Review article

Antipsychotic Interactions – Why do They Matter?

Marina Šagud
Alma Mihaljević-Peleš
Bjanka Vuksan Ćusa
Ivana Klinar

Abstract

Antipsychotics are the cornerstone in the treatment of schizophrenia and are frequently used for several other mental disorders. Monotherapy with antipsychotics is strongly advised, but is often insufficient due to complex symptomatology and frequent comorbidities. Antipsychotics are commonly prescribed in combination with another antipsychotic, other psychotropic and somatic medications, which raises the risk for drug interactions (DIs). Those can be both pharmacodynamic (PD) and pharmacokinetic (PK). The former occur at the receptor level and are common but incompletely understood, while the latter are well-studied and easily verified by a change in the drug concentration. Those DIs mostly involve inhibition or induction of antipsychotic metabolism by hepatic CYP450 1A2, 2D6 and 3A4 enzymes. Drug interactions are particularly important for antipsychotics with a narrow therapeutic range, such as clozapine, or those that are extensively metabolized by a single pathway, such as quetiapine. The importance of an efflux protein, P-glycoprotein P (P-gp) is increasingly recognized but still poorly understood. Given that many agents, including antipsychotics, are substrates, inhibitors or inducers of P-gp, those DIs might have a role in unexplained drug reactions. DIs might be beneficial and harmful. For example, there is substantial evidence that aripiprazole addition to current antipsychotic regimen, due to its unique receptor profile, improves metabolic profiles and hyperprolactinemia. This review describes mechanisms of relevant DIs and provides information on different combinations, ranging from contraindicated to safe to potentially beneficial. Individualized treatment, careful consideration of risks and benefits, and a good therapeutic alliance, paves the way for best treatment outcome.

Keywords

antipsychotics; drug interactions; CYP450; P-glycoprotein

Hrčak ID:

189039

URI

https://hrcak.srce.hr/189039

Publication date:

8.11.2017.

Article data in other languages: croatian

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