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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 13 of 13. This is the beginning of the thread.
Posted by linkadge on November 16, 2002, at 13:26:32
The acne drug Acutane has been linked to
CNS depressant effects that usually set
in after 6 months of use.I have a theory.
Acutane is supposed to somehow inhibit the
production of oil to the skin, while not
having direct CNS effects, it possibly
inhibits the brain's utilization of fat
in some way. The drug literally dries out
the fat from the skin, perhaps this extends
to the brain as well.Any comments ?
Linkadge
Posted by Larry Hoover on November 16, 2002, at 14:09:50
In reply to Acutane Model for Depression, posted by linkadge on November 16, 2002, at 13:26:32
> The acne drug Acutane has been linked to
> CNS depressant effects that usually set
> in after 6 months of use.
>
> I have a theory.
> Acutane is supposed to somehow inhibit the
> production of oil to the skin, while not
> having direct CNS effects, it possibly
> inhibits the brain's utilization of fat
> in some way. The drug literally dries out
> the fat from the skin, perhaps this extends
> to the brain as well.
>
> Any comments ?
>
> Linkadge
I had never heard of this link before, so I just did a Medline search on the topic. I could not find any reference to a possible mechanism of linkage, let alone a causal mechanism. Even the correlation between isotretinoin and mood is controversial; a large Canadian study found a relative risk of 0.95, CI 0.3-2.4.I'm going to shrug on this one.
Lar
Posted by utopizen on November 17, 2002, at 20:13:54
In reply to Re: Acutane Model for Depression, posted by Larry Hoover on November 16, 2002, at 14:09:50
I took two 5-mos. therapies of accutane. accutane.
It does NOT even have a CASUAL link to mood. My mood was never affected at all.
It does NOT have any casual link to mood.
And oil is not necessarily the cause for acne. People can have dry skin and still have acne. Or oily skin and no acne. There's no casual link between acne and oil, either.
And NO, that 15 year old DID NOT have Accutane in his blood at the time of crashing his plane.
Millions of teens take this drug, trust me, we'd know by know if there was any casual relationship-- the real problem is that some kids take it with pre-existing depressive conditions that are not diagnosed, they commit suicide, and their parents go "oh, must be these evil acne pills."
Posted by oracle on November 17, 2002, at 22:58:13
In reply to Re: Accutane Model for Depression, posted by utopizen on November 17, 2002, at 20:13:54
I have always thought it was due to the toxic level of vit A like products. I do agree that
it is more likely that existing conditions are made worse. But then a psychotic friend took
accutane with no problems, so everyone is different.
Posted by djmmm on November 18, 2002, at 7:44:51
In reply to Re: Accutane Model for Depression, posted by oracle on November 17, 2002, at 22:58:13
I believe that isotretinoin has some effect on inhibiting histamine release...I'm not sure if this has any effect on mood (as far as depression/suicide in concerned).
I think the more realistic connection is between severe, painful(cystic) acne and suicide, which can be socially and psychiologically devistating for teens, and the actually physical side-effects of accutane (redness, dry skin, lips, peeling)
Posted by utopizen on November 18, 2002, at 10:04:00
In reply to Re: Accutane Model for Depression, posted by djmmm on November 18, 2002, at 7:44:51
> I believe that isotretinoin has some effect on inhibiting histamine release...I'm not sure if this has any effect on mood (as far as depression/suicide in concerned).
>
> I think the more realistic connection is between severe, painful(cystic) acne and suicide, which can be socially and psychiologically devistating for teens, and the actually physical side-effects of accutane (redness, dry skin, lips, peeling)
>>>
I got pretty bad dry skin, but I didn't think using Cetaphil was worse than death....And as for the acne thing, acne alone cannot organically dispose someone to depression, that's just silly. I had it, and I've never been depressed. I'm sure lots of kids may casually link their acne to the root of their problems, but these kids probably haven't thought their more realistic causes of depression.
