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13-cis-retinoic acid Poison/"Vitamin A" (Accutane, a form of retinoic acid) causing "affective disorders" aka losing their minds and becoming suicidal

Before one tries to blow this off and say "oh, that's a synthetic retinoid, it's uh, duh-different!"  No.  You would be incorrect.  13-cis-RA is found naturally in the human body:

13-cis-Retinoic acid is an endogenous compound in human serum
Determination of endogenous levels of 13-cis-retinoic acid (isotretinoin), all-trans-retinoic acid (tretinoin) and their 4-oxo metabolites in human and animal plasma by high-performance liquid chromatography with automated column switching and ultraviolet detection.

You are welcome to go read the papers.  Endogenous means "originating from within an organism".  The body can convert the retinol form of Poison/"Vitamin A" into 13-cis-RA and other retinoic acids.  It doesn't mean the body is "making" it like it does Vitamin D.

Then, don't make the mistake of ASSuming that just because something can be found in the body, that it is supposed to be there.  Eating fish will put mercury in your system that can be measured, that doesn't mean it's good for you, right?

Now, on to the research showing 13-cis-RA, sold to people as isotretinoin aka Accutane, is driving some people to suicide:

Retinoic Acid and Affective Disorders: The Evidence for an Association

Isotretinoin (13-cis-retinoic acid, or 13-cis-RA) (Accutane), approved by the FDA for the treatment of acne, carries a black box warning related to the risk of depression, suicide, and psychosis. Retinoic acid (RA), the active form of vitamin A, regulates gene expression in the brain, and isotretinoin is its 13-cisisomer. Retinoids represent a group of compounds derived from vitamin A that perform a large variety of functions in many systems, in particular the CNS, and abnormal retinoid levels can have neurological effects. Although infrequent, proper recognition and treatment of psychiatric side effects in acne patients is critical given the risk of death and disability. This paper reviews the evidence for a relationship between isotretinoin, depression and suicidality.
The literature reviewed is consistent with an association between isotretinoin administration, depression and suicide in some individuals.
3.2.3 The evidence of an isotretinoin/depression association from large databases studies
Studies analyzing large databases have been used to assess the relationship between isotretinoin and depression. In one study funded by the manufacturer of isotretinoin,93 a retrospective study from a database of 2,281 patients who had used isotretinoin and/or an antidepressant found that patients treated with isotretinoin were no more likely to receive antidepressant than those not using isotretinoin.

If you read the above bolded part closely, and you know what is coming, that should make you VERY angry.

However this study is limited by the possibility that dermatologists may stop isotretinoin in the setting of depression without antidepressant treatment, or that patients may refuse psychiatric referral or treatment. In the study of Ng and colleagues{Ng, 2002 #2511 described above, this was in fact the case of all five patients who developed mood changes on isotretinoin. In another study funded by the manufacturer,15 medical data was examined for the association between isotretinoin use and the frequency of suicide, attempted suicide, and “neurotic and psychotic disorders” in patients in the UK and Canada; there was not found to be an increase in these parameters with isotretinoin treatment. Wysowski94 pointed out limitations of this study, including the lack of standardized diagnosis or inclusion of data on psychoactive drug treatment, lack of patient interview for depression, under-ascertainment of suicides (the death certificate data was not examined), lack of data on acne severity, lack of control group, absence of information about length of treatment, differences in prescribing between the U.K. and Canada, and the limited sample size for the U.K. sample. Another study involved an analysis of the United Healthcare database. Although a published abstract from 2001 showed no increase in coding for depression in isotretinoin users,95 if instead coding for diagnosis of depression and/or antidepressant prescription is used to compare control and isotretinoin treated groups then a statistically significant increase in depression is evident in isotretinoin prescribed patients.

Or maybe they were simply not telling the truth.  It will be simply amazing when you see that the manufacturer of this medication (Roche) couldn't find ANY psychological issues with users of the drug, when what you're about to read about the real-world side effects is astonishingly bad.

