Are Dermatologists Dippy? The Depressing Accutane Tale
Rather than admit that one of their silver bullets, Accutane (isotretinoin), which was a “goose laying the golden egg” for F. Hoffmann-La Roche Pharmaceuticals (and their various “Roche” associates world-wide) to the tune of a billion dollars a year, could make kids depressed or kill themselves or cause grotesque birth defects in the kids of over half of women exposed when pregnant, dermatologists have sung themselves a lullaby that their magic pills don’t make kids depressed, they actually make them better, by clearing up those ugly zits that drive them to despair. In what can only be described as a tragic collusion of conflicts of interest (COI) amongst their Key Opinion Leaders (KOLs) and willful denial amongst the lowly rank and file, they have decided to say “What? Me Worry?”
When the heat got turned up on Roche Pharmaceuticals after the son of Congressman Bart Stupak’s (D-Mich) son Bart Jr. died of suicide while on Accutane in 2000, they got busy and called a “Scientific Advisory Board” meeting at the Ritz Carlton in Alexandria, Virginia, to opine on the topic of the relationship between Accutane treatment and depression. This meeting included figures from psychiatry like Kathleen Merikangas, PhD, Stuart Montgomery, PhD, and David Nutt, MD, Chair of Dermatology David Bickers MD, and psychiatrist Douglas Jacobs, MD. Between the lot of them I think they have written about one paper total in the literature on the subject. But they did get paid a nice consulting fee for their efforts, of course.
Their conclusion? No relationship, of course.
I wasn’t aware you were an Accutane expert, Kathleen!
I challenge them all to a debate. I’ll fight them with one hand behind my back!
Fact is Accutane’s efficacy for acne was discovered a decade before Roche put a patent on it, in a paper in the New England Journal of Medicine.
I have communicated with two of the authors, both dermatologists, Frank Yoder MDand Gary Peck, MD.
Both of them agreed with my opinion that Accutane can cause depression in some individuals.
What is really sad about this whole sordid tale is how degenerated the so-called dermatology “literature” has become on the topic.
For example, the most commonly cited study to support the statement that acne is associated with depression, a study that has been cited several hundred times by dermatologists writing in the literature, involved only ten patients with acne and no comparison subjects (Gupta et al., 1990). No statistics were performed (obviously since there was no comparison group). Scores on the questionnaires for anxiety and depression were not related to severity of acne.
And the fact is that the rest of the literature isn’t any better. Objective measures of acne do not correlate with severity of anxiety or depression. Acne does not cause major depression. It is simple as that.
Sure, kids worry about their zits and feel better when they go away, but the studies do not support the conclusion that acne causes major depression, and that treatment of acne cures depression.
In spite of this the manufacturer of Accutane, Hoffmann-LaRoche, has consistently downplayed the risks of suicide and depression and has denied a causal association (McCoy, 2004). The dermatology community has joined with the manufacturer in praising the merits of this medication for the treatment of acne which they describe as the “penicillin of dermatology”. It took only 10 months for the FDA to approve Accutane for the treatment of cystic and nodular acne in May of 1982, however controversy has followed it from the time of its initial launch. In January of 1983 one of the authors of the first paper to describe the use of isotretinoin for the treatment of acne in 1977, Dr. Frank Yoder, wrote about the potential dangers of Accutane (Yoder, 1983). In 1990 Dr. David Graham of the FDA highlighted the inability of the Dermatological Medications Advisory Committee to the FDA to be impartial since it was made up entirely of dermatologists (Green & Hutt, 2002). At that time he stated that Accutane should be taken off of the market, mainly because of the risk of birth defects. Indeed its use has always been curtailed or highly restricted in European countries, unlike the US where it is often prescribed for minor blemishes. Strong feelings about the utility of isotretinoin for the treatment of acne in the dermatology community, and forceful marketing by the manufacturer in the US, have caused a delay in awareness of the potential risks in the US. In 1998, the year that the FDA first approached Hoffmann-LaRoche about adding a warning related to suicide with Accutane to its label, the manufacturer ran an ad that stated, “Effective treatment of severe recalcitrant nodular acne minimizes progressive physical scarring, as well as negative psychosocial effects such as depression and poor self image” (Green & Hutt, 2002). This was in spite of the fact that less than half of patients prescribed the medication actually had nodular acne. The FDA required that Hoffman-LaRoche pull the ad.
