Sample records for antidepressant drug design

  1. [Antidepressives and antidepressive interactions with other drugs].

    Zavrsnik, Davorka; Spirtović, Selma; Becić, Fahir


    During the therapy with antidepressive agents, for the reason of its duration, numerous drug-drug interactions may occur. Antidepressive agents inhibit P450 enzyme activity and interfere with other drug metabolism. Many interactions are acceptable from the clinical point of view, and some are seriously dangerous indicating a need for their better knowledge. The aim of this work is to point out the possible interactions between antidepressive agents and other drugs. PMID:16425539

  2. [Antidepressant drugs and breastfeeding].

    Bellantuono, Cesario; Migliarese, Giovanni; Maggioni, Francesca; Imperadore, Giuseppe


    The post-partum period, as well as pregnancy, is associated with an increased risk of anxiety and/or affective disorders. Postnatal depression, frequently in co-morbidity with anxiety symptoms, is recognised as the most frequent form of maternal morbidity after delivery, with a prevalence rate estimated between 5% to 15%. Among antidepressant drugs, the SSRIs are considered the drugs of choice in the treatment of post-partum affective disorders, particularly in the major depression. It is, thus, crucial from a clinical standpoint to establish, in the newborn whose mother needs to be treated with an SSRI, the safety profile of these drugs during breastfeeding. The benefits of breastfeeding, on the other hand, both for the nursing mother and the infant, are in fact very well documented. Unfortunately, all antidepressant drugs, including SSRIs, cross into breast milk and the milk-to-plasma ratio, a measure proposed to establish the amount of drug transferred to maternal milk, does not seem to be a reliable parameter to predict the safety of these drugs. From the available literature, however, it seems that among SSRIs, paroxetina and sertralina offer the best safety profile, as these drugs has never been associated with unsafe reports in suckling infants. Despite these reassuring but preliminary data, more studies are needed to better assess the safety of the antidepressant drugs in the infants exposed during breastfeeding. As general rule, it is important to recommend if the mother wishes to breastfeed her infant while taking an antidepressant, that the baby should be closely monitored in order to detect, as soon as possible, any unwanted drug-related side effect. PMID:17345878

  3. Spadin, a Sortilin-derived peptide: a new concept in the antidepressant drug design

    Heurteaux Catherine


    Full Text Available Depression is the most common of psychiatric illnesses. The design of effective treatments for this disorder is a challenging process. 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. Deletion of TREK-1 gene results in a depression-resistant phenotype that mimics antidepressant treatments. Here, we validate the fast antidepressant effects of spadin, a secreted peptide derived from the propeptide generated by the maturation of the sortilin receptor and acting through TREK-1 inhibition.

  4. 21 CFR 862.3910 - Tricyclic antidepressant drugs test system.


    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Tricyclic antidepressant drugs test system. 862... Test Systems § 862.3910 Tricyclic antidepressant drugs test system. (a) Identification. A tricyclic antidepressant drugs test system is a device intended to measure any of the tricyclic antidepressant drugs...

  5. Antidepressant drugs: evaluation of price variation

    Bhumika Jayantilal Patel


    Conclusion: Price variation was wide for antidepressant drugs. Generic drug prescribing can decrease the expenditure of patient on the drug. Prescribers should be provided updated knowledge of the cost of different drugs. Modifications in pharmaceutical policy are required, and prices of the drug should be controlled in effective way for all the drugs. [Int J Basic Clin Pharmacol 2015; 4(3.000: 432-437

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

    Jean Mazella

    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

  7. Association between antidepressant drug use during pregnancy and child healthcare utilisation

    Ververs, T. F.; van Wensen, K.; Freund, M. W.; van der Heide, M.; Visser, G. H. A.; Schobben, A. F. A. M.; de Jong-van den Berg, L. T. W.; Egberts, A. C. G.


    Objective To evaluate healthcare utilisation by children who were exposed to antidepressant drug use during pregnancy and those whose mothers stopped using antidepressants before pregnancy compared with a control group. Design Cohort study. Setting Health insurance records in the Netherlands. Popula

  8. [Driving fitness in therapy with antidepressive drugs].

    Soyka, M; Dittert, S; Gartenmeier, A; Schäfer, M


    The driving ability of patients under therapy with antidepressives is seen less restrictive than some years ago. The inhibition of psychomotor performance is of special interest. Some empirical studies point at antidepressives increasing the risk for accidents at least in elderly patients. Different groups of antidepressants apparently show different effects. Tricyclic antidepressants were shown to worsen cognitive and psychomotor performance in some patients while serotonin reuptake inhibitors and some other new antidepressants may cause less behavioral toxicity. Methodological problems in assessing driving ability and some recent findings are discussed. PMID:9587241

  9. Antidepressants and local anesthetics: drug interactions of interest to dentistry

    Lea Rosa Chioca


    Full Text Available Introduction: Since there is a vast variety of pharmacological treatments for mental conditions, it has been increasingly more common that patients seeking dentistry treatment are continually using psychoactive drugs as antidepressants. The number of people taking antidepressants is increasing; consequently, dentists should update their knowledge on the interaction between this drug class and those used in dental daily practice, such as local anesthetics and vasoconstrictors. Objective: To conduct a literature review on this subject. Literature review and conclusion: Literature data suggest that sympathomimetic vasoconstrictors (epinephrine, norepinephrine, and phenylephrine associated with local anesthetics may potentiate the side effects of antidepressants, particularly tricyclics and MAO inhibitors, on the cardiovascular system. There are few clinical trials and preclinical studies on this subject, and most of them were carried out between the 60s and 80s. Current studies are needed, since many new antidepressant drugs with different mechanisms of action are currently marketed and being used.

  10. Effects of antidepressant drugs on different receptors in the brain

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

  11. Antidepressants

    Antidepressants are medicines that treat depression. Your doctor can prescribe them for you. They work to balance ... them to help. There are several types of antidepressants. You and your doctor may have to try ...

  12. Database processing for identification of concomitant drug frequencies in a forensic material positive for antidepressant drugs

    Björn, Niklas


    This article presents a study conducted on data containing drug concentrations. The data was obtained from femoral venous blood samples collected at medico legal autopsies in Sweden. Cases positive for antidepressant drugs were scrutinized and divided in to two groups for 15 antidepressant drugs: B‑cases, where the cause of death was intoxication with more than one drug detected in the blood sample. C‑cases, where the cause of death was NOT intoxication and at least one drug (the antidepressa...

  13. Acute antidepressant drug administration and autobiographical memory recall

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


    effect 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. (PsycINFO Database Record (c) 2012 APA, all...

  14. Interaction of antidepressant drug fluoxetine with the metabolism of triiodothyronine

    Pavelka, Stanislav

    Athens: University of Athens, 2009, s. 178-184. [International Symposium on Trace Elements in Human : New Perspectives /7./. Athens (GR), 13.10.2009-15.10.2009] R&D Projects: GA ČR(CZ) GA304/08/0256 Institutional research plan: CEZ:AV0Z50110509 Keywords : antidepressant drug * metabolism * thyroid hormone Subject RIV: ED - Physiology

  15. Reconsidering GHB: orphan drug or new model antidepressant?

    Bosch, Oliver G; Quednow, Boris B; Seifritz, Erich; Wetter, Thomas C


    For six decades, the principal mode of action of antidepressant drugs is the inhibition of monoamine re-uptake from the synaptic cleft. Tricyclic antidepressants, selective serotonin re-uptake inhibitors (SSRIs) and the new generation of dual antidepressants all exert their antidepressant effects by this mechanism. In the early days of the monoaminergic era, other efforts have been made to ameliorate the symptoms of depression by pharmacological means. The gamma-aminobutyric acid (GABA) system was and possibly still is one of the main alternative drug targets. Gammahydroxybutyrate (GHB) was developed as an orally active GABA analogue. It was tested in animal models of depression and human studies. The effects on sleep, agitation, anhedonia and depression were promising. However, the rise of benzodiazepines and tricyclic antidepressants brought GHB out of the scope of possible treatment alternatives. GHB is a GABA(B) and GHB receptor agonist with a unique spectrum of behavioural, neuroendocrine and sleep effects, and improves daytime sleepiness in various disorders such as narcolepsy, Parkinson's disease and fibromyalgia. Although it was banned from the US market at the end of the 1990s because of its abuse and overdose potential, it later was approved for the treatment of narcolepsy. New research methods and an extended view on other neurotransmitter systems as possible treatment targets of antidepressant treatment brought GHB back to the scene. This article discusses the unique neurobiological effects of GHB, its misuse potential and possible role as a model substance for the development of novel pharmacological treatment strategies in depressive disorders. PMID:21926421

  16. Drug Interaction in Psycho-Oncology: Antidepressants and Antineoplastics

    de Miguel, C; E. Albuquerque


    Background and Objectives: Although there is a growing impact of psychiatric and depressive disorders in cancer patients, literature on the idiosyncrasies of antidepressants (ADs) used in those conditions and their interactions with antineoplastic agents (ANs) is scarce. Sharing the same biotransformation pathways enhances the risk of drug interaction between ADs and ANs, specifically when compounds are inducers, inhibitors or substrates of cytochrome P450 (CYP 450). In cancer patients, such ...

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

    Christos Papandreou


    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.

  18. Prediction of drug-drug interactions between various antidepressants and ritonavir using a physiologically based pharmacokinetic model

    M Siccardi


    not or weakly impacted by RTV. Although from a pharmacokinetic point of view, venlafaxine or citalopram represent better candidates for patients on RTV, there are many considerations in seeking to optimize antidepressant therapy. The next stage in this work is to simulate DDI between boosted protease inhibitors and antidepressants. IVIVE is a useful tool for both prediction of drug-drug interactions and design of prospective clinical trials, simulating optimal sample size, and selection of doses.

  19. Effects of antidepressant drugs on histamine-H1 receptors in the brain

    The histamine-H1 receptor blocking properties of a number of structurally different antidepressant drugs have been evaluated using a 3H-mepyramine binding assay and a guinea-pig ileum preparation. The tricyclic antidepressants all inhibited the histamine-H1 receptor. Some newer antidepressant drugs, such as zimeldine and nomifensine were devoid of activity while others, such as iprindole and mianserin were very potent. It is concluded that antagonistic effects on the histamine-H1 receptor is not associated with the therapeutic efficacy in depression, but may contribute to the sedative effects of the antidepressant drugs

  20. Provide optimized antidepressant monotherapy with multiple drugs before considering antidepressant polypharmacy

    SAAH, Tammy; Garlow, Steven J.; Rapaport, Mark H.


    Summary Many patients with chronic or recurring major depressive disorder have suboptimal responses to the wide range of antidepressant medications available. When confronted with these patients, clinicians may augment the original antidepressant with other medications, including adjunctive treatment with a second or third antidepressant. Although it is a widely-used practice among psychiatrists and primary care physicians in high-income countries, evidence for the benefits of this type of an...

  1. Drug treatment episodes in pharmacoepidemiology - antidepressant use as a model

    Gardarsdottir, H.


    In the Netherlands, antidepressants are indicated for treating depression, generalized anxiety disorders, obsessive-compulsive disorders, social phobia, panic disorders, eating disorders, neuropathic pain and nocturnal enuresis. In addition, antidepressants are sometimes used for treating off-label

  2. Prescribing Pattern of Antidepressant Drugs among General Practitioners and Psychiatrists: a study from Iran

    Hamid Reza Motevallyzadeh; Mohammad Reza Baneshi; Maryam Rameshk; Nouzar Nakhaee


    Aim – This study was aimed to investigate the pattern of antidepressant drugs prescription among general practitioners and psychiatrists of Kerman/Iran with the goal of preventing irrational drug use. Methods – A total of 279737 prescriptions by general practitioners and psychiatrists of Kerman in 2010-2011 were reviewed. The frequency of antidepressant drugs prescription based on patients’ sex and age group (10-year age groups), the prescribed drug group and the prescriber (general practitio...

  3. Thermodynamic properties of amphiphilic antidepressant drug citalopram HBr

    Association characteristics of antidepressant during Citalopram hydrobromide in water Have been examined and its thermodynamic parameters have been calculated using tensiometery and conductometry. The critical micelle concentration (cmc) was determined by surface tension measurement at 30 deg. C and Surface activity was studied by measuring surface parameters i.e. surface pressure, JI, surface excess concentration, area per molecule of drug and standard Gibbs free energy of adsorption, delta G. The electrical conductivity was measured as a function of concentration at various temperatures and cmc was calculated in the temperature range 20-50 deg. C. Thermodynamic parameters i.e. standard free energy of micellization, delta G standard enthalpy of micellization, delta H/sub m/ and standard entropy of micellization, delta S/sub m/ were calculated from cmc value using closed association model. (author)

  4. The Food and Drug Administration’s Deliberations on Antidepressant Use in Pediatric Patients

    Leslie, Laurel K.; Newman, Thomas B.; Chesney, P. Joan; Perrin, James M


    On February 2, 2004, the Food and Drug Administration organized a joint meeting of the Neuro-Psychopharmacologic Advisory Committee and Pediatric Subcommittee of the Anti-Infective Drugs Advisory Committee to examine the occurrence of suicidality in clinical trials that investigate the use of the newer anti-depressant drugs in pediatric patients. Committee members reconvened on September 13–14, 2004, and concluded that there was a causal link between the newer antidepressants and pediatric su...

  5. Drug treatment episodes in pharmacoepidemiology - antidepressant use as a model

    Gardarsdottir, H.


    In the Netherlands, antidepressants are indicated for treating depression, generalized anxiety disorders, obsessive-compulsive disorders, social phobia, panic disorders, eating disorders, neuropathic pain and nocturnal enuresis. In addition, antidepressants are sometimes used for treating off-label indications such as sleeping disorders, urinary incontinence and headache. The diversity in the nature of these conditions results in a variety of antidepressant treatment patterns. The common use ...

  6. Caffeine enhances the antidepressant-like activity of common antidepressant drugs in the forced swim test in mice.

    Szopa, Aleksandra; Poleszak, Ewa; Wyska, Elżbieta; Serefko, Anna; Wośko, Sylwia; Wlaź, Aleksandra; Pieróg, Mateusz; Wróbel, Andrzej; Wlaź, Piotr


    Caffeine is the most widely used behaviorally active drug in the world which exerts its activity on central nervous system through adenosine receptors. Worrying data indicate that excessive caffeine intake applies to patients suffering from mental disorders, including depression. The main goal of the present study was to evaluate the influence of caffeine on animals' behavior in forced swim test (FST) as well as the effect of caffeine (5 mg/kg) on the activity of six typical antidepressants, such as imipramine (15 mg/kg), desipramine (10 mg/kg), fluoxetine (5 mg/kg), paroxetine (0.5 mg/kg), escitalopram (2 mg/kg), and reboxetine (2.5 mg/kg). Locomotor activity was estimated to verify and exclude false-positive/negative results. In order to assess the influence of caffeine on the levels of antidepressant drugs studied, their concentrations were determined in murine serum and brains using high-performance liquid chromatography. The results showed that caffeine at a dose of 10, 20, and 50 mg/kg exhibited antidepressant activity in the FST, and it was not related to changes in locomotor activity in the animals. Caffeine at a dose of 5 mg/kg potentiated the activity of all antidepressants, and the observed effects were not due to the increase in locomotor activity in the animals. The interactions between caffeine and desipramine, fluoxetine, escitalopram, and reboxetine were exclusively of pharmacodynamic character, because caffeine did not cause any changes in the concentrations of these drugs neither in blood serum nor in brain tissue. As a result of joint administration of caffeine and paroxetine, an increase in the antidepressant drug concentrations in serum was observed. No such change was noticed in the brain tissue. A decrease in the antidepressant drug concentrations in brain was observed in the case of imipramine administered together with caffeine. Therefore, it can be assumed that the interactions caffeine-paroxetine and caffeine-imipramine occur at least in

  7. Recent advances in the understanding of the interaction of antidepressant drugs with serotonin and norepinephrine transporters

    Andersen, Jacob; Kristensen, Anders Skov; Bang-Andersen, Benny;


    The biogenic monoamine transporters are integral membrane proteins that perform active transport of extracellular dopamine, serotonin and norepinephrine into cells. These transporters are targets for therapeutic agents such as antidepressants, as well as addictive substances such as cocaine and...... antidepressant drugs that act on the serotonin and/or the norepinephrine transporters. Specifically, we focus on structure-activity relationships of these drugs with emphasis on relationships between their molecular properties and the current knowledge of transporter structure....

  8. Testing the antidepressant properties of the peptide ARA290 in a human neuropsychological model of drug action

    Cerit, Hilâl; Veer, Ilya M; Dahan, Albert;


    hematopoietic side-effects but may have neurotrophic and antidepressant effects. The aim of this study was to investigate the possible antidepressant effects of ARA290 in a neuropsychological model of drug action. Healthy participants (N=36) received ARA290 (2mg) or placebo in a double-blind, randomized......Studies on the neural effects of Erythropoietin (EPO) indicate that EPO may have antidepressant effects. Due to its hematopoietic effects, EPO may cause serious side-effects with repeated administration if patients are not monitored extensively. ARA290 is an EPO-analog peptide without such......, parallel-group design. Neural and cognitive effects were assessed one week after administration. Primary outcome measures were the neural processing of fearful vs happy faces and the behavioral recognition of emotional facial expressions. ARA290-treated individuals displayed lower neural responses to happy...

  9. 5HT3 receptors: Target for new antidepressant drugs.

    Gupta, Deepali; Prabhakar, Visakh; Radhakrishnan, Mahesh


    5HT3 receptors (5HT3Rs) have long been identified as a potential target for antidepressants. Several studies have reported that antagonism of 5HT3Rs produces antidepressant-like effects. However, the exact role of 5HT3Rs and the mode of antidepressant action of 5HT3R antagonists still remain a mystery. Here, we provide a comprehensive overview of 5HT3Rs: (a) regional and subcellular distribution of 5HT3Rs in discrete brain regions, (b) preclinical and clinical evidence supporting the antidepressant effect of 5HT3R antagonists, and (c) neurochemical, biological and neurocellular signaling pathways associated with the antidepressant action of 5HT3R antagonists. 5HT3Rs located on the serotonergic and other neurotransmitter interneuronal projections control their release and affect mood and emotional behavior; however, new evidence suggests that apart from modulating the neurotransmitter functions, 5HT3R antagonists have protective effects in the pathogenic events including hypothalamic-pituitary-adrenal-axis hyperactivity, brain oxidative stress and impaired neuronal plasticity, pointing to hereby unknown and novel mechanisms of their antidepressant action. Nonetheless, further investigations are warranted to establish the exact role of 5HT3Rs in depression and antidepressant action of 5HT3R antagonists. PMID:26976353

  10. Considering the case for an antidepressant drug trial involving temporary deception: a qualitative enquiry of potential participants

    Wigglesworth Mark


    Full Text Available Abstract Background Systematic reviews of randomised placebo controlled trials of antidepressant medication show small and decreasing differences between pharmacological and placebo arms. In part this finding may relate to methodological problems with conventional trial designs, including their assumption of additivity between drug and placebo trial arms. Balanced placebo designs, which include elements of deception, may address the additivity question, but pose substantial ethical and pragmatic problems. This study aimed to ascertain views of potential study participants of the ethics and pragmatics of various balanced placebo designs, in order to inform the design of future antidepressant drug trials. Methods A qualitative approach was employed to explore the perspectives of general practitioners, psychiatrists, and patients with experience of depression. The doctors were chosen via purposive sampling, while patients were recruited through participating general practitioners. Three focus groups and 12 in-depth interviews were conducted. A vignette-based topic guide invited views on three deceptive strategies: post hoc, authorised and minimised deception. The focus groups and interviews were tape-recorded and transcribed. Transcripts were analysed thematically using Framework. Results Deception in non-research situations was typically perceived as acceptable within specific parameters. All participants could see the potential utility of introducing deception into trial designs, however views on the acceptability of deception within antidepressant drug trials varied substantially. Authorized deception was the most commonly accepted strategy, though some thought this would reduce the effectiveness of the design because participants would correctly guess the deceptive element. The major issues that affected views about the acceptability of deception studies were the welfare and capacity of patients, practicalities of trial design, and the question

  11. International variation in drug utilization: Antidepressant utilization in North America, Greece, and Ireland

    Muhammad Mamdani


    Materials and Methods: We conducted a population-based cross-sectional time series analysis of antidepressant utilization in Canada, the United States, Greece, and Ireland from January 2007 to September 2011 using data from IMS Healthcare Inc., which tracks over 80% of global prescription sales of over 1.3 million products. We studied 23 antidepressants from five drug classes, namely, 1 serotonin-specific reuptake inhibitors (SSRIs, 2 serotonin-norepinephrine reuptake inhibitors (SNRIs, 3 tricyclic antidepressants (TCAs, 4 monoamine oxidase inhibitors (MAOIs, and 5 ′other′ antidepressants. We used time series analysis to examine trends in utilization patterns. Results: Overall antidepressant utilization increased steadily over time for all study regions, although regions differed considerably in the magnitude of antidepressant utilization and the rates of increase. While overall antidepressant utilization rates were similar between Canada (2,876 units per 1,000 population per month and the United States (2,815 units per 1,000 population per month, these rates were approximately 83% higher than in Greece (1,558 units per 1,000 population per month and approximately 50% higher than in Ireland (1,898 units per 1,000 population per month. Although the use of SSRIs, SNRIs, and other antidepressants generally increased over time, the use of TCAs and MAOIs generally decreased over time. Utilization of specific drug classes varied widely between regions, ranging from an 80% relative difference in SSRI utilization between the United States and Greece to a nearly 700% difference in the utilization of MAOIs between Canada and the United States. Conclusions: The findings of our study, using antidepressants as the case example, are consistent with previous studies demonstrating significant variation in drug utilization levels internationally. Future studies are needed to document regional variation in light of appropriateness of drug therapies to determine optimal


    A. Anita Margret* and S. Aishwarya


    Full Text Available Drug delivery is the most essential feature in drug administration facility and the design of Nanosystems makes the action more consistent an appropriate. Polymer nano particles bind efficiently to the drug and disperse the drug proficiently into the system. The efficacy of many drugs is often limited by their potential to reach the site of therapeutic action. In most cases (conventional dosage forms, only a small amount of administered dose reaches the target site, while the majority of the drug distributes throughout the rest of the body in accordance with its physicochemical and biochemical properties. Therefore, developing a drug delivery system that optimizes the pharmaceutical action of a drug while reducing its toxic side effects in vivo is a challenging task. This study focuses on the preparation and characterization of biopolymeric alginate and chitosan nanoparticles for encapsulating the antidepressant drug Venlafaxine XR and analyzing it as an effective drug carrier and delivery system. The study reports a method to predict the encapsulation efficiency of chitosan as an effective biopolymer. The profiles of FTIR’s spectra reveal the entrapment of chitosan, alginate and Venlafaxine XR. A comparative analysis was done by isolating chitosan from mushrooms and with that of commercially obtained chitosan. The distinct peak values enumerate the similarity in both the chitosans assayed. The binding affinity for the compounds chitosan and Alginate proves to be good and binding energy was found to be 0.21K Cal/mol. The Quantitative Structure Activity Relationship of the two compounds chitosan and alginate satisfied all the necessary parameters of LIPINSKI’S rule of five. It was observed that strong electrostatic interaction exists in the nanoparticles. Quantification of the drugs in a nano scale improves the dispersal and absorption rate of the drug. Entrapment of the drug venlafaxine XR is also significant because depression is nowadays

  13. Drug Design and Emotion

    Folkers, Gerd; Wittwer, Amrei


    "Geteiltes Leid ist halbes Leid." The old German proverb reflects the fact that sharing a bad emotion or feeling with someone else may lower the psychological strain of the person experiencing sorrow, mourning or anger. On the other hand the person showing empathy will take literally a load from its counterpart, up to physiological reaction of the peripheral and central nervous pain system. Though subjective, mental and physical states can be shared. Visual perception of suffering may be important but also narrative description plays a role, all our senses are mixing in. It is hypothetized that literature, art and humanities allow this overlap. A change of mental states can lead to empirically observable effects as it is the case for the effect of role identity or placebo on pain perception. Antidepressants and other therapeutics are another choice to change the mental and bodily states. Their development follows today's notion of "rationality" in the design of therapeutics and is characterized solely by an atomic resolution approach to understand drug activity. Since emotional states and physiological states are entangled, given the difficulty of a physical description of emotion, the future rational drug design should encompass mental states as well.

  14. The unlicensed lives of antidepressants in India: generic drugs, unqualified practitioners, and floating prescriptions.

    Ecks, Stefan; Basu, Soumita


    Antidepressant uses have been rising rapidly over the past decades. Two main theories have been advanced to explain this. One claims that socio-economic change causes a global rise of depressive illness. The other holds that European and North American corporations are aggressively marketing antidepressants to expand their global reach. Both theories assume that multinational capitalism drives rising depression rates. Based on ethnographic data from India, this article shows that antidepressants are increasingly used in this country as well, but for reasons than have been little explored yet. Taking fluoxetine (Prozac) as the main example, it is argued that the spread of antidepressants in India is ;unlicensed' by Euro-American corporations in at least three ways: (i) drug marketing is driven by Indian generic producers; (ii) fluoxetine is given by practitioners who have no license to do so; and (iii) knowledge of fluoxetine is spread through unlicensed ;floating' prescriptions that patients take from one prescriber to another. PMID:19293281

  15. Extrapyramidal symptoms and antidepressant drugs: neuropharmacological aspects of a frequent interaction in the elderly.

    Govoni, S; Racchi, M; Masoero, E; Zamboni, M; Ferini-Strambi, L


    Depression is the most prevalent functional psychiatric disorder in late life. The problem of motor disorders associated with antidepressant use is relevant in the elderly. Elderly people are physically more frail and more likely to be suffering from physical illness, and any drug given may exacerbate pre-existing diseases, or interact with other drug treatments being administered for physical conditions. Antidepressants have been reported to induce extrapyramidal symptoms, including parkinsonism. These observations prompted us to review the neurobiological mechanism that may be involved in this complex interplay including neurotransmitters and neuronal circuits involved in movement and emotion control and their changes related to aging and disease. The study of the correlations between motor and mood disorders and their putative biochemical bases, as presented in this review, provide a rationale either to understand or to foresee motor side effects for psychotropic drugs, in particular antidepressants. PMID:11317214

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

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


    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. PMID:26501179

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

    Yapko, Michael D


    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. PMID:23488253

  18. Drug use pattern of antidepressant agents in psychiatric patients – A prospective study

    Aksha Memon


    Full Text Available Background: Depression is a major public health problem. It causes clinically significant distress, impairment of social, occupational or other important areas of function. Objective: To evaluate the prescribing pattern of antidepressant agents in patients attending psychiatry OPD at a tertiary care teaching hospital. Method: A prospective study was carried out at psychiatry outpatient department (OPD at VS General Hospital for 6 months. Patients who were prescribed any of the antidepressant medications irrespective of clinical indication either as monotherapy or in combination with other psychotherapeutic agents were included in the study. Result: Total 455 patients were enrolled for 6 months. Major Depressive Disorder (MDD was the most common diagnosis (85.93%. Tricyclic antidepressants (TCAs was the most commonly prescribed drug group (56.7% followed by selective serotonin reuptake inhibitors (SSRIs (46.8%. Amongst TCAs, imipramine was most frequently prescribed drug (65.89% followed by sertraline (56.8% among the SSRIs. Both the TCAs and newer antidepressants were prescribed with equal frequencies. Conclusion: Amongst antidepressants most frequently prescribed medication was imipramine followed by sertraline.

