Augmentation of olanzapine in treatment-resistant schizophrenia

OBJECTIVE: Up to 40% of patients with schizophrenic psychoses have symptoms that are resistant to monotherapy with antipsychotic drugs. In consequence, combinations of drugs are often used, especially based on the antipsychotic agents clozapine and olanzapine because of their broad receptor-interaction profile. The aim of this review was to provide a critical overview of the published results of olanzapine augmentation. METHODS: A systematic database search was performed of MEDLINE and BIOSIS (Ovid), looking for publications on augmented therapeutic approaches involving olanzapine. The search terms used were "augmentation," "combination," "schizophrenia," "olanzapine," and the names of other antipsychotic drugs and non-antipsychotic agents, including brand names, spanning publications from 1966 until the end of December 2004. RESULTS: Of 14 reports dealing with 8 different antipsychotic augmentation strategies (83 patients), only 1 trial, of sulpiride-olanzapine therapy, was performed in a randomized manner. Based on clinical observation, a significant number of the treatments led to favourable results. In contrast to adjuvant therapy with antipsychotic drugs, augmentation of olanzapine with glycine, antidepressants or mood stabilizers was evaluated in well-designed clinical trials (8 publications, 989 patients), with distinct improvements of positive and/or negative symptoms reported. CONCLUSIONS: The combination of olanzapine with antidopaminergic atypical antipsychotic agents seems to follow a neurobiological rationale. The augmentation trials with non-antipsychotic agents, for example, mood stabilizers, were successful and showed that randomized and placebo-controlled trials are feasible. Therefore, systematic evaluations of antipsychotic agents as adjuvant therapy are possible as well as necessary to determine the benefits and risks of any new treatment strategy.