A Naturalistic Comparison of Methylphenidate and Risperidone Monotherapy in Drug-Naive Youth With Attention-Deficit/Hyperactivity Disorder Comorbid With Oppositional Defiant Disorder and Aggression

J Clin Psychopharmacol. 2017 Oct;37(5):590-594. doi: 10.1097/JCP.0000000000000747.


Background/purpose: Attention-deficit/hyperactivity disorder (ADHD) and oppositional defiant disorder (ODD) are frequently co-occurring in youth, but data about the pharmacological management of this comorbidity are scarce, especially when impulsive aggression is prominent. Although stimulants are the first-line medication for ADHD, second-generation antipsychotics, namely, risperidone, are frequently used. We aimed to assess effectiveness and safety of monotherapy with the stimulant methylphenidate (MPH) and risperidone in a consecutive sample of 40 drug-naive male youths diagnosed as having ADHD-combined presentation, comorbid with ODD and aggression, without psychiatric comorbidities, according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition criteria and a structured clinical interview (Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version).

Methods: Twenty males treated with MPH (mean age, 8.95 ± 1.67 years) and 20 males treated with risperidone (mean age, 9.35 ± 2.72 years), followed up to 6 months, were assessed according to efficacy measures (Child Behavior Checklist [CBCL], Clinical Global Impression-Severity [CGI-S] and Improvement [CGI-I], Children Global Assessment Scale), and safety measures. At the end of the follow-up, both medications were similarly effective based on CBCL subscales of aggression and rule-breaking behaviors, on Diagnostic and Statistical Manual of Mental Disorders-oriented oppositional defiant problems and conduct problems, and on CGI-S, CGI-I, and Children Global Assessment Scale, but only MPH was effective on CBCL attention problems and attention-deficit/hyperactivity problems. Risperidone was associated with weight gain and elevated prolactin levels.

Implications/conclusions: Although the nonrandomized, nonblind design limits the conclusions of our exploratory study, our findings suggest that when ADHD is comorbid with ODD and aggression MPH and risperidone are both effective on aggressive behavior, but only stimulants are effective on ADHD symptoms.

Publication types

  • Clinical Trial
  • Comparative Study

MeSH terms

  • Aggression / drug effects*
  • Antipsychotic Agents / therapeutic use
  • Attention Deficit Disorder with Hyperactivity / drug therapy*
  • Attention Deficit and Disruptive Behavior Disorders / drug therapy*
  • Central Nervous System Stimulants / therapeutic use
  • Child
  • Comorbidity
  • Humans
  • Italy / epidemiology
  • Male
  • Methylphenidate / adverse effects
  • Methylphenidate / therapeutic use*
  • Risperidone / adverse effects
  • Risperidone / therapeutic use*


  • Antipsychotic Agents
  • Central Nervous System Stimulants
  • Methylphenidate
  • Risperidone