depressive disorder, major

Importance: Approximately 9% of US adults experience major depression each year, with a lifetime prevalence of approximately 17% for men and 30% for women.

Observations: Major depression is defined by depressed mood, loss of interest in activities, and associated psychological and somatic symptoms lasting at least 2 weeks. Evaluation should include structured assessment of severity as well as risk of self-harm, suspected bipolar disorder, psychotic symptoms, substance use, and co-occurring anxiety disorder. First-line treatments include specific psychotherapies and antidepressant medications. A network meta-analysis of randomized clinical trials reported cognitive therapy, behavioral activation, problem-solving therapy, interpersonal therapy, brief psychodynamic therapy, and mindfulness-based psychotherapy all had at least medium-sized effects in symptom improvement over usual care without psychotherapy (standardized mean difference [SMD] ranging from 0.50 [95% CI, 0.20-0.81] to 0.73 [95% CI, 0.52-0.95]). A network meta-analysis of randomized clinical trials reported 21 antidepressant medications all had small- to medium-sized effects in symptom improvement over placebo (SMD ranging from 0.23 [95% CI, 0.19-0.28] for fluoxetine to 0.48 [95% CI, 0.41-0.55] for amitriptyline). Psychotherapy combined with antidepressant medication may be preferred, especially for more severe or chronic depression. A network meta-analysis of randomized clinical trials reported greater symptom improvement with combined treatment than with psychotherapy alone (SMD, 0.30 [95% CI, 0.14-0.45]) or medication alone (SMD, 0.33 [95% CI, 0.20-0.47]). When initial antidepressant medication is not effective, second-line medication treatment includes changing antidepressant medication, adding a second antidepressant, or augmenting with a nonantidepressant medication, which have approximately equal likelihood of success based on a network meta-analysis. Collaborative care programs, including systematic follow-up and outcome assessment, improve treatment effectiveness, with 1 meta-analysis reporting significantly greater symptom improvement compared with usual care (SMD, 0.42 [95% CI, 0.23-0.61]).

Conclusions and relevance: Effective first-line depression treatments include specific forms of psychotherapy and more than 20 antidepressant medications. Close monitoring significantly improves the likelihood of treatment success.

Author/s:

Gregory E Simon, Nathalie Moise, David C Mohr

Treatment of Depression in Children and Adolescents: A Systematic Review. Comparative Effectiveness Review No. 224

John Bayhi — Fri, 17 Apr 2020 17:32:46 +0000

Date Added:

April 17, 2020

Journal/Publication:

AHRQ Publication No. 20-EHC005-EF

Publisher:

Agency for Healthcare Research and Quality

Publication Date:

April 10, 2020

URL:

Treatment of Depression in Children and Adolescents: A Systematic Review. Comparative Effectiveness Review No. 224

Type:

Meta-analyses, Reviews, and Guidelines

Format:

Article

DOI (1):

10.23970/AHRQEPCCER224

Keywords

cognitive behavioral therapy

selective serotonin reuptake inhibitors

MeSH

serotonin uptake inhibitors

paroxetine

Depressive Disorder

depressive disorder, major

united states food and drug administration

risk

Inpatients

Confidence Intervals

antidepressive agents

Cognitive Behavioral Therapy

The key findings are listed on the third page (page ii). James W. Mold, MD, MPH

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Background. Depressive disorders can affect long-term mental and physical health functioning among children and adolescents, including increased risk of suicide. Despite access to several nonpharmacological, pharmacological, and combined treatment options for childhood depression, clinicians contend with sparse evidence and are concerned about harms associated with treatment.

Methods. We conducted a systematic review to evaluate the efficacy, comparative effectiveness, and moderators of benefits and harms of available nonpharmacological and pharmacological treatments for children and adolescents with a confirmed diagnosis of a depressive disorder (DD)—major depressive disorder (MDD), persistent depressive disorder (previously termed dysthymia) or DD not otherwise specified. We searched five databases and other sources for evidence available from inception to May 29, 2019, dually screened the results, and analyzed eligible studies.

