Molecular mechanisms underlying synergistic effects of SSRI-antipsychotic augmentation in treatment of negative symptoms in schizophrenia.

Negative symptoms in schizophrenia respond poorly to antipsychotics, but may improve when these are augmented with selective serotonin reuptake inhibitors (SSRIs). The molecular mechanisms underlying the augmentation are unclear. Nevertheless, significant progress has been made, pointing to some candidate systems which may be involved in SSRI-antipsychotic synergism.

Multifunctional pharmacotherapy: what can we learn from study of selective serotonin reuptake inhibitor augmentation of antipsychotics in negative-symptom schizophrenia?

Many patients suffering from major psychiatric disorders do not respond adequately to monotherapy and require additional drugs. To date, there are no objective guidelines for deciding which combination may be effective, and the choice is based on previous clinical experience and on trial and error. Even when combination drugs are effective, the biochemical mechanisms responsible for the value-added effect are unknown.

Gene expression changes in peripheral mononuclear cells from schizophrenic patients treated with a combination of antipsychotic with fluvoxamine.

Antipsychotic treatment combined with Selective Serotonin Reuptake Inhibitor (SSRI) antidepressant can improve negative symptoms in schizophrenic patients that are unresponsive to antipsychotic drugs alone. The mechanism of this therapeutic effect is not clear. The current study examined molecular changes induced by the combined treatment in human peripheral mononuclear cells (PMC) in order to get insight into its mechanism of action.

The effect of chronic co-administration of fluvoxamine and haloperidol compared to clozapine on the GABA system in the rat frontal cortex.

Clinical studies in schizophrenia patients have shown that adding a selective serotonin reuptake inhibitor (SSRI) to antipsychotics can ameliorate negative symptoms that frequently resist standard treatments. It has been proposed that this combined treatment produces a 'net effect', different from that of the individual drugs and possibly common to that of the atypical antipsychotic, clozapine, which also ameliorates negative symptoms. The present study was initiated to determine the molecular events in the rat frontal cortex resulting from combined treatment of fluvoxamine and haloperidol compared to clozapine.