CLINICALLY SIGNIFICANT INTERACTIONS OF PSYCHOTROPIC AGENTS WITH ANTIPSYCHOTIC-DRUGS

Various psychotropic drugs are commonly combined with antipsychotic ag ents. Such combinations can induce pharmacodynamically based, presumab ly additive, beneficial (e.g. sedative or mood-altering) effects or ad verse autonomic, cardiac depressant and CNS intoxicating effects. Clin ically significant interactions also arise through competition with or induction of hepatic microsomal cytochrome P450 (CYP) enzymes, partic ularly the CYP1A2 and CYP2D6 isozymes by which most antipsychotics are oxidised. Such pharmacokinetic interactions can elevate circulating c oncentrations of antipsychotics (both typical agents and the atypical antipsychotic clozapine) to potentially toxic ranges, which may lead t o increased risks of adverse effects. Such interactions occur particul arly with serotonin (5-hydroxytryptamine; 5-HT) reuptake inhibitor ant idepressants. Metabolic interactions that lead to lesser increases in antipsychotic concentrations may arise in combining these drugs with o ther antidepressants, benzodiazepines or propranolol. In contrast, mos t anticonvulsants, except valproic acid (sodium valproate), induce the oxidative metabolism of antipsychotics and can lower their plasma con centrations to potentially subtherapeutic levels, with unpredictable i ncreases after their discontinuation. Since simultaneous use of multip le psychotropic agents is increasingly common, special caution is requ ired to avoid untoward consequences of interactive adverse effects due to drug interactions, which can sometimes be severe or life-threateni ng.