An analysis of reports of depression and suicide in patients treated with isotretinoin.
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.


CONCLUSIONS
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.
Wysowski
D K
DK
Division of Drug Risk Evaluation I, Office of Post-Marketing Drug Risk Assessment, Center for Drug Evaluation and Research, Food and Drug Administration, Rockville, MD 20857, USA. wysowski@cder.fda.gov
Pitts
M
M
Beitz
J
J
D000293:Adolescent; D000328:Adult; D016907:Adverse Drug Reaction Reporting Systems; D000339:Affect / Q000187:drug effects; D016208:Databases, Factual; D003863:Depression / Q000139:chemically induced* / Q000453:epidemiology*; D005260:Female; D006801:Humans; D015994:Incidence; D015474:Isotretinoin / Q000009:adverse effects* / Q000627:therapeutic use; D008297:Male; D012189:Retrospective Studies; D013405:Suicide / Q000706:statistics & numerical data*; D013406:Suicide, Attempted; D014481:United States / Q000453:epidemiology; D014486:United States Food and Drug Administration
D015474:Isotretinoin