The Practical Importance of Half-Life in Psychopharmacology

Chittaranjan Andrade, MD

J Clin Psychiatry 2022;83(4):22f14584

ABSTRACT

The half-life of a drug is most commonly defined as the time taken for the plasma or blood level of the drug to fall by half. Elimination half-life, pharmacologic half-life, and biologic half-life are interchangeably used most commonly to describe the half-life of drugs that follow first-order or linear pharmacokinetics; that is, in single-compartment models, where the fall in blood level is proportionate to the concentration of the drug in blood. In 2 compartment models, where the drug equilibrates between blood and (for example) adipose tissue, during elimination there is a sharp initial fall in blood levels followed by a gradual subsequent fall; when drugs display this biphasic elimination pattern, the half-life corresponding to the second phase is what is clinically relevant, and this half-life is known as the terminal half-life. Half-life is influenced by drug distribution, drug metabolism, and drug excretion, each of which can be influenced by many factors such as age, use of concurrent medications, and presence of liver or renal disease. In order to maintain uniform blood levels and reduce the adverse effect risk, drugs with short half-lives need to be dosed more frequently. Drugs with short half-lives are more likely to be associated with withdrawal or discontinuation syndromes. The duration of action of a drug, time to steady state levels, and time to washout are each influenced by the value of the drug half-life. All these terms and concepts are defined and explained with the help of clinically relevant examples. Mental health care professionals who prescribe to patients need to know the half-lives of the drugs that they prescribe, the half-lives of active metabolites, if any, how these half-lives may differ with individual patient characteristics, and how to use this knowledge to prescribe to best advantage.

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