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This review considers evidence for the efficacy of pharmacotherapy among primary care patients with depressive disorders and reviews knowledge regarding the effectiveness of current practice. Strong evidence supports the efficacy of antidepressant pharmacotherapy for primary care patients with major depression and dysthymia with some evidence for pharmacotherapy of less severe depression. In general, available antidepressants appear equal in both efficacy and effectiveness. Treatment selection for any individual patient remains largely empirical, with few clinical characteristics predicting better or worse response to specific treatments. Strong evidence supports continuation treatment (i.e., at least six months of pharmacotherapy) for all patients and maintenance treatment (i.e., at least 24 months of pharmacotherapy) for those with chronic or recurrent depression. Unfortunately, few patients in primary care or specialty practice receive recommended levels of pharmacotherapy or recommended frequency of follow-up care. A number of recent studies have evaluated strategies to improve the quality of antidepressant treatment in primary care. Educational programs (including academic detailing and continuous quality improvement) have had little impact on patient outcomes. Key elements of effective care improvement programs include specific, evidence-based treatment protocols, organized patient education and active follow-up care. [Copyright &y& Elsevier]

The second-generation antidepressants (SGAs) are used widely in patients with Alzheimer's disease (AD) for the treatment of mood disorder, sleep disturbance and psychiatric symptoms. Several evidences from AD mice confirmed that antidepressants could delaying cognitive decline. However, the conclusions varied in randomized controlled trials (RCTs) based on patients. This meta-analysis summarizes the cognitive impact of SGAs on AD patients with different neuropsychiatric symptoms (NPS). Results show there is no effect on cognition and depression between SGAs treatment and controls, and this remains in subgroups analyses of duration of medication (<12 weeks or ≥12 weeks), drug classes (SSRIs or non-SSRIs), combination with anti-dementia medication, various NPS, and degree of AD. The available evidence provides no support for the efficacy of SGAs for cognition and depression of AD patients. The implications of the findings and their mechanism relevance are also discussed in this paper. [ABSTRACT FROM AUTHOR]

Backgrounds: Bipolar depression is still a very difficult to treat condition with low success rates of antidepressant drugs, high rates of morbidity and suicide risk and antidepressant-emergent mania risk. Despite a growing body of evidence has been generated over the last decade about Light Therapy (LT) as an effective treatment for depression the management of it continues to be a point of debate for Bipolar Disorder especially when considering non-seasonal pattern.Methods: We systematically screened current literature using the PubMed electronic platform. We considered "mood disorder", "depression" and "light therapy" as keywords for the search.Results: We retrieved 1907 papers. After the screening, we selected 11 papers to be included in the analysis, treating 195 patients affected by bipolar depression. 5 studies were RCT studies. The overall analysis, including non-RCTs, showed a positive effect of the treatment in all the included studies (ESs: -1.46, 95% CI:-1.677 to -1.242; p<0.001). A significant effect of LT compared to placebo was found also in RCTs (ESs: -0.501, 95% CI: - 0.777 to -0.225; p<0.001).Limitations: A high heterogeneity between the studies was found when including non-RCTs and the number of RCTs was small CONCLUSION: We confirmed the -efficacy of LT as antidepressant non-pharmacological therapy also in bipolar depression. [ABSTRACT FROM AUTHOR]

Background: Repetitive transcranial magnetic stimulation (rTMS) is an increasingly used treatment for patients with depression. The use of rTMS in depression is supported by over 20 years of clinical trials. There has been a significant increase in knowledge around the use of rTMS in recent years.Objective: The aim of this paper was to review the use of rTMS in depression to provide an update for rTMS practitioners and clinicians interested in the clinical use of this treatment.Methods: A targeted review of the literature around the use of rTMS treatment of depression with a specific focus on studies published in the last 3 years.Results: High-frequency rTMS applied to the left dorsolateral prefrontal cortex is an effective treatment for acute episodes of major depressive disorder. There are several additional methods of rTMS delivery that are supported by clinical trials and meta-analyses but no substantive evidence that any one approach is any more effective than any other. rTMS is effective in unipolar depression and most likely bipolar depression. rTMS courses may be repeated in the management of depressive relapse but there is less evidence for the use of rTMS in the maintenance phase.Conclusions: The science around the use of rTMS is rapidly evolving and there is a considerable need for practitioners to remain abreast of the current state of this literature and its implications for clinical practice. rTMS is an effective antidepressant treatment but its optimal use should be continually informed by knowledge of the state of the art. [ABSTRACT FROM AUTHOR]

Depression and depressive symptoms are prevalent in patients with cancer. Depression is underdiagnosed and therefore, patients often receive inadequate treatment for depression. We have assessed the evidence of primary prophylactic treatment for depression in patients with cancer. The systematic review was prospectively registered at PROSPERO and was conducted according to the Preferred Reporting Items for Systematic Review and Meta-Analysis guidelines. Five electronic databases were searched on the 31st of May 2018 and two independent reviewers screened the papers. Randomized controlled trials of adult patients with cancer treated prophylactically with an antidepressive intervention of any kind using validated assessment tools to measure depression or depressive symptoms were included. No language or publication year restrictions were applied. Seven out of eighteen studies reported a statistically significant prophylactic effect on depression. The studies were classified into three groups based on the type of intervention. The meta-analyses showed a significant difference in favour of pharmacotherapy (RR 0.34, 95% CI 0.18; 0.63), psychotherapy (SMD -0.23,95% CI -0.46; 0.00), and other interventions (SMD -0.17, 95% CI -0.31; −0.03). Only one study had overall low risk of bias and the rest had high risk of bias predominantly due to blinding, incomplete data, or allocation concealment. Preventive measures have been examined in patients with cancer, but no convincing evidence for any specific intervention is present. Depression in patients with cancer can be prevented and prophylactic treatment should be given during oncological treatment but further high quality studies testing safe interventions are still needed. [ABSTRACT FROM AUTHOR]

