variables, and clinical variables between remission and nonremission groups.  Results: The aripiprazole augmentation remission rate was 36.5%. Multiple logistic regression analysis indicated that aripiprazole augmentation was significantly more effective for bipolar depression than for major depressive disorder, and both absence of comorbid anxiety disorders and current episode duration >3 months were significantly associated with the efficacy of aripiprazole augmentation.  Conclusion: Polarity of depression, comorbidity of anxiety disorders, and current episode duration may predict the efficacy of aripiprazole augmentation for TRD including both major depressive disorder and

Indoleamine 2,3-dioxygenase and immune changes under antidepressive treatment in major depression in females.

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Zoga, Margarita; Oulis, Panagiotis; Chatzipanagiotou, Stylianos; Masdrakis, Vasilios G; Pliatsika, Paraskevi; Boufidou, Fotini; Foteli, Stefania; Soldatos, Constantin R; Nikolaou, Chryssoula; Papageorgiou, Charalampos

2014-01-01

Indoleamine 2, 3-dioxygenase (IDO) induction has been suggested as a mechanism by which immune activation affects tryptophan metabolism and serotonin synthesis in major depressive disorder (MDD). We investigated IDO and changes in inflammatory mediators in patients with MDD undergoing effective treatment. Forty female patients with MDD and 40 controls were recruited. Serum IDO was assessed by enzyme-linked immunosorbent assay (ELISA). We also determined tumor necrosis factor-α (TNFα), interferon-γ (IFNγ), C-reactive protein (CRP) and serotonin concentrations. Patients' baseline concentrations of IDO and immune mediators were higher and serotonin concentrations were lower compared to controls. IDO and TNFα concentrations decreased under treatment and IDO changes were positively correlated with patient improvement. IFNγ and CRP concentrations remained unchanged. Serotonin concentration tended to increase. IDO might play an important role in the pathophysiology of MDD. Moreover, antidepressant therapy might reduce IDO production through an IFNγ-independent pathway. Finally, peripheral concentration of IDO assessed by ELISA might be a useful marker of MDD. Copyright © 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

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 ...

Antidepressants normalize the default mode network in patients with dysthymia.

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Posner, Jonathan; Hellerstein, David J; Gat, Inbal; Mechling, Anna; Klahr, Kristin; Wang, Zhishun; McGrath, Patrick J; Stewart, Jonathan W; Peterson, Bradley S

2013-04-01

The default mode network (DMN) is a collection of brain regions that reliably deactivate during goal-directed behaviors and is more active during a baseline, or so-called resting, condition. Coherence of neural activity, or functional connectivity, within the brain's DMN is increased in major depressive disorder relative to healthy control (HC) subjects; however, whether similar abnormalities are present in persons with dysthymic disorder (DD) is unknown. Moreover, the effect of antidepressant medications on DMN connectivity in patients with DD is also unknown. To use resting-state functional-connectivity magnetic resonance imaging (MRI) to study (1) the functional connectivity of the DMN in subjects with DD vs HC participants and (2) the effects of antidepressant therapy on DMN connectivity. After collecting baseline MRI scans from subjects with DD and HC participants, we enrolled the participants with DD into a 10-week prospective, double-blind, placebo-controlled trial of duloxetine and collected MRI scans again at the conclusion of the study. Enrollment occurred between 2007 and 2011. University research institute. Volunteer sample of 41 subjects with DD and 25 HC participants aged 18 to 53 years. Control subjects were group matched to patients with DD by age and sex. We used resting-state functional-connectivity MRI to measure the functional connectivity of the brain's DMN in persons with DD compared with HC subjects, and we examined the effects of treatment with duloxetine vs placebo on DMN connectivity. Of the 41 subjects with DD, 32 completed the clinical trial and MRI scans, along with the 25 HC participants. At baseline, we found that the coherence of neural activity within the brain's DMN was greater in persons with DD compared with HC subjects. Following a 10-week clinical trial, we found that treatment with duloxetine, but not placebo, normalized DMN connectivity. The baseline imaging findings are consistent with those found in patients with major

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

Antidepressant-like effect of celecoxib piroxicam in rat models of depression.

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Santiago, Ronise M; Barbiero, Janaína; Martynhak, Bruno J; Boschen, Suelen L; da Silva, Luisa M; Werner, Maria F P; Da Cunha, Claudio; Andreatini, Roberto; Lima, Marcelo M S; Vital, Maria A B F

2014-06-01

Beyond the current hypothesis of depression, several new biological substrates have been proposed for this disorder. The present study investigated whether the anti-inflammatory drugs celecoxib and piroxicam have antidepressant activity in animal models of depression. After acute administration, we observed antidepressant-like effects of celecoxib (10 mg/kg) and piroxicam (10 mg/kg) in the modified forced swim test in rats. Piroxicam increased serotonin and norepinephrine levels in the hippocampus. Prolonged (21-day) treatment with celecoxib (10 mg/kg) and piroxicam (10 mg/kg) rescued sucrose preference in a chronic mild stress model of depression. Additionally, the chronic mild stress-induced reduction of hippocampal glutathione was prevented by treatment with celecoxib and piroxicam. Superoxide dismutase in the hippocampus was increased after chronic mild stress compared with the non-stressed saline group. The non-stressed celecoxib and piroxicam groups and stressed piroxicam group exhibited an increase in hippocampal superoxide dismutase activity compared with the stressed saline group. Lipid hydroperoxide was increased in the stressed group treated with vehicle and non-stressed group treated with imipramine but not in the stressed groups treated with celecoxib and piroxicam. These results suggest that the antidepressant-like effects of anti-inflammatory drugs might be attributable to enhanced antioxidant defenses and attenuated oxidative stress in the hippocampus.

Interactive effects of N-acetylcysteine and antidepressants.

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Costa-Campos, Luciane; Herrmann, Ana P; Pilz, Luísa K; Michels, Marcus; Noetzold, Guilherme; Elisabetsky, Elaine

2013-07-01

N-acetylcysteine (NAC), a glutathione precursor and glutamate modulator, has been shown to possess various clinically relevant psychopharmacological properties. Considering the role of glutamate and oxidative stress in depressive states, the poor effectiveness of antidepressant drugs (ADs) and the benefits of drug combination for treating depression, the aim of this study was to explore the possible benefit of NAC as an add on drug to treat major depression. For that matter we investigated the combination of subeffective and effective doses of NAC with subeffective and effective doses of several ADs in the mice tail suspension test. The key finding of this study is that a subeffective dose of NAC reduced the minimum effective doses of imipramine and escitalopram, but not those of desipramine and bupropion. Moreover, the same subeffective dose of NAC increased the minimum effective dose of fluoxetine in the same model. In view of the advantages associated with using the lowest effective dose of antidepressant, the results of this study suggest the potential of a clinically useful interaction of NAC with imipramine and escitalopram. Further studies are necessary to better characterize the molecular basis of such interactions, as well as to typify the particular drug combinations that would optimize NAC as an alternative for treating depression. Copyright © 2013 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....

Clinical Use of Mood Stabilizers With Antidepressants in Asia: Report From the Research on Asian Psychotropic Prescription Patterns for Antidepressants (REAP-AD) Projects in 2004 and 2013.

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Rajaratnam, Kamini; Xiang, Yu-Tao; Tripathi, Adarsh; Chiu, Helen F K; Si, Tian-Mei; Chee, Kok-Yoon; Avasthi, Ajit; Grover, Sandeep; Chong, Mian-Yoon; Kuga, Hironori; Kanba, Shigenobu; He, Yan-Ling; Lee, Min-Soo; Yang, Shu-Yu; Udomratn, Pichet; Kallivayalil, Roy A; Tanra, Andi J; Maramis, Margarita M; Shen, Winston W; Sartorius, Norman; Kua, Ee-Heok; Tan, Chay-Hoon; Mahendran, Rathi; Shinfuku, Naotaka; Sum, Min Yi; Baldessarini, Ross J; Sim, Kang

2017-04-01

As most reports concerning treatment with combinations of mood stabilizer (MS) with antidepressant (AD) drugs are based in the West, we surveyed characteristics of such cotreatment in 42 sites caring for the mentally ill in 10 Asian countries. This cross-sectional, pharmacoepidemiologic study used 2004 and 2013 data from the REAP-AD (Research Study on Asian Psychotropic Prescription Patterns for Antidepressants) to evaluate the rates and doses of MSs given with ADs and associated factors in 4164 psychiatric patients, using standard bivariate methods followed by multivariable logistic regression modeling. Use of MS + AD increased by 104% (5.5% to 11.2%) between 2004 and 2013 and was much more associated with diagnosis of bipolar disorder than major depression or anxiety disorder, as well as with hospitalization > outpatient care, psychiatric > general-medical programs, and young age (all P contemporary use of MSs with ADs in Asia, support predictions that such treatment increased in recent years, and was associated with diagnosis of bipolar disorder, treatment in inpatient and psychiatric settings, and younger age.

Clinical and psychopathological features associated with treatment-emergent mania in bipolar-II depressed outpatients exposed to antidepressants.

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Fornaro, Michele; Anastasia, Annalisa; Monaco, Francesco; Novello, Stefano; Fusco, Andrea; Iasevoli, Felice; De Berardis, Domenico; Veronese, Nicola; Solmi, Marco; de Bartolomeis, Andrea

2018-07-01

Treatment-emergent affective switch (TEAS), including treatment-emergent mania (TEM), carry significant burden in the clinical management of bipolar depression, whereas the use of antidepressants raises both efficacy, safety and tolerability concerns. The present study assesses the prevalence and clinical correlates of TEM in selected sample of Bipolar Disorder (BD) Type-II (BD-II) acute depression outpatients. Post-hoc analysis of the clinical and psychopathological features associated with TEM among 91 BD-II depressed outpatients exposed to antidepressants. Second-generation antipsychotics (SGA) (p = .005), lithium (≤ .001), cyclothymic/irritable/hyperthymic temperaments (p = ≤ .001; p = .001; p = .003, respectively), rapid-cycling (p = .005) and depressive mixed features (p = .003) differed between TEM + cases vs. TEM - controls. Upon multinomial logistic regression, the accounted psychopathological features correctly classified as much as 88.6% of TEM + cases (35/91 overall sample, or 38.46% of the sample), yet not statistically significantly [Exp(B) = .032; p = ns]. Specifically, lithium [B = - 2.385; p = .001], SGAs [B = - 2.354; p = .002] predicted lower rates of TEM + in contrast to the number of lifetime previous psychiatric hospitalizations [B = 2.380; p = .002], whereas mixed features did not [B = 1.267; p = ns]. Post-hoc analysis. Lack of systematic pharmacological history record; chance of recall bias and Berkson's biases. Permissive operational criterion for TEM. Relatively small sample size. Cyclothymic temperament and mixed depression discriminated TEM + between TEM - cases, although only lithium and the SGAs reliably predicted TEM +/- grouping. Larger-sampled/powered longitudinal replication studies are warranted to allow firm conclusions on the matter, ideally contributing to the identification of clear-cut sub-phenotypes of BD towards patient-tailored-pharmacotherapy. Copyright © 2018 Elsevier B.V. All rights reserved.

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

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.

Epigenetic Mechanisms of Depression and Antidepressants Action

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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

Involvement of monoaminergic systems in the antidepressant-like effect of Eugenia brasiliensis Lam. (Myrtaceae) in the tail suspension test in mice.

