Isotretinoin, a drug for severe chronic acne, has long been linked to miscarriages, birth defects, and other serious problems, but a research review suggests much of data on the drug's safety, effectiveness, and side effects may be unreliable.
The analysis in the Cochrane Database of Systematic Reviews concludes that the available evidence is of such low quality that it's hard to say for sure how well isotretinoin works or how dangerous it may be.
"After 35 years of use, oral isotretinoin is widely accepted among dermatologists as the most effective available treatment for acne," said a co-author of the analysis, Dr. Edileia Bagatin of the Universidade Federal de Sao Paulo in Brazil.
Brand-name version of isotretinoin
"But lack of high-quality evidence observed in this systematic review raises uncertainties regarding its real effectiveness and safety," Bagatin said by email.
Almost a decade ago, Hoffmann-LaRoche stopped selling its brand-name version of isotretinoin, Accutane, in the wake of lawsuits over side effects and diminishing sales.
Generic versions of isotretinoin are still prescribed for severe acne and carry a "black box" warning, the strictest issued by the U.S. Food and Drug Administration, barring use by women who are or may become pregnant, because of the risk of birth defects.
The FDA also warns that isotretinoin may increase the risk of inflammatory bowel disease and psychiatric side effects including depression, psychosis, and suicidal thoughts.
But the American Academy of Dermatology maintains that evidence for these risks is inconclusive and still supports the use of isotretinoin for severe acne as long as doctors monitor patients for side effects.
More than four in five teens eventually develop acne, Bagatin and colleagues note, usually on the face but sometimes also on the back and chest. Untreated severe acne has been linked to depression and other mental health problems.
For the Cochrane analysis, researchers examined data from 31 previous studies with a total of 3,836 patients. Most were male. Three studies comparing oral isotretinoin to antibiotics for 20 to 24 weeks found no difference in the reduction of acne, but the researchers felt the evidence was low quality.
Fourteen studies compared different doses of isotretinoin for 12 to 32 weeks and failed to detect serious side effects; again, researchers said the evidence was low quality.
Less serious side effects, including dry skin, hair loss, and itching, were assessed in 13 studies but researchers were uncertain whether there were any meaningful differences based on different doses of the drug.
From clinical experience, however, doctors consider isotretinoin the "gold standard" for treating severe acne, said Dr. Felix Boon-Bin Yap of the University Tunku Abdul Rahman and Sunway Medical Centre in Selangor, Malaysia.