Bupleurum scorzonerifolium (BS) is one of the sources of Bupleuri Radix, which was first recorded in Shennong's classic of materia medica. It has a medicinal history of 2000 years and is now widely used for the treatment of depression clinically. However, the material basis of antidepressant effects is unclear, and the quality evaluation method is lacking. The paper aims to investigate the antidepressant quality markers (Q-markers) of BS by electrospray ionization quadrupole time-of-flight tandem mass spectrometry (UPLC-ESI-Q-TOF-MS). Firstly, the rat depression model was established by using chronic unpredictable mild stress (CUMS) combined with the solitary confinement method to evaluate the pharmacodynamics of BS. After verification of the antidepressant effect of BS, UPLC-ESI-Q-TOF-MS was used to analyze BS and the blood components of BS. A total of 34 components were identified in BS, in which 8 components, including saikosaponin a (SSa), saikosaponin c (SSc), saikosaponin d (SSd), saikosaponin b 1 (SSb 1), saikosaponin b 2 (SSb 2), glycyrrhetinic acid, nootkatone and valerenic acid, were detected in serum. SSa, SSc, SSd, SSb 1 and SSb 2 were found as metabolites, and glycyrrhetinic acid, nootkatone and valerenic Acid were identified as the prototypes in the blood. The depression model of zebrafish was established with reserpine to verify the antidepressant effect of the potential eight active components. The results showed that all these components could markedly improve the depressive behavior of zebrafish, increase the content of 5-HT and reduce the cortisol content. Finally, according to the principles of effectiveness, accessibility and measurability for Q-markers, SSa, SSc, and SSd were confirmed as Q-markers of BS, and the contents of 3 Q-markers in 10 batches of BS from different origins were determined to be 0.0728–1.465%. In addition, the total contents of 3 Q-markers in BS produced in Lindian, Heilongjiang Province, were higher than those in other origins. This paper provided a reliable method for the quality evaluation of BS for depression treatment. [Display omitted] • Eight antidepressant components of BS have been discovered. • 34 components of BS have been analyzed and identified. • SSa, SSc and SSd have been identified as anti-depression Q-markers of BS. • HPLC-ELSD detection method for anti-depression Q-markers have been established. [ABSTRACT FROM AUTHOR]

Phenelzine (β-phenylethylhydrazine) is a monoamine oxidase (MAO)-inhibiting antidepressant with anxiolytic properties. It possesses a number of important pharmacological properties which may alter the effects of oxidative stress. After conducting a comprehensive literature search, the authors of this review paper aim to provide an overview and discussion of the mechanisms by which phenelzine may attenuate oxidative stress. It inhibits γ-aminobutyric acid (GABA) transaminase, resulting in elevated brain GABA levels, inhibits both MAO and primary amine oxidase and, due to its hydrazine-containing structure, reacts chemically to sequester a number of reactive aldehydes (e.g. acrolein and 4-hydroxy-2-nonenal) proposed to be implicated in oxidative stress in a number of neurodegenerative disorders. Phenelzine is unusual in that it is both an inhibitor of and a substrate for MAO, the latter action producing at least one active metabolite, β-phenylethylidenehydrazine (PEH). This metabolite inhibits GABA transaminase, is a very weak inhibitor of MAO but a strong inhibitor of primary amine oxidase, and sequesters aldehydes. Phenelzine may ameliorate the effects of oxidative stress by reducing formation of reactive metabolites (aldehydes, hydrogen peroxide, ammonia/ammonia derivatives) produced by the interaction of MAO with biogenic amines, by sequestering various other reactive aldehydes and by inhibiting primary amine oxidase. In PC12 cells treated with the neurotoxin MPP+, phenelzine has been reported to reduce several adverse effects of MPP+. It has also been reported to reduce lipid peroxidative damage induced in plasma and platelet proteins by peroxynitrite. In animal models, phenelzine has a neuroprotective effect in global ischemia and in cortical impact traumatic brain injury. Recent studies reported in the literature on the possible involvement of acrolein in spinal cord injury and multiple sclerosis indicate that phenelzine can attenuate adverse effects of acrolein in these models. Results from studies in our laboratories on effects of phenelzine and PEH on primary amine oxidase (which catalyzes formation of toxic aldehydes and is overexpressed in Alzheimer's disease), on sequestration of the toxic aldehyde acrolein, and on reduction of acrolein-induced toxicity in mouse cortical neurons are also reported. • The antidepressant phenelzine reduces several adverse effects of oxidative stress. • It acts through inhibition of MAO and PrAO and through scavenging reactive aldehydes. • These actions may be relevant to treating several neurodegenerative disorders. • Its metabolite PEH is also a strong inhibitor of PrAO and scavenges aldehydes. [ABSTRACT FROM AUTHOR]

Abstract Methoxetamine (MXE) is an N -methyl-D-aspartate (NMDA) receptor antagonist that is chemically and pharmacologically similar to other dissociative substances, such as ketamine and phencyclidine. There are reports on the misuse of MXE, which sometimes resulted in adverse consequences and death. Studies have also shown that MXE has abuse liability and stimulates dopamine neurotransmission in the mesolimbic reward pathway in the brain. These findings have contributed to the negative impression on MXE. However, recent preclinical studies have identified the antidepressant properties of MXE, which are attributed to its ability to affect the glutamatergic and serotonergic systems. MXE is also reported to have analgesic effects. These findings show some of the "redeeming qualities" of MXE and indicate its possible therapeutic uses. In this paper, we have reviewed the findings that provide insights into the adverse and potential therapeutic effects of MXE. We compiled studies on the toxicity, psychotomimetic effects, and abuse liability of MXE, as well as its promising antidepressant and analgesic properties. We also have discussed the mechanism of action that might mediate the somewhat paradoxical effects observed. Importantly, this review provides valuable information on MXE for future research and will enable a better understanding of its psychopharmacological properties and the mechanisms responsible for its unique effects. Highlights • We review the adverse and potential therapeutic effects of methoxetamine (MXE). • MXE, a structural analogue of ketamine, is an NMDA receptor antagonist. • MXE produces toxic and dissociative effects and has abuse liability. • MXE also has antidepressant and analgesic properties like ketamine. • MXE can affect the dopaminergic, glutamatergic, and serotonergic system. [ABSTRACT FROM AUTHOR]

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 divergence of commercial and scientific priorities may exist in the trajectory of other drugs. [ABSTRACT FROM AUTHOR]

