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Aim: Selective serotonin reuptake inhibitors (SSRIs) are used to treat major depressive disorder (MDD) and other psychiatric disorders (e.g., obsessive compulsive disorder, social anxiety disorder, and panic disorder). In MDD treatment, SSRIs do not show remission in approximately 30% of patients, indicating a need for a better treatment option. Forced swimming test (FST) is a behavioral assay to evaluate depression‐like behavior and antidepressant efficacy in rodents. In the present study, we evaluated the combination effect of brexpiprazole with SSRIs on FST in mice, in order to investigate their synergistic effect. Methods: Brexpiprazole (0.003 mg/kg) was intraperitoneally injected to mice 15 min before testing. Escitalopram (10 mg/kg), fluoxetine (75 mg/kg), paroxetine (10 mg/kg), or sertraline (15 mg/kg) were orally administered to mice 60 min before testing. Then, the mice were placed in water and immobility time was measured. Data from animals treated with escitalopram, fluoxetine, paroxetine, and sertraline were pooled as SSRI‐treated group data. Results: Combination treatment of brexpiprazole with SSRIs reduced immobility time in FST more than vehicle or each single treatment. A significant interaction effect was confirmed in the combination of brexpiprazole and SSRIs (p = 0.0411). Conclusion: Efficacy of adjunctive brexpiprazole has already been demonstrated in clinical trials in MDD patients not adequately responding to antidepressants including escitalopram, fluoxetine, paroxetine, and sertraline. The synergistic antidepressant‐like effect of brexpiprazole with SSRIs found in this study supports the already known clinical findings. [ABSTRACT FROM AUTHOR]

Despite advances in clinical trial design, failure rates near 80% in phase 2 and 50% in phase 3 have recently been reported. The challenges to successful drug development are particularly acute in central nervous system trials such as for pain, schizophrenia, mania, and depression because high‐placebo response rates lessen assay sensitivity, diminish estimated treatment effect sizes, and thereby decrease statistical power. This paper addresses the importance of rigorous patient selection in major depressive disorder trials through an enhanced enrichment paradigm. This approach led to a redefinition of an ongoing, blinded phase 3 trial algorithm for patient inclusion (1) to eliminate further randomization of transient placebo responders and (2) to exclude previously randomized transient responders from the primary analysis of the double blind phase of the trial. It is illustrated for a case study for the comparison between brexpiprazole + antidepressant therapy and placebo + antidepressant therapy. Analysis of the primary endpoint showed that efficacy of brexpiprazole versus placebo could not be established statistically if the original algorithm for identification of placebo responders was used, but the enhanced enrichment approach did statistically demonstrate efficacy. Additionally, the enhanced enrichment approach identified a target population with a clinically meaningful treatment effect. Through its successful identification of a target population, the innovative enhanced enrichment approach enabled the demonstration of a positive treatment effect in a very challenging area of depression research. [ABSTRACT FROM AUTHOR]

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

Objective: Atypical antipsychotics (AAPs) have been hypothesized to be beneficial in treatment-resistant depression (TRD). This paper will review a biochemical rationale and will summarize the data regarding the effectiveness of AAPs in TRD. Method: Studies were identified using searches of Pubmed/Medline, EMBase and the Cochrane databases by cross-referencing the term ‘depression’ with each of the six AAPs. Results: After initial positive, short case reports and clinical trials, larger studies failed to show the effectiveness of AAPs combined with antidepressants for TRD. More recently, larger scale clinical trials have supported the effectiveness of at least some of these medications. While AAPs have gained in popularity for TRD, there are nagging concerns regarding risks such as metabolic syndrome and tardive dyskinesia. Conclusion: The existing research provides some support for the beneficial effects of AAPs when combined with SSRI’s in TRD. These medications pose significant risks that must be considered in their use. [ABSTRACT FROM AUTHOR]

