Risperidone vs. haloperidol on reaction time, manual dexterity, and motor learning in treatment-resistant schizophrenia patients

Abstract

Background: The present study compared the effects of risperidone vs. haloperidol on reaction time, manual dexterity, and two types of motor learning in a sample of treatment-resistant schizophrenia patients.

Methods: Fifty-six DSM-III-R diagnosed schizophrenia inpatients participated in a randomized, double-blind comparison of risperidone vs. haloperidol. Measures of reaction time, manual dexterity, motor sequence learning, and gross motor learning were administered at baseline, after 4 weeks of fixed-dose medication, and after 4 weeks of flexible-dose medication.

Results: The results indicated that patients receiving risperidone showed greater improvement in reaction time and manual dexterity than patients receiving haloperidol. After covarying symptom changes and movement disorder ratings, the results remained significant. The two treatment groups did not differ on either measure of motor learning.

Conclusions: The differences in performance in reaction time and manual dexterity may be due to a specific beneficial effect of risperidone, as opposed to a general reduction in extrapyramidal symptom liability, compared to haloperidol.

Introduction

Schizophrenia patients are generally slower than normal adults on tasks of fine motor speed, a consistent finding from the mid 1930s Huston et al 1937, Shakow and Huston 1936. Impairment is noted on measures that involve quick initiation of response (e.g., reaction time measures), maintenance of maximal speed over brief periods of time (e.g., finger tapping), and rapid fingertip manipulations (e.g., Pin Test, Purdue Pegboard) (King 1991). On the other hand, motor learning appears to be relatively preserved, a finding supported by most, but not all, of the recent studies Clare et al 1993, Goldberg et al 1993b, Granholm et al 1993, Green et al 1997a, Kern et al 1997.

Among measures of psychomotor speed and dexterity, reaction time has been examined in relation to clinical and functional outcome Cancro et al 1971, Wykes and Dunn 1992, Wykes et al 1990, Zahn and Carpenter 1978. Zahn and Carpenter (1978) found that acute schizophrenic patients who had faster reaction times at admission tended to show greater clinical improvement over the course of a brief hospital stay (3–4 months) than patients with slower reaction times. Similarly, Cancro et al (1971), using a longer period of follow-up, found reaction time to be predictive of clinical outcome 3 years later. It was speculated that the overall level of reaction time reflects an individual’s “environmental responsivity,” which may be a critical factor in the recovery process that potentiates the effects of treatment.

Two lines of evidence suggest that the types of psychomotor deficits noted in schizophrenia are largely independent of the effects of conventional neuroleptics. First, the observation of psychomotor slowing was documented well before the introduction of antipsychotic medication into clinical treatment in the 1950s. Second, a number of studies have examined the effects of chlorpromazine and similar acting antipsychotic agents on reaction time and other measures of psychomotor functioning. The preponderance of evidence indicates that conventional antipsychotic medications neither facilitate nor impede reaction time at either acute or chronic dose administrations (for a review see Cassens et al 1990, King 1990, Spohn and Strauss 1989). Patient performances on other types of psychomotor tasks show more varied effects (Gold et al 1991; for a review see Medalia et al 1988). Performance on measures that involve the maintenance of fine motor movement at maximal speed (e.g., finger tapping test) or ones that involve more gross musculature in the execution of perceptuomotor tracking (e.g., pursuit rotor) are unaffected by acute administration of low doses of chlorpromazine (<150 mg), but are impaired by acute administration of higher doses (200–300 mg) (Kornetsky et al 1959); however, chronic administration of chlorpromazine appears to yield no adverse effect on performance on tasks of fine motor speed, fine manipulative movements, or perceptuomotor tracking Pearl 1962, Pugh 1968, Small et al 1972, Whitehead and Thune 1958.

Relatively little is known about the pharmacologic effects of the new generation of antipsychotic medications on psychomotor movement. Although the newer antipsychotic medications are associated with reduced risk for the development of extrapyramidal symptoms, this finding may not necessarily translate directly to improvements in speed and coordination. Studies thus far have been limited to clozapine, and the results show no clear-cut effect. A nonblind comparison between haloperidol and clozapine failed to reveal any advantage for clozapine on measures of reaction time, finger tapping, or a task requiring fine motor precision (e.g., pegboard; Classen and Laux 1988). Also, Goldberg et al (1993a) reported no beneficial effect of clozapine on a number of neurocognitive functions that included two measures of psychomotor speed. More recently though, Hoff et al (1996) tested patients on conventional neuroleptics (unspecified) and then after 12 weeks on clozapine on tasks of motor speed and other neurocognitive functions using a within-subject design. Clozapine was associated with improvement in motor speed (finger tapping); other neurocognitive functions were differentially affected (e.g., verbal fluency improved, visual memory and executive functioning decreased). In one other study, a single-blind investigation that compared clozapine with placebo medication and fluphenazine, clozapine failed to improve performance on a complex reaction time measure of attention despite yielding clinical improvement (Zahn et al 1994). It is not known whether other atypical antipsychotic drugs will yield any beneficial effects for psychomotor functioning.

Risperidone is a relatively new atypical antipsychotic agent. Although risperidone shares some pharmacologic characteristics with clozapine (i.e., they both act on dopaminergic and serotonergic neurotransmitter systems), risperidone’s receptor binding profile is considerably different than that of clozapine’s. Hence, the largely negative findings for clozapine on motor speed and dexterity may or may not be relevant to patients treated with risperidone. The present study compared the effects of haloperidol vs. risperidone on measures of reaction time, manual dexterity, and two types of motor learning in a group of treatment-resistant schizophrenia patients using a double-blind design.