Of course we want acne
drugs and treatments to be both effective and safe, but somehow this is easier
said than done.
Recently, on the
CyberShrink Forum, a mother reported that her daughter had developed severe
anxiety, depression and suicidal thoughts after a few weeks on Accutane (used
to treat severe acne), and still hadn’t recovered after four months of treatment.
(This article is about the drug Isotretinoin, which will be referred to as
Accutane [formerly Roccutane], the name under which it is sold in South
The question about the
dangerous side-effects of Accutane remains annoyingly unsettled. We may hear stories from friends about horrible
side-effects, but doctors are often strangely reluctant to discuss important
facts about any of the drugs they prescribe and don’t explain possible
Read: Computer can predict drug side effects
There is however no
good excuse for them not to do so. Some doctors have explained that they
believe that if they mention side-effects, the person will inevitably
experience them. This is superstition, not fact. Not only is there no evidence that this
actually happens, but research actually shows that people who’ve been given a
proper explanation of benefits and risks, are no more likely to experience
side-effects – and if they do, they’re more likely to remain on the drug and
benefit from it.
Since Accutane was
first released in America in 1982, there have been repeated reports of serious
problems like birth defects, suicidal depression, and bowel disorders. The parent company, Roche, stopped making it
in 2009, not because of safety issues, but because the exclusive patent had lapsed
and it was no longer guaranteed to be a profitable product, even though it
remained very expensive. It has remained available in generic versions.
Usually drug companies try very hard to find
creative ways to extend their patent rights to any profitable drug and discourage
the advent of generics. Roche did not choose to do so in this case, perhaps
because there are reports of close to 1,000 lawsuits against the company, with
many more pending. Such litigation is expensive – with a potential for punitive
damages and compensation.
Dermatologists had been
delighted to have a treatment that could produce dramatic improvements in
chronic severe acne that was not responding to routine treatments. Indeed, in
many cases the condition was described as cured, an uncommon outcome in
medicine. South African guidelines for its use, written by dermatologists, are
highly enthusiastic, warning only of “foetal damage”, and describing other
side-effects as “uncomfortable rather than dangerous”.
Permanent facial scarring and disfigurement
But over the past 30
years thousands of patients across the world have complained of serious
Accutane is only supposed
to be used in severe nodular acne when there are large, painful red lumps on
the skin, potentially causing permanent facial scarring and disfigurement, which
can lead to psychological distress and severe depression.
That Accutane can
cause serious birth defects when taken by pregnant women is a fact, and great
care needs to be taken by the prescribing doctor to make sure that the woman is
not pregnant, and is using effective contraception to avoid pregnancy during
treatment. In a 2007 study of 90 women
who became pregnant while taking Accutane (isotretinoin), only 9 had a live
birth and 76 had elective abortions. Obviously this is unacceptable, and care
to avoid pregnancy is paramount.
Read: Abortion: religion plays small role
gastroenterology have indicated that shown that Accutane users have a higher
incidence of various digestive disorders (about double the usual risk), inflammatory
bowel disease (four times the normal risk). Raised cholesterol levels and liver
toxicity have also been recorded.
There have been a
multitude of reports of severe depression associated with Accutane use. However, it is important to remember that
things may be associated in the sense that they often occur together, without
one actually causing the other. Whether Accutane actually causes depression is
not yet clear.
In 1998 the American
FDA (Food and Drug Administration) issued a formal warning to doctors of a
possible association between isotretinoin and depression, psychosis, suicidal
thinking and suicide. The FDA recommended that patients should sign informed
consent forms and receive a printed guide.
The evidence for an association
Between 1982 and 2000,
the FDA received 394 reports of cases of depression and 37 suicides in patients
taking isotretinoin. Of all drugs
reported to the US system for reporting adverse drug effects, it’s the 5th
most often reported as associated with depression, and the 10th most
often reported with regards to suicide. A similar situation presented itself in
Canada, Australia and Britain.
It’s worth noting that
in a number of the reported cases the depression resolved when the person
stopped taking the Accutane, and returned when it was started again.
Read: The depressed child
Such situations can be
more complex than they seem. One case appeared very clear: a 17 year-old boy in
Korea behaved oddly while taking isotretinoin, improved when it was stopped,
and started acting strangely again when it was re-started – and the drug was
blamed. Then they discovered he had also
been taking street LSD and cannabis at those times.
Another way to study these
issues is to analyse very large volumes of information about large numbers of
patients, and this has produced different results. Analysis of the Canadian
Health Database and the British General Practice Research Database found no
increase in the risk of depression, or suicide, attempted or completed, when
comparing people with acne treated by Accutane and those treated with antibiotics.
There have been concerns about the fact that that this study was sponsored by the drug industry, and
with aspects of the research itself. It
ignored the severity of the acne and the doses of the drug, among other flaws.
An actual improvement in depression in some patients
Another large scale
study showed no relationship between the drug and depression. But another calculated that if there was no
causal effect, there should have been only 6 suicides in those taking Accutane,
whereas there were actually 36 reported, thus suggesting it might indeed have
On the other hand, because
having severe, painful and ugly acne is in itself depressing, some researchers
have reported an actual improvement in depression in some patients on
Accutane. But remember that the issue
isn’t whether everyone who takes the drug becomes severely depressed. The question is whether some people run an
increased risk of severe and dangerous depression.
Read: Causes of depression
A chemically similar
drug, etretinate, also used for skin disease, has been reported to be
associated with depression as well.
Accutane has also been reported to show a range of other possible side-effects
suggesting psychiatric/neurological impact: such as irritability, unstable
emotions, memory problems, tiredness, incoordination and marked dreaming.
There is already a
significant risk of depression and suicide attempts in adolescents, the very group
most likely to need Accutane. Some studies found a greater degree of impairment
of mental health due to acne than from asthma, epilepsy, diabetes, pain or
arthritis, so this is far from a trivial condition. Acne by itself has been
associated with depression and suicide.
So how should we deal
with the question about whether and how to use Accutane? As I see it, there is not enough convincing
evidence to assume a high risk of depression or suicide, but also not enough
evidence of safety to allow us to assume that there is no risk. The risk may not
be the same for everyone, and the severe depression and suicidality reported
with Accutane use may be a high risk for a small number of people we can’t
identify in advance, and a very low or no risk for many others.
There have been a
surprising number of studies with really significant flaws, failing to
satisfactorily resolve this important question. The lack of enough research to
answer the question definitively is not a matter of negligence – to try to do
it properly would be very expensive and difficult. Considering how effective
the drug is for the severe acne, there would be ethical problems both in
administering it to some patients, and in withholding it from others, in such
Read: Ethics in health research
As a precaution it
would be wise for the drug to be prescribed only by specialists such as
dermatologists after screening for existing depression, and obtaining a
psychiatric opinion where this is present. It should be reserved for really
severe cases and not be used for mild acne.
Patients and their
families should be informed that there is a risk of depression so that they can
be vigilant. (They should also be informed of other potential risks and
There appears to be no
evidence suggesting that Accutane has any effect on the standard treatments for
Acne linked to thoughts of suicide
Symptoms of acne
Overweight teen girls have higher acne risk
depression and suicide: a review of the evidence. Magin & Smith. Br J Gen
Pract. 2005 Feb 1; 55(511): 134–138.
Image: Depressed teenager from Shutteerstock
Professor MA Simpson is Health24's CyberShrink. A South African psychiatrist, he qualified in medicine and in psychiatry in Britain. He has been a senior academic, researcher, and Professor in several countries. Read more of his columns.