ABSTRACT Nefazodone, an antidepressant agent with a phenylpiperazine structure, has a pharmacological profile that is distinct from other antidepressant drugs. Like many other antidepressants, nefazodone inhibits the reuptake of norepinephrine and serotonin from the synaptic cleft. Unlike other antidepressants, nefazodone is also a potent antagonist of 5-HT2 serotonergic receptors. In addition, nefazodone is a weak antagonist of α1-adrenergic receptors, but has little or no affinity for cholinergic, histaminergic, or dopaminergic receptors. In placebo-controlled clinical trials, nefazodone has been found to be an effective antidepressant drug with minimal cardiovascular action and significantly fewer side effects than imipramine. Since nefazodone is an effective antidepressant with a low incidence of serious adverse effects, it may be particularly useful in major depressive disorder patients who are intolerant of the anticholinergic or serotonergic side effects of other antidepressants, or who do not respond to treatment with other antidepressant agents. In this paper, we review the mechanisms of action, the pharmacokinetics, and the antidepressant efficacy of nefazodone. [ABSTRACT FROM AUTHOR]

Introduction: Despite frequent recognition of emotional blunting in the published literature, either as a primary symptom of depression or as an adverse effect of antidepressants, there is no systematic synthesis on this topic to our knowledge. We undertook this scoping review to assess the prevalence, clinical features, implicated causes and management of emotional blunting, outlining the phenomenological and clinical gaps in research. Method: A systematic search was done until March 15, 2022, to include all original studies (i.e., interventional trials, cohort & cross‐sectional studies, case reports, and case series). All reviewed data were delineated to answer pertinent clinical, phenomenological, and management questions related to the phenomenon of emotional blunting. Results: A total of 25 original studies were included in our scoping review. Emotional blunting was described as a persistent diminution in both positive and negative feelings in depressed patients, who could subjectively differentiate it from their acute symptoms. However, the literature lacked the distinction between emotional blunting as a primary symptom of depression or an adverse effect of antidepressants. Common clinical strategies to manage antidepressant‐induced emotional blunting included dose reduction or switching to a different antidepressant. Conclusion: Emotional blunting was a significant patient‐reported concern with antidepressants. Future research should clarify phenomenological and neurobiological constructs underlying emotional blunting to improve diagnostic and management skills. [ABSTRACT FROM AUTHOR]

Objective: Drugs can be divided into two major categories, symptomatic and disease modifying. This review explores whether and how psychiatric drugs fall into one or the other of those categories, and the implications of those results for clinical practice and research in psychopharmacology. Method: Narrative review. Results: Most psychiatric drugs have only short‐term effects of improving active symptoms. They do not show long‐term benefits for the underlying disease, such as improving the course of illness and improving mortality. Evidence is provided for this claim in the treatment literature of antidepressants for depressive illness and antipsychotics for schizophrenia. Developing truly beneficial drugs for disease modification also is limited by the poor clinical and biological validity of Diagnostic and Statistical Manual diagnoses as well as the use of invalid falsely positive maintenance efficacy randomized discontinuation trial designs. Conclusions: Current psychopharmacology is limited mostly to symptomatic effects, not transformative treatments for the diseases underlying those symptoms. A change in approach is needed in psychopharmacology practice and research, focusing on long‐term disease modification rather than short‐term symptom improvement. [ABSTRACT FROM AUTHOR]

