OBJECTIVE: Negative symptoms are core features of schizophrenia that are 
functionally debilitating, associated with poor outcomes, and resistant to 
existing pharmacotherapies. We performed a randomized, double-blind, 
placebo-controlled study of modafinil, a medication approved for the treatment 
of excessive daytime sleepiness, to explore its efficacy as an adjunctive 
therapy for negative symptoms in schizophrenia.
METHOD: Twenty subjects with DSM-IV schizophrenia or schizoaffective disorder 
were randomly assigned to double-blind treatment with modafinil or placebo for 8 
weeks. The study ran from March 2002 through March 2006. Outcome measures 
included the Scale for the Assessment of Negative Symptoms (SANS), Brief 
Psychiatric Rating Scale (BPRS), Clinical Global Impressions (CGI) scale, 
Quality of Life Interview, neurocognitive assessments (California Verbal 
Learning Test, Degraded Performance-Continuous Performance Test, Trail-Making 
Test B), and somatic measures (sleep, weight, side effects).
RESULTS: Modafinil treatment was associated with a greater rate (CGI-Improvement 
[CGI-I] score < or = 3, 7/10 vs. 1/10) and degree (mean CGI-I score, 3.2 vs. 
4.1) of global improvement at study endpoint compared with placebo. However, 
modafinil did not significantly improve global negative symptoms as measured by 
the total SANS or SANS individual global items. Modafinil did not significantly 
worsen psycho-pathology (according to the BPRS), compared with placebo, and was 
well tolerated.
CONCLUSIONS: Although no effect on negative symptoms was found, adjunctive 
therapy with modafinil may result in global improvements in patients with 
schizophrenia who have prominent negative symptoms.