Oral isotretinoin is highly effective in treatment of patients with severe acne, but has been concerned with causing occasional depression. Clinicians should be alert to the high prevalence of depression among people with acne. Isotretinoin has many unwanted effects, among which possible unproven effects on mood have to be included. If depression or other mood change occurs, then isotretinoin treatment should be discontinued. If treatment is continued, psychiatric support should be obtained.