Selective serotonin re-uptake inhibitor augmentation in the treatment of negative symptoms of schizophrenia

Negative symptoms are core features of schizophrenia that respond poorly to first-generation antipsychotics and present a major obstacle in rehabilitation. Patients may be somewhat more responsive to clozapine and second-generation antipsychotics but even then, considerable impairment remains. This paper reviews the use of selective serotonin re-uptake inhibitor (SSRI) augmentation of antipsychotics in the treatment of negative symptoms in schizophrenia. Important methodological issues particular to the study of negative symptoms are also discussed. Current evidence indicates that at least two SSRIs, fluvoxamine and fluoxetine, can ameliorate primary negative symptoms in chronic schizophrenic patients treated with first-generation antipsychotics. Onset of improvement may be detected within 2 weeks of starting treatment. The combination is well-tolerated, although as antipsychotic drug concentrations may rise, close monitoring of drug doses and possibly drug concentrations is needed. So far, evidence regarding SSRI augmentation of second-generation antipsychotics is limited and in view of the increasing use of these newer agents, controlled studies are urgently needed. SSRI augmentation may be a useful addition to the treatment of schizophrenic patients with persistent negative symptoms. The paradoxical findings that both clozapine, a serotonin antagonist, and an SSRI antidepressant added to antipsychotics, can improve negative symptoms suggests that these pharmacologically distinct treatments may share common final mechanisms. A better understanding of these mechanisms can shed light on the pathogenesis of negative symptoms and provide new targets for drug development.