Preclinical and clinical investigation of antipsychotic polypharmacy: What is the evidence?

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Antipsychotic polypharmacy is a common clinical practice whose implications have not been thoroughly assessed to date. There is a paucity of preclinical studies investigating the effects of antipsychotic combinations on animal models. These models are focusing on the effects of antipsychotic combinations on psychiatric and extrapyramidal symptoms’ simulations and on antipsychotic-induced metabolic abnormalities. Although most guidelines favour the use of antipsychotic monotherapy, clinical trials and meta-analyses examining the merits and disadvantages of polypharmacy are contradictory. A recent synthetic approach suggests that antipsychotic polypharmacy could be useful under conditions of acute symptoms’ exacerbation non-responsive to monotherapy but not so beneficial in chronic refractory illness. It also recommends that antipsychotic polypharmacy should always have a rational pharmacological basis. The role of antipsychotic combination strategies other than clozapine augmentation in treatment resistant patients needs to be clarified in future research. The specific effects of antipsychotic co-treatment in different symptoms dimensions, its interactions, adverse reactions and associations with medical morbidity and mortality remain to be further examined through rigorously designed clinical trials and prospective epidemiological studies.




Kontis, D., & Theochari, E. (2013). Preclinical and clinical investigation of antipsychotic polypharmacy: What is the evidence? In Polypharmacy in Psychiatry Practice Volume I: Multiple Medication Use Strategies (pp. 75–105). Springer Netherlands.

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