Departments of Psychiatry and Radiology, Emory University School of Medicine, Atlanta, GA, USA.
J Clin Psychiatry. 2012 Jan;73(1):37-50. doi: 10.4088/JCP.10r05993. Epub 2011 Aug 23.
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.
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.
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.
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.
The literature reviewed is consistent with associations of isotretinoin administration with depression and with suicide in a subgroup of vulnerable individuals.
The relationship between isotretinoin and depression may have implications for a greater understanding of the neurobiology of affective disorders.
异维 A 酸（13-顺式维 A 酸）已被美国食品和药物管理局批准用于治疗痤疮，其带有与抑郁、自杀和精神病相关的黑框警告。视黄酸，维生素 A 的活性形式，调节大脑中的基因表达，而异维 A 酸是其 13-顺式异构体。维 A 酸类是一组源自维生素 A 的化合物，在许多系统中发挥着各种各样的功能，特别是在中枢神经系统中，异常的维 A 酸水平会产生神经效应。尽管不太常见，但鉴于死亡和残疾的风险，适当识别和治疗痤疮患者的精神副作用至关重要。本文综述了异维 A 酸与抑郁和自杀意念关系的证据。
使用关键词“异维 A 酸”、“维 A 酸类”、“视黄酸”、“抑郁”、“抑郁障碍”和“维生素 A”，从 1960 年至 2010 年 6 月，在 PsycINFO、MEDLINE 和 PubMed 可搜索数据库索引中搜索发表在英语文献中的文章。检查的证据包括：（1）病例报告；（2）抑郁发作与药物暴露之间的时间关联；（3）挑战-再挑战病例；（4）类效应（同一类中的其他化合物，如维生素 A，具有类似的神经精神效应）；（5）剂量反应；和（6）生物学上合理的机制。
综述了与异维 A 酸、抑郁和自杀相关的文献中的所有文章，以及与类效应、剂量反应和生物学合理性相关的文章。
从文献中的各个文章中提取信息，包括抑郁发作、自杀意念、自杀、精神病、暴力和攻击、既往精神病史、与异维 A 酸使用相关的发作时间、药物剂量、治疗持续时间以及撤药和再挑战史。
综述的文献与异维 A 酸治疗与易感个体中抑郁和自杀的关联一致。
异维 A 酸与抑郁之间的关系可能对更深入了解情感障碍的神经生物学具有重要意义。