Objective: In recent decades, significant numbers of pharmaceutical trials have gradually been relocated to low‐ and middle‐income countries. However, there is little evidence regarding the transferability of trial outcomes across countries. Analysing duloxetine randomised controlled trials (RCTs) conducted in different countries, we investigated whether per capita gross national income (GNI) and healthcare expenditure (HE) are associated with pre‐post mean changes of depression severity and differences in duloxetine‐placebo effect sizes. Method: Meta‐analyses included RCTs investigating duloxetine efficacy in patients with depression. Individual participant data (IPD) from multi‐centre duloxetine trials were provided by the manufacturer. Data extracted from published reports also entered analyses in case of trials conducted in only one country. A meta‐regression approach was applied to analyse associations of GNI and HE with standardised pre‐post mean change using raw score standardisation (SMCR) and comparative effect size, that is, the mean differences (MD) in pre‐post effect size between duloxetine and placebo treatment. Results: 23 trials with 8417 randomised participants entered analyses. Regression coefficients indicated a negative linear relationship of SMCR with GNI (z‐standardised β = −3.61, R2 = 14.8%, p < 0.001) and HE (β = −4.72, R2 = 24.8%, p < 0.001) for participants treated with duloxetine. Similar associations were found for placebo treatment (GNI: β = −3.52, R2 = 23.8%, p < 0.001; β = −3.34, R2 = 21.0% p < 0.001). Neither GNI nor HE was associated with the MD between duloxetine and placebo pre‐post differences. Conclusions: Findings challenge the idea of the universal transferability of antidepressant trial outcomes across countries. Understanding the results of antidepressant RCTs demands more sophisticated clarification of context factors involved in determining effectiveness of antidepressant medication and should be discussed with a view to socio‐economic context in their countries of origin. [ABSTRACT FROM AUTHOR]

SUMMARY: Background: Depression is common in patients on haemodialysis and associated with adverse outcomes. Antidepressant use is widespread though evidence of efficacy is limited. Objectives: To study antidepressant management practices in patients on haemodialysis with reference to NICE guidelines on management of depression in adults with chronic physical health problems. Design: Prospective, multicentre, longitudinal cohort study with 6–15 month follow‐up. Participants: Patients on haemodialysis established on antidepressant medication. Measurements: Baseline assessment of mood was undertaken using Beck Depression Inventory (BDI‐II). Demographic, clinical and medication data were also collected. Changes in clinical and life circumstances and medication during follow‐up were recorded. At follow‐up, BDI‐II was reassessed and diagnostic psychiatric assessment undertaken. Results: Forty‐one patients were studied. General practitioners were the main prescribers (68%). Ten agents were in use, the commonest being Citalopram (39%). Doses were often suboptimal. At baseline, 30 patients had high BDI‐II scores (≥16) and 22 remained high at follow‐up. Eleven had BDI‐II < 16 at baseline. In five, this increased on follow‐up to ≥16. Sixteen patients (39%) had no medication review during follow‐up, 14 (34%) had a dose review, and 11 (27%) a medication change. On psychiatric assessment at follow‐up, eight patients had current major depressive disorder (MDD), seven recurrent and 20 evidence of past MDD. Six displayed no evidence of ever having MDD. Conclusions: Antidepressant management in patients on haemodialysis reflected poor drug selection, overprescription, under‐dosing and inadequate follow‐up suggesting sub‐optimal adherence to NICE guidelines. Most patients had high depression scores at follow‐up. Antidepressant use in haemodialysis requires reappraisal. [ABSTRACT FROM AUTHOR]

