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Immediate Neurocognitive Effects of Methylphenidate on Learning-Impaired Survivors of Childhood Cancer

From the Divisions of Neurology, Neuro-Oncology, Behavioral Medicine, and Endocrinology, Departments of Pharmaceutical Sciences, Biostatistics and Epidemiology, Diagnostic Imaging, Radiation Oncology, and Hematology-Oncology, St Jude Children’s Research Hospital; Department of Pediatrics, University of Tennessee College of Medicine; and Departments of Electrical and Biomedical Engineering, University of Memphis, Memphis, TN.

Address reprint requests to Raymond K. Mulhern, PhD, Division of Behavioral Medicine, St Jude Children’s Research Hospital, 332 N Lauderdale, Memphis, TN 38105; email: raymond.mulhern{at}stjude.org

PURPOSE: To test if methylphenidate (MPH) has an objective beneficial effect on immediate performance on tests of neurocognitive functions among learning-impaired survivors of childhood acute lymphoblastic leukemia (ALL) and malignant brain tumors (BT).

PATIENTS AND METHODS: From July 1, 1997 through December 31, 1998, 104 long-term survivors of childhood ALL or a malignant BT completed neurocognitive screening for learning impairments and concurrent problems with sustained attention. Eligibility criteria for the MPH trial included an estimated intelligence quotient greater than 50, academic achievement in the 16^th percentile or lower for age in reading, math, or spelling, and an ability to sustain attention on a computerized version of the Conners’ Continuous Performance Test (CPT) in the 16^th percentile or lower for age and sex. Of the 104, 32 (BT, n = 25; ALL, n = 7) were eligible on the basis of these a priori criteria for a randomized, double-blinded, placebo-controlled trial of MPH. The patients ingested a placebo (lactose) or MPH (0.6 mg/kg; 20 mg maximum) and repeated selected portions of the screening battery 90 minutes later.

RESULTS: Compared to the 17 patients randomized to the placebo group, the 15 patients randomized to the MPH group had a significantly greater improvement on the CPT for sustained attention (errors of omission, P = .015) and overall index (P = .008) but not for errors of commission (indicative of impulsiveness) nor reaction times. A trend for greater improvement in the MPH group on a measure of verbal memory failed to reach statistical significance. No trend was observed for MPH effectiveness in improving learning of a word association task. No significant side effects from MPH were observed.

CONCLUSION: MPH resulted in a statistically significant improvement on measures of attention abilities that cannot be explained by placebo or practice effects.

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