A Placebo-Controlled Trial of Modafinil (Provigil) Added to Clozapine in Patients With Schizophrenia

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.

Inclusion criteria

• Diagnosis of Schizophrenia, any subtype or schizoaffective disorder
• Ages 18-65 years
• Capable of providing informed consent, or capable of providing assent with a guardian who provides informed consent
• Stable dose of clozapine for at least 1 month
• Three months of stable psychotic symptoms

Exclusion criteria

• Serious medical or neurological illness (unstable cardiac disease, seizure disorder, malignancy, liver or renal impairment, etc.)
• Current substance abuse
• Pregnancy, nursing, or unwilling to use appropriate birth control measures during participation if female and fertile.
• Unable to complete neuropsychological tests
• History of serious blood dyscrasia requiring discontinuation of clozapine
• Serious suicidal or homicidal risk within the past six months
• Current treatment with a psychostimulant