This pilot study is an eight-week, randomized, double-blind, placebo-controlled, escalating dose trial of the novel vigilance-promoting drug, modafinil, added to a stable dose of clozapine in 40 patients with schizophrenia or schizoaffective disorder. Modafinil will be initiated at 100 mg/d. After 2 weeks, the study drug may be increased to 200 mg/d and after 4 weeks, study drug may be increased to a maximum of 300 mg/d. Dose escalation will be based upon persistence of sedation versus emergence of side effects.~Evaluate tolerability and safety of modafinil compared to placebo using the SAFTEE and vital signs.~Evaluate the effect size of modafinil compared to placebo upon wakefulness and fatigue using the Epworth Sleepiness Scale (ESS) and the Fatigue Severity Scale (FSS).~Evaluate the effect size of modafinil compared to placebo upon negative symptoms using the SANS total score.~Evaluate the effect size of modafinil compared to placebo upon cognitive functioning using a standard battery of cognitive tests.~Evaluate the effect size of modafinil compared to placebo upon weight, BMI, waist/hip circumference and fasting glucose and lipids.~Effect the variability of response in placebo and modafinil groups for each of the outcome measures.
This pilot study is an eight-week, randomized, double-blind, placebo-controlled, escalating dose trial of the novel vigilance-promoting drug, modafinil, added to a stable dose of clozapine in 40 patients with schizophrenia or schizoaffective disorder. Modafinil will be initiated at 100 mg/d. After 2 weeks, the study drug may be increased to 200 mg/d and after 4 weeks, study drug may be increased to a maximum of 300 mg/d. Dose escalation will be based upon persistence of sedation versus emergence of side effects.