Antidepressant medications: The FDA-approval process and the need for updates

Abstract

Antidepressant drug development first began in the mid-twentieth century with the discovery of monoamine oxidase inhibitors and tricyclic antidepressants. Soon after, additional molecular targets and drug entities were created, eventually leading to the development of selective serotonin reuptake inhibitors. Today, antidepressants now rank among the top 10 most commonly used medications in the United States (US) and account for over $11 billion in annual sales. To help ensure the safety and efficacy of these commonly used products, in 1977 the US Food and Drug Administration (FDA) created guidelines to standardize antidepressant studies and the approval process. Although many of the recommendations outlined by FDA are still relevant, the document remains vague when describing key aspects of antidepressant trial design and much of the clinical information is outdated by today's standards. This paper will provide a general overview of the FDA-approval process, summarize FDA's position related to antidepressant trial design, and discuss the need for updates in the approval process.