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Studies Evaluating Link Between Isotretinoin and Depression Produce Conflicting Results

Studies have produced conflicting results on whether isotretinoin, and other isotretinoin retinoids such as vitamin A and etretinate, may be associated with depression, psychosis, and suicide, according to the findings of a new meta-analysis on the subject.

According to Peter R. Hull, MD and Carl D'Arcy, MD, with the Department of Medicine at the University of Saskatchewan, Saskatoon, Canada, the growing number of reported cases of depression and suicide associated with isotretinoin use in patients with acne has triggered new warnings from regulators including depression-related, patient-informed consent forms.

A pharmacological mechanism that would account for psychiatric symptomatology as a result of isotretinoin treatment has not been found, the authors note. But retinoid receptors are widely distributed in the brain and more research is needed to ascertain whether they have a role in depression.

Hoffmann-La Roche, the manufacturer of AccutaneŽ (isotretinoin), estimates that by April 2001, approximately 12 million patients worldwide used isotretinoin, including 5 million patients in the US.

Dr. Hull and Dr. D'Arcy searched the MEDLINE database for studies published between January 1966 and May 14 2003 that evaluate a link between isotretinoin compounds and depression. In addition, an Internet search of the FDA Adverse Event Reporting System (AERS) files was also conducted.

Of the published medical literature, 24 documented cases of isotretinoin-associated depression were found, including 3 suicides. One additional patient committed suicide during a fourth month of isotretinoin treatment and 3 patients attempted suicide by taking an overdose of isotretinoin.

The US FDA's AERS contained almost 23,000 reports for isotretinoin from its approval in 1982 to December 2002. As of November 30, 2002, AERS contained 3104 reports (US and foreign) with at least one reported psychiatric event. The FDA is aware of 173 reports of suicide (both US and foreign) in association with isotretinoin.

"Reports of positive dechallenge and rechallenge present a strong signal pointing to an association between isotretinoin and depression," the authors note. However, they add that the obvious benefit of isotretinoin in treating acne should encourage continued use, although "patients and their relatives must be informed and depressive symptoms should be actively assessed at each visit and, if necessary, referral to a psychiatrist, antidepressant therapy or discontinuation of isotretinoin should be considered."
Am J Clin Dermatol 2003;4:7:493-505. "Isotretinoin use and subsequent depression and suicide : presenting the evidence"

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