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Colla, André R S; Machado, Daniele G; Bettio, Luis E B; Colla, Guilherme; Magina, Michele D A; Brighente, Inês M C; Rodrigues, Ana Lúcia S

2012-09-28

Several species of Eugenia L. are used in folk medicine for the treatment of various diseases. Eugenia brasiliensis is used for the treatment of inflammatory diseases, whereas Eugenia. uniflora is used for the treatment of symptoms related to depression and mood disorders, and is used in Brazil by the Guarani Indians as a tonic stimulant. To investigate the antidepressant-like effect of hydroalcoholic extracts of different plant species of genus Eugenia and to characterize the participation of the monoaminergic systems in the mechanism of action of the specie that afforded the most prominent antidepressant-like efficacy. In the first set of experiments, the effects of hydroalcoholic extracts of Eugenia beaurepaireana, Eugenia brasiliensis, Eugenia catharinae, Eugenia umbelliflora and Eugenia uniflora and the antidepressant fluoxetine (positive control) administered acutely by p.o. route were evaluated in the tail suspension test (TST) and locomotor activity was assessed in the open-field test in mice. In the second set of experiments, the involvement of the monoaminergic systems in the antidepressant-like activity of Eugenia brasiliensis was evaluated by treating mice with several pharmacological agonists and antagonists. The effects of the combined administration of sub-effective doses of Eugenia brasiliensis and the antidepressants fluoxetine, imipramine and bupropion were also evaluated. The administration of the extracts from Eugenia brasiliensis, Eugenia catharinae and Eugenia umbelliflora, but not Eugenia beaurepaireana and Eugenia uniflora, exerted a significant antidepressant-like effect, without altering locomotor activity. The behavioral profile was similar to fluoxetine. Pre-treatment of mice with ketanserin, haloperidol, SCH23390, sulpiride, prazosin and yohimbine prevented the reduction of immobility time induced by Eugenia brasiliensis. Treatment with sub-effective doses of WAY100635, SKF38393, apomorphine, phenylephrine, but not clonidine, combined

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.

Antidepressive and BDNF effects of enriched environment treatment across ages in mice lacking BDNF expression through promoter IV

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Jha, S; Dong, B E; Xue, Y; Delotterie, D F; Vail, M G; Sakata, K

2016-01-01

Reduced promoter IV-driven expression of brain-derived neurotrophic factor (BDNF) is implicated in stress and major depression. We previously reported that defective promoter IV (KIV) caused depression-like behavior in young adult mice, which was reversed more effectively by enriched environment treatment (EET) than antidepressants. The effects of promoter IV-BDNF deficiency and EET over the life stages remain unknown. Since early-life development (ED) involves dynamic epigenetic processes, we hypothesized that EET during ED would provide maximum antidepressive effects that would persist later in life due to enhanced, long-lasting BDNF induction. We tested this hypothesis by determining EET effects across three life stages: ED (0–2 months), young adult (2–4 months), and old adult (12–14 months). KIV mice at all life stages showed depression-like behavior in the open-field and tail-suspension tests compared with wild-type mice. Two months of EET reduced depression-like behavior in ED and young adult, but not old adult mice, with the largest effect in ED KIV mice. This effect lasted for 1 month after discontinuance of EET only in ED mice. BDNF protein induction by EET in the hippocampus and frontal cortex was also the largest in ED mice and persisted only in the hippocampus of ED KIV mice after discontinuance of EET. No gender-specific effects were observed. The results suggest that defective promoter IV causes depression-like behavior, regardless of age and gender, and that EET during ED is particularly beneficial to individuals with promoter IV-BDNF deficiency, while additional treatment may be needed for older adults. PMID:27648918

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.

Efficacy and safety of antidepressant augmentation of continued antipsychotic treatment in patients with schizophrenia

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Galling, B; Vernon, J A; Pagsberg, A K

2018-01-01

adjunctive antidepressants vs. placebo in schizophrenia. RESULTS: In a random-effects meta-analysis (studies = 42, n = 1934, duration = 10.1 ± 8.1 weeks), antidepressant augmentation outperformed placebo regarding total symptom reduction [standardized mean difference (SMD) = -0.37, 95% confidence interval...... (CI) = -0.57 to -0.17, P SMD = -0.25, 95% CI = -0.44-0.06, P = 0.010), but not positive (P = 0.190) or general (P = 0.089) symptom reduction. Superiority regarding negative symptoms was confirmed in studies augmenting first-generation antipsychotics (FGAs) (SMD = -0.......42, 95% CI = -0.77, -0.07, P = 0.019), but not second-generation antipsychotics (P = 0.144). Uniquely, superiority in total symptom reduction by NaSSAs (SMD = -0.71, 95% CI = -1.21, -0.20, P = 0.006) was not driven by negative (P = 0.438), but by positive symptom reduction (SMD = -0.43, 95% CI = -0...

Inhibition of the L-arginine-nitric oxide pathway mediates the antidepressant effects of ketamine in rats in the forced swimming test.

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Zhang, Guang-Fen; Wang, Nan; Shi, Jin-Yun; Xu, Shi-Xia; Li, Xiao-Min; Ji, Mu-Huo; Zuo, Zhi-Yi; Zhou, Zhi-Qiang; Yang, Jian-Jun

2013-09-01

Converging evidence shows that the acute administration of a sub-anaesthetic dose ketamine produces fast-acting and robust antidepressant properties in patients suffering from major depressive disorder. However, the underlying mechanisms have not been fully elucidated. The present study aimed to investigate the role of the L-arginine-nitric oxide pathway in the antidepressant effects of ketamine in rats performing the forced swimming test (FST). Ketamine (10 mg/kg) significantly decreased immobility times in the FST and the activities of total nitric oxide synthases (T-NOS), inducible NOS (iNOS), and endothelial NOS (eNOS) in the rat hippocampus. Interestingly, the plasma activities of T-NOS, iNOS, and eNOS increased after administration of ketamine. Furthermore, the activities of neuronal NOS (nNOS) did not change significantly in either the hippocampus or plasma after ketamine administration. The antidepressant effects of ketamine were prevented by pre-treatment with l-arginine (750 mg/kg). Pre-treatment with the NOS inhibitor L-NG-nitroarginine methyl ester at a sub-antidepressant dose of 50 mg/kg and ketamine at a sub-antidepressant dose of 3 mg/kg reduced immobility time in the FST compared to treatment with either drug alone. None of the drugs affected crossing and rearing scores in the open field test. These results suggest that the L-arginine-nitric oxide pathway is involved in the antidepressant effects of ketamine observed in rats in the FST and this involvement is characterised by the inhibition of brain T-NOS, iNOS, and eNOS activities. Copyright © 2013 Elsevier Inc. All rights reserved.

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

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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.

Evaluation of the antidepressant-like effects of acute and sub-acute administration of crocin and crocetin in mice

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Bahareh Amin

2015-08-01

Full Text Available Objective: The present study was designed to investigate the putative antidepressant effects of crocin and crocetin, two major active ingredients of Crocus sativus L. (saffron using mice in two different regimens of acute and sub-acute administration. Material and Methods: In acute treatment, antidepressant-like activities of crocin and crocetin (10, 20 and 40 mg/kg, i.p. were evaluated using forced swim test (FST. In sub-acute study (21 times with 24-h intervals, antidepressant-like effects of oral administration of drugs were examined using FST and tail suspension test (TST. Locomotor activity and motor coordination were studied using open field and rotarod tests, respectively. Results: Acute treatment with crocin (40 mg/kg and crocetin (20 and 40 mg/kg produced antidepressant-like effect in FST without affecting the baseline locomotion in mice. Sub-acute oral administration of crocin significantly decreased immobility time only at the highest dose (100 mg/kg. Crocetin (12.5, 25 and 50 mg/kg was able to decrease immobility time in FST and TST. Locomotor activity and coordination of mice were not affected by crocin or crocetin. Conclusion: Since higher doses of crocin was required to show antidepressant effects, more efficacy of crocetin may be concluded. This observation provides further support for metabolism of crocin to crocetin following oral administration.

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...

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 

White matter tract integrity is associated with antidepressant response to lurasidone in bipolar depression.

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Lan, Martin J; Rubin-Falcone, Harry; Motiwala, Fatima; Chen, Ying; Stewart, Jonathan W; Hellerstein, David J; Mann, J John; McGrath, Patrick J

2017-09-01

Patients with bipolar disorder spend the most time in the depressed phase, and that phase is associated with the most morbidity and mortality. Treatment of bipolar depression lacks a test to determine who will respond to treatment. White matter disruptions have been found in bipolar disorder. Previous reports suggest that white matter disruptions may be associated with resistance to antidepressant medication, but this has never been investigated in a prospective study using a Food and Drug Administration (FDA)-approved medication. Eighteen subjects with bipolar disorder who were in a major depressive episode and off all medications were recruited. Magnetic resonance imaging was acquired using a 64-direction diffusion tensor imaging sequence on a 3T scanner. Subjects were treated with 8 weeks of open-label lurasidone. The Montgomrey-Asberg Depression Rating Scale (MADRS) was completed weekly. Tract-Based Spatial Statistics were utilized to perform a regression analysis of fractional anisotropy (FA) data with treatment outcome as assessed by percent change in MADRS as a regressor while controlling for age and sex, using a threshold of P (threshold-free cluster enhancement-corrected) bipolar disorder were associated with poorer antidepressant response to lurasidone. The disruptions may potentially indicate treatment with a different antidepressant medication class. These results are limited by the open-label study design, sample size and lack of a healthy control group. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

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.

Opioid system contribution to the antidepressant-like action of m-trifluoromethyl-diphenyl diselenide in mice: A compound devoid of tolerance and withdrawal syndrome.

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Rosa, Suzan G; Pesarico, Ana P; Tagliapietra, Carolina F; da Luz, Sônia Ca; Nogueira, Cristina W

2017-09-01

Animal and clinical researches indicate that the opioid system exerts a crucial role in the etiology of mood disorders and is a target for intervention in depression treatment. This study investigated the contribution of the opioid system to the antidepressant-like action of acute or repeated m-trifluoromethyl-diphenyl diselenide administration to Swiss mice. m-Trifluoromethyl-diphenyl diselenide (50 mg/kg, intragastric) produced an antidepressant-like action in the forced swimming test from 30 min to 24 h after treatment. This effect was blocked by the µ and δ-opioid receptor antagonists, naloxonazine (10 mg/kg, intraperitoneally) and naltrindole (3 mg/kg, intraperitoneally), and it was potentiated by a κ-opioid receptor antagonist, norbinaltrophimine (1 mg/kg, subcutaneously ). Combined treatment with subeffective doses of m-trifluoromethyl-diphenyl diselenide (10 mg/kg, intragastric) and morphine (1 mg/kg, subcutaneously) resulted in a synergistic antidepressant-like effect. The opioid system contribution to the m-trifluoromethyl-diphenyl diselenide antidepressant-like action was also demonstrated in the modified tail suspension test, decreasing mouse immobility and swinging time and increasing curling time, results similar to those observed using morphine, a positive control. Treatment with m-trifluoromethyl-diphenyl diselenide induced neither tolerance to the antidepressant-like action nor physical signs of withdrawal, which could be associated with the fact that m-trifluoromethyl-diphenyl diselenide did not change the mouse cortical and hippocampal glutamate uptake and release. m-Trifluoromethyl-diphenyl diselenide treatments altered neither locomotor nor toxicological parameters in mice. These findings demonstrate that m-trifluoromethyl-diphenyl diselenide elicited an antidepressant-like action by direct or indirect μ and δ-opioid receptor activation and the κ-opioid receptor blockade, without inducing tolerance, physical signs of withdrawal and

Effect of co-administration of memantine and sertraline on the antidepressant-like activity and brain-derived neurotrophic factor (BDNF) levels in the rat brain.