  19. Effect of lipopolysaccharide and antidepressant drugs on glucocorticoid receptor-mediated gene transcription

    Budziszewska, B.; Basta-Kaim, A.; Kubera, M.; Jaworska, L.; Leskiewicz, M.; Tetich, M.; Otczyk, M.; Zajícová, Alena; Holáň, Vladimír; Lasoń, W.


    Roč. 57, č. 4 (2005), s. 540-544. ISSN 1734-1140 Grant ostatní: State Committee for Scientific Research (KBN)(PL) 6P05A076 Institutional research plan: CEZ:AV0Z5052915 Keywords : glucocorticoid receptor * antidepressant drugs * interleukin-6 Subject RIV: EB - Genetics ; Molecular Biology

  20. Binding of the Multimodal Antidepressant Drug Vortioxetine to the Human Serotonin Transporter

    Andersen, Jacob; Ladefoged, Lucy Kate; Wang, Danyang;


    Selective inhibitors of the human serotonin transporter (hSERT) have been first-line treatment against depression for several decades. Recently, vortioxetine was approved as a new therapeutic option for the treatment of depression. Vortioxetine represents a new class of antidepressant drugs...

  1. The Utility of Impulsive Bias and Altered Decision Making as Predictors of Drug Efficacy and Target Selection: Rethinking Behavioral Screening for Antidepressant Drugs.

    Marek, Gerard J; Day, Mark; Hudzik, Thomas J


    Cognitive dysfunction may be a core feature of major depressive disorder, including affective processing bias, abnormal response to negative feedback, changes in decision making, and increased impulsivity. Accordingly, a translational medicine paradigm predicts clinical action of novel antidepressants by examining drug-induced changes in affective processing bias. With some exceptions, these concepts have not been systematically applied to preclinical models to test new chemical entities. The purpose of this review is to examine whether an empirically derived behavioral screen for antidepressant drugs may screen for compounds, at least in part, by modulating an impulsive biasing of responding and altered decision making. The differential-reinforcement-of-low-rate (DRL) 72-second schedule is an operant schedule with a documented fidelity for discriminating antidepressant drugs from nonantidepressant drugs. However, a theoretical basis for this empirical relationship has been lacking. Therefore, this review will discuss whether response bias toward impulsive behavior may be a critical screening characteristic of DRL behavior requiring long inter-response times to obtain rewards. This review will compare and contrast DRL behavior with the five-choice serial reaction time task, a test specifically designed for assessing motoric impulsivity, with respect to psychopharmacological testing and the neural basis of distributed macrocircuits underlying these tasks. This comparison suggests that the existing empirical basis for the DRL 72-second schedule as a pharmacological screen for antidepressant drugs is complemented by a novel hypothesis that altering impulsive response bias for rodents trained on this operant schedule is a previously unrecognized theoretical cornerstone for this screening paradigm. PMID:26699144

  2. Identification of antidepressant drug leads through the evaluation of marine natural products with neuropsychiatric pharmacophores

    Diers, Jeffrey A.; Ivey, Kelly D.; El-Alfy, Abir; Shaikh, Jamaluddin; Wang, Jiajia; Kochanowska, Anna J.; Stoker, John F.; Mark T. Hamann; Matsumoto, Rae R.


    The marine environment is a valuable resource for drug discovery due to its diversity of life and associated secondary metabolites. However, there is very little published data on the potential application of marine natural products to treat neuropsychiatric disorders. Many natural products derived from chemically defended organisms in the marine environment have pharmacophores related to serotonin or clinically utilized antidepressant drugs. Therefore, in the present study, compounds selecte...

  3. Genotoxicity induced by drug-drug interaction between the antidepressant sertraline and the antibiotic erythromycin in micebone marrow cells.

    Amany A. Tohamy


    Full Text Available Drug-drug interaction represents a widely distributed health problem. The pharmacological action and side effects of two or more drugs can act additively or antagonistically. The present study was designed to evaluate the possible genotoxicity of concurrent treatment with the antidepressant sertraline, one of the serotonin reuptake inhibitors (SSRI and the broad spectrum macrolide antibiotic erythromycin. Sertraline and erythromycin are metabolized through CYP3A4 which is one of the cytochrome P-450 enzymes in liver and are responsible for the metabolism of large number of endogenous substrates and therapeutic agents. The frequency of micronucleated polychromatic erythrocytes (MNPCEs, micronucleated normochromatic erythrocytes (MNNCEs and the ratio PCE/NCE were evaluated to measure the genotoxicity of separate and combined treatment with the tested two drugs. Clinical doses of both sertraline (0.71 mg /kg b.w. and erythromcyin strearate (14.30 mg / kg b.w. were used. Groups of animals received single separate or combined doses of either sertraline and/or erythromycin, and sacrificed after 24 hours. Other groups of mice were treated in the same way but for five consecutive days and sacrificed 24 hours after the last injection. In all treated groups, the percentage of PCEs increased significantly when compared with that of the negative control group which may indicate a stimulation of proliferative activity to an early phase of cell depletion. The genotoxicity of multiple treatment for 5 consecutive days with sertraline alone or in combination with erythromcyin was expressed in increased number of MNPCEs. The observed increased genotoxicity after multiple combined treatment with sertraline and erythromycin may indicate increased risk of toxicity-based drug-drug interaction. This toxicity may be due to the ability of sertraline and erythromycin to inhibit the activity of CYP3A4 which lead to a prolonged storage period of drugs in the body and hence

  4. Repeatedly administered antidepressant drugs modulate humoral and cellular immune response in mice through action on macrophages.

    Nazimek, Katarzyna; Kozlowski, Michael; Bryniarski, Pawel; Strobel, Spencer; Bryk, Agata; Myszka, Michal; Tyszka, Anna; Kuszmiersz, Piotr; Nowakowski, Jaroslaw; Filipczak-Bryniarska, Iwona


    Depression is associated with an altered immune response, which could be normalized by antidepressant drugs. However, little is known about the influence of antidepressants on the peripheral immune response and function of macrophages in individuals not suffering from depression. Our studies were aimed at determining the influence of antidepressant drugs on the humoral and cellular immune response in mice. Mice were treated intraperitoneally with imipramine, fluoxetine, venlafaxine, or moclobemide and contact immunized with trinitrophenyl hapten followed by elicitation and measurement of contact sensitivity by ear swelling response. Peritoneal macrophages from drug-treated mice were either pulsed with sheep erythrocytes or conjugated with trinitrophenyl and transferred into naive recipients to induce humoral or contact sensitivity response, respectively. Secretion of reactive oxygen intermediates, nitric oxide, and cytokines by macrophages from drug-treated mice was assessed, respectively, in chemiluminometry, Griess-based colorimetry and enzyme-linked immunosorbent assay, and the expression of macrophage surface markers was analyzed cytometrically. Treatment of mice with fluoxetine, venlafaxine, and moclobemide results in suppression of humoral and cell-mediated immunity with a reduction of the release of macrophage proinflammatory mediators and the expression of antigen-presentation markers. In contrast, treatment with imipramine enhanced the humoral immune response and macrophage secretory activity but slightly suppressed active contact sensitivity. Our studies demonstrated that systemically delivered antidepressant drugs modulate the peripheral humoral and cell-mediated immune responses, mostly through their action on macrophages. Imipramine was rather proinflammatory, whereas other tested drugs expressed immunosuppressive potential. Current observations may be applied to new therapeutic strategies dedicated to various disorders associated with excessive

  5. The Comparison of Efficacy of Tricyclic Antidepressant with and without Non Steroidal Anti Inflammatory Drugs in Chronic Low Back Pain

    A.R. Yavarikia


    Introduction & Objectives: Low back pain (LBP) is one of common medical problems with several accepted medical modalities such as drugs, physiotherapy, surgery, etc. We studied the efficacy of tricyclic antidepressant (TCA), and tricyclic antidepressant plus non steroidal anti inflammatory drugs (TCA + NSAID) in 200 patients with chronic LBP. Materials & Methods: In an experimental clinical trial study on patients with chronic low back pain without organic findings, patients were divided in t...

  6. Clinically significant pharmacokinetic drug interactions of antiepileptic drugs with new antidepressants and new antipsychotics.

    Spina, Edoardo; Pisani, Francesco; de Leon, Jose


    Antiepileptic drugs (AEDs) are frequently co-prescribed with new antidepressants (ADs) or new antipsychotics (APs). A PubMed search with no time limit was used to update the review of the clinically significant pharmacokinetic (PK) drug interactions DIs (DIs) between AEDs with new ADs and APs. Our best interpretation of what to expect regarding dosing changes in the average patient after combining AEDs with new ADs or new APs is summarized on updated tables that integrate the information on in vitro metabolism studies, therapeutic drug monitoring (TDM) studies, case report/series and prospective studies. There will be a need to periodically update these dose correction factors as new knowledge becomes available. These tables will provide some orientation to clinicians with no TDM access and may also encourage clinicians to further study TDM. The clinical relevance of the inductive properties of carbamazepine, phenytoin, phenobarbital and primidone on new ADs and new APs and the inhibitory properties of valproic acid and some new ADs, are relatively well understood. On the other hand, PK DI studies combining new AEDs with weak inductive properties (particularly oxcarbazepine doses≥1200mg/day), topiramate doses≥400mg/day, clobazam, eslicarbazepine, and rufinamide), with new ADs and new APs are needed. Valproic acid may be 1) an inhibitor and/or inducer of clozapine and olanzapine with potential for clinically relevant DIs, 2) an inhibitor of paliperidone, and 3) a weak inducer of aripiprazole. Fluoxetine and fluvoxamine are relevant inhibitors of phenytoin and valproic acid and possibly of clobazam, lacosamide, phenobarbital, or primidone. PMID:26896788

  7. Detection of antidepressant and antipsychotic drugs in human hair.

    Shen, Min; Xiang, Ping; Wu, Hejian; Shen, Baohua; Huang, Zhongjie


    The presence of therapeutic drugs and their metabolites in the hair of psychiatric patients was investigated using gas chromatography (GC)-mass spectroscopy (MS)-electron ionization (EI) and GC-MS-chemical ionization (CI). In hair samples tested from 35 subjects, carbamazepine, amitriptyline, doxepin, trihexyphenidyl, chlorpromazine, chlorprothixene, trifluoperazine, clozapine and haloperidol were detected, with maximal concentrations of 22.5, 57.7, 183.3, 15.6, 68.2, 30.0, 36.8, 59.2 and 20.1 ng/mg of hair sample, respectively. Chlorpromazine and clozapine concentrations in the hair were found to be dependent on the dosage used and their correlation coefficients were 0.8047 (P<0.001, n=16) and 0.7097 (P<0.001, n=16), respectively. Segmental analysis demonstrated that there was a correlation between the history of subject's drug exposure and the distribution of drug along the hair shaft. Our results also show that drug analysis in hair may provide useful information about drug treatment and the history of usage, and that drugs can be detected in normally kept hair for at least 16 months after intake. PMID:12084493

  8. Antidepressants and antipsychotic drugs colocalize with 5-HT3 receptors in raft-like domains.

    Eisensamer, Brigitte; Uhr, Manfred; Meyr, Sabrina; Gimpl, Gerald; Deiml, Tobias; Rammes, Gerhard; Lambert, Jeremy J; Zieglgänsberger, Walter; Holsboer, Florian; Rupprecht, Rainer


    Despite different chemical structure and pharmacodynamic signaling pathways, a variety of antidepressants and antipsychotics inhibit ion fluxes through 5-HT3 receptors in a noncompetitive manner with the exception of the known competitive antagonists mirtazapine and clozapine. To further investigate the mechanisms underlying the noncompetitive inhibition of the serotonin-evoked cation current, we quantified the concentrations of different types of antidepressants and antipsychotics in fractions of sucrose flotation gradients isolated from HEK293 (human embryonic kidney 293) cells stably transfected with the 5-HT3A receptor and of N1E-115 neuroblastoma cells in relation to the localization of the 5-HT3 receptor protein within the cell membrane. Western blots revealed a localization of the 5-HT3 receptor protein exclusively in the low buoyant density (LBD) fractions compatible with a localization within raft-like domains. Also, the antidepressants desipramine, fluoxetine, and reboxetine and the antipsychotics fluphenazine, haloperidol, and clozapine were markedly enriched in LBD fractions, whereas no accumulation occurs for mirtazapine, carbamazepine, moclobemide, and risperidone. The concentrations of psychopharmacological drugs within LBD fractions was strongly associated with their inhibitory potency against serotonin-induced cation currents. The noncompetitive antagonism of antidepressants at the 5-HT3 receptor was not conferred by an enhancement of receptor internalization as shown by immunofluorescence studies, assessment of receptor density in clathrin-coated vesicles, and electrophysiological recordings after coexpression of a dominant-negative mutant of dynamin I, which inhibits receptor internalization. In conclusion, enrichment of antidepressants and antipsychotics in raft-like domains within the cell membrane appears to be crucial for their antagonistic effects at ligand-gated ion channels such as 5-HT3 receptors. PMID:16267227

  9. Treating Depression: Should You Consider an Antidepressant?

    Treating Depression: Should You Consider An Antidepressant? What are antidepressants? Antidepressants are drugs used to treat the symptoms of depression. Do I need an antidepressant? You probably do not ...

  10. Antidepressant chronotherapeutics in a group of drug free outpatients.

    Dallaspezia, Sara; van Jaarsveld, Astrid


    The combination of Total Sleep Deprivation (TSD) and Light Therapy (LT) has been shown to prevent the early relapses characterizing response to TSD. Despite their proved efficacy, TSD and LT are still far from being considered standard therapy in the inpatient units and no study has assessed their efficacy and feasibility in outpatient settings. We studied 27 drug-free out-patients affected by Major Depression, divided in 7 groups according to the date of the wake night. Patients were administered one night of TSD and received LT during consecutive mornings following a predictive algorithm based on Morningness-Eveningness Questionnaire scores. Severity of depression was rated on Back Depression Inventory Scale (BDI) at baseline, one week and three months after the end of treatment. BDI scores significantly decreased during treatment with no difference between the seven consecutively treated groups of patients. Significant differences in BDI scores were confirmed between the baseline and both one week and three months after the end of treatment. TSD and LT caused a significant amelioration of depressive symptoms in an outpatient setting. Similar effects were observed in seven independent groups, suggesting that there is repeatability in findings. Chronotherapeutics confirmed their efficacy in the treatment of depression. PMID:27173655

  11. Effect of molecular structure on the hydration of structurally related antidepressant drugs

    Cheema, M. A.; Taboada, P.; Barbosa, S.; Siddiq, M.; Mosquera, V.

    Apparent molal volumes and adiabatic compressibilities of aqueous solutions of the amphiphilic cationic antidepressant drugs butriptyline and doxepin hydrochlorides have been determined from density and ultrasound velocity measurements in the temperature range 20-50°C. Critical concentrations for aggregation of these drugs were obtained from ultrasound velocity measurements. Negative deviations from the Debye-Hückel limiting law of the apparent molal volume were obtained from both drugs in all temperature ranges, except for doxepin at 50°C, which provides evidence of no pre-association at concentrations below the critical concentration. Apparent molal adiabatic compressibilities of the aggregates formed by these drugs were typical of those corresponding for an aggregate formed by a stacking process.

  12. Potential of Glutamate-Based Drug Discovery for Next Generation Antidepressants

    Shigeyuki Chaki


    Full Text Available Recently, ketamine has been demonstrated to exert rapid-acting antidepressant effects in patients with depression, including those with treatment-resistant depression, and this discovery has been regarded as the most significant advance in drug development for the treatment of depression in over 50 years. To overcome unwanted side effects of ketamine, numerous approaches targeting glutamatergic systems have been vigorously investigated. For example, among agents targeting the NMDA receptor, the efficacies of selective GluN2B receptor antagonists and a low-trapping antagonist, as well as glycine site modulators such as GLYX-13 and sarcosine have been demonstrated clinically. Moreover, agents acting on metabotropic glutamate receptors, such as mGlu2/3 and mGlu5 receptors, have been proposed as useful approaches to mimicking the antidepressant effects of ketamine. Neural and synaptic mechanisms mediated through the antidepressant effects of ketamine have been being delineated, most of which indicate that ketamine improves abnormalities in synaptic transmission and connectivity observed in depressive states via the AMPA receptor and brain-derived neurotrophic factor-dependent mechanisms. Interestingly, some of the above agents may share some neural and synaptic mechanisms with ketamine. These studies should provide important insights for the development of superior pharmacotherapies for depression with more potent and faster onsets of actions.

  13. Olfactory bulb ablation in the rat: behavioural changes and their reversal by antidepressant drugs.

    van Riezen, H; Schnieden, H; Wren, A F


    1. The effects of bilateral olfactory bulbectomy, sham-operation and inducement of peripheral anosmia were studied on locomotor activity, passive avoidance acquisition and irritability. 2. Bulbectomized rats were hyperactive, deficient at learning a step-down passive avoidance response and hyperirritable. Peripheral anosmia, induced by intranasal infusion of ZnSO4 solution resulted in no behavioural changes. 3. Chronic pretreatment with amitriptyline (3 and 10 mg/kg) and a tetracyclic antidepressant mianserin (Org GB 94, 5 and 15 mg/kg) reversed the hyperactivity and reduced the learning deficit of bulbectomized rats. These drugs had no significant effects on sham-operated animals. 4. Neither amitriptyline nor mianserin reduced the exaggerated responses of bulbectomized rats to external stimuli. 5. (+)-Amphetamine (1 and 3 mg/kg) accelerated the acquisition of the passive avoidance response, greatly enhanced the locomotor activity and slightly increased the irritability score of both sham-operated and bulbectomized rats. 6. Chlorpromazine (1 and 3 mg/kg) and chlordiazepoxide (10 mg/kg) significantly reduced the acquisition, locomotor activity and irritability of experimental and control rats. 7. Lithium sulphate (1 and 3 mg/kg) had no effect on activity or irritability but produced a small impairment in acquistion of bulbectomized rats. 8. It is concluded that the reversal by antidepressant drugs of the behavioural syndrome seen after olfactory bulb ablation could constitute a new model for the detection of this group of centrally acting compounds. PMID:907867

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

    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

  15. Drug interactions of new antidepressants%新型抗抑郁药物的药物相互作用

    管晓波; 陆峥


    New types of antidepressants are widely used as therapeutic alliance and often in combination with other medications. It may modify the pharmacokinetics mediated by cytochrome P450. The investigation on drug interactions has important significance for rational use of medicine. This paper reviews the drug interactions of the new antidepressants to provide a guideline for combination therapy of antidepressants in clinic.%新型抗抑郁药物的联合治疗及其与其他药物的联合应用可引起经细胞色素P450酶介导的多种药物的药动学改变,药物相互作用研究对临床合理用药具有重要意义.本文综述新型抗抑郁药物的药物相互作用,以期为临床用药提供参考.

  16. Polymorphism in the metabolism of drugs, including antidepressant drugs: comments on phenotyping.

    Coutts, R T


    In neurochemistry there are advantages in determining how patients are likely to react to psychoactive drugs prior to the commencement of drug therapy. Explanations of a patient's nonresponse, or unexpected adverse reactions to drugs are required. In many instances, a knowledge of the drug metabolism status of a patient can be helpful in the selection of a drug and its dosage regimen, and in the prediction of possible drug/drug interactions when two or more drugs have to be administered conco...

  17. Immunomodulatory effects of fluoxetine: A new potential pharmacological action for a classic antidepressant drug?

    Di Rosso, María Emilia; Palumbo, María Laura; Genaro, Ana María


    Selective serotonin reuptake inhibitors are frequently used antidepressants. In particular, fluoxetine is usually chosen for the treatment of the symptoms of depression, obsessive-compulsive, panic attack and bulimia nervosa. Antidepressant therapy has been associated with immune dysfunction. However, there is contradictory evidence about the effect of fluoxetine on the immune system. Experimental findings indicate that lymphocytes express the serotonin transporter. Moreover it has been shown that fluoxetine is able to modulate the immune function through a serotonin-dependent pathway and through a novel independent mechanism. In addition, several studies have shown that fluoxetine can alter tumor cell viability. Thus, it was recently demonstrated in vivo that chronic fluoxetine treatment inhibits tumor growth by increasing antitumor T-cell activity. Here we briefly review some of the literature referring to how fluoxetine is able to modify, for better or worse, the functionality of the immune system. These results of our analysis point to the relevance of the novel pharmacological action of this drug as an immunomodulator helping to treat several pathologies in which immune deficiency and/or deregulation is present. PMID:26644208

  18. Various effects of antidepressant drugs on bone microarchitectecture, mechanical properties and bone remodeling

    The aim of this study was to evaluate the effects of various drugs which present antidepressant properties: selective serotonin-reuptake inhibitors (SSRIs, fluoxetine), serotonin and noradrenaline-reuptake inhibitors (Desipramine) and phosphodiesterase inhibitors (PDE, rolipram and tofisopam) on bone microarchitecture and biomechanical properties. Twelve female mice were studied per group starting at an age of 10 weeks. During 4 weeks, they received subcutaneously either placebo or 20 mg kg-1 day-1 of desipramine, fluoxetine or 10 mg kg-1 day-1 of rolipram or tofisopam. Serum Osteocalcin and CTx were evaluated by ELISA. Bone microarchitecture of the distal femur was characterized by X-ray microCT (Skyscan1072). Mechanical properties were assessed by three-point bending test (Instron 4501) and antidepressant efficacy by forced swimming and open field tests. Fluoxetine displayed lower TbTh (- 6.1%, p -1, 6431 ± 1182 MPa) than in placebo (101 ± 9 N mm-1, 8441 ± 1180 MPa). Bone markers indicated a significantly higher bone formation in tofisopam (+ 8.6%) and a lower in fluoxetine (- 56.1%) compared to placebo. These data suggest deleterious effects for SSRIs, both on trabecular and cortical bone and a positive effect of PDE inhibitors on trabecular bone. Furthermore tofisopam anabolic effect in terms of bone markers, suggests a potential therapeutic effect of the PDE inhibitors on bone

  19. Tricyclic Antidepressants

    Schmidt, Gary J.

    The use of tricyclic antidepressant drugs is becoming increasingly prevalent for the treatment of depressed patients. It has been suggested that, analogous to many other drug substances, the tricyclic drugs exhibit clinical effectiveness within a defined therapeutic concentration range (1-10). Very recently, both Dito (11) and Orsulak and Schildkraut (12) have summarized the usefulness of measuring serum concentrations of these drugs. These authors suggest that knowledge of the plasma concentrations of these drugs aid the physician in determining patient compliance and initiating the best possible drug treatment.

  20. Selenoenzymes iodothyronine deiodinases: 1. Effects of their activities in various rat tissues by administered antidepressant drug Fluoxetine

    Pavelka, Stanislav

    Leiden: CRC Press, 2016 - (Baňuelos, G.; Lin, Z.; de Moraes, M.; Guilherme, L.; dos Reis, A.), s. 55-56 ISBN 978-1-138-02731-2 Institutional support: RVO:67985823 Keywords : iodothyronine deiodinase * selenoenzyme * antidepressant drug Subject RIV: CE - Biochemistry

  1. I-125-labelled iodothyronines: useful tools for studies of effects of an antidepressant drug fluoxetine in the rat

    Pavelka, Stanislav


    Roč. 286, č. 3 (2010), s. 867-871. ISSN 0236-5731 R&D Projects: GA ČR(CZ) GA304/08/0256 Institutional research plan: CEZ:AV0Z50110509 Keywords : antidepressant drug * radiometric enzyme assay * thyroid hormone Subject RIV: FR - Pharmacology ; Medidal Chemistry Impact factor: 0.777, year: 2010

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

    Secher, Anna; Bukh, Jens; Bock, Camilla; Koefoed, Pernille; Rasmussen, Henrik Berg; Werge, Thomas; Kessing, Lars Vedel; Mellerup, Erling


    examine the association of antidepressive-drug-induced bodyweight gain with polymorphisms in genes within the serotonin or catecholamine systems. Participants (N = 165) were selected from the Danish Psychiatric Central Research Register from June 2005 through May 2007 as patients with a diagnosis 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...

  3. Adherence to Antidepressant Medication

    Åkerblad, Ann-Charlotte


    Non-adherence to medication is a major obstacle in the treatment of depression. The objectives of the present study were to explore the effect of two interventions aiming to increase antidepressant treatment adherence, and to examine long-term consequences and costs of depression in adherent and non-adherent primary care patients. A randomised controlled design was used to assess the respective effects of a written educational adherence enhancing programme and therapeutic drug monitoring in ...

  4. Variability in the effect of antidepressants upon Wfs1-deficient mice is dependent on the drugs' mechanism of actions.

    Reimets, Riin; Raud, Sirli; Loomets, Maarja; Visnapuu, Tanel; Volke, Vallo; Reimets, Ain; Plaas, Mario; Vasar, Eero


    There is significant comorbidity between mood disorders and diabetes. Wolfram syndrome-related to deficient WFS1 gene function-causes diabetes and mood disorders in humans. Mice lacking the Wfs1 gene display impaired emotional behaviour and glucose metabolism. Various antidepressant drugs are used for alleviating the symptoms of mood disorders. For this study the tail suspension test and locomotor activity test were used to compare the effects of different antidepressants upon homozygous Wfs1-deficient, heterozygous Wfs1-deficient and wild-type mice. Mouse glucose metabolism was concurrently studied using the glucose tolerance test. We showed that ketamine(10mg/kg),NMDA antagonist, escitalopram(2.5-10mg/kg), selective serotonin reuptake inhibitor(SSRI), and amitriptyline(10mg/kg), noradrenaline and serotonin reuptake inhibitor, elicited a stronger antidepressant-like effect in homozygous Wfs1-deficient mice compared to wild-type mice. The effect of noradrenaline and serotonin reuptake inhibitor desipramine(10 and 20mg/kg) did not differ between genotypes. The dopamine and noradrenaline reuptake inhibitor bupropion(5-20mg/kg) had no significant antidepressant-like effect upon any genotype. Amitriptyline and desipramine potentiated a glucose elevation, escitalopram and bupropion did not affect glucose concentrations, and ketamine improved impaired glucose metabolism in homozygous Wfs1-deficient mice. Therefore, the results of this study suggest that SSRIs are the drugs of choice for the treatment of depressive symptoms in diabetic patients. The efficacy of ketamine for these patients remains to be established. Nonetheless, employing the mechanism of action of ketamine that affected glucose metabolism positively, could be an approach for development of improved antidepressants. Wfs1-deficient mice are likely the good animal model to develop new antidepressants more suitable for depressed patients with diabetes. PMID:27080063

  5. The Polarographic Reduction and Electrode Kinetics of Anti-depressant Drug Bupropion Hydrochloride

    Sharda Samota


    Full Text Available The electroreduction of the antidepressant drug Bupropion hydrochloride has been studied in aqueous media at dme. Single well defined wave was obtained in different supporting electrolytes, like, KNO3, ammonium citrate buffer, acetate buffer, B. R. buffer, etc. The effect of pH on this reduction has been studied in B. R. buffer in the pH range 3.13 - 11.0. The Bupropion hydrochloride is best reduced in slightly acidic medium. This behavior was attributed to the reduction of >C=O group present in the drug. The effect of concentration and temperature on half wave potential has also been investigated. The reduction of drug was found to be irreversible and diffusion controlled, hence kinetic parameters (K0fh, αn are evaluated using Meites Israel and Gaur Bharagav,s method. Further, with increase in temperature the values of K0fh also increase, showing that irreversibility of the system decreases on increasing the temperature.

