Niks aan de Hand – Nothing out of hand.
This item has just appeared in the BMJ: An expert group has been reconvened to review recent safety data relating to the acne drug isotretinoin (Roaccutane) and evaluate the risk of sexual and psychiatric adverse effects, including suicide.
The Medicines and Healthcare Products Regulatory Agency’s isotretinoin expert working group had looked at the risk of psychiatric adverse reactions suspected to be associated with isotretinoin in 2014, but it has now reformed to look at more recently reported adverse reactions. In 2019 12 deaths were recorded among people to whom isotretinoin had been prescribed, 10 by suicide, MHRA data show.
The working group will include experts in clinical pharmacology, psychopharmacology, psychiatry, and general practice. They will be the bestest, the very bestest of experts. It will hold its first meeting as early as possible in 2020.
As part of its review the group will consider whether regulatory action is needed to minimise risks or raise awareness of the risks, after reports of sexual and psychiatric adverse reactions linked to isotretinoin.
The group’s findings and recommendations will be passed to the Commission on Human Medicines, another MHRA body, a very expert body, which will advise the MHRA and relevant ministers on whether regulatory action is needed. Action could take the form of restrictions on when to use the drug, updates to the product information, additional risk minimisation materials, further study of the issue, or a communication strategy.
A Swedish cohort study published in The BMJ in 2010 found an increased risk of attempted suicide up to six months after the end of treatment with isotretinoin but that the risk was already rising before treatment, so an additional risk due to the isotretinoin treatment could not be established.
Sundström A et al Association of suicide attempts with acne and treatment with isotretinoin: retrospective Swedish cohort study. BMJ 2010; 341: c5812.
The MHRA’s working group’s 2014 review concluded that “acne, whether or not it is treated with isotretinoin, is associated with psychiatric disorders.” However, it said that the available data were “insufficient to establish a causal association but could not rule out an association between isotretinoin and psychiatric disorders.”
It recommended that patients be routinely screened and monitored for psychiatric disorders, and that education on and awareness of risks should be considered for patients and their family and friends.
The report also called for a “carefully designed prospective study” to look at the possible association between isotretinoin and psychiatric disorders, although it added that “standard epidemiological studies were unlikely to provide sufficient data to establish a causal association.”
A spokesperson for Roche, which markets Roaccutane, said, “The usual guff” (my paraphrase.
This small study uses patient exposure years which is misleading and inappropriate. The results should be expressed in terms of people only and not patient exposure years.
Second, the 6-month data show an absolute increase in serious suicidal events over the population norm.
The authors idea that acne causes suicidality is based on data that in the period prior to isotretinoin prescription there is an increase in serious suicidal events.
They also note many of these patients will have had tetracyclines, primarily doxycycline.
They claim not to be aware of a suicide signal for doxycycline.
The data for suicidal events and suicide-related events in OpenFDA data is shown below. Close to one third of reports on doxycycline are for behavioural events (around 9000). Roughly one sixth of MHRA reports on this drug are for similar behavioural events. These reports are from some patients taking this drug for acne, but mostly for malaria prophylaxis or for other infections with no reason to believe they are suicidal.
The Sundstrom study provides compelling evidence that doxycycline (tetracycline) increases the risk of serious suicidal events in people taking it for acne and that isotretinoin likely produces an even higher rate of suicidal events and that in all likelihood the populations becoming suicidal on doxycycline and those becoming suicidal on isotretinoin are distinct and that therefore dermatologists are inducing suicidal events in a relatively large number of people.
I emailed Dr Sundstrom months ago hoping to get access to his raw data but to date have had no reply.
When Roche can depend on the authors of an article that ends up in BMJ, showing very clear risks from drugs not to spot those risks, and can depend on the editors of BMJ not to spot the risks, and can depend on MHRA and any expert panel they convene not to spot the risks, there are no risks from falling back on the usual guff.
One of the mistakes, the families of people killed or seriously harmed by Accutane, isotretinoin or whatever make is to think MHRA are interested in patient safety.
MHRA is a bureaucracy that regulates the wording of adverts or claims that pharmaceutical companies make. As long as the claim can be backed up by some kind of Guff, the company is on safe ground. The box has been ticked. Dead youngsters – pity but not our problem.
MHRA have access to a much larger dataset than Sundstrom through GPRD. If they were really interested to check things out there is a lot they could do.
At the same time as a study on suicidality was undertaken in GPRD, it might be possible to track what proportion of males in particular who are given isotretinoin are later given a script for Viagra, Cialis or other phosphodiesterase inhibitor – a possible marker of enduring sexual dysfunction.
While undertaking this, something similar could be done for finasteride and for SSRI and related antidepressants.
Simple stuff, easily done, but you’d have to interested. Others could do it but MHRA control access.
Its not MHRA’s job to keep people safe but it is doctors. There may be more drugs used by dermatologists that cause suicide than are used by any other specialism except psychiatrists. In addition to Accutane and doxycycline, there is Siliq, Taltz, Otezla and many others.
I have yet to meet a dermatologist who recognised any treatment related suicidality in any patient he gave a drug to – see Sylvia’s Story – even good dermatologists.