In 2000 Congressman Bart Stupak’s son, Bart Jr., committed suicide while on Accutane. Congressman Stupak called for congressional hearings on the safety of the drug and in September of that year the FDA called a Dermatologic Advisory Committee meeting on the topic. In November of 2001 an educational grant from Roche funded a supplement of the Journal of the American Academy of Dermatology on isotretinoin which followed the Scientific Advisory Board Meeting in Alexandria VA they held on the topic. The basic science-related articles focused on retinoids and the skin, essentially ignoring the large extant literature on retinoids and the central nervous system. Psychiatric side effects merited literally two sentences, and one article, written by one of Roche’s hired guns, stated that there was no evidence for any association (Jacobs et al., 2001), ignoring the reported challenge-rechallenge cases which have been cited in the pharmacoepidemiology literature as adequate in and of themselves to establish causality (Strom, 2005). This led members of the FDA to write a letter of response, “in the interest of public health,” admonishing the authors of these articles for the short shrift they paid to the issue of Accutane and psychiatric side effects (O’Connell, Wilkin, Pitts, 2002).
The degree to which dermatologists have thrown science and logic out of the window in order to protect their magic bullet is simply remarkable. For instance in a 2004 article entitled “Myths of Isotretinoin Therapy” (Alcalay, 2004) “isotretinoin causes depression and suicide attempts” was listed as a “myth”. The article went on to state that any risk needed to be “weighed against the increasing prevalence of depression among adolescents and young adults and the psychological impact of acne.” [In fact, depression is not increasing amongst teenagers and acne has not been associated with clinical depression, rather only changes in self esteem].
Here are some authentic mythic figures for you, Dr. Alcalay! And they don’t have any pharmaceutical industry COIs!
Aktan, S., Ozmen, E., Sanli, B. (2000). Anxiety, depression, and nature of acne vulgaris in adolescents. International Journal of Dermatology, 39, 354-357.
Alcalay, J. (2004). Myths of isotretinoin therapy in patients with acne: A personal opinion. Journal of Drugs in Dermatology, 3(2), 179-182.
Green, J., Hutt, P. (2002). Babies, blemishes, and FDA: A history of Accutane regulation in the United States., Leda. Cambridge, MA.
Gupta, M. A., Gupta, A. K., Schork, N. J., Ellis, C. N., Voorhees, J. J. (1990). Psychiatric aspects of the treatment of mild to moderate facial acne: Some preliminary observations. International Journal of Dermatology, 29(10), 719-721.
Jacobs, D. G., Deutsch, N., Brewer, M. (2001). Suicide, depression, and isotretinoin: Is there a causal link? Journal of the American Academy of Dermatology, 45, S168.
Kellett, S. C., Gawkrodger, D. J. (1999). The psychological and emotional impact of acne and the effect of treatment with isotretinoin. British Journal of Dermatology, 273-282.
McCoy, K. (2004, December 7, 2004). Drug Maker rebuffed call to monitor users. USA Today, pp. 1-2.
O’Connell, K. A., Wilkin, J. K., Pitts, M. (2002). Isotretinoin (Accutane) and serious psychiatric adverse events. Journal of the American Academy of Dermatology, 48(2), 306-307.
Shuster, S., Fisher, G. H., Harris, E., Binnel, D. (1978). The effect of skin disease on self-image. British Journal of Dermatology, 99(Suppl 16), 18-19.
Smithard, A., Glazebrook, C., Williams, H. C. (2001). Acne prevalence, knowledge about acne and psychological morbidity in mid-adolescence: a community-based study. British Journal of Dermatology, 145, 274-279.
Strom, B. L. (Ed.). (2005). Pharmacoepidemiology (4 ed.). New York: Wiley.
Van der Meeren, H. L. M., van der Schaar, W. W., van den Hurk, C. M. A. M. (1985). The psychological impact of severe acne. Cutis, 36(1), 84-86.
Wu, S. F., Kinder, B. N., Trunnell, T. N., Fulton, J. E. (1988). Role of anxiety and anger in acne patients: Relationship with the severity of the disorder. Journal of the American Academy of Dermatology, 18, 325-333.
Yoder, F. W. (1983). Isotretinoin: A word of caution. Journal of the American Medical Association, 249(3), 350-351.
