Adjunctive Trazodone in the Treatment of Negative Symptoms of Schizophrenia

Objective: The study examined whether adjunctive treatment with trazodone would reduce negative symptomatology in patients with chronic, residual schizophrenia. Methods: Patients selected for the study had an established clinical diagnosis of chronic schizophrenia with stable symptomatology, an absence of florid psychotic symptons; a stable regimen of neuroleptic medication, and an absence of depressive disorder. Active psychotic symptoms were assessed using the Brief Psychiatric Rating Scale (BPRS) score on the thinking disturbance factor. Negative symptoms were assessed using the BPRS withdrawal retardation factor as well as the affective flattening and alogia subscales from the Scale for Assessment of Negative Symptoms. Forty-nine patients were randomly assigned to either trazodone or placebo in a six-week doubleblind trial. Results: Forty-seven patients, 23 men and 24 women with an average age of 60 years, completed the six-week trial. Twenty-six of the patients received trazodone. Adjunctive treatment with trazodone significantly reduced the severity ratings on two of three measures of negative symptoms and did not significantly increase the severity of positive symptoms; however, the magnitude of the therapeutic effect was modest. The scores for negative symptoms were reduced by approximately 10 to 15 percent, and only three of the 26 actively treated patients showed moderate clinical improvement. Conclusions: Trazodone, used in conjunction with neuroleptics, mildly reduces the severity of negative symptoms in residual schizophrenia and does not exacerbate florid psychosis. The potential benefits of adjunctive trazodone therapy may outweigh the risk of worsening psychosis.