Who calls the shots? Acne & Isotretinoin II – Big Pharma & research

Investigation by Carolyn Skelton. [Part I. Part II.] The bigger picture In the first part of this series, I outlined issues related to acne and to the powerful drug Isotretinoin and the devastating consequences for some users.  In today’s appearance-focused world acne can be pretty depressing and confidence-sapping for many young people. At its most extreme it can lead to brutal bullying and/or suicidal thoughts. The powerful drug isotretinoin can seem to be a magical cure for acne.  However, after starting the medicine, some have experienced extremely negative psychological disturbances.. Professor J Douglas Bremner tells of one father’s story about his son taking Accutane.  The young man

told the family that the deceased rocker Jim Morrison was talking to him through monkeys and telling him to commit suicide On April 15, 2004…. After he stopped taking Accutane his psychosis and suicidal thinking stopped, and he continues to be free of symptoms to this day. 

(Before You Take That Pill, 2008: p49)

 The story of this drug provides insights into the processes of the research and marketing of powerful prescription medicines.  The drug companies have a lot of influence over the kinds of research conducted, with the aim of producing financially profitable “cures”.  Some governments are being criticised for increasingly prioritising such commercial imperatives over people’s health and well-being. The isotretinoin story: birth defects Isotretinoin was first developed by Dr Werner Bollag for possible use in cancer chemotherapy.  It was found to effectively clear severe acne.  Bollag dissociated himself from the use of the drug to treat acne.  He allegedly said that,

 deploying such a toxic substance for such a trivial matter would be like using a thermonuclear warhead to demolish a garden shed.

As reported by Julia Green at Harvard Law School in 2002, the Swiss company Roche rushed to make it available in 1982, using the brand name Accutane. Very soon people began to claim some very horrific side effects, most particularly being associated with birth defects in the babies of a large percentage of US women who were pregnant when they took Accutane.   Green puts some of the blame down to Roche’s rush to market the drug because of its potential for profits, while also suppressing the results of some of their own research. There were also later concerns that Roche was promoting Accutane for moderate acne, and not using it as a last resort medication. Following publicity for of the birth defects in the US, strong warnings were put on the medicine cautioning that it should not be taken by pregnant women, or if it is used by sexually active heterosexual women they should use two different forms of contraception.  Roche has had thousands of law suits against them, resulting in Accutane being withdrawn from the US market.  Other drug companies now supply the US, while Roche continues to sell the drug in the UK and Europe under the name RoAccutane. Isotretinoin and adverse psychiatric reactions [caption id="attachment_3453" align="alignleft" width="300"] From mercola.com[/caption]   With the decrease in cases of birth defects in the US, and the low number of such cases in the more strongly regulated European context, the controversy shifted to focus on associations between isotretinoin and psychological disturbances, depression and suicidal thoughts.  Statistics show that a minority of users experience negative side effects, but there may be significant under-reporting of such incidents.  The side effects usually occur up to a few months after starting to use the medication.  Consequently, many people probably don’t make the connection. Last November, the UK government drug monitoring agency published the results of their latest review of isotretinoin and adverse psychiatric reactions. Their conclusions were in keeping with previous arguments that there is no proof of such side effects. It is argued that such reactions can be caused by acne itself.  However, they also state there is no absolute proof that it doesn’t have such effects.  Consequently they call for education and information for users.  They also state that the “Group” that considered the available research concluded that such studies had limitations, and further research was needed.  They expressed concern that

standard epidemiological studies were unlikely to provide sufficient data to establish a causal association

Epidemiological studies look for patterns in selected populations of the causes and impacts of health issues and diseases. The UK report does not mention some earlier research done in the US by professor of psychiatry, J Douglas Bremner. It was funded by Liam Grant, the parent of a young man who had suicided following taking Accutane. Bremner did PET scans of brains of isotretinoin and non-isotretinoin users, as reported in his book, Before You take That Pill (link above). His findings showed that Accutane resulted in the decrease in functioning of the orbitofrontal cortex, “identical to what we found in patients who developed depression.” (p47-9) In other research funded by Grant, it was shown that

Accutane inhibited the growth of neurons in an area of the brain called the hippocampus, which is involved with memory and emotion.  This area is smaller in patients with depression. Other studies showed that Accutane caused behavior abnormalities in animals.

Roche remained committed to the view there was no “causal relationship”, even though one of their senior staff members acknowledged their research showed Accutane “‘probably caused” depression and other psychiatric ailments in some users ….” (p49) The neurological line of research has not been continued. Bremner met with intense opposition from Roche. A review of Bremner’s later book, The Goose that Laid the Golden Egg, explains that Bremner was put under intense pressure by Roche’s defense lawyers.  Roche was also implicated in encouraging the ethics charges brought against Bremner at the university where he worked.

 …Bremner’s life slipped out of control as one of the world’s richest corporations did everything they could to publicly discredit him.

It is astounding that more than a decade after Bremner’s books, the research has not gone beyond the epidemiological focus to look more intensely and directly at the impact of isotretinoin on brain functioning. Many now look to the US Ipledge system as a way of regulating the use of isotretinoin. It outlines some of the negative associations, though unproven, after taking Isotretinnoin. Prescribers, pharmacists, wholesalers  and users of isotretinoin must all be registered. The bigger picture: scientific research and NZ There are also concerns in NZ, that scientific research in general is being skewed by powerful organisations. On 10th April, 2015, on RNZ Dr Nicola Gaston, President of the Association of Scientists reported that a recent survey shows scientists reported they were being gagged, their integrity questioned or their results tampered with. A climate of fear, including in universities, was resulting in scientists self-censoring the kinds of research they conducted. Gaston stated that funders can choose sympathetic authors and have unfavourable ones removed from reports. She talked of studies very often being commercially directed or funded. Furthermore, government funding was often on subject matter where a group has a commercial relationship. http://podcast.radionz.co.nz/ntn/ntn-20150410-0932-scientists_speak_out_about_fears_of_attacks_on_freedom-048.mp3 In the next part, I will look at the isotretinoin situation in NZ. –]]>