  6. Influence of External factors on Self-Aggregation of Amphiphilic Antidepressant Drug: A Thermodynamic Study

    Apparent molar volumes, (V phi adiabatic compressibilities, (K phi and thermal expansivities (E0) of venlafaxine hydrochloride, an amphiphilic antidepressant drug, have been determined in water and aqueous 0.01 mol/kg CaCl/sub 2/ 2H/sub 2/O solutions. The densities and ultrasound velocities were measured at 298.15 and 303.15 K by using an Anton Paar density sound analyzer (DSA 5000M). The critical micelle concentrations (cmc) of this drug were obtained from ultrasound velocity (u) measurement by using recently developed least square fitting algorithm. Negative deviations from Debye-Huckel limiting law of apparent molar volume for this drug was obtained at 298.15 and 303.15 K in water and 0.01 mol/kg CaCl/sub 2/ 2H/sub 2/O solutions showing no pre-association below the critical micellar concentration. The volumetric parameters indicating the interactions of venlafaxine hydrochloride with CaCl/sub 2/ 2H/sub 2/2O and in water have been obtained by using transfer molar volume and the resulting values are in good agreement within each other within experimental error. The Partial molar expansivity, (E0), and second derivative values, have also been estimated. (author)

  7. Optical sensors for therapeutic drug monitoring of antidepressants for a better medication adjustment

    Krieg, Anne K.; Hess, Stefan; Gauglitz, Günter


    Therapeutic drug monitoring provides the attending physicians with detailed information on a patient's individual serum level especially during long-term medication. Due to the fact that each patient tolerates drugs or their metabolites differently a medication adjustment can reduce the number and intensity of noticeable side-effects. In particular, psychotropic drugs can cause unpleasant side-effects that affect a patient's life almost as much as the mental disease itself. The tricyclic antidepressants amitriptyline is commonly used for treatment of depressions and was selected for the development of an immunoassay using the direct optical sensor technique Reflectometric Interference Spectroscopy (RIfS). RIfS is a simple, robust and label-free method for direct monitoring of binding events on glass surfaces. Binding to the surface causes a shift of the interference spectrum by a change of the refractive index or physical thickness. This technique can be used for time-resolved observation of association and dissociation of amitriptyline (antigen) and a specific antibody using the binding inhibition test format. An amitriptyline derivative is immobilized on the sensor surface and a specific amount of antibodies can bind to the surface unless the binding is inhibited by free amitriptyline in a sample. No fluorescent label is needed making the whole assay less expensive than label-based methods. With this recently developed immunoassay amitriptyline concentrations in buffer (PBS) can easily be detected down to 500 ng/L.

  8. Drug evaluation and the permissive principle: continuities and contradictions between standards and practices in antidepressant regulation.

    Abraham, John; Davis, Courtney


    Pharmaceuticals are not permitted on to the market unless they are granted regulatory approval. The regulatory process is, therefore, crucial in whether or not a drug is widely prescribed. Regulatory agencies have developed standards of performance that pharmaceuticals are supposed to meet before entering the market. Regulation of technologies is often discussed by reference to the precautionary principle. In contrast, this paper develops the concept of the 'permissive principle' as a way of understanding the departure of regulators' practices from standards of drug efficacy to which regulatory agencies themselves subscribe. By taking a case study of antidepressant regulation in the UK and the USA, the mechanisms of permissive regulatory practices are examined. An STS methodology of both spatial (international) and temporal comparisons of regulatory practices with regulatory standards is employed to identify the nature and extent of the permissive regulation. It is found that the permissive principle was adopted by drug regulators in the UK and the USA, but more so by the former than the latter. Evidently, permissive regulation, which favours the commercial interests of the drug manufacturer, but is contrary to the interests of patients, may penetrate to the heart of regulatory science. On the other hand, permissive regulation of specific drugs should not be regarded as an inevitable result of marketing strategies and concomitant networks deployed by powerful pharmaceutical companies, because the extent of permissive regulation may vary according to the intra-institutional normative commitments of regulators to uphold their technical standards against the commercial interests of the manufacturer. Likely sociological factors that can account for such permissive regulatory practices are 'corporate bias', secrecy and excessive regulatory trust in the pharmaceutical industry in the UK, political expediency and ideological capture in the USA, combined in both countries

  9. Effect of two non tricyclic antidepressant drugs on [14C]5-hydroxytryptamine uptake by rat platelets

    The uptake of 14C-5-HT by rat blood platelets was examined in vitro in experimental conditions which allowed measurement of the initial velocity and excluded other passive processes across the cell membrane. In these conditions, the effect of two non tricyclic antidepressant drugs (Lilly110140 and trazodone) was investigated. Lilly 110140 was as active as chlorimipramine and several times more active than imipramine as an inhibitor of 14C-5-HT uptake. Like chlorimipramine, Lilly 110140 appeared to be either a non-competitive or an uncompetitive inhibitor, according to the concentration of drug used. Trazodone also inhibited 14C-5-HT uptake by platelets but to a lesser extent than chlorimipramine, imipramine or Lilly 110140. m-chlorophenylpiperazine, a possible metabolite of trazodone, was about 3 times more potent an inhibitor than the parent molecule. Both compounds acted non-competitively. Compared with published data on the effect of Lilly 110140 and trazodone on brain 5-Ht, the present results support the suggestion that rat platelets are a useful pharmacological model of serotoninergic nerve endings. (author)

  10. Indications for antidepressant drug prescribing in general practice in the Netherlands.

    Gardarsdottir, H.; Heerdink, E.R.; Dijk, L. van; Egberts, A.C.G.


    BACKGROUND: The intensity of the use of antidepressants in large populations can nowadays relatively easily be estimated using databases encompassing prescription data. There are shortcomings when using prescription databases as they contain no clinical data on patient illness. Antidepressants are p

  11. 抗抑郁药在老年人群中的应用%Application of antidepressant drugs in the elderly



    老年抑郁和焦虑障碍患者常和躯体疾病共病,主诉较多的是身体症状和睡眠障碍.老年患者对躯体疾病和药物不良反应比较敏感,临床抗抑郁药使用可能出现药物代谢和血药浓度改变,本文针对老年患者的特殊生理和心理变化,分析疗效和不良反应,综述抗抑郁药在老年人群中的使用原则、药物选用和注意事项等.%The elderly patients with depression or anxiety disorders usually have the complication of physical diseases, and they complain of more physical symptoms and sleep disorders. The elderly patients are more susceptible to physical diseases and adverse reactions. The use of antidepressant drugs may change the metabolism and plasma concentration of other medications. This review focuses on the antidepressant drugs usage to treat the elderly patients' symptoms and frequently to reassess the dosage of antidepressant drugs and their adverse reactions.

  12. The question of feedback at the somadendritic region and antidepressant drug action.

    Kalsner, S


    Presynaptic receptor theory has been expanded to encompass the regulation of the firing rate of serotonergic neurons through negative feedback mediated by the somadendritic release of transmitter. This has encouraged hypotheses as to the mechanisms of action of several classes of antidepressants and anxiolytics. One conspicuous example is the attribution of the clinical efficacy of 5-HT uptake inhibitors, such as fluoxetine and paroxetine, to desensitization of somadendritic 5-HT autoreceptors. An examination of the available evidence, mainly observations made with agonists, antagonists, monoamine oxidase inhibitors and uptake blockers, taken along with the theoretical expectations for a negative feedback loop, and the operational characteristics of inactivation pathways, indicates that negative feedback does not function at somadendritic sites to set firing rate or transmitter density, and suggests that the process may not function at all physiologically. The attribution of the effectiveness of neuroactive drugs to desensitization of raphe 5-HT inhibitory receptors, or to other interactions with feedback, is highly speculative and unlikely. PMID:10974485

  13. The search for new off-label indications for antidepressant, antianxiety, antipsychotic and anticonvulsant drugs

    Chouinard, Guy


    Most drugs are prescribed for several illnesses, but it took several years for psychotropic drugs to have multiple clinical indications. Our search for serotonergic drugs in affective illnesses and related disorders led to new off-label indications for fluoxetine, sertraline, tryptophan, clonazepam, alprazolam, tomoxetine, buproprion, duloxetine, risperidone and gabapentin. Various clinical trial designs were used for these proof-of-concept studies. Novel therapeutic uses of benzodiazepines, ...

  14. Highly Sensitive and Validated Spectrophotometric Technique for the Assay of Some Antidepressant Drugs

    Deepakumari, H. N.; Prashanth, M. K.; Kumar, B. C. Vasantha; Revanasiddappa, H. D.


    The present paper describes a simple, rapid, reproducible, and highly sensitive spectrophotometric method for the determination of the tricyclic antidepressant drugs: amitriptyline hydrochloride (AMT), imipramine hydrochloride (IMH), clomipramine hydrochloride (CPH) and desipramine hydrochloride (DPH) in pure and in pharmaceutical preparations. The method is based on the bromination of the above drugs with known excess of bromine. The unreacted bromine is determined based on its ability to bleach the dye methyl red quantitatively at 520 nm. Regression analysis of Beer-Lambert plots showed a good correlation in the concentration range 0.0-2.5, 0-1.4, 0-1.4, and 0-1.0 μg/ml for AMT, IMH, CPH, and DPH, respectively. The molar absorptivity values were found to be 0.65 × 105, 1.41 × 105, 1.93 × 105, and 2.96 × 105l/mol/cm, with the corresponding Sandell's sensitivity values were 0.0048, 0.0022, 0.0018, and 0.0010 μg/cm2 for AMT, IMH, CPH, and DPH, respectively. The limits of detection (LOD) and quantification (LOQ) are also reported for the developed method. Intra- and inter-day accuracy and precision was established according to the current ICH guidelines. Application of the procedure to the analysis of various pharmaceutical preparations gave reproducible and accurate results. Further, the validity of the proposed method was confirmed by applying the standard addition technique, and the results obtained are in good agreement with those obtained by the official method.

  15. Antidepressant-like drug effects in juvenile and adolescent mice in the tail suspension test: Relationship with hippocampal serotonin and norepinephrine transporter expression and function.

    Nathan C Mitchell


    Full Text Available Depression is a major health problem for which most patients are not effectively treated. This problem is further compounded in children and adolescents where only two antidepressants [both selective serotonin reuptake inhibitors (SSRIs] are currently approved for clinical use. Mouse models provide tools to identify mechanisms that might account for poor treatment response to antidepressants. However, there are few studies in adolescent mice and none in juvenile mice. The tail suspension test (TST is commonly used to assay for antidepressant-like effects of drugs in adult mice. Here we show that the TST can also be used to assay antidepressant-like effects of drugs in C57Bl/6 mice aged 21 (juvenile and 28 (adolescent days post-partum (P. We found that the magnitude of antidepressant-like response to the SSRI escitalopram was less in P21 mice than in P28 or adult mice. The smaller antidepressant response of juveniles was not related to either maximal binding (Bmax or affinity (Kd for [3H]citalopram binding to the serotonin transporter (SERT in hippocampus, which did not vary significantly among ages. Magnitude of antidepressant-like response to the tricyclic desipramine was similar among ages, as were Bmax and Kd values for [3H]nisoxetine binding to the norepinephrine transporter (NET in hippocampus. Together, these findings suggest that juvenile mice are less responsive to the antidepressant-like effects of escitalopram than adults, but that this effect is not due to delayed maturation of SERT in hippocampus. Showing that the TST is a relevant behavioral assay of antidepressant-like activity in juvenile and adolescent mice sets the stage for future studies of the mechanisms underlying the antidepressant response in these young populations.

  16. Milnacipran: a unique antidepressant?

    Siegfried Kasper


    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

  17. The Comparison of Efficacy of Tricyclic Antidepressant with and without Non Steroidal Anti Inflammatory Drugs in Chronic Low Back Pain

    A.R. Yavarikia


    Full Text Available Introduction & Objectives: Low back pain (LBP is one of common medical problems with several accepted medical modalities such as drugs, physiotherapy, surgery, etc. We studied the efficacy of tricyclic antidepressant (TCA, and tricyclic antidepressant plus non steroidal anti inflammatory drugs (TCA + NSAID in 200 patients with chronic LBP. Materials & Methods: In an experimental clinical trial study on patients with chronic low back pain without organic findings, patients were divided in two groups of 100 cases. At certain times the response to treatment protocols were collected and compared using VAS system. Patient’s data including age, sex, smoking and response to treatment were recorded and analyzed using chi-square, t-tests, ANOVA and SPSS software. Results: 83 (41.5% of patients were males and 117 (58.5% were females. The age range was 21 to 75 (mean age 43.1 14.1y there was no meaning full statistical difference in demographic characteristics such as age, sex (respectively p=0.66, p=0.78 the ultimate pain was less (p0.05.Conclusion: TCA prescription is an efficient method of treatment of low back pain with or with out NSAIDS. But using NSAID+TCA will be almost more powerful and efficient method in the long term period.

  18. Dispersion of hydrophobic magnetic nanoparticles using ultarsonic-assisted in combination with coacervative microextraction for the simultaneous preconcentration and determination of tricyclic antidepressant drugs in biological fluids.

    Jannesar, Ramin; Zare, Fahimeh; Ghaedi, Mehrorang; Daneshfar, Ali


    A two-step sample preparation technique based on dispersive micro solid-phase extraction combined with coacervative microextraction is presented for preconcentration and determination of tricyclic antidepressant drugs in biological samples. An important feature of the method is the application of hydrophobic magnetic nanoparticles, which in combination with coacervative microextraction method enables development of rapid and efficient extraction procedure in order to achievement of a high extraction efficiency. Simultaneous optimization by experimental design lead to improvement of method with low cost which supply useful information about interaction among variables. Under the optimized conditions, a linear range of 5-1000ngmL(-1) with detection limits from 0.51 to 1.4ngmL(-1) were obtained for target analytes. The method was successfully used for the determination of analytes in biological fluids (plasma and urine) with relative recoveries in the range of 89-105% (RSDs<3.5%). PMID:27150784

  19. Study on Commonly Used Antidepressant Drugs and Reasonable Application%常用抗抑郁药物及合理应用的探讨



    目的:了解常见抗抑郁药物的特点,作用原理和对患者的不良反应及注意事项。方法通过网上和资料室查阅相关文献,对抗抑郁药的临床应用进行分析归纳和总结。结果常用抗抑郁药可分为3类,三环类药物、选择性5-HT再摄取抑制药、非典型抗抑郁药。最后对药物的合理应用分为三个方面进行详述。结论应用抗抑郁药应重视常用抑郁药分类及药物的合理使用,根据临床效应选择抗抑郁药,避免药物相互作用与过度使用。%Objective To understand the characteristics of common antidepressants, action principle and the patient's adverse reactions and precautions.Methods The literature search online and by reference room, for the clinical application of antidepressants were analyzed and summarized. ResultsCommon antidepressants can be divided into three categories, tricyclics, selective 5-HT reuptake inhibitors, atypical antidepressants. Finally, the rational use of drugs in three aspects in detail. ConclusionThe application should pay attention to the rational use of antidepressants commonly used antidepressant drugs classification and choose based on clinical antidepressant effect, avoid drug interactions and overuse.

  20. 抗抑郁药物致性功能障碍的临床研究进展%Clinical Research Progress of Antidepressant Drugs Causing Sexual Dysfunction

    林国华(综述); 江回春(审校)


    Antidepressants not only has the antidepressant and anxiolytic clinical effects , but also adverse reactions.General adverse antidepressant effects can be divided into central and peripheral side effects,where the influence of antidepressants on sexual function belongs to peripheral side effects .Antide-pressant drugs causing sexual dysfunction has become a consensus.Therefore,when selecting antidepressant, the adverse effect on sexual function should be taken into account,and the patient′s sexual function change after medication should be inquired ,so as to develop individualized treatment program ..%抗抑郁药除了具有抗抑郁及抗焦虑的临床治疗作用外,同样具有不良反应。抗抑郁药物的不良反应一般可分为中枢性不良反应和外周性不良反应。其中抗抑郁药物对患者性功能的影响属于外周性不良反应。抗抑郁药物会引起性功能障碍已成为共识。因此,在选择抗抑郁药物时应考虑到性功能方面的不良反应,了解患者服药后性功能的变化,以制订个性化的处理方案。

  1. Effects of self-aggregation on the hydration of an amphiphilic antidepressant drug in different aqueous media

    Apparent molal volumes and adiabatic compressibilities of aqueous solutions of the amphiphilic antidepressant drug clomipramine hydrochloride have been determined from density and ultrasound velocity measurements in the temperature range 288.15-313.15 K in buffered aqueous solution of pH 3.0 and 5.5. Critical concentrations of aggregation of this drug were obtained from inflections on the plots of the sound velocity against drug concentration. Apparent molal adiabatic compressibilities of the aggregates formed by the drug, calculated by combining the ultrasound velocity and density data, were typical of those for a stacked aggregate. From the temperature dependence of the critical concentration and using the mass action model combined with the Phillips definition of the critical concentration the thermodynamic standard quantities: free Gibbs energy, enthalpy and entropy of aggregate formation were calculated. The critical concentration and energy involved in the aggregation process of this drug have been also evaluated experimentally using isothermal titration calorimetry at 298.15 K. The solvent-drug interactions have been discussed from compressibility and calorimetry data

  2. Effects of self-aggregation on the hydration of an amphiphilic antidepressant drug in different aqueous media

    Taboada, Pablo; Gutierrez-Pichel, Manuel; Mosquera, Victor


    Apparent molal volumes and adiabatic compressibilities of aqueous solutions of the amphiphilic antidepressant drug clomipramine hydrochloride have been determined from density and ultrasound velocity measurements in the temperature range 288.15-313.15 K in buffered aqueous solution of pH 3.0 and 5.5. Critical concentrations of aggregation of this drug were obtained from inflections on the plots of the sound velocity against drug concentration. Apparent molal adiabatic compressibilities of the aggregates formed by the drug, calculated by combining the ultrasound velocity and density data, were typical of those for a stacked aggregate. From the temperature dependence of the critical concentration and using the mass action model combined with the Phillips definition of the critical concentration the thermodynamic standard quantities: free Gibbs energy, enthalpy and entropy of aggregate formation were calculated. The critical concentration and energy involved in the aggregation process of this drug have been also evaluated experimentally using isothermal titration calorimetry at 298.15 K. The solvent-drug interactions have been discussed from compressibility and calorimetry data.

  3. Antidepressants versus placebo in major depression: an overview.

    Khan, Arif; Brown, Walter A


    Although the early antidepressant trials which included severely ill and hospitalized patients showed substantial drug-placebo differences, these robust differences have not held up in the trials of the past couple of decades, whether sponsored by pharmaceutical companies or non-profit agencies. This narrowing of the drug-placebo difference has been attributed to a number of changes in the conduct of clinical trials. First, the advent of DSM-III and the broadening of the definition of major depression have led to the inclusion of mildly to moderately ill patients into antidepressant trials. These patients may experience a smaller magnitude of antidepressant-placebo differences. Second, drug development regulators, such as the U.S. Food and Drug Administration and the European Medicines Agency, have had a significant, albeit underappreciated, role in determining how modern antidepressant clinical trials are designed and conducted. Their concerns about possible false positive results have led to trial designs that are poor, difficult to conduct, and complicated to analyze. Attempts at better design and patient selection for antidepressant trials have not yielded the expected results. As of now, antidepressant clinical trials have an effect size of 0.30, which, although similar to the effects of treatments for many other chronic illnesses, such as hypertension, asthma and diabetes, is less than impressive. PMID:26407778

  4. A Review for the Analysis of Antidepressant, Antiepileptic and Quinolone Type Drugs in Pharmaceuticals and Environmental Samples.

    Rani, Susheela; Malik, Ashok Kumar; Kaur, Ramandeep; Kaur, Ripneel


    The analysis of drugs in various biological fluids is an important criterion for the determination of the physiological performance of a drug. After sampling of the biological fluid, the next step in the analytical process is sample preparation. Sample preparation is essential for isolation of desired components from complex biological matrices and greatly influences their reliable and accurate determination. The complexity of biological fluids adds to the challenge of direct determination of the drug by chromatographic analysis, therefore demanding a sample preparation step that is often time consuming, tedious and frequently overlooked. However, direct online injection methods offer the advantage of reducing sample preparation steps and enabling effective pre-concentration and clean-up of biological fluids. These procedures can be automated and therefore reduce the requirements for handling potentially infectious biomaterial, improve reproducibility, and minimize sample manipulations and potential contamination. This review is focused on the discovery and development of high-performance liquid chromatography (HPLC) and gas chromatography (GC) with different detectors. The drugs covered in this review are antiepileptics, antidepressant (AD), and quinolones. The application of these methods for determination of these drugs in biological, environmental and pharmaceutical samples has also been discussed. PMID:26939618

  5. Combining antidepressants

    Dunner, David L.


    Summary Treatment-resistant depression is a common problem encountered by psychiatrists. These patients are often difficult to treat effectively. Strategies for addressing patients with treatment-resistant depression include changing medications, adding another antidepressant (antidepressant polypharmacy), and augmenting treatment with a non-antidepressant.

  6. Emergency Department Visits for Drug-Related Suicide Attempts Involving Antidepressants by Adolescents and Young Adults: 2004 to 2008. The DAWN Report

    Substance Abuse and Mental Health Services Administration, 2011


    In 2008, adolescents made 23,124 visits to the emergency department (ED) for drug-related suicide attempts, and young adults made 38,036 such visits; of these visits, 23.0 percent (5,312 visits) among adolescents and 17.6 percent (6,700 visits) among young adults involved antidepressants. Among ED visits for suicide attempts involving…

  7. Chronic treatment with antidepressant drugs and the analgesia induced by 5-methoxy-N,N-dimethyltryptamine: attenuation by desipramine.

    Danysz, W; Minor, B G; Post, C; Archer, T


    The effect of chronic and acute oral or intraperitoneal treatment with the antidepressant drugs, desipramine, amitriptyline, alaproclate and iprindole, upon pain thresholds in the tail flick, hot plate and shock titration tests of nociception in saline- and 5-MeODMT-treated rats was studied. Chronic desipramine treatment increased the pre-test tail flick latencies. In the saline-treated rats, chronic oral desipramine treatment increased tail flick latencies, whereas chronic oral amitriptyline treatment decreased tail flick latencies. In 5-MeODMT-treated rats, chronic oral desipramine treatment attenuated the effects of 5-MeODMT (1 mg/kg) in all three tests of nociception, whereas chronic amitriptyline caused a potentiation in the tail flick and hot plate tests. Chronic oral iprindole treatment attenuated 5-MeODMT-induced analgesia in the hot plate test. Chronic intraperitoneal desipramine treatment attenuated 5-MeODMT analgesia in the tail flick and shock titration tests. In a different chronic treatment experiment, oral desipramine treatment attenuated 5-MeODMT analgesia in the tail flick test and zimeldine did for both the tail flick and hot plate tests, whereas mianserin potentiated 5-MeODMT-induced analgesia in both the tail flick and hot plate tests. In the saline-treated rats, acute treatment with all four drugs, desipramine, amitriptyline, iprindole and alaproclate, elevated the shock thresholds, whereas in 5-MeODMT-treated rats, desipramine and amitriptyline elevated shock thresholds. Two main conclusions can be drawn: chronic desipramine caused a quite consistent attenuation of 5-MeODMT-induced analgesia and the effects of acute treatment differed strongly from that of the chronic treatment. The effects of chronic administration with these antidepressants were compared with other findings using different measures of behavioural and receptor function. PMID:3776549

  8. Tattoo designs among drug abusers.

    Borokhov, Alexander; Bastiaans, Roland; Lerner, Vladimir


    Forty-one males with drug abuse who had tattoos with designs related to drug use were selected from a larger sample of tattooed males in forensic psychiatric wards, prisons and military recruitment centers during the period 1986-2000 in the former Soviet Union. Two-thirds of the tattoo images were related to a specific drug, some served to hide signs of repeated drug use, others to identify ideal sites for injection. Knowledge of these details may be helpful to clinicians, although images may be influenced by current trends. PMID:16910382

  9. Impact of brand-name drug worship and expectation psychology on antidepressant efficacy

    Cai, Jian; Ye, Meirong; Fei, Chunhua; Xu, Feng


    The choice of the generic drug is reasonable if there is evidence for its therapeutic equivalence with the brand-name drug. However, the reduced effectiveness of switching from brand-name drug to generic drug is not rare. The impact of brand-name worship and expectation psychology on drug efficacy is noteworthy to report. A 45-year-old woman suffered from depression mood disorder. She experienced profound improvement in her depressive symptoms after a switch from domestic generic venlafaxine ...

  10. Ketamine decreases resting state functional network connectivity in healthy subjects: implications for antidepressant drug action.

    Milan Scheidegger

    Full Text Available Increasing preclinical and clinical evidence underscores the strong and rapid antidepressant properties of the glutamate-modulating NMDA receptor antagonist ketamine. Targeting the glutamatergic system might thus provide a novel molecular strategy for antidepressant treatment. Since glutamate is the most abundant and major excitatory neurotransmitter in the brain, pathophysiological changes in glutamatergic signaling are likely to affect neurobehavioral plasticity, information processing and large-scale changes in functional brain connectivity underlying certain symptoms of major depressive disorder. Using resting state functional magnetic resonance imaging (rsfMRI, the "dorsal nexus "(DN was recently identified as a bilateral dorsal medial prefrontal cortex region showing dramatically increased depression-associated functional connectivity with large portions of a cognitive control network (CCN, the default mode network (DMN, and a rostral affective network (AN. Hence, Sheline and colleagues (2010 proposed that reducing increased connectivity of the DN might play a critical role in reducing depression symptomatology and thus represent a potential therapy target for affective disorders. Here, using a randomized, placebo-controlled, double-blind, crossover rsfMRI challenge in healthy subjects we demonstrate that ketamine decreases functional connectivity of the DMN to the DN and to the pregenual anterior cingulate (PACC and medioprefrontal cortex (MPFC via its representative hub, the posterior cingulate cortex (PCC. These findings in healthy subjects may serve as a model to elucidate potential biomechanisms that are addressed by successful treatment of major depression. This notion is further supported by the temporal overlap of our observation of subacute functional network modulation after 24 hours with the peak of efficacy following an intravenous ketamine administration in treatment-resistant depression.

  11. Divergence and convergence of commercial and scientific priorities in drug development: The case of Zelmid, the first SSRI antidepressant.

