Lack of Effect of Stimulant Combination with Second-Generation Antipsychotics on Weight Gain, Metabolic Changes, Prolactin Levels, and Sedation in Youth with Clinically Relevant Aggression or Oppositionality

Background: Second-generation antipsychotics (SGAs) are associated with weight gain, metabolic abnormalities, sedation/sleep disturbance, and prolactin abnormalities, especially in youths. Although stimulants have opposing dopamine receptor and adverse effects, it is unclear whether stimulant co-treatment counteracts the therapeutic or side effects of antipsychotics. Methods: This was a naturalistic cohort study including 153 antipsychotic trials in youths aged 4-19 (mean, 11.3 +/- 3.0) years, started on an SGA for clinically significant aggression or oppositionality associated with oppositional defiant disorder, conduct disorder, disruptive behavior disorder not otherwise specified (NOS), impulse control disorder NOS, intermittent explosive disorder, Tourette's disorder, autistic disorder, and pervasive developmental disorder NOS. Patients underwent fasting assessments of body composition, lipids, glucose, insulin, prolactin, sedation, and general efficacy at baseline, weeks 4, 8, and 12, comparing patients co-prescribed stimulants (n = 71) with those not co-prescribed stimulants (n = 82). Results: Patients received risperidone (33.3%), aripiprazole (29.4%), quetiapine (18.4%), olanzapine (11.8%), ziprasidone (5.9%), or clozapine (0.7%). With and without adjustment for differences in baseline variables (sex, prior stimulant use, primary Diagnostic and Statistical Manual of Mental Disorders, 4(th) edition [DSM-IV] disorders, co-morbid attention-deficit/hyperactivity disorder [ADHD], present in 46.3% of youths not receiving stimulants, and some body composition parameters), patients on versus off stimulants did not differ on any of the assessed outcomes (all p values >= 0.1). Conclusions: In contrast to guidelines, stimulant use did not precede or accompany antipsychotic use during the current episode of aggression/oppositionality in almost half of those youths who had aggressive/oppositional behavior and a DSM-IV diagnosis of ADHD. At the clinically prescribed doses, stimulant co-treatment of SGAs did not seem to significantly reduce antipsychotic effects on body composition, metabolic parameters, prolactin, sedation, and broad efficacy.