Accutane: Focus on Psychiatric Toxicity and Suicide

Accutane: Focus on Psychiatric Toxicity and Suicide
Chapter 20
Donald H. Marks, M.D., Ph.D. and Tzarina Middlekoop, Ph.D.

https://www.researchgate.net/publication/328240372_Accutane_Focus_on_Psychiatric_Toxicity_and_Suicide

20.1 Introduction Since early this century, animal research revealed modifications of epithelial structure, such as increased epidermal keratinization and squamous metaplasia of the mucous membrane, under conditions of vitamin A deficiency. The finding that these defects could be corrected by administering vitamin A lead to the emergence of vitamin A as an anti- keratinizing factor. The first synthesis of vitamin A fifty years ago opened a new era into the chemical synthesis of vitamin A derivatives, collectively known as retinoids. First synthesized in 1955, Accutane (Ro 4-3780, isotretinoin), a first generation retinoid, was shown to be highly efficacious in the therapy of disorders of keratinization (e.g., Dariers disease, ichthyosis). Peck was the first investigator to demonstrate this drug’s value in the treatment of severe acne and in September of 1982, it was approved for use in the U.S. by the Food and Drug Administration (FDA). Accutane is Roche’s second biggest seller, generating about $300 million in sales through the first half of 1998. From 1993 to 1997, prescriptions in the U.S. jumped 52 percent (to 1.5 million). 

20.2 Mechanism of Action Acne is due to an interaction of the normal skin bacteria with the patient’s abnormal type of sebaceous lipids, and is associated with an increased sebum production and ductal cornification. The acne bacteria, Propionibacterium acnes reside on the surface of the skin in quite high numbers, especially in oil-rich areas. If they colonize the pilosebaceous duct in the presence of comedones (blackheads and whiteheads), t hen inflammation is likely to be triggered, resulting in papules, pustules and, if inflammation is more expansive, nodules. Although the exact mechanism of the anti-acne action of isotretinoin is unknown, it is unique in its ability to a ffect—albeit not to the same degree—all the known etiological factors of acne, including reduction of sebum production, lessening of comedogenesis, and the decrease of surface and ductal colonization by Propionibacterium acnes. 3