Acne drug linked to depression in animal tests

Amy Norton

The active ingredient in the acne drug Accutane seems to cause depression-related behavior in mice, a study has found.

Accutane, also sold generically as isotretinoin, has been linked to reports of depression and suicidal behavior among users. However, human studies have yielded conflicting results as to whether the drug itself contributes to these problems.

Depression is a complex disorder and, therefore, difficult to pin down to a single cause. For example, Accutane users often have severe acne, which itself may lead to depression.

Because the new study was conducted in mice, researchers were able to examine the direct effects of Accutane's active ingredient on signs of depression -- which, in mice, manifests as listless, sedentary behavior.

They found that mice given the drug every day for six weeks began to show such lethargy during tests that gauged their stress responses. In contrast, the animals showed no movement problems in other situations, including tests of physical coordination.

This suggests the drug's effects were depression-related, according to the researchers, led by Dr. Kally C. O'Reilly of the University of Texas at Austin.

They report the findings in the journal Neuropsychopharmacology.

For now, it's unclear whether the results might also apply to humans, study co-author Dr. Michelle A. Lane, also of UT Austin, told Reuters Health.

These findings are "just the beginning," she explained, and more work needs to be done before a conclusive link can be made between Accutane use and depression.

The acne drug belongs to a family of compounds called retinoids, derivatives of vitamin A. It's known that retinoids can damage the developing fetal nervous system, which is why Accutane cannot be given to pregnant women.

In addition, there is growing interest in how retinoids might affect the adult brain, according to O'Reilly's team.

Based on evidence from previous research, they note, Accutane might alter the regulation of brain chemicals like dopamine and serotonin, which are implicated in depression. Another possibility is that the drug might affect the production or survival of cells in brain regions linked to depression.

This is, however, still speculation. Little is known about how Accutane may work in the human brain. One brain-scan study of acne patients found that those treated with Accutane showed lesser activity in an area of the brain related to depression, but they weren't more likely than other patients to suffer depression.

Between 1982 and 2000, the U.S. Food and Drug Administration received 431 reports of depression, suicide or suicidal behavior among Accutane users.

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