This paper presents a computer-aided insight into the receptor-ligand interaction for novel analogs of the lead structure 5-(4-fluorophenyl)-3-(2-hydroxy-3-(4-(2-methoxyphenyl)piperazin-1-yl)propyl)-5-methylimidazolidine-2,4-dione ( 1, MF-8), as part of the search for potent and selective serotonin 5-HT 7 receptor (5-HT 7 R) agents. New hydantoin derivatives ( 4 - 19 ) were designed and synthesized. For 5-phenyl-3-(2-hydroxy-3-(4-(2-ethoxyphenyl)piperazin-1-yl)propyl)-5-methylimidazolidine-2,4-dione ( 4 ), its crystal structure was determined experimentally. Molecular modeling studies were performed, including both pharmacophore and structure-based approaches. New compounds were investigated in radioligand binding assays (RBA) for their affinity toward 5-HT 7 R and selectivity over 5-HT 1A R, dopamine D 2 R and α 1 -, α 2 -and β-adrenoceptors. Selected compounds ( 5 - 8 ) were assessed for their antidepressant and anxiolytic effects in vivo in mice. Most of the tested compounds displayed potent affinity and selectivity for 5-HT 7 R in RBA, in particular seven compounds ( 4, 5, 7, 8 and 10-12, K i  ≤ 10 nM). Antidepressant-like activity in vivo for all tested compounds ( 5 - 8 ) was confirmed. SAR analysis based on both crystallography-supported molecular modeling and RBA results indicated that mono -phenyl substituents at both hydantoin and piperazine are more favorable for 5-HT 7 R affinity than the di -phenyl ones. [ABSTRACT FROM AUTHOR]

Objective: Efficacy and safety of long-term use of antidepressants (AD) in bipolar disorder (BD) patients remains highly controversial. Here we performed a meta-analysis of randomized controlled trials (RCTs) exploring the efficacy and safety of long-term AD use in BD patients.Methods: English-written literature published in peer-reviewed journal was systematically searched from Pubmed, EMBASE, CENTRAL, PsycINFO and Clinicaltrials.gov. Each database was searched from its first available time to August 31, 2016. Additional papers were searched from recent guidelines, expert consensus and systematic reviews by hand. RCTs exploring the efficacy and safety of long-term (≥4m) antidepressant treatment for patients with bipolar disorder were eligible. Two authors (HF, JL) independently extracted the data. Risk ratio (RR), number needed to treat (NNT) and/or number needed to harm (NNH) for new depressive episodes and new manic/hypomanic episodes were calculated. Subgroup analyses were performed based on treatment regimen (AD monotherapy or combined with MS), types of antidepressants, funding source, bipolar subtypes and treatment duration.Results: Eleven trials with 692 bipolar disorder patients were included in the meta-analysis. The risk of bias assessment demonstrated moderate bias risk. Antidepressants were superior to placebo in reducing new depressive episodes in bipolar disorders without increasing risk of new manic/hypomanic episodes either used as monotherapy or in combination with MS. Subgroup analyses revealed that greater benefit and lower risk may be achieved in BD II than in BD I. However, compared with MS monotherapy, AD monotherapy significantly increased the risk of affective switch with no improvement in prophylaxis of new depressive episodes.Conclusions: Reduced new depressive episodes may be achieved by long-term AD treatment with no significantly increased risk of new manic/hypomanic episodes in BD, particularly in BD II. The elevated risk of affective switch of AD monotherapy compared with MS monotherapy may be contributed to the protective effect of MS in diminishing manic/hypomanic episodes. Further studies are needed to verify our findings. [ABSTRACT FROM AUTHOR]

Introduction: St John's wort is a popular herbal remedy recommended by Traditional Chinese Medicine (TCM) practitioners and licensed and widely prescribed for depression in many European countries. However, conflicting data regarding its benefits and risks exist, and the last large meta-analysis on St John's wort use for depression was done in 2008, with no updated meta-analysis available.Methods: Using the keywords [St John's Wort OR Hypericum perforatum OR hypericin OR hyperforin OR johanniskraut OR] AND [depression OR antidepressant OR SSRI], a preliminary search (without language restriction) on the PubMed, Ovid, Clinical Trials Register of the Cochrane Collaboration Depression, Anxiety and Neurosis Group, Cochrane Field for Complementary Medicine, China National Knowledge Infrastructure and WanFang database yielded 5428 papers between 1-Jan-1960 and 1-May-2016.Results: 27 clinical trials with a total of 3808 patients were reviewed, comparing the use of St John's wort and SSRI. In patients with depression, St John's wort demonstrated comparable response (pooled RR 0.983, 95% CI 0.924-1.042, p<0.001) and remission (pooled RR 1.013, 95% CI 0.892-1.134, p<0.001) rate, and significantly lower discontinuation/dropout (pooled OR 0.587, 95% CI 0.478-0.697, p<0.001) rate compared to standard SSRIs. The pooled SMD from baseline HAM-D scores (pooled SMD -0.068, 95% CI -0.127 to 0.021, p<0.001) also support its significant clinical efficacy in ameliorating depressive symptoms.Limitations: Evidence on the long-term efficacy and safety of St. John's wort is limited as the duration of all available studies ranged from 4 to 12 weeks. It is also unclear if St John's wort would be beneficial for patients with severe depression, high suicidality or suicide risk.Conclusion: For patients with mild-to-moderate depression, St John's wort has comparable efficacy and safety when compared to SSRIs. Follow-up studies carried out over a longer duration should be planned to ascertain its benefits. [ABSTRACT FROM AUTHOR]

Abstract: Background: It is widely believed that in randomized controlled trials of antidepressants the difference between drug and placebo response rates is rather small (around 20%), leading to a common perception that antidepressants have limited efficacy. Aim: The aim of the present paper was to present an alternative calculation and interpretation of antidepressant–placebo difference in the treatment response to antidepressant in drug trials which may shed a new light on the efficacy of antidepressants. Issues: We have previously highlighted several controversial points concerning the calculation of antidepressant and placebo response rates in randomised controlled trials, which may influence views concerning the efficacy of drugs, and demonstrated several factors which may lead to overestimation of the placebo effect and underestimation of antidepressant efficacy. The traditional interpretation of antidepressant–placebo difference in randomized controlled trials on major depression has been also challenged previously from at least five points of view but all leading to a conclusion that currently prevailing opinions concerning relative placebo and antidepressant response rates overestimate placebo response, and thereby underestimate efficacy of antidepressant drugs. In our present paper we propose another method for calculating placebo and antidepressant response rates which may shed new light on an overlooked aspect of the efficacy of these drugs. Conclusions: We contend that opinions on the effectiveness of antidepressants should be reconsidered, and comparisons with placebo should be more carefully applied. Interpretation of the placebo response is of crucial importance for establishing the efficacy of antidepressive medications, and psychiatry should not become the hostage of placebo. [Copyright &y& Elsevier]

