Combining antipsychotics; is this strategy useful?

Antipsychotic drugs are commonly combined in psychiatric practice in an attempt to treat schizophrenia. Such practice is widespread, despite the lack of explicit endorsement by many of the main regulatory bodies. There are varying rationales behind combining these potent drugs-either to augment the effect of a drug whose action alone is inadequate for patients with treatment resistant schizophrenia (TRS), or to improve the side effects seen due to treatment. Augmentations are most frequently observed with clozapine, a drug reserved for use when other antipsychotic medications have failed. Several drugs have been chosen as adjuvants, including aripiprazole, sulpiride, amisulpiride and risperidone. A small number of RCTs (randomized controlled trials) have been performed but, despite this data and numerous case reports showing positive changes in symptomatology, Cochrane reviews of available studies have been unable to definitively confirm the efficacy of these combinations, frequently citing the need for larger, longer term, prospective studies.Evidence for benefits of combination therapy on side effects is also inadequate. Some RCTs and case series have shown they can positively alter side effects due to drugs such as clozapine, e.g. metabolic side effects. However, despite many of the combinations being relatively well tolerated, there is some evidence they can cause adverse effects of their own. More evidence is essential as, on the current data alone, it is not possible to make a firm recommendation on the efficacy and safety of antipsychotic combinations. In addition it is vital that the importance of a fair trial of monotherapy at adequate dosages is reinforced to clinicians, so that patients are not put onto these relatively unknown treatment strategies unnecessarily.