Combined stimulant and antipsychotic treatment in adolescents with attention-deficit/hyperactivity disorder: a cross-sectional observational structural MRI study.

Meta-analyses suggest normalizing effects of methylphenidate on structural fronto-striatal abnormalities in patients with attention-deficit/hyperactivity disorder (ADHD). A subgroup of patients receives atypical antipsychotics concurrent with methylphenidate. Long-term safety and efficacy of combined treatment are unknown. The current study provides an initial investigation of structural brain correlates of combined methylphenidate and antipsychotic treatment in patients with ADHD. Structural magnetic resonance imaging was obtained in 31 patients who had received combined methylphenidate and antipsychotic treatment, 31 matched patients who had received methylphenidate but not antipsychotics, and 31 healthy controls (M age 16.7 years). We analyzed between-group effects in total cortical and subcortical volume, and in seven frontal cortical and eight subcortical-limbic volumes of interest, each involved in dopaminergic neurotransmission. Patients in the combined treatment group, but not those in the methylphenidate only group, showed a reduction in total cortical volume compared to healthy controls (Cohen's d = 0.69, p < 0.004), which was apparent in most frontal volumes of interest. Further, the combined treatment group, but not the methylphenidate group, showed volume reduction in bilateral ventral diencephalon (Left Cohen's d = 0.48, p < 0.04; Right Cohen's d = 0.46, p < 0.05) and the left thalamus (Cohen's d = 0.47, p < 0.04). These findings may indicate antipsychotic treatment counteracting the normalizing effects of methylphenidate on brain structure. However, it cannot be ruled out that pre-existing clinical differences between both patient groups may have resulted in anatomical differences at the time of scanning. The absence of an untreated ADHD group hinders unequivocal interpretation and implications of our findings.