Posted by Larry Hoover on November 18, 2002, at 13:47:04
In reply to Re: Accutane Model for Depression, posted by linkadge on November 18, 2002, at 13:18:26
> I do blieve there is a link and that
> the drug company is probably making
> less of it than need be.I don't think anybody is trying to suppress any evidence. In fact, policy is now guided by what is known as the 'precautionary principle'. By that, associations between drugs and adverse outcomes, *even in the absence of evidence for a link between the two*, will be treated as if the link has been established. The precautionary principle is the political equivalent of "better safe than sorry".
Here's the political statement, from the FDA. Note that total numbers of Accutane users are not revealed in this statement. Surely rates of adverse events are important, not just severity.
J Am Acad Dermatol 2001 Oct;45(4):515-9
An analysis of reports of depression and suicide in patients treated with isotretinoin.Wysowski DK, Pitts M, Beitz J.
Division of Drug Risk Evaluation I, Office of Post-Marketing Drug Risk Assessment, Center for Drug Evaluation and Research, Food and Drug Administration, Rockville, MD 20857, USA. wysowski@cder.fda.gov
BACKGROUND: The Food and Drug Administration (FDA) has received reports of depression and suicide in patients treated with isotretinoin. OBJECTIVE: Our purpose was to provide the number and describe the cases of depression and suicide reported to the FDA in US patients treated with isotretinoin and to consider the nature of a possible association between isotretinoin and depression. METHODS: An analysis was made of reports of depression, suicidal ideation, suicide attempt, and suicide in US isotretinoin users voluntarily submitted to the manufacturer and the FDA from 1982 to May 2000 and entered in the FDA's Adverse Event Reporting System database. RESULTS: From marketing of isotretinoin in 1982 to May 2000, the FDA received reports of 37 US patients treated with isotretinoin who committed suicide; 110 who were hospitalized for depression, suicidal ideation, or suicide attempt; and 284 with nonhospitalized depression, for a total of 431 patients. Factors suggesting a possible association between isotretinoin and depression include a temporal association between use of the drug and depression, positive dechallenges (often with psychiatric treatment), positive rechallenges, and possible biologic plausibility. Compared with all drugs in the FDA's Adverse Event Reporting System database to June 2000, isotretinoin ranked within the top 10 for number of reports of depression and suicide attempt. CONCLUSION: The FDA has received reports of depression, suicidal ideation, suicide attempt, and suicide in patients treated with isotretinoin. Additional studies are needed to determine whether isotretinoin causes depression and to identify susceptible persons. In the meantime, physicians are advised to inform patients prescribed isotretinoin (and parents, if appropriate) of the possibility of development or worsening of depression. They should advise patients (and parents) to immediately report mood swings and symptoms suggestive of depression such as sadness, crying, loss of appetite, unusual fatigue, withdrawal, and inability to concentrate so that patients can be promptly evaluated for appropriate treatment, including consideration of drug discontinuation and referral for psychiatric care.
Now, here's a post-hoc analysis (after the fact, looking at evidence already collected) of accutane users *compared both to themselves (pre-treatment) and others undergoing alternative (antibiotic) treatment for acne*.
Arch Dermatol 2000 Oct;136(10):1231-6
Comment in:
Arch Dermatol. 2001 Aug;137(8):1102-3.
Isotretinoin use and risk of depression, psychotic symptoms, suicide, and attempted suicide.Jick SS, Kremers HM, Vasilakis-Scaramozza C.
Boston Collaborative Drug Surveillance Program, 11 Muzzey St, Lexington, MA 02421, USA. sjick@bu.edu
BACKGROUND: It has been suggested that there is a causal association between isotretinoin therapy and the risk of depression, psychotic symptoms, suicide, and attempted suicide. OBJECTIVE: To further investigate the proposed association between isotretinoin therapy and the risk of depression, psychotic symptoms, suicide, and attempted suicide using a formal study design. DESIGN: Large population-based cohort studies. SETTING: The Canadian Saskatchewan Health Database and the United Kingdom General Practice Research Database. PATIENTS: Data were analyzed for 7195 isotretinoin users and 13,700 oral antibiotic users with acne from the Canadian Saskatchewan Health Database and for 340 isotretinoin users and 676 oral antibiotic users with acne from the United Kingdom General Practice Research Database. All subjects had computer-recorded histories of between 6 months and 5 years before, and at least 12 months after, their first isotretinoin or antibiotic prescription. OUTCOME MEASURE: Prevalence rates of neurotic and psychotic disorders, suicide, and attempted suicide were compared between isotretinoin and antibiotic users and within isotretinoin users as their own comparison (pretreatment vs posttreatment). The results were expressed as relative risks, calculated using multiple logistic regression analyses. RESULTS: Relative risk estimates, comparing isotretinoin use and oral antibiotic use with nonexposure to either drug for newly diagnosed depression or psychosis, were approximately 1.0 regardless of the data source. Similarly, relative risk estimates were all around 1.0 when comparing before with after isotretinoin use. The relative risk estimate for suicide and attempted suicide was 0.9 (95% confidence interval, 0.3-2.4) when comparing current isotretinoin exposure with nonexposure. CONCLUSION: This study provides no evidence that use of isotretinoin is associated with an increased risk for depression, suicide, or other psychiatric disorders.
In my humble opinion, if you look at any large group of people undergoing treatment, you're going to find adverse outcomes. The risk to understanding comes from coincidental correlation. It has long been understood that it is a logical fallacy to link by coincidence; post hoc ergo propter hoc (after this, therefore because of this) comes to us across the millenia, from the debates of the ancient Greeks.
poster:Larry Hoover
thread:127928
URL: http://www.dr-bob.org/babble/20021116/msgs/128140.html