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Studies Published which Review the link between Accutane / Roaccutane and Psychiatric Adverse Events including Depression and Suicide

A selection of published review studies are listed below. The paper published by Bremner et al in 2003 provides a review of all the available evidence on the association between Accutane, depression and suicide.

2004 Expert Opin Drug Saf. Mar;3(2):119-29. Charakida A et al Safety and side effects of the acne drug, oral isotretinoin. Isotretinoin is a very effective medication for the treatment of severe recalcitrant acne. However, its use is associated with many side effects, some of which can be very serious. The most important issue is its teratogenicity, which has resulted in new pregnancy prevention policies and programmes implemented by the manufacturer. Recently, the association of isotretinoin with depression has been recognised and new guidelines have been adopted for this possible side effect. The most common adverse events, observed during treatment, are mucocutaneous and ophthalmological. In addition, laboratory abnormalities and effects in the nervous, musculoskeletal, gastrointestinal, pulmonary and other systems have been described.
2004 J Am Acad Dermatol. Jun;50(6):900-6. Goldsmith LA et al American Academy of Dermatology Consensus Conference on the safe and optimal use of isotretinoin: summary and recommendations The paper highlights that epidemiological studies have not been able to show an association between Isotretinoin and depression or suicide due to confounding factors and that "there is a paucity of basic science literature on the effect of retinoids on the adult brain function". The Academy also request further research in basic research, population-oriented research and individual-oriented research.
2003 Psychopharmacology Bremner, JD Does Isotretinoin Cause Depression and Suicide Review of evidence for a possible relationship between isotretinoin administration and depression and suicide concentration on 1) Pharmacology and Mechanism of Action of Isotretinoin 2) Depression and Suicide in General Population 3) Case Reports of a relationship between Isotretinoin and Depression and Suicide 4) Epidemiological Studies of Isotretinoin and Depression and Suicide 5) Reporting of Adverse Events to Government Agencies 6) Positive Behaviora Effects of Acne Remittance with Isotretinoin 7) Possible Neurobiological Mechanisms Mediating the Effects of Isotretinoin on Depression and 8) Discussion and Recommedations.
2003 Am J Clin Dermatol. ;4(7):493-505. Hull PR et al Isotretinoin use and subsequent depression and suicide: presenting the evidence. The growing number of reported cases of depression and suicide associated with isotretinoin (a retinoid receptor agonist) use in patients with acne has prompted concern among dermatologists, patients, and their relatives and has triggered new warnings from regulators including depression-related, patient-informed consent forms. In establishing a cause-effect relationship, it is useful to judiciously consider whether there is an association, what is the nature of that association, if there is a plausible biological mechanism of action, the validity and reliability of measures used and the strength of study designs. Hoffmann-La Roche estimates that by April 2001 approximately 12 million patients worldwide have used isotretinoin, with 5 million patients in the US.A MEDLINE search between January 1966 and May 14 2003 of the published medical literature found 24 documented cases of isotretinoin-associated depression, with 3 suicides. One additional patient committed suicide during the fourth month of isotretinoin treatment and 3 further patients attempted suicide by taking an overdose of isotretinoin. The US FDA's Adverse Event Reporting System (AERS) contains almost 23,000 reports for isotretinoin from its approval in 1982 to December 2002. As of November 30, 2002, AERS contained 3,104 reports (US and foreign) with at least one reported psychiatric event. The FDA is aware of 173 reports of suicide (both US and foreign) in association with isotretinoin. Reports of positive dechallenge and rechallenge present a strong signal pointing to an association between isotretinoin and depression. A Hoffmann-La Roche sponsored epidemiological study failed to find any evidence of an association between isotretinoin and depression or suicide. However, the design of the study was flawed and the evidence was deemed inconclusive. Further studies using strong study designs, reliable and valid measures, and adequate sample sizes may bring us closer to the answer. The evidence suggesting a relationship between isotretinoin and depression needs to be weighed against the increasing prevalence of depression among adolescents and young adults and the psychological impact of acne. The literature contains credible evidence that isotretinoin treatment may reduce the psychosocial impact of acne in some patients. At the present time, there is no known pharmacological mechanism that would account for psychiatric symptomatology as a result of isotretinoin treatment; however, retinoid receptors are widely distributed in the brain and more research is needed to ascertain whether they have a role in depression. In the meantime, for the practitioner, the obvious benefit of isotretinoin in treating acne should encourage continued use. However, patients and their relatives must be informed and depressive symptoms should be actively assessed at each visit and, if necessary, referral to a psychiatrist, antidepressant therapy or discontinuation of isotretinoin should be considered.
