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

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

Psychological and Pharmacological Treatments for Adults With Posttraumatic Stress Disorder: A Systematic Review Update

Jeffrey Wilson — Thu, 23 Aug 2018 16:35:02 +0000

Date Added:

August 23, 2018

Journal/Publication:

Comparative Effectiveness Review

Publisher:

Agency for Healthcare Research and Quality

Publication Date:

May 17, 2018

Issue:

URL:

Psychological and Pharmacological Treatments for Adults With Posttraumatic Stress Disorder: A Systematic Review Update

Type:

Meta-analyses, Reviews, and Guidelines, Meta-analyses, Reviews, and Guidelines

Format:

Article

DOI (1):

10.23970/AHRQEPCCER207

Keywords

PTSD

therapy

MeSH

stress disorders, post-traumatic

This AHRQ evidence review summarizes the effectiveness of various non-pharmacologic and pharmacologic treatments for PTSD. The tabular results are on pages E3 – E6.

Free full text

Objective. To assess efficacy, comparative effectiveness, and harms of psychological and pharmacological treatments for adults with posttraumatic stress disorder (PTSD) and to update the original 2013 review.

Data sources. MEDLINE®, CINAHL®, Cochrane Library, Cochrane Clinical Trials Registry, PILOTS (Published International Literature on Traumatic Stress), PsycINFO®, and reference lists of published literature (May 2012–September 2017).

Review methods. Two investigators independently selected, extracted data from, and rated risk of bias of relevant studies. We conducted meta-analyses or network meta-analyses using random-effects models when we had evidence from three or more studies with low heterogeneity. We graded strength of evidence (SOE) following established Agency for Healthcare Research and Quality guidance.

Results. We included 193 randomized controlled trials (207 articles) for this review.

Several psychological treatments were associated with the reduction of PTSD symptoms and loss of PTSD diagnosis compared with inactive comparators; high SOE supports efficacy of cognitive behavioral therapy (CBT)-exposure and CBT-mixed treatments, and moderate SOE supports efficacy of cognitive processing therapy (CPT), cognitive therapy (CT), eye movement desensitization and reprocessing (EMDR), and narrative exposure therapy (NET). When directly comparing two treatments of interest, moderate SOE favors CBT-exposure over relaxation therapy.

Several pharmacological treatments reduced PTSD symptoms; moderate SOE supports the efficacy of fluoxetine, paroxetine, and venlafaxine compared with placebo. Our network meta-analysis (33 trials; N=4,817) of Clinician-Administered PTSD Scale (CAPS)-measured PTSD symptoms showed no differences in effectiveness between medications with at least moderate SOE of efficacy (fluoxetine, paroxetine, and venlafaxine) (low SOE for no difference).

Studies provided insufficient strength of evidence for serious adverse events associated with any treatments of interest. The majority of psychological studies reported no information about adverse events. Among pharmacological treatments with evidence of efficacy (moderate SOE), we found increased risk of nausea with venlafaxine compared with placebo (moderate SOE).

Our review found insufficient strength of evidence for the comparative effectiveness of any psychological versus pharmacological treatment and for differences in the efficacy or comparative effectiveness of treatments by patient characteristics (e.g., co-occurring conditions) or type, number, severity, or chronicity of trauma exposure(s). We did not find evidence for many of our outcomes of interest or interventions of interest, including the newer treatments added since our prior review.

Conclusions. Several psychological and pharmacological treatments have moderate to high SOE of efficacy for treating adults with PTSD. Future research is needed on the comparative effectiveness of treatments (including different comparisons of psychological and pharmacological treatments), differences in treatment benefits by trauma type or other patient characteristics, and adverse events associated with treatments.

Author/s:

Forman-Hoffman, Valerie, Middleton, Jennifer Cook, Feltner, Cynthia, Gaynes, Bradley N., Weber, Rachel Palmieri, Bann, Carla, Viswanathan, Meera, Lohr, Kathleen N., Baker, Claire, Green, Joshua