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Amidfar, Meysam; Réus, Gislaine Z; Quevedo, João; Kim, Yong-Ku; Arbabi, Mohammad

2017-01-01

A developing body of data has drawn attention to the N-methyl-d-aspartate (NMDA) receptor antagonists as potential drugs for the treatment of major depressive disorder (MDD). We investigated the possibility of synergistic interactions between the antidepressant sertraline with the uncompetitive NMDA receptor antagonist, memantine. The present study was aimed to evaluate behavioural and molecular effects of the chronic treatment with memantine and sertraline alone or in combination in rats. To this aim, rats were chronically treated with memantine (2.5 and 5mg/kg) and sertraline (5mg/kg) for 14days once a day, and then exposed to the forced swimming test. The brain-derived neurotrophic factor (BDNF) levels were assessed in the hippocampus and prefrontal cortex in all groups by ELISA sandwich assay. Sertraline and memantine (2.5mg/kg) alone did not have effect on the immobility time; however, the effect of sertraline was enhanced by both doses of memantine. Combined treatment with memantine and sertraline produced stronger increases in the BDNF protein levels in the hippocampus and prefrontal cortex. Our results indicate that co-administration of antidepressant memantine with sertraline may induce a more pronounced antidepressant activity than treatment with each antidepressant alone. Antidepressant properties using the combination of memantine and sertraline could be attributed to increased levels of BDNF. This finding may be of particular importance in the case of drug-resistant patients and could suggest a method of obtaining significant antidepressant actions whereas limiting side effects. Copyright © 2016 Elsevier Inc. All rights reserved.

Serotonin(4) (5-HT(4)) receptor agonists are putative antidepressants with a rapid onset of action

DEFF Research Database (Denmark)

Lucas, Guillaume; Rymar, Vladimir V; Du, Jenny

2007-01-01

parameters considered to be key markers of antidepressant action, but that are observed only after 2-3 week treatments with classical molecules: desensitization of 5-HT(1A) autoreceptors, increased tonus on hippocampal postsynaptic 5-HT(1A) receptors, and enhanced phosphorylation of the CREB protein...... intake consecutive to a chronic mild stress. These findings point out 5-HT(4) receptor agonists as a putative class of antidepressants with a rapid onset of action. Udgivelsesdato: 2007-Sep-6...

Multiple antidepressant potential modes of action of curcumin: a review of its anti-inflammatory, monoaminergic, antioxidant, immune-modulating and neuroprotective effects.

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Lopresti, Adrian L; Hood, Sean D; Drummond, Peter D

2012-12-01

Curcumin is the principal curcuminoid of the popular Indian spice turmeric and has attracted increasing attention for the treatment of a range of conditions. Research into its potential as a treatment for depression is still in its infancy, although several potential antidepressant mechanisms of action have been identified. Research completed to date on the multiple effects of curcumin is reviewed in this paper, with a specific emphasis on the biological systems that are compromised in depression. The antidepressant effects of curcumin in animal models of depression are summarised, and its influence on neurotransmitters such as serotonin and dopamine is detailed. The effects of curcumin in moderating hypothalamus-pituitary-adrenal disturbances, lowering inflammation and protecting against oxidative stress, mitochondrial damage, neuroprogression and intestinal hyperpermeability, all of which are compromised in major depressive disorder, are also summarised. With increasing interest in natural treatments for depression, and efforts to enhance current treatment outcomes, curcumin is presented as a promising novel, adjunctive or stand-alone natural antidepressant.

Antidepressant Therapy in Severe Depression May Have Different Effects on Ego-Dystonic and Ego-Syntonic Suicidal Ideation

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Louise Brådvik

2011-01-01

Full Text Available The objective of the present study was to investigate whether ego-dystonic and ego-syntonic suicidal ideation occurred at different frequencies during antidepressant therapy. A blind evaluation has been performed on records of 100 suicides with a primary severe depression and 100 matched controls, admitted to the Department of Psychiatry, Lund, Sweden. Ego-dystonic suicidal ideation was more commonly reported during adequate treatment as compared to ego-syntonic ideation (P=.004. Men who committed suicide during adequate antidepressant therapy more often reported ego-dystonic suicidal ideation earlier in their lives compared with those who were not treated (P=.0377. This may indicate that treatment failure for ego-dystonic ideation was a precursor of their suicides. Consequently, ego-dystonic ideation seems to show a poorer response to antidepressant therapy as compared to ego-syntonic ideation, which may be more directly related to depression. Ego-dystonic ideation is proposed to be related to depressive psychosis.

Pattern and predictors of sick leave among users of antidepressants: a Danish retrospective register-based cohort study.

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Gasse, Christiane; Petersen, Liselotte; Chollet, Julien; Saragoussi, Delphine

2013-12-01

Depression is associated with work absenteeism, reduced productivity, and significant personal and societal economic burden. We describe patterns and determinants of sick leave among working Danish antidepressant users. Persons starting antidepressant treatment (January 1, 2004 through December 31, 2005) were identified from a representative 25% sample of the Danish population by linking Danish national registries. Inclusion criteria were age 18-64 years, being in the workforce the week prior to the first antidepressant prescription (index prescription, IP), and no antidepressant prescription in the year prior to the IP. Only sick leaves >2 weeks are centrally registered in Denmark and could be assessed. Cox regression analyses identified predictors of sick leave during the year following the IP, based on previous history of sick leave and clinical and socio-demographic baseline characteristics. In the cohort of 25,908 (59.7% women), sick leave prevalence increased from 37.5% (year prior to IP) to 45.3% (year after the IP); 30.7% were on sick leave for >8 weeks. Incidence peaked (35.5% of individuals) the week after the IP. Of persons with sick leave in the year before the IP, 62.7% were on sick leave the first week after the IP, vs 5.7% of those without previous sick leave. Predictors associated with increased risk of sick leave among those without previous sick leave were unemployment, female gender, age 25-54 years, couples with children, and vocational and higher intermediate education (including e.g. teachers and nurses). Reasons for sick leave, sick leaves of less than 14 days and the indications for antidepressant treatment were unknown. Sick leave was prevalent in persons starting new antidepressant use, often lasting >8 weeks. Previous sick leave was the strongest predictor of subsequent sick leave. © 2013 Elsevier B.V. All rights reserved.

Antidepressant-selective gynecomastia.

Science.gov (United States)

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

Antidepressant effects of total tertiary alkaloid fraction of Cissampelos sympodialis Eichler in rodents

Directory of Open Access Journals (Sweden)

Sueli Mendonça-Netto

Full Text Available The purpose of the present study was to evaluate the effects of total tertiary alkaloid fraction (TTAF of Cissampelos sympodialis Eichler (Menispermaceae on two animal models of depression: a forced swim test and b reserpine test. Treatment of mice with TTAF (12.5 mg/kg reduced the total immobility time. It also reversed the reserpine-induced hypothermia, demonstrating an antidepressant effect in both models. Additionally, TTAF treatment did not modify the ambulation and rearing evaluated in open field test in order to investigate if the immobility time reduction found in the forced swimming test was caused by locomotive activity stimulation. Since warifteine is one of the main alkaloids present in the TTAF of C. sympodialis, and it has inhibitory activity of the phosphodiesterase enzyme, it may be responsible by the antidepressant effect found in the fraction studied.

Antidepressant monotherapy vs sequential pharmacotherapy and mindfulness-based cognitive therapy, or placebo, for relapse prophylaxis in recurrent depression.

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Segal, Zindel V; Bieling, Peter; Young, Trevor; MacQueen, Glenda; Cooke, Robert; Martin, Lawrence; Bloch, Richard; Levitan, Robert D

2010-12-01

Mindfulness-based cognitive therapy (MBCT) is a group-based psychosocial intervention designed to enhance self-management of prodromal symptoms associated with depressive relapse. To compare rates of relapse in depressed patients in remission receiving MBCT against maintenance antidepressant pharmacotherapy, the current standard of care. Patients who met remission criteria after 8 months of algorithm-informed antidepressant treatment were randomized to receive maintenance antidepressant medication, MBCT, or placebo and were followed up for 18 months. Outpatient clinics at the Centre for Addiction and Mental Health, Toronto, Ontario, Canada, and St Joseph's Healthcare, Hamilton, Ontario. One hundred sixty patients aged 18 to 65 years meeting DSM-IV criteria for major depressive disorder with a minimum of 2 past episodes. Of these, 84 achieved remission (52.5%) and were assigned to 1 of the 3 study conditions. Patients in remission discontinued their antidepressants and attended 8 weekly group sessions of MBCT, continued taking their therapeutic dose of antidepressant medication, or discontinued active medication and were switched to placebo. Relapse was defined as a return, for at least 2 weeks, of symptoms sufficient to meet the criteria for major depression on module A of the Structured Clinical Interview for DSM-IV. Intention-to-treat analyses showed a significant interaction between the quality of acute-phase remission and subsequent prevention of relapse in randomized patients (P = .03). Among unstable remitters (1 or more Hamilton Rating Scale for Depression score >7 during remission), patients in both MBCT and maintenance treatment showed a 73% decrease in hazard compared with placebo (P = .03), whereas for stable remitters (all Hamilton Rating Scale for Depression scores ≤7 during remission) there were no group differences in survival. For depressed patients achieving stable or unstable clinical remission, MBCT offers protection against relapse

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.

Possible involvement of ATP-sensitive potassium channels in the antidepressant-like effects of gabapentin in mouse forced swimming test.

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Ostadhadi, Sattar; Akbarian, Reyhaneh; Norouzi-Javidan, Abbas; Nikoui, Vahid; Zolfaghari, Samira; Chamanara, Mohsen; Dehpour, Ahmad-Reza

2017-07-01

Gabapentin as an anticonvulsant drug also has beneficial effects in treatment of depression. Previously, we showed that acute administration of gabapentin produced an antidepressant-like effect in the mouse forced swimming test (FST) by a mechanism that involves the inhibition of nitric oxide (NO). Considering the involvement of NO in adenosine triphosphate (ATP)-sensitive potassium channels (K ATP ), in the present study we investigated the involvement of K ATP channels in antidepressant-like effect of gabapentin. Gabapentin at different doses (5-10 mg/kg) and fluoxetine (20 mg/kg) were administrated by intraperitoneal route, 60 and 30 min, respectively, before the test. To clarify the probable involvement of K ATP channels, mice were pretreated with K ATP channel inhibitor or opener. Gabapentin at dose 10 mg/kg significantly decreased the immobility behavior of mice similar to fluoxetine (20 mg/kg). Co-administration of subeffective dose (1 mg/kg) of glibenclamide (inhibitor of K ATP channels) with gabapentin (3 mg/kg) showed a synergistic antidepressant-like effect. Also, subeffective dose of cromakalim (opener of K ATP channels, 0.1 mg/kg) inhibited the antidepressant-like effect of gabapentin (10 mg/kg). None of the treatments had any impact on the locomotor movement. Our study, for the first time, revealed that antidepressant-like effect of gabapentin in mice is mediated by blocking the K ATP channels.

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.

Evidences for the agmatine involvement in antidepressant like effect of bupropion in mouse forced swim test.

