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

Abstract

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 AE 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 ¼ 71) with those not co-prescribed stimulants (n ¼ 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 attentiondeficit=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.

Prolactin Serum Concentrations During Aripiprazole Treatment in Youth

“…Other children in trials with ARI were co-prescribed stimulants at baseline and throughout the study (Biederman et al 2005;Findling et al 2012;Geller et al 2012). Stimulants in children have been shown to slightly decrease PRL levels (Lurie and O'Quinn 1991), although other investigators found stimulants did not reduce PRL concentrations (Calarge et al 2009;Penzner et al 2009). Consequently, such add-on drugs were not adjusted for in the following analyses.…”

Predictors of Concomitant Use of Antipsychotics and Stimulants and Its Impact on Stimulant Persistence in Pediatric Attention Deficit Hyperactivity Disorder

“…25 Existing literature suggests increased risk for adverse effects such as extrapyramidal symptoms, seizures, sedation, obesity, type 2 diabetes mellitus, hyperprolactinemia, gynecomastia, and cerebrovascular or cardiovascular morbidity in children and adolescents using AAPs. 6,[26][27][28][29] A recent literature review by the Agency for Healthcare Research and Quality found limited evidence for the effectiveness of secondgeneration antipsychotics in the treatment of ADHD. 30 Although concomitant use of LAS and AAPs is common in pediatric settings, little is known about the prevalence of and factors associated with concomitant use of LAS and AAPs in youth with ADHD.…”

Metabolic Consequences of Antipsychotic Therapy: Preclinical and Clinical Perspectives on Diabetes, Diabetic Ketoacidosis, and Obesity

“…In addition to reductions in abdominal obesity, weight-related improvements in glycemic control and plasma lipid profiles were reported (Maayan et al 2010). The effect of stimulant medication in children and adolescents with ADHD, who were receiving SGAs for management of their behavioral disorders, has been determined (Penzner et al 2009). The stimulants did not reduce weight gain or improve other cardio-metabolic risk factors.…”