Originally posted Jan 5 2008
23 Comments
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By Catherine Cocciolone, May 19, 2009 @ 6:00 pm
Our highly intelligent and capable son, with obvious and abundant potential, who at only 19 years of had a range of humanitarian and intellectual interests committed suicide after 8 months of continuous treatment with Isotretinoin (marketed in Australia as Roaccutane). His dermatologist did not acknowldege that his depression was caused by Roaccutaene and did not treat it. This is a crime. Why is this drug still on the market? How many more young people have to die? How many more families have to suffer watching their teenagers decline and then suffer the hopelessness that leads to suicide? The manufacturers of this drug are without humanity.
By Doug Bremner, May 19, 2009 @ 8:49 pm
The Australian Drug Regulatory Agency had commented on the risk of Accutane and suicide several years ago, as well.
By Doug Bremner, July 1, 2009 @ 9:07 am
You are citing a single abstract you picked up trolling the internet while I have spent hours reviewing the literature and the so called link between acne and depression does not exist. Your numbers on suicide related to Accutane are way off and the FDA says that reported adverse events correspond to as little as 1% of true cases. Roche has pulled Accutane off the market, so they must not think the risk-benefit ratio is that great either.
By Stephany, July 1, 2009 @ 10:59 am
As an FYI, Supremacy Claus was banned from my blog as well as 2 other well-known blogs you are familiar with Doug.
By Stephany, July 1, 2009 @ 12:17 pm
Yeah, SC and you used to write that I believed 911 was a conspiracy on another mental health blog.
By Doug Bremner, July 2, 2009 @ 6:57 am
I deleted some comments by a drug rep from Tap Pharmaceuticals who has made a career as a troll writing gratuitous comments insulting myself and other commenters and who has been banned from several other web sites. I am all for the free exchange of ideas but those who insult others are not welcome here.
By C, July 6, 2009 @ 1:41 pm
I find your post to be ridiculous and unprofessional. My face was completely deformed from cystic acne three years ago. I was fortunate that there was a drug that could help me – while I acknowledge that accutane may cause medical problems, you seem to ignore all the good effects people have seen from it. Perhaps next time you decide to write a post, you will be more professional and include the arguments for and against. There are a lot of people out there who have experienced many benefits from accutane – I am one of them.
By Morgan, July 21, 2009 @ 4:57 am
The time for this toxin on the market is approaching it’s end, even if it has helped many, the long-term risks are just too great. Retinoids are casual to schizo, depression, psychosis, etc. isotretinion needs to go
By Morgan, July 21, 2009 @ 5:38 am
My list of side effects :
Started months after treatment and slowly got worse
Psychological effects -
depression : I do not enjoy life like I did, actually I enjoy absolutely nothing, I’m restless, I can’t find peace, accutane partly killed my soul. Suicidal impulses come throughout the day.
problems concentrating : I’m not as sharp as I used to be, I can’t think as clearly, I’m just not mentally on top of my game.
fatigue : major apathy, tired, no energy, don’t respond to feelings like I used to.
memory loss : I forget where I put things and so on, I forget what I talk about
physical effects -
Joint pains : All my joints click and crack especially my neck, they are sore as well.
Hairloss : I had a thick full head of hair, now I’m balding
sexual dysfunction/lowered libido : I’ve lost all interest in sex, and it is no longer pleasurable.
Painful intercourse : skin on urethra has been thinned out to the point I have troubles wearing underwear because of the pain
IBS : I have no craving for food or any appetite at all, severe abdominal pains come and go.
sjogrens syndrome : my eyes, hair, skin, mouth, lips, nasal passage are all extremely dry.
Intolerance to alcohol : 1 beer gives me body cramps and severe head aches, never did before accutane.
I can cope with most of these symptoms, it’s the psych effects and the sexual problems that really bother me. I guess there is not much to do anymore, various treatments have failed, the problem with ssri’s is the effect doesn’t last, and they don’t solve the problem, Dr. Bremner do you know the best anti depressants to treat accutane-induced depressions?
By Amy Philo, July 21, 2009 @ 2:29 pm
Um… Morgan was your last sentence a joke? I have a hard time knowing. If you were on SSRIs while on Accutane, you barely stand a chance at not being depressed. You’re lucky you’re alive.
