Comparative Effects of Methylphenidate and Thioridazine in Hyperkinetic Children I. Clinical Results Rachel Gittelman-Klein, PhD; Donald F. Klein, MD; Sidney Katz, MD; Kishore Saraf, MD; Edith Pollack \s=b\ The effects of three pharmacological treatments, methyl- phenidate hydrochloride, thioridazine hydrochloride, a methyl- phenidate/thioridazine combination, and placebo were studied in outpatient hyperkinetic children rated hyperactive both in school and at home or clinic. Active treatment lasted 12 weeks; placebo lasted four weeks. Significant clinical improvement was obtained in a variety of settings\p=n-\all treatments were superior to placebo on ratings filled out by parents, teachers, and clinic staff. Though initially the combination of methylphenidate and thioridazine tended to produce greater clinical improvement, it was not superior to methylphenidate alone after 12 weeks of treatment. Methylphenidate alone and the methylphenidate/ thioridazine combination were more effective than thioridazine alone. The salient side effects with methylphenidate treatment were decrease in appetite, difficulty in falling asleep, and increased mood sensitivity. In contrast, thioridazine administra- tion was associated with appetite increase and enuresis. (Arch Gen Psychiatry 33:1217-1231, 1976) The purpose of this study was to evaluate the relative efficacy of a stimulant and a phenothiazine in the treatment of hyperkinetic children. This pediatrie popula¬ tion represents the largest single group of prepuberty children being referred for treatment to pediatricians and psychiatrists. The therapeutic value of stimulants has been well documented in several investigations.1 The clinical merits of several phenothiazines have been investigated. Prochloperazine" was not superior to placebo. Chlorproma¬ zine, on the other hand, induced significant therapeutic effects over placebo (P < .005) in hyperkinetic children.'4 Pooling results obtained in several separate, nonconcur- rent studies, Werry et al4 reported that chlorpromazine was as effective as dextroamphetamine sulfate and methylphenidate hydrochloride in the control of hyperkine- sis, but that the stimulants had a broader scope of action. Chlorpromazine was reported to induce marked control of hyperactivity without concomitant attentional improve¬ ment.56 Greenberg et al4 compared chlorpromazine, dextroam¬ phetamine, hydroxyzine hydrochloride, and placebo for an eight-week period. The authors concluded that dextroam¬ phetamine and chlorpromazine were equivalently effective in hyperkinetic children. In view of a significantly greater dropout in the placebo than drug groups (P < .001) and other methodological problems discussed elsewhere,1 ' the results are difficult to interpret. Saletu et al8 investigated the effects of eight-week trials of dextroamphetamine, thioridazine, and placebo among children referred by schools for a variety of behavior and learning problems, diagnosed either hyperkinetic or unso- cialized reactions. No consistent advantage was found for either drug. On some clinical ratings, placebo was superior to thioridazine. The results fail to corroborate numerous previous findings that demonstrated the marked effective¬ ness of dextroamphetamine in modifying the activity and attention levels of hyperactive children. Further, the results are unique in indicating some superiority for placebo treatment over active drug. The unusual pattern of results may stem from at least two causes. The first is the likely diagnostic heterogeneity of the sample, possibly leading to large placebo and peculiar drug effects; the second is the uncommonly low dosages used, which in our clinical experience are at homeopathic levels for many hyperkinetic children (mean doses for thioridazine and dextroamphetamine were 51 and 12 mg daily, respective- Accepted for publication Jan 14, 1976. From Queens College, Flushing, New York (Dr Gittelman-Klein), and the Long Island Jewish-Hillside Medical Center, Hillside Division, Glen Oaks, NY (Drs Gittelman-Klein, Klein, Katz, Saraf, and Ms Pollack). Reprint requests to Long Island Jewish-Hillside Medical Center, PO Box 38, Glen Oaks, NY 11004 (Dr Gittelman-Klein). at Mt Sinai School Of Medicine, on March 15, 2012 www.archgenpsychiatry.com Downloaded from