Objective: We consider how to choose an antidepressant (AD) medication for the treatment of clinical depression. Method: A narrative review was undertaken addressing antidepressant 'choice' considering a range of parameters either weighted by patients and clinicians or suggested in the scientific literature. Findings were synthesised and incorporated with clinical experience into a model to assist AD choice. Results: Efficacy studies comparing ADs offer indicative guidance, while precision psychiatry prediction based on genetics, developmental trauma, neuroimaging, behavioural and cognitive biomarkers, currently has limited clinical utility. Our model offers guidance for AD choice by assessing first for the presence of a depressive subtype or symptom cluster and matching choice of AD class accordingly. Failing this, an AD can be chosen based on depression severity. Within‐class choice can be determined by reference to personality style, patient preference, medical or psychiatric comorbidities and side‐effect profile. Conclusion: Clarification of AD choice would occur if medications are trialled in specific depressive subtypes rather than using the generic diagnosis of major depressive disorder (MDD). Such 'top‐down' methods could be enhanced by 'bottom‐up' studies to classify individuals according to symptom clusters and biomarkers with AD efficacy tested in these categories. Both methods could be utilised for personalised AD choice. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the efficacy and safety of using adjunctive antipsychotics in patients with major depressive disorder. Method: Studies published since the last Cochrane review conducted in 2010 were identified via a literature search of recognised databases, using the keywords "adjunct*", "augment*", "antipsychotic" and "depression", and systematically evaluated. A targeted review of relevant guidelines was undertaken. Results: Adjunctive antipsychotics produce a small but significant improvement in depressive symptoms in most studies. Most of the studies focussed on patients with an inadequate response to antidepressants rather than patients with treatment resistant depression. Treatment guidelines were variable but generally supported the use of adjunctive antipsychotics while cautioning about the risk of side effects. Most were non‐specific about the length of time adjunctive antipsychotics should be prescribed. Conclusions: The studies do not support the routine use of adjunctive antipsychotics in patients with an inadequate response to antidepressants. They may be beneficial when used short‐term in patients with treatment resistant depression who have specific symptoms (severe ruminations, melancholia, major sleep disturbance) that appear to respond well to adjunctive antipsychotics. There is no support for long‐term use. Research should focus on specifying which symptom profiles are responsive and how adjunctive antipsychotics compare to other strategies in treatment resistant depression. [ABSTRACT FROM AUTHOR]

Objective: This paper discusses strategies for achieving remission in major depressive disorder, summarizing the results of comparative studies of various antidepressants. Method: Antidepressant efficacy was determined as either response or remission, measured using the Hamilton Depression Rating Scale, the Clinical Global Impressions scale and other widely used instruments. Results: Study results suggest an advantage to pharmacotherapy that interacts with more than one neurotransmitter system, either as single mixed-activity drugs (e.g. clomipramine, mirtazapine and venlafaxine extended-release) or combinations of medications that are individually specific for a single neurotransmitter system. Conclusion: Remission should be the goal of antidepressant therapy. Treatment strategies include increasing the dosage of the chosen antidepressant; switching to an antidepressant with a different mechanism of action; augmenting one antidepressant with another agent; or using combination therapy. A substantial body of data indicates that for a subset of depressed patients, activation of multiple neurotransmitter systems is beneficial in achieving remission. [ABSTRACT FROM AUTHOR]

Aims To measure the effectiveness of antidepressants for adolescents and young adults with co-occurring depression and substance use disorder. Design, Setting and Participants Meta-analysis of randomized controlled clinical trials. A comprehensive literature search of Pub Med, Cochrane, Embase, Web of Science and PsychINFO was conducted (from 1970 to 2013). Prospective, parallel groups, double-blind, controlled trials with random assignment to an antidepressant or placebo on young patients (age ≤ 25 years) who met diagnostic criteria of both substance use and unipolar depressive disorder were included. Five trials were selected for this analysis and included 290 patients. Measurements Our efficacy outcome measures were depression outcomes (dichotomous and continuous measures) and substance-use outcomes (change of frequency or quantity of substance-use). Secondary analysis was conducted to access the tolerability of antidepressant treatment. Findings For dichotomous depression outcome, antidepressants group was significantly more effective than placebo group [risk ratio ( RR) = 1.21; 95% confidence interval ( CI) 1.01-1.45], with low heterogeneity ( I2 = 0%). Although no statistically significant effects for continuous depression outcome [standardized mean differences ( SMD) = −0.13; 95% CI, −0.55 to 0.30] were found with moderate heterogeneity ( I2 = 63%), subgroup analysis showed that the medicine group with a sample size of more than 50 showed statistically significant efficacy compared with the placebo group ( SMD −0.53, 95% CI −0.82 to −0.25). Moreover, there was no significant difference for substance-use outcomes and tolerability outcomes between the medication and placebo groups. Conclusions Antidepressant medication has a small overall effect in reducing depression in young patients with combined depressive and substance-use disorders, but does not appear to improve substance use outcomes. [ABSTRACT FROM AUTHOR]