    Mulinari, Shai


    Based on a realist conceptualization of interests, this paper explores how commercial and scientific priorities appear to have converged and diverged during the development of the antidepressant Zelmid. The drug represents the first of the selective serotonin reuptake inhibitors (SSRIs) to reach the market. Zelmid was synthesized in 1971 and launched by the Swedish firm Astra in 1982, but subsequently withdrawn the next year because of adverse neurological effects. This paper draws on in-depth interviews with scientists representing both industry and academia who had high-level involvement in various phases of the project (experimental, pre-clinical and clinical), as well as on textual sources such as scientific articles and memoirs. Zelmid was a product of mechanism-based or "rational" drug discovery from the early 1960s and the associated intermingling of science and commerce. It is argued that both scientists and the pharmaceutical company shared an interest in embracing mechanism-based drug discovery because it simultaneously promised medico-scientific advances and profits. However, the intermingling of science and commerce also strained the relationship between scientific and commercial priorities further along the trajectory of the drug; for example, concerning issues such as dosage strategy and drug use in primary care, where corporate management allegedly took decisions contrary to the recommendations of both academic and company scientists. On such occasions the asymmetry in power became apparent in scientists' narratives: commercial considerations trumped those of science since, ultimately, decisions rest with management, not with scientists. In addition, temporality appears to be associated with the divergence of commercial and scientific priorities. While rare during experimental and pre-clinical phases, divergence was concentrated downstream to the clinical testing and post-marketing phases. It is hypothesized that a similar pattern of convergence and

  12. New Framework To Diagnose the Direct Disposal of Prescribed Drugs in Wastewater - A Case Study of the Antidepressant Fluoxetine.

    Petrie, Bruce; Youdan, Jane; Barden, Ruth; Kasprzyk-Hordern, Barbara


    Intentional or accidental release (direct disposal) of high loads of unused pharmaceuticals into wastewater can go unnoticed. Here, direct disposal of a pharmaceutical drug via the sewer network was identified for the first time using wastewater analysis. An irregularly high load of the antidepressant fluoxetine in raw wastewater (10.5 ± 2.4 g d(-1)) was up to 11 times greater than any other day. National prescription data revealed a predicted daily fluoxetine load for the studied treatment works to be 0.4-1.6 g d(-1). Enantio-selective analysis showed the high load of fluoxetine was present as a racemic mixture, which is typical for fluoxetine in dispensed formulations. As fluoxetine undergoes stereoselective metabolism within the body, a racemic mixture in wastewater suggests a nonconsumed drug was the major contributor of the high load. This was confirmed by its major metabolite norfluoxetine whose load did not increase on this day. Considering the most commonly prescribed formulation of fluoxetine, this increased load accounts for the disposal of ∼915 capsules. Furthermore, as fluoxetine is prescribed as one capsule per day, disposal is unlikely to be at the patient level. It is postulated that direct disposal was from a facility which handles larger quantities of the drug (e.g., a pharmacy). PMID:26974167

  13. The Safety, Tolerability and Risks Associated with the Use of Newer Generation Antidepressant Drugs: A Critical Review of the Literature.

    Carvalho, André F; Sharma, Manu S; Brunoni, André R; Vieta, Eduard; Fava, Giovanni A


    Newer generation antidepressant drugs (ADs) are widely used as the first line of treatment for major depressive disorders and are considered to be safer than tricyclic agents. In this critical review, we evaluated the literature on adverse events, tolerability and safety of selective serotonin reuptake inhibitors, serotonin noradrenaline reuptake inhibitors, bupropion, mirtazapine, trazodone, agomelatine, vilazodone, levomilnacipran and vortioxetine. Several side effects are transient and may disappear after a few weeks following treatment initiation, but potentially serious adverse events may persist or ensue later. They encompass gastrointestinal symptoms (nausea, diarrhea, gastric bleeding, dyspepsia), hepatotoxicity, weight gain and metabolic abnormalities, cardiovascular disturbances (heart rate, QT interval prolongation, hypertension, orthostatic hypotension), genitourinary symptoms (urinary retention, incontinence), sexual dysfunction, hyponatremia, osteoporosis and risk of fractures, bleeding, central nervous system disturbances (lowering of seizure threshold, extrapyramidal side effects, cognitive disturbances), sweating, sleep disturbances, affective disturbances (apathy, switches, paradoxical effects), ophthalmic manifestations (glaucoma, cataract) and hyperprolactinemia. At times, such adverse events may persist after drug discontinuation, yielding iatrogenic comorbidity. Other areas of concern involve suicidality, safety in overdose, discontinuation syndromes, risks during pregnancy and breast feeding, as well as risk of malignancies. Thus, the rational selection of ADs should consider the potential benefits and risks, likelihood of responsiveness to the treatment option and vulnerability to adverse events. The findings of this review should alert the physician to carefully review the appropriateness of AD prescription on an individual basis and to consider alternative treatments if available. PMID:27508501

  14. Design, Synthesis, and Potential Antidepressant-like Activity of 7-prenyloxy-2,3-dihydroflavanone Derivatives.

    Zhen, Xing-Hua; Quan, Ying-Chun; Peng, Zhou; Han, Yan; Zheng, Zhou-Jun; Guan, Li-Ping


    A series of 7-prenyloxy-2, 3-dihydroflavanone derivatives were synthesized and screened for their antidepressant-like activity. Among them, it was observed that compounds 5j and 5k were found to be the most antidepressant-like activity. In addition, it was found that compounds 5j and 5k significantly increased the concentrations of the main neurotransmitters 5-HT and NE in the hippocampus, hypothalamus, and cortex. Compounds 5j and 5k also significantly increased the contents of 5-HIAA in the hippocampus and cortex, shut down 5-HT metabolism compared with mice treated with stress vehicle. These results suggested that compounds 5j and 5k displayed potent antidepressant-like properties that were mediated via neurochemical systems. PMID:26705885

  15. Simultaneous Determination of 24 Antidepressant Drugs and Their Metabolites in Wastewater by Ultra-High Performance Liquid Chromatography–Tandem Mass Spectrometry

    Ling-Hui Sheng


    Full Text Available Antidepressants are a new kind of pollutants being increasingly found in wastewater. In this study, a fast and sensitive ultra-high performance liquid chromatography-tandem mass spectrometry method was developed and validated for the analysis of 24 antidepressant drugs and six of their metabolites in wastewater. This is the first time that the antidepressant residues in wastewater of Beijing (China were systematically reported. A solid-phase extraction process was performed with 3 M cation disk, followed by ultra-high performance liquid chromatography–tandem mass spectrometry measurements. The chromatographic separation and mass parameters were optimized in order to achieve suitable retention time and good resolution for analytes. All compounds were satisfactorily determined in one single injection within 20 min. The limit of quantification (LOQ, linearity, and extraction recovery were validated. The LOQ for analytes were ranged from 0.02 to 0.51 ng/mL. The determination coefficients were more than 0.99 within the tested concentration range (0.1–25 ng/mL, and the recovery rate for each target compound was ranged from 81.2% to 118% at 1 ng/mL. This new developed method was successfully applied to analysis the samples collected from Beijing municipal wastewater treatment plants. At least ten target antidepressants were found in all samples and the highest mean concentration of desmethylvenlafaxin was up to 415.6 ng/L.

  16. Pharmacokinetic Drug Interactions Involving Vortioxetine (Lu AA21004), a Multimodal Antidepressant

    Chen, Grace; Lee, Ronald; Højer, Astrid-Maria; Buchbjerg, Jeppe Klint; Serenko, Michael; Zhao, Zhen


    Background and Objective The identification and quantification of potential drug–drug interactions is important for avoiding or minimizing the interaction-induced adverse events associated with specific drug combinations. Clinical studies in healthy subjects were performed to evaluate potential pharmacokinetic interactions between vortioxetine (Lu AA21004) and co-administered agents, including fluconazole (cytochrome P450 [CYP] 2C9, CYP2C19 and CYP3A inhibitor), ketoconazole (CYP3A and P-glyc...

  17. Active metabolites as antidepressant drugs: The role of norquetiapine in the mechanism of action of quetiapine in the treatment of mood disorders



    Full Text Available Active metabolites of some antipsychotic drugs exhibit pharmacodynamic and pharmacokinetic properties that may be similar to or differ from the original compound and that can be translated by a different profile of responses and interactions to clinical level. Some of these antipsychotics’ active metabolites might participate in mechanisms of antidepressant activity, as m-chlorophenylpiperazine (aripiprazole, 9-OH-risperidone and norquetiapine. Norquetiapine exhibits distinct pharmacological activity from quetiapine and plays a fundamental role in its antidepressant efficacy. In this review, we analyze the differential pharmacological aspects between quetiapine and norquetiapine, both from the pharmacokinetic and pharmacodynamic perspectives (affinity for dopaminergic, noradrenegic and/or serotonergic receptors, etc., as well as differential neuroprotective role. The pharmacological differences between the two drugs could explain the differential clinical effect, as well as some differences in tolerability profile and drug interactions. The available data are sufficient to arrive at the conclusion that antidepressant activity of quetiapine is mediated, at least in part, by the active metabolite norquetiapine, which selectively inhibits noradrenaline reuptake, is a partial 5-HT1A receptor agonist, and acts as an antagonist at presynaptic α2, 5-HT2C and 5-HT7 receptors.

  18. [Switching and combining strategies of antidepressant medications].

    Charpeaud, Thomas; Moliere, Fanny; Bubrovszky, Maxime; Haesebaert, Frédéric; Allaïli, Najib; Bation, Rémy; Nieto, Isabel; Richieri, Raphaëlle; Saba, Ghassen; Bellivier, Frank; Bennabi, Djamila; Holtzmann, Jérôme; Camus, Vincent; Courtet, Philippe; Courvoisier, Pierre; d'Amato, Thierry; Doumy, Olivier; Garnier, Marion; Bougerol, Thierry; Lançon, Christophe; Haffen, Emmanuel; Leboyer, Marion; Llorca, Pierre-Michel; Vaiva, Guillaume; El-Hage, Wissam; Aouizerate, Bruno


    Switching antidepressant medication may be helpful in depressed patients having no benefit from the initial antidepressant treatment. Before considering switching strategy, the initial antidepressant treatment should produce no therapeutic effect after at least 4 weeks of administration at adequate dosage. Choosing an antidepressant of pharmacologically distinct profile fails to consistently demonstrate a significant superiority in terms of effectiveness over the switching to another antidepressant within the same pharmacological class. Augmenting SSRI/SNRIs with mirtazapine/mianserin has become the most recommended strategy of antidepressant combinations. Augmenting SSRI with tricyclic drugs is now a less recommended strategy of antidepressant combinations given the increased risk for the occurrence of pharmacokinetic drug-drug interactions and adverse effects. PMID:26995511

  19. [3H]adrenaline release from hypothalamic synaptosomes and its modulation by clonidine: effects of chronic antidepressant drug regimens

    [3H]Adrenaline ([3H]ADR, 40nM) was accumulated by rat hypothalamic synaptosomes (P2) more rapidly and in significantly greater amounts than by similar preparations from cerebral cortex. There was no significant difference between these two tissues in the rate or amount of [3H]noradrenaline ([3H]NA, 40nM) accumulation. Talusupram (10μM), maximally inhibited the uptake of [3H]ADR into hypothalamic synaptosomes by 60%. Nomifensine further inhibited uptake by 14%. From these observations it was concluded that some [3H]ADR was accumulated into non adrenergic neuronal terminals. The effects of desipramine (DMI, 10mg/kg/day and clorgyline (1mg/kg/day) administration for 28 days on K+-evoked release of [3H]ADR was investigated using superfused hypothalamic synaptosomes. After both chronic antidepressant drug regimens, total [3H]ADR release (spontaneous + evoked) was significantly reduced. Evoked release of [numberH]ADR (by KCl, 16mM) was significantly reduced after the DMI but not the clorgyline regimens. Presynaptic α2-adrenoceptor function in the hypothalamus was assessed during superfusion by measuring the reduction in +-evoked release of [3H]ADR caused by clonidine (1+M). 30 references, 3 figures, 1 table

  20. Drug-Induced Liver Injury Associated With Antidepressive Psychopharmacotherapy: An Explorative Assessment Based on Quantitative Signal Detection Using Different MedDRA Terms.

    Gahr, Maximilian; Zeiss, René; Lang, Dirk; Connemann, Bernhard J; Hiemke, Christoph; Schönfeldt-Lecuona, Carlos


    Drug-induced liver injury is a major problem of pharmacotherapy and is also frequent with antidepressive psychopharmacotherapy. However, there are only few studies using a consistent methodologic approach to study hepatotoxicity of a larger group of antidepress ants. We performed a quantitative signal detection analysis using data from the Uppsala Monitoring Centre from the WHO that records adverse drug reaction (ADR) data from worldwide sources; we retrieved substance- and country-specific (Australia, France, Germany, Italy, Spain, the United Kingdom, and the United States) ADR data and calculated reporting odds ratios as measures for disproportionality within a case/noncase approach. To allow for identification of agents that cause severe forms of hepatotoxic ADRs, we used 2 terms of the MedDRA ("drug-related hepatic disorders-comprehensive search" [DRHD-CS] and "… -severe events only" [DRHD-SEO]). Distribution of signals was heterogeneous throughout the different data sets, and consistent findings were present for only a few substances: agomelatine (AGM) and tianeptine as well as both positive control agents (amineptine, nefazodone) generated signals related to DRHD-CS and DRHD-SEO in all analyzed data sets. Tri- and tetracyclic antidepressants (here amitriptyline, clomipramine, mianserin, mirtazapine, trimipramine) were associated with hepatotoxicity in several data sets. Using 2 MedDRA terms did not allow for detection of agents that cause severe hepatotoxic ADR. Our results support the findings of previous, primarily literature-based, systematic analyses of hepatotoxicity related to antidepressive psychopharmacotherapy. No new safety information could be generated. Application of 2 MedDRA terms did not increase the substance-specific safety information. PMID:26470856

  1. A Fluorescence Displacement Assay for Antidepressant Drug Discovery Based on Ligand-Conjugated Quantum Dots

    Chang, Jerry [Vanderbilt University; Tomlinson, Ian [Oak Ridge National Laboratory (ORNL); Warnement, Michael [Vanderbilt University; Iwamoto, Hideki [Vanderbilt University


    The serotonin (5-hydroxytryptamine, 5-HT) transporter (SERT) protein plays a central role in terminating 5-HT neurotransmission and is the most important therapeutic target for the treatment of major depression and anxiety disorders. We report an innovative, versatile, and target-selective quantum dot (QD) labeling approach for SERT in single Xenopus oocytes that can be adopted as a drug-screening platform. Our labeling approach employs a custom-made, QD-tagged indoleamine derivative ligand, IDT318, that is structurally similar to 5-HT and accesses the primary binding site with enhanced human SERT selectivity. Incubating QD-labeled oocytes with paroxetine (Paxil), a high-affinity SERT-specific inhibitor, showed a concentration- and time-dependent decrease in QD fluorescence, demonstrating the utility of our approach for the identification of SERT modulators. Furthermore, with the development of ligands aimed at other pharmacologically relevant targets, our approach may potentially form the basis for a multitarget drug discovery platform.

  2. Optimization of ultrasound assisted dispersive liquid-liquid microextraction of six antidepressants in human plasma using experimental design.

    Fernández, P; Taboada, V; Regenjo, M; Morales, L; Alvarez, I; Carro, A M; Lorenzo, R A


    A simple Ultrasounds Assisted-Dispersive Liquid Liquid Microextraction (UA-DLLME) method is presented for the simultaneous determination of six second-generation antidepressants in plasma by Ultra Performance Liquid Chromatography with Photodiode Array Detector (UPLC-PDA). The main factors that potentially affect to DLLME were optimized by a screening design followed by a response surface design and desirability functions. The optimal conditions were 2.5mL of acetonitrile as dispersant solvent, 0.2mL of chloroform as extractant solvent, 3min of ultrasounds stirring and extraction pH 9.8.Under optimized conditions, the UPLC-PDA method showed good separation of antidepressants in 2.5min and good linearity in the range of 0.02-4μgmL(-1), with determination coefficients higher than 0.998. The limits of detection were in the range 4-5ngmL(-1). The method precision (n=5) was evaluated showing relative standard deviations (RSD) lower than 8.1% for all compounds. The average recoveries ranged from 92.5% for fluoxetine to 110% for mirtazapine. The applicability of DLLME/UPLC-PDA was successfully tested in twenty nine plasma samples from antidepressant consumers. Real samples were analyzed by the proposed method and the results were successfully submitted to comparison with those obtained by a Liquid Liquid Extraction-Gas Chromatography - Mass Spectrometry (LLE-GC-MS) method. The results confirmed the presence of venlafaxine in most cases (19 cases), followed by sertraline (3 cases) and fluoxetine (3 cases) at concentrations below toxic levels. PMID:26955756

  3. Liquid-phase microextraction for simultaneous chromatographic analysis of three antidepressant drugs in plasma

    Carlos Eduardo Dobrovolskni Porto


    Full Text Available A method using Liquid Phase Microextraction for simultaneous detection of citalopram (CIT, paroxetine (PAR and fluoxetine (FLU, using venlafaxine as internal standard, in plasma by high performance liquid chromatography with fluorescence detection was developed. The linearity was evaluated between 5.0 and 500 ng mL-1 (r > 0.99 and the limit of quantification was 2.0, 3.0 and 5.0 ng mL-1 for CIT, PAR and FLU, respectively. Therefore, it can be applied to therapeutic drug monitoring, pharmacokinetics or bioavailability studies and its advantages are that it necessary relatively inexpensive equipment and sample preparation techniques.

  4. Trend analysis of antidepressant drug use in a three grade mental hospital%我院抗抑郁药使用趋势分析

    李永红; 靳自斌; 朱静


    Objective Through the investigation, to understand our use of antidepressants, and trends.Methods A retrospective analysis of our hospital from January 2014 to January 2014 outpatient prescriptions and medicinal drugs in hospital prescription for depression during frequency statistics, sales amount, and so on and so forth.Results From January 2014 to January 2014 in the spirit of specialized pharmacy antidepressants for total sales of 5.3387 million yuan, the highest sales amount of paroxetine, followed by venlafaxine, again for sertraline. DDDs occupies the top three, respectively is paroxetine, followed by grammar Racine, sertraline for clinical commonly used antidepressant drugs. Paroxetine, venlafaxine, sertraline are new type of antidepressant drugs, the new depressive drugs sales amount is higher than traditional drugs (P < 0.05). Antidepressants and sedative hypnotic drugs most often used in combination, with mood stabilizers, antipsychotic medication use is also more frequent; Drugs are used for female patients, patients aged more than 40 or higher. Conclusion The spirit of our specialized pharmacy antidepressant use new drug use, this kind of adverse drug reaction, the effect is good, strong normative.%目的:通过用药调查,了解我院抗抑郁药使用情况及趋势.方法:回顾性分析我院2014年1月~2015年1月期间门诊处方与住院处方对抑郁药用药频度、销售金额等情况进行统计信息.结果:我院2014年1月~2015年1月年精神专科药房抗抑郁药物销售总量为533.87万元,销售金额最高的是帕罗西汀,其次为文拉法辛,再次为舍曲林.DDDs居于前三位的分别是帕罗西汀,其次为文法拉辛,舍曲林为临床较常用抗抑郁药.帕罗西汀、文拉法辛、舍曲林均为新型抗抑郁药,新型抗郁药物销售金额高于传统药物(P<0.05).抗抑郁药物最常与镇静催眠类药物联合使用,与心境稳定剂、抗精神病药物使用也较频繁;药物均多用于

  5. Clinical perspectives on the influence of drug formulation on patient tolerability and use of commonly prescribed antidepressants in major depressive disorder

    Matthew A Fuller


    Full Text Available The purpose of this review is to summarize the formulation options for currently available antidepressants, and discuss examples of the influence that formulation may have on the pharmacologic and clinical profiles of the medications. A review of current literature suggests that differences in drug-delivery technologies can lead to variations in the pharmacokinetic and pharmacodynamic profiles of generic and branded drugs, despite generic drugs being required to meet bioequivalence standards compared with their branded counterparts. These differences may influence the effectiveness and tolerability of treatment. Recent reports have highlighted the need for individualized treatment regimens and careful assessment of tolerability and efficacy when switching patients from brand to generic formulations. There is a growing body of evidence indicating that differences in formulation can substantially impact drug pharmacokinetics and pharmacodynamics, which in turn, can affect drug effects. The clinical impact of these differences remains unclear. Further research is needed to clarify the influence of antidepressant formulations on treatment adherence, patient preference, and quality of life, and how this impacts clinical practice with regard to brand versus generic treatment selection.

  6. Antiepileptic, behavioral, and antidepressant effects of adjuvant lamotrigine therapy in drug-resistant epilepsy

    Martinović Žarko J.


    Full Text Available Aim. To evaluate the behavioral effects of lamotrigine as add-on therapy in treatment-resistant epilepsy. Methods. An open, prospective, long-term study of lamotrigine as adjuvant therapy was performed in 56 patients with drug-resistant epilepsy (female/male ratio 35/21, age range 16-51 years. All the patients kept seizure diaries, and electroencephalograms were recorded at baseline and during 24 months of the treatment. Quality of life questionnaire, Hamilton depression scale (HMD, Beck depression scale (BDI, and Hamilton anxiety scale (HMA were used before and during lamotrigine therapy. Comparative assessments were made in an age- and sex-matched control group treated with other antiepileptic drugs. Results. Overall, seizure control was improved in 55.3% of the patients, remained unchanged in 39.3%, and deteriorated in 5.4%. Improvement in some quality of life measures occurred in 50% of the patients. The HMD subscales and BDI scale showed significant improvement in lamotrigine treated patients compared to the control group (ANOVA, p < 0.01. Negative behavioral effects occurred in 10.7% of the patients. Conclusion. Lamotrigine demonstrated significant antiepileptic long-term efficacy, and its positive effects on the mood and quality of life, which surpassed the negative behavioral effects, and contributed highly to the favorable treatment outcome.

  7. 125I-labelled iodothyronines. Useful tools for studies of effects of an antidepressant drug fluoxetine in the rat

    Thyroid hormones (TH) are supposed to control the activity of some neurotransmitters (e.g., serotonin), which are hypothetically involved in the pathogenesis of depressive illness. A new group of non-tricyclic antidepressant drugs includes selective serotonine re-uptake inhibitors. The most frequently used representative of this group is fluoxetine (Fluox). We followed in the present paper the effects of Fluox, administered subchronicaly (for 25 days) to Wistar rats by itself, or in combination with 3,3',5-triiodo-l-thyronine (T3). In studies of the interaction of Fluox with the metabolism of TH, we applied adapted radiometric enzyme assays for iodothyronine sulfotransferases (ST) and uridine 5'-diphospho-glucuronyltransferase (UDP-GT), as well as our newly developed radiometric assays for iodothyronine deiodinases (IDs) of types 1, 2 and 3 (D1, D2 and D3), using 125I-labelled iodothyronines of high specific radioactivity as substrates. We found about two-fold higher UDP-GT enzyme activities in samples of liver microsomes of rats treated with Fluox, in comparison with control rats. In contrast, the radiometric determination of ST activities in liver and kidney cytosolic fractions did not demonstrate any significant effects of the administration of Fluox, alone or together with T3, on the induction of these enzymes. However, profound changes in enzyme activities were determined in case of IDs, especially in the pituitary and cerebellum of treated rats. The adapted and newly elaborated radiometric enzyme assays proved to be very sensitive and rapid and, at the same time, reliable and robust. (author)

  8. Cytogenetic and Developmental Effects of Antidepression Drug (Cipralex on Female Mice and Embryos

    Hanaa M. Roshdy & Thanaa M.T Shoman


    Full Text Available Escitalopram (cipralex® a new highly selective serotonin reuptake inhibitor, it is effective in the treatment of patients with major depression. To evaluate the cytogenetics and developmental effects of cipralex throughout major organgenesis, mice were administrated orally with a doses of 0.06, 0.12 and 0.24 mg/kg/day cipralex on gestation days 1-18 and examined on the 19th day of gestation for evidence of maternal and fetal toxicity. Cipralex at different doses tested produce significant toxic effects in reproductive parameters. Significant embryo fetotoxic effects were observed at tested dose levels as evidenced by total number of implantations, post. Implantation loss and embryo malformations. There were increases in the frequencies of micronuclei and chromosomal aberrations in both maternal and embryonic cells treated with cipalex, these increases were dose dependent. These results indicate that cipralex is considered to be cytogenetic and embryo toxic drug when administered during pregnancy.

  9. Performance of Cpred/Cobs concentration ratios as a metric reflecting adherence to antidepressant drug therapy

    Yan Feng


    Full Text Available Yan Feng1, Marc R Gastonguay2, Bruce G Pollock3,5, Ellen Frank3, Gail H Kepple4, Robert R Bies5,6,71Discovery Medicine and Clinical Pharmacology, Bristol-Myers Squibb, Lawrenceville, NJ, USA; 2Metrum Institute, Tariffville, CT, USA; 3Department of Psychiatry, School of Medicine, 4Department of Depression Prevention, University of Pittsburgh, PA, USA; 5Centre for Addiction and Mental Health, University of Toronto, Toronto, Canada; 6Division of Clinical Pharmacology, School of Medicine and Center for Computational Biology and Bioinformatics, Indiana University School of Medicine, Indianapolis, IN, USA; 7Indiana Clinical Translational Research Institute, Indiana University School of Medicine, IN, USABackground: Nonadherence is very common among subjects undergoing pharmacotherapy for schizophrenia and depression. This study aimed to evaluate the performance of the ratio of the nonlinear mixed effects pharmacokinetic model predicted concentration to observed drug concentration (ratio of population predicted to observed concentration (Cpred/Cobs and ratio of individual predicted to observed concentration (Cipred/Cobs as a measure of erratic drug exposure, driven primarily by variable execution of the dosage regimen and unknown true dosage history.Methods: Modeling and simulation approaches in conjunction with dosage history information from the Medication Event Monitoring System (MEMS, provided by the “Depression: The search for treatment relevant phenotypes” study, was applied to evaluate the consistency of exposure via simulation studies with scenarios representing a long half-life drug (escitalopram. Adherence rates were calculated based on the percentage of the prescribed doses actually taken correctly during the treatment window of interest. The association between Cpred/Cobs, Cipred/Cobs ratio, and adherence rate was evaluated under various assumptions of known dosing history.Results: Simulations for those scenarios representing a known

  10. Carbonic anhydrase inhibitors drug design.

    McKenna, Robert; Supuran, Claudiu T


    Inhibition of the metalloenzyme carbonic anhydrase (CA, EC has pharmacologic applications in the field of antiglaucoma, anticonvulsant, antiobesity, and anticancer agents but is also emerging for designing anti-infectives (antifungal and antibacterial agents) with a novel mechanism of action. As a consequence, the drug design of CA inhibitors (CAIs) is a very dynamic field. Sulfonamides and their isosteres (sulfamates/sulfamides) constitute the main class of CAIs which bind to the metal ion in the enzyme active site. Recently the dithiocarbamates, possessing a similar mechanism of action, were reported as a new class of inhibitors. Other families of CAIs possess a distinct mechanism of action: phenols, polyamines, some carboxylates, and sulfocoumarins anchor to the zinc-coordinated water molecule. Coumarins and five/six-membered lactones are prodrug inhibitors, binding in hydrolyzed form at the entrance of the active site cavity. Novel drug design strategies have been reported principally based on the tail approach for obtaining all these types of CAIs, which exploit more external binding regions within the enzyme active site (in addition to coordination to the metal ion), leading thus to isoform-selective compounds. Sugar-based tails as well as click chemistry were the most fruitful developments of the tail approach. Promising compounds that inhibit CAs from bacterial and fungal pathogens, of the dithiocarbamate, phenol and carboxylate types have also been reported. PMID:24146385

  11. Designer drugs: the evolving science of drug discovery.

    Wanke, L A; DuBose, R F


    Drug discovery and design are fundamental to drug development. Until recently, most drugs were discovered through random screening or developed through molecular modification. New technologies are revolutionizing this phase of drug development. Rational drug design, using powerful computers and computational chemistry and employing X-ray crystallography, nuclear magnetic resonance spectroscopy, and three-dimensional quantitative structure activity relationship analysis, is creating highly specific, biologically active molecules by virtual reality modeling. Sophisticated screening technologies are eliminating all but the most active lead compounds. These new technologies promise more efficacious, safe, and cost-effective medications, while minimizing drug development time and maximizing profits. PMID:10185235

  12. Nitric Oxide Synthase Inhibitors as Antidepressants

    Wegener, Gregers; Volke, Vallo


    , including serotonin, glutamate and GABA, are intimately regulated by NO, and distinct classes of antidepressants have been found to modulate the hippocampal NO level in vivo. The NO system is therefore a potential target for antidepressant and anxiolytic drug action in acute therapy as well...... as in prophylaxis. This paper reviews the effect of drugs modulating NO synthesis in anxiety and depression....

