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Clinically Significant Interactions of Psychotropic Agents with Antipsychotic Drugs

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  • Drug Experience
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Summary

Various psychotropic drugs are commonly combined with antipsychotic agents. Such combinations can induce pharmacodynamically based, presumably additive, beneficial (e.g. sedative or mood-altering) effects or adverse autonomic, cardiac depressant and CNS intoxicating effects.

Clinically significant interactions also arise through competition with or induction of hepatic microsomal cytochrome P450 (CYP) enzymes, particularly the CYP1A2 and CYP2D6 isozymes by which most antipsychotics are oxidised. Such pharmacokinetic interactions can elevate circulating concentrations of antipsychotics (both typical agents and the atypical antipsychotic clozapine) to potentially toxic ranges, which may lead to increased risks of adverse effects. Such interactions occur particularly with serotonin (5-hydroxytryptamine; 5-HT) reuptake inhibitor antidepressants. Metabolic interactions that lead to lesser increases in antipsychotic concentrations may arise in combining these drugs with other antidepressants, benzodiazepines or propranolol. In contrast, most anticonvulsants, except valproic acid (sodium valproate), induce the oxidative metabolism of antipsychotics and can lower their plasma concentrations to potentially subtherapeutic levels, with unpredictable increases after their discontinuation.

Since simultaneous use of multiple psychotropic agents is increasingly common, special caution is required to avoid untoward consequences of interactive adverse effects due to drug interactions, which can sometimes be severe or life-threatening.

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Authors and Affiliations

  1. Department of Psychiatry and Neuroscience Program, Harvard Medical School, Boston, Massachusetts, USA

    Michele C. Meyer, Ross J. Baldessarini, Donald C. Goff & Franca Centorrino

  2. Department of Psychiatry, Massachusetts General Hospital, ACC-725, Boston, MA, 02114, USA

    Michele C. Meyer, Ross J. Baldessarini & Donald C. Goff

  3. Mailman Research Center, McLean Division of Massachusetts General Hospital, Belmont, Massachusetts, USA

    Ross J. Baldessarini & Franca Centorrino

  4. Lindemann Mental Health Center, Boston, Massachusetts, USA

    Donald C. Goff

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  4. Franca Centorrino
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Meyer, M.C., Baldessarini, R.J., Goff, D.C. et al. Clinically Significant Interactions of Psychotropic Agents with Antipsychotic Drugs. Drug-Safety 15, 333–346 (1996). https://doi.org/10.2165/00002018-199615050-00004

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