Reports
An analysis of reports of depression and suicide in patients treated with isotretinoin,☆☆,,★★

https://doi.org/10.1067/mjd.2001.117730Get rights and content

Abstract

Background: The Food and Drug Administration (FDA) has received reports of depression and suicide in patients treated with isotretinoin. Objective: Our purpose was to provide the number and describe the cases of depression and suicide reported to the FDA in US patients treated with isotretinoin and to consider the nature of a possible association between isotretinoin and depression. Methods: An analysis was made of reports of depression, suicidal ideation, suicide attempt, and suicide in US isotretinoin users voluntarily submitted to the manufacturer and the FDA from 1982 to May 2000 and entered in the FDA's Adverse Event Reporting System database. Results: From marketing of isotretinoin in 1982 to May 2000, the FDA received reports of 37 US patients treated with isotretinoin who committed suicide; 110 who were hospitalized for depression, suicidal ideation, or suicide attempt; and 284 with nonhospitalized depression, for a total of 431 patients. Factors suggesting a possible association between isotretinoin and depression include a temporal association between use of the drug and depression, positive dechallenges (often with psychiatric treatment), positive rechallenges, and possible biologic plausibility. Compared with all drugs in the FDA's Adverse Event Reporting System database to June 2000, isotretinoin ranked within the top 10 for number of reports of depression and suicide attempt. Conclusion: The FDA has received reports of depression, suicidal ideation, suicide attempt, and suicide in patients treated with isotretinoin. Additional studies are needed to determine whether isotretinoin causes depression and to identify susceptible persons. In the meantime, physicians are advised to inform patients prescribed isotretinoin (and parents, if appropriate) of the possibility of development or worsening of depression. They should advise patients (and parents) to immediately report mood swings and symptoms suggestive of depression such as sadness, crying, loss of appetite, unusual fatigue, withdrawal, and inability to concentrate so that patients can be promptly evaluated for appropriate treatment, including consideration of drug discontinuation and referral for psychiatric care. (J Am Acad Dermatol 2001;45:515-9.)

Section snippets

Methods

The Office of Post-Marketing Drug Risk Assessment of the FDA receives reports of adverse drug events primarily from physicians and pharmacists who submit them on a standardized form directly to the FDA or indirectly through pharmaceutical companies. Reports are entered into a computerized database, the Adverse Event Reporting System (AERS) using a coding thesaurus of adverse reaction terms used for searching and retrieval purposes. From 1969 through September 2000, more than 2 million reports

Results

In the 18-year period from marketing of isotretinoin to May 2000, the FDA received reports of depression, suicidal ideation, suicide attempts, and completed suicide for 431 exposed patients. Data describing these patients are given in the following paragraphs.

Discussion

There are several pieces of evidence that suggest a possible causal association between depression and isotretinoin. These include the relatively large number of reports of serious depression submitted to the FDA for isotretinoin; the temporal relationship between use of the drug and the onset, or worsening, of depression; positive dechallenges with isotretinoin discontinuation and initiation of psychiatric treatment; and positive rechallenges. In addition, the relationship between use of

Acknowledgements

Several persons at the FDA have been involved over time in the analysis and interpretation of psychiatric case reports with isotretinoin exposure, including Kathryn O'Connell, MD, Jonathan Wilkin, MD, Amarilys Vega, MD, Roger Goetsch, RPh, MPH, David Graham, MD, Anne Trontell, MD, Claudia Karwoski, PharmD, and Erick Turner, MD. We acknowledge the assistance of Ana Szarfman, MD, PhD, for data mining analyses. We also thank physicians, pharmacists, patients and their families, and other reporters

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    Conflict of interest: None.

    ☆☆

    The views expressed are those of the authors and do not necessarily represent the official position of the Food and Drug Administration.

    Reprints not available from authors.

    ★★

    Correspondence: Diane K. Wysowski, PhD, Division of Drug Risk Evaluation I, HFD-430, Food and Drug Administration, Parklawn Building, Room 15B-08, Rockville, MD 20857. E-mail: [email protected].

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