Results. We included in our analyses data from 60 studies (94 articles) that met our review eligibility criteria. For adolescents (study participants’ ages range from 12 to 18 years) with MDD, cognitive behavioral therapy (CBT), fluoxetine, escitalopram, and combined fluoxetine and CBT may improve depressive symptoms (1 randomized controlled trial [RCT] each, n ranges from 212 to 311); whether the magnitude of improvement is clinically significant is unclear. Among adolescents or children with MDD, CBT plus medications (8–17 years) may be associated with lower rates of relapse (1 RCT [n = 121]). In the same population (6–17 years), selective serotonin reuptake inhibitors (SSRIs) may be associated with improved response (7 RCTs [n = 1,525]; risk difference [RD], 72/1,000 [95% confidence interval (CI), 2 to 24], I2 = 9%) and functional status (5 RCTs [n = 941]; standardized mean difference, 0.16 [95% CI, 0.03 to 0.29]; I2 = 0%). For adolescents or children with any DD (7–18 years), CBT or family therapy may be associated with improvements in symptoms, response, or functional status (1 RCT each, n ranges from 64 to 99). Among children with any DD (7–12 years), family-based interpersonal therapy may be associated with improved symptoms (1 RCT, n = 38). Psychotherapy trials did not report harms. SSRIs may be associated with a higher risk of serious adverse events among adolescents or children with MDD (7–18 years; 9 RCTs [n = 2,206]; RD, 20/1,000 [95% CI, 1 to 440]; I2, 4%) and with a higher risk of withdrawal due to adverse events among adolescents with MDD (12–18 years; 4 RCTs [n = 1,296], RD, 26/1,000 [95% CI, 6 to 45]; I2, 0%). Paroxetine (1 RCT [n = 180]) may be associated with a higher risk of suicidal ideation or behaviors among adolescents with MDD (12–18 years). Evidence was insufficient to judge the risk of suicidal ideation or behavior for other SSRIs for adolescents and children with MDD or other DD (7–18 years) (10 RCTs [n = 2,368]; relative risk, 1.14 [95% CI, 0.89 to 1.45]; I2, 8%). However, this report excluded data on inpatients and those without depressive disorders, whom the Food and Drug Administration included in finding an increased risk of suicidality for all antidepressants across all indications.

Conclusion. Efficacious treatments exist for adolescents with MDD. SSRIs may be associated with increased withdrawal and serious adverse events. No evidence on harms of psychotherapy were identified.

Author/s:

Viswanathan, M, Kennedy, SM, McKeeman, J, Christian, R, Coker-Schwimmer, Cook Middleton, Bann, C, Lux, L, Randolph, Forman-Hoffman, V

Testosterone Treatment in Adult Men With Age-Related Low Testosterone: A Clinical Guideline From the American College of Physicians

John Bayhi — Tue, 07 Jan 2020 19:22:41 +0000

Date Added:

January 7, 2020

Journal/Publication:

Annals of Internal Medicine

Publisher:

American College of Physicians

Publication Date:

January 7, 2020

URL:

Testosterone Treatment in Adult Men With Age-Related Low Testosterone: A Clinical Guideline From the American College of Physicians

Type:

Meta-analyses, Reviews, and Guidelines

Format:

Article

DOI (1):

10.7326/M19-0882

Keywords

testosterone

guidelines

age-related testosterone deficiency

PMID (1):

31905405

MeSH

depressive disorder, major

Sexual Dysfunction

Physiological

Cognition

cardiovascular diseases

It appears that testosterone replacement in men with documented age-related testosterone deficiency may have small benefits in terms of sexual function and quality of life with no effect on physical function and no increase in significant adverse events. James W. Mold, MD, MPH

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DESCRIPTION:

The American College of Physicians (ACP) developed this guideline to provide clinical recommendations based on the current evidence of the benefits and harms of testosterone treatment in adult men with age-related low testosterone. This guideline is endorsed by the American Academy of Family Physicians.