Science.gov (United States)

Kotagale, Nandkishor R; Tripathi, Sunil J; Aglawe, Manish M; Chopde, Chandrabhan T; Umekar, Milind J; Taksande, Brijesh G

2013-06-01

Although bupropion has been widely used in the treatment of depression, the precise mechanism of its therapeutic actions is not fully understood. The present study investigated the role of agmatine in an antidepressant like effect of bupropion in mouse forced swim test. The antidepressant like effect of bupropion was potentiated by pretreatment with agmatine (10-20mg/kg, ip) and by the drugs known to increase endogenous agmatine levels in brain viz., l-arginine (40 μg/mouse, icv), an agmatine biosynthetic precursor, ornithine decarboxylase inhibitor, dl-α-difluoromethyl ornithine hydrochloride, DFMO (12.5 μg/mouse, icv), diamine oxidase inhibitor, aminoguanidine (6.5 μg/mouse, icv) and agmatinase inhibitor, arcaine (50 μg/mouse, icv) as well as imidazoline I1 receptor agonists, moxonidine (0.25mg/kg, ip) and clonidine (0.015 mg/kg, ip) and imidazoline I2 receptor agonist, 2-(2-benzofuranyl)-2-imidazoline hydrochloride, 2-BFI (5mg/kg, ip). Conversely, prior administration of I1 receptor antagonist, efaroxan (1mg/kg, ip) and I2 receptor antagonist, idazoxan (0.25mg/kg, ip) blocked the antidepressant like effect of bupropion and its synergistic combination with agmatine. These results demonstrate involvement of agmatine in the antidepressant like effect of bupropion and suggest agmatine and imidazoline receptors as a potential therapeutic target for the treatment of depressive disorders. Copyright © 2013 Elsevier Inc. All rights reserved.

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...

Testimony on Drug Treatment Alternatives to Incarceration

National Research Council Canada - National Science Library

Iguchi, Martin

2000-01-01

... treatment within the criminal justice system. Players in that policy game focused, as we are doing today, on the need to provide criminal offenders with drug abuse treatment as an alternative to incarceration...

The monoaminergic pathways and inhibition of monoamine transporters interfere with the antidepressive-like behavior of ketamine

Directory of Open Access Journals (Sweden)

Glauce Socorro de Barros Viana

2018-06-01

Full Text Available Ketamine (KET, a NMDA receptor antagonist, has been studied for its rapid and efficacious antidepressant effect, even for the treatment-resistant depression. Although depression is a major cause of disability worldwide, the treatment can be feasible, affordable and cost-effective, decreasing the population health burden. We evaluated the antidepressive-like effects of KET and its actions on monoamine contents (DA and its metabolites, as well as 5-HT and on tyrosine hydroxylase (TH. In addition DAT and SERT (DA and 5-HT transporters, respectively were also assessed. Male Swiss mice were divided into Control and KET-treated groups. The animals were acutely treated with KET (2, 5 or 10 mg/kg, i.p. and subjected to the forced swimming test, for evaluation of the antidepressive-like behavior. Imipramine and fluoxetine were used as references. The results showed that KET decreased dose-dependently the immobility time and shortly after the test, the animals were euthanized for striatal dissections and monoamine determinations. In addition, the brain (striata, hippocampi and prefrontal cortices was immunohistochemically processed for TH, DAT and SERT. KET at its higher dose increased DA and its metabolites (DOPAC and HVA and mainly 5-HT contents, in mice striata, effects associated with increases in TH and decreases in DAT immunoreactivities. Furthermore, reductions in SERT immunoreactivities were observed in the striatum and hippocampus. The results indicate that KET antidepressive-like effect probably involves, among other factors, monoaminergic pathways, as suggested by the increased striatal TH immunoreactivity and reduced brain DA (DAT and 5-HT (SERT transporters. Keywords: Ketamine, Antidepressive effect, Dopaminergic neurotransmission, Serotonergic neurotransmission, Monoamine transporters

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

Investigations of morning and laboratory dream recall and content in depressive patients during baseline conditions and under antidepressive treatment with trimipramine.

Science.gov (United States)

Riemann, D; Löw, H; Schredl, M; Wiegand, M; Dippel, B; Berger, M

1990-06-01

REM sleep abnormalities like shortened REM (rapid eye movement) latency, prolongation of the first REM period and heightening of REM density often found in patients with a major depression have prompted an increasing number of studies investigating the neurobiology and neurophysiology of REM sleep in depressive patients, as well as in healthy humans and animals. On the other hand, since the early 1970s investigation of the psychological concomitant of REM sleep, i.e., dreaming, in depressive patients has been extremely sparse. The present study aimed at investigating morning and laboratory dream recall and content in patients with a major depressive disorder to shed more light on this neglected area. In short, morning as well as laboratory dream recall in depressive inpatients was drastically reduced. The low number of scorable dream reports collected did not reveal a heightened incidence of "masochistic" or "negative" content, indeed were rather mundane. In contrast, depressive outpatients (probably less depressed) had a higher rate of morning dream recall. Interestingly, antidepressive treatment with trimipramine (an antidepressant which does not suppress REM sleep) led to a positive influence on patients' mood that was paralleled by a change of dream mood in a positive direction.

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

Science.gov (United States)

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.

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

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.

Antidepressants for depressive disorder in children and adolescents: a database of randomised controlled trials.

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Zhang, Yuqing; Zhou, Xinyu; Pu, Juncai; Zhang, Hanping; Yang, Lining; Liu, Lanxiang; Zhou, Chanjuan; Yuan, Shuai; Jiang, Xiaofeng; Xie, Peng

2018-05-31

In recent years, whether, when and how to use antidepressants to treat depressive disorder in children and adolescents has been hotly debated. Relevant evidence on this topic has increased rapidly. In this paper, we present the construction and content of a database of randomised controlled trials of antidepressants to treat depressive disorder in children and adolescents. This database can be freely accessed via our website and will be regularly updated. Major bibliographic databases (PubMed, the Cochrane Library, Web of Science, Embase, CINAHL, PsycINFO and LiLACS), international trial registers and regulatory agencies' websites were systematically searched for published and unpublished studies up to April 30, 2017. We included randomised controlled trials in which the efficacy or tolerability of any oral antidepressant was compared with that of a control group or any other treatment. In total, 7377 citations from bibliographical databases and 3289 from international trial registers and regulatory agencies' websites were identified. Of these, 53 trials were eligible for inclusion in the final database. Selected data were extracted from each study, including characteristics of the participants (the study population, setting, diagnostic criteria, type of depression, age, sex, and comorbidity), characteristics of the treatment conditions (the treatment conditions, general information, and detail of pharmacotherapy and psychotherapy) and study characteristics (the sponsor, country, number of sites, blinding method, sample size, treatment duration, depression scales, other scales, and primary outcome measure used, and side-effect monitoring method). Moreover, the risk of bias for each trial were assessed. This database provides information on nearly all randomised controlled trials of antidepressants in children and adolescents. By using this database, researchers can improve research efficiency, avoid inadvertent errors and easily focus on the targeted subgroups in

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.

Kappa opioid receptor antagonism and chronic antidepressant treatment have beneficial activities on social interactions and grooming deficits during heroin abstinence.

Science.gov (United States)

Lalanne, L; Ayranci, G; Filliol, D; Gavériaux-Ruff, C; Befort, K; Kieffer, B L; Lutz, P-E

2017-07-01

Addiction is a chronic brain disorder that progressively invades all aspects of personal life. Accordingly, addiction to opiates severely impairs interpersonal relationships, and the resulting social isolation strongly contributes to the severity and chronicity of the disease. Uncovering new therapeutic strategies that address this aspect of addiction is therefore of great clinical relevance. We recently established a mouse model of heroin addiction in which, following chronic heroin exposure, 'abstinent' mice progressively develop a strong and long-lasting social avoidance phenotype. Here, we explored and compared the efficacy of two pharmacological interventions in this mouse model. Because clinical studies indicate some efficacy of antidepressants on emotional dysfunction associated with addiction, we first used a chronic 4-week treatment with the serotonergic antidepressant fluoxetine, as a reference. In addition, considering prodepressant effects recently associated with kappa opioid receptor signaling, we also investigated the kappa opioid receptor antagonist norbinaltorphimine (norBNI). Finally, we assessed whether fluoxetine and norBNI could reverse abstinence-induced social avoidance after it has established. Altogether, our results show that two interspaced norBNI administrations are sufficient both to prevent and to reverse social impairment in heroin abstinent animals. Therefore, kappa opioid receptor antagonism may represent a useful approach to alleviate social dysfunction in addicted individuals. © 2016 Society for the Study of Addiction.

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

Science.gov (United States)

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.

[Αnti-Inflammatory medication as adjunctive antidepressive treatment].

Science.gov (United States)

Boufidou, F; Nikolaou, C

2016-01-01

Mounting data of evidence that have emerged during the last twenty years, point towards the existence of an inflammatory mechanism underlying the pathophysiology of depressive disorder. These data have inspired a number of clinical studies characterized by the administration of inflammatory response altering medication in addition to conventional medication in depressive disorder patients. The drugs were either Non Steroid Anti-inflammatory Drugs (NSAIDs) or Tumor Necrosis Factor-alpha (TNFa) inhibitors and were selected among those that are already in use for various diseases related to the immune system. The choice of these specific immunomodulatory agents for the co-administration with conventional antidepressive medication was based on a number of laboratory data and clinical evidence. A total of seven relevant clinical trials have been conducted, all of them with promising results that have been published between 2006 and 2013. However, only four out of them were eligibly designed regarding the homogeneity of the study groups, randomization, double-blinding and placebo controlling. These three studies showed clinical advantages of the adjunctive medication as estimated by significant drops in Hamilton scores. Of interest are the findings of the most recent and largest clinical trial of the TNF-a antagonist infliximab which show that treatment with anti-inflammatory agents may be beneficial only in depressive patients with raised levels of baseline inflammatory markers. A limitation of the studies was that, since no guidelines currently exist for anti-inflammatory agents and depression, adjunctive medication could have been under or overdosed. Other limitations were the follow-up period that was rather small and the number of the participants that was also small. Recently, a lot of progress has been made in identifying therapeutic targets along metabolic pathways in the brain relevant to depression, which could be manipulated by immune mediators. In fact

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.

Suicidality: risk factors and the effects of antidepressants. The example of parallel reduction of suicidality and other depressive symptoms during treatment with the SNRI, milnacipran

Directory of Open Access Journals (Sweden)

Philippe Courtet

2010-08-01

Full Text Available Philippe CourtetCHRU Montpellier, Inserm U888, University of Montpellier I, Montpellier, FranceAbstract: Suicidal behavior (SB represents a major public health issue. Clinical and basic research suggests that SB is a specific entity in psychiatric nosology involving a combination of personality traits, genetic factors, childhood abuse and neuroanatomical abnormalities. The principal risk factor for suicide is depression. More than 60% of patients who complete suicide are depressed at the time of suicide, most of them untreated. There has been a controversy concerning a possible increased risk of SB in some depressed patients treated with antidepressants. Most recent evidence suggests, however, that treatment of depressed patients is associated with a favorable benefit-risk ratio. A recent study has determined the effects of 6 weeks of antidepressant treatment with the serotonin and norepinephrine reuptake inhibitor, milnacipran, on suicidality in a cohort of 30 patients with mild to moderate depression. At baseline, mild suicidal thoughts were present in 46.7% of patients. Suicidal thoughts decreased progressively throughout the study in parallel with other depressive symptoms and were essentially absent at the end of the study. At no time during treatment was there any indication of an increased suicidal risk. Retardation and psychic anxiety decreased in parallel possibly explaining the lack of any “activation syndrome” in this study.Keywords: suicide, milnacipran, SNRI, activation syndrome

P-glycoprotein Inhibition Increases the Brain Distribution and Antidepressant-Like Activity of Escitalopram in Rodents

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O'Brien, Fionn E; O'Connor, Richard M; Clarke, Gerard; Dinan, Timothy G; Griffin, Brendan T; Cryan, John F

