Oral isotretinoin is generally a safe and effective drug for the treatment of acne vulgaris in the majority of patients, according to a literature review in the British Journal of Dermatology.
The systematic review was limited to randomized controlled trials in acne, involving a total of 760 patients (mostly men) comparing isotretinoin to control.
For all the studies, isotretinoin therapy reduced acne lesion counts by a clinically relevant amount, which was always by a greater amount than control. The control groups consisted of placebo (two studies), oral antibiotics (seven studies) or another control (two studies).
“Over the past few years, isotretinoin has been a contentious topic,” says co-lead author Isabelle Vallerand, Ph.D., of University of Calgary School of Medicine in Alberta, Canada. “The drug is widely used in dermatology as the go to medication for severe or treatment-resistant acne, yet there have been concerns over possible severe adverse effects such as suicide, pancreatitis and idiopathic intracranial hypertension.”
When the investigators looked into the scientific literature, they found mixed reports on adverse events.
“We noticed that there had not been any systematic review of randomized controlled trials to summarize available data on adverse events or on isotretinoin efficacy,” she said.
The finding that isotretinoin was superior to placebo and other therapies in reducing lesion counts “will not come as a surprise to dermatologists, but provides solid, reaffirming scientific data in support of using the medication for acne,” Dr. Vallerand says.
Secondly, while adverse effects are more common with isotretinoin compared to other treatments, “as might be expected, the majority of these adverse events are dryness relate. We documented no occurrences of suicide, pancreatitis or idiopathic intracranial hypertension with isotretinoin,” she said.
The review found roughly two adverse events in the isotretinoin groups compared to one in the control groups, for a total of 751 and 388, respectively.
Dermatological adverse events constituted 64.8 percent of overall adverse events in the isotretinoin groups, whereas ear, nose and throat adverse events were 11.6 percent.
Similarly, ocular adverse events like eye dryness, irritation and conjunctival infection occurred in 7.2 percen of patients in the isotretinoin groups.
On the other hand, gastrointestinal complications was the only adverse event more frequently reported in control groups, for which nausea and vomiting were associated with antibiotic therapy.
But adverse events severe enough to cause participant withdrawal from trials were rare -- just 3.2 percent of patients randomized to isotretinoin and 1.8 percent to control groups. Events for withdrawal from isotretinoin included Stevens-Johnson syndrome, cheilitis, zerosis, acne flare, photophobia, elevated liver enzymes, decreased appetite, headaches and depressed mood.
“Our review did not find an association between isotretinoin use and the onset of psychiatric disorders or suicide, although the presence of some psychiatric or psychosomatic symptoms was more commonly reported in those patients being treated with isotretinoin.
“These results may be surprising to some dermatologists, as they appear to contradict some of the cases portrayed in the media, which attribute isotretinoin as a cause of suicide or mental illness. However, we believe that the cause of mental illness is multifactorial and not likely explained by the use of isotretinoin alone, as evidenced by the data in our review,” Dr. Vallerand said.
The review lends strong support for the recommendations of using isotretinoin found in current clinical practice guidelines in America, Canada and Europe. “We believe that dermatologists are well positioned to prescribe isotretinoin to their patients in a safe manner,” she said.
Limitations of the review include the lack of long-term follow-up data and differences in dosing, methodology, reporting and study samples. The paucity of female patients, due to excluding pregnancy to prevent teratogenicity, might also skew the findings, especially psychiatric adverse events, as depression is more common among women.
“Future research should aim to determine whether there are specific groups of patients for whom isotretinoin is not safe or should aim to predict which patients may have the best response while mitigating potential adverse effects,” Dr. Vallerand said.
I.A. Vallerand, R.T. Lewinson, M.S. Farris, C.D. Sibley, M.L. Ramien, A.G.M. Bulloch, S.P. Patten. “Efficacy and Adverse Events of Oral Isotretinoin for Acne: A Systematic Review.” British Journal of Dermatology. January 2018. DOI:10.1111bjd.15668