METHODS:

The ACP Clinical Guidelines Committee based these recommendations on a systematic review on the efficacy and safety of testosterone treatment in adult men with age-related low testosterone. Clinical outcomes were evaluated by using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) system and included sexual function, physical function, quality of life, energy and vitality, depression, cognition, serious adverse events, major adverse cardiovascular events, and other adverse events.

TARGET AUDIENCE AND PATIENT POPULATION:

The target audience includes all clinicians, and the target patient population includes adult men with age-related low testosterone.

RECOMMENDATION 1A:

ACP suggests that clinicians discuss whether to initiate testosterone treatment in men with age-related low testosterone with sexual dysfunction who want to improve sexual function (conditional recommendation; low-certainty evidence). The discussion should include the potential benefits, harms, costs, and patient's preferences.

RECOMMENDATION 1B:

ACP suggests that clinicians should reevaluate symptoms within 12 months and periodically thereafter. Clinicians should discontinue testosterone treatment in men with age-related low testosterone with sexual dysfunction in whom there is no improvement in sexual function (conditional recommendation; low-certainty evidence).

RECOMMENDATION 1C:

ACP suggests that clinicians consider intramuscular rather than transdermal formulations when initiating testosterone treatment to improve sexual function in men with age-related low testosterone, as costs are considerably lower for the intramuscular formulation and clinical effectiveness and harms are similar.

RECOMMENDATION 2:

ACP suggests that clinicians not initiate testosterone treatment in men with age-related low testosterone to improve energy, vitality, physical function, or cognition (conditional recommendation; low-certainty evidence).

Author/s:

Qaseem, A., Horwitch, CA, Vijan, S, Etxeandia-Ikobaltzeta, I, Kansagara, D, Clinical Guidelines Committee of the American College of Physicians

The efficacy and safety of nutrient supplements in the treatment of mental disorders: a meta-review of meta-analyses of randomized controlled trials

John Bayhi — Fri, 13 Sep 2019 17:29:29 +0000

Date Added:

September 13, 2019

Journal/Publication:

World Psychiatry

Publisher:

World Psychiatric Association

Publication Date:

October 1, 2019

Issue:

Volume:

Pages:

308-324

URL:

The efficacy and safety of nutrient supplements in the treatment of mental disorders: a meta-review of meta-analyses of randomized controlled trials

Type:

Meta-analyses, Reviews, and Guidelines

Format:

Article

DOI (1):

10.1002/wps.20672

Keywords

depression

dietary supplements

mineral supplements

attention deficit disorder with hyperactivity

omega-3 fatty acids

PMID (1):

31496103

MeSH

depressive disorder, major

depression

attention deficit disorder with hyperactivity

mood disorders

mental health

folic acid

eicosapentaenoic acid

fatty acids

unsaturated

Several nutritional supplements appear to be helpful in the treatment of some mental health problems. The strongest evidence was found for eicosapentaenoic acid (an omega 3 fatty acid) as an adjunctive treatment for depression. More nascent evidence suggested that PUFAs may also be beneficial for attention‐deficit/hyperactivity disorder. High‐dose methylfolate appears to be helpful as an adjunct to antidepressants and counseling in major depressive disorder. There was emergent evidence for N‐acetylcysteine as a useful adjunctive treatment in mood disorders and schizophrenia. James W. Mold, MD, MPH