2013-01-01

Despite the clinical prevalence of the antidepressant escitalopram, over 30% of escitalopram-treated patients fail to respond to treatment. Recent gene association studies have highlighted a potential link between the drug efflux transporter P-glycoprotein (P-gp) and response to escitalopram. The present studies investigated pharmacokinetic and pharmacodynamic interactions between P-gp and escitalopram. In vitro bidirectional transport studies revealed that escitalopram is a transported substrate of human P-gp. Microdialysis-based pharmacokinetic studies demonstrated that administration of the P-gp inhibitor cyclosporin A resulted in increased brain levels of escitalopram without altering plasma escitalopram levels in the rat, thereby showing that P-gp restricts escitalopram transport across the blood–brain barrier (BBB) in vivo. The tail suspension test (TST) was carried out to elucidate the pharmacodynamic impact of P-gp inhibition on escitalopram effect in a mouse model of antidepressant activity. Pre-treatment with the P-gp inhibitor verapamil enhanced the response to escitalopram in the TST. Taken together, these data indicate that P-gp may restrict the BBB transport of escitalopram in humans, potentially resulting in subtherapeutic brain concentrations in certain patients. Moreover, by verifying that increasing escitalopram delivery to the brain by P-gp inhibition results in enhanced antidepressant-like activity, we suggest that adjunctive treatment with a P-gp inhibitor may represent a beneficial approach to augment escitalopram therapy in depression. PMID:23670590

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

Derivation and validation of a multivariable model to predict when primary care physicians prescribe antidepressants for indications other than depression

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Wong J

2018-04-01

Full Text Available Jenna Wong, Michal Abrahamowicz, David L Buckeridge, Robyn Tamblyn Department of Epidemiology, Biostatistics, and Occupational Health, McGill University, Montreal, QC, Canada Objective: Physicians commonly prescribe antidepressants for indications other than depression that are not evidence-based and need further evaluation. However, lack of routinely documented treatment indications for medications in administrative and medical databases creates a major barrier to evaluating antidepressant use for indications besides depression. Thus, the aim of this study was to derive a model to predict when primary care physicians prescribe antidepressants for indications other than depression and to identify important determinants of this prescribing practice. Methods: Prediction study using antidepressant prescriptions from January 2003–December 2012 in an indication-based electronic prescribing system in Quebec, Canada. Patients were linked to demographic files, medical billings data, and hospital discharge summary data to create over 370 candidate predictors. The final prediction model was derived on a random 75% sample of the data using 3-fold cross-validation integrated within a score-based forward stepwise selection procedure. The performance of the final model was assessed in the remaining 25% of the data. Results: Among 73,576 antidepressant prescriptions, 32,405 (44.0% were written for indications other than depression. Among 40 predictors in the final model, the most important covariates included the molecule name, the patient’s education level, the physician’s workload, the prescribed dose, and diagnostic codes for plausible indications recorded in the past year. The final model had good discrimination (concordance (c statistic 0.815; 95% CI, 0.787–0.847 and good calibration (ratio of observed to expected events 0.986; 95% CI, 0.842–1.136. Conclusion: In the absence of documented treatment indications, researchers may be able to use

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

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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.

Serum brain-derived neurotrophic factor and glucocorticoid receptor levels in lymphocytes as markers of antidepressant response in major depressive patients: a pilot study.

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Rojas, Paulina Soledad; Fritsch, Rosemarie; Rojas, Romina Andrea; Jara, Pablo; Fiedler, Jenny Lucy

2011-09-30

Depressive patients often have altered cortisol secretion, an effect that likely derives from impaired activity of the glucocorticoid receptor (GR), the main regulator of the hypothalamus-pituitary-adrenal (HPA) axis. Glucocorticoids reduce the levels of brain-derived neurotrophic factor (BDNF), a downstream target of antidepressants. Antidepressants promote the transcriptional activity of cyclic adenosine monophosphate (cAMP) response element binding protein (CREB), a regulator of BDNF expression. To identify potential biomarkers for the onset of antidepressant action in depressive patients, GR and phospho-CREB (pCREB) levels in lymphocytes and serum BDNF levels were repeatedly measured during the course of antidepressant treatment. Thirty-four depressed outpatients (10 male and 24 female) were treated with venlafaxine (75mg/day), and individuals exhibiting a 50% reduction in their baseline 17-Item Hamilton Depression Rating Scale score by the 6th week of treatment were considered responders. Responders showed an early improvement in parallel with a rise in BDNF levels during the first two weeks of treatment. Non-responders showed increased GR levels by the third week and reduced serum BDNF by the sixth week of treatment. In contrast, venlafaxine did not affect levels of pCREB. We conclude that levels of BDNF in serum and GR levels in lymphocytes may represent biomarkers that could be used to predict responses to venlafaxine treatment. Copyright © 2011 Elsevier Ltd. All rights reserved.

Generic penetration in the retail antidepressant market.

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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.

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.

Investigation of the Anxiolytic and Antidepressant Effects of Curcumin, a Compound From Turmeric (Curcuma longa), in the Adult Male Sprague-Dawley Rat.

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Ceremuga, Tomás Eduardo; Helmrick, Katie; Kufahl, Zachary; Kelley, Jesse; Keller, Brian; Philippe, Fabiola; Golder, James; Padrón, Gina

As the use of herbal medications continues to increase in America, the potential interaction between herbal and prescription medications necessitates the discovery of their mechanisms of action. The purpose of this study was to investigate the anxiolytic and antidepressant effects of curcumin, a compound from turmeric (Curcuma longa), and its effects on the benzodiazepine site of the γ-aminobutyric acid receptor A (GABAA) receptor. Utilizing a prospective, between-subjects group design, 55 male Sprague-Dawley rats were randomly assigned to 1 of the 5 intraperitoneally injected treatment groups: vehicle, curcumin, curcumin + flumazenil, midazolam, and midazolam + curcumin. Behavioral testing was performed using the elevated plus maze, open field test, and forced swim test. A 2-tailed multivariate analysis of variance and least significant difference post hoc tests were used for data analysis. In our models, curcumin did not demonstrate anxiolytic effects or changes in behavioral despair. An interaction of curcumin at the benzodiazepine site of the GABAA receptor was also not observed. Additional studies are recommended that examine the anxiolytic and antidepressant effects of curcumin through alternate dosing regimens, modulation of other subunits on the GABAA receptor, and interactions with other central nervous system neurotransmitter systems.

Antidepressants and changes in concentration of endocannabinoids and N-acylethanolamines in rat brain structures.

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Smaga, Irena; Bystrowska, Beata; Gawliński, Dawid; Pomierny, Bartosz; Stankowicz, Piotr; Filip, Małgorzata

2014-08-01

The endocannabinoid (eCB) system has recently been implicated in both the pathogenesis of depression and the action of antidepressants. Here, we investigated the effect of acutely or chronically administering antidepressants [imipramine (IMI) (15 mg/kg), escitalopram (ESC) (10 mg/kg), and tianeptine (10 mg/kg)] on the levels of both eCBs [anandamide (AEA) and 2-arachidonoylglycerol (2-AG)] and N-acylethanolamines (NAEs) [palmitoylethanolamide (PEA) and oleoylethanolamide (OEA)] in various rat brain regions. We also examined the ability of the acute and chronic administration of N-acetylcysteine (NAC) (a mucolytic drug; 100 mg/kg) or URB597 (a fatty acid amide hydrolase inhibitor; 0.3 mg/kg), which have both elicited antidepressant activity in preclinical studies, to affect eCB and NAE levels. Next, we determined whether the observed effects are stable 10 days after the chronic administration of these drugs was halted. We report that the chronic administration of all investigated drugs increased AEA levels in the hippocampus and also increased both AEA and 2-AG levels in the dorsal striatum. NAE levels in limbic regions also increased after treatment with IMI (PEA/OEA), ESC (PEA), and NAC (PEA/OEA). Removing chronic ESC treatment for 10 days affected eCB and NAE levels in the frontal cortex, hippocampus, dorsal striatum, and cerebellum, while a similar tianeptine-free period enhanced accumbal NAE levels. All other drugs maintained their effects after the 10-day washout period. Therefore, the eCB system appears to play a significant role in the mechanism of action of clinically effective and potential antidepressants and may serve as a target for drug design and discovery.

Role of Serum Brain Derived Neurotrophic Factor and Central N-Acetylaspartate for Clinical Response under Antidepressive Pharmacotherapy

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Sarah Nase

2016-02-01

Full Text Available Background: The predictive therapeutic value of brain derived neurotrophic factor (BDNF and its changes associated with the use of specific antidepressants are still unclear. In this study, we examined BDNF as a peripheral and NAA as a central biomarker over the time course of antidepressant treatment to specify both of their roles in the response to the medication and clinical outcome. Methods: We examined serum BDNF (ELISA kit in a sample of 76 (47 female and 29 male depressed patients in a naturalistic setting. BDNF was assessed before medication and subsequently after two, four and six weeks of antidepressant treatment. Additionally, in fifteen patients, N-acetylaspartate (NAA was measured in the anterior cingulate cortex (ACC with magnetic resonance spectroscopy (MRS. Over a time course of six weeks BDNF and NAA were also examined in a group of 41 healthy controls. Results: We found significant lower serum BDNF concentrations in depressed patients compared to the sample of healthy volunteers before and after medication. BDNF and clinical symptoms decreased significantly in the patients over the time course of antidepressant treatment. Serum BDNF levels at baseline predicted the symptom outcome after eight weeks. Specifically, responders and remitters had lower serum BDNF at baseline than the nonresponders and nonremitters. NAA was slightly decreased but not significantly lower in depressed patients when compared with healthy controls. During treatment period, NAA showed a tendency to increase. Limitations: A relative high drop-out rate and possibly, a suboptimal observation period for BDNF. Conclusion: Our data confirm serum BDNF as a biomarker of depression with a possible role in response prediction. However, our findings argue against serum BDNF increase being a prerequisite to depressive symptom reduction.

Feasibility of nurse-led antidepressant medication management of depression in an HIV clinic in Tanzania.

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Adams, Julie L; Almond, Maria L G; Ringo, Edward J; Shangali, Wahida H; Sikkema, Kathleen J

2012-01-01

Sub-Saharan Africa has the highest HIV prevalence worldwide and depression is highly prevalent among those infected. The negative impact of depression on HIV outcomes highlights the need to identify and treat it in this population. A model for doing this in lower-resourced settings involves task-shifting depression treatment to primary care; however, HIV-infected individuals are often treated in a parallel HIV specialty setting. We adapted a model of task-shifting, measurement-based care (MBC), for an HIV clinic setting and tested its feasibility in Tanzania. MBC involves measuring depressive symptoms at meaningful intervals and adjusting antidepressant medication treatment based on the measure of illness. Twenty adults presenting for care at an outpatient HIV clinic in Tanzania were enrolled and followed by a nurse care manager who measured depressive symptoms at baseline and every 4 weeks for 12 weeks. An algorithm-based decision-support tool was utilized by the care manager to recommend individualized antidepressant medication doses to participants' HIV providers at each visit. Retention was high and fidelity of the care manager to the MBC protocol was exceptional. Follow through of antidepressant prescription dosing recommendations by the prescriber was low. Limited availability of antidepressants was also noted. Despite challenges, baseline depression scores decreased over the 12-week period. Overall, the model of algorithm-based nursing support of prescription decisions was feasible. Future studies should address implementation issues of medication supply and dosing. Further task-shifting to relatively more abundant and lower-skilled health workers, such as nurses' aides, warrants examination.

Alternative methods of ophthalmic treatment in Russia.

