A review of vilazodone, serotonin, and major depressive disorder.

Objective: To review the mechanism of selective serotonin reuptake inhibitor (SSRI)-mediated serotonergic neurotransmission, focusing on serotonin 1A (5-HT1A) autoreceptors, which are proposed to be involved in delaying therapeutic efficacy. Vilazodone was specifically designed to function both as an SSRI and a partial agonist at 5-HT1A receptors. This combined mechanism is proposed to decrease time to efficacy, minimize sexual side effects, and provide concomitant anxiolytic properties.

The risk of switch to mania in patients with bipolar disorder during treatment with an antidepressant alone and in combination with a mood stabilizer.

Objective: This study examined the risk of antidepressant-induced manic switch in patients with bipolar disorder treated either with antidepressant monotherapy or with an antidepressant in conjunction with a mood stabilizer.

Method: Using Swedish national registries, the authors identified 3,240 patients with bipolar disorder who started treatment with an antidepressant and had no antidepressant treatment during the previous year. Patients were categorized into those receiving antidepressant monotherapy and those receiving an antidepressant plus a mood stabilizer.

Translating clinical science into effective therapies.

Identifying a patient with treatment-resistant depression involves ensuring that at least 2 evidence-based antidepressant trials from two different pharmacologic classes have been undertaken and determining their impact on patients' symptoms, functioning, quality-of-life and social relationships as outcomes. When assessing depressive symptoms throughout the course of treatment, clinical judgment should be supplemented by using standardized tools such as the 9-item Patient Health Questionnaire (PHQ-9) and the Quick Inventory of Depressive Symptomatology (QIDS). Adjunctive treatment strategies preserve the benefits of first-line antidepressants in partial responders and potentially enhance the initial antidepressant's effect through complementary mechanisms of action.

Desvenlafaxine for the treatment of major depressive disorder.

Introduction: Major depressive disorder (MDD) is a chronic and debilitating condition often characterized by inadequate treatment. Notwithstanding the availability of more than a dozen first-line agents across disparate classes (e.g.

A novel application of the Intent to Attend assessment to reduce bias due to missing data in a randomized controlled clinical trial.

Background: Missing data are unavoidable in most randomized controlled clinical trials, especially when measurements are taken repeatedly. If strong assumptions about the missing data are not accurate, crude statistical analyses are biased and can lead to false inferences. Furthermore, if we fail to measure all predictors of missing data, we may not be able to model the missing data process sufficiently.

Efficacy and safety of olanzapine/fluoxetine combination vs fluoxetine monotherapy following successful combination therapy of treatment-resistant major depressive disorder.

This study assessed prevention of relapse in patients with treatment-resistant depression (TRD) taking olanzapine/fluoxetine combination (OFC). Patients with major depressive disorder (MDD) who failed to satisfactorily respond to ≥ 2 different antidepressants for ≥ 6 weeks within the current MDD episode were acutely treated for 6-8 weeks, followed by stabilization (12 weeks) on OFC. Those who remained stable were randomized to OFC or fluoxetine for up to 27 weeks.

Effect of adjunctive benzodiazepines on clinical outcomes in lithium- or quetiapine-treated outpatients with bipolar I or II disorder: results from the Bipolar CHOICE trial.

Background: Little is known about the longer-term effects of adjunctive benzodiazepines on symptom response during treatment in patients with bipolar disorders.

Methods: The study sample consisted of 482 patients with bipolar I or II disorder enrolled in a 6-month, randomized, multi-site comparison of lithium- and quetiapine-based treatment. Changes in clinical measures (BISS total and subscales, CGI-BP, and CGI-Efficacy Index) were compared between participants who did and did not receive benzodiazepine treatment at baseline or during follow-up.

Extreme nonresponse to acute phase cognitive therapy for depression: an attempt to replicate and extend.

As with other interventions for major depressive disorder (MDD), cognitive therapy (CT) results in treatment failure for about half of all participants. In 2007, Coffman and colleagues in Seattle studied this topic by identifying a group of patients who demonstrated an extremely poor response to CT (i.e.

Neural substrates of trait ruminations in depression.

Rumination in depression is a risk factor for longer, more intense, and harder-to-treat depressions. But there appear to be multiple types of depressive rumination-whether they all share these vulnerability mechanisms, and thus would benefit from the same types of clinical attention is unclear. In the current study, we examined neural correlates of empirically derived dimensions of trait rumination in 35 depressed participants.

Levomilnacipran: a newly approved drug for treatment of major depressive disorder.