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The role of nutrition in mental health is becoming increasingly acknowledged. Along with dietary intake, nutrition can also be obtained from "nutrient supplements", such as polyunsaturated fatty acids (PUFAs), vitamins, minerals, antioxidants, amino acids and pre/probiotic supplements. Recently, a large number of meta-analyses have emerged examining nutrient supplements in the treatment of mental disorders. To produce a meta-review of this top-tier evidence, we identified, synthesized and appraised all meta-analyses of randomized controlled trials (RCTs) reporting on the efficacy and safety of nutrient supplements in common and severe mental disorders. Our systematic search identified 33 meta-analyses of placebo-controlled RCTs, with primary analyses including outcome data from 10,951 individuals. The strongest evidence was found for PUFAs (particularly as eicosapentaenoic acid) as an adjunctive treatment for depression. More nascent evidence suggested that PUFAs may also be beneficial for attention-deficit/hyperactivity disorder, whereas there was no evidence for schizophrenia. Folate-based supplements were widely researched as adjunctive treatments for depression and schizophrenia, with positive effects from RCTs of high-dose methylfolate in major depressive disorder. There was emergent evidence for N-acetylcysteine as a useful adjunctive treatment in mood disorders and schizophrenia. All nutrient supplements had good safety profiles, with no evidence of serious adverse effects or contraindications with psychiatric medications. In conclusion, clinicians should be informed of the nutrient supplements with established efficacy for certain conditions (such as eicosapentaenoic acid in depression), but also made aware of those currently lacking evidentiary support. Future research should aim to determine which individuals may benefit most from evidence-based supplements, to further elucidate the underlying mechanisms.

Author/s:

Firth, J, Teasdale, SB, Allott, K, Siskind, D, Marx, W, Cotter, J, Veronese, N, Schuch, F, Smith, L, Solmi, M, Carvalho, AF, Vancampfort, D, Berk, M, Stubbs, B, Sarris, J

New Approaches to Management of Depression

Tracy Ashby — Tue, 28 May 2019 05:00:00 +0000

Date Added:

May 28, 2019

Journal/Publication:

JAMA

Publisher:

American Medical Association

Publication Date:

May 24, 2019

URL:

https://edhub.ama-assn.org/jn-learning/audio-player/17623571?utm_source=silverch…

Type:

Meta-analyses, Reviews, and Guidelines

Format:

Video

Keywords

depression

podcast

MeSH

depressive disorder, major

A 20 minute podcast with a neuropsychiatrist at Harvard on emerging therapies for depression in adults.

His comments begin at 5:00 min. (ketamine). He then talks about nutrition at 8:25 min., exercise at 11:00 min., and neuroimaging and repeated transcutaneous magnetic stimulation at 13:50 min.

Interestingly he never mentions cognitive behavioral therapy, which is as effective as and much safer than drugs. James W. Mold, MD, MPH.

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Interview with Andrew A. Nierenberg, MD, author of Evolving Issues in the Treatment of Depression

Author/s:

Nierenberg, Andrew A.

Adverse Effects of First-line Pharmacologic Treatments of Major Depression in Older Adults

Jeffrey Wilson — Sat, 06 Apr 2019 18:24:42 +0000

Date Added:

April 6, 2019

Journal/Publication:

Comparative Effectiveness Review

Publisher:

Agency for Healthcare Research and Quality

Publication Date:

March 28, 2019

Issue:

215

Volume:

URL:

Adverse Effects of First-line Pharmacologic Treatments of Major Depression in Older Adults

Type:

Meta-analyses, Reviews, and Guidelines

Format:

Article

DOI (1):

10.23970/AHRQEPCCER215

Keywords

SSRI

SNRI

MeSH

serotonin uptake inhibitors

antidepressive agents, tricyclic

depressive disorder, major

serotonin

A summary of what we know about the adverse effects of SSRIs and SNRIs in people over the age of 65 (not much). James W. Mold, MD, MPH

Objective. To assess selected adverse events of antidepressants in the treatment of major depressive disorder (MDD) in adults 65 years old or older. Antidepressants included in this review, as determined by expert opinion, are selective serotonin reuptake inhibitors (SSRIs), serotonin norepinephrine reuptake inhibitors (SNRIs), bupropion, mirtazapine, trazodone, vilazodone, and vortioxetine.