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

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


    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...

  14. Antidepressants and testicular cancer: cause versus association.

    Andrade, Chittaranjan


    A data mining study that examined associations between 105 drugs and 55 cancer sites found significant associations between 2 selective serotonin reuptake inhibitors (fluoxetine and paroxetine) and testicular cancer. The study suggested several reasons why these associations merited further investigation. A later study tested specific relationships between 12 antidepressant drugs and testicular cancer and subtypes thereof; whereas significant relationships were again found, these disappeared after adjusting for confounding variables. These 2 studies are educative because they illustrate how false-positive results can easily arise in exploratory research and how confounding may be responsible for statistically significant relationships in study designs that are not randomized controlled trials. PMID:24717391

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

    Miskowiak, Kamilla W; Favaron, Elisa; Hafizi, Sepehr; Inkster, Becky; Goodwin, Guy M; Cowen, Philip J; Harmer, Catherine J


    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...... study investigates the effects of Epo on the neural and cognitive response to emotional facial expressions in depressed patients....

  16. Antidepressant drugs transactivate TrkB neurotrophin receptors in the adult rodent brain independently of BDNF and monoamine transporter blockade.

    Tomi Rantamäki

    Full Text Available BACKGROUND: Antidepressant drugs (ADs have been shown to activate BDNF (brain-derived neurotrophic factor receptor TrkB in the rodent brain but the mechanism underlying this phenomenon remains unclear. ADs act as monoamine reuptake inhibitors and after prolonged treatments regulate brain bdnf mRNA levels indicating that monoamine-BDNF signaling regulate AD-induced TrkB activation in vivo. However, recent findings demonstrate that Trk receptors can be transactivated independently of their neurotrophin ligands. METHODOLOGY: In this study we examined the role of BDNF, TrkB kinase activity and monoamine reuptake in the AD-induced TrkB activation in vivo and in vitro by employing several transgenic mouse models, cultured neurons and TrkB-expressing cell lines. PRINCIPAL FINDINGS: Using a chemical-genetic TrkB(F616A mutant and TrkB overexpressing mice, we demonstrate that ADs specifically activate both the maturely and immaturely glycosylated forms of TrkB receptors in the brain in a TrkB kinase dependent manner. However, the tricyclic AD imipramine readily induced the phosphorylation of TrkB receptors in conditional bdnf⁻/⁻ knock-out mice (132.4±8.5% of control; P = 0.01, indicating that BDNF is not required for the TrkB activation. Moreover, using serotonin transporter (SERT deficient mice and chemical lesions of monoaminergic neurons we show that neither a functional SERT nor monoamines are required for the TrkB phosphorylation response induced by the serotonin selective reuptake inhibitors fluoxetine or citalopram, or norepinephrine selective reuptake inhibitor reboxetine. However, neither ADs nor monoamine transmitters activated TrkB in cultured neurons or cell lines expressing TrkB receptors, arguing that ADs do not directly bind to TrkB. CONCLUSIONS: The present findings suggest that ADs transactivate brain TrkB receptors independently of BDNF and monoamine reuptake blockade and emphasize the need of an intact tissue context for the

  17. Adherence to antidepressants

    Abimbola Farinde


    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.

  18. VGF, a New Player in Antidepressant Action?

    Malberg, Jessica E.; Monteggia, Lisa M.


    Recent studies have identified adaptations of intracellular signaling pathways and target genes that could contribute or modulate the action of antidepressant drugs, as well as exercise-mediated antidepressant responses. Understanding these adaptations, particularly those changes that are common to diverse antidepressant treatments, is important for the development of more potent and specific treatments of depression. There is growing evidence that growth factors may be important mediators of...

  19. Neurogenesis and The Effect of Antidepressants

    Philippe Taupin


    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.

  20. Analysis on the Use of Antidepressant Drugs in 285 Patients With Psychological Hospital in Changchun City%长春市心理医院285例住院患者使用抗抑郁药用药分析



    Objective To understand the application of antidepressant drugs in open ward in our hospital, and provide reference for clinical rational drug use. Source: Changchun city hospital open area, from January 1st, 2014 to December 31st, hospitalized patients. Methods Self designed survey form was recorded in the patient's gender, age, diagnosis, the name of the antidepressant drugs, and the combination of drug use, and the contents of the general demographic data, medical records and drug use. Results One kind of antidepressant, which was mainly new type of antidepressants, was used in 206 cases (72.3%), combined application of two kinds of antidepressants was used in 79 cases, while mirtazapine combined with venlafaxine was most common used 38 cases. Conclusion References for clinical rational drug use. Most patients use only one kind of antidepressant, and the ratio of new type of antidepressants was higher than traditional antidepressants. Mirtazapine combined with venlafaxine works faster and better in the cases which combination of two kinds of antidepressants was used.%目的:了解我院开放病区住院患者抗抑郁药的应用情况,为临床合理用药提供参考。资料来源:长春市心理医院开放病区,2014年1月1日~12月31日住院患者。方法自行设计调查表格,记录患者性别、年龄、诊断、服用抗抑郁药名称及合并用药情况,内容涉及一般人口学资料,病案资料和用药情况。结果单一使用1种抗抑郁药治疗者206例(72.3%);目前应用以新型抗抑郁药为主;联合2种抗抑郁药物治疗者79例,以米氮平+文拉法辛最为多见38例。结论为临床合理用药提供参考;患者单一使用1种抗抑郁药治疗者较多;新型抗抑郁药物应用比例高于传统抗抑郁药;联合2种抗抑郁药物治疗的,米氮平+文拉法辛抗抑郁速度和疗效俱佳。

  1. Tricyclic antidepressant radioreceptor assay

    A receptor assay for tricyclic antidepressants described here is based on the ability of these drugs to compete with [3H]-3-guinuclidnyl benzilate (3H-QNB) for binding to muscarinic cholinergic receptors in rat brain membranes. The assay is sensitive, in that it can detect, for example, 2ng/ml nortriptyline in plasma. Seven plasma samples from depressed patients treated with nortriptyline were assayed with the radioreceptor and gas liquid chromatographic methods, and the results from these two methods were almost identical. This assay should be used cautiously, if at all, in patients treated with other drugs that have potent anticholinergic effects. (Auth.)

  2. 我院门诊抗抑郁药处方分析%Analysis of Outpatient Prescriptions of Antidepressant Drugs

    李燕平; 胡新伟


    目的:研究我院抗抑郁药的应用情况。方法:选取我院门诊2012年7-9月1080张诊断为抑郁症的处方进行分析。结果:1080例患者中,男425例(39.35%),女655例(60.65%),女性多于男性。各类抗抑郁药中,以选择性5-羟色胺再摄取抑制剂(SSRI)使用频率最高。各种抗抑郁药的平均使用剂量均在安全范围之内。697例(64.54%)患者联用苯二氮类药物治疗,476例(44.07%)患者联用抗精神病药,233例(21.57%)患者联用心境稳定剂。结论:以SSRI为主的新型抗抑郁药已经成为我院临床抗抑郁治疗的主流药物,抗抑郁药的使用以单一用药为主。%Objective:To evaluate the utilization of antidepressants in our hospital. Methods:The prescription analy-sis was conducted of 1 080 depression outpatients during Jul.-Sep. of 2012. Results:Of the selected patients female and male patients were 655(60.65%) and 425(39.35%) respectively. Among the antidepressants used,selective serotonin re-uptake inhibitors (SSRIs) were the most frequently used.The average dose of various antidepressants was all within the range of safety. The frequency of combined use of benzodiazepines,antipsychotics and mood stabilizers used was 64.54%, 44.07%and 21.57%respectively. Conclusion:New types of antidepressants based on SSRIs have become the mainstream treatment of depression in our hospital and antidepressants were mainly used as the single agent.

  3. Solid phase extraction of antidepressant drugs amitriptyline and nortriptyline from plasma samples using core-shell nanoparticles of the type Fe3O4-ZrO2-N- cetylpyridinium, and their subsequent determination by HPLC with UV detection

    The solid phase extraction (SPE) is described for preconcentration of the antidepressant drugs amitriptyline and nortriptyline prior to their determination by HPLC with UV detection. It is based on the use of water-dispersible core-shell nanoparticles (NPs) of the Fe3O4-ZrO2-N-cetylpyridinium type. The positively charged surfactant N-cetylpyridinium forms mixed aggregates with the drugs on the surface of the core-shell and thereby improves the adsorption of amitriptyline and nortriptyline through hydrophobic and/or ionic interactions. Their extraction depends on the type and amount of surfactant, sample pH, extraction time, desorption conditions, sample volume and amount of NPs that were optimized by application of experimental design. The enrichment factors are 220 and 250, respectively, for amitriptyline and nortriptyline, and the detection limits are 0.04 and 0.08 ng·mL-1. This protocol enables accurate and precise quantification of the two drugs in complex and low content samples. It was applied to the determination of the two drugs in plasma samples with relative recoveries in the range from 89 to 105 % and RSDs less than 4 %. (author)

  4. Ultra-high-pressure liquid chromatography tandem mass spectrometry determination of antidepressant and anxiolytic drugs in neonatal meconium and maternal hair.

    Pichini, Simona; Cortes, Laura; Marchei, Emilia; Solimini, Renata; Pacifici, Roberta; Gomez-Roig, Maria Dolores; García-Algar, Oscar


    A procedure based on ultra-high-pressure liquid chromatography tandem mass spectrometry has been developed for the determination of 22 antidepressant and anxiolytic drugs ad metabolites in the three consecutive maternal hair segments representing the pregnancy trimesters and paired neonatal meconium samples. After hair washing with methyl alcohol and diethyl ether and subsequent addition of internal standards, hair samples were treated with 500 μl VMA-T M3 reagent for 1h at 100 °C. After cooling, 100 μl M3 extract were diluted with 400 μl water and a volume of 10 μl was injected into chromatographic system. Meconium samples were firstly treated with 1 ml methyl alcohol and the organic layer back-extracted twice with 1.5 ml of a mixture of ethylacetate:hexane (80:20, v/v). Chromatographic separation was achieved at ambient temperature using a reverse-phase column and a linear gradient elution with two solvents: 0.3% formic acid in acetonitrile and 5mM ammonium formate pH 3. The mass spectrometer was operated in positive ion mode, using multiple reaction monitoring via positive electrospray ionization. The method was linear from the limit of quantification (0.05-1 ng/mg hair and 5-25 ng/g meconium depending on analyte under investigation;) to 10 ng/mg hair and 1000 ng/g meconium, with an intra- and inter-assay imprecision and inaccuracy always less than 20% and an analytical recovery between 66.6% and 95.3%, depending on the considered analyte and biological matrix. Using the validated method, 7 mothers were found positive to one or more hair segments and 5 meconium samples were found positive to one or more antidepressant and anxiolytic drugs, assessing prenatal exposure to these drugs following maternal consumption in one or more pregnancy trimesters. PMID:26512994

  5. 21 CFR 316.24 - Granting orphan-drug designation.


    ... 21 Food and Drugs 5 2010-04-01 2010-04-01 false Granting orphan-drug designation. 316.24 Section...) DRUGS FOR HUMAN USE ORPHAN DRUGS Designation of an Orphan Drug § 316.24 Granting orphan-drug designation. (a) FDA will grant the request for orphan-drug designation if none of the reasons described in §...

  6. Clinical application of antidepressants in the treatment of insomnia symptoms

    WONG Iok-man


    Full Text Available Insomnia is one of the common complaints among all clinical departments. In recent years, some studies have demonstrated that insomnia symptoms can be improved or treated by some antidepressants. Based on literature search both at home and abroad, this paper summarized the effect of various antidepressants with different pharmacological properties on sleep, and the progress of clinical application of antidepressants in treating insomnia according to the classification of antidepressant drugs.

  7. 21 CFR 316.23 - Timing of requests for orphan-drug designation; designation of already approved drugs.


    ... 21 Food and Drugs 5 2010-04-01 2010-04-01 false Timing of requests for orphan-drug designation..., DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE ORPHAN DRUGS Designation of an Orphan Drug § 316.23 Timing of requests for orphan-drug designation; designation of already approved drugs....

  8. Antidepressant-like activity of flunarizine in modified tail suspension test in rats

    Vinod Shinde


    Full Text Available Background: Flunarizine, a Ca 2+ channel blocker, crosses blood brain barrier (BBB, antagonizes calcium influx and interferes with neurotransmitter system. Flunarizine 20 mg/kg exhibited significant antidepressant activity in our previous study using forced swim test (FST in mice, which was contradictory to the findings of other authors. Hence, the present study was designed to strengthen the results of our previous study, using the modified tail suspension test (TST in rats. Aim: Aim of this study was to evaluate the antidepressant activity of flunarizine versus standard antidepressant drug fluoxetine in modified TST in rats. Materials and Methods: The study approved by Institutional Animal Ethics Committee was conducted using 24 adult albino rats (n = 6 in each group. Antidepressant effect of normal saline (0.1 ml/100 g, fluoxetine (10 mg/kg, intraperitoneally (ip, and flunarizine (2 and 10 mg/kg, ip was evaluated by using modified TST in rats. Thirty minutes after administration of all test drugs the duration of immobility was recorded for a period of 5 min in all rats by using modified TST. The data was analyzed by Student′s t-test and one-way analysis of variance (ANOVA and P 0.05. Also, currently used human dose of flunarizine when extrapolated to rats (i. e., 2 mg/kg, ip failed to show significant antidepressant effect in modified TST in rats. Conclusion: The results of the present study indicate antidepressant-like activity of flunarizine.

  9. Designer Drug Confusion: A Focus on MDMA.

    Beck, Jerome; Morgan, Patricia A.


    Discusses the competing definitions and issues surrounding various designer drugs, primarily 3, 4-methylenedioxy-methamphetamine (MDMA). Offers a rationale for why interest in MDMA, which possesses both stimulant and psychedelic properties, will continue to grow despite the drug's recent illegality and increasing evidence of neurotoxicity.…

  10. Smarter Drugs: How Protein Crystallography Revolutionizes Drug Design

    According to Smith, protein crystallography allows scientists to design drugs in a much more efficient way than the standard methods traditionally used by large drug companies, which can cost close to a billion dollars and take 10 to 15 years. 'A lot of the work can be compressed down,' Smith said. Protein crystallography enables researchers to learn the structure of molecules involved in disease and health. Seeing the loops, folds and placement of atoms in anything from a virus to a healthy cell membrane gives important information about how these things work - and how to encourage, sidestep or stop their functions. Drug design can be much faster when the relationship between structure and function tells you what area of a molecule to target. Smith will use a timeline to illustrate the traditional methods of drug development and the new ways it can be done now. 'It is very exciting work. There have been some failures, but many successes too.' A new drug to combat the flu was developed in a year or so. Smith will tell us how. He will also highlight drugs developed to combat HIV, Tuberculosis, hypertension and Anthrax.

  11. Radiation chemistry applied to drug design

    Radiation chemistry can contribute to drug design by quantifying redox properties of drugs and where free radicals are suspected intermediates in drug action, radiation can be used to generate these putative species and help characterise relevant reactions. Steady radiolysis produces radicals at a readily-varied but quantified rate; pulse radiolysis with fast spectrophotometric and/or conductimetric detection enables the kinetic properties of radicals to be monitored directly. Using these methods, radical intermediates from drugs with specific cytotoxicity towards hypoxic cells have been shown to react rapidly with oxygen. Radical oxidants from activated neutrophils include superoxide and hydroxyl radicals, and radiation-chemical methods have an important role to play in rational drug design to exploit such oxidative chemistry. Antioxidants can also be evaluated quantitatively by radiolysis methods; the conjugation reactions of thiyl radicals with thiolate and oxygen are now recognised to be major contributions of pulse radiolysis to thiol biochemistry. (author)

  12. Radiation chemistry applied to drug design

    Wardman, P.; Candeias, L.P.; Everett, S.A. (Mount Vernon Hospital, Northwood (United Kingdom). Cancer Research Campaign Gray Lab.); Tracy, M. (SRI International, Menlo Park, CA (United States))


    Radiation chemistry can contribute to drug design by quantifying redox properties of drugs and where free radicals are suspected intermediates in drug action, radiation can be used to generate these putative species and help characterise relevant reactions. Steady radiolysis produces radicals at a readily-varied but quantified rate; pulse radiolysis with fast spectrophotometric and/or conductimetric detection enables the kinetic properties of radicals to be monitored directly. Using these methods, radical intermediates from drugs with specific cytotoxicity towards hypoxic cells have been shown to react rapidly with oxygen. Radical oxidants from activated neutrophils include superoxide and hydroxyl radicals, and radiation-chemical methods have an important role to play in rational drug design to exploit such oxidative chemistry. Antioxidants can also be evaluated quantitatively by radiolysis methods; the conjugation reactions of thiyl radicals with thiolate and oxygen are now recognised to be major contributions of pulse radiolysis to thiol biochemistry. (author).

  13. Antidepressant chronotherapeutics for bipolar depression.

    Benedetti, Francesco


    Chronotherapeutics refers to treatments based on the principles of circadian rhythm organization and sleep physiology, which control the exposure to environmental stimuli that act on biological rhythms, in order to achieve therapeutic effects in the treatment of psychiatric conditions. It includes manipulations of the sleep-wake cycle such as sleep deprivation and sleep phase advance, and controlled exposure to light and dark. The antidepressant effects of chronotherapeutics are evident in difficult-to-treat conditions such as bipolar depression, which has been associated with extremely low success rates of antidepressant drugs in naturalistic settings and with stable antidepressant response to chronotherapeutics in more than half of the patients. Recent advances in the study of the effects of chronotherapeutics on neurotransmitter systems, and on the biological clock machinery, allow us to pinpoint its mechanism of action and to transform it from a neglected or "orphan" treatment to a powerful clinical instrument in everyday psychiatric practice. PMID:23393416

  14. Designer Drugs: A Synthetic Catastrophe

    James Fratantonio


    Full Text Available Synthetic stimulants can cause hallucinations, aggressive behaviors, death and are sometimes legal. These substances are sold as plant food and bath salts that are "Not for Human Consumption", therefore skirting the 1986 Federal Analogue Act and giving a false pretense of safety. Studies have proved that these substances are toxic, have a high abuse potential, and are becoming extremely prevalent in the United States. This creates a dilemma for law enforcement agents, hospitals, and substance use disorder treatment centers. Urine Drug Testing is utilized as a clinical diagnostic tool in substance use disorder treatment centers, and the furious pace at which new synthetic stimulants are introduced to the black market are making the detection via urine increasingly difficult. This article will discuss the prevalence, pharmacology and difficulty developing laboratory assays to detect synthetic stimulants.

  15. Evolution and intelligent design in drug development

    Dorothee eKern


    Full Text Available Sophisticated protein kinase networks, empowering complexity in higher organisms, are also drivers of devastating diseases such as cancer. Accordingly, these enzymes have become major drug targets of the 21st century. However, the holy grail of designing specific kinase inhibitors aimed at specific cancers has not been found. Can new approaches in cancer drug design help win the battle with this multi-faced and quickly evolving enemy? In this perspective we discuss new strategies and ideas that were born out of a recent breakthrough in understanding the molecular basis underlying the clinical success of the cancer drug Gleevec. An old method, stopped-flow kinetics, combined with old enzymes, the ancestors dating back up to about billion years, provides an unexpected outlook for future intelligent design of drugs.

  16. Running is rewarding and antidepressive

    Brené, Stefan; Bjørnebekk, Astrid; Åberg, Elin; Mathé, Aleksander A.; Olson, Lars; Werme, Martin


    Natural behaviors such as eating, drinking, reproduction and exercise activate brain reward pathways and consequently the individual engages in these behaviors to receive the reward. However, drugs of abuse are even more potent to activate the reward pathways. Rewarding behaviors and addictive drugs also affect other parts of the brain not directly involved in the mediation of reward. For instance, running increases neurogenesis in hippocampus and is beneficial as an antidepressant in a genet...

  17. Volumetric and ultrasonic studies of an antidepressant drug in aqueous and alcoholic medium over temperature range 298.15-313.15 k

    Escitalopram oxalate is an amphiphilic serotonin specific reuptake inhibitor-antidepressant drug. Ultrasonic velocity (u) and density (d) measurements were carried out for Escitalopram oxalate in aqueous and alcoholic systems as a function of concentration in a range of molality, m (0.0075-0.04) mol Kg-1 at 298.15-313.15 K using an Anton Paar density sound analyzer (DSA 5000M). Using these experimental values, the acoustical parameters such as apparent molar adiabatic compressibility and partial molar volume (V phi) was apparent molar volume (V phi (K computed for all the systems. The Partial molar expansivity (E/sup 0/) and second derivative values, (partial drive V/sup 0/partial drive T/sup 2/), have also been estimated. The critical micelle concentrations of this drug were obtained from ultrasound velocity measurement by using recently developed least square fitting algorithm. The results are interpreted in the light of structure-making or structure-breaking effects of escitalopram oxalate in the mixtures. (author)

  18. Automated capillary GC/NPD assay for the determination in plasma of McN-5707, a potential antidepressant drug

    McN-5707 x HBr [trans-6-(2-chlorophenyl)-1,2,3,5,6,10b-hexa-hydropyrrolo[2,1-a]isoquinoline hydrobromide (1:1)] is a novel, potential antidepressant which is currently under pre-clinical evaluation. The present study reports the development of a sensitive and reproducible capillary gas chromatographic (GC) assay with nitrogen-phosphorus ionization detection (NPD) for McN-5707 in plasma. The assay includes a three step extraction as follows: McN-5707 and the internal standard (IS) are extracted from alkalinized plasma (1 mL) into hexane and back-extracted into 0.1 N HCl. Following alkalinization of the aqueous layer, McN-5707 and IS are re-extracted into hexane. The solvent is evaporated and the residue is reconstituted with 50 μL of a solution of 10% methanol in toluene. A 2.5 μL aliquot is injected into an HP 5880A capillary GC using the HP 7672A auto-sampler. Separation is accomplished using a 15 m x 0.32 mm i.d. DB-5 fused silica capillary column and temperature programming from 160 to 2000C at 100/min. Calibration curves are linear from 1 to 100 ng/mL. Accuracy and precision, expressed as relative deviation from the true value and coefficient of variation are 3H-norepinephrine uptake inhibition assay

  19. The theoretical investigation of solvent effects on the relative stability and 15N NMR shielding of antidepressant heterocyclic drug

    Tahan, Arezoo; Khojandi, Mahya; Salari, Ali Akbar


    The density functional theory (DFT) and Tomasi's polarized continuum model (PCM) were used for the investigation of solvent polarity and its dielectric constant effects on the relative stability and NMR shielding tensors of antidepressant mirtazapine (MIR). The obtained results indicated that the relative stability in the polar solvents is higher than that in non-polar solvents and the most stable structure was observed in the water at the B3LYP/6-311++G ( d, p) level of theory. Also, natural bond orbital (NBO) interpretation demonstrated that by increase of solvent dielectric constant, negative charge on nitrogen atoms of heterocycles and resonance energy for LP(N10) → σ* and π* delocalization of the structure's azepine ring increase and the highest values of them were observed in water. On the other hand, NMR calculations showed that with an increase in negative charge of nitrogen atoms, isotropic chemical shielding (σiso) around them increase and nitrogen of piperazine ring (N19) has the highest values of negative charge and σiso among nitrogen atoms. NMR calculations also represented that direct solvent effect on nitrogen of pyridine ring (N15) is more than other nitrogens, while its effect on N19 is less than other ones. Based on NMR data and NBO interpretation, it can be deduced that with a decrease in the negative charge on nitrogen atoms, the intramolecular effects on them decrease, while direct solvent effect increases.

  20. Drug: D08511 [KEGG MEDICUS

    Full Text Available D08511 Drug Setiptiline (INN) C19H19N 261.1518 261.3609 D08511.gif Antidepressant tetracyclic antidepress...47+148) Salivary secretion map07027 Antidepressants Target-based classification o

  1. Drug: D08257 [KEGG MEDICUS

    Full Text Available apeutic Chemical (ATC) classification [BR:br08303] N NERVOUS SYSTEM N06 PSYCHOANALEPTICS N06A ANTIDEPRESSANTS N06AX Other antidepress...ants N06AX06 Nefazodone D08257 Nefazodone (INN) USP drug

  2. Application of antidepressant drugs in the treatment of pregnancy and breastfeeding women%抗抑郁药在妊娠期及哺乳期妇女中的应用



    尽管抗抑郁药已广泛应用于抑郁发作的治疗,但抗抑郁药在妊娠期或哺乳期妇女中的应用,如针对该人群使用抗抑郁药应注意些什么和哪些药物使用相对安全等问题一直是临床关注的焦点.本文综合文献及笔者的临床经验综述上述相关问题.%Antidepressant drugs have been widely used in the treatment of depressive disorders. However, the application of antidepressant drugs used in the pregnancy and breastfeeding women has been a clinical concern. Based on literature and author's clinical experience, this review describes what attention should be paid when antidepressant drugs are used in the pregnancy and breastfeeding women and which drugs are relatively safer.

