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Nonpharmacological Versus Pharmacological Treatment for Patients With Major Depressive Disorder: Current State of the Evidence

This is a summary of a systematic review evaluating the evidence regarding the comparative benefits and adverse effects of second-generation antidepressants (SGAs) and of psychological, complementary and alternative medicine (CAM), and exercise treatment options as first-step interventions for adult outpatients with acute-phase major depressive disorder (MDD) and as second-step interventions for patients with MDD who did not achieve remission after a first treatment attempt with SGAs. The systematic review included 44 trials published between January 1, 1990, and January 13, 2015. Patients in the included studies had mild to severe MDD. The full report, listing all studies, is available at www.effectivehealthcare.ahrq.gov/major-depressive-disorder. This summary is provided to assist in informed clinical decisionmaking. However, reviews of evidence should not be construed to represent clinical recommendations or guidelines.

Comparative Effectiveness Review Summary Guides for Clinicians [Internet] - Agency for Healthcare Research and Quality (US).

Version: September 13, 2016

Aripiprazole (Abilify): Depression, Major Depressive Disorder (MDD) [Internet]

Major depressive disorder (MDD) is characterized by the occurrence of one or more major depressive episodes (MDEs), which persist for at least two weeks and are characterized by a depressed mood and/or markedly diminished interest or pleasure in all, or almost all, activities. The clinical manifestation of MDD is heterogeneous. The duration of MDEs can also vary significantly in duration, ranging from weeks to years. MDD is one of the most prevalent chronic conditions in Canada, with an annual prevalence reaching 4.8% and a lifetime prevalence of 10.8% of the population. The prevalence of MDD is twice as high for women as for men, but this difference declines with age. According to the Global Burden of Disease Study and other studies, MDD is a major cause of disability. Because of its early age of onset and frequent recurrences, MDD is also among the leading causes of disability, as measured by disability-adjusted life-years, worldwide.

Common Drug Review - Canadian Agency for Drugs and Technologies in Health.

Version: November 2016
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Second Generation Antidepressants for Pediatric Patients with Major Depressive Disorder and Anxiety Disorder: A Review of the Clinical Effectiveness and Safety [Internet]

Major depressive disorders (MDD) and anxiety disorders fall within a spectrum of psychiatric disorders that are characterized by severe and/or persistent symptoms of sadness and irritability that can cause considerable distress and interfere with daily activities. Untreated, they may lead to serious developmental, personal and societal difficulties that may prejudice school success, work productivity, adult development and the forming of relationships. In Canada, it is estimated that approximately 5% of male youth and 12% of female youth have experienced a major depressive episode during their childhood or adolescent years.

Rapid Response Report: Summary with Critical Appraisal - Canadian Agency for Drugs and Technologies in Health.

Version: June 11, 2015
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Nonpharmacological Versus Pharmacological Treatments for Adult Patients With Major Depressive Disorder [Internet]

To compare the benefits and harms of second-generation antidepressants (SGAs), psychological, complementary and alternative medicine, and exercise treatment options as first-step interventions for adult outpatients with acute-phase major depressive disorder (MDD), and as second-step interventions for patients with MDD who did not achieve remission after a first treatment attempt with SGAs.

Comparative Effectiveness Reviews - Agency for Healthcare Research and Quality (US).

Version: December 2015
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VA Evidence-based Synthesis Program Evidence Briefs [Internet]

The Department of Veterans Affairs, Health Services Research & Development Service (HSR&D) Evidence-based Synthesis Program (ESP) provides timely and accurate evidence briefs on targeted healthcare topics of particular importance to VA managers and policymakers, as they work to improve the health and healthcare of Veterans. The ESP disseminates these briefs throughout VA.

Department of Veterans Affairs (US).

Version: 2011
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An Overview of Complementary and Alternative Medicine Therapies for Anxiety and Depressive Disorders: Supplement to Efficacy of Complementary and Alternative Medicine Therapies for Posttraumatic Stress Disorder [Internet]

VA is committed to expanding the breadth of posttraumatic stress disorder (PTSD)-related services available to Veterans. Since depressive and anxiety disorders share common features with PTSD, this report was commissioned to examine the efficacy of complementary and alternative medicine (CAM) therapies for the treatment of depressive and anxiety disorders as a means to detect treatments that might be applicable to PTSD.

Evidence-based Synthesis Program - Department of Veterans Affairs (US).

Version: August 2011
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Computerized Cognitive Behavioral Therapy for Adults with Depressive or Anxiety Disorders [Internet]

Given the high rates of mental illness among Veterans returning from Iraq and Afghanistan, it is not surprising that the demand for mental health services in Veterans Health Administration (VHA) has increased 132 percent since 2006. The most commonly diagnosed and treated disorders among Veterans receiving care at VHA include (1) PTSD, (2) depressive disorders, (3) episodic mood disorders, (4) anxiety disorders, and (5) substance use disorders. Unfortunately, shortages in trained mental health providers and logistical barriers limit Veterans’ access to evidence-based therapies.

