Extreme variability in the course of schizophrenia has promoted a search for alternatives to continuous maintenance pharmacotherapy. Alternative maintenance treatment strategies to utilize reduced neuroleptic exposure techniques as a maintain antipsychotic prophylaxis while reducing side effect liabilities. There are, however, no validated measures to identify candidates for periods of extended drug withdrawal or dose reduction. In addition, increasing emphasis is being placed on """"""""early warning"""""""" or """"""""prodromal"""""""" signs of relapse. Since many of these signs and symptoms are nonspecific and non-psychotic (i.e. anxiety, dysphoria, insomnia) it is necessary to establish their relationship to relapse. Otherwise patients may be unnecessarily or prematurely retreated with neuroleptics. This study will continue to investigate the use of a methylphenidate challenge test (METH-CTP) as a predictor of relapse vulnerability following drug discontinuation and the value of prodromal signs and symptoms in predicting imminent relapse. Seventy-five clinically stable outpatients with schizophrenia who are candidates for neuroleptic discontinuation will undergo MCTs and be carefully followed drug free for one year or until recurrence of psychopathology. During follow-up patients experiencing prodromal symptoms will be randomly assigned to drug or placebo and be intensively monitored for relapse. CTP's will be repeated at 24 weeks in patients who have remained stable to determine the temporal limits of the METH-CTP predictive efficacy. To evaluate the selective vulnerability of specific schizophrenic subgroups to the psychotogenic effects of methylphenidate, exploratory studies of patient with tardive dyskinesia, the defect state and negative symptoms and treatment refractory schizophrenia will also be conducted. This study will provide important information on predicting relapse in schizophrenia and identifying patients for alternative treatment strategies which would ultimately lead to safer and more effective long-term treatment strategies.
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