Up to one third of patients adequately treated for Major Depressive Disorder (MDD) do not respond to multiple interventions. Many studies investigated predictors in MDD outcome, but no study focused on predictors of non-response or non-remission to antidepressants in subjects with treatment resistant depression (TRD). The present study aimed to evaluate possible socio-demographic and clinical predictors of non-response and non-remission in MDD patients who failed to benefit from at least one antidepressant trial. A total of 51 papers were included. A number of severity indicators, such as longer duration of depressive episode, moderate-high suicidal risk, anxious comorbidity, higher number of hospitalizations and higher dosage of antidepressants, were associated with non-response as well as age. Interestingly, severity of illness, as well as comorbid personality disorders and anxiety symptoms, had also a predictive value in non-remission with the addition of marital status. Considering limitations, selected studies were observational or randomized non controlled/controlled trials and different TRD definitions and outcome measures were used. Overall, predictors of outcome were similar to MDD, but specific socio-demographic and clinical factors should be considered in clinical practice to formulate a more focused treatment in TRD patients. [ABSTRACT FROM AUTHOR]

Background: In the last few decades, there has been a growing interest in anxiety disorders (AnxD) in the perinatal period. Although AnxD are diagnosed in 4-39% of pregnant women and in up to 16% of women after delivery, evidence on their clinical management is limited.Methods: A systematic review was conducted on pharmacological and non-pharmacological treatment of AnxD in the perinatal period. Relevant papers published from January 1st 2015 were identified searching the electronic databases MEDLINE, Embase, PsycINFO and the Cochrane Library.Results: 18 articles met inclusion criteria. Selected studies supported the use of cognitive-behavioural therapy (CBT) for obsessive-compulsive disorder (OCD), panic disorder (PD) and specific phobia both in pregnancy and postpartum. Selective serotonin reuptake inhibitors (SSRIs) led to significant OCD and PD improvement both in pregnancy and postpartum with no side effects for the babies. In the largest clinical sample to date, 65% of postpartum patients who entered the open-label trial of fluvoxamine (up to 300mg/day) experienced a 30% or greater decrease in the total score of the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS). During pregnancy, SSRIs and tricyclic antidepressants (TCAs) led to remission of panic symptoms and healthy outcomes for the babies.Limitations: Study design, mostly case reports, and enrolment of subjects mainly from outpatient specialty units might have limited community-wide generalisability.Conclusions: Keeping in mind the scantiness and heterogeneity of the available literature, the best interpretation of the available evidence appears to be that CBT should be the first treatment offered to pregnant and breastfeeding women with AnxD. However SSRIs can represent a first line treatment strategy, and not exclusively in cases where AnxD is refractory to CBT. [ABSTRACT FROM AUTHOR]

In this paper, a novel nano-sorbent is fabricated by the surface grafting of poly[β-CD/allylamine-co- N -isopropylacrylamide] onto modified magnetite nano-particles by 3-mercaptopropyltrimethoxysilane. The polymer grafted magnetite nano-particles was characterized by Fourier transform infrared spectroscopy, thermogravimetric analysis, elemental analysis, scanning electron microscopy, and transmission electron microscopy. The feasibility of employing this nano-sorbent for extraction of trace venlafaxine in pharmaceutical samples and human biological fluids are investigated. The effect of various parameters such as pH, reaction temperature, and contact time was evaluated. The result revealed that the best sorption of venlafaxine by the magnetite nano-sorbent occurred at 35 °C at an optimum pH of 5. The kinetics of the venlafaxine shows accessibility of active sites in the grafted polymer onto the drug. The equilibrium data of venlafaxine by grafted magnetite nano-sorbent are well represented by the Langmuir and Freundlich isotherm models. The adsorption capacity of venlafaxine is found 142.8 mg g −1 and indicated the homogeneous sites onto polymer grafted magnetite nano-sorbent surface. Nearly 80% of venlafaxine was released in simulated intestinal fluid, pH 7.4, in 30 h and 90% in simulated gastric fluid, pH 1.2, in 1 h. The venlafaxine loaded-polymer grafted magnetite nano-particles were successfully applied for the extraction in urine and pharmaceutical samples. [ABSTRACT FROM AUTHOR]

Background Major depressive disorder (MDD) is a common disease with high morbidity and still unsatisfying treatment response. Both MDD pathogenesis and antidepressant effect are supposed to be strongly affected by genetic polymorphisms. Among promising candidate genes, distrupted in schizophrenia 1 (DISC1), translin-associated factor X (TSNAX) and D-amino acid oxidase activator (DAOA) were suggested since their regulator role in neurodevelopment, neuroplasticity and neurotransmission, and previous evidence of cross-involvement in major psychiatric diseases. Methods The present paper investigated the role of 13 SNPs within the reported genes in MDD susceptibility through a case-control (n=320 and n=150, respectively) study and in citalopram efficacy (n=157). Measures of citalopram efficacy were response (4th week) and remission (12th week). Pharmacogenetic findings were tested in the STAR?D genome-wide dataset (n=1892) for replication. Results Evidence of association among rs3738401 (DISC1), rs1615409 and rs766288 (TSNAX) and MDD was found (p=0.004, p=0.0019, and p=0.008, respectively). A trend of association between remission and DISC1 rs821616 and DAOA rs778294 was detected, and confirmation was found for rs778294 by repeated-measure ANOVA (p=0.0008). In the STAR?D a cluster of SNPs from 20 to 40 Kbp from DISC1 findings in the original sample was associated with citalopram response, as well as rs778330 (12,325 bp from rs778294). Limitations Relatively small size of the original sample and focus on only three candidate genes. Conclusions The present study supported a role of DISC1-TSNAX variants in MDD susceptibility. On the other hand, genetic regions around DAOA rs778294 and DISC1 rs6675281-rs1000731 may influence citalopram efficacy. [ABSTRACT FROM AUTHOR]

This paper updates our previous review of the evidence base for managing depression in old age while focusing more specifically on the use of antidepressants. Overall, recent systematic reviews and meta-analyses indicate that antidepressants are effective in the acute treatment of depression in old age but that the superiority of active drug over placebo is quite modest. The depression of Alzheimer's disease is probably not treated effectively with antidepressants. The most consistent evidence is for the effectiveness of continued antidepressant treatment in those depressed patients who respond well to acute treatment. There remains a clear need for more research to identify effective treatments for resistant depression though therapeutic nihilism should be avoided if first-line treatment fails. [ABSTRACT FROM AUTHOR]

