Common Acne Treatment Lacks Strong Support


Isotretinoin is considered an effective medication for acne but there is controversy between recommendations and FDA warnings.

While oral isotretinoin is recommended by the American Academy of Dermatology for moderate to severe acne,1 the drug has been associated with several adverse effects, including birth defects, depression, and inflammatory bowel disease. It includes black box warnings and the FDA requires enrollment in iPLEDGE, a risk evaluation and management program, for patients prescribed the therapy.

In a recent meta-analysis, researchers were unable to determine both the efficacy and safety of oral isotretinoin due to low-quality evidence in the majority of studies.2 They searched the literature and identified 31 studies that included a total of 3836 participants with mild to severe acne. Studies included in the analysis compared various doses of isotretinoin, oral isotretinoin with placebo, as well as other treatments including antibiotics.

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“Evidence was low-quality for most outcomes assessed,” the researchers wrote, including reported adverse events, inflammatory lesion counts, and improvements in severity.

They found no difference in the number of inflammatory lesions in 3 studies that compared isotretinoin with any oral antibiotic plus topical therapy. However, evidence was of low quality. One adverse event (Stevens-Johnson syndrome) associated with isotretinoin treatment was reported.

The researchers found slight improvements in acne severity when assessed by physician’s global evaluation, as well as less serious adverse events associated with isotretinoin, including dry skin, cheilitis, nausea, and vomiting. This evidence was also of low quality.

Fourteen studies that compared different doses of isotretinoin were analyzed. In 2 studies, the researchers found greater improvements associated with higher doses of isotretinoin. Another study showed that continuous, daily use of either low or conventional dosing of isotretinoin improved acne severity. In addition, a study found that conventional dosing lowered lesion count compared with low dosing, but “this was based on very low-quality evidence, indicating uncertainty,” the researchers wrote. 

Adverse events reported in the 14 studies were less serious and included dry skin, hair loss, and itching but the researchers are uncertain if there were any differences between dosing as evidence was low or very low quality. No birth defects were reported in any of the studies included in analysis.

“The overall quality of evidence for all of our key outcomes was low, due to serious limitations of study design and the limited amount of data,” the researchers concluded. “Thus, we are uncertain about the effects of oral isotretinoin on people with acne.” 

The researchers noted that future studies should clearly report long- and short-term standardized assessment of improvements in total inflammatory lesion counts, participant-reported outcomes, and safety. In addition, “oral isotretinoin for acne that has not responded to oral antibiotics plus topical agents needs further assessment, as well as different dose/regimens of oral isotretinoin in acne of all severities,” they wrote.


1. Zaenglein AL, Pathy AL, Schlosser BJ, et al. Guidelines of care for the management of acne vulgaris. J Am Acad Dermatol. 2016;74(5):945-73.e33.

2. Costa CS, Bagatin E, Martimbianco ALC, et al. Oral isotretinoin for acne [published online November 24, 2018]. Cochrane Database Syst Rev. doi:10.1002/14651858.CD009435.pub2