Antipsychotic and Psychostimulant Drug Combination Therapy in Attention Deficit/Hyperactivity and Disruptive Behavior Disorders: A Systematic Review of Efficacy and Tolerability

  • David Linton
  • Alasdair M. Barr
  • William G. Honer
  • Ric M. ProcyshynEmail author
Attention-Deficit Disorder (R Bussing, Section Editor)
Part of the following topical collections:
  1. Topical Collection on Attention-Deficit Disorder


This systematic review examines treatment guidelines, efficacy/effectiveness, and tolerability regarding the use of antipsychotics concurrently with psychostimulants in treating aggression and hyperactivity in children and adolescents. Articles examining the concurrent use of antipsychotics and psychostimulants to treat comorbid attention deficit/hyperactivity disorder (ADHD) and disruptive behavior disorders (DBDs) were identified and their results were summarized and critically analyzed. Antipsychotic and stimulant combination therapy is recommended by some guidelines, but only as a third-line treatment following stimulant monotherapy and stimulants combined with behavioral interventions to treat aggression in patients with ADHD. Some studies suggest efficacy/effectiveness for an antipsychotic and stimulant combination in the treatment of aggression and hyperactivity in children and adolescents. However, the data do not clearly demonstrate superiority compared to antipsychotic or psychostimulant monotherapy. Most studies were performed over short time periods, several lacked blinding, few studies used any placebo control, and no comparisons were made with behavioral interventions. There are concerns about the tolerability of combination therapy, but data do not suggest significantly worse adverse effects for combination compared to either antipsychotic or stimulant monotherapy. Conversely, and contrary to speculation, use of a stimulant does not significantly reduce metabolic effects of antipsychotics. Combination treatment with antipsychotics and psychostimulants is used frequently, and increasingly more often. Few studies have directly examined this combination for the treatment of ADHD and DBDs. Further studies are necessary to confirm the efficacy and tolerability of the concurrent use of antipsychotics and psychostimulants in children and adolescents.


Antipsychotic agents Central nervous system stimulants Combination therapy Guidelines Attention-deficit/hyperactivity disorder ADHD Disruptive behavior disorders DBD Oppositional defiant disorder ODD Conduct disorder CD Children Adolescents Psychiatry 



This research was supported by a grant from the Canadian Institutes of Health Research and BC Mental Health & Addictions Services, an agency of the Provincial Health Services Authority.

Conflict of Interest

D. Linton declares that he has no conflict of interest.

A.M. Barr has received grants from Bristol-Myers Squibb and the Canadian Institutes of Health Research.

W.G. Honer has received consulting fees or sat on paid advisory boards for MDH Consulting, In Silico (no honorarium), Novartis, Roche, Otsuka, and Lundbeck; has received honoraria from Rush University, the Korean Society for Schizophrenia Research, the Centre for Addiction and Mental Health (Toronto), the BC Schizophrenia Society, the Fraser Health Authority, the Vancouver Coastal Health Authority, Providence Health Care, and the Canadian Agency for Drugs and Technology in Health; provided expert testimony for Fasken Martineau DuMoulin, Cave and Company, and Hartshorne & Mehl; and received grants from the Canadian Institutes of Health Research.

R.M. Procyshyn has received consulting fees and speaker fees from AstraZeneca, Bristol-Myers Squibb, Janssen, Otsuka, and Pfizer.


Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

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Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • David Linton
    • 1
    • 2
  • Alasdair M. Barr
    • 1
    • 2
  • William G. Honer
    • 1
    • 3
  • Ric M. Procyshyn
    • 1
    • 3
    • 4
    Email author
  1. 1.British Columbia Mental Health and Addictions Research InstituteVancouverCanada
  2. 2.Department of Anesthesiology, Pharmacology & TherapeuticsUniversity of British ColumbiaVancouverCanada
  3. 3.Department of PsychiatryUniversity of British ColumbiaVancouverCanada
  4. 4.BC Mental Health & Addictions Research InstituteVancouverCanada

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