• This paper reviews the pharmacogenetics of the serotonin reuptake inhibitors currently endorsed for the treatment of PTSD. • The focus is on genes implicated both in PTSD and the pharmacokinetics or pharmacodynamics of these medications. • It concludes with overview of emerging commercial platforms and directions for future pharmacogenetic research on PTSD. Progress in PTSD pharmacotherapy has lagged far behind that of other major mental illnesses. Unfortunately, due to the enormous costs and lengthy process involved in bringing drugs to market, delivering new treatments to patients with PTSD in the near future will remain a challenge. However, by capitalizing on recent advances in the pharmacogenetics of antidepressants, precision psychiatry approaches can be leveraged to optimize the delivery of currently-available medications in a fraction of the time and cost required to develop novel therapeutics. This paper provides a review of the pharmacogenetics of the four serotonin reuptake inhibitors (SRIs) that are currently endorsed for the treatment of PTSD (paroxetine, sertraline, fluoxetine and venlafaxine). It focuses on genes involved in SRI pharmacokinetics (including the liver enzyme genes CYP2D6 and CYP2C19 and blood-brain barrier-relevant gene ABCB1) as well as those implicated in both SRI pharmacodynamics and the pathophysiology of PTSD and related conditions (e.g., BDNF , FKBP5, HTR1A, HTR2A , TPH2). The review concludes with an overview of emerging commercial platforms for pharmacogenetic-guided prescription and a discussion of challenges and directions for future pharmacogenetic research on PTSD. [ABSTRACT FROM AUTHOR]

Abstract: Ethnopharmacological relevance: Acanthopanax senticosus, classified into the family of Araliaceae, has been known for thousands of years as a remedy and is used to treat various diseases in traditional Chinese medicine system including hypertension, ischemic heart disease and hepatitis. Aim of the study: This study aimed to examine the protective effects of aqueous extract from Acanthopanax senticosus (ASE) on corticosterone-induced neurotoxicity and its possible mechanisms, using PC12 cells as a suitable in vitro model of depression. Materials and methods: In this paper, PC12 cells were treated with 200μM of corticosterone in the absence or presence of ASE in varying concentrations for 24h. Then, cell viability was measured by MTT assay. The release amount of lactate dehydrogenase (LDH) was quantified using LDH assay kit. Apoptosis of PC12 cells was measured by Annexin V-FITC and PI labeling. The intracellular Ca2+ content was tested by fluorescent labeling. The mRNA level of brain-derived neurotrophic factor (BDNF) was examined by real-time RT-PCR, and the expression of cAMP response element binding protein (CREB) was determined by western blotting. Results: The results showed that treatment with 200μM of corticosterone could induce cytotoxicity in PC12 cells. However, different concentrations of ASE (50, 100, 200, and 400μg/mL) significantly increased the cell viability, decreased the LDH release, suppressed the apoptosis of PC12 cells, attenuated the intracellular Ca2+ overloading, up-regulated the BDNF mRNA level and CREB protein expression compared with the corresponding corticosterone-treated group. Conclusion: The present results suggest that ASE exerts a neuroprotective effect on corticosterone-induced neurotoxicity in PC12 cells, which may be one of the acting mechanisms that accounts for the in vivo antidepressant activity of ASE. [Copyright &y& Elsevier]

Abstract: This paper analyzes local and regional geographic variability in the use of antidepressant, antipsychotic and stimulant medications in the United States. Using a data set that covers 60% of prescriptions written in the United States, we find that use of antidepressants in three digit postal codes ranged from less than 1% of residents to more than 40% residents. Stimulant and antipsychotic use exhibited similar levels of local geographic variability. A Kulldorf Spatial Scan identified clusters of elevated use of antidepressants (RR 1.46; p<0.001), antipsychotics (RR 1.42; p<0.001), and stimulants (RR 1.77; p<0.001). Using a multilevel model, we find that access to health care, insurance coverage and pharmaceutical marketing efforts explain much of the geographic variation in use. [Copyright &y& Elsevier]

Abstract: The growing body of evidence implicates the significance of oxidative stress in the pathophysiology of depression. The aim of this paper was to examine N-acetylcysteine (NAC) – a putative precursor of the most important tissue antioxidant glutathione – in an animal model of depression and in ex vivo assays to detect oxidative stress parameters. Imipramine (IMI), a classical and clinically-approved antidepressant drug was also under investigation. Male Wistar rats which underwent either bulbectomy (BULB; removal of the olfactory bulbs) or sham surgery (SHAM; olfactory bulbs were left undestroyed) were treated acutely or repeatedly with NAC (50–100mg/kg, ip) or IMI (10mg/kg, ip). Following 10-daily injections with NAC or IMI or their solvents, or 9-daily injections with a corresponding solvent plus acute NAC or acute IMI forced swimming test on day 10, and locomotor activity were performed; immediately after behavioral tests animals were decapitated. Biochemical tests (the total antioxidant capacity — TAC and the superoxide dismutase activity — SOD) were performed on homogenates in several brain structures. In behavioral studies, chronic (but not acute) administration of NAC resulted in a dose-dependent reduction in the immobility time seen only in BULB rats while chronic IMI produced a significant decrease in this parameter in both SHAM and BULB animals. On the other hand, chronic administration of NAC and IMI resulted in a significant increase in cellular antioxidant mechanisms (SOD activity) that reversed the effects of BULB in the frontal cortex, hippocampus and striatum. Our study further supports the antidepressant-like activity of NAC and links its effect as well as IMI actions with the enhancement of brain SOD activity. [Copyright &y& Elsevier]

Abstract: Background: Knowledge regarding the relative cost-effectiveness of different antidepressants is crucial for the planning of depression treatment. However, there have been only a small number of reviews of such evidence and synthesizing economic evidence across studies is methodologically challenging. In particular, there have been few reviews of the methods employed in database analyses (studies that use data from real-world practice). Methods: Published economic evaluations based on database analyses were systematically reviewed to compare antidepressant treatments in depression. Prospective studies of cost-effectiveness were also reviewed to highlight unanswered questions through comparisons between these two different study designs. Results: Forty papers met the criteria and were included. A relatively large number of industry-sponsored evaluations of escitalopram were identified and these found escitalopram to be potentially cost-effective in depression treatment. Evidence of cost-effectiveness differences between other individual SSRIs was not unequivocally established. Inconsistent findings further emerged concerning the cost-effectiveness of SSRIs versus TCAs between retrospective database analyses and prospective studies. Limitations: Different outcome measures and cost perspectives make it difficult to make comparisons across studies. Conclusions: Evidence regarding the cost-effectiveness of different antidepressants in depression continues to accumulate. Beyond the efficacy or tolerability data found for newer antidepressants in controlled trials, further research from real-world settings is needed to examine the relative cost-effectiveness of different antidepressant agents. [Copyright &y& Elsevier]