  3. Targeted proteins for diabetes drug design

    Type 2 diabetes mellitus is a common metabolism disorder characterized by high glucose in the bloodstream, especially in the case of insulin resistance and relative insulin deficiency. Nowadays, it is very common in middle-aged people and involves such dangerous symptoms as increasing risk of stroke, obesity and heart failure. In Vietnam, besides the common treatment of insulin injection, some herbal medication is used but no unified optimum remedy for the disease yet exists and there is no production of antidiabetic drugs in the domestic market yet. In the development of nanomedicine at the present time, drug design is considered as an innovative tool for researchers to study the mechanisms of diseases at the molecular level. The aim of this article is to review some common protein targets involved in type 2 diabetes, offering a new idea for designing new drug candidates to produce antidiabetic drugs against type 2 diabetes for Vietnamese people. (review)

  4. Drug: D07591 [KEGG MEDICUS

    Full Text Available D07591 Drug Bupropion (INN) C13H18ClNO 239.1077 239.7411 D07591.gif Antidepressant ...SYSTEM N06 PSYCHOANALEPTICS N06A ANTIDEPRESSANTS N06AX Other antidepressants N06A...atment Agents Smoking Cessation Agents Bupropion D07591 Bupropion (INN) Antidepressants Antidepressants, Oth

  5. Defining Patient Centric Pharmaceutical Drug Product Design.

    Stegemann, Sven; Ternik, Robert L; Onder, Graziano; Khan, Mansoor A; van Riet-Nales, Diana A


    The term "patient centered," "patient centric," or "patient centricity" is increasingly used in the scientific literature in a wide variety of contexts. Generally, patient centric medicines are recognized as an essential contributor to healthy aging and the overall patient's quality of life and life expectancy. Besides the selection of the appropriate type of drug substance and strength for a particular indication in a particular patient, due attention must be paid that the pharmaceutical drug product design is also adequately addressing the particular patient's needs, i.e., assuring adequate patient adherence and the anticipate drug safety and effectiveness. Relevant pharmaceutical design aspects may e.g., involve the selection of the route of administration, the tablet size and shape, the ease of opening the package, the ability to read the user instruction, or the ability to follow the recommended (in-use) storage conditions. Currently, a harmonized definition on patient centric drug development/design has not yet been established. To stimulate scientific research and discussions and the consistent interpretation of test results, it is essential that such a definition is established. We have developed a first draft definition through various rounds of discussions within an interdisciplinary AAPS focus group of experts. This publication summarizes the outcomes and is intended to stimulate further discussions with all stakeholders towards a common definition of patient centric pharmaceutical drug product design that is useable across all disciplines involved. PMID:27317470

  6. IC Treatment: Antidepressants

    ... in Combined Federal Campaign ICA Resources for Donors Social Media ... you first hear the name antidepressant you may think of a medicine used to treat depression. Did you know that antidepressants are also effective ...

  7. Evaluation of Antidepressant activity of Simvastatin, Lovastatin and Atorvastatin in Male Swiss Mice - An Experimental Study

    Gudadappanavar Anupama M


    Full Text Available Context: Depression is the commonest mood disorder, could also be secondary to a number of physical disorders. Pharmacological treatment of such co-morbidities is difficult. If statins show antidepressant activity that could appear to be better lipid-lowering agents as they provide additional benefits in cardiovascular disorders with co-morbidity like depression. Aims: To investigate the effect of simvastatin, lovastatin and atorvastatin for their antidepressant activity using forced swim test and tail suspension test on behavioral models of depression in male swiss mice. Design: Experimental Study Methods and Material: The in vivo antidepressant activity of simvastatin and lovastatin was studied using forced swim test and tail suspension test. The mice received the drug as per their weight and subjected for experimentation. Group mean immobility time was calculated in treated and control groups for comparison. Statistical analysis used: One-way analysis of variance (ANOVA followed by Bonferroni’s multiple comparison test. (P / 0.05 Results: Simvastatin and Lovastatin used in the present study showed significant antidepressant activity in both behavioral models of depression (p<0.05 while atorvastatin failed to show significant antidepressant action. Conclusion: The study suggests that the antidepressant activity of simvastatin and lovastatin, if could be extrapolated to clinical situations, appear to be better lipid-lowering agents as they provide additional benefits in cardiovascular disorders with co-morbidity like depression.

  8. Antidepressive interventions : On state and vulnerability of the brain

    Korf, J


    An attempt is made to relate drug and non-drug antidepressive interventions to brain processes. In the present context two concepts are proposed: vulnerability towards depressogenic factors and depression as a state of the brain. Accordingly, it is assumed that the current antidepressants make the b

  9. The effects of antidepressants on gastric ulcer

    Mehmet Latif Güneş


    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

  10. Design, Characterization, and Optimization of Controlled Drug Delivery System Containing Antibiotic Drug/s.

    Patel, Apurv; Dodiya, Hitesh; Shelate, Pragna; Shastri, Divyesh; Dave, Divyang


    The objective of this work was design, characterization, and optimization of controlled drug delivery system containing antibiotic drug/s. Osmotic drug delivery system was chosen as controlled drug delivery system. The porous osmotic pump tablets were designed using Plackett-Burman and Box-Behnken factorial design to find out the best formulation. For screening of three categories of polymers, six independent variables were chosen for Plackett-Burman design. Osmotic agent sodium chloride and microcrystalline cellulose, pore forming agent sodium lauryl sulphate and sucrose, and coating agent ethyl cellulose and cellulose acetate were chosen as independent variables. Optimization of osmotic tablets was done by Box-Behnken design by selecting three independent variables. Osmotic agent sodium chloride, pore forming agent sodium lauryl sulphate, and coating agent cellulose acetate were chosen as independent variables. The result of Plackett-Burman and Box-Behnken design and ANOVA studies revealed that osmotic agent and pore former had significant effect on the drug release up to 12 hr. The observed independent variables were found to be very close to predicted values of most satisfactory formulation which demonstrates the feasibility of the optimization procedure in successful development of porous osmotic pump tablets containing antibiotic drug/s by using sodium chloride, sodium lauryl sulphate, and cellulose acetate as key excipients. PMID:27610247

  11. Chronic treatment with the potential antidepressant drug rolipram: the effect on the behavioural responses to adrenergic and dopaminergic receptor agonists with some biochemical correlates

    We studied the effect of acute and chronic treatment with rolipram, a potential antidepressant drug, on the behavioural responses induced by adrenergic and dopaminergic receptor agonists in mice and rats, and on (3H)prazosin and (3H)dihydroalprenolol binding to cortical membranes and whole brain noradrenaline and dopamione utilization in rats. Chronic, but not acute, administration of rolipram potentiated a behavioural response mediated through central α1-adrenoceptors, attenuated an α2-adrenoceptor-mediated response and inhibited a β-adrenoceptor-mediated response. Neither treatment affected the behavioural response to dopaminergic stimulants. Repeated treatment with rolipram decreased the density of cortical (3H)dihydroalprenolol, but not (3H)prazosin binding sites, and reduced brain noradrenaline, but not dopamine utilization. These results suggest that chronic administration of rolipram induces the down-regulation of the central β- and α2-adrenoceptors and enhances the responsiveness of the central α1-adrenoceptors with no apparent changes in the α1-adrenoceptor density. (Author)

  12. Antidepressants modulate glycine action in rat hippocampus

    Chang, Hyun-Kyung; Kim, Khae Hawn; Kang, Ki-Woon; Kang, Yoo-Jin; Kim, Tae-Wook; Park, Hun-Kyung; Kim, Sung-Eun; Kim, Chang-Ju


    Antidepressants are drugs that relieve symptoms of depressive disorders. Fluoxetine, tianeptine, and milnacipran are different types of antidepressants, and they have widely been used for relieving of depression symptoms. In the present study, the effects of fluoxetine, tianeptine, and milnacipran on the glycine-induced ion current by nystatin-perforated patch clamp and on the amplitude of field potential in the hippocampal CA1 region by multichannel extracellular recording, MED64, system, we...

  13. Antidepressant prescribing in five European countries

    Abbing-Karahagopian, V; Huerta, C; Souverein, P C;


    PURPOSE: Drug utilization studies have applied different methods to various data types to describe medication use, which hampers comparisons across populations. The aim of this study was to describe the time trends in antidepressant prescribing in the last decade and the variation in the prevalen......-69% for depression respectively). CONCLUSION: Despite applying uniform methods, variations in the prevalence of antidepressant prescribing were obvious in the different populations. Database characteristics and clinical factors may both explain these variations....

  14. Influence of antidepressants on hemostasis.

    Halperin, Demian; Reber, Guido


    Antidepressants, particularly selective serotonin reuptake inhibitors (SSRIs), are widely used for the treatment of depression and anxious disorders. The observation that depression is an independent risk factor for cardiovascular mortality and morbidity in patients with ischemic heart disease, the assessment of the central role of serotonin in pathophysiological mechanisms of depression, and reports of cases of abnormal bleeding associated with antidepressant therapy have led to investigations of the influence of antidepressants on hemostasis markers. In this review, we summarize data regarding modifications of these markers, drawn from clinical studies and case reports. We observed an association between the type of antidepressant drug and the number of abnormal bleeding case reports, with or without modifications of hemostasis markers. Drugs with the highest degree of serotonin reuptake inhibition--fluoxetine, paroxetine, and sertraline--are more frequently associated with abnormal bleeding and modifications of hemostasis markers. The most frequent hemostatic abnormalities are decreased platelet aggregability and activity, and prolongation of bleeding time. Patients with a history of coagulation disorders, especially suspected or documented thrombocytopenia or platelet disorder, should be monitored in case of prescription of any serotonin reuptake inhibitor (SRI). Platelet dysfunction, coagulation disorder, and von Willebrand disease should be sought in any case of abnormal bleeding occurring during treatment with an SRI. Also, a non-SSRI antidepressant should be favored over an SSRI or an SRI in such a context. Considering the difficulty in performing platelet aggregation tests, which are the most sensitive in SRI-associated bleeding, and the low sensitivity of hemostasis tests when performed in case of uncomplicated bleeding in the general population, establishing guidelines for the assessment of SRI-associated bleeding complications remains a challenge. PMID

  15. Psychosocial work environment and antidepressant medication: a prospective cohort study

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


    antidepressant medication. METHODS: Information on all antidepressant drugs (AD) purchased at pharmacies from 1995 through 2006 was obtained for a cohort of 21,129 Danish public service workers that participated in work climate surveys carried out during the period 2002-2005. Individual self-reports of...... alone. None of the measured psychosocial work environment factors were consistently related to prescription of antidepressant drugs during the follow-up period. CONCLUSION: The study does not indicate that a poor psychosocial work environment among public service employees is related to prescription of...... antidepressant pharmaceuticals. These findings need cautious interpretation because of lacking individual exposure assessments Udgivelsesdato: 2009...

  16. An algorithm to identify antidepressant users with a diagnosis of depression from prescription data.

    Gardarsdottir, H.; Egberts, T.C.G.; Dijk, L. van; Sturkenboom, M.; Heerdink, E.R.


    Background: Investigating depression treatment outcomes in prescription databases is problematic when information on indication for antidepressant prescriptions is unavailable. Objectives: To develop and validate an algorithm using prescription data to identify antidepressant drug users who suffer f

  17. Antidepressants and dementia

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


    Denmark during a period from 1995 to 2005. RESULTS: Persons who purchased antidepressants once (N=687,552) had an increased rate of dementia compared to persons unexposed to antidepressants (N=779,831). Nevertheless, the rate of dementia changed over time; thus during the initial prescription periods the......-SSRI antidepressants and older antidepressants). All findings were replicated in sub-analyses with Alzheimer's disease as outcome. LIMITATIONS: Methodological reasons for the findings cannot be excluded due to the non-randomized nature of data. CONCLUSIONS: Continued long-term antidepressant treatment was associated...

  18. Application analysis on antidepressant drugs of 22 hospitals in Beijing from 2010 to 2014%2010-2014年北京地区22家医院抗抑郁药物应用研究

    陈瑞玲; 赵志刚; 王雅杰


    Objective:To investigate the status and the development tendency of clinical application of antidepressants in Beijing area, and provide evidence for rational usage of antidepressants. Methods: Using the analytical method of the deifned daily dose (DDD) recommended by WHO, consumption sum, DDDs and deifned daily cost (DDC) of antidepressants in 22 hospitals in Beijing area from 2010 to 2014 were analyzed retrospectively.Results:Within 5 years, 19 kinds of antidepressants were used. DDDs and consumption sum of antidepressants showed increased trend year by year in 22 hospital of Beijing. Average annual growth rates of consumption sum and DDDs were 14.79%and 16.47%respectively. DDC remained unchanged. Selective serotonin reuptake inhibitors (SSRIs), selective serotonin and norepinephrine reuptake inhibitors (sSNRIs) used predominantly. The consumption sum of SSRIs and sSNRIs accounted for over 60%–70%and 20%among the total consumption sum of antidepressant drugs respectively. The top 3 drugs in DDDs were paroxetine, lfupentixol and melitracen compound tablets, citalopram or escitalopram. Conclusion:Antidepressant drugs played an increasingly important role in clinical treatment. New types of antidepressants, such as SSRIs and sSNRIs, have already become the ifrst-line antidepressants in clinic practice.%目的:了解北京地区抗抑郁药物使用情况,为临床合理用药提供参考。方法:采用回顾性分析方法,以WHO推荐的限定日剂量(DDD)作为药物利用研究评价单位,对2010–2014年北京地区22家医院抗抑郁药物的销售金额、DDDs以及DDC进行统计分析。结果:2010–2014年,北京地区22家医院共使用了19种抗抑郁药物;抗抑郁药物的用药金额和DDDs均呈增长趋势;用药金额和DDDs年均增幅分别为14.79%和16.47%;各品种各年度的DDC保持不变。SSRIs和sSNRIs分别占用药金额的60%~70%和20%。DDDs排序前3位是帕罗西汀、氟哌噻吨/美利曲辛复

  19. Antidepressants and dementia


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

  20. Antidepressant medications and osteoporosis

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


    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...... 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...

  1. Comparison of the antidepressant effects of venlafaxine and dosulepin in a naturalistic setting

    Bukh, Jens Drachmann; Jørgensen, Martin Balslev; Dam, Henrik;


    The relative efficacy of the various classes of antidepressants has not been established. Observational studies in naturalistic settings are important in evaluating treatment outcomes with antidepressants, since controlled clinical trials include only a minority of patients present in clinical...... practice. This study sought to evaluate in a naturalistic setting the treatment outcomes of dosulepin and venlafaxine for patients with depressive episodes. At the university hospital in Copenhagen, Denmark, between 1998 and early 2001, the first-line treatment for psychiatric inpatients with depression...... because of an underpowered design) after replacing dosulepin with venlafaxine as first-line drug for depression in a naturalistic inpatient setting....

  2. Counting on natural products for drug design

    Rodrigues, Tiago; Reker, Daniel; Schneider, Petra; Schneider, Gisbert


    Natural products and their molecular frameworks have a long tradition as valuable starting points for medicinal chemistry and drug discovery. Recently, there has been a revitalization of interest in the inclusion of these chemotypes in compound collections for screening and achieving selective target modulation. Here we discuss natural-product-inspired drug discovery with a focus on recent advances in the design of synthetically tractable small molecules that mimic nature's chemistry. We highlight the potential of innovative computational tools in processing structurally complex natural products to predict their macromolecular targets and attempt to forecast the role that natural-product-derived fragments and fragment-like natural products will play in next-generation drug discovery.

  3. Antidepressant mechanism of ketamine: perspective from preclinical studies

    Scheuing, Lisa; Chiu, Chi-Tso; Liao, Hsiao-Mei; Chuang, De-Maw


    A debilitating mental disorder, major depressive disorder is a leading cause of global disease burden. Existing antidepressant drugs are not adequate for the majority of depressed patients, and large clinical studies have demonstrated their limited efficacy and slow response onset. Growing evidence of low-dose ketamine's rapid and potent antidepressant effects offers strong potential for future antidepressant agents. However, ketamine has considerable drawbacks such as its abuse potential, ps...

  4. Antidepressants are selective serotonin neuronal reuptake inhibitors: 40-year history

    D. S. Danilov


    Full Text Available The paper presents historical prerequisites for designing antidepressants from a group of selective serotonin neuronal reuptake inhibitors (SSRIs: to determine a lower serotonin concentration in the different tissues of depressed patients; to establish a higher serotonin concentration in the treatment of depressed patients with tricyclic antidepressants, and to formulate the serotonergic theory of depression. It also provides a consecutive account of the history of clinical introduction of individual SSRI representatives, such as fluoxetine, zimelidine, fluvoxamine, indalpine, citalopram, sertraline, paroxetine, and escitalopram. There are data from the history of studying the mechanism of SSRI action: from the theory of the importance of an increase in the concentration of serotonin in the synaptic cleft to the current understanding of complex successive intracellular rearrangements at the level of the postsynaptic neuron. The history of studying the efficacy of SSRIs in treating depression is considered in detail. Emphasis is laid on the reasons for a paradoxical difference in the evaluations of the efficiency of therapy with SSRIs versus other groups of antidepressants at different developmental stages of psychopharmacology. The role of marketing technologies in disseminating the data on the efficacy of this or that group of antidepressants is described. The practical significance of differences in individual SSRI representatives (the potency of serotonin uptake inhibition; the degree of selectivity and activity against the serotonergic system; the likelihood of an unfavorable pharmacokinetic interaction with other drugs; the half-life of elimination; the quickness of achieving a therapeutic dose is analyzed. Whether it is possible and reasonable to differentially choose different SSRI representatives in the treatment of depressions at the present stage is discussed. The authors state their belief that researches should be continued to

  5. Drug: D08222 [KEGG MEDICUS

    Full Text Available D08222 Drug Milnacipran (INN) C15H22N2O 246.1732 246.348 D08222.gif Antidepressant ...rgic synapse map07027 Antidepressants map07234 Neurotransmitter transporter inhib...S N06A ANTIDEPRESSANTS N06AX Other antidepressants N06AX17 Milnacipran D08222 Milnacipran (INN) USP drug cla

  6. Accessible haptic technology for drug design applications.

    Zonta, Nicola; Grimstead, Ian J; Avis, Nick J; Brancale, Andrea


    Structure-based drug design is a creative process that displays several features that make it closer to human reasoning than to machine automation. However, very often the user intervention is limited to the preparation of the input and analysis of the output of a computer simulation. In some cases, allowing human intervention directly in the process could improve the quality of the results by applying the researcher intuition directly into the simulation. Haptic technology has been previously explored as a useful method to interact with a chemical system. However, the need of expensive hardware and the lack of accessible software have limited the use of this technology to date. Here we are reporting the implementation of a haptic-based molecular mechanics environment aimed for interactive drug design and ligand optimization, using an easily accessible software/hardware combination. PMID:19048316

  7. New generation of antidepressants in pregnant women

    Ladan Kashani


    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

  8. The VMAT-2 inhibitor tetrabenazine affects effort-related decision making in a progressive ratio/chow feeding choice task: reversal with antidepressant drugs.

    Patrick A Randall

    Full Text Available Behavioral activation is a fundamental feature of motivation, and organisms frequently make effort-related decisions based upon evaluations of reinforcement value and response costs. Furthermore, people with major depression and other disorders often show anergia, psychomotor retardation, fatigue, and alterations in effort-related decision making. Tasks measuring effort-based decision making can be used as animal models of the motivational symptoms of depression, and the present studies characterized the effort-related effects of the vesicular monoamine transport (VMAT-2 inhibitor tetrabenazine. Tetrabenazine induces depressive symptoms in humans, and also preferentially depletes dopamine (DA. Rats were assessed using a concurrent progressive ratio (PROG/chow feeding task, in which they can either lever press on a PROG schedule for preferred high-carbohydrate food, or approach and consume a less-preferred lab chow that is freely available in the chamber. Previous work has shown that the DA antagonist haloperidol reduced PROG work output on this task, but did not reduce chow intake, effects that differed substantially from those of reinforcer devaluation or appetite suppressant drugs. The present work demonstrated that tetrabenazine produced an effort-related shift in responding on the PROG/chow procedure, reducing lever presses, highest ratio achieved and time spent responding, but not reducing chow intake. Similar effects were produced by administration of the subtype selective DA antagonists ecopipam (D1 and eticlopride (D2, but not by the cannabinoid CB1 receptor neutral antagonist and putative appetite suppressant AM 4413, which suppressed both lever pressing and chow intake. The adenosine A2A antagonist MSX-3, the antidepressant and catecholamine uptake inhibitor bupropion, and the MAO-B inhibitor deprenyl, all reversed the impairments induced by tetrabenazine. This work demonstrates the potential utility of the PROG/chow procedure as a

  9. Evaluation of the binding of the radiolabeled antidepressant drug, {sup 18}F-fluoxetine in the rodent brain: an in vitro and in vivo study

    Mukherjee, Jogeshwar E-mail:; Das, Malay K.; Yang Zhiying; Lew, Robert


    We have developed {sup 18}F-fluoxetine as a radiotracer analog of the antidepressant drug fluoxetine (Prozac). In vitro saturation experiments of {sup 18}F-fluoxetine were carried out on rat midbrain tissue and citalopram was used for measuring nonspecific binding. A saturation curve for the binding of {sup 18}F-fluoxetine was not obtained. Even when fluoxetine (10 {mu}M) was used for measurements of nonspecific binding, a saturation curve was difficult to obtain. Other compounds, such as deprenyl, clorgyline, amphetamine, and reserpine were also not able to reduce the binding of {sup 18}F-fluoxetine. Ex vivo autoradiographic experiments with {sup 18}F-fluoxetine did not reveal any specific uptake in various brain regions. In vivo administration of {sup 18}F-fluoxetine in rats showed similar uptake in all the brain regions with little regional selectivity. A subcellular analysis of rat brain tissue after intravenous (IV) administration of {sup 18}F-fluoxetine indicated significant amounts of binding in mitochondria and synaptosomes. In summary, in vitro experiments with {sup 18}F-fluoxetine indicate little specific binding. Binding to the serotonin transporter was not identifiable. High nonspecific binding of the tracer resulting from its subcellular nature in the brain masks the ability to detect binding to the serotonin uptake sites in vivo. These findings indicate that a large portion of the binding of {sup 18}F-fluoxetine in rat brains is subcellular and clears slowly out of the cells. Other sites, such as monoamine oxidase, may also play a significant role in the action of fluoxetine.

  10. Evaluation of the binding of the radiolabeled antidepressant drug, 18F-fluoxetine in the rodent brain: an in vitro and in vivo study

    We have developed 18F-fluoxetine as a radiotracer analog of the antidepressant drug fluoxetine (Prozac). In vitro saturation experiments of 18F-fluoxetine were carried out on rat midbrain tissue and citalopram was used for measuring nonspecific binding. A saturation curve for the binding of 18F-fluoxetine was not obtained. Even when fluoxetine (10 μM) was used for measurements of nonspecific binding, a saturation curve was difficult to obtain. Other compounds, such as deprenyl, clorgyline, amphetamine, and reserpine were also not able to reduce the binding of 18F-fluoxetine. Ex vivo autoradiographic experiments with 18F-fluoxetine did not reveal any specific uptake in various brain regions. In vivo administration of 18F-fluoxetine in rats showed similar uptake in all the brain regions with little regional selectivity. A subcellular analysis of rat brain tissue after intravenous (IV) administration of 18F-fluoxetine indicated significant amounts of binding in mitochondria and synaptosomes. In summary, in vitro experiments with 18F-fluoxetine indicate little specific binding. Binding to the serotonin transporter was not identifiable. High nonspecific binding of the tracer resulting from its subcellular nature in the brain masks the ability to detect binding to the serotonin uptake sites in vivo. These findings indicate that a large portion of the binding of 18F-fluoxetine in rat brains is subcellular and clears slowly out of the cells. Other sites, such as monoamine oxidase, may also play a significant role in the action of fluoxetine

  11. Drug: D00563 [KEGG MEDICUS

    Full Text Available 265.3529 D00563.gif Antidepressant Same as: C07570 Therapeutic category: 1179 ATC code: N06AX11 5-HT2-recep...6 [HSA:1565], CYP3A4 [HSA:1576] map07027 Antidepressants Therapeutic category of ...ANTIDEPRESSANTS N06AX Other antidepressants N06AX11 Mirtazapine D00563 Mirtazapine (JAN/USAN/INN) USP drug c...lassification [BR:br08302] Antidepressants Antidepressants, Other Mirtazapine D00563 Mirtazapine (JAN/USAN/I

  12. Activation of a ventral hippocampus-medial prefrontal cortex pathway is both necessary and sufficient for an antidepressant response to ketamine.