Levomilnacipran is a novel serotonin and norepinephrine reuptake inhibitor (SNRI) for the treatment of major depressive disorder. This paper reviews up-to-date data on the pharmacology, short- and long-term efficacy, safety and tolerability of levomilnacipran. The drug differs from previously available SNRIs in having twice the potency for norepinephrine versus serotonin reuptake inhibition.

Efficacy and tolerability of flexibly-dosed adjunct TC-5214 (dexmecamylamine) in patients with major depressive disorder and inadequate response to prior antidepressant.

This paper reports the efficacy and tolerability of the nicotinic channel modulator TC-5214 (dexmecamylamine) as adjunct therapy for patients with major depressive disorder who have an inadequate response to initial antidepressant treatment in 2 Phase III studies. These double-blind, placebo-controlled studies (NCT01157078, D4130C00002 [Study 002] conducted in the US and India; NCT01180400, D4130C00003 [Study 003] conducted in Europe) comprised 8 weeks of open-label antidepressant treatment followed by 8 weeks of active treatment during which patients were randomized to flexibly-dosed TC-5214 1-4 mg twice daily (BID) or placebo as an adjunct to ongoing therapy with SSRI/SNRI. The primary efficacy endpoint in both studies was change in Montgomery Åsberg Depression Rating Scale (MADRS) total score from randomization (week 8) to treatment end (week 16).

Efficacy and safety of duloxetine 60 mg once daily in major depressive disorder: a review with expert commentary.

Objective: Major depressive disorder (MDD) is a significant public health concern and challenges health care providers to intervene with appropriate treatment. This article provides an overview of efficacy and safety information for duloxetine 60 mg/day in the treatment of MDD, including its effect on painful physical symptoms (PPS).

Design: A literature search was conducted for articles and pooled analyses reporting information regarding the use of duloxetine 60 mg/day in placebo-controlled trials.

Are Improvements in Cognitive Content and Depressive Symptoms Correlates or Mediators during Acute-Phase Cognitive Therapy for Recurrent Major Depressive Disorder?

The cognitive model of depression posits that cognitive therapy's (CT) effect on depressive symptoms is mediated by changes in cognitive content (e.g., automatic negative thoughts dysfunctional attitudes, failure attributions).

Comparative assessment of adherence measures and resource use in SSRI/SNRI-treated patients with depression using second-generation antipsychotics or L-methylfolate as adjunctive therapy.

Background: Antidepressant monotherapy is effective in achieving treatment remission in only approximately one third of patients with depression, and even switching to a second antidepressant brings the cumulative remission rate to only 50%-55%. This has led to an interest in augmentation therapy for the management of treatment-resistant depression.

Objectives: To assess (a) selective serotonin reuptake inhibitor/selective norepinephrine reuptake inhibitor (SSRI/SNRI) adherence when augmented with second-generation atypical antipsychotics (SGAs) or L-methylfolate using a modified application of the Healthcare Effectiveness Data and Information Set (HEDIS) acute medication management (AMM) measures at the time of augmentation, and (b) the depression-specific and total health care cost, comparing the 2 forms of augmentation therapy in the treatment of depressive disorder.

Clinical and Health Outcomes Initiative in Comparative Effectiveness for Bipolar Disorder (Bipolar CHOICE): a pragmatic trial of complex treatment for a complex disorder.

Background: Classic and second-generation antipsychotic mood stabilizers are recommended for treatment of bipolar disorder, yet there are no randomized comparative effectiveness studies that have examined the 'real-world' advantages and disadvantages of these medications.

Purpose: We describe the strategic decisions in the design of the Clinical and Health Outcomes Initiative in Comparative Effectiveness for Bipolar Disorder (Bipolar CHOICE). This article outlines the key issues and solutions the investigators faced in designing a clinical trial that would maximize generalizability and inform real-world clinical treatment of bipolar disorder.

Influence of sex and menopausal status on response, remission, and recurrence in patients with recurrent major depressive disorder treated with venlafaxine extended release or fluoxetine: analysis of data from the PREVENT study.

Objective: To evaluate the effects of sex and menopausal status on acute-, continuation-, and maintenance-phase treatment outcomes in patients with recurrent major depressive disorder (MDD).

Method: This was a secondary analysis of data from the Prevention of Recurrent Episodes of Depression With Venlafaxine for Two Years (PREVENT) trial, a multiphase, multicenter, double-blind study in which adult outpatients with recurrent MDD (by DSM-IV criteria) were randomly assigned to 10 weeks of acute-phase venlafaxine extended release (ER) (75-300 mg/d) or fluoxetine (20-60 mg/d). Patients achieving response or remission had 6 months of continuation-phase treatment.

