RATIONALE: Sedation is a common side effect of clozapine treatment and may 
exacerbate metabolic consequences of poor diet and exercise habits that are 
common in patients with schizophrenia. Modafinil has been proposed as a 
treatment for clozapine-induced sedation and metabolic abnormalities.
OBJECTIVE: To estimate the effect sizes and person-to-person variation in 
anthropometric measures, glucose and lipid metabolism, and diet on modafinil 
treatment for future randomized control trials.
METHODS: A double-blind, placebo-controlled, flexible-dosed 8-week pilot trial 
was conducted, adding modafinil up to 300 mg/day to stabilized schizophrenia 
outpatients receiving clozapine. Blood pressure, weight, BMI, laboratory assays, 
and dietary intake were tracked to monitor changes in metabolic markers.
RESULTS: Thirty-five participants were randomly assigned to treatment with study 
drug or placebo and were included in the analysis. Modafinil did not improve 
blood pressure, weight, BMI, glucose or lipid metabolism compared to placebo. 
Modafinil was well tolerated and did not worsen psychosis.
CONCLUSIONS: Results of this pilot trial do not support routine use of modafinil 
to counteract increased weight and metabolic diseases in patients taking 
clozapine. However, the effects of modafinil on weight and insulin regulation 
warrant further investigation with effect sizes of 0.4 to 0.6.