Objective Depressive and anxiety disorders are common in youth who are at risk for bipolar disorder (i.e., youth who have at least one parent with bipolar disorder) and antidepressants are commonly prescribed as treatment. However, there are few data regarding the safety and tolerability of antidepressants in this population. Therefore, we sought to prospectively examine the effects of these medications in children and adolescents who are diagnosed with depressive or anxiety disorders and have a parent with bipolar I disorder. Methods Youth aged 9-20 years, with at least one parent with bipolar I disorder [high risk ( HR)], were recruited (n = 118) and assessed using semi-structured diagnostic interviews. Participants were prospectively evaluated using a modified version of the Longitudinal Interval Follow-up Evaluation to assess changes in affective and anxiety symptoms and were treated naturalistically. Results Over the course of 43-227 weeks (mean duration of follow-up: 106 ± 55 weeks), 21% (n = 25) of youth had antidepressant exposure and, of these, 57% (n = 12) had an adverse reaction (e.g., irritability, aggression, impulsivity, or hyperactivity) that led to antidepressant discontinuation. Those patients who experienced an adverse reaction were significantly younger than those who did not (p = 0.02) and discontinuation of antidepressant therapy secondary to an adverse event occurred at an average of 16.7 ± 17.4 weeks (median: 11 weeks, range: 2-57 weeks). Cox proportional hazard analyses yielded a hazard ratio of 0.725 (p = 0.03), suggesting that there is a 27% decrease in the likelihood of an antidepressant-related adverse event leading to discontinuation with each one-year increase in age. Conclusions Antidepressant medications may be poorly tolerated in youth with a familial risk for developing mania. Controlled studies further assessing treatments for depression and anxiety in HR youth are urgently needed. [ABSTRACT FROM AUTHOR]

Objective To be used in conjunction with 'Psychological management of unipolar depression' [Lampe et al. Acta Psychiatr Scand 2013; 127(Suppl. 443):24-37] and 'Lifestyle management of unipolar depression' [Berk et al. Acta Psychiatr Scand 2013; 127(Suppl. 443):38-54]. To provide clinically relevant recommendations for the use of pharmacological treatments in depression derived from a literature review. Method Using our previous Clinical Practice Guidelines [Malhi et al. Clinical practice recommendations for bipolar disorder. Acta Psychiatr Scand 2009; 119(Suppl. 439):27-46] as a foundation, these clinician guidelines target key practical considerations when prescribing pharmacotherapy. A comprehensive review of the literature was conducted using electronic database searches (PubMed, MEDLINE), and the findings have been synthesized and integrated alongside clinical experience. Results The pharmacotherapy of depression is an iterative process that often results in partial and non-response. Beyond the initiation of antidepressants, the options within widely used strategies, such as combining agents and switching between agents, are difficult to proscribe because of the paucity of pertinent research. However, there is some evidence for second-line strategies, and a non-prescriptive algorithm can be derived that is based broadly on principles rather than specific steps. Conclusion Depression is by its very nature a heterogeneous illness that is consequently difficult to treat. Invariably, situation-specific factors often play a significant role and must be considered, especially in the case of partial and non-response. Consulting with colleagues and trialling alternate treatment paradigms are essential strategies in the management of depression. [ABSTRACT FROM AUTHOR]

