Psychotropic Drugs With Long Half-Lives: Implications for Drug Discontinuation, Occasional Missed Doses, Dosing Interval, and Pregnancy Planning

Abstract

The half-life of a drug is the time taken for the blood level of the drug to fall by half, provided that no more doses of the drug are administered in the intervening period. Many psychotropic drugs and their active metabolites, if any, have very long half-lives that extend for 2 days or longer. Examples are chlordiazepoxide, diazepam, fluoxetine, vortioxetine, aripiprazole, brexpiprazole, cariprazine, penfluridol, donepezil, and memantine. Other drugs with long half-lives that psychiatrists may prescribe include levothyroxine and zonisamide. Psychotropic drugs with long half-lives take long to reach steady state; this is seldom a problem. They also take long to wash out; this is an advantage because the risk of drug withdrawal or discontinuation syndromes is small, and a disadvantage if rapid washout is desired for any reason, including the experience of drug adverse effects or toxicity, or the discovery of an unplanned pregnancy. Other clinical issues related to drugs with long half-lives include the relevance of occasional missed doses, the possibility of once-weekly dosing, and the need for pregnancy planning.