Purpose of review: Although most guidelines recommend monotherapy in schizophrenia, the combined application of multiple psychotropic agents is very common, especially in treatment-refractory cases. We review the empirical basis supporting these attempts and their relevance for clinical practice.
Recent findings: Polypharmacy intends to address different aspects of treatment resistance, most importantly insufficient response of psychotic positive and negative symptoms, but also cognitive disturbances, affective comorbidity, obsessive–compulsive syndromes and side-effects of antipsychotic drugs. This review summarizes the current state of evidence of combined antipsychotic treatment strategies and the augmentation of antipsychotics with mood stabilizers, antidepressants and experimental substances.
Summary: In general, rigorous data on combination therapy in schizophrenia are rare and further randomized controlled trials, naturalistic trials and head-to-head-trials are necessary. Some evidence supports a combination of antipsychotics and antidepressants for negative symptoms and comorbid major depressive episodes. The add-on of lithium and mood stabilizers lacks compelling evidence, but might be beneficial for specific subgroups. For treatment-resistant cognitive symptoms, antipsychotic medication should be combined with cognitive remediation, as no pharmacological add-on strategy has gained convincing evidence so far. Treatment-emergent positive and/or negative symptoms under clozapine monotherapy might benefit from adding a second atypical substance.