Objective Bipolar disorder (BD) is frequently misdiagnosed as major depressive disorder (MDD), which may lead to inappropriate treatment and poor outcomes. This study aimed to examine prescribing patterns of antidepressants, antipsychotics and mood stabilizers in BD patients misdiagnosed with MDD in China. Methods A total of 1487 patients originally diagnosed with MDD were consecutively screened for diagnostic revision in 13 psychiatric hospitals or psychiatric units of general hospitals in China nationwide. The patients' sociodemographic and clinical characteristics were recorded using a standardized protocol and data collection procedure. The Mini International Neuropsychiatric Interview (MINI) was used to establish DSM-IV diagnoses. Data on psychotropic prescriptions were collected by a review of medical records. Results Three hundred and nine of the 1487 patients (20.8%) fulfilled DSM-IV criteria for BD; 118 (7.9%) for BD-I and 191 (12.8%) for BD-II on the MINI. Of the BD patients ( n = 309), 227 (73.5%) received any use of antidepressants, 73 (23.6%) antipsychotics and 33 (10.7%) mood stabilizers. In multiple logistic regression analyses, compared with those with MDD, patients with BD-I were more likely to receive antidepressants (OR 1.7, 95% CI 1.1-2.8, p = 0.02), antipsychotics (OR 1.6, 95% CI 1.04-2.5, p = 0.04) and mood stabilizers (OR 3.9, 95% CI 2.1-7.2, p < 0.001), whereas patients with BD-II were more likely to receive mood stabilizers (OR 2.4, 95% CI 1.3-4.4, p = 0.003). There was no difference in the use of antidepressants (OR 1.1, 95% CI 0.8-1.5, p = 0.7) and antipsychotics (OR 1.3, 95% CI 0.9-1.9, p = 0.2) between BD-II and MDD. In addition, there was no difference between BD-I and BD-II in any use of antidepressants, antipsychotics and mood stabilizers. Conclusions The prescription of antidepressants for BD patients misdiagnosed with MDD is very common, and only a very small proportion of patients received guideline-concordant treatment. Considering the potentially hazardous effects of inappropriate pharmacotherapy in this population, continuing education and training addressing the correct diagnosis of BD and rational use of psychotropic medications are needed in China. Copyright © 2012 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Objective The aim of our work is to study the possible role of clinical variables, neuropsychological performance, and the 5HTTLPR, rs25531, and val108/58Met COMT polymorphisms on the prediction of depression remission after 12 weeks' treatment with fluoxetine. These variables have been studied as potential predictors of depression remission, but they present poor prognostic sensitivity and specificity by themselves. Methods Seventy-two depressed patients were genotyped according to the aforementioned polymorphisms and were clinically and neuropsychologically assessed before a 12-week fluxetine treatment. Results Only the La allele of rs25531 polymorphism and the GG and AA forms of the val 108/158 Met polymorphism predict major depressive disorder remission after 12 weeks' treatment with fluoxetine. None of the clinical and neuropsychological variables studied predicted remission. Conclusions Our results suggest that clinical and neuropsychological variables can initially predict early response to fluoxetine and mask the predictive role of genetic variables; but in remission, where clinical and neuropsychological symptoms associated with depression tend to disappear thanks to the treatment administered, the polymorphisms studied are the only variables in our model capable of predicting remission. However, placebo effects that are difficult to control require cautious interpretation of the results. Copyright © 2012 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Sjöberg, R. L. & Blomstedt, P. (2011). The psychological neuroscience of depression: Implications for understanding effects of deep brain stimulation. Scandinavian Journal of Psychology 52, 411-419. In this article it is suggested that current psychological theories of depression presuppose that this condition will develop as a result of a vicious circle involving negatively biased communication between systems of emotional stress-/alarm-signaling, executive functions and mood regulation. These systems may from a neuroanatomical point of view be located in the limbic system, the orbitofrontal and lateral prefrontal cortex and the hypothalamus-pituitary-adrenal (HPA-) axis respectively. The theoretical and practical implications of this model for the understanding of pharmacological treatments of depression are briefly discussed and this theory is related to the catecholamine hypothesis of depression. The model is furthermore discussed in relation to deep brain stimulation (DBS) of treatment resistant major depression. Similarities and differences between this perspective and the one advocated by the 'homeostatic theory' of depression are discussed. It is concluded that a topographical psychological theory may offer a useful heuristic in thinking about depression and that it offers several testable predictions about treatments of the disorder. [ABSTRACT FROM AUTHOR]