2003 Am J Ther. Mar-Apr;10(2):148-59. O'Donnell J. Overview of existing research and information linking isotretinoin (accutane), depression, psychosis, and suicide. Isotretinoin (Accutane; Hoffmann-La Roche, Nutley, NJ) is a drug closely related to the chemical structure of vitamin A. The pharmacology and toxicology of these two retinoids are similar enough to warrant comparison. Accutane is a powerful drug that its manufacturer, Roche, indicates is limited for severe recalcitrant nodular acne. This potency is also reflected in Accutane's well-known ability to produce severe birth defects if taken during pregnancy. Less well known is the risk of this lipid-soluble chemical to affect the central nervous system. Reports of intracranial hypertension, depression, and suicidal ideation with Accutane use have prompted an examination of its serious and life-threatening potential. Although Roche has added a warning to its product label for signs of depression, and suicidal ideation, this product is overprescribed for all forms of acne, including mild and moderate cases that have not been treated with alternative medications with less risk of depression and suicide. There is no contesting that this drug is effective at clearing up the most severe forms of acne, but the public must be informed of the proper limited indication for its use, because depression and suicide can follow in patients with no prior history of psychiatric symptoms or suicide attempts.
2003 Aust N Z J Psychiatry. Feb;37(1):78-84. Ng CH et al The association between depression and isotretinoin use in acne. OBJECTIVE: The association between isotretinoin and depression has received little attention in the psychiatric literature despite an increasing number of reports in medical journals. The purpose of this paper is to highlight this association, examine the possible link and review the clinical implications. METHOD: A critical review of the literature pertaining to depression in patients with acne who were treated with isotretinoin was conducted. RESULTS AND CONCLUSIONS: The causal relationship between isotretinoin therapy and depression has not been clearly established and needs further study. Isotretinoin is likely to have a positive psychological impact for the majority of patients who benefit from such a highly efficacious anti-acne treatment. However, it is important to recognize that depression can occur as an idiosyncratic side-effect that requires urgent and appropriate treatment. Therefore, having a low threshold for detection of this uncommon complication and early psychiatric referral to address both the depression and its contributing factors may prevent serious consequences.
2001 J Am Acad Dermatol. Nov;45(5):S168-75. Jacobs DG et al Suicide, depression, and isotretinoin: is there a causal link? This paper examines the existing literature and MedWatch reports concerning a proposed relationship between isotretinoin and depression and suicide. The authors provide a brief overview of the biology of isotretinoin and depressive disorder and find no basis for a putative molecular mechanism linking the two. They also address the complexities of Substance-Induced Mood Disorder (SIMD) as a psychiatric diagnosis and its relevance to isotretinoin. Based on this review, the authors conclude that there is no evidence to support a causal connection between isotretinoin and major depression or suicide, because reported cases do not meet the established criteria for causality. The authors also conclude, however, that it is important for dermatologists to be aware of the risk factors for suicide and to monitor patients who exhibit depressive symptoms.
2003 J Am Acad Dermatol. 2003 Feb;48(2):306-8; author reply 308. O'Connell KA et al Isotretinoin (Accutane) and serious psychiatric adverse events. Excellent article - concludes "We are not aware of any study, or combination of studies, adequate to support a conclusion that there is no causal association between isotretinoin and serious psychiatric events. Faced with uncertainty about causlity, we urge clinicans to consider very carefully the possibility of isotreinoin-induced psychiatric adverse events. Recognizing these events and implementing appropiate intervention may prevent significant morbidity, and even be life-saving."


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