title: Retinoic acid and affective disorders: the evidence for an association.
abstract: OBJECTIVE
  Isotretinoin (13-cis-retinoic acid), approved by the US Food and Drug Administration for the treatment of acne, carries a black box warning related to the risk of depression, suicide, and psychosis. Retinoic acid, the active form of vitamin A, regulates gene expression in the brain, and isotretinoin is its 13-cis isomer. Retinoids represent a group of compounds derived from vitamin A that perform a large variety of functions in many systems, in particular the central nervous system, and abnormal retinoid levels can have neurologic effects. Although infrequent, proper recognition and treatment of psychiatric side effects in acne patients is critical given the risk of death and disability. This article reviews the evidence for isotretinoin's relationships with depression and suicidality.
  
  
  METHODS
  The PsycINFO, MEDLINE, and PubMed searchable database indexes were searched for articles published in the English language from 1960 to June 2010 using the key words isotretinoin, retinoids, retinoic acid, depression, depressive disorders, and vitamin A. Evidence examined includes (1) case reports; (2) temporal association between onset of depression and exposure to the drug; (3) challenge-rechallenge cases; (4) class effect (other compounds in the same class, like vitamin A, having similar neuropsychiatric effects); (5) dose response; and (6) biologically plausible mechanisms.
  
  
  METHODS
  All articles in the literature related to isotretinoin, depression, and suicide were reviewed, as well as articles related to class effect, dose response, and biologic plausibility.
  
  
  METHODS
  Information from individual articles in the literature was extracted, including number of episodes of depression, suicidality, suicide, psychosis, violence and aggression, past psychiatric history, time of onset in relation to isotretinoin usage, medication dosage, duration of treatment, and dechallenge and challenge history.
  
  
  RESULTS
  The literature reviewed is consistent with associations of isotretinoin administration with depression and with suicide in a subgroup of vulnerable individuals.
  
  
  CONCLUSIONS
  The relationship between isotretinoin and depression may have implications for a greater understanding of the neurobiology of affective disorders.
authors: Departments of Psychiatry and Radiology, Emory University School of Medicine, Atlanta, GA, USA. jdbremn@emory.edu
authors: J Douglas
authors: JD
authors: Bremner
authors: Kirsty D
authors: KD
authors: Shearer
authors: Peter J
authors: PJ
authors: McCaffery
mesh_terms: D000152:Acne Vulgaris / Q000150:complications / Q000188:drug therapy; D001921:Brain / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006801:Humans; D015474:Isotretinoin / Q000009:adverse effects*; D008954:Models, Biological; D019964:Mood Disorders / Q000139:chemically induced* / Q000150:complications / Q000523:psychology; D012176:Retinoids / Q000009:adverse effects*; D012649:Self Concept; D013405:Suicide / Q000523:psychology*
chemical_list: D012176:Retinoids; D015474:Isotretinoin