Data sources. MEDLINE®, Embase®, Cochrane Central, and PsycINFO® bibliographic databases from earliest date through May 15, 2018; hand searches of references of relevant studies; www.clinicaltrials.gov; and the International Controlled Trials Registry Platform.

Review methods. Two investigators screened abstracts and subsequently reviewed full-text files. We abstracted data, performed meta-analyses when appropriate, assessed the risk of bias of each individual study, and graded the strength of evidence (SOE) for each comparison and selected outcomes. Number needed to harm (NNH) is reported for graded outcomes with statistically significant findings.

Results. Nineteen randomized controlled trials (RCTs) and two observational studies reported in 41 articles were included. Studies mostly evaluated treatment of the acute phase (<12 weeks) of MDD that was of moderate severity in patients 65 years and older, required subjects to be free from uncontrolled medical comorbidities or psychological conditions, and relied on spontaneous reporting of adverse events. Evidence was scarce and conclusions (based on statistical significance) for a given comparison and outcome are based often on a single study, particularly for specific adverse events. None of the RCTs were powered or designed to capture adverse events and most RCTs studied low doses of antidepressants. Observational data were limited by residual confounding.

SSRIs (escitalopram and fluoxetine, moderate SOE), vortioxetine (high SOE), and bupropion extended release (moderate SOE) had a statistically similar frequency of adverse events compared with placebo, whereas SNRIs (duloxetine and venlafaxine) were found to cause a greater number of adverse events (high SOE, NNH 10) compared with placebo during treatment of the acute phase of MDD. Both SSRIs (citalopram, escitalopram, and fluoxetine) and SNRIs caused a greater number of withdrawals due to adverse events than placebo (SSRIs, low SOE, NNH 11; SNRIs, moderate SOE, NNH 17). Duloxetine led to a greater number of falls compared with placebo (moderate SOE, NNH 10) over 24 weeks of treatment. A single observational study provided evidence on long-term use of antidepressants (low SOE) and suggested increased risk of adverse events (SSRIs), falls (SSRIs, SNRI venlafaxine, mirtazapine, trazadone), fractures (SSRIs, SNRI venlafaxine, mirtazapine), and mortality (SSRIs, SNRI venlafaxine, mirtazapine, trazadone) compared to no antidepressant.

Evidence for the comparative harms of different antidepressants was limited to single RCTs, mostly studying treatment of the acute phase of MDD (<12 weeks). Comparing SSRIs to each other or SSRIs to SNRIs showed statistically similar rates of adverse events (moderate SOE). SSRIs (paroxetine, citalopram, sertraline) had fewer withdrawals due to adverse events than tricyclic antidepressants (amitriptyline or nortriptyline) (low SOE, number needed to treat [NNT] 13), as did mirtazapine compared with paroxetine (low SOE, NNT 9). Vortioxetine had fewer adverse events than with duloxetine (high SOE, NNT 6).

Increasing age was associated with greater incidence of serious adverse events with escitalopram (low SOE). The increased risk of falls on duloxetine may be associated with the presence of cardiopulmonary conditions (low SOE).

Conclusions. In patients 65 years of age or older, treatment of the acute phase of MDD with SNRIs (duloxetine and venlafaxine) led to a greater number of adverse events compared with placebo, while adverse events were statistically similar to placebo with SSRIs (escitalopram, fluoxetine), vortioxetine, and bupropion. SSRIs (citalopram, escitalopram, and fluoxetine) and SNRIs (duloxetine and venlafaxine) led to a greater number of study withdrawals due to adverse events than placebo, and duloxetine increased the risk of falls. Further characterization of the comparative safety of antidepressants is difficult because few studies were identified, comparisons were based on statistical significance, trials were not powered to identify small differences in adverse events, and observational studies may be confounded. Comparative, long-term, well-designed studies that report specific adverse events are needed to better inform decision making in this population.

Author/s:

Sobieraj, D.M., Baker, W.L., Martinez, B.K., Hernandez, A.V., Coleman, C.I., Ross, J.S., Berg, K.M., Steffens, D.C.