Abstract
Antidepressants are prescribed for the treatment of a number of psychiatric disorders in children and adolescents, however there is still controversy about whether they should be used in this population. This meta-review aimed to assess the effects of antidepressants for the acute treatment of attention-deficit/hyperactivity disorder (ADHD), anxiety disorders (ADs), autistic spectrum disorder (ASD), enuresis, major depressive disorder (MDD), obsessive-compulsive disorder (OCD), and posttraumatic stress disorder (PTSD) in children and adolescents. Efficacy was measured as response to treatment (either as mean overall change in symptoms or as a dichotomous outcome) and tolerability was measured as the proportion of patients discontinuing treatment due to adverse events. Suicidality was measured as suicidal ideation, behavior (including suicide attempts) and completed suicide. PubMed, EMBASE, and Web of Science were systematically searched (until 31 October 2019) for existing systematic reviews and/or meta-analyses of double-blind randomized controlled trials. The quality of the included reviews was appraised using AMSTAR-2. Our meta-review included nine systematic reviews/meta-analyses (2 on ADHD; 1 on AD; 2 on ASD; 1 on enuresis; 1 on MDD, 1 on OCD and 1 on PTSD). In terms of efficacy this review found that, compared to placebo: fluoxetine was more efficacious in the treatment of MDD, fluvoxamine and paroxetine were better in the treatment of AD; fluoxetine and sertraline were more efficacious in the treatment of OCD; bupropion and desipramine improved clinician and teacher-rated ADHD symptoms; clomipramine and tianeptine were superior on some of the core symptoms of ASD; and no antidepressant was more efficacious for PTSD and enuresis. With regard to tolerability: imipramine, venlafaxine, and duloxetine were less well tolerated in MDD; no differences were found for any of the antidepressants in the treatment of anxiety disorders (ADs), ADHD, and PTSD; tianeptine and citalopram, but not clomipramine, were less well tolerated in children and adolescents with ASD. For suicidal behavior/ideation, venlafaxine (in MDD) and paroxetine (in AD) were associated with a significantly increased risk; by contrast, sertraline (in AD) was associated with a reduced risk. The majority of included systematic reviews/meta-analyses were rated as being of high or moderate in quality by the AMSTAR-2 critical appraisal tool (one and five, respectively). One included study was of low quality and two were of critically low quality. Compared to placebo, selected antidepressants can be efficacious in the acute treatment of some common psychiatric disorders, although statistically significant differences do not always translate into clinically significant results. Little information was available about tolerability of antidepressants in RCTs of OCD and in the treatment of ADHD, ASD, MDD, and PTSD. There is a paucity of data on suicidal ideation/behavior, but paroxetine may increase the risk of suicidality in the treatment of AD and venlafaxine for MDD. Findings from this review must be considered in light of potential limitations, such as the lack of comparative information about many antidepressants, the short-term outcomes and the quality of the available evidence.
Highlights
There are many classes of antidepressants, which include selective serotonin reuptake inhibitors (SSRIs), serotoninnoradrenaline reuptake inhibitors (SNRIs), noradrenaline and specific serotonergic antidepressants (NASSAs), tricyclic antidepressants (TCAs), and monoamine oxidase inhibitors (MAOIs)
Cross-referencing with the other eligible systematic reviews/meta-analyses identified two individual randomized controlled trials (RCTs) in Tsapakis et al (17) that were not included in Cipriani et al (6) [Avci et al (18); Simeon et al (19)]
With regard to tolerability, compared to placebo: (1) imipramine, venlafaxine, and duloxetine were less well tolerated in young people with acute major depression; (2) no significant differences were found for any of the antidepressants in the treatment of anxiety disorder (AD), attention-deficit/hyperactivity disorder (ADHD), and posttraumatic stress disorder (PTSD); (3) tianeptine and citalopram, but not clomipramine, were less well tolerated in children with autistic spectrum disorder (ASD)
Summary
There are many classes of antidepressants, which include selective serotonin reuptake inhibitors (SSRIs), serotoninnoradrenaline reuptake inhibitors (SNRIs), noradrenaline and specific serotonergic antidepressants (NASSAs), tricyclic antidepressants (TCAs), and monoamine oxidase inhibitors (MAOIs). Several antidepressants are currently licensed for the treatment of child and adolescent psychiatric disorders, with specific indications varying across countries. In the USA, fluoxetine and escitalopram are Food and Drug Administration (FDA)-approved for major depressive disorder (MDD), fluoxetine, sertraline, fluvoxamine, and clomipramine for obsessive-compulsive disorder (OCD), duloxetine for generalized anxiety disorder (GAD) and the combination of olanzapine and fluoxetine for bipolar depression (1). In the UK, fluoxetine is licensed for MDD, fluvoxamine and sertraline for OCD, and imipramine for nocturnal enuresis (2). Some antidepressants are used by clinicians for non-licensed indications, such as amitriptyline for neuropathic pain and, historically, TCAs, in particular imipramine, have been used for the management of attention-deficit/hyperactivity disorder (ADHD)
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