Safety of 80 antidepressants, antipsychotics, anti‐attention‐deficit/hyperactivity medications and mood stabilizers in children and adolescents with psychiatric disorders: a large scale systematic meta‐review of 78 adverse effects

Abstract

Mental disorders frequently begin in childhood or adolescence. Psychotropic medications have various indications for the treatment of mental dis­orders in this age group and are used not infrequently off‐label. However, the adverse effects of these medications require special attention during developmentally sensitive periods of life. For this meta‐review, we systematically searched network meta‐analyses and meta‐analyses of randomized controlled trials (RCTs), individual RCTs, and cohort studies reporting on 78 a priori selected adverse events across 19 categories of 80 psychotropic medications – including antidepressants, antipsychotics, anti‐attention‐deficit/hyperactivity disorder (ADHD) medications and mood stabilizers – in children and adolescents with mental disorders. We included data from nine network meta‐analyses, 39 meta‐analyses, 90 individual RCTs, and eight cohort studies, including 337,686 children and adolescents. Data on ≥20% of the 78 adverse events were available for six antidepressants (sertraline, escitalopram, paroxetine, fluoxetine, venlafaxine and vilazodone), eight antipsychotics (risperidone, quetiapine, aripiprazole, lurasidone, paliperidone, ziprasidone, olanzapine and asenapine), three anti‐ADHD medications (methylphenidate, atomoxetine and guanfacine), and two mood stabilizers (valproate and lithium). Among these medications with data on ≥20% of the 78 adverse events, a safer profile emerged for escitalopram and fluoxetine among antidepressants, lurasidone for antipsychotics, methylphenidate among anti‐ADHD medications, and lithium among mood stabilizers. The available literature raised most concerns about the safety of venlafaxine, olanzapine, atomoxetine, guanfacine and valproate. Nausea/vomiting and discontinuation due to adverse event were most frequently associated with antidepressants; sedation, extrapyramidal side effects, and weight gain with antipsychotics; anorexia and insomnia with anti‐ADHD medications; sedation and weight gain with mood stabilizers. The results of this comprehensive and updated quantitative systematic meta‐review of top‐tier evidence regarding the safety of antidepressants, antipsychotics, anti‐ADHD medications and mood stabilizers in children and adolescents can inform clinical practice, research and treatment guidelines.

Analysis of the status of drug treatment in 746 inpatients with early-onset schizophrenia in China: a retrospective study

“…Despite the efficacy of APs having been proven, its use in children and adolescents still faces compounding challenges. An unmet challenge is the side effects caused by atypical antipsychotics, especially metabolic syndrome [ 17 , 18 ]. Rates of metabolic problems are higher in young first-episode patients [ 19 ], and children and adolescents appear to be at greater risk of weight gain from antipsychotics than adults [ 20 ].…”

DSM-5 Attenuated Psychosis Syndrome in Adolescents Hospitalized With Non-psychotic Psychiatric Disorders

“…However, it is also true that rates of antipsychotics were high in other diagnostic groups in this sample, including bipolar-spectrum disorders (49), which supports that atypical antipsychotic use is likely related to the reason for admission to the psychiatric unit and not only to efforts to treat attenuated psychotic symptoms or to prevent full-blown psychosis. Nevertheless, the widespread use of antipsychotics in adolescents for non-psychotic, predominantly depressive disorders is concerning due to the established adverse effects risks that atypical antipsychotics have in youth (73)(74)(75)(76)(77).…”

There are no “side” effects, just “core” effects of antipsychotic pharmacotherapy

“…7 Prescription of antipsychotics for conditions other than schizophrenia is on the increase, often-in the long-term-resulting in varying safety and tolerability problems, which may affect patients of all ages. 8 Also, the antipsychotic drugs are just as heterogenous as are the clinical manifestations of schizophrenia.…”

“…The overall recommendations drawn by Stahl et al 1 are in line with both qualitative 4 and quantitative evidence about the safety and tolerability of short‐ (emergency use) and long‐acting antipsychotics in the acute treatment of adults with multi‐episode, 5 as well as first‐episode 6 schizophrenia, especially concerning the cardio‐metabolic impact of the atypical antipsychotics 7 . Prescription of antipsychotics for conditions other than schizophrenia is on the increase, often—in the long‐term—resulting in varying safety and tolerability problems, which may affect patients of all ages 8 . Also, the antipsychotic drugs are just as heterogenous as are the clinical manifestations of schizophrenia.…”