Efficacy and safety of second-generation antipsychotics in children and adolescents with psychotic and bipolar spectrum disorders: comprehensive review of prospective head-to-head and placebo-controlled comparisons.
OBJECTIVE
To review data on efficacy and safety of second-generation antipsychotics (SGAs) in children and adolescents with psychotic and bipolar spectrum disorders.


METHODS
Medline/PubMed/Google Scholar search for studies comparing efficacy and/or tolerability: (i) between two or more SGAs; (ii) between SGAs and placebo; and (iii) between at least one SGA and one first-generation antipsychotic (FGA). The review focused on three major side-effect clusters: 1. body weight, body mass index, and cardiometabolic parameters, 2. prolactin levels, and 3. neuromotor side effects.


RESULTS
In total, 34 studies with 2719 children and adolescents were included. Studies lasted between 3 weeks and 12 months, with most studies (79.4%) lasting 3 months or less. Nine studies (n=788) were conducted in patients with schizophrenia, 6 (n=719) in subjects with bipolar disorder, and 19 (n=1212) in a mixed population. Data on efficacy showed that, except for clozapine being superior for refractory schizophrenia, there were no significant differences between SGAs. By contrast, safety assessments showed relevant differences between SGAs. Mean weight gain ranged from 3.8 kg to 16.2 kg in patients treated with olanzapine (n=353), from 0.9 kg to 9.5 kg in subjects receiving clozapine (n=97), from 1.9 kg to 7.2 kg in those on risperidone (n=571), from 2.3 kg to 6.1 kg among patients taking quetiapine (n=133), and from 0 kg to 4.4 kg in those treated with aripiprazole (n=451). Prolactin levels increased the most in subjects on risperidone (mean change ranging from 8.3 ng/mL to 49.6 ng/mL), followed by olanzapine (-1.5 ng/mL to +13.7 ng/mL). Treatment with aripiprazole was associated with decreased prolactin levels, while clozapine and quetiapine were found to be mostly neutral. With respect to neuromotor side effects, SGAs were associated with less parkinsonism and akathisia than FGAs. Most of the studies comparing neuromotor side effects between SGAs found no significant differences.


CONCLUSIONS
SGAs do not behave as a homogeneous group in children and adolescents with psychotic and mood disorders. Except for clozapine, the heterogeneity within the SGA group is mainly due to differences in the rates and severity of adverse events, especially regarding weight gain as a proxy for the risk of cardiometabolic disturbances.
Fraguas
David
D
Servicio de Salud Mental, Complejo Hospitalario Universitario de Albacete, Centro de Investigación Biomédica en Red de Salud Mental, CIBERSAM, Albacete, Spain.
Correll
Christoph U
CU
Merchán-Naranjo
Jessica
J
Rapado-Castro
Marta
M
Parellada
Mara
M
Moreno
Carmen
C
Arango
Celso
C
D000293:Adolescent; D014150:Antipsychotic Agents / Q000009:adverse effects* / Q000627:therapeutic use*; D001714:Bipolar Disorder / Q000188:drug therapy*; D002648:Child; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008297:Male; D010919:Placebos; D011618:Psychotic Disorders / Q000188:drug therapy*; D016032:Randomized Controlled Trials as Topic; D013997:Time Factors; D055815:Young Adult
D014150:Antipsychotic Agents; D010919:Placebos