By Morgan, July 22, 2009 @ 1:28 am
I was never depressed before accutane, nor on ssri’s, didnt even know what they were
By Morgan, July 22, 2009 @ 1:32 am
sorry for the miscommunication
By Amy Philo, July 22, 2009 @ 1:46 am
No my point is that SSRIs cause depression and suicide etc. So if you were on both Accutane and SSRIs at the same time, or if you are off Accutane (obviously) but still depressed, SSRIs may be the cause too. Both of them cause depression is my point. Other antidepressants are similar. All of them can cause depression. Look for alternatives or allow yourself to heal from the Accutane.
By Morgan, July 22, 2009 @ 9:28 pm
Accutane’s effects are permanent. The healing of the brain, even if it exists is minimal. Accutane differs from many other medicines. It is one of the only on the market, for non deadly conditions that influence gene-expression in such a severe way, that it is permanently harmful to the brain.
The brain changes it´s structure all through life, and being negative is not the same as being depressed. I can think with a positive mind lots, but I still don´t have the feelings that I should have. Not because of a mental block, but because I am physically unable to feel them.
Roche pharmaceuticals are the ones to blame for this. They knew from the very beginning that some people were to kill themselves on the drug, or after ingesting the drug. They knew that some were going to suffer from it, life long, with the knowledge that it was the drug that ruined it all for them.
The patient is of no whatsoever concern in the Hoffman La-Roche culture. They do not have feelings, what counts is how much they can profit, nothing else.
That is the way it is. They would easily kill 50% of their patients if they just earned from it. They will never admit do anything, or donate money for cures. One can count on nothing from Hoffman La-Roche, there is people in this world that are such.
By Doug Bremner, July 23, 2009 @ 12:02 am
A psychiatrist went from being deeply involved with the psychotropic drug industry to someone who eventually took on a multibillion dollar drug company over their acne drug Accutane. This drug, which made a billion dollars a year for the company at one point, was causing teenagers to commit suicide. The drug company tried to discredit him which led to a crisis in his career and family life. He then went back and re-visited the trauma of the death of his mother in early childhood and eventually was able to come back and fight against the drug company. The drug was taken off the
market two weeks ago.
The story is true, and it is based on my life.
I am writing a screenplay about this story which is almost finished.
If anyone is interested in this story, let me know.
By Amy Philo, July 23, 2009 @ 3:22 pm
Good for you Dr. Bremner. Morgan can you email me at amy@uniteforlife.org so I can send you a private message?
By bosox88, September 2, 2009 @ 11:35 pm
Hello
I’m a 21 year old male who took accutane for six months in 2005(I believe I was on a generic and I definately had my dosage increased over the 6 month course). I have experienced anxiety,depression,possibly psychosis,hair loss, insomnia and jaundice(especially around inner eye) Currently I’m trying to learn all I can about the long term side effects of the drug/effects of drug when combined with alcohol while taking it/any information that might helpe with these side effects.
Morgan, do you have any articles that explain what you are talking about with accutane and gene expression.
By Anne, February 27, 2010 @ 9:55 pm
Generic Accutane had our 15 year old son commit himself to a psychiatric hospital, because he started having thoughts that he wanted to hurt himself and/or others.
My husband took brand name Accutane over 10 years ago. He told me that it caused him great anxiety and a lot of muscle aches, but it did work for him.
An age limit should most definitely be put on prescriptions for this medicine. A grown man was much better able to handle the side effects than a young teenage boy.
By fale, March 9, 2010 @ 9:50 pm
I was on this at 13-14, about 20 years ago. What surprises me is that no one studied these kids BEFORE the drug for suicide. I remember seeing myself in a mirror brought thoughts of suicide before I even took Accutane. The thoughts continued until my skin cleared (during the second round). The round ended about a month or two after I cleared…and I was totally happy…still on the drug. People with severe acne are depressed way before they start accutane, because of the way they look and the way they are treated because of it. This was a miracle, without this drug, I would have killed myself, because of it, I am alive and happy with my appearance.
By Jan, April 16, 2010 @ 11:14 am
I have 5 children. 4 used Accutane in the 90’s. All 4 of them have moderate to severe depression. Talks of suicide. They are in their late 20’s and early 30’s now. Does this ever leave their systems? What do we do now?
By Jen C, May 19, 2010 @ 12:13 pm
I like to know who is going to take on the gerincs companies of Accutane???? Does anyone even care anymore??? Beware they are in phase III of a new form of Accutane. More will be damaged or dead.
Good work Dr. Bremner, I hope you keep us updated on the appeal won in the suicide case.