Abstract: Background: The insertion/deletion (I/D) polymorphism of angiotensin-converting enzyme (ACE) gene has been implicated in susceptibility to major depressive disorder (MDD) and its treatment response; however, a large number of studies have reported inconsistent results. The aim of this study is to examine the role of I/D polymorphism of ACE gene in MDD risk and its treatment response by a case–control study and meta-analysis. Methods: Three hundred and sixty eight depressed patients who met DSM-IV criteria for major depressive disorder and 371 normal controls were recruited for the study. We searched Pubmed, Embase, CNKI, Wanfang, and Weipu database, covering all papers until March 31, 2011. Statistical analysis was performed using the software STATA 10.0. Results: Genotype and allele distributions of ACE I/D were not significantly different between case and control groups. No significant association with treatment response was discovered. A total of 2479 cases and 7744 controls in 15 case–control studies were included in this meta-analysis. The results indicated that the D/D homozygote carriers had an 18% increased risk of MDD, when compared with the homozygotes I/I and heterozygote I/D [odds ratio (OR)=1.18, 95% confidence interval (CI):1.04–1.33]. In the subgroup analysis, significant elevated risks were associated with D/D homozygote carriers in Caucasians (OR=1.20 and 95% CI: 1.04–1.38 for D/D vs I/D+I/I) but not in Asians. Moderate trends of an increased risk in the D allele carriers from total sample (OR, 1.15; 95% CI: 1.02–1.30) was also observed. The D/D homozygote carriers were associated with a 28% increased risk of MDD relative to the homozygotes I/I (OR 1.28; 95% CI: 1.11–1.49). In subgroup analysis, Caucasians showed significant association (OR 1.30; 95% CI: 1.09–1.56). No association was found in the Asian groups. No publication bias was observed in this meta-analysis by using the Egger method. Conclusions: The ACE I/D polymorphism is not associated with MDD and its treatment response in a Chinese case–control study. Meta-analysis evidence suggests that the I/D polymorphism of ACE gene may be a risk factor of major depressive disorder in Caucasians. [Copyright &y& Elsevier]

Abstract: Research in the area of herbal psychopharmacology has increased markedly over the past decades. To date however, a comprehensive review of herbal antidepressant, anxiolytic and hypnotic psychopharmacology and applications in depression, anxiety and insomnia has been absent. A search of MEDLINE (PubMed), CINAHL, PsycINFO, and the Cochrane Library databases was conducted (up to February 21st 2011) on commonly used psychotropic herbal medicines. A review of the literature was conducted to ascertain mechanisms of action of these botanicals, in addition to a systematic review of controlled clinical trials for treatment of mood, anxiety and sleep disorders, which are common comorbid psychiatric disorders. Specific emphasis was given to emerging phytomedicines. Analysis of evidence levels was conducted, as were effect sizes (Cohen''s d) where data were available. Results provided evidence of a range of neurochemical, endocrinological, and epigenetic effects for 21 individual phytomedicines, which are detailed in this paper. Sixty six controlled studies were located involving eleven phytomedicines. Several of these provide a high level of evidence, such as Hypericum perforatum for major depression, and Piper methysticum for anxiety disorders. Several human clinical trials provide preliminary positive evidence of antidepressant effects (Echium amoenum, Crocus sativus, and Rhodiola rosea) and anxiolytic activity (Matricaria recutita, Ginkgo biloba, Passiflora incanata, E. amoenum, and Scutellaria lateriflora). Caution should however be taken when interpreting the results as many studies have not been replicated. Several herbal medicines with in vitro and in vivo evidence are currently unexplored in human studies, and along with use of emerging genetic technologies “herbomics”, are areas of potential future research. [Copyright &y& Elsevier]

Abstract: Cloud point (CP) of an amphiphile can be considered as the limit of its solubility as it phase separates at temperatures above the CP. The clouding components release their solvated water and separate out from the solution. In the present paper, we report the thermodynamics of clouding in amphiphilic drug, imipramine hydrochloride (IMP—a tricyclic antidepressant drug), in the presence of additives (viz., alcohols and surfactants). Surfactants are extensively used in drug delivery as drug carriers. For all cases the standard Gibbs energy change of solubilization () is evaluated and, found to be positive. However, the standard enthalpy change (), and the product of standard entropy change and temperature () values are found negative as well as positive. These values are depending upon the type and nature of the additive, and the results are discussed on the basis of these factors. [Copyright &y& Elsevier]

Abstract: In this paper, a fast, sensitive and selective LC–MS/MS method is described for the simultaneous determination of amitriptyline, imipramine, clomipramine, fluoxetine, paroxetine, sertraline, fluvoxamine, citalopram and venlafaxine, as well as some of their main metabolites (nortriptyline, desipramine, norclomipramine and norfluoxetine), in oral fluid and plasma. The sample (0.2mL) was extracted with an automated solid-phase extraction system (ASPEC XL), using mixed mode OASIS MCX cartridges. Chromatographic separation was performed in a Sunfire C18 IS column (20mm×2.1mm, 3.5μm), using a gradient of acetonitrile and ammonium formate (pH 3; 2mM) as mobile phase, which allowed the elution of all the compounds in less than 5min. The method has been fully validated in both specimens. This method was initially applied to the analysis of oral fluid and plasma samples from patients on antidepressant treatment in order to assess for which compounds it was likely to find a good correlation between both matrices. The best results were obtained for venlafaxine, so the study was extended for this compound, comparing the ratio between oral fluid and plasma concentrations (R OF/PL) in five patients on venlafaxine treatment when both samples were collected simultaneously on four different occasions. An important inter and intraindividual variability was found in oral fluid concentrations for 150mg dose (mean=287.5ng/m, range 58.8–531.2ng/mL) and for 75mg dose (mean=186.3ng/mL, range=82.1–289.2ng/mL). R OF/PL was calculated for each patient on the four different occasions, showing also a high variability (CV=24.2–69.6%). [Copyright &y& Elsevier]

Abstract: Background: Reduced dopaminergic function may occur in depressive disorders. In this paper the results of two pilot studies examining different aspects of the dopamine system in depression are presented. First, the binding of [11C]FLB 457 to extrastriatal D2 receptors was measured in a group of depressed patients. Second, the hypothesis that selective serotonin reuptake inhibiting (SSRI) antidepressants affect the striatal binding of [11C]raclopride was tested. Methods: In the first study the binding of [11C]FLB 457 was compared between 7 people with depression and 7 healthy controls. In the second study the binding of [11C]raclopride to striatal D2/3 receptors was compared between 8 people taking SSRI antidepressant medication and 8 healthy controls. Results: There was no difference in the binding of [11C]FLB 457 between the two groups. [11C]raclopride binding was reduced in the dorsal striatum of people taking antidepressants suggesting either that D2/3 expression was reduced, or that dopamine release was increased, compared to untreated controls. Limitations: The depressed patients were not severely depressed and were not matched for gender with controls. In the raclopride group the patients and controls were not matched by gender and were taking different SSRI antidepressants. Conclusion: We found no support for the hypothesis that dopamine D2 receptor expression is altered in extrastriatal brain regions in depression. SSRI antidepressants were associated with reduced [11C]raclopride binding in the dorsal striatum supporting the hypothesis that therapeutic effects of such drugs may, in part, be due to changes in the dopamine system. [Copyright &y& Elsevier]

