There is considerable evidence that adding selective serotonin reuptake inhibitor (SSRI) antidepressants to antipsychotic treatment improves negative symptoms of schizophrenia. This augmentation effect may be due to "nonspecific" antidepressant action or be specifically related to action on the serotonergic system. This study examined the serotonergic specificity of SSRI augmentation by comparing an SSRI antidepressant with a comparably effective antidepressant acting via the noradrenergic system. Consenting patients having chronic schizophrenia with prominent negative symptoms were studied. Either fluvoxamine or maprotiline was added to their regular antipsychotic treatment in a double-blind manner for 6 weeks. Patients were assessed using the Brief Psychiatric Rating Scale, the Scale for the Assessment of Negative Symptoms, the Scale for the Assessment of Positive Symptoms, the Montgomery-Asberg Depression Rating Scale (MADRS), and the Neurological Rating Scale for Extrapyramidal Side Effects. Twenty-five patients completed the study. Negative symptoms improved significantly in the fluvoxamine group, but not in the maprotiline group. MADRS scores, which were low, did not change significantly in either group. Positive symptoms were not affected by either treatment. It is concluded that the mechanism by which fluvoxamine augmentation improves negative symptoms involves the serotonergic system and is distinct from its antidepressant action.

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