Spijker J, Nolen WA. An algorithm for the pharmacological treatment of depression. Objective: Non-response to treatment with antidepressants (AD) is a clinical problem. Method: The algorithm for pharmacological treatment of the Dutch multidisciplinary guideline for depression is compared with four other algorithms. Results: The Dutch algorithm consists of five subsequent steps. Treatment is started with one out of many optional ADs (step 1); in case of non-response after 4–10 weeks, best evidence is for switching to another AD (step 2); next step is augmentation with lithium as the best option (step 3); the next step is a monoamine oxidase inhibitor (MAOI) (step 4); and finally electroconvulsive therapy (step 5). There are major differences with other algorithms regarding timing of augmentation step, best agents for augmentation and role of MAOI. Conclusion: Algorithms for AD treatment vary according to national and local preferences. Although the evidence for most of the treatment strategies is rather meagre, an AD algorithm appears to be an useful instrument in clinical practice. [ABSTRACT FROM AUTHOR]

The authors evaluated the trait/state issues of harm avoidance in depressive-spectrum disorders and its predictive potential for antidepressant response. Subjects with Diagnostic and Statistical Manual of Mental Disorders (4th edn; DSM-IV) major depressive disorder ( n = 39), dysthymic disorder ( n = 37), depressive personality disorder ( n = 39), and healthy control subjects ( n = 40) were evaluated with the Temperament and Character Inventory and the 17-item Hamilton Depression Rating Scale (HDRS-17) at baseline and after a 12 week antidepressant treatment period. Higher harm avoidance scores predicted lesser improvement in subjects with dysthymic disorder and major depressive disorder, as determined by lesser decrease in HDRS-17 scores. Mean harm avoidance scores in depressed subjects were consistently greater than those in healthy controls, controlling for age, gender and diagnosis. Mean harm avoidance scores decreased significantly in all depressive-spectrum disorders after treatment, but still remained higher than harm avoidance scores in control subjects. The present study reports that harm avoidance is a reliable predictor of antidepressant treatment in subjects with major depressive disorder and dysthymic disorder and that harm avoidance is both trait- and state-dependent in depressive-spectrum disorders. [ABSTRACT FROM AUTHOR]

Rolipram improves signal transmission in central noradrenergic neurones with a novel mechanism of action: enhanced noradrenaline (first messenger) synthesis and release, and inhibition of cAMP (second messenger) breakdown. Several comparative trials to prove antidepressant activity are under way. Results of a multicentre double-blind trial with three different dosages of rolipram involving 98 patients will be presented. Response rates in all dosages were similar and comparable to those reported in the literature on tricyclic antidepressants. In addition rolipram was tolerated well. A significant relationship between dosages and effects, however, could not be established. [ABSTRACT FROM AUTHOR]

Selecting the most effective antidepressant for depressed subjects having failed previous treatments is difficult; the rates of success are relatively low. There is a clear need for objective biomarkers which could assist and optimize such treatment selection. We review here the current literature and recent developments on the role of quantitative EEG (QEEG) predictors of treatment outcome in major depressive disorder. [ABSTRACT FROM AUTHOR]

Objective: To evaluate data supporting the ability of venlafaxine, an antidepressant with a dual mechanism of action, to produce remission from depression. Method: Review of multicentre, double-blind, randomized studies comparing venlafaxine or venlafaxine extended release (XR) with a selective serotonin reuptake inhibitor (SSRI), using Hamilton Depression Rating Scale total scores in the range of ≤7 and <10 as the final outcome measure, to evaluate the ability of venlafaxine/venlafaxine XR to produce full remission from depression. Results: Venlafaxine/venlafaxine XR demonstrated higher rates of remission than did the SSRIs and placebo. Conclusion: With full remission rather than response as the measure of outcome, venlafaxine/venlafaxine XR demonstrated more robust antidepressant efficacy than the SSRIs and placebo. This finding suggests that venlafaxine/venlafaxine XR are appropriate standard-of-care therapies for the treatment of patients with major depressive disorder. [ABSTRACT FROM AUTHOR]