Abstract: In the search of predictors of antidepressant efficacy, much interest has recently focused on pro-inflammatory proteins, as they were found to be elevated during major depressives states and decreased by antidepressant drugs. In the present paper we investigated the role of the genes coding for heat-shock-70 family proteins, recently hypothesized to be activated by antidepressants and thus mediate the reduction of pro-inflammatory cytosines. One hundred and forty two hospitalised patients, affected by major depression and treated with antidepressants drugs for a major depressive episode were evaluated for depressive severity at the baseline and at the discharge and genotyped for five SNPs within the genes HSPA1L, HSPA1A and HSPA1B. Markers were not individually associated with symptom severity after treatment. Instead, we found a three markers haplotype, including SNPs within HSPA1L and HSPA1A, associated with a poorer response to antidepressant treatment (p =0.005). Single markers as well as haplotypes were not associated with other clinical features. In conclusion, genetic variants within the genes coding for HSP-70 family proteins may affect the action of antidepressants and thus their therapeutic efficacy. [Copyright &y& Elsevier]

Abstract: Objective: Treatment resistant depression is a common clinical problem and a major public health concern. The use of antidepressant combinations to overcome treatment resistance, while somewhat controversial, is a popular strategy in practice. This paper reviews published trials on combination antidepressants with a view to inform clinical practice. Method: A systematic but selective review of the published literature was conducted using EMBASE, PSYCHLIT and MEDLINE with relevant search terms. Results: A number of trials suggesting efficacy of combination antidepressants were found. These are incorporated into a number of treatment guidelines for the management of treatment refractory depression. Clinicians should be cautious regarding pharmacokinetic and pharmacodynamic interactions, including the serotonin syndrome, however combination strategies are an effective option. Conclusions: Many antidepressants can be usefully combined especially if they engage separate mechanisms of action. Clinically, antidepressant combinations provide a useful resort in otherwise treatment resistant individuals. However, much further research is needed to determine relative efficacy and determine long term outcome. [Copyright &y& Elsevier]

The forced swim test (FST) and the tail suspension test (TST) are used widely for measuring the pharmacological effects of antidepressant drugs or changes in stress-evoked behavior in mice. However, inconsistent scoring techniques and poor reproducibility may result from their reliance on subjective ratings by observers to score behavioral changes. In this paper, automated versions of the mouse FST and TST were characterized and validated against observer ratings. For the FST, a commercially available video tracking system (SMART II; San Diego Instruments) measured the duration that mice swam in water-filled cylinders at a set velocity. For the TST, a commercially available automated device (Med Associates, St. Albans, VT) measured input from a strain gauge to detect movements of mice suspended from an elevated bar. Dose-dependent effects of the antidepressant desipramine on FST and TST immobility were measured in CD-1 mice using both automated devices and manual scoring from videotapes. Similar dose–response curves were obtained using both methods. However, a wide range of correlations for raters in the FST indicated that scoring criteria varied for individual raters despite similar instructions. Automated versions of the mouse FST and TST are now available and provide several advantages, including an opportunity to standardize methods across laboratories. [Copyright &y& Elsevier]

Although the effects of antidepressants on glucocorticoid hormones and their receptors are relevant for the therapeutic action of these drugs, the molecular mechanisms underlying these effects are unclear. Studies in depressed patients, animals and cellular models have demonstrated that antidepressants increase glucocorticoid receptor (GR) and mineralocorticoid receptor (MR) expression and function; this, in turn, is associated with enhanced negative feedback by endogenous glucocorticoids, and thus with reduced resting and stimulated hypothalamic–pituitary–adrenal (HPA) axis activity. In a series of studies conducted over the last few years, we have shown that antidepressants modulate GR function in vitro by inhibiting membrane steroid transporters that regulate the intracellular concentration of glucocorticoids. In this paper, we will review the effects of membrane steroid transporters and antidepressants on corticosteroid receptors. We will then present our unpublished data on GR live microscopy in vitro, showing that ligand-induced translocation of the GR starts within 30 seconds and is completed within minutes. Furthermore, we will present our new data using an in situ brain perfusion model in anaesthetised guinea-pigs, showing that entry of cortisol to the brain of these animals is limited at the blood–brain barrier (BBB). Finally, we will present a comprehensive discussion of our published findings on the effects of chemically unrelated antidepressants on membrane steroid transporters, in mouse fibroblasts and rat cortical neurones. We propose that antidepressants in humans could inhibit steroid transporters localised on the BBB and in neurones, like the multidrug resistance p-glycoprotein, and thus increase the access of cortisol to the brain and the glucocorticoid-mediated negative feedback on the HPA axis. Enhanced cortisol action in the brain might prove to be a successful approach to maximise therapeutic antidepressant effects. [Copyright &y& Elsevier]

The purpose of this review is to integrate what is currently known about the role of brain-derived neurotrophic factor (BDNF) in the pathophysiology of mood disorders including major depressive disorder (MDD) and bipolar disorder (BD). We reviewed the pre-clinical and clinical papers demonstrating that BDNF plays a role in the pathophysiology of mood disorders and in the mechanism of action of therapeutic agents. Pre-clinical studies suggest that the expression of BDNF might be a downstream target of antidepressant treatments and mood stabilizers such as lithium and valproate, and that BDNF exerts antidepressant activity in animal models of depression. Furthermore, BDNF protects against stress-induced neuronal damage, and it might affect neurogenesis in the hippocampus, which is thought to be involved in the pathogenesis of mood disorders. Clinical studies have demonstrated that serum levels of BDNF in drug-naive patients with MDD are significantly decreased as compared with normal controls, and that BDNF might be an important agent for therapeutic recovery from MDD. Moreover, recent findings from family-based association studies have suggested that the BDNF gene is a potential risk locus for the development of BD. These findings suggest that BDNF plays a critical role in the pathophysiology of mood disorders and in the activity of therapeutic agents in patients with mood disorders. New agents capable of enhancing BDNF levels may lead aid the development of novel therapeutic drugs for patients with mood disorders. [Copyright &y& Elsevier]

