Risperidone Added to Psychostimulant in Children with Severe Aggression and Attention-Deficit/Hyperactivity Disorder: Lack of Effect on Attention and Short-Term Memory

Abstract

Objective: Professionals have periodically expressed concern that atypical antipsychotics may cause cognitive blunting in treated patients. In this study, we report data from a double-blind, randomized, controlled study of stimulant plus placebo versus combined stimulant and risperidone to evaluate the effects of the atypical antipsychotic on attention and short-term memory.

Methods: A total of 165 (n = 83 combined treatment; n = 82 stimulant plus placebo) children with attention-deficit/hyperactivity disorder and severe physical aggression, aged 6-12 years, were evaluated with Conners' Continuous Performance Test (CPT-II) and the Wechsler Intelligence Scale for Children-III (WISC) Digit Span subscale at baseline, after 3 weeks of stimulant-only treatment, and after six additional weeks of randomized treatment (stimulant+placebo vs. stimulant+risperidone).

Results: At 3 weeks, improvement on CPT-II performance (Commissions and Reaction Time Standard Error; p < 0.001) and on Digit Span memory performance (p < 0.006) was noted for the full sample. At study week 9, no difference in CPT-II or Digit Span performance was observed between the randomized groups (ps = 0.41 to 0.83).

Conclusions: Similar to other studies, we found no deleterious effects on attention and short-term memory associated with short-term use of risperidone. NCT00796302.

Keywords: CNS stimulants; Risperidone; attention-deficit/hyperactivity disorder; conduct disorder; oppositional defiant disorder.

Conflict of interest statement

Dr. M.G.A. has received research contracts, consulted with, or served on advisory boards of Biomarin Pharmaceuticals, Bristol-Myers Squibb, Cog State, Confluence Pharmaceutica, Coronado Biosciences, Forest Research, Hoffmann-La Roche, Johnson and Johnson, MedAvante Inc., Novartis, Pfizer, ProPhase LLC, and Supernus Pharmaceuticals. Dr. K.D.G. is a shareholder in Checkmate Plus, publisher of the Child and Adolescent Symptom Inventory-4R. Dr. O.G.B. has received royalties from Routledge Press and acted as a consultant for Ezra Innovations and PRIME CME. Dr. L.E.A. has received research funding from Curemark, Forest, Lilly, Neuropharm, Novartis, Noven, and Shire (as well as NIH and Autism Speaks) and has consulted or been on advisory boards for Neuropharm, Novartis, Noven, Organon, Roche, Seaside Therapeutics, Shire, Tris Pharma, Pfizer, and Gowlings. Dr. N.K.M. has received research support from Forest Research, GlaxoSmithKline, Eli Lilly and Co., Lundbeck, Merck, the NIH, Novartis, Otsuka, Pfizer, Rhodes Pharmaceuticals, Roche, Shire, Stanley Medical Research Institute, Sunovion, and Supernus Pharmaceuticals. Dr. V.R.R. has received research support from GlaxoSmithKline, Merck/Schering Plough, the NIMH, Covance/Otsuka, and Pfizer. Dr. S.B. has received research support from Supernus Pharmaceuticals. Dr. R.L.F. receives or has received research support, acted as a consultant, and/or served on a speaker's bureau for Alcobra, American Academy of Child & Adolescent Psychiatry, American Physician Institute, American Psychiatric Press, AstraZeneca, Bracket, Bristol-Myers Squibb, CogCubed, Cognition Group, Coronado Biosciences, Dana Foundation, Elsevier, Forest, GlaxoSmithKline, Guilford Press, Johns Hopkins University Press, Johnson and Johnson, Jubilant Clinsys, KemPharm, Lilly, Lundbeck, Merck, NIH, Neurim, Novartis, Noven, Otsuka, Oxford University Press, Pfizer, Physicians Postgraduate Press, Purdue, Rhodes Pharmaceuticals, Roche, Sage, Shire, Sunovion, Supernus Pharmaceuticals, Transcept Pharmaceuticals, Validus, and WebMD. Drs. J.N.E., C.A.F., D.J.K., B.S.G.M., and J.S., and Ms. H.K. report no conflicts of interest.

Figures

FIG. 1.

Numbers of participants and valid CPT-II administrations used in each analysis. BASIC = stimulant+parent training+placebo. AUGMENTED (AUG) = stimulant+parent training+risperidone. The total number of participants included in this report, with at one CPT-II administration for at least one analysis (Baseline to week 3 and week 3 to 9), appears on the top row. For each set of analyses, participants with at least one data point were included (second row). Participants without data at either visit for each analysis were excluded. The third row reports the number of participants with data from both visits in each analysis, and the fourth row shows the simple counts of participants with valid CPT-II administrations at each visit. CPT-II, Conners' Continuous Performance Test, Second Edition.