Little evidence exists to establish a clear and understandable association between exposure to isotretinoin, a prescription retinoid commonly used in treatment-resistant acne, and psychiatric adverse events, according to the results of a literature review published in Current Therapeutic Research, Clinical and Experimental.
The researchers searched PubMed for literature containing the terms “isotretinoin,” as well as “psychosis,” “psychiatric,” and “teratogenic.” Articles included in the review reported that high levels of vitamin A can be teratogenic if administered during pregnancy. Current evidence states that the safe estimated level of vitamin A during pregnancy is between 25,000 IU/day and 37,000 IU/day. Isotretinoin also appears to be associated with birth defects, such as craniofacial and heart malformations, and some research suggests that the retinoid can induce cleft palate in humans “by sustaining the expression of epidermal growth factor receptors in medial epithelial cells of the palate at a time when these cells would normally undergo apoptosis, resulting in continued DNA synthesis, proliferation, survival, and shift in cell phenotype.”
A total of 400 case reports between 1982 and 2000 have indicated that isotretinoin may increase the risk for depression, the researchers found. In a survey, only 37% of a total of 591 board-certified dermatologists reported that they believed isotretinoin can result in psychiatric issues. Other studies suggest that isotretinoin may be associated with depression and suicidal ideation only on an individual basis. Conversely, some studies indicate that no link between isotretinoin and depression exists, suggesting “instead an amelioration of depressive or anxious symptoms with treatment.”
Limitations of this review include the lack of a pooled meta-analysis of the treatment’s true effects on psychiatric issues.
“Further study could help to tailor the information provided to individuals considering undergoing or prescribing treatment with isotretinoin, and increase attention to, and improve management of, possible side effects,” the researchers added. “Particular vigilance may be warranted in the case of patients with a personal or family history of bipolar disorder or other psychiatric illness.”
Suuberg A. Psychiatric and developmental effects of isotretinoin (retinoid) treatment for acne vulgaris. Curr Ther Res Clin Exp. 2019;90:27-31.