The objective of this paper is to evaluate the efficacy of gepirone immediate-release (gepirone-IR) for relapse prevention in outpatients with MDD who had responded to initial gepirone-IR therapy. Patients with MDD and a HAM-D25 score ⩾20 were treated with open-label gepirone-IR 20 to 90 mg/day for 6 weeks. Responders with a HAM-D17 total score ⩽12 or with a ⩾50% reduction in total HAM-D17 score and at least a “much improved” or “very much improved” CGI improvement score, were randomized to gepirone-IR or placebo for six additional weeks. Time to relapse was defined in six ways [(1) return to ⩾75% of baseline HAM-D17 total score; (2) CGI improvement score of “no change” or “minimally worse,” “much worse” or “very much worse” than baseline (⩾4); and four more definitions combining the HAM-D17 or CGI criteria with discontinuation, or discontinuation due to lack of efficacy] and analyzed for the ITT population using the LOCF method. Of 134 patients in the open-label phase, 70 were responders. In the double-blind phase, the relapse rate was significantly lower with gepirone-IR than with placebo (P⩽0.05) for four of the six definitions of relapse. Discontinuations of gepirone-IR due to adverse events were observed for 26.9% of patients in the open-label phase, and four patients (6%) during the double-blind phase. The most frequent adverse events with gepirone-IR were dizziness, nausea, headache, and somnolence, and with placebo were headache and paresthesia. A relapse-prevention study of longer duration is needed to confirm these preliminary results. Gepirone-IR was significantly more effective than placebo for relapse prevention and demonstrated acceptable tolerability in outpatient responders with MDD. [Copyright &y& Elsevier]

One of the most prevalent disorders in present society is depression. The development of treatments for this disorder, beginning with the tricyclic antidepressants and leading to the development of selective serotonin reuptake inhibitors, has focused on compounds that block the function of the serotonin transporter (SERT). In this paper, we have performed Comparative Molecular Field Analysis (CoMFA) using data generated from rat brain synaptosomes and heterologous expression systems expressing rat SERT. Using these models, we have described the molecular requirements for the interactions of antidepressants with SERTs. In addition, molecular studies were performed using chimeric human/Drosophila SERTs and SERT point mutants. These studies focused on identifying regions or discrete amino acids on SERT that may be responsible for recognizing antidepressants. [Copyright &y& Elsevier]

Background: venlafaxine has been available for use as an antidepressant in the United States for a decade.Objective: Comprehensive reviews of venlafaxine have been published elsewhere; thus, this update focuses on newer issues of treatment remission in depression, treatment-resistant depression, and extended-release venlafaxine for generalized anxiety disorder (GAD).Methods: Relevant clinical literature from 1993 through 2003 was identified from database searches of MEDLINE and International Pharmaceutical Abstracts, and from manual searches of reference lists of the identified papers. Search terms included venlafaxine extended-release, venlafaxine XR, treatment-resistant depression, depressive disorders, anxiety disorders, generalized anxiety disorder, and antidepressive agents second generation.Results: With its dual action of serotonin and noradrenergic reuptake inhibition, venlafaxine has been shown to be superior in efficacy to selective serotonin reuptake inhibitors for severe major depressive disorder, treatment-resistant depression, and depressive symptom remission. Its demonstrated efficacy for both short- and long-term treatment of GAD has led to its use for obsessive-compulsive disorder and chronic pain syndromes, although inadequate clinical literature currently exists to support these latter 2 uses. In the past decade, no new or unexpected adverse events have been identified with venlafaxine therapy, except a possibly greater risk of fatal overdose compared with other serotonergic drugs, suggesting the need for caution in patients with suicidal ideation. Because venlafaxine is a potent serotonin agonist, caution must also be exercised to prevent the possibility of serotonin syndrome when used with other serotonin agonists, and its dose should be tapered very gradually to minimize the risk of a serotonin withdrawal reaction.Conclusion: Venlafaxine has emerged as a successful post-SSRI-era antidepressant with an expanded range of uses since it was first marketed. [Copyright &y& Elsevier]

While most patients with depression, anxiety, or at-risk drinking receive care exclusively in primary care settings, primary care providers experience challenges in diagnosing and treating these common problems. Over the past two decades, the collaborative care model has addressed these challenges. However, this model has been adopted very slowly due to the high costs of care managers; inability to sustain their role in small practices; and the perceived lack of relevance of interventions focused on a specific psychiatric diagnosis. Thus, we designed an innovative randomized clinical trial (RCT), the Primary Care Assessment and Research of a Telephone Intervention for Neuropsychiatric Conditions with Education and Resources study (PARTNERs). This RCT compared the outcomes of enhanced usual care and a novel model of collaborative care in primary care patients with depressive disorders, generalized anxiety, social phobia, panic disorder, at-risk drinking, or alcohol use disorders. These conditions were selected because they are present in almost a third of patients seen in primary care settings. Innovations included assigning the care manager role to trained lay providers supported by computer-based tools; providing all care management centrally by phone - i.e., the intervention was delivered without any face-to-face contact between the patient and the care team; and basing patient eligibility and treatment selection on a transdiagnostic approach using the same eligibility criteria and the same treatment algorithms regardless of the participants' specific psychiatric diagnosis. This paper describes the design of this RCT and discusses the rationale for its main design features. [ABSTRACT FROM AUTHOR]

• First report of comprehensive screening method of antipsychotics in equine plasma. • Simultaneous detection of over 80 antipsychotics and other prohibited substances. • Development of an efficient liquid chromatography/tandem mass spectrometry method. • Drug targets detected at low-parts-per-billion levels after solid phase extraction. Antipsychotics are banned substances and considered by the Fédération Equestrian Internationale (FEI) to have no legitimate use in equine medicine and/or have a high potential for abuse. These substances are also prohibited in horseracing according to Article 6 of the International Agreement on Breeding, Racing and Wagering (published by the International Federation of Horseracing Authorities). Over the years, antipsychotics have been abused or misused in equestrian sports and horseracing. A recent review of literature shows that there is yet a comprehensive screening method for antipsychotics in equine samples. This paper describes an efficient liquid chromatography/tandem mass spectrometry (LC/MS/MS) method for the simultaneous detection of over 80 antipsychotics and other prohibited substances at sub-parts-per-billion (ppb) to low-ppb levels in equine plasma after solid-phase extraction (SPE). [ABSTRACT FROM AUTHOR]