Saturday, November 13, 2010

Acne and Suicide

There have been many reports on acne, depression, and suicide over the years, mostly because a primary treatment for severe acne, isotretinoin (accutane), is known to increase the risk of depression and suicide. However, a new paper in the British Medical Journal, Association of suicide attemps with acne and treatment with isotretinoin: retrospective Swedish cohort study adds a new twist.

The researchers followed 5756 people in Sweden from 1980-2001, before, during, and after accutane treatment for severe acne. Sure enough, admissions to the hospital for suicide attempts were increased in patients during and for up to six months after completion of accutane treatment. Three years after treatment, and for the next 12 years, attempted suicide rates were back to normal levels, so the treatment didn't seem to have permanent effects. The effect size was such that it would take 2300 people treated with accutane for 6 months to result in one additional first suicide attempt. In addition, the effect of accutane on suicide attempts seemed to be stronger in women than for men, and the risk was higher among women who received two or more treatment courses.

Here's the twist. Attempted suicide rates were also higher in the population in the months prior to treatment with accutane. And some (admittedly small) studies have shown that accutane leads to an improvement in anxiety and depression (1)(2) due to a clearing up of the disfiguring acne. And one wonders about the increased risk in women - women who undergo more than one course of treatment would have worse acne, and it is plausible that, as a cohort, young women would be more concerned about disfiguring acne than young men. And of course, we know that acne is a disease of civilization (the Kitavans and Masai are unafflicted, for example) and obviously associated with inflammation, just like psoriasis and obesity and those other diseases all independently associated with depression and anxiety. I have heard of a case of someone with years of unsuccessful standard medical acne treatment (though not accutane, as that is not routinely used in young women in the US due to the risk of birth defects) who responded well to Cordain's dietary cure and also had increased energy on the Cordain paleo-inspired diet.

On the other hand, there are very plausible biological brain mechanisms for accutane causing depression, and accutane has caused depression behaviors in studies of young adult mice (3). Various mechanisms include disrupting hippocampal neurons and their communication (4) and interfering with the serotonin machinery (5 - this link is rather interesting, as accutane seems to be rather the opposite of an SSRI in mice, increasing serotonin reuptake and increasing the post synaptic serotonin receptors).

In addition, cillikat brought up some links between accutane, cholesterol, and vitamin D in her recent comment on this post. Though she mentioned that accutane lowered cholesterol, I found it to be a cause of increased cholesterol, LDL, and triglycerides in several studies (here is the first one from 1983, I believe.) But there is a link between accutane treatment and vitamin D. Accutane is basically a super-strong variety of vitamin A, and vitamin A and D work in concert as their receptor complexes attach together to do a variety of actions in the nucleus (6). Exceedingly high A intake could result in there being a ton of vitamin A receptor complexes swimming around and very few vitamin D complexes to join the party. This issue would be exacerbated by the typical advice to accutane users to stay out of the sun. Studies combining accutane and active vitamin D3 have used the synergistic receptor complex effect to try to kill cancer cells more effectively (7).

Vitamin D deficiency has links to depression. It is plausible that high levels of vitamin A from accutane would interfere with vitamin D doing its job and also contribute to the depression side effect, but to my knowledge this is all speculation.

But back to the original paper! What to do about acne? It shouldn't be ignored or dismissed as a non-serious condition, but treatment has to be carefully considered, and people suffering from acne carefully monitored for depression and suicidal thoughts. To me the obvious first choice for treatment would be dietary - however I am not in agreement with dermatologists (about a lot of things, actually), and it is a certainty that they know more about the skin than I do (though likely much less about traditional diets).

11 comments:

  1. owww....i have acne lol... and yea, depression rears its ugly head, especially during recovery. im definitely not suicidal though, just a hormonal mess :) but hopefully time and good eats will fix this

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  2. My partner had endured 30 years of every treatment the NHS had to offer for acne, but it was a low carb diet that fixed it, and that within week. If she eats bread or sweets two days running she knows there will be spots, but she also knows that they will go if she keeps off the carbs. Having control means that now it's not an issue any more.

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  3. I thought you might pick up on that one Emily.

    I had very severe acne from late my teens onward (I also had a high glycaemic load diet - potatoes were counted as a vegetable in our house and if I had money for lunch, I would usually spend it all on lollies at the canteen - protein quality would have been low - sausages were considered a good meat - and added fats were almost exclusively margarine - I was always hungry and lived on toast drowned in margarine or bowls of shredded wheat with 2-3 tbsp of sugar and skim milk on top). By late teens I was well over the large painful eruptions I was getting on my face, chest, and back... and multiple courses of antibiotics were not working (anyone see a pattern develop?). I got a referral to a dermatologist and shortly after started taking Roaccutane (as it was marketed here in NZ). As I started to load up on it, I had to endure my mucous membranes drying out, leading to bleeding noses, cracked lips, dry eyes, etc. By this point I was in my first year at university, my diet had changed a little bit - I was starting to buy more 'wholegrain' foods such as cookies with dried apricot and dark chocolate - because these are health you know. I was also just starting to learn how bad all fat was. And I was beginning to train in the gym - circuits twice per day, commute 25-50km per day on my bike, and race my mountain bike. I was 19 years old and weighed 58kg!

