The majority of patients with schizophrenia receive continuous maintenance neuroleptic treatment to prevent psychotic relapse. Low dose treatment strategies have been employed to reduce the potential for adverse effects from cumulative neuroleptic exposure, (e.g. behaviorally manifest extrapyramidal side effects, tardive dyskinesia). The rationale for this approach is that patients, once stabilized, may only require a fraction of the amount of medication that was needed for treatment of their acute episode, and that is generally used for standard maintenance treatment. Previous studies have shown that low dose treatment is effective for some patients but not for others as it entails a higher risk of relapse than occurs with standard dose maintenance treatment. A major limitation of the use of the low dose strategy is the lack of validated predictors of relapse on low dose treatment. Preliminary studies indicate that behavioral response to a methylphenidate challenge test is correlated with relapse in patients following neuroleptic withdrawal while prolactin response to a haloperidol challenge test is correlated with the risk of relapse in patients maintained on low dose neuroleptic treatment. This study proposes to test the predictive efficacy of the methylphenidate and haloperidol challenge tests in a clinically naturalistic low dose maintenance treatment design. Ninety stable outpatients with schizophrenia or schizoaffective disorder who are receiving standard neuroleptic maintenance treatment will undergo methylphenidate and haloperidol challenge tests in a randomized counterbalanced order. Following the tests each patient's neuroleptic dose will be reduced by 75%. Patients will be followed biweekly with clinical evaluations for 52 weeks or until they relapse. Validation of predictive tests would facilitate general clinical use of low dose strategies for maintenance treatment as well as lead to further understanding of the neurobiology of schizophrenia.
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