Fluvoxamine as an adjunctive agent in schizophrenia

Schizophrenia is a common mental disorder that has an early onset and rates high as a cause of medical disability. Antipsychotic agents are the mainstay of treatment but response is often inadequate. Negative symptoms (disturbances in volition, social interaction and affective functions) are particularly difficult to treat and form a major obstacle to rehabilitation. A promising approach to improve response of negative symptoms has been to add a selective serotonin reuptake inhibitor (SSRI) antidepressant to antipsychotic treatment. This review examines evidence pertaining to the efficacy, tolerability, and safety of the SSRI fluvoxamine, combined with antipsychotic agents, in the treatment of negative symptoms in schizophrenia. Important methodological issues, such as differentiating primary and secondary negative symptoms, are discussed. The balance of available evidence indicates that fluvoxamine can improve primary negative symptoms in chronic schizophrenia patients treated with typical antipsychotics and suggests that it may also do so in some patients treated with clozapine. This combination is generally safe and well tolerated although, as antipsychotic drug concentrations may be elevated, attention to dose and drug monitoring should be considered appropriately. Combination with clozapine may require particular caution because of potential toxicity if serum clozapine levels rise steeply. The fluvoxamine doses effective in augmentation are lower than those usually used to treat depression. Evidence regarding the use of fluvoxamine augmentation to treat phenomena, such as obsessions and aggression, which may be associated with schizophrenia, is also examined. An important goal of future studies will be to define which patient groups can benefit from combined treatment.