DOI: 10.1097/JCP.0b013e31822c94fd
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PMID: 21881450
Issn Print: 0271-0749
Publication Date: 2011/10/01
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Excerpt
Cognitive deficits in schizophrenia are core features of the illness that may be related to the daily functioning of patients.1 The relationship between cognitive deficits and psychosocial functioning is complex and probably mediated by several factors, namely, positive, negative, and depressive symptoms.2,3 Furthermore, the beneficial effect of atypical antipsychotic drugs on several domains of cognitive function is still a controversial issue.4
Cilostazol, a selective inhibitor type 3 phosphodiesterase, has been widely used as an antiplatelet agent for the treatment of chronic cerebral infarction and intermittent claudication.5 Recently, Hashimoto et al6 reported that cilostazol could attenuate hyperlocomotion and prepulse inhibition deficits in mice after administration of the N-methyl-d-aspartate receptor antagonist dizocilpine. Furthermore, the N-methyl-d-aspartate receptor antagonist phencyclidine-induced cognitive deficits in mice could be ameliorated by subsequent subchronic administration of cilostazol.7 These preclinical findings suggest that cilostazol may have a potential antipsychotic activity in schizophrenia, although precise mechanisms underlying any antipsychotic activity of this drug are currently unclear. In the present study, we conducted an open-label study of cilostazol, added to ongoing atypical antipsychotic drug in patients with schizophrenia.
The subjects consisted of 6 schizophrenic patients (mean [SD] age, 33.4 [10.3] years). All patients were recruited from the outpatient clinics of Teikyo University Chiba Medical Center. All patients met the Diagnostic and Statistical Manual of Mental Disorder, Fourth Edition, criteria for schizophrenia and had no other psychiatric disorders. All patients were evaluated as the residual type. They did not show depressive symptoms. They had been clinically stable for at least 6 months. All patients were receiving second-generation neuroleptics: risperidone (n = 5) or quetiapine (n = 1). All patients were being treated with the anticholinergic drug biperiden (mean dose, 2.0 mg/d). Five patients were treated with benzodiazepine drugs for the anxiolytic effects and to improve sleep quality. Patients received 25 mg/d for 2 weeks and subsequent 50 mg/d for 6 weeks cilostazol (Pretal; Otsuka Pharmaceutical Ltd, Tokyo, Japan).
Intelligence quotient scores were estimated from the information, digit span, and picture completion subscales using the short version of the Wechsler Adult Intelligence Scale-Revised. The mean estimated IQ was 88.2 (SD, 19.2). To assess the cognitive functioning of the prefrontal cortex, 6 neuropsychological test, the verbal fluency tests, the Wisconsin Card Sorting Test (Keio version; 48 cards), the Trail-Making Tests (TMTs; part A and part B), the Stroop test, the Digit Span Distraction Test, and the Iowa Gambling Task were administered. The memory test used in the present study was Rey Auditory Verbal Learning Test (RAVLT). Cognitive tests were evaluated at baseline and 8 weeks after treatment of cilostazol. The data were analyzed using a paired Student t test. Differences were set to be significant when P < 0.05. The research was approved by the ethics committee of Teikyo University Chiba Medical Center. Written informed consent was obtained after the procedure had been fully explained.
There were no adverse side effects associated with the treatment of cilostazol. Cilostazol (25 and 50 mg/kg per day for 8 weeks) was well tolerated. Table 1 show the summary of the cognitive function tests at baseline and 8 weeks after the treatment with cilostazol. The score of the TMT part A was significantly (t = 3.297, P = 0.022) decreased after cilostazol treatment. Other cognition tests were not statistically altered after cilostazol treatment. However, in the TMT part B, 4 patients improved, and 2 patients worsened. In the Stroop test, 5 patients improved, and 1 patient worsened. In the RAVLT (maximum memory), 4 patients improved, 1 patient worsened, and 1 patient did not change.