The prevalence and severity of depressive symptoms along the spectrum of unipolar depressive disorders: a post hoc analysis.

Objective: To explore which symptoms are common in patients who experience a range of symptom severity that spans minor depression and major depressive disorder (MDD).

Method: A post hoc analysis of subjects entering outpatient, pharmacologic treatment studies for minor depression or MDD who provided baseline data on the Inventory for Depressive Symptomatology-Clinician Rated (IDS-C) was performed in November 2000. The minor depression sample included 161 patients diagnosed according to the National Institute of Mental Health Diagnostic Interview Schedule, while the MDD subjects included 969 subjects diagnosed according to the Structured Clinical Interview for DSM-III-R.

The multifactorial presentation of depression in acute care.

Depression is by its very nature a heterogeneous disorder; 2 patients with the same diagnosis (ie, major depressive disorder) may have few symptoms in common. This heterogeneity is evidenced by the fact that depression presents in a wide variety forms related to polarity (unipolar vs bipolar), symptoms (melancholic, atypical, psychotic, or anxious), onset (specific events, seasons, or age), recurrence, and severity. These diagnostic specifiers and subgroups can guide treatment decisions in several ways.

Medication adherence in a comparative effectiveness trial for bipolar disorder.

Objective: Psychopharmacology remains the foundation of treatment for bipolar disorder, but medication adherence in this population is low (range 20-64%). We examined medication adherence in a multisite, comparative effectiveness study of lithium.

Method: The Lithium Moderate Dose Use Study (LiTMUS) was a 6-month, six-site, randomized effectiveness trial of adjunctive moderate dose lithium therapy compared with optimized treatment in adult out-patients with bipolar I or II disorder (N=283).

Clinical relevance of fatigue as a residual symptom in major depressive disorder.

Residual symptoms of major depressive disorder (MDD) following treatment are increasingly recognized as having a negative impact on the patient because of their association with lack of remission, poorer psychosocial functioning, and a more chronic course of depression. Although the effects of specific residual symptoms have not been as systematically studied, several symptoms, including fatigue, sleep disturbance, anxiety, and concentration difficulties, commonly occur as part of the residual state in MDD. In particular, the relatively high prevalence of residual fatigue suggests that this symptom is not being adequately addressed by standard antidepressant therapies.

Pooled analysis of adjunct extended-release quetiapine fumarate in patients with major depressive disorder according to ongoing SSRI or SNRI treatment.

This pooled analysis evaluated the efficacy of extended-release quetiapine fumarate (quetiapine XR) adjunct to selective serotonin reuptake inhibitors (SSRIs) or serotonin-norepinephrine reuptake inhibitors (SNRIs) in patients with major depressive disorder (MDD). Pooled data were analyzed from two 6-week, double-blind, randomized, placebo-controlled trials of adjunct quetiapine XR (150 and 300 mg/day) in patients with MDD and inadequate response to initial antidepressant monotherapy. This post-hoc analysis included evaluation of change from randomization at week 6 in Montgomery Åsberg Depression Rating Scale (MADRS) total scores (primary endpoint), and week 6 MADRS response and remission rates for quetiapine XR as an adjunct to ongoing SSRI or SNRI.

Computer-assisted cognitive-behavior therapy for depression.

This article reviews the use of computer technology in treating depression as a substitute or adjunct for standard therapy. It discusses advantages and disadvantages of introducing computer technology as a treatment option, problems and barriers to expanded use, the varieties of computer-assisted psychotherapy for major depression, and relevant research. Three specific Internet-based programs are described, assessed and compared: Good Days Ahead, Beating the Blues, and MoodGYM.

Antidepressant combinations: cutting edge psychopharmacology or passing fad?

This article reviews the rationale for and history of combining antidepressants, as well as the current state of the evidence, in the treatment of major depression. Although it has long been suggested that some individuals may benefit from regimens that combine two dissimilar antidepressants, enthusiasm for this practice has waxed and waned and there was never a strong empirical foundation to support this practice. The tangibly better safety profiles of the newer generation antidepressants, both singly and in combination, have permitted greater use of such combinations in contemporary practice than ever before.

The International Society for Bipolar Disorders (ISBD) task force report on antidepressant use in bipolar disorders.

Objective: The risk-benefit profile of antidepressant medications in bipolar disorder is controversial. When conclusive evidence is lacking, expert consensus can guide treatment decisions. The International Society for Bipolar Disorders (ISBD) convened a task force to seek consensus recommendations on the use of antidepressants in bipolar disorders.