    The first course of Roaccutane certainly seemed to clear the vast majority of my acne. My skin was clearer, but I was very much socially isolated. The most fun I had experienced all year was when I deliberately had myself caught up in a student riot that saw a group of us occupy the university registry for 4 days... I was in there with a bunch of vegetarian misfits.

    I transferred to Otago University to begin my studies in exercise science, and my acne was starting to return. Back on the Roaccutane I went. I ended up going through 3x 3 month courses on it. I would get blistered if I was in the sun for anything more than 10 minutes. I was now flatting - with a mixture of vegetarians and vegans, and was mostly vegetarian myself - which meant taking mince out of a vegetable dish and replacing it with pasta and beans. I occasionally had tuna, but only if it was in springwater as fat was pure evil. I still consumed a massive amount of sugar and grains. My biggest exposure to fat would have been when we did all you can eat feeds at Pizza Hutt... mmm - fat from cheese and salami - fat of the gods.

    During all of this, I had a strange mix of being more socialable but still feeling incredibly socially isolated. I was estranged from the vast majority of my family, choosing to have nothing to do with them. This made things very 'quiet' at the end of the year when everyone else went home and you are stuck in a small university town for summer by one's self.

    I had a succession of relationships (for me at least), and was generally hit pretty hard by these. I spent time in some very dark places in my mind, a suffered from the likes of suicide ideation, etc. It wasn't long after being at my absolute lowest and 'surviving' that I began to hear of the links with Roaccutane causing mental health issues.

    To recap, yes I had taken Roaccutane, but I was an acne-covered, semi-vegetarian, grain-eating, fructose-eating, fat-avoiding (except for vegetable oils), over-trained, meat-deficient 60kg weakingly, with the stress of mounting student debt and no family support, who had a history of taking antibiotics. I lived in one of the Southern-most cities in New Zealand, would have been vitamin D deficient as a result, plus would have been running multiple other deficiencies as well. So what caused the problems??

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  4. Acne is considered a mere adolescent right of passage - but it is such a sign of everything that is going wrong with insulin, inflammation, and hormones.

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  5. Very interesting. The inflammation/depression link the most intriguing. Have you seen any studies on mood effects of the antibiotic treatments used more long term for adolescent acne? I think I read of some. Have a kid with trouble with both.

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  6. Retriever - the most common chronic antibiotic used for acne is doxycycline. I didn't find depression as a side effect in the PDR quick reference, and on pubmed a review and comparison of malaria prophylaxis with doxycycline ( while not as long term as acne, the typical treatment starts 4 days before the trip and continues for 4 weeks after getting home) showed no depression or other mood symptoms. Doesn't mean it couldn't happen, but I'm not finding it on a quick search. Sorry your son is struggling!

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  7. Hi Emily,
    Oh, dear, suicide ideation. We have had that. Just being the mother of two small children, after a while I got to the conclusion that they're better off with me than without me, although I'm useless, they don't notice it. Inability to cope with 'life', social isolation as an immigrant, feelings of inadequacy and being a failure, non existent self-esteem, etc. Plus scarring acne, serious hairloss, bad relationship giving me the heart disease risk of two packs of cigarettes a day, stress due to the inability to focus on/write well/finish my Ph.D., guilt for the excessive procrastination, all the bad decisions and weaknesses. Did somebody say mess? Or ticking bomb? You think it can't get worse and then one day it does...
    Tendency to high androgens due to high insulin? But on low carb? I only started having bad acne in my early 30s, it's been on and off, but back with a vengeance. Is it high cortisol? The endo didn't even do a day test.

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  8. It's funny or maybe not... My daughter made today a drawing of her family in school and she made me with a sad face, like this :( saying Hm. So, yes, I was wrong, they do notice it, they both prefer to be with their father (it saddens me of course) but I suppose they're not as judgemental and critical as a grown-up. I totally understand, when I was a child I would have wanted to have another mother, I liked a friend of my mother's more.
    There's your therapy session for today.

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  9. Hang in there light can. I'm not the biggest hormone whiz but an endocrinologist ought to be. When I see late-onset acne though I always think hormones, or PCOS or something, which is also associated with depression.

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  10. you might be interested to know that the suicide of Charles Bishop ~ a 16-year old, he flew his light plane into a skyscraper in Florida, 2 weeks after 9.11 ~ was linked, by his family and the newsprint media, with roacutane treatment of his acne.

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  11. 2 weeks after 9.11 the 16-year old Charles Bishop flew his light plane into a sky scraper in Tampa, Florida. His family, and the news media, credited his suicide as a side effect of taking roacutane for his acne. Only 5% of the 120+ news articles at the time played up the matters of his broken home, or of his Syrian-American identity concerns at the time of Operation Desert Storm. Bishop was a popular, high achieving student. His suicide is surely also a casualty of 'civilization.'

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