Azoulay et al studied a group of patients in Quebec who between 1984 and 2003 had obtained an isotretinoin prescription. Cases were defined as individuals who were diagnosed or hospitalized for depression and who filled a prescription for an antidepressant within 30 days after the diagnosis or hospitalization. Subjects who received an antidepressant in the prior 12 months were excluded. Rates of exposure to isotretinoin in the five months before the event were compared to a five month control period. Out of 30,496 subjects examined, 126 met criteria. The adjusted relative risk of depression after receiving isotretinoin was 2.68 (CI = 1.10-6.48), providing a strong case for the increased risk of depression with isotretinoin treatment.96

An analysis of reports of adverse drug reactions (ADR) was performed from data from Roche, WHO and the United Kingdom Medicines Control Agency (MCA) from 1982-1998.69This found that the association between isotretinoin and suicides or psychiatric adverse events is much greater than that of antibiotics when used for acne treatment; 60% of all adverse psychiatric events associated with acne treatment were coupled with isotretinoin use despite the fact that antibiotics are employed more frequently than isotretinoin. Detailing the numbers from WHO, there were 47 reports of suicide, 67 attempted suicides and 56 cases of suicidal ideation.69 Description of the reported psychiatric symptoms included mood swings, depression, amnesia, anxiety and insomnia as well as suicide.

The FDA reported 431 ADRs for isotretinoin between the years 1982 and 2000 16. Of these 37 had committed suicide, 110 were hospitalized for either depression, suicidal ideation, or suicide attempts while 284 suffered depression without hospitalization. The Adverse Events Reporting System (AERS) database placed isotretinoin as the 5th ranking drug for reports of serious depression, 4th ranking for depression.For attempted suicide isotretinoin ranks number 10 and it is the only nonpsychiatric drug that ranks in this top ten list. A study of the ADRs from the FDA also suggests a challenge/dechallenge effect for isotretinoin with remission of depression resulting between cessation and restarting the drug. When the 2002 FDA reports were examined 3104 cases of psychiatric adverse effects were found for isotretinoin, 173 of which were suicides.97

A 2004 analysis of the FDA’s Medwatch database showed that between 1989 and June 2003, there were 216 reported drug-linked suicides in under 18 year olds. Of these, 72 suicides were linked to Accutane.98The FDA states that MedWatch reflects as few as 1% of actual adverse drug events,16 meaning that 72 Accutane suicide reports could represent as many as 7,200 suicides.

A number of drug regulatory bodies from countries outside of the US have reported psychiatric side effects of isotretinoin administration. For example, the Canadian Adverse Drug Reaction Monitoring Program (CADRMP) reported 16 psychiatric reactions with isotretinoin including depression (5), aggressive reaction (4), emotional lability (4), irritability (3), suicidal tendency (3), amnesia (2), abnormal thinking (1), aggravated depression (1), manic reaction (1) and suicide attempt (1). In the reports that indicated an outcome, 7 patients recovered with discontinuation of isotretinoin, 3 recovered with residual effects, and 1 had not yet recovered at the time of reporting.99 222 adverse events were reported to Health Canada between 1983-2002, and 56 (25%) of these were psychiatric adverse events and included depression and suicidal ideation.100 An analysis of a subset of Canadian ADRs reported in children from 1998-2002 showed that isotretinoin was the medication most commonly associated with ADRs 101. Of 1193 reported ADRs, 56 were for isotretinoin, including two deaths and 26 cases of psychiatric ADRs. The Australian Adverse Drug Reactions Committee, between 1985 and 1998, catalogued 129 reports of adverse reactions, 12 of which included depression. In four cases there were symptoms of psychosis. Three patients had suicidal thoughts, two attempted suicide and one completed suicide. Three recovered with withdrawal of isotretinoin and one with antidepressant.102 The Irish Medicine Boards, between 1983 to 1988, received 6 reports of depression associated with isotretinoin treatment, one of which was suicide 103. The Australian ADR Committee, up to June 2005, received 21 reports or either suicide attempts or ideation with isotretinoin use, one which led to a Coronial investigation.104. The Danish Medicine Agency, between 1997 and 2001, recorded 34 psychiatric adverse events with isotretinoin treatment, 23 of which included depression.105

Studies from databases allow trends to be observed in a large population and a number of these analyses link the use of isotretinoin to an increased occurrence of depressive behavior and suicide. The lack of a finding of an association between isotretinoin in some of the studies may be due to the lack of standardized diagnosis, lack of patient interview for depression, under-ascertainment of suicides, and the absence of control groups. The relatively small increase in risk of depression, for instance from the Azoulay et alstudy which found a 2.68 fold rise96, likely accounts for this increase not being found significant in all studies.

Don't trade getting rid of acne for suicide, please.

Dr. Garrett Smith, the "Nutrition Detective"
Licensed Naturopathic Physician (NMD) in Arizona, home of the Love Your Liver program
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