    Carreno, F R; Donegan, J J; Boley, A M; Shah, A; DeGuzman, M; Frazer, A; Lodge, D J


    A single sub-anesthetic dose of ketamine exerts rapid and sustained antidepressant effects. Here, we examined the role of the ventral hippocampus (vHipp)-medial prefrontal cortex (mPFC) pathway in ketamine's antidepressant response. Inactivation of the vHipp with lidocaine prevented the sustained, but not acute, antidepressant-like effect of ketamine as measured by the forced swim test (FST). Moreover, optogenetic as well as pharmacogenetic specific activation of the vHipp-mPFC pathway using DREADDs (designer receptors exclusively activated by designer drugs) mimicked the antidepressant-like response to ketamine; importantly, this was pathway specific, in that activation of a vHipp to nucleus accumbens circuit did not do this. Furthermore, optogenetic inactivation of the vHipp/mPFC pathway at the time of FST completely reversed ketamine's antidepressant response. In addition, we found that a transient increase in TrkB receptor phosphorylation in the vHipp contributes to ketamine's sustained antidepressant response. These data demonstrate that activity in the vHipp-mPFC pathway is both necessary and sufficient for the antidepressant-like effect of ketamine. PMID:26619811

  13. 我院2007-2011年抗抑郁药物应用情况分析%Analysis of the utilization of antidepressant drug in our hospital during 2007-2011

    肖林; 成孝林


      目的:通过分析我院抗抑郁药使用特点,了解我院抗抑郁药物的应用现状,分析用药特点,预测用药趋势,为促进临床合理用药提供参考.方法:采用回顾性分析方法,对我院2007-2011年抗抑郁药物的销售金额、用药频度(defined daily dose, DDDs)和日均费用(defined daily cost, DDC)等进行统计、分析.结果:新型药物的使用量逐年上升,5年销售金额增长2.2倍,DDDs增长1.89倍;三环类抗抑郁药(TCAs)类药物使用量则逐年下降,5年销售金额下降近40%,DDDs下降近30%.抗抑郁药物的DDC稳中有降,新型药物的DDC是TCAs类药物的10倍.结论:我院抗精神病药物应用基本合理.选择性5-羟色胺再摄取抑制剂(SSRIs)类药物使用的品种最多,使用份额最大;SNRIs类药物呈现快速增长;更多使用国产药物能有效降低抗抑郁药物的DDC.%  Objective:To understand the application status of the antidepressants in our hospital, analysis of drug characteristics, forecast of medication trends so as to provide a reference for the promotion of rational clinical use of drugs. Methods:The sales of antidepressant,defined daily dose(DDDs)and defined daily cost(DDC)in our hospital during 2007-2011 were statistically analyzed by retrospective analysis. Results:The use of new classes of drugs increased year by year and the sales increased by 2.2 times in five years, and DDDs increased by 1.89 times. Tricyclic antidepressants(TCAs)drugs has been declining and five-year sales of TCAs and DDDs have dropped by nearly 40%and 30%, respectively. DDC of antidepressant drugs is flat to down while DDC of the new drug increases 10 times than that of the TCAs drugs. Conclusion:The application of antipsychotics in our hospital is reasonable. Selective 5-serotonin reuptake inhibitors(SSRIs)class of drugs were used in the most varieties and largest share and the SNRIs drugs showed a rapid growth. A great use of domestic drug can effectively

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

    Caroline Ann Browne


    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

  15. Antidepressants modulate glycine action in rat hippocampus.

    Chang, Hyun-Kyung; Kim, Khae Hawn; Kang, Ki-Woon; Kang, Yoo-Jin; Kim, Tae-Wook; Park, Hun-Kyung; Kim, Sung-Eun; Kim, Chang-Ju


    Antidepressants are drugs that relieve symptoms of depressive disorders. Fluoxetine, tianeptine, and milnacipran are different types of antidepressants, and they have widely been used for relieving of depression symptoms. In the present study, the effects of fluoxetine, tianeptine, and milnacipran on the glycine-induced ion current by nystatin-perforated patch clamp and on the amplitude of field potential in the hippocampal CA1 region by multichannel extracellular recording, MED64, system, were studied. In the present results, fluoxetine, tianeptine, and milnacipran reduced glycine-induced ion current in the hippocampal CA1 neurons in nystatin-perforated patch clamp method. These drugs enhanced the amplitude of the field potential in the hippocampal CA1 region in MED64 system. These results suggest that antidepressants may increase neuronal activity by enhancing field potential through inhibition on glycine-induced ion current. PMID:26730381

  16. Phytosterols and anabolic agents versus designer drugs

    Brabander, H.F. de [Ghent University, Faculty of Veterinary Medicine, Research group of Veterinary Public Health and Zoonoses, Laboratory of Chemical Analysis, Salisburylaan 133, B-9820 Merelbeke (Belgium)]. E-mail:; Verheyden, K. [Ghent University, Faculty of Veterinary Medicine, Research group of Veterinary Public Health and Zoonoses, Laboratory of Chemical Analysis, Salisburylaan 133, B-9820 Merelbeke (Belgium); Mortier, V. [Ghent University, Faculty of Veterinary Medicine, Research group of Veterinary Public Health and Zoonoses, Laboratory of Chemical Analysis, Salisburylaan 133, B-9820 Merelbeke (Belgium); Le Bizec, B. [LABERCA, Ecole Nationale Veterinaire de Nantes, BP 50707, F-44087 Nantes Cedex 03 (France); Verbeke, W. [Ghent University, Department of Agricultural Economics, Coupure links 653, B-9000 Ghent (Belgium); Courtheyn, D. [Federal Feed and Food Laboratory, Braemkasteelstraat 59, B-9050 Ghentbruges (Belgium); Noppe, H. [Ghent University, Faculty of Veterinary Medicine, Research group of Veterinary Public Health and Zoonoses, Laboratory of Chemical Analysis, Salisburylaan 133, B-9820 Merelbeke (Belgium)


    Cholesterol is a well-known component in fats of animal origin and it also is the precursor of natural hormones. Phytosterols appear in plants and only differ slightly in structure from cholesterol. An important difference however is the low absorption in the gut of phytosterols and their saturated derivatives, the phytostanols. As a result, there is time for all kind of reactions in faecal material inside and outside of the gut. Determination of the abuse of natural hormones may be based on gas chromatography-combustion-isotope ratio mass spectrometry (GC-C-IRMS). Abuse of natural hormones changes the {sup 13}C/{sup 12}C ratio of some metabolites during a relatively long time. The formation of (natural) hormones in the gut may interfere with this method. Designer drugs are mainly known from sports doping. In animal fattening, designer drugs may be used as well. Small changes in the structure of (natural) hormones may lead to a new group of substances asking for new strategies for their detection and the constatation of their abuse.

  17. Phytosterols and anabolic agents versus designer drugs

    Cholesterol is a well-known component in fats of animal origin and it also is the precursor of natural hormones. Phytosterols appear in plants and only differ slightly in structure from cholesterol. An important difference however is the low absorption in the gut of phytosterols and their saturated derivatives, the phytostanols. As a result, there is time for all kind of reactions in faecal material inside and outside of the gut. Determination of the abuse of natural hormones may be based on gas chromatography-combustion-isotope ratio mass spectrometry (GC-C-IRMS). Abuse of natural hormones changes the 13C/12C ratio of some metabolites during a relatively long time. The formation of (natural) hormones in the gut may interfere with this method. Designer drugs are mainly known from sports doping. In animal fattening, designer drugs may be used as well. Small changes in the structure of (natural) hormones may lead to a new group of substances asking for new strategies for their detection and the constatation of their abuse

  18. Drug: D08288 [KEGG MEDICUS

    Full Text Available D08288 Drug Nortriptyline (INN); Nortrilen (TN) C19H21N 263.1674 263.3767 D08288.gif Antidepress...ant, tricyclic Same as: C07274 ATC code: N06AA10 Tricyclic antidepressants serotonin transporte... Serotonergic synapse Enzyme: CYP2D6 [HSA:1565] Genomic biomarker: CYP2D6 [HSA:1565] map07027 Antidepress... D08288 Nortriptyline (INN) USP drug classification [BR:br08302] Antidepressants Tricyclics Nortriptyline D0

  19. Drug: D07727 [KEGG MEDICUS

    Full Text Available D07727 Drug Clomipramine (INN); Anafranil (TN) C19H23ClN2 314.155 314.8523 D07727.gif Antidepress...ant, tricyclic Same as: C06918 ATC code: N06AA04 Tricyclic antidepressants serotonin norepinep...YP inhibition: CYP2D6 [HSA:1565] map07027 Antidepressants map07234 Neurotransmitter transporter inhibitors A...amine D07727 Clomipramine (INN) USP drug classification [BR:br08302] Antidepressants Tricyclics Clomipramine

  20. Drug: D07793 [KEGG MEDICUS

    Full Text Available D07793 Drug Desvenlafaxine (INN) C16H25NO2 263.1885 263.3752 D07793.gif Antidepress...ynapse CYP inhibition: CYP2D6 [HSA:1565] map07027 Antidepressants map07234 Neurot...S SYSTEM N06 PSYCHOANALEPTICS N06A ANTIDEPRESSANTS N06AX Other antidepressants N06AX23 Desvenlafaxine D07793... Desvenlafaxine (INN) USP drug classification [BR:br08302] Antidepressants SSRIs/

  1. Drug: D00394 [KEGG MEDICUS

    Full Text Available D00394 Drug Trimipramine (USAN/INN) C20H26N2 294.2096 294.4338 D00394.gif Antidepress...ant ATC code: N06AA06 Tricyclic antidepressants noradrenalin transporter inhibitor [HSA:6530] [KO:K05035];...HSA:1565] Genomic biomarker: CYP2D6 [HSA:1565] map07027 Antidepressants map07234 ...06AA06 Trimipramine D00394 Trimipramine (USAN/INN) USP drug classification [BR:br08302] Antidepress

  2. Drug: D07448 [KEGG MEDICUS

    Full Text Available D07448 Drug Amitriptyline (INN); Laroxyl (TN) C20H23N 277.1831 277.4033 D07448.gif Antidepress...ant, tricyclic Same as: C06824 ATC code: N06AA09 Tricyclic antidepressants serotonin transporter ...44], CYP3A4 [HSA:1576] Genomic biomarker: CYP2D6 [HSA:1565] map07027 Antidepressants map07048 Antimigraines ...USP drug classification [BR:br08302] Antidepressants Tricyclics Amitriptyline D07448 Amitriptyline (INN) Tar

  3. 我院2014年抗抑郁药应用分析%Analysis of Antidepressant Drugs Application in Our Hospital During 2014



    目的:分析我院抗抑郁药的用药情况,促进临床合理应用。方法对我院2014年抗抑郁药的销售金额、用药频度( DDDs)、日均费用(DDC)等进行统计分析。结果我院抗抑郁药销售金额排序列前3的是氟哌噻吨美利曲辛片、米氮平(派迪生)、氟西汀;DDDs排序列前3位的是氟哌噻吨美利曲辛片、米氮平(派迪生)、帕罗西汀。结论说明我院抗抑郁药使用合理,新型的抗抑郁药物在临床上得到了广泛应用,符合抗抑郁药的应用趋势。%ABSTRACT:OBJECTIVE To analyze the application of antidepressant durgs in our hospital and provide refer -ence for clinical rational administration.METHODS Antidepressant durgs used in our hospital during in 2014 were performed the statistical analysis in respect of consumption sum ,DDDs,DDC etc.RESULTS The top 3 consump-tion sum of antidepressant durgs included flupentixol melitmcen , mirtazapin fluoxetine;the top 3 DDDs included flu-pentixol melitmcen ,mirtazapin ,paroxetine.CONCLUSION\\ The application of antidepressant durgs in our hospital is rational .New-type antidepressant durgs were widely used in the clinic and consistent with the trend of their ap -plication.

  4. Drug: D00812 [KEGG MEDICUS

    Full Text Available 55 302.8416 D00812.gif Antidepressant ATC code: N06AA01 Tricyclic antidepressants serotonin transporter inhi...1565] Genomic biomarker: CYP2D6 [HSA:1565] map07027 Antidepressants map07234 Neur...01 Desipramine D00812 Desipramine hydrochloride (JAN/USP) USP drug classification [BR:br08302] Antidepress

  5. Drug: D08472 [KEGG MEDICUS

    Full Text Available D08472 Drug Reboxetine (INN); Edronax (TN) C19H23NO3 313.1678 313.3908 D08472.gif Antidepress...hibitor [HSA:6530] [KO:K05035] map07027 Antidepressants map07234 Neurotransmitter transporter inhibitors Ana...06 PSYCHOANALEPTICS N06A ANTIDEPRESSANTS N06AX Other antidepressants N06AX18 Reboxetine D08472 Reboxetine (I

  6. Drug: D07872 [KEGG MEDICUS

    Full Text Available D07872 Drug Dosulepin (INN); Dothiepin; Dothep (TN) C19H21NS 295.1395 295.4417 D07872.gif Antidepress...ant, trycyclic ATC code: N06AA16 Tricyclic antidepressants serotonin transporter inhibitor... [HSA:6532] [KO:K05037]; noradrenalin transporter inhibitor [HSA:6530] [KO:K05035] map07027 Antidepressants

  7. Drug: D02408 [KEGG MEDICUS

    Full Text Available 06 410.506 D02408.gif Antidepressant Same as: C14029 Therapeutic category: 1174 ATC code: N06AA06 Tricyclic antidepress...5] Genomic biomarker: CYP2D6 [HSA:1565] map07027 Antidepressants map07234 Neurotransmitter transporter inhib...6AA06 Trimipramine D02408 Trimipramine maleate (JAN/USAN) USP drug classification [BR:br08302] Antidepress

  8. Synthesis of the Commercial Antidepressant Moclobemide

    More, Jesse D.


    An experiment for the undergraduate organic chemistry laboratory is described in which students synthesize the commercial antidepressant drug moclobemide, marketed under the trade name Manerix. This one-step synthesis starts from commercially available material and produces moclobemide in high yield. The product is initially isolated as its…

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

    Nguyen, Linda; Matsumoto, Rae R


    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. PMID:25804358

  10. Hippocampal Neurogenesis, Depressive Disorders, and Antidepressant Therapy

    Eleni Paizanis


    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.

  11. 21 CFR 316.29 - Revocation of orphan-drug designation.


    ... 21 Food and Drugs 5 2010-04-01 2010-04-01 false Revocation of orphan-drug designation. 316.29... (CONTINUED) DRUGS FOR HUMAN USE ORPHAN DRUGS Designation of an Orphan Drug § 316.29 Revocation of orphan-drug designation. (a) FDA may revoke orphan-drug designation for any drug if the agency finds that: (1) The...

  12. Exposure to antidepressants during pregnancy--prevalences and outcomes

    Jimenez-Solem, Espen


    still conflicting. The main challenge is how to discern between the effects of the drug and the effect of the depression itself. We approached this dire problem conducting a nation-wide register based study analyzing the relation between use of antidepressants during pregnancy and the risk of congenital...... malformations and perinatal mortality. We performed our analysis with focus on women pausing treatment before pregnancy to account for special characteristics associated with women redeeming a prescription for an antidepressant. Furthermore, we reported prevalences of antidepressant use, in Denmark, in relation...... in utero to an antidepressant in any of the three trimesters. The overall conclusion is that antidepressants are not associated with increased risks of congenital malformations and perinatal mortality. However, we cannot rule out a possible causal relation, and treatment must therefore be based on an...

  13. Evaluation of antidepressant activity of tramadol in mice

    Tayal Vandana


    Full Text Available Objective: To evaluate antidepressant like effect of tramadol in mice. Materials and Methods: Tramadol was administered at three different doses (10,20 and 40 mg/kg,i.p once daily for 7 days to Swiss albino mice of either sex. The immobility period of control and drug treated mice were recorded in tail suspension test (TST.The antidepressant effect of tramadol was compared to that of fluoxetine (20 mg/kg, i.p, administered for seven days. Results: Tramadol produced significant antidepressant effect at all the doses, as indicated by reduction in immobility times as compared to control. The efficacy of tramadol at doses of 20 and 40 mg/kg was comparable with that of fluoxetine. Tramadol at 10 mg/kg dose showed significantly less antidepressant activity compared to fluoxetine. Conclusion: The results of the present study indicate antidepressant like activity of tramadol.

  14. Molecular Rift: Virtual Reality for Drug Designers.

    Norrby, Magnus; Grebner, Christoph; Eriksson, Joakim; Boström, Jonas


    Recent advances in interaction design have created new ways to use computers. One example is the ability to create enhanced 3D environments that simulate physical presence in the real world--a virtual reality. This is relevant to drug discovery since molecular models are frequently used to obtain deeper understandings of, say, ligand-protein complexes. We have developed a tool (Molecular Rift), which creates a virtual reality environment steered with hand movements. Oculus Rift, a head-mounted display, is used to create the virtual settings. The program is controlled by gesture-recognition, using the gaming sensor MS Kinect v2, eliminating the need for standard input devices. The Open Babel toolkit was integrated to provide access to powerful cheminformatics functions. Molecular Rift was developed with a focus on usability, including iterative test-group evaluations. We conclude with reflections on virtual reality's future capabilities in chemistry and education. Molecular Rift is open source and can be downloaded from GitHub. PMID:26558887

  15. Bioinformatics in cancer therapy and drug design

    One of the mechanisms of external signal transduction (ionizing radiation, toxicants, stress) to the target cell is the existence of membrane and intracellular proteins with intrinsic tyrosine kinase activity. No wonder that etiology of malignant growth links to abnormalities in signal transduction through tyrosine kinases. The epidermal growth factor receptor (EGFR) tyrosine kinases play fundamental roles in development, proliferation and differentiation of tissues of epithelial, mesenchymal and neuronal origin. There are four types of EGFR: EGF receptor (ErbB1/HER1), ErbB2/Neu/HER2, ErbB3/HER3 and ErbB4/HER4. Abnormal expression of EGFR, appearance of receptor mutants with changed ability to protein-protein interactions or increased tyrosine kinase activity have been implicated in the malignancy of different types of human tumors. Bioinformatics is currently using in investigation on design and selection of drugs that can make alterations in structure or competitively bind with receptors and so display antagonistic characteristics. (authors)


    Anupam Ghosh


    Full Text Available Each and every biological function in living organism happens as a result of protein-protein interactions. The diseases are no exception to this. Identifying one or more proteins for a particular disease and then designing a suitable chemical compound (known as drug to destroy these proteins has been an interesting topic of research in bio-informatics. In previous methods, drugs were designed using only seven chemical components and were represented as a fixedlength tree. But in reality, a drug contains many chemical groups collectively known as pharmacophore. Moreover, the chemical length of the drug cannot be determined before designing the drug.

  17. [Antidepressants and their onset of action: a major clinical, methodological and pronostical issue].

    Gourion, D


    substance abuse. In addition, the magnitudes of the size-effects of antidepressants versus placebo are clearly higher in severely depressed patients. Fourth, specific items on depression rating scales may induce greater antidepressant/placebo differences. For instance, the 17-item HAM-D contains three questions pertaining to sleep. It questions the fact that earlier onset may appear not only via a specific antidepressant effect but also via a non-specific effect on anxiety, sleep, physical pain or other accessory symptoms. Thus, current data do not clearly support claims that one drug reduces the symptoms of depression faster than another, though the existing literature suggests that escitalopram displays some superiority in terms of rapidity of action. Given the potential benefits of early-acting antidepressant treatments, the possibility of superior speed of onset of escitalopram presented here merits further study in adequately designed, prospective clinical trials. A definitive demonstration of early onset of action awaits the results of appropriately designed and powered clinical studies, which may include (1) a prospective definition of early onset of action, (2) more focused assessments of core emotional symptoms and cognitive deficits of depression by using specific and sensitive tools, (3) a data-analytic approach capable of capturing the dynamic nature of symptomatic change (for example, survival analysis), and (4) strategies to minimize biases and heterogeneity of response. PMID:18514154

  18. Nanogel Carrier Design for Targeted Drug Delivery

    Eckmann, D.M.; Composto, R. J.; Tsourkas, A; Muzykantov, V. R.


    Polymer-based nanogel formulations offer features attractive for drug delivery, including ease of synthesis, controllable swelling and viscoelasticity as well as drug loading and release characteristics, passive and active targeting, and the ability to formulate nanogel carriers that can respond to biological stimuli. These unique features and low toxicity make the nanogels a favorable option for vascular drug targeting. In this review, we address key chemical and biological aspects of nanoge...

  19. Effects of calcium channel blocker, nifedipine, on antidepressant activity of fluvoxamine, venlafaxine and tianeptine in mice

    SHARMA, Ashok K.; Anjan Khadka; Navdeep Dahiya


    Background: Cardiovascular diseases are commonly associated with depression. Calcium channel blockers (CCBs) form commonly used group of drugs for the treatment of a number of cardiovascular diseases. Nifedipine, a CCB, has been shown to possess antidepressant activity and potentiate antidepressant activity of imipramine and sertraline, however, literature on its interaction with newer antidepressant drugs such as fluvoxamine, venlafaxine and tianeptine is limited. Hence, the present study wa...

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

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


    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. PMID:24652522

  1. Antipsychotics as antidepressants.

    Roberts, Rona Jeannie; Lohano, Kavita K; El-Mallakh, Rif S


    Three second-generation antipsychotic (SGA) agents have received FDA approval for adjunctive treatment, to antidepressant, of major depressive disorder: quetiapine, aripiprazole, and olanzapine. Additionally, quetiapine and lurasidone have been approved for the treatment of bipolar depression. There are data suggesting that quetiapine is effective for major depressive disorder as monotherapy. These agents are effective for depression only at subantipsychotic doses. Receptor profiles predict that all SGA will have anxiolytic effects as subantipsychotic doses but that all will be dysphorogenic at full antipsychotic doses (i.e., produce a depression-like clinical picture). The antidepressant effect appears to be unique to some agents, with direct evidence of insignificant antidepressant action for ziprasidone. Three general principles can guide the use of antipsychotics as antidepressants: (i) All SGAs may have anxiolytic effects; (ii) full antipsychotic doses are dysphorogenic, and therefore, subantipsychotic doses are to be used; and (iii) SGAs do not have a general antidepressant effect, rather, this appears to be unique to quetiapine and aripiprazole, and possibly lurasidone. PMID:25963405

  2. Antidepressant-like effects of curcumin in WKY rat model of depression is associated with an increase in hippocampal BDNF

    Hurley, Laura L.; Akinfiresoye, Luli; Nwulia, Evaristus; Kamiya, Atsushi; Kulkarni, Amol; Tizabi, Yousef


    Curcumin is the principal active ingredient found in turmeric (Curcuma longa), a plant used in traditional Asian diets and herbal medicines. It is known to have a wide range of biological actions including antidepressant-like effects which have been observed in stress-induced depression models. This study was designed to investigate the antidepressant potential of curcumin in a non-induced model of depression. Moreover, since brain derived neurotrophic factor (BDNF) has been implicated in antidepressant effects of many drugs, we also evaluated the effects of curcumin on BDNF in the hippocampus. Adult male Wistar Kyoto (WKY) rats, a putative model of depression, were injected acutely or chronically (10 d) with 50, 100, and 200mg/kg curcumin. Open field locomotor activity (OFLA) and forced swim test (FST), a measure of helplessness, were measured 1 hour after acute and 18–20 hours after last chronic injection. Results showed a dose-dependent reduction of immobility in the FST by curcumin in both acute and chronic studies, without any significant effect on OFLA. The effect of higher chronic curcumin dose in FST was still evident a week later. Chronic curcumin also resulted in a dose-dependent increase in hippocampal BDNF. This data provides evidence for an antidepressant-like effect of curcumin, possibly through increased neurotrophic activity, in the WKY model of depression, and support the notion that curcumin may prove an effective and lasting natural antidepressant. PMID:23142609

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

    Bahareh Amin


    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.

  4. 21 CFR 316.28 - Publication of orphan-drug designations.


    ... 21 Food and Drugs 5 2010-04-01 2010-04-01 false Publication of orphan-drug designations. 316.28... (CONTINUED) DRUGS FOR HUMAN USE ORPHAN DRUGS Designation of an Orphan Drug § 316.28 Publication of orphan-drug designations. Each month FDA will update a publically available list of drugs designated as...

  5. 21 CFR 316.26 - Amendment to orphan-drug designation.


    ... 21 Food and Drugs 5 2010-04-01 2010-04-01 false Amendment to orphan-drug designation. 316.26... (CONTINUED) DRUGS FOR HUMAN USE ORPHAN DRUGS Designation of an Orphan Drug § 316.26 Amendment to orphan-drug designation. (a) At any time prior to approval of a marketing application for a designated orphan drug,...

  6. 21 CFR 316.25 - Refusal to grant orphan-drug designation.


    ... 21 Food and Drugs 5 2010-04-01 2010-04-01 false Refusal to grant orphan-drug designation. 316.25... (CONTINUED) DRUGS FOR HUMAN USE ORPHAN DRUGS Designation of an Orphan Drug § 316.25 Refusal to grant orphan-drug designation. (a) FDA will refuse to grant a request for orphan-drug designation if any of...

  7. Design of Nanoparticle-Based Carriers for Targeted Drug Delivery

    Xiaojiao Yu; Ian Trase; Muqing Ren; Kayla Duval; Xing Guo; Zi Chen


    Nanoparticles have shown promise as both drug delivery vehicles and direct antitumor systems, but they must be properly designed in order to maximize efficacy. Computational modeling is often used both to design new nanoparticles and to better understand existing ones. Modeled processes include the release of drugs at the tumor site and the physical interaction between the nanoparticle and cancer cells. In this paper, we provide an overview of three different targeted drug delivery methods (p...

  8. Serotonergic antidepressants decrease hedonic signals but leave learning signals in the nucleus accumbens unaffected.

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


    Investigating the effects of serotonergic antidepressants on neural correlates of visual erotic stimulation revealed decreased reactivity within the dopaminergic reward network along with decreased subjective sexual functioning compared with placebo. However, a global dampening of the reward system under serotonergic drugs is not intuitive considering clinical observations of their beneficial effects in the treatment of depression. Particularly, learning signals as coded in prediction error processing within the dopaminergic reward system can be assumed to be rather enhanced as antidepressant drugs have been demonstrated to facilitate the efficacy of psychotherapeutic interventions relying on learning processes. Within the same study sample, we now explored the effects of serotonergic and dopaminergic/noradrenergic antidepressants on prediction error signals compared with placebo by functional MRI. A total of 17 healthy male participants (mean age: 25.4 years) were investigated under the administration of paroxetine, bupropion and placebo for 7 days each within a randomized, double-blind, within-subject cross-over design. During functional MRI, we used an established monetary incentive task to explore neural prediction error signals within the bilateral nucleus accumbens as region of interest within the dopaminergic reward system. In contrast to diminished neural activations and subjective sexual functioning under the serotonergic agent paroxetine under visual erotic stimulation, we revealed unaffected or even enhanced neural prediction error processing within the nucleus accumbens under this antidepressant along with unaffected behavioural processing. Our study provides evidence that serotonergic antidepressants facilitate prediction error signalling and may support suggestions of beneficial effects of these agents on reinforced learning as an essential element in behavioural psychotherapy. PMID:26555033

  9. Cardiovascular Effects of Antidepressants and Mood Stabilizers

    Shahin Akhondzadeh


    Full Text Available Depression is a serious disorder in today’s society, with the estimates of lifetime prevalence being as high as 21% of the general population in some developed countries. As defined by the American Psychiatric Association, depression is a heterogeneous disorder often manifested with symptoms at the psychological, behavioral, and physiological levels. Such patients are often reluctant to take synthetic antidepressants in their appropriate doses due to their anticipated side effects including inability to drive a car, dry mouth, constipation, and sexual dysfunction. As a therapeutic alternative, effective herbal drugs may offer advantages in terms of safety and tolerability, possibly also improving patient compliance. The advent of the first antidepressants, Monoamine Oxidase Inhibitors (MAOIs and Tricyclic Antidepressants (TCAs, in the 1950s and 1960s represented a dramatic leap forward in the clinical management of depression. The subsequent development of the Selective Serotonin Reuptake Inhibitors (SSRIs and the Serotonin Norepinephrine Reuptake Inhibitor (SNRI venlafaxine in the past decade and a half has greatly enhanced the treatment of depression by offering patients medications that are as effective as the older agents but are generally more tolerable and safer in an overdose. The introduction of atypical antidepressants, such as bupropion, nefazadone, and mirtazapine, has added substantially to the available pharmacopoeia for depression. Nonetheless, rates of remission tend to be low and the risk of relapse and recurrence remains high. One of the concerns regarding the safety of antidepressant is its potential risk of cardiotoxicity and cardiovascular side effects. In this review, we will focus on the cardiovascular side effects of different types of antidepressants.

  10. Prognosis in heart failure and the value of {beta}-blockers are altered by the use of antidepressants and depend on the type of antidepressants used

    Fosbøl, Emil Loldrup; Gislason, Gunnar H; Poulsen, Henrik Enghusen;


    BACKGROUND: Depression worsens the prognosis in patients with cardiac disease, and treatment with antidepressants may improve survival. Guidelines recommend use of selective serotonin reuptake inhibitors (SSRIs), but knowledge of the prognostic effect of different classes of antidepressants...... death associated with antidepressants, HF medication, and coadministration of these 2 drug classes was estimated by Cox proportional hazard analyses. Propensity adjusted models were performed as sensitivity analysis. During the study period, there were 53 988 deaths, of which 83.0% were due...

  11. Ketamine: A New Antidepressant?

    Feride Karacaer


    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

  12. Drug: D08349 [KEGG MEDICUS

    Full Text Available D08349 Drug Phenelzine (BAN) C8H12N2 136.1 136.1943 D08349.gif Antidepressant, MAO-... metabolism - cytochrome P450 hsa04726(4128+4129) Serotonergic synapse hsa04728(4128+4129) Dopaminergic synapse map07027 Antidepress...drug classification [BR:br08302] Antidepressants Monoamine Oxidase Inhibitors Phe

  13. Drug: D00505 [KEGG MEDICUS

    Full Text Available D00505 Drug Phenelzine sulfate (USP); Nardil (TN) C8H12N2. H2SO4 234.0674 234.2728 D00505.gif Antidepress...129) Dopaminergic synapse map07027 Antidepressants map07216 Catecholamine transfe... Phenelzine sulfate (USP) USP drug classification [BR:br08302] Antidepressants Mo

  14. Drug: D08625 [KEGG MEDICUS

    Full Text Available D08625 Drug Tranylcypromine (INN); Parnate (TN) C9H11N 133.0891 133.1903 D08625.gif Antidepress...29) Dopaminergic synapse map07027 Antidepressants map07216 Catecholamine transfer...8625 Tranylcypromine (INN) USP drug classification [BR:br08302] Antidepressants M

  15. Drug: D07875 [KEGG MEDICUS

    Full Text Available D07875 Drug Doxepin (INN); Sinequan (TN) C19H21NO 279.1623 279.3761 D07875.gif Antidepressant, t ... r08303] N NERVOUS SYSTEM N06 PSYCHOANALEPTICS N06A ANTIDEPRESSANTS ... N06AA Non-selective monoamine reuptake inhibitors ... Doxepin (INN) USP drug classification [BR:br08302] Antidepressants ... Tricyclics Doxepin D07875 Doxepin (INN) Anxiolytic ...

