Combination and augmentation strategies in treatment-resistant schizophrenia

Treatment resistance in schizophrenia puts guideline-recommended monotherapy to a challenge, and polypharmacy is used to address treatment-refractory psychotic features, affective symptoms, cognitive impairment, secondary obsessive–compulsive syndromes and treatment-emergent side effects caused by antipsychotics. Hereunto, both combinations of different antipsychotic agents and augmentation with mood stabilizers, antidepressants and experimental substances are applied. This review will discuss risks, benefits and levels of evidence of combination strategies involving multiple psychotropic substances, with a focus on their clinical relevance.