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As a consequence of individualized antipsychotic pharmacotherapy, many patients need more than a single drug, since they do not respond sufficiently to monotherapy. Other patients suffer from comorbid diseases and therefore require additional drugs from other pharmacological classes. Drug combinations, however, can give rise to pharmacokinetic and/or pharmacodynamic drug-drug interactions. Evaluation of pharmacokinetic interactions with antipsychotic drugs must consider substrate, inhibitor, and inducer properties for the cytochrome P450 (CYP) isoenzymes of all combined drugs. For consideration of pharmacodynamic interactions, special attention must be given to effects on dopamine D(2), histamine H(1), and acetylcholine M(1) receptors and on cardiac potassium channels. Additive pharmacological actions of combined drugs on these target structures can induce adverse reactions such as extrapyramidal symptoms, drowsiness, metabolic disturbances leading to weight gain and cardiac problems, cognitive impairment, delirium, or ventricular arrhythmia. Measuring plasma concentrations, i.e., therapeutic drug monitoring (TDM), is valuable to adjust antipsychotic medication when drug combinations contain inhibitors or inducers that alter plasma concentrations of the antipsychotic drugs. Amalgamating the broad knowledge on drug-drug interactions and using appropriately the option to monitor plasma concentrations in blood will help to apply complex combination therapies with antipsychotic drugs with maximal efficiency and safety.


Christoph Hiemke, Bruno Pfuhlmann. Interactions and monitoring of antipsychotic drugs. Handbook of experimental pharmacology. 2012(212):241-65

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PMID: 23129335

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