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A.
The debate about the safety of isotretinoin (Accutane) parallels the debate about the safety of antidepressant drugs—huge benefits versus what some think are serious risks. A chemical derivative of vitamin A (retinol), isotretinoin is a wonder drug for the treatment of severe acne. It cuts the output of the sebaceous glands, source of the oils that contribute to acne lesions. It changes the cells that line Does the hair follicles, so they become less likely to acne drug, block the follicle openings and permit a lesion isotretinoin (Accutane), to develop. And it reduces inflammation (redcause depression and ness and pain). For those with the most severe suicide, or are the form of acne, about 90% improve substantially psychiatric risks during the 20-week course of treatment. If exaggerated? acne returns, it is usually mild enough to be treated by more conservative methods. Isotretinoin has some serious side effects. It dries the skin and nasal passages, and it can cause peeling skin, thinning hair, and brittle nails. Joint pain, high blood lipid levels, weakened night vision, headache, and liver inflammation can also occur. And the drug is so dangerous to a fetus that, to receive a prescription, women must understand the dangers, have two negative pregnancy tests, and use two forms of effective contraception to avoid becoming pregnant. Then there is the issue of neuropsychiatric effects. High doses of vitamin A can cause headache, depression, fatigue, irritability, aggression, even personality change and psychosis—a syndrome called hypervitaminosis A. So it’s no surprise that isotretinoin is suspected of causing intolerable or deadly psychiatric effects. Correction: In the Clinical trials have been reassuring. For August 2005 issue, we example, this year, researchers in St. Louis reported in error that reported a study in which they treated 101 methamphetamine is teens and preteens for acne over four months, not smuggled into the United States. In fact, half of them with isotretinoin. They found no a significant amount of difference in depressive symptoms between the drug used in the U.S. the two groups, and no suicidal thoughts in is produced in Mexico. patients who took isotretinoin. For more information, see Suicide, thankfully, is rare, so it would not be http://www.whitehouseexpected to occur in a study this small. In large drugpolicy.gov/drugfact/ surveys, though, it is also hard to find increased methamphetamine. depression or suicide risk. One review found
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HARVARD MENTAL HEALTH LETTER
that suicide reports to the FDA following isotretinoin use are one-fifth the number expected by looking at rates in the general population. Other surveys of thousands of patients have found no increase in depression, suicide, or antidepressant drug use in patients taking isotretinoin. But critics point out that depression and suicide are probably under-reported and that some of the authors of these reports had links to the drug’s manufacturer, Hoffmann-La Roche. Individual case reports do link isotretinoin to depression—especially patients who say they became depressed for the first time after taking isotretinoin, recovered when they stopped, and became depressed again after restarting. Also, when compared to other drugs, isotretinoin has a relatively high frequency of FDA case reports of depression and suicide. And now there is scientific evidence that isotretinoin acts on the brain. Using brain scans, researchers at Emory University showed this year that the drug reduces activity in the orbitofrontal cortex; so does depression. Patients whose orbitofrontal activity slowed the most were not more likely to become depressed, but they were more likely to have headaches. And another recent report suggests a connection between headache and depressive symptoms in isotretinoin users. This new evidence and the troubling case reports, should be enough to keep dermatologists and their patients alert. Patients taking isotretinoin should let their physicians know about any depressive symptoms, self-destructive thoughts, or other mood changes, and maybe about headaches as well. But depressed persons need not avoid isotretinoin. Severe acne itself often lowers mood and damages self-esteem, so effective treatment can improve emotional health. As long as they stay informed and attentive, patients and physicians should be able to negotiate this medical treatment safely.
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Michael Craig Miller, M.D. Editor in Chief Because of the volume of correspondence we receive, we can’t answer every letter or message. Nor can we provide personal medical advice.
OCTOBER 2005