  16. Drug: D08447 [KEGG MEDICUS

    Full Text Available D08447 Drug Protriptyline (INN) C19H21N 263.1674 263.3767 D08447.gif Antidepressant, tricyclic S ... r08303] N NERVOUS SYSTEM N06 PSYCHOANALEPTICS N06A ANTIDEPRESSANTS ... N06AA Non-selective monoamine reuptake inhibitors ... ptyline (INN) USP drug classification [BR:br08302] Antidepressants ... Tricyclics Protriptyline D08447 Protriptyline (INN ...

  17. Multiscale Modeling in the Clinic: Drug Design and Development.

    Clancy, Colleen E; An, Gary; Cannon, William R; Liu, Yaling; May, Elebeoba E; Ortoleva, Peter; Popel, Aleksander S; Sluka, James P; Su, Jing; Vicini, Paolo; Zhou, Xiaobo; Eckmann, David M


    A wide range of length and time scales are relevant to pharmacology, especially in drug development, drug design and drug delivery. Therefore, multiscale computational modeling and simulation methods and paradigms that advance the linkage of phenomena occurring at these multiple scales have become increasingly important. Multiscale approaches present in silico opportunities to advance laboratory research to bedside clinical applications in pharmaceuticals research. This is achievable through the capability of modeling to reveal phenomena occurring across multiple spatial and temporal scales, which are not otherwise readily accessible to experimentation. The resultant models, when validated, are capable of making testable predictions to guide drug design and delivery. In this review we describe the goals, methods, and opportunities of multiscale modeling in drug design and development. We demonstrate the impact of multiple scales of modeling in this field. We indicate the common mathematical and computational techniques employed for multiscale modeling approaches used in pharmacometric and systems pharmacology models in drug development and present several examples illustrating the current state-of-the-art models for (1) excitable systems and applications in cardiac disease; (2) stem cell driven complex biosystems; (3) nanoparticle delivery, with applications to angiogenesis and cancer therapy; (4) host-pathogen interactions and their use in metabolic disorders, inflammation and sepsis; and (5) computer-aided design of nanomedical systems. We conclude with a focus on barriers to successful clinical translation of drug development, drug design and drug delivery multiscale models. PMID:26885640

  18. Anti-malarial Drug Design by Targeting Apicoplasts: New Perspectives

    Avinaba Mukherjee


    Full Text Available Objectives: Malaria has been a major global health problem in recent times with increasing mortality. Current treatment methods include parasiticidal drugs and vaccinations. However, resistance among malarial parasites to the existing drugs has emerged as a significant area of concern in anti-malarial drug design. Researchers are now desperately looking for new targets to develop anti-malarials drug which is more target specific. Malarial parasites harbor a plastid-like organelle known as the ‘apicoplast’, which is thought to provide an exciting new outlook for the development of drugs to be used against the parasite. This review elaborates on the current state of development of novel compounds targeted againstemerging malaria parasites. Methods: The apicoplast, originates by an endosymbiotic process, contains a range of metabolic pathways and housekeeping processes that differ from the host body and thereby presents ideal strategies for anti-malarial drug therapy. Drugs are designed by targeting the unique mechanism of the apicoplasts genetic machinery. Several anabolic and catabolic processes, like fatty acid, isopenetyl diphosphate and heme synthess in this organelle, have also been targeted by drugs. Results: Apicoplasts offer exciting opportunities for the development of malarial treatment specific drugs have been found to act by disrupting this organelle’s function, which wouldimpede the survival of the parasite. Conclusion: Recent advanced drugs, their modes of action, and their advantages in the treatment of malaria by using apicoplasts as a target are discussed in this review which thought to be very useful in desigining anti-malarial drugs. Targetting the genetic machinery of apicoplast shows a great advantange regarding anti-malarial drug design. Critical knowledge of these new drugs would give a healthier understanding for deciphering the mechanism of action of anti-malarial drugs when targeting apicoplasts to overcome drug

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

    Marić Nađa P.


    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

  20. The multiple outcomes bias in antidepressants research.

    Procopio, Marco


    Despite the widespread use of antidepressant medication, there are no signs that the burden of depression and suicide is decreasing in the industrialised world. This is generating mounting scepticism on the effectiveness of this class of drugs as an approach for the treatment of mood disorders. These doubts are also fuelled by the increasing awareness that the literature on antidepressants is fundamentally flawed and under the control of the pharmaceutical companies. This article describes systematically for the first time what is probably the most insidious and misleading of the biases that affect this area of research: the "multiple outcomes bias". Most trials on the effectiveness of antidepressants, instead of first establishing a hypothesis and then trying to demonstrate it, following the scientific method, start instead "data mining", without a clear hypothesis, and then select for publication, amongst a multitude of outcomes, only the ones that favour the antidepressant drug, ignoring the others. This method has obviously no scientific validity and is very misleading, allowing the manipulation of the data without any overt fraudulent action. There is the need to generate new research, independently funded and with clear hypotheses established "a priori ". What is at stake is not only the appraisal of the balance between benefits and potential damage to the patients when using this class of medications, after the realisation that they are not as harmless as believed. It is also to establish whether the research on antidepressant medication has gone on a "wild goose chase" over the last half century, concentrating almost exclusively on molecules that modify the monoaminergic transmission at synaptic level and virtually ignoring any other avenue. PMID:15922120

  1. Antidepressants and seizure-interactions at the GABA-receptor chloride-ionophore complex

    Convulsive seizures are a potential side effect of antidepressant drug treatment and can be produced by all classes of antidepressants. It is also know that some convulsant and anticonvulsant drug actions are mediated by the GABA-receptor chloride-ionophore complex. Drugs acting at this complex appear to induce convulsions by inhibiting chloride conductance through the associated chloride channel. Using the method of GABA-stimulated 36Cl-uptake by rat cerebral cortical vesicles, we show that some antidepressant drugs can inhibit the GABA-receptor chloride uptake, and that the degree of chloride channel inhibition by these drugs correlates with the frequency of convulsive seizures induced by them

  2. Ab initio and density functional computations of the vibrational spectrum, molecular geometry and some molecular properties of the antidepressant drug sertraline (Zoloft) hydrochloride

    Sagdinc, Seda; Kandemirli, Fatma; Bayari, Sevgi Haman


    Sertraline hydrochloride is a highly potent and selective inhibitor of serotonin (5HT). It is a basic compound of pharmaceutical application for antidepressant treatment (brand name: Zoloft). Ab initio and density functional computations of the vibrational (IR) spectrum, the molecular geometry, the atomic charges and polarizabilities were carried out. The infrared spectrum of sertraline is recorded in the solid state. The observed IR wave numbers were analysed in light of the computed vibrational spectrum. On the basis of the comparison between calculated and experimental results and the comparison with related molecules, assignments of fundamental vibrational modes are examined. The X-ray geometry and experimental frequencies are compared with the results of our theoretical calculations.

  3. Meta-analysis of the antidepressant response to sleep deprivation and its correlates: towards a better antidepressant therapy

    Pollock, Michael


    Unlike antidepressant drugs, which typically require several weeks to produce an antidepressant response, sleep deprivation produces a response literally overnight. Quantification (meta-analysis) of 166 articles, including data from a total of 3951 depressed patients, reveals that consistently half of all depressed patients are responders to a night of sleep deprivation, with the degree of response shown by these responders being on average a 55% decrease in depression levels. While the level...

  4. Depression, Antidepressants, and Neurogenesis: A Critical Reappraisal

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


    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 summa...

  5. Antidepressant activity of fingolimod in mice

    di Nuzzo, Luigi; Orlando, Rosamaria; Tognoli, Cristina; Di Pietro, Paola; Bertini, Giuseppe; Miele, Jessica; Bucci, Domenico; Motolese, Marta; Scaccianoce, Sergio; Caruso, Alessandra; Mauro, Gianluca; De Lucia, Carmine; Battaglia, Giuseppe; Bruno, Valeria; Fabene, Paolo Francesco


    Recent findings indicate that fingolimod, the first oral drug approved for the treatment of multiple sclerosis (MS), acts as a direct inhibitor of histone deacetylases (HDACs) and enhances the production of brain-derived neurotrophic factor (BDNF) in the CNS. Both mechanisms are relevant to the pathophysiology and treatment of major depression. We examined the antidepressant activity of fingolimod in mice subjected to chronic unpredictable stress (CUS), a model of reactive depression endowed ...

  6. Drug: D07791 [KEGG MEDICUS

    Full Text Available D07791 Drug Desipramine (INN) C18H22N2 266.1783 266.3807 D07791.gif Antidepressant,... tricyclic Same as: C06943 ATC code: N06AA01 Tricyclic antidepressants serotonin transporter inhibitor [HSA:...ic biomarker: CYP2D6 [HSA:1565] map07027 Antidepressants map07234 Neurotransmitte...ine D07791 Desipramine (INN) USP drug classification [BR:br08302] Antidepressants

  7. Drug: D10184 [KEGG MEDICUS

    Full Text Available D10184 Drug Vortioxetine (USAN) C18H22N2S 298.1504 298.4457 D10184.gif Antidepressant, anxiolyti ... r08303] N NERVOUS SYSTEM N06 PSYCHOANALEPTICS N06A ANTIDEPRESSANTS ... N06AX Other antidepressants ... N06AX26 Vortioxetine D ... xetine (USAN) USP drug classification [BR:br08302] Antidepressants ... SSRIs/SNRIs (Selective Serotonin Reuptake Inhibito ...

  8. Drug: D09698 [KEGG MEDICUS

    Full Text Available D09698 Drug Vilazodone (USAN/INN) C26H27N5O2 441.2165 441.5249 D09698.gif Antidepressant ATC cod ... r08303] N NERVOUS SYSTEM N06 PSYCHOANALEPTICS N06A ANTIDEPRESSANTS ... N06AX Other antidepressants ... N06AX24 Vilazodone D09 ... ne (USAN/INN) USP drug classification [BR:br08302] Antidepressants ... SSRIs/SNRIs (Selective Serotonin Reuptake Inhibito ...


    L. K. Omray


    Gastro retentive drug delivery system of diltiazem hydrochloride was designed and evaluated for its effectiveness for the management of mild to moderate hypertension. Gastro retentive drug delivery system were prepared using polyvinyl alcohol and sodium carboxy methyl cellulose as the polymers and sodium bicarbonate as a gas generating agent for the reduction of floating lag time. Gastro retentive drug delivery system tablets were prepared by wet granulation method by compression in tablet co...

  10. Experience With and Attitudes Toward Psychotherapy and Antidepressants Among Patients With Inflammatory Bowel Disease and Functional Gastrointestinal Disorders: An Online Patient Survey to Inform System Design.

    Mikocka-Walus, Antonina; Andrews, Jane M


    This study aimed to explore and compare experiences with and attitudes toward psychotherapy and antidepressants of patients with inflammatory bowel disease (IBD) and functional gastrointestinal disorders (FGiDs). Patients from gastroenterology clinic databases were invited to an online survey. Student's t test, Mann-Whitney U test, chi-square test, and Fisher's test were used to compare patients with IBD and FGiD on demographics and variables of interest. Of 86 participants, 56 (65%) had IBD and 30 (35%) had FGiDs. Mean levels of anxiety, depressive, and stress symptoms were within the moderate to severe range. Psychological care and antidepressants were offered to significantly more FGiD than to IBD respondents (37% vs. 9%; p = .009). Although the symptoms were generally reduced after the prescription of antidepressants, only 30% of IBD respondents and 21% of FGiD respondents using antidepressants would recommend them to others. In contrast, 53% of IBD respondents and 69% of FGiD respondents who used psychotherapy would recommend it to others. Both these therapies were valued by recipients; however, neither was reported to improve gastrointestinal (GI) symptoms. Given the high desire for and positive experiences of psychological care for these 2 common GI conditions, access to formal psychological support services within GI clinics would appear to be the most efficient model. PMID:27148830

  11. Sub-threshold depression and antidepressants use in a community sample: searching anxiety and finding bipolar disorder

    Hardoy Maria; Faravelli Carlo; Di Sciascio Guido; Dell'Osso Liliana; Caraci Filippo; Balestrieri Matteo; Tondo Leonardo; Carta Mauro G; Lecca Maria E; Moro Maria; Bhat Krishna M; Casacchia Massimo; Drago Filippo


    Abstract Background To determine the use of antidepressants (ADs) in people with sub-threshold depression (SD); the lifetime prevalence of mania and hypomania in SD and the link between ADs use, bipolarity and anxiety disorders in SD. Methods Study design: community survey. Study population: samples randomly drawn, after stratification from the adult population of municipal records. Sample size: 4999 people from seven areas within six Italian regions. Tools: Questionnaire on psychotropic drug...

  12. Antidepressant Induced Mania : Is it a risk factor for Antidepressant Abuse?

    Ramesh, S; Khandelwal, Sudhir K


    Induction of mania is a common occurrence with antidepressant use. A case of antidepressant induced hypomania leading to antidepressant abuse is presented. The clinical implications of antidepressant abuse in bipolar disorder are discussed.

  13. Acute effect of different antidepressants on glycemia in diabetic and non-diabetic rats

    Gomez, R.; Huber, J.; G. Tombini; H.M.T. Barros


    Diabetic patients have a 20% higher risk of depression than the general population. Treatment with antidepressant drugs can directly interfere with blood glucose levels or may interact with hypoglycemic agents. The treatment of depression in diabetic patients must take into account variations of glycemic levels at different times and a comparison of the available antidepressant agents is important. In the present study we evaluated the interference of antidepressants with blood glucose levels...

  14. PARP1 Inhibitors: antitumor drug design

    MALYUCHENKO N.V.; Kotova, E. Yu.; Kulaeva, O. I.; Kirpichnikov, M P; STUDITSKIY V.M.


    The poly (ADP-ribose) polymerase 1 (PARP1) enzyme is one of the promising molecular targets for the discovery of antitumor drugs. PARP1 is a common nuclear protein (1–2 million molecules per cell) serving as a “sensor” for DNA strand breaks. Increased PARP1 expression is sometimes observed in melanomas, breast cancer, lung cancer, and other neoplastic diseases. The PARP1 expression level is a prognostic indicator and is associated with a poor survival prognosis. There is evidence that high PA...


    MALYUCHENKO N.V.; KOTOVA E. YU.; Kulaeva, O. I.; Kirpichnikov, M P; STUDITSKIY V.M.


    The poly (ADP-ribose) polymerase 1 (PARP1) enzyme is one of the promising molecular targets for the discovery of antitumor drugs. PARP1 is a common nuclear protein (1-2 million molecules per cell) serving as a “sensor” for DNA strand breaks. Increased PARP1 expression is sometimes observed in melanomas, breast cancer, lung cancer, and other neoplastic diseases. The PARP1 expression level is a prognostic indicator and is associated with a poor survival prognosis. There is evidence that high PA...

  16. Design and Optimization of Floating Drug Delivery System of Acyclovir

    Kharia A; Hiremath S; Singhai A; Omray L; Jain S


    The purpose of the present work was to design and optimize floating drug delivery systems of acyclovir using psyllium husk and hydroxypropylmethylcellulose K4M as the polymers and sodium bicarbonate as a gas generating agent. The tablets were prepared by wet granulation method. A 32 full factorial design was used for optimization of drug release profile. The amount of psyllium husk (X1) and hydroxypropylmethylcellulose K4M (X2) were selected as independent variables. The times required for 50...

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

    Ioannidis John PA


    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

  18. Increased risk of antidepressant use in childhood cancer survivors

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


    AIM: Childhood cancer survivors are at risk of both somatic and mental late effects, but large population-based studies of depression are lacking. METHODS: Risk of antidepressant use was evaluated in a population-based cohort of 5452 Danish children treated for cancer in 1975-2009 by linkage to the...... National Prescription Drug Database, which worldwide is the oldest nationwide registry of prescription medication. Hazard ratios (HRs) for antidepressant use were estimated in a Cox proportional hazards model stratified on sex, with population comparisons as referents. RESULTS: Overall, childhood cancer...... survivors were at increased risk of having antidepressants prescribed (HR, 1.4; 95% confidence interval (CI), 1.3-1.5). The excess absolute risk of antidepressant use was 2.5 per 1000 person-years (95% CI, 1.7-3.3), equivalent to an excess of 2.5 survivors for every 100 survivors followed for 10years...

  19. Interaction of tricyclic antidepressants with cholestyramine in vitro.

    Bailey, D N; Coffee, J J; Anderson, B; Manoguerra, A S


    The adsorption of amitriptyline, desipramine, doxepin, imipramine, and nortriptyline onto cholestyramine was demonstrated in vitro with use of 1.2 mol/L HCl at 37 degrees C to simulate gastric fluid. Binding to cholestyramine was approximately 80% for each of the tricyclic antidepressants, and this was about the same degree of binding noted with a nonpharmaceutical, non-ionic resin widely used in the diagnostic toxicology laboratory (Amberlite XAD-2). In contrast, five other non-antidepressants (acetaminophen, chlordiazepoxide, procainamide, quinidine, and theophylline) showed only minimal binding to cholestyramine under these conditions. Activated charcoal completely bound all drugs studied. These findings suggest that cholestyramine should be used with caution in patients receiving tricyclic antidepressants. They also suggest that cholestyramine may be a potentially useful adjunctive therapy in treatment of overdose with the tricyclic antidepressants. PMID:1519310

  20. Design and optimization of floating drug delivery system of acyclovir

    Kharia A


    Full Text Available The purpose of the present work was to design and optimize floating drug delivery systems of acyclovir using psyllium husk and hydroxypropylmethylcellulose K4M as the polymers and sodium bicarbonate as a gas generating agent. The tablets were prepared by wet granulation method. A 32 full factorial design was used for optimization of drug release profile. The amount of psyllium husk (X1 and hydroxypropylmethylcellulose K4M (X2 were selected as independent variables. The times required for 50% (t 50% and 70% (t 70% drug dissolution were selected as dependent variables. All the designed nine batches of formulations were evaluated for hardness, friability, weight variation, drug content uniformity, swelling index, in vitro buoyancy, and in vitro drug release profile. All formulations had floating lag time below 3 min and constantly floated on dissolution medium for more than 24 h. Validity of the developed polynomial equation was verified by designing two check point formulations (C1 and C2. The closeness of predicted and observed values for t 50% and t 70% indicates validity of derived equations for the dependent variables. These studies indicated that the proper balance between psyllium husk and hydroxypropylmethylcellulose K4M can produce a drug dissolution profile similar to the predicted dissolution profile. The optimized formulations followed Higuchi′s kinetics while the drug release mechanism was found to be anomalous type, controlled by diffusion through the swollen matrix.

  1. Design and optimization of floating drug delivery system of acyclovir.

    Kharia, A A; Hiremath, S N; Singhai, A K; Omray, L K; Jain, S K


    The purpose of the present work was to design and optimize floating drug delivery systems of acyclovir using psyllium husk and hydroxypropylmethylcellulose K4M as the polymers and sodium bicarbonate as a gas generating agent. The tablets were prepared by wet granulation method. A 3(2) full factorial design was used for optimization of drug release profile. The amount of psyllium husk (X1) and hydroxypropylmethylcellulose K4M (X2) were selected as independent variables. The times required for 50% (t(50%)) and 70% (t(70%)) drug dissolution were selected as dependent variables. All the designed nine batches of formulations were evaluated for hardness, friability, weight variation, drug content uniformity, swelling index, in vitro buoyancy, and in vitro drug release profile. All formulations had floating lag time below 3 min and constantly floated on dissolution medium for more than 24 h. Validity of the developed polynomial equation was verified by designing two check point formulations (C1 and C2). The closeness of predicted and observed values for t(50%) and t(70%) indicates validity of derived equations for the dependent variables. These studies indicated that the proper balance between psyllium husk and hydroxypropylmethylcellulose K4M can produce a drug dissolution profile similar to the predicted dissolution profile. The optimized formulations followed Higuchi's kinetics while the drug release mechanism was found to be anomalous type, controlled by diffusion through the swollen matrix. PMID:21694992

  2. 21 CFR 316.30 - Annual reports of holder of orphan-drug designation.


    ... 21 Food and Drugs 5 2010-04-01 2010-04-01 false Annual reports of holder of orphan-drug... SERVICES (CONTINUED) DRUGS FOR HUMAN USE ORPHAN DRUGS Designation of an Orphan Drug § 316.30 Annual reports of holder of orphan-drug designation. Within 14 months after the date on which a drug was...

  3. 21 CFR 316.27 - Change in ownership of orphan-drug designation.


    ... 21 Food and Drugs 5 2010-04-01 2010-04-01 false Change in ownership of orphan-drug designation... SERVICES (CONTINUED) DRUGS FOR HUMAN USE ORPHAN DRUGS Designation of an Orphan Drug § 316.27 Change in ownership of orphan-drug designation. (a) A sponsor may transfer ownership of or any beneficial interest...

  4. Breastfeeding and Antidepressants

    Field, Tiffany


    Although a large literature supports the benefits of breastfeeding, this review suggests that breastfeeding is less common among postpartum depressed women, even though their infants benefit from the breastfeeding. Depressed mothers, in part, do not breastfeed because of their concern about potentially negative effects of antidepressants on their infants. Although sertraline (Zoloft) and paroxetine (Paxol) concentrations are not detectable in infants’ sera, fluoxetine (Prozac) and citalopram ...

  5. [Critical evaluation of the use of antidepressives in childhood].

    Conde López, V J; Ballesteros Alcalde, M C; Franco Martín, M A; Geijo Uribe, M S


    In the introduction the authors study some technical, methodological, ethical, administrative and marketing problems about the evaluation and investigation in child and adolescence psychopharmacology. They make a revision and critical evaluation about. As a whole the clinic use of antidepressive drugs in childhood psychiatry. Then, some open and controlled trial about tricyclic antidepressives are evaluated. After this, the authors present the most important advances about the open and controlled clinic trials with several antidepressives: tricyclic, tetracyclic, ISSR and MAO-Inhibitors and other drugs (placebo response, psychotherapy, imipramine, nortryptiline, amitriptyline, fluoxetine, MAO-Inhibitors, lithium, mianserin, maprotyline, etc.). Beside, placebo effect, response prediction factors, biologic markers, diagnostic criteria, evaluation methods and technics, drugs associations, clinic types of child depression, etc, are studied. In the last, the authors present some clinical conclusions about this subject. PMID:9245188

  6. A drug-specific nanocarrier design for efficient anticancer therapy

    Shi, Changying; Guo, Dandan; Xiao, Kai; Wang, Xu; Wang, Lili; Luo, Juntao


    The drug-loading properties of nanocarriers depend on the chemical structures and properties of their building blocks. Here we customize telodendrimers (linear dendritic copolymer) to design a nanocarrier with improved in vivo drug delivery characteristics. We do a virtual screen of a library of small molecules to identify the optimal building blocks for precise telodendrimer synthesis using peptide chemistry. With rationally designed telodendrimer architectures, we then optimize the drug-binding affinity of a nanocarrier by introducing an optimal drug-binding molecule (DBM) without sacrificing the stability of the nanocarrier. To validate the computational predictions, we synthesize a series of nanocarriers and evaluate systematically for doxorubicin delivery. Rhein-containing nanocarriers have sustained drug release, prolonged circulation, increased tolerated dose, reduced toxicity, effective tumour targeting and superior anticancer effects owing to favourable doxorubicin-binding affinity and improved nanoparticle stability. This study demonstrates the feasibility and versatility of the de novo design of telodendrimer nanocarriers for specific drug molecules, which is a promising approach to transform nanocarrier development for drug delivery.

  7. Preventing relapse in recurrent depression using mindfulness-based cognitive therapy, antidepressant medication or the combination: trial design and protocol of the MOMENT study

    Huijbers Marloes J


    Full Text Available Abstract Background Depression is a common psychiatric disorder characterized by a high rate of relapse and recurrence. The most commonly used strategy to prevent relapse/recurrence is maintenance treatment with antidepressant medication (mADM. Recently, it has been shown that Mindfulness-Based Cognitive Therapy (MBCT is at least as effective as mADM in reducing the relapse/recurrence risk. However, it is not yet known whether combination treatment of MBCT and mADM is more effective than either of these treatments alone. Given the fact that most patients have a preference for either mADM or for MBCT, the aim of the present study is to answer the following questions. First, what is the effectiveness of MBCT in addition to mADM? Second, how large is the risk of relapse/recurrence in patients withdrawing from mADM after participating in MBCT, compared to those who continue to use mADM after MBCT? Methods/design Two parallel-group, multi-center randomized controlled trials are conducted. Adult patients with a history of depression (3 or more episodes, currently either in full or partial remission and currently treated with mADM (6 months or longer are recruited. In the first trial, we compare mADM on its own with mADM plus MBCT. In the second trial, we compare MBCT on its own, including tapering of mADM, with mADM plus MBCT. Follow-up assessments are administered at 3-month intervals for 15 months. Primary outcome is relapse/recurrence. Secondary outcomes are time to, duration and severity of relapse/recurrence, quality of life, personality, several process variables, and incremental cost-effectiveness ratio. Discussion Taking into account patient preferences, this study will provide information about a the clinical and cost-effectiveness of mADM only compared with mADM plus MBCT, in patients with a preference for mADM, and b the clinical and cost-effectiveness of withdrawing from mADM after MBCT, compared with mADM plus MBCT, in patients with a

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

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


    Treatment with some types of antidepressants has been associated with sudden cardiac death. It is unknown whether the increased risk is due to a class effect or related to specific antidepressants within drug classes. All patients in Denmark with an out-of-hospital cardiac arrest (OHCA) were...... identified (2001-2007). Association between treatment with specific antidepressants and OHCA was examined by conditional logistic regression in case-time-control models. We identified 19,110 patients with an OHCA; 2,913 (15.2%) were receiving antidepressant treatment at the time of OHCA, with citalopram...... 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...

  9. Rational design of purely peptidic amphiphiles for drug delivery applications

    Bruyn Ouboter, Dirk de


    A broad range of new properties is emerging from supramolecular aggregates. Self-assembled structures of purely peptidic amphiphiles exploit these properties to produce biocompatible, biodegradable, smart materials for drug administration. This thesis explores the design, synthesis, purification, characterization of purely peptidic amphiphiles, and evaluates potential applications. The first chapter provides a general introduction to the field of self-assembly, and of drug delivery as com...

  10. Drug: D07339 [KEGG MEDICUS

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