Isotretinoin (Accutane) and Depression: No Association
Bibliographic record
Abstract
Source: Jick SS,Kremers HM,Vastlakis-Scaramozza C. Isotretinoin use and risk of depression, psychotic symptoms, suicide, and attempted suicide. Arch Dermatol. 2000;136:1231–1236.To investigate a proposed association between isotretinoin (Accutane) therapy and the risk of depression, psychotic symptoms, suicide, and attempted suicide, the authors analyzed information from the Canadian Saskatchewan Health Database and the United Kingdom General Practice Research Database (GPRD). In the Saskatchewan database, 7195 isotretinoin users and 13,700 antibiotic users aged 10 to 29 years were identified between 1983 and 1996; in the GPRD, 340 isotretinoin and 676 antibiotic users were identified over an unspecified time period. Medical histories for all subjects were available for 6 months to 5 years before and at least 12 months after initiating treatment. Prevalence rates of mental health disorders in acne patients who received isotretinoin were compared to those of acne patients taking antibiotics. In addition, prevalence rates of mental health disorders among patients taking isotretinoin were compared to prevalence rates in those same patients before the start of treatment. The study was funded by Hoffmann-LaRoche, Ltd., Accutane’s manufacturer.Relative risk (RR) estimates for developing depression or psychosis were calculated by comparing current or recent use of isotretinoin or antibiotics with nonexposure (defined as no use of either study drug for more than 6 months). The RR of depression or psychosis among current isotretinoin users was 1.0 (Saskatchewan Health Database) and 1.8 (GPRD) as compared to non-exposed patients. The RR of depression or psychosis among current antibiotic users was 1.3 (Saskatchewan) and 1.5 (GPRD). Compared with pre-treatment, the RR of depression or psychosis among current isotretinoin users was 1.2 (Saskatchewan) and 1.3 (GPRD). Using data from Saskatchewan, the RR for suicide or attempted suicide was 0.9 for current isotretinoin use when compared to nonexposed patients. None of these RRs were statistically significant and, therefore, the authors conclude that there is no evidence that isotretinoin use is associated with an increased risk for depression, suicide or other psychiatric disorders.The possibility that isotretinoin use, through mechanisms unknown, might be associated with an increased risk of mental health disorders (including depression and suicide) has been the subject of some debate1 and media reports, most recently a report on a nationally-televised program.2 Concern about this association led the FDA to include the following warning in the drug’s prescribing information: “Accutane may cause depression, psychosis, and, rarely, suicidal ideation, suicide attempts and suicide. Discontinuation of Accutane therapy may be insufficient; further evaluation may be necessary.”1There seems little doubt that acne may have a significant impact on an adolescent’s emotional well-being. Before treatment, many adolescents with acne experience some psychosocial consequence of their disease that ranges from anxiety or embarrassment to lowered self-esteem, perceived social rejection or depression.3–6 In general, successful treatment with conventional agents (eg, antibiotics) or isotretinoin is associated with reduced anxiety and depression.1,3–7 The results of the present study, conducted using a large population-based sample, do not support an association between isotretinoin use and depression or psychosis. Although the number of completed or attempted suicides was small, these events do not appear to be associated with isotretinoin use. Nonetheless, clinicians caring for patients receiving Accutane should remain alert to the possible coexistence of mental health disorders, including depression.Are the results of this study sufficient to reject the hypothesis that isotretinoin increases the risk of depression? In the court of scientific opinion the evidence would appear sufficient, but what about the court of public opinion or the courts that hear product liability cases? Medicine, law, and the public at large frequently differ about what constitutes a causative link and what criteria should be used in establishing causation. Today, the scientific process by which a hypothesis is tested and then either accepted or rejected has been distorted by the media and internet. The hypothesis that isotretinoin is linked to depression and suicide is deemed worthy of a TV newsmagazine but a well-done epidemiologic study refuting it is not.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".