Efficacy and Safety of Selective Serotonin Reuptake Inhibitors, Serotonin-Norepinephrine Reuptake Inhibitors, and Placebo for Common Psychiatric Disorders Among Children and Adolescents

Abstract

Importance Depressive disorders (DD), anxiety disorders (AD), obsessive-compulsive disorder (OCD), and posttraumatic stress disorder (PTSD) are common mental disorders in children and adolescents. Objective To examine the relative efficacy and safety of SSRIs, SNRIs and placebo for the treatment of DD, AD, OCD, and PTSD in children and adolescents. Data Sources PubMed, Embase, PsycINFO, Web of Science, and Cochrane through August 2016. Study Selection Published and unpublished randomized, double-blind, placebo-controlled studies of SSRIs or SNRIs in youths diagnosed with DD, AD, OCD, or PTSD were included. Trials using other antidepressants (e.g. tricyclic antidepressants, MAOIs) were excluded. Data Extraction and Synthesis Effect sizes, (ES) calculated as standardized mean differences (Hedges’g) and Risk Ratios (RR) for adverse events, were assessed in a random-effects model. Main Outcome(s) and Measure(s) Primary outcomes, as defined by authors on pre- and post-intervention data, mean change data, and side effect data, were extracted independently by multiple observers following PRISMA guidelines. Results We deemed 36 studies eligible, including 6778 participants; 17 studies for DD, 10 for AD, 8 for OCD and one for PTSD., SSRIs and SNRIs were significantly more effective compared to placebo, yielding a small effect size (g=0.32, p<.001). AD (g=0.56, p<.001) showed significantly larger between-group ES than DD (g=0.20, p<.001). This difference was driven primarily by the placebo response: patients with DD exhibited significantly larger placebo responses (g=1.57, p<.001) compared to those with AD (g=1.03, p<.001). Of note is the relatively large effect size for SSRIs for anxiety disorders g=0.71, p<.001. Compared to placebo, patients taking an antidepressant reported significantly more treatment emergent adverse events (RR=1.07, p=.001 or RR=1.49, p<.001, depending on the reporting method), serious adverse events (RR=1.76, p<.001) and study discontinuation due to side effects (RR=1.79, p<.001). Conclusion and Relevance SSRIs and SNRIs are more effective than placebo, however, the effect is small and disorder-specific, yielding a larger effect for AD than for other conditions. Response to placebo is large, especially in DD. Serious adverse events are significantly more common in SSRIs and SNRIs than placebo.

Adverse Drug Reactions Across the Age Continuum: Epidemiology, Diagnostic Challenges, Prevention, and Treatments

“…A potentially important and largely unexplored consideration germane to ontogeny is the potential impact of developmental changes in receptor and transporter expression and activity on risk for ADRs. The controversy over the efficacy and safety of serotonin selective reuptake inhibitors and serotonin‐norepinephrine reuptake inhibitors when used for psychiatric disorders demonstrates that there are major knowledge gaps in our understanding of pharmacodynamics and receptor ontogeny . Given the growing appreciation that changes in transporter function in some circumstances may have a substantial impact on risk for both drug efficacy and drug safety, this also suggests that studies in this area are important to determine efficacy and safety of drugs used in children for which drug transport is an important part of drug disposition …”

A novel concurrent TMS‐fMRI method to reveal propagation patterns of prefrontal magnetic brain stimulation

“…Treatment resistant patients are treated with electro‐convulsive therapy or, in rare cases, with deep brain stimulation. Both psychotherapy and pharmacotherapy have small effect sizes of around 0.3, leaving a substantial amount of patients without adequate therapy due to intolerance or unresponsiveness (Cuijpers, Cristea, Karyotaki, Reijnders, & Hollon, 2017; Little, 2009; Locher et al, 2017). Up to two thirds of the patients with MDD do not respond to the first medication prescribed and approximately 15–33% of patients suffer from treatment resistance, which is defined as unresponsiveness or intolerance to at least two different classes of antidepressants (Cain, 2007).…”

Use of psychotropic medications in general paediatric practice

“…Potential paediatric indications for antidepressant medications include enuresis, ADHD, anxiety, OCD, selective mutism, anxiety or obsessionality associated with autism and intellectual disability aggression, bulimia and depression. Despite their name, antidepressant medications are more effective compared with placebos for anxiety disorders and OCD than they are for depression . In addition, while anxiety and OCD respond to most antidepressants, only fluoxetine and escitalopram separate convincingly from placebo for depressive symptoms .…”