Posted by linkadge on November 18, 2002, at 13:18:26
In reply to Re: Accutane Model for Depression, posted by utopizen on November 18, 2002, at 10:04:00
I do blieve there is a link and that
the drug company is probably making
less of it than need be.Just because acutaine did not affect you does
not mean that it did not affect others.I agree that oily skin is not always the source
of acne but, acutaine does work by causing the
skin to be less oily. It is a form of vitamin
A that inhibits the production or conversion of
some oils. I believe that it would need to be
combined with someone who is already low
on brain fat to cause a CNS disorder.If there were a link I would not the kind of thing
you'd notice after one pill. But it is possible that it somehow has an inhibiting effect of the brain's utilization of fat as well.Was there acutaine in that boy's system? (I don't really know the case you were talking about but)
It wouldn't matter. If he had been taking it long enought it may have decreased his brain fat levels. I honestly have no clue, but there are other acne remedies out there that don't even have half the reported cases of depression in association.Montel Williams believed there was enought of a link to do a show based on it.
I personally have never takin the drug, but with the emergance of such crutial evidence as to the importance of the fatty transport system in mood disorders, I think more testing should be done on such agents.
I personally had a friend that entered a major depression after a 6 month trial of the drug, he said it took another 2 yrs to feel better again after it was done
Linkadge
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.
Posted by utopizen on November 18, 2002, at 15:30:55
In reply to Re: Accutane Model for Depression, posted by linkadge on November 18, 2002, at 13:18:26
> Montel Williams believed there was enought of a link to do a show based on it.
>
Um, are you joking? Seriously, are you?PLENTY of people can get depressed on Accutane, and have. And many of these people weren't depressed before starting the drug. But that doesn't mean Accutane caused it...
And as far as the oil "theory" I have, it's not coming from me, it's coming from my Harvard school of dema-grad dermatologist. Teens happen to get oily skin while on acne, as you get older and continue to have cystic acne, it tends to exist without oil. I'm 19 now and have little oil, but some acne (not much, as result of two accutane therapies).
As for the fat thing, I really don't know what to say about that. What would that have to do with interferering with neurotransmitters?
Posted by djmmm on November 18, 2002, at 15:43:22
In reply to Re: Accutane Model for Depression, posted by utopizen on November 18, 2002, at 10:04:00
> > I believe that isotretinoin has some effect on inhibiting histamine release...I'm not sure if this has any effect on mood (as far as depression/suicide in concerned).
> >
> > I think the more realistic connection is between severe, painful(cystic) acne and suicide, which can be socially and psychiologically devistating for teens, and the actually physical side-effects of accutane (redness, dry skin, lips, peeling)
> >>>
> I got pretty bad dry skin, but I didn't think using Cetaphil was worse than death....
>
> And as for the acne thing, acne alone cannot organically dispose someone to depression, that's just silly. I had it, and I've never been depressed. I'm sure lots of kids may casually link their acne to the root of their problems, but these kids probably haven't thought their more realistic causes of depression.
>
>Severe cystic acne, even mild acne, coupled with peer scrutiny, and poor self esteem can certainly lead to depression or suicide in susceptible individuals. This is a well documented fact.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9892952&dopt=Abstract
Posted by djmmm on November 18, 2002, at 16:13:21
In reply to Re: Accutane Model for Depression, posted by utopizen on November 17, 2002, at 20:13:54
> I took two 5-mos. therapies of accutane. accutane.
>
> It does NOT even have a CASUAL link to mood. My mood was never affected at all.
>
> It does NOT have any casual link to mood.
>
> And oil is not necessarily the cause for acne. People can have dry skin and still have acne. Or oily skin and no acne. There's no casual link between acne and oil, either.
>
> And NO, that 15 year old DID NOT have Accutane in his blood at the time of crashing his plane.
>
> Millions of teens take this drug, trust me, we'd know by know if there was any casual relationship-- the real problem is that some kids take it with pre-existing depressive conditions that are not diagnosed, they commit suicide, and their parents go "oh, must be these evil acne pills."
>
>Your reasoning and conclusions are flawed because you are presenting something as a universal fact, that is based solely on YOUR personal experience.
you wrote "It does NOT even have a CASUAL link to mood. My mood was never affected at all..."
and your conclusion, again was "It does NOT have any casual link to mood."