Science.gov (United States)

Vader, L

1994-04-01

Russian ophthalmic nurses and physicians are using alternative methods of treatment to supplement traditional eye care. As acupuncture and iridology become more popular in the United States, ophthalmic nurses need to be more knowledgeable about these treatments and the implications for patients.

Erythropoietin modulates neural and cognitive processing of emotional information in biomarker models of antidepressant drug action in depressed patients

DEFF Research Database (Denmark)

Miskowiak, Kamilla W; Favaron, Elisa; Hafizi, Sepehr

2010-01-01

Erythropoietin (Epo) has neuroprotective and neurotrophic effects, and may be a novel therapeutic agent in the treatment of psychiatric disorders. We have demonstrated antidepressant-like effects of Epo on the neural and cognitive processing of facial expressions in healthy volunteers. The curren...... study investigates the effects of Epo on the neural and cognitive response to emotional facial expressions in depressed patients.......Erythropoietin (Epo) has neuroprotective and neurotrophic effects, and may be a novel therapeutic agent in the treatment of psychiatric disorders. We have demonstrated antidepressant-like effects of Epo on the neural and cognitive processing of facial expressions in healthy volunteers. The current...

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...

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

Treatment emergent psychosis associated with mirtazapine and ...

African Journals Online (AJOL)

Psychosis, in vulnerable individuals, may emerge on anti - depressant treatment. Treatment emergent psychosis is reported with two newer generation antidepressants. Keywords: Antidepressants, Psychosis, Mirtazapine, Tianeptine South African Psychiatry Review - November 2002 ...

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.

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.

S 47445 Produces Antidepressant- and Anxiolytic-Like Effects through Neurogenesis Dependent and Independent Mechanisms

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Indira Mendez-David

2017-07-01

Full Text Available Glutamatergic dysfunctions are observed in the pathophysiology of depression. The glutamatergic synapse as well as the AMPA receptor’s (AMPAR activation may represent new potential targets for therapeutic intervention in the context of major depressive disorders. S 47445 is a novel AMPARs positive allosteric modulator (AMPA-PAM possessing procognitive, neurotrophic properties and enhancing synaptic plasticity. Here, we investigated the antidepressant/anxiolytic-like effects of S 47445 in a mouse model of anxiety/depression based on chronic corticosterone administration (CORT and in the Chronic Mild Stress (CMS model in rats. Four doses of S 47445 (0.3 to 10 mg/kg, oral route, 4 and 5 weeks, respectively were assessed in both models. In mouse, behavioral effects were tested in various anxiety-and depression-related behaviors : the elevated plus maze (EPM, open field (OF, splash test (ST, forced swim test (FST, tail suspension test (TST, fur coat state and novelty suppressed feeding (NSF as well as on hippocampal neurogenesis and dendritic arborization in comparison to chronic fluoxetine treatment (18 mg/kg, p.o.. In rats, behavioral effects of S 47445 were monitored using sucrose consumption and compared to those of imipramine or venlafaxine (10 mg/kg, i.p. during the whole treatment period and after withdrawal of treatments. In a mouse model of genetic ablation of hippocampal neurogenesis (GFAP-Tk model, neurogenesis dependent/independent effects of chronic S 47445 treatment were tested, as well as BDNF hippocampal expression. S 47445 reversed CORT-induced depressive-like state by increasing grooming duration and reversing coat state’s deterioration. S 47445 also decreased the immobility duration in TST and FST. The highest doses (3 and 10 mg/kg seem the most effective for antidepressant-like activity in CORT mice. Furthermore, S 47445 significantly reversed the anxiety phenotype observed in OF (at 1 mg/kg and EPM (from 1 mg/kg. In the CMS

Modulation of the activity of N-methyl-D-aspartate receptors as a novel treatment option for depression: current clinical evidence and therapeutic potential of rapastinel (GLYX-13

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Vasilescu AN

2017-03-01

Full Text Available Andrei-Nicolae Vasilescu,1,* Nina Schweinfurth,2,* Stefan Borgwardt,2,* Peter Gass,1 Undine E Lang,2,* Dragos Inta,1,2,* Sarah Eckart2,* 1Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Heidelberg, Germany; 2Department of Psychiatry (Universitäre Psychiatrische Kliniken, University of Basel, Basel, Switzerland *These authors contributed equally to this work Abstract: Classical monoaminergic antidepressants show several disadvantages, such as protracted onset of therapeutic action. Conversely, the fast and sustained antidepressant effect of the N-methyl-d-aspartate receptor (NMDAR antagonist ketamine raises vast interest in understanding the role of the glutamate system in mood disorders. Indeed, numerous data support the existence of glutamatergic dysfunction in major depressive disorder (MDD. Drawback to this short-latency therapy is its side effect profile, especially the psychotomimetic action, which seriously hampers the common and widespread clinical use of ketamine. Therefore, there is a substantial need for alternative glutamatergic antidepressants with milder side effects. In this article, we review evidence that implicates NMDARs in the prospective treatment of MDD with focus on rapastinel (formerly known as GLYX-13, a novel synthetic NMDAR modulator with fast antidepressant effect, which acts by enhancing NMDAR function as opposed to blocking it. We summarize and discuss current clinical and animal studies regarding the therapeutic potential of rapastinel not only in MDD but also in other psychiatric disorders, such as obsessive–compulsive disorder and posttraumatic stress disorder. Additionally, we discuss current data concerning the molecular mechanisms underlying the antidepressant effect of rapastinel, highlighting common aspects as well as differences to ketamine. In 2016, rapastinel received the Breakthrough Therapy designation for the treatment

The Oxford Questionnaire on the Emotional Side-effects of Antidepressants (OQuESA): development, validity, reliability and sensitivity to change.

Science.gov (United States)

Price, Jonathan; Cole, Victoria; Doll, Helen; Goodwin, Guy M

2012-09-01

Some patients with major depression report a restricted range of emotions that may appear to arise as a side-effect of treatment with antidepressants. It is uncertain whether this phenomenon, sometimes called emotional blunting, represents residual symptoms of depression or side-effects of antidepressant treatment. There is currently no adequate instrument to measure this phenomenon. A draft questionnaire was developed from patient-derived qualitative data, refined using cognitive interviewing, and administered on three occasions to patients taking antidepressants. Statistical methods including factor analysis were used to reduce the size of the draft questionnaire, and to assess the performance of the resulting Oxford Questionnaire on the Emotional Side-effects of Antidepressants (OQuESA). 207 patients completed the OQuESA on at least one occasion. Their BDI-II scores and self-reported emotional blunting were spread across the possible range. The factor analysis resulted in four dimensions: 'not caring', 'emotional detachment', 'reduction in positive emotions', and 'general reduction in emotions'. The OQuESA appears to be acceptable, valid, and reliable, with sensitivity to change. The OQuESA offers promise as an effective self-report measure of the symptoms of emotional blunting in patients with depression. It can be used as a clinical tool, to facilitate the identification of patients with the syndrome of emotional blunting. It should also be used in research studies, to advance our understanding of the nature, causes and treatment of this phenomenon. Copyright © 2012 Elsevier B.V. All rights reserved.

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

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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

Changes of cortical excitability as markers of antidepressant response in bipolar depression: preliminary data obtained by combining transcranial magnetic stimulation (TMS) and electroencephalography (EEG).

Science.gov (United States)

Canali, Paola; Sferrazza Papa, Giovanna; Casali, Adenauer G; Schiena, Giandomenico; Fecchio, Matteo; Pigorini, Andrea; Smeraldi, Enrico; Colombo, Cristina; Benedetti, Francesco

2014-12-01

It is still unclear which biological changes are needed to recover from a major depressive episode. Current perspectives focus on cortical synaptic neuroplasticity. Measures of cortical responses evoked by transcranial magnetic stimulation (TMS) change with sleep homeostasic pressure in humans and approximate measures of synaptic strength in animal models. Using repeated total sleep deprivation as a model of antidepressant treatment, we aimed to correlate recovery from depression with these measures of cortical excitability. We recorded electroencephalographic responses to TMS in the prefrontal cortex of 21 depressed inpatients with bipolar disorder treated with repeated sleep deprivation combined with light therapy. We performed seven TMS/electroencephalography sessions during one week and calculated three measures of cortical excitability. Cortical excitability progressively increased during the antidepressant treatment and as a function of time awake. Higher values differentiated responders from non-responders at baseline and during and after treatment on all measures. Changes in measures of cortical excitability parallel and predict antidepressant response to combined sleep deprivation and light therapy. Data suggest that promoting cortical plasticity in bipolar depression could be a major effect of successful antidepressant treatments, and that patients not responding could suffer a persistent impairment in their neuroplasticity mechanisms. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

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 ...

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

Science.gov (United States)

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.

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

The Prodrug 4-Chlorokynurenine Causes Ketamine-Like Antidepressant Effects, but Not Side Effects, by NMDA/GlycineB-Site Inhibition.

Science.gov (United States)

Zanos, Panos; Piantadosi, Sean C; Wu, Hui-Qiu; Pribut, Heather J; Dell, Matthew J; Can, Adem; Snodgrass, H Ralph; Zarate, Carlos A; Schwarcz, Robert; Gould, Todd D

2015-10-01

Currently approved antidepressant drug treatment typically takes several weeks to be effective. The noncompetitive N-methyl-d-aspartate (NMDA) receptor antagonist ketamine has shown efficacy as a rapid-acting treatment of depression, but its use is associated with significant side effects. We assessed effects following blockade of the glycineB co-agonist site of the NMDA receptor, located on the GluN1 subunit, by the selective full antagonist 7-chloro-kynurenic acid (7-Cl-KYNA), delivered by systemic administration of its brain-penetrant prodrug 4-chlorokynurenine (4-Cl-KYN) in mice. Following administration of 4-Cl-KYN, 7-Cl-KYNA was promptly recovered extracellularly in hippocampal microdialysate of freely moving animals. The behavioral responses of the animals were assessed using measures of ketamine-sensitive antidepressant efficacy (including the 24-hour forced swim test, learned helplessness test, and novelty-suppressed feeding test). In these tests, distinct from fluoxetine, and similar to ketamine, 4-Cl-KYN administration resulted in rapid, dose-dependent and persistent antidepressant-like effects following a single treatment. The antidepressant effects of 4-Cl-KYN were prevented by pretreatment with glycine or the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonist 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo[f]quinoxaline-2,3-dione (NBQX). 4-Cl-KYN administration was not associated with the rewarding and psychotomimetic effects of ketamine, and did not induce locomotor sensitization or stereotypic behaviors. Our results provide further support for antagonism of the glycineB site for the rapid treatment of treatment-resistant depression without the negative side effects seen with ketamine or other channel-blocking NMDA receptor antagonists. Copyright © 2015 by The American Society for Pharmacology and Experimental Therapeutics.

Antidepressants for chronic non-cancer pain in children and adolescents.