Evidence-based Synthesis Program - Department of Veterans Affairs (US).

Version: October 2013
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Bipolar Disorder: The Management of Bipolar Disorder in Adults, Children and Adolescents, in Primary and Secondary Care

This guideline has been developed to advise on the treatment and management of bipolar disorder. The guideline recommendations have been developed by a multidisciplinary team of healthcare professionals, patients and guideline methodologists after careful consideration of the best available evidence. It is intended that the guidelines will be useful to clinicians and service commissioners in providing and planning high quality care for those with bipolar disorder while also emphasising the importance of the experience of care for patients and carers.

NICE Clinical Guidelines - National Collaborating Centre for Mental Health (UK).

Version: 2006
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Depression: The Treatment and Management of Depression in Adults (Updated Edition)

This clinical guideline on depression is an updated edition of the previous guidance (published in 2004). It was commissioned by NICE and developed by the National Collaborating Centre for Mental Health, and sets out clear, evidence- and consensus-based recommendations for healthcare staff on how to treat and manage depression in adults.

NICE Clinical Guidelines - National Collaborating Centre for Mental Health (UK).

Version: 2010
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Efficacy of continuation/maintenance electroconvulsive therapy for the prevention of recurrence of a major depressive episode in adults with unipolar depression: a systematic review

OBJECTIVE: Divergent opinion surrounds the use of continuation/maintenance electroconvulsive therapy (c/mECT) as a recurrence prevention strategy in depression because of limited data on efficacy and adverse effects. In an effort to synthesize what is known about its efficacy, a systematic review of controlled studies reporting efficacy of c/mECT for the prevention of relapse or recurrence of a depressive episode in adults with unipolar major depression was conducted.

Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet] - Centre for Reviews and Dissemination (UK).

Version: 2014

Clinical review of treatment options for major depressive disorder in patients with coronary heart disease

It is established that the prevalence of major depressive disorder (MDD) in coronary heart disease (CHD) populations is high and is associated with increased mortality. In this systematic review, we examined the evidence for the effective treatment of MDD in CHD patients by reviewing randomized control trials (RCTs) between 1980 and 2011 and then assessing whether these treatments were clinically meaningful. A total of 8 RCTs were retrieved. Sertraline, citalopram, and mirtazapine were safe from a cardiac perspective, but only sertraline and citalopram were clearly more effective than placebo in CHD patients with moderate-to-severe type, recurrent MDD, or MDD episode onset before the CHD event. Augmenting sertraline with omega-3 fatty acids did not result in superior depression outcomes. Cognitive-behavioral therapy was equivocally superior to usual care. Interpersonal psychotherapy was only superior to clinical management in patients with high baseline functional status. Exercise is a potential treatment for those with mild depression.

Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet] - Centre for Reviews and Dissemination (UK).

Version: 2012

Antidepressants in Elderly Patients with Major and Minor Depression: A Review of Clinical Effectiveness and Guidelines [Internet]

While clinical trials of antidepressants may include some individuals over the age of 65, it is not clear that evidence of safety and efficacy in such subgroup analyses are reflective of this age group more broadly. The generalizability of outcome data across populations can potentially be uncertain and the comparative efficacy of different antidepressants in older adults could potentially differ than what is seen in younger populations. As well, age-related changes that affect the pharmacokinetics and pharmacodynamics of drugs can affect the safety and potential harms with antidepressants in older adults. Older adults are at increased risk of anticholinergic side effects (common to a number of antidepressant classes), and orthostatic and sedative effects. These effects can exacerbate underlying conditions such as cardiovascular disease, cognitive impairment, delirium and can increase the risk of falls and fractures.

Rapid Response Report: Summary with Critical Appraisal - Canadian Agency for Drugs and Technologies in Health.

Version: August 17, 2015
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Mindfulness-based interventions for people diagnosed with a current episode of an anxiety or depressive disorder: a meta-analysis of randomised controlled trials

The authors concluded that, compared with control conditions, mindfulness-based interventions resulted in significantly lower levels of primary symptom severity in people with a current episode of depression, but suggested that these interventions should not be a first-line therapy for primary anxiety disorder. Although the review was largely well-conducted, lack of review process reporting means that the overall reliability is unclear.

Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet] - Centre for Reviews and Dissemination (UK).

Version: 2014

Efficacy and tolerability of mirtazapine versus paroxetine in the treatment of major depressive disorder

The authors concluded that mirtazapine was effective earlier, but at six to eight weeks, paroxetine was equally effective for the treatment of major depressive disorder. There were some methodological limitations, and no validity assessment, leaving the reliability of the conclusions uncertain.

Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet] - Centre for Reviews and Dissemination (UK).

Version: 2012

Efficacy of the sequential integration of psychotherapy and pharmacotherapy in major depressive disorder: a preliminary meta-analysis

The review found that sequential administration of psychotherapy after response to acute-phase pharmacotherapy, either alone or in combination with antidepressant drugs, may prevent relapse or recurrence in major depressive disorder. The authors' cautious conclusions reflect the evidence presented and are likely to be reliable.

Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet] - Centre for Reviews and Dissemination (UK).

Version: 2011

Placebo response in randomized controlled trials of antidepressants for pediatric major depressive disorder

The review found that number of study sites was the best predictor of placebo response in short-term randomised controlled trials of second-generation antidepressants in children and adolescents with major depressive disorder. The authors' conclusions are appropriate but, due to shortcomings in the review process and the relatively small number of studies, the reliability of the conclusions is not clear.

Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet] - Centre for Reviews and Dissemination (UK).

Version: 2009

Switching antidepressants after a first selective serotonin reuptake inhibitor in major depressive disorder: a systematic review

The authors concluded that, after a first SSRI, switching within or between any of the current classes of antidepressants appears reasonable. However, little randomised evidence is available. There is no conclusive evidence of any advantage in switching between classes. The review was well-conducted in most respects and these conclusions seem likely to be reliable.

Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet] - Centre for Reviews and Dissemination (UK).

Version: 2006

Evidence that patients with single versus recurrent depressive episodes are differentially sensitive to treatment discontinuation: a meta-analysis of placebo-controlled randomized trials

The review found antidepressants robustly reduced relapse risk during maintenance treatment of patients with major depressive disorders. There was evidence that, with increasing numbers of episodes, patients developed resistance to antidepressant medication prophylaxis. These conclusions broadly reflected the evidence, but should be considered with some caution given the potential for clinical heterogeneity and lack of explicitly reported trial quality assessment.

Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet] - Centre for Reviews and Dissemination (UK).

Version: 2008

Specificity profile of venlafaxine and sertraline in major depression: metaregression of double-blind, randomized clinical trials

Despite the well-known efficacy of selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) in the treatment of major depressive disorder, there is a lack of indications for each drug in different groups of patients. The aim of this study is to investigate the possible role of clinical sociodemographic factors as moderators of clinical response to venlafaxine (SNRI) and sertraline (SSRI). Research was performed on Medline and EMBASE for randomized control trials in English focused on sertraline and venlafaxine in the treatment of major depressive disorder and 59 studies were included. Clinical efficacy of each treatment was assessed on the basis of Hamilton Depressive Rating Scale and Montgomery-Asberg Depression Rating Scale. A metaregression analysis was performed to evaluate the role of clinical and sociodemographic factors as moderators of outcome, calculating the effect of each variable with the random-effects method. Gender, ethnicity and duration of depressive episode could have a role in prediction of clinical response to both antidepressants. Venlafaxine seems to have better effects in females and in Caucasian patients. Sertraline seems to be more efficacious in the treatment of females. Both drugs were more efficacious in patients who suffered a shorter episode of illness. Our results could represent an interesting point of view in the perspective of choosing the most suitable therapy based on clinical and social features for each patient. Metaregression is a retrospective analysis, based on the cumulative results of previous studies, so the lack of original data could represent the main limitation in this report and in the interpretation of the results obtained.

Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet] - Centre for Reviews and Dissemination (UK).

Version: 2014

Transcranial direct current stimulation for major depression: an updated systematic review and meta-analysis

Transcranial direct cranial stimulation (tDCS) is a promising non-pharmacological intervention for treating major depressive disorder (MDD). However, results from randomized controlled trials (RCTs) and meta-analyses are mixed. Our aim was to assess the efficacy of tDCS as a treatment for MDD. We performed a systematic review in Medline and other databases from the first RCT available until January 2014. The main outcome was the Hedges' g for continuous scores; secondary outcomes were the odds ratio (ORs) to achieve response and remission. We used a random-effects model. Seven RCTs (n = 259) were included, most with small sample sizes that assessed tDCS as either a monotherapy or as an add-on therapy. Active vs. sham tDCS was significantly superior for all outcomes (g = 0.37; 95% CI 0.04-0.7; ORs for response and remission were, respectively, 1.63; 95% CI = 1.26-2.12 and 2.50; 95% CI = 1.26-2.49). Risk of publication bias was low. No predictors of response were identified, possibly owing to low statistical power. In summary, active tDCS was statistically superior to sham tDCS for the acute depression treatment, although its role as a clinical intervention is still unclear owing to the mixed findings and heterogeneity of the reviewed studies. Further RCTs with larger sample sizes and assessing tDCS efficacy beyond the acute depressive episode are warranted.

Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet] - Centre for Reviews and Dissemination (UK).

Version: 2014

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