The facts are, as of december 2000 the fda has received 1,373 report of psychiatric problems associated with accutaine, of these 66 were suicides. Depression has been listed as a possible side effect on Accutane's label since 1986.
another fact, During the drug trial, 26 out of 600 patients experienced psychiatric problems.
Also, there is a condition known as hypervitaminosis, in this case, hypervitaminosis A. There have been a few documented reports of psychiatric reactions, including schizophrenia and psychosis.
Posted by linkadge on November 20, 2002, at 9:55:30
In reply to Re: Accutane Model for Depression, posted by djmmm on November 18, 2002, at 16:13:21
Fat is an important factor in the proper development and functionality of the brain.
When properly nourished, the brain uses many
fats for the creation and maintainance of the
myalin shealths which greatly affect neurotransmission speed. I am just wondering if the affects the Acutaine has on the production and utilization of fat has anything to do with some of the psychiatric complaints that have been reported.The only problem I forsee is that, if it were to cause problems via this mechanizm, it wouldn't be evident for quite some time, which seems to be conisistant with the delayed reports of depression in Acutain users about 6 months. The brain's fat content cannot be changed over night.
Again this is just a theory.
Linkadge
Posted by Larry Hoover on November 20, 2002, at 10:19:34
In reply to Re: Accutane Model for Depression, posted by linkadge on November 20, 2002, at 9:55:30
> Fat is an important factor in the proper development and functionality of the brain.
> When properly nourished, the brain uses many
> fats for the creation and maintainance of the
> myalin shealths which greatly affect neurotransmission speed. I am just wondering if the affects the Acutaine has on the production and utilization of fat has anything to do with some of the psychiatric complaints that have been reported.Doesn't look like it.
Int J Dermatol 1996 Mar;35(3):216-8
Effect of systemic administration of isotretinoin on blood lipids and fatty acids in acne patients.
Ostlere LS, Harris D, Morse-Fisher N, Wright S.
Department of Dermatology, Royal Free Hospital, School of Medicine, London, England.
BACKGROUND. In many studies, an increase in total cholesterol and triglycerides with isotretinoin therapy have been shown and investigators have commented on potential cardiovascular risk. A low intake of linoleic acid, the main essential fatty acid in man, may act as an independent risk factor for coronary heart disease. In vitro etretin alters both the incorporation of extracellular fatty acids into cell membranes and the fatty acid composition of the cell membrane itself. It is, therefore, important to establish whether isotetinoin has any effect on the metabolism of polyunsaturated fatty acids. METHODS. The effect of treatment with isotretinoin for 4 months on the metabolism of polyunsaturated fatty acids in patients with acne was assessed. Quantitative total cholesterol and triglycerides as well as plasma phospholipid, triglycerides, and cholesteryl ester fatty acids were measured in 12 patients and red cell phosphatidylethanolamine, phosphatidylcholine, and phosphatidylinositol fatty acids were measured in 13 patients before and after isotretinoin therapy. RESULTS. There was a significant increase in the concentrations of cholesterol (P < 0.02) and triglycerides (P < 0.04) during treatment. There was no significant difference is plasma phospholipids, triglycerides, and cholesterol esters, or in the red cell phosphatidylethanolamine, phosphatidylcholine, and phosphatidylinositol during isotretinoin therapy. CONCLUSIONS. This study failed to demonstrate any effect of isotretinon on the metabolism of polyunsaturated fatty acids. There was a significant increase in total cholesterol and triglyceride levels following isotretinoin therapy supporting the findings of many previous studies.
> The only problem I forsee is that, if it were to cause problems via this mechanizm, it wouldn't be evident for quite some time, which seems to be conisistant with the delayed reports of depression in Acutain users about 6 months. The brain's fat content cannot be changed over night.
> Again this is just a theory.
>
>
> LinkadgeAccutane reduces endothelial proliferation, which would reduce the tendency to encyst inflamed glands. And, it competitively inhibits the production of certain oxidation products of polyunsaturated fatty acids, which not only mediate inflammation, but which have been associated with mood in some studies. This latter effect may be the link (but we're way out on a conceptual limb, here).
This is the end of the thread.
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