Science.gov (United States)

Cooper, Tess E; Heathcote, Lauren C; Clinch, Jacqui; Gold, Jeffrey I; Howard, Richard; Lord, Susan M; Schechter, Neil; Wood, Chantal; Wiffen, Philip J

2017-08-05

Pain is a common feature of childhood and adolescence around the world, and for many young people, that pain is chronic. The World Health Organization guidelines for pharmacological treatments for children's persisting pain acknowledge that pain in children is a major public health concern of high significance in most parts of the world. While in the past pain was largely dismissed and was frequently left untreated, views on children's pain have changed over time and relief of pain is now seen as important.We designed a suite of seven reviews on chronic non-cancer pain and cancer pain (looking at antidepressants, antiepileptic drugs, non-steroidal anti-inflammatory drugs, opioids, and paracetamol) in order to review the evidence for children's pain utilising pharmacological interventions.As the leading cause of morbidity in the world today, chronic disease (and its associated pain) is a major health concern. Chronic pain (that is pain lasting three months or longer) can arise in the paediatric population in a variety of pathophysiological classifications (nociceptive, neuropathic, or idiopathic) from genetic conditions, nerve damage pain, chronic musculoskeletal pain, and chronic abdominal pain, as well as for other unknown reasons.Antidepressants have been used in adults for pain relief and pain management since the 1970s. The clinical impression from extended use over many years is that antidepressants are useful for some neuropathic pain symptoms, and that effects on pain relief are divorced and different from effects on depression; for example, the effects of tricyclic antidepressants on pain may occur at different, and often lower, doses than those on depression. Amitriptyline is one of the most commonly used drugs for treating neuropathic pain in the UK. To assess the analgesic efficacy and adverse events of antidepressants used to treat chronic non-cancer pain in children and adolescents aged between birth and 17 years, in any setting. We searched the

Comparison of alternatives for the treatment of non-fuel-bearing hardware

International Nuclear Information System (INIS)

Ross, W.A.; Clark, L.L.; Oma, K.H.

1987-01-01

This evaluation compares four alternatives for the treatment or processing of non-fuel-bearing hardware (NFBH) to reduce its volume and prepare it for disposal. These treatment alternatives are: shredding; shredding and low-pressure compaction; shredding and supercompaction; and melting. The alternatives are compared on the bases of system costs, waste form characteristics, and process considerations. The two alternatives with high volume reduction are estimated to save $400 million to $500 million compared with the shredding-only alternative. The study recommends that melting and supercompaction alternatives be considered further and that additional testing be conducted for these two alternatives

D-serine plasma concentration is a potential biomarker of (R,S)-ketamine antidepressant response in subjects with treatment-resistant depression.

Science.gov (United States)

Moaddel, Ruin; Luckenbaugh, David A; Xie, Ying; Villaseñor, Alma; Brutsche, Nancy E; Machado-Vieira, Rodrigo; Ramamoorthy, Anuradha; Lorenzo, Maria Paz; Garcia, Antonia; Bernier, Michel; Torjman, Marc C; Barbas, Coral; Zarate, Carlos A; Wainer, Irving W

2015-01-01

(R,S)-ketamine is a rapid and effective antidepressant drug that produces a response in two thirds of patients with treatment-resistant depression (TRD). The underlying biochemical differences between a (R,S)-ketamine responder (KET-R) and non-responder (KET-NR) have not been definitively identified but may involve serine metabolism. The aim of the study was to examine the relationship between baseline plasma concentrations of D-serine and its precursor L-serine and antidepressant response to (R,S)-ketamine in TRD patients. Plasma samples were obtained from 21 TRD patients at baseline, 60 min before initiation of the (R,S)-ketamine infusion. Patients were classified as KET-Rs (n = 8) or KET-NRs (n = 13) based upon the difference in Montgomery-Åsberg Depression Rating Scale (MADRS) scores at baseline and 230 min after infusion, with response defined as a ≥50 % decrease in MADRS score. The plasma concentrations of D-serine and L-serine were determined using liquid chromatography-mass spectrometry. Baseline D-serine plasma concentrations were significantly lower in KET-Rs (3.02 ± 0.21 μM) than in KET-NRs (4.68 ± 0.81 μM), p < 0.001. A significant relationship between baseline D-serine plasma concentrations and percent change in MADRS at 230 min was determined using a Pearson correlation, r = 0.77, p < 0.001, with baseline D-serine explaining 60 % of the variance in (R,S)-ketamine response. The baseline concentrations of L-serine (L-Ser) in KET-Rs were also significantly lower than those measured in KET-NRs (66.2 ± 9.6 μM vs 242.9 ± 5.6 μM, respectively; p < 0.0001). The results demonstrate that the baseline D-serine plasma concentrations were significantly lower in KET-Rs than in KET-NRs and suggest that this variable can be used to predict an antidepressant response following (R,S)-ketamine administration.

The role of neuropeptide-Y in nandrolone decanoate-induced attenuation of antidepressant effect of exercise.

Directory of Open Access Journals (Sweden)

Jovana Joksimovic

Full Text Available Since the increased prevalence of anabolic androgenic steroids abuse in last few decades is usually accompanied by various exercise protocols, the scope of our study was to evaluate the effects of chronic nandrolone decanoate administration in supraphysiological dose and a prolonged swimming protocol (alone and simultaneously with nandrolone decanoate on depressive state in male rats. Simultaneously, we investigated the possible alterations in neuropeptide Y (NPY content in blood and the hippocampus, in order to determine the role of NPY in the modulation of depressive-like behavior.Exercise induced antidepressant effects in tail suspension test (decrease of the total duration of immobility, as well as significant increase in the number of hippocampal NPY-interneurons in CA1 region. Chronic nandrolone decanoate treatment attenuated the beneficial antidepressant effects of exercise as measured by the tail suspension test parameters. Simultaneously, nandrolone decanoate treatment resulted in diminution of NPY content both in blood (decreased serum levels and in hippocampus (the significant decrease in NPY expression in all three investigated hippocampal regions-CA1, CA2/3 and DG. Our findings indicate that alterations in serum and hippocampal NPY contents may underlie the changes in depressive state in rats. The exercise was beneficial as it exerted antidepressant effect, while chronic nandrolone decanoate treatment resulted in depressive-like behavior. Furthermore, the behavioral indicators of depression showed strong correlations with the serum levels and the hippocampal content of NPY.

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

Science.gov (United States)

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

Do social functioning and symptoms improve with continuation antidepressant treatment of persistent depressive disorder? An observational study.

Science.gov (United States)

Hellerstein, David J; Hunnicutt-Ferguson, Kallio; Stewart, Jonathan W; McGrath, Patrick J; Keller, Samantha; Peterson, Bradley S; Chen, Ying

2017-03-01

To determine efficacy of continued treatment with the serotonin norepinephrine reuptake inhibitor duloxetine on symptom reduction and functional improvement in outpatients with dysthymia. Fifty outpatients with DSM-IV-TR diagnosed dysthymia who had participated in a 10 week double-blind, placebo-controlled study of duloxetine received open treatment for three months. Nineteen duloxetine responders continued duloxetine, 24 patients initially treated with placebo started open duloxetine treatment, and 7 duloxetine non-responders were treated with desvenlafaxine or bupropion, selected by clinician choice. Patients continuing duloxetine maintained symptom improvement, 84% meeting response and 63% remission criteria at week 22. Patients initially treated with placebo showed similarly high levels of response (83%) and remission (62%) at week 22, and most duloxetine non-responders subsequently responded to other antidepressants. Duloxetine-continuation patients improved modestly between weeks 10 and 22 on measures of social and cognitive functioning and temperament. Despite this improvement concurrently across several functional domains, 66.7% of patients continuing duloxetine remained in the impaired range of functioning according to the Social Adjustment Scale (SAS). Continued duloxetine treatment appears to be effective in maintaining symptom response in dysthymic disorder, and has positive effects on social functioning. However, the majority of patients do not show normalization of functioning, even when controlling for remission status. Additional treatments should be considered to target residual impairments in social functioning in mood remitted patients with persistent depressive disorder. Copyright © 2016 Elsevier B.V. All rights reserved.

Quality of life and functioning of Hispanic patients with Major Depressive Disorder before and after treatment.

Science.gov (United States)

López, Enrique; Steiner, Alexander J; Manier, Karra; Shapiro, Bryan B; Vanle, Brigitte; Parisi, Thomas; Dang, Jonathan; Chang, Tiffany; Ganjian, Shaina; Mirocha, James; Danovitch, Itai; IsHak, Waguih William

2018-01-01

Similar rates of remission from Major Depressive Disorder (MDD) have been documented between ethnic groups in response to antidepressant treatment. However, ethnic differences in functional outcomes, including patient-reported quality of life (QOL) and functioning, have not been well-characterized. We compared symptomatic and functional outcomes of antidepressant treatment in Hispanic and non-Hispanic patients with MDD. We analyzed 2280 nonpsychotic treatment-seeking adults with MDD who received citalopram monotherapy in Level 1 of the Sequenced Treatment Alternatives to Relieve Depression study. All subjects (239 Hispanic, 2041 non-Hispanic) completed QOL, functioning, and depressive symptom severity measures at entry and exit. Hispanic participants had significantly worse QOL scores at entry and exit (p depressive symptom severity or functioning. Both groups had significant improvements in depressive symptom severity, QOL, and functioning from entry to exit (all p values depressive symptom severity, greater QOL, and better functioning at exit compared to patients without private insurance. This study was a retrospective data analysis, and the Hispanic group was relatively small compared to the non-Hispanic group. Hispanic and non-Hispanic participants with MDD had similar responses to antidepressant treatment as measured by depressive symptom severity scores, quality of life, and functioning. Nevertheless, Hispanic patients reported significantly worse quality of life at entry. Copyright © 2017 Elsevier B.V. All rights reserved.

Antidepressant utilization after hospitalization with depression

DEFF Research Database (Denmark)

Wallach-Kildemoes, Helle; Thomsen, Louise Thirstrup; Kriegbaum, Margit

2014-01-01

Background: Antidepressant (AD) therapy is recommended for patients 4-12months after remission from depression. The aim was to examine whether immigrants (refugees or family reunited immigrants) from non-Western countries are at greater risk than Danish-born residents of 1) not initiating AD...... therapy after discharge and 2) early AD discontinuation. Methods: A cohort of immigrants from non-Western countries (n=132) and matched Danish-born residents (n=396) discharged after first admission with moderate to severe depression between 1 January 1996 and 31 May 2008 was followed in the Danish...... treatment after hospitalization with depression. This may indicate a need for a better understanding of the circumstances of this vulnerable group....

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

Geriatric characteristics in randomised controlled trials on antidepressant drugs for older adults: a systematic review

NARCIS (Netherlands)

Benraad, Carolien E. M.; Kamerman-Celie, Floor; van Munster, Barbara C.; Oude Voshaar, Richard C.; Spijker, Jan; Olde Rikkert, Marcel G. M.

2016-01-01

Objective: Meta-analyses of antidepressant drug treatment trials have found that increasing age is associated with a less favourable outcome. Because the prevalence of geriatric characteristics, like disability, medical co-morbidity, malnutrition, cognitive (dys) function and frailty increase with

Geriatric characteristics in randomised controlled trials on antidepressant drugs for older adults : a systematic review

NARCIS (Netherlands)

Benraad, Carolien E. M.; Kamerman-Celie, Floor; van Munster, Barbara C.; Oude Voshaar, Richard C.; Spijker, Jan; Rikkert, Marcel G. M. Olde

Objective: Meta-analyses of antidepressant drug treatment trials have found that increasing age is associated with a less favourable outcome. Because the prevalence of geriatric characteristics, like disability, medical co-morbidity, malnutrition, cognitive (dys) function and frailty increase with

Signaling pathways underlying the antidepressant-like effect of inosine in mice.

