The focus of this study was the systematic evaluation of the clinical effects of the extract of ginkgo biloba (EGb) as an adjunct to the atypical antipsychotic clozapine in the treatment of refractory schizophrenia. In a placebo-controlled study, 42 patients with chronic, treatment-resistant schizophrenia, who were maintained on optimal doses of clozapine, were administered either 120 mg/day of EGb (N=20) or placebo (N=22) for 12 weeks. Clinical evaluations with the Brief Psychiatric Rating Scale, the Scale for the Assessment of Positive Symptoms, and the Scale for the Assessment of Negative Symptoms were completed biweekly. The use of EGb as an adjunct to clozapine was effective in decreasing negative symptoms, but not positive and overall psychopathology symptoms. EGb produced a mean 7.9+/-7.0 point reduction in the total Scale for the Assessment of Negative Symptoms score compared with a mean 1.8+/-3.5 point reduction in the placebo group (P=0.034). These preliminary data suggested that EGb was found useful for enhancing the effect of clozapine on negative symptoms in patients with treatment-resistant schizophrenia.