Science.gov (United States)

Gonçalves, Filipe Marques; Neis, Vivian Binder; Rieger, Débora Kurrle; Lopes, Mark William; Heinrich, Isabella A; Costa, Ana Paula; Rodrigues, Ana Lúcia S; Kaster, Manuella P; Leal, Rodrigo Bainy

2017-06-01

Inosine is a purine nucleoside formed by the breakdown of adenosine that elicits an antidepressant-like effect in mice through activation of adenosine A 1 and A 2A receptors. However, the signaling pathways underlying this effect are largely unknown. To address this issue, the present study investigated the influence of extracellular-regulated protein kinase (ERK)1/2, Ca 2+ /calmoduline-dependent protein kinase (CaMKII), protein kinase A (PKA), phosphoinositide 3-kinase (PI3K)/Akt, and glycogen synthase kinase 3beta (GSK-3β) modulation in the antiimmobility effect of inosine in the tail suspension test (TST) in mice. In addition, we attempted to verify if inosine treatment was capable of altering the immunocontent and phosphorylation of the transcription factor cyclic adenosine monophosphatate (cAMP) response-binding element protein (CREB) in mouse prefrontal cortex and hippocampus. Intracerebroventricular administration of U0126 (5 μg/mouse, MEK1/2 inhibitor), KN-62 (1 μg/mouse, CaMKII inhibitor), H-89 (1 μg/mouse, PKA inhibitor), and wortmannin (0.1 μg/mouse, PI3K inhibitor) prevented the antiimmobility effect of inosine (10 mg/kg, intraperitoneal (i.p.)) in the TST. Also, administration of a sub-effective dose of inosine (0.1 mg/kg, i.p.) in combination with a sub-effective dose of AR-A014418 (0.001 μg/mouse, GSK-3β inhibitor) induced a synergic antidepressant-like effect. None of the treatments altered locomotor activity of mice. Moreover, 24 h after a single administration of inosine (10 mg/kg, i.p.), CREB phosphorylation was increased in the hippocampus. Our findings provided new evidence that the antidepressant-like effect of inosine in the TST involves the activation of PKA, PI3K/Akt, ERK1/2, and CaMKII and the inhibition of GSK-3β. These results contribute to the comprehension of the mechanisms underlying the purinergic system modulation and indicate the intracellular signaling pathways involved in the antidepressant-like effect of inosine

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 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....

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.

Age-related changes in the antidepressant-like effect of desipramine and fluoxetine in the rat forced-swim test.

Science.gov (United States)

Olivares-Nazario, Maribel; Fernández-Guasti, Alonso; Martínez-Mota, Lucía

2016-02-01

Some reports suggest that older patients are less responsive to antidepressants than young adults, but this idea has not been fully supported. Here, we investigated the role of aging in the behavioral effects of the antidepressants, desipramine (DMI) (5, 10, and 20 mg/kg) and fluoxetine (FLX) (5, 10, and 20 mg/kg) in young adults (3-5 months), middle-aged (MA, 12-15 months), and senescent (SE, 23-25 months) male rats in the forced-swim test. In addition, locomotor activity and motor coordination were assessed as side-effects. DMI and fluoxetine produced an antidepressant-like effect in YA and MA animals, although in the latter group, a shift to the right in the dose-response curve was found for DMI. Importantly, neither drug was effective in SE animals. Motor side-effects were produced mainly by DMI in MA and SE rats. Therefore, a decrease in the antidepressant-like effect is associated strongly with senescence as well as an increased vulnerability to motor side-effects, particularly of tricyclics. This study is significant because SE animals are scarcely studied in pharmacological screening tests, and our findings might be useful for improving antidepressant treatments for the increasing aged population.

Seasonal changes in antibiotics, antidepressants/psychiatric drugs, antihistamines and lipid regulators in a wastewater treatment plant.

Science.gov (United States)

Golovko, Oksana; Kumar, Vimal; Fedorova, Ganna; Randak, Tomas; Grabic, Roman

2014-09-01

Seasonal changes in the concentration of 21 pharmaceuticals in a wastewater treatment plant (WWTP) in České Budějovice were investigated over 12months. The target compounds were 10 antibiotics, 4 antidepressants, 3 psychiatric drugs, 2 antihistamines and 2 lipid regulators. 272 Wastewater samples (136 influents and 136 effluents) were collected from March 2011 to February 2012 and analyzed using two-dimensional liquid chromatography coupled with tandem mass spectrometry. All studied pharmaceuticals were frequently detected in both the influent and the effluent wastewater samples, except for meclozine, which was only found in the influent. The mean concentration of pharmaceuticals varied from 0.006μgL(-1) to 1.48μgL(-1) in the influent and from 0.003μgL(-1) to 0.93μgL(-1) in the effluent. The concentration of most pharmaceuticals was higher during winter. Copyright © 2014 Elsevier Ltd. All rights reserved.

Inhibition of G protein-activated inwardly rectifying K+ channels by different classes of antidepressants.

Directory of Open Access Journals (Sweden)

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.

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...

GLYX-13, a NMDA receptor glycine-site functional partial agonist, induces antidepressant-like effects without ketamine-like side effects.

Science.gov (United States)

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.

Harmane induces anxiolysis and antidepressant-like effects in rats.

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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.

Cognitive-emotional reactivation during deep transcranial magnetic stimulation over the prefrontal cortex of depressive patients affects antidepressant outcome.

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Isserles, Moshe; Rosenberg, Oded; Dannon, Pinchas; Levkovitz, Yechiel; Kotler, Moshe; Deutsch, Frederic; Lerer, Bernard; Zangen, Abraham

2011-02-01

Transcranial magnetic stimulation (TMS) enables non-surgical activation of specific brain areas. TMS over the prefrontal cortex (PFC) is emerging as a significant tool that can augment or replace non/partially effective antidepressant medications. Deep TMS (DTMS) utilizes newly developed coils that enable effective stimulation of deeper cortical layers involved in the pathophysiology of depression. We aimed to assess the H1-DTMS coil as an add-on to antidepressants in treating patients with major depression. We also intended to evaluate whether the antidepressant outcome of DTMS treatment is affected by a cognitive-emotional procedure performed during stimulation. 57 patients were enrolled in the study that included 4 weeks of daily 20 Hz stimulation sessions and additional 4 weekly sessions as a short maintenance phase. Two subgroups of patients received either positive or negative cognitive-emotional reactivation along with the stimulation sessions. 21 of 46 patients (46%) who received at least 10 stimulation sessions achieved response (improvement of ≥ 50% in the Hamilton Depression Rating Scale (HDRS)) and 13 of them (28%) achieved remission (HDRS-24 ≤ 10) by the end of the daily treatment phase. Improvements were smaller in the negatively reactivated group and Beck Depression Inventory scores were not significantly improved in this group. DTMS over the PFC proved to be safe and effective in augmenting antidepressant medications. Negative cognitive-emotional reactivation can disrupt the therapeutic effect of DTMS. A large sham controlled study is required to further establish the effectiveness of DTMS as an augmentation treatment and the role of cognitive reactivation during stimulation. © 2010 Elsevier B.V. All rights reserved.

40 CFR 268.49 - Alternative LDR treatment standards for contaminated soil.

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2010-07-01

... 40 Protection of Environment 26 2010-07-01 2010-07-01 false Alternative LDR treatment standards for contaminated soil. 268.49 Section 268.49 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) SOLID WASTES (CONTINUED) LAND DISPOSAL RESTRICTIONS Treatment Standards § 268.49 Alternative LDR treatment standards for contaminated...

The antidepressant-like effects of topiramate alone or combined with 17β-estradiol in ovariectomized Wistar rats submitted to the forced swimming test.

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Molina-Hernández, Miguel; Téllez-Alcántara, N Patricia; Olivera-López, Jorge I; Jaramillo, M Teresa

2014-09-01

There is a significant delay in the clinical response of antidepressant drugs, and antidepressant treatments produce side effects. We examined the relationship between 17β-estradiol and topiramate in ovariectomized Wistar rats submitted to the forced swimming test (FST). Topiramate was administered alone or combined with 17β-estradiol to ovariectomized rats submitted to the FST. Topiramate (20 mg/kg, P swimming; these effects were antagonized by finasteride (50 mg/kg). In interaction experiments, topiramate (10 mg/kg) plus 17β-estradiol (5 micrograms per rat; P swimming behavior. Besides, 17β-estradiol (2.5 micrograms per rat) shortened the onset of the antidepressant-like effects of topiramate (P < 0.05). In the open field test, topiramate alone or combined with 17β-estradiol (P < 0.05) reduced locomotion. Topiramate alone or combined with 17β-estradiol produced antidepressant-like actions; and 17β-estradiol shortened the onset of the antidepressant-like effects of topiramate.

Pharmacological repositioning of Achyranthes aspera as an antidepressant using pharmacoinformatic tools PASS and PharmaExpert: a case study with wet lab validation.

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Goel, R K; Gawande, D Y; Lagunin, A A; Poroikov, V V

2018-01-01

Traditional knowledge guides the use of plants for restricted therapeutic indications, but their pharmacological actions may be found beyond their ethnic therapeutic indications employing emerging computational tools. In this context, the present study was envisaged to explore the novel pharmacological effect of Achyranthes aspera (A. aspera) using PASS and PharmaExpert software tools. Based on the predicted mechanisms of the antidepressant effect for all analysed phytoconstituents of A. aspera, one may suggest its significant antidepressant action. The possible mechanism of this novel pharmacological effect is the enhancement of serotonin release, in particular caused by hexatriacontane. Therefore, pharmacological validation of the methanolic extract, hexatriacontane rich (HRF) and hexatriacontane lacking fraction (HLF) of A. aspera was carried out using the Forced Swimming Test and Tail suspension test in mice. The cortical and hippocampal monoamine and their metabolite levels were measured using high performance liquid chromatography (HPLC). A. aspera methanolic extract, HRF treatments showed a significant antidepressant effect comparable to imipramine. Further, the corresponding surge in cortical and hippocampal monoamine and their metabolite levels was also observed with these treatments. In conclusion, A. aspera has shown a significant antidepressant effect, possibly due to hexatriacontane, by raising monoamine levels.

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

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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

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...

Sex differences in the rapid and the sustained antidepressant-like effects of ketamine in stress-naïve and "depressed" mice exposed to chronic mild stress.

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Franceschelli, A; Sens, J; Herchick, S; Thelen, C; Pitychoutis, P M

2015-04-02

During the past decade, one of the most striking discoveries in the treatment of major depression was the clinical finding that a single infusion of a sub-anesthetic dose of the N-methyl-d-aspartate receptor antagonist ketamine produces a rapid (i.e. within a few hours) and long-lasting (i.e. up to two weeks) antidepressant effect in both treatment-resistant depressed patients and in animal models of depression. Notably, converging clinical and preclinical evidence support that responsiveness to antidepressant drugs is sex-differentiated. Strikingly, research regarding the antidepressant-like effects of ketamine has focused almost exclusively on the male sex. Herein we report that female C57BL/6J stress-naïve mice are more sensitive to the rapid and the sustained antidepressant-like effects of ketamine in the forced swim test (FST). In particular, female mice responded to lower doses of ketamine (i.e. 3mg/kg at 30 min and 5mg/kg at 24h post-injection), doses that were not effective in their male counterparts. Moreover, tissue levels of the excitatory amino acids glutamate and aspartate, as well as serotonergic activity, were affected in a sex-dependent manner in the prefrontal cortex and the hippocampus, at the same time-points. Most importantly, a single injection of ketamine (10mg/kg) induced sex-dependent behavioral effects in mice subjected to the chronic mild stress (CMS) model of depression. Intriguingly, female mice were more reactive to the earlier effects of ketamine, as assessed in the open field and the FST (at 30 min and 24h post-treatment, respectively) but the antidepressant potential of the drug proved to be longer lasting in males, as assessed in the splash test and the FST (days 5 and 7 post-treatment, respectively). Taken together, present data revealed that ketamine treatment induces sex-dependent rapid and sustained neurochemical and behavioral antidepressant-like effects in stress-naïve and CMS-exposed C57BL/6J mice. Copyright © 2015 IBRO

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

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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.

Antidepressant-like effect of the organoselenium compound ebselen in mice: evidence for the involvement of the monoaminergic system.

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