Note: Numbers in Brackets [] refer to links and sources listed at the
end of this answer.
Hello Chloe!
First of all, let me say that I'm sorry for all your friend has
obviously been going through. I hope I will be of assistance in
extending your understanding of the drug Roaccutane(R)/Isotretinoin
and hopefully be able to aid in reducing his suffering. According to
your question, I will split up my answer into the following parts:
1) What is Roaccutane?
2) What side effects have been reported and what are known
contra-indications, with respect to your friend's problems?
3) Overview of the "Roaccutane Opposition" and its supporters
4) Summary and what your friend might do
---------------
1) Roaccutane(R) (active ingredient Isotretinoin) is a dermatological
preparation used for the treatment of severe acne, especially when the
lesions have become 5mm or greater in diameter and multiple in number;
the condition is then referred to as nodular acne. Isotretinoine is a
derivative of Vitamin A. As with so many medications, Roaccutane's
mechanism of action is not yet fully understood. When taken, it seems
to influence the size and, temporarily, activity of the sebaceous
glands. Also, it has general anti-inflammatory properties and
interferes with keratinization (the developement of skin cells, as
they move upwards within the epidermis, i.e. the topmost layer of the
skin). [1][2]
2) A wide number of side effects have been reported with this drug.
However, reading those, please bear in mind that it is very common for
almost any medication to show a large number of side effects in a
clinical study. It can be very difficult to determine whether for
example the 2 people that took part in a study feel actually dizzy
because of the medication they took or because they, say, had too much
coffee in the morning. I remember I once got hold of a leaflet listing
the side effects of chocolate. Frightening to look at. :) So it is not
only the actual number of side effects that should be considered, but
rather their relative occurrence and severity.
These are the most common side effects that Roche reports for their
product [3]:
Their disclaimer:
"The adverse reactions listed below reflect the experience from
investigational studies of Accutane, and the postmarketing experience.
The relationship of some of these events to Accutane therapy is
unknown. Many of the side effects and adverse reactions seen in
patients receiving Accutane are similar to those described in patients
taking very high doses of vitamin A (dryness of the skin and mucous
membranes, eg, of the lips, nasal passage, and eyes)."
(The latter does not surprise us, remember, Roaccutane is a Vitamin A
derivative.)
- dryness of lips (prevalence in clinical studies with dosis of 0,5
mg/kg: 80%*)
- inflammation of lips (i.e., redness, swelling etc., 90%)
- inflammation of face (55%)
- scurfing of skin (65%)
- dry nose (mucous membranes, 35%)
- itching (40%)
- dry mouth (30%)
- red eyes (conjunctivitis, 20%)
- thinning of the skin (15%)
- hair loss (20%)
- muscle/joint pain (15%)
- nose bleeding (15%)
Other possible (less common) adverse reactions are also reported [2],
among those:
"Psychiatric: suicidal ideation, suicide attempts, suicide,
depression, psychosis, aggression, violent behaviors (see WARNINGS:
Psychiatric Disorders), emotional instability. Of the patients
reporting depression, some reported that the depression subsided with
discontinuation of therapy and recurred with reinstitution of
therapy."
and
"Skin and Appendages: acne fulminans, alopecia (which in some cases
persists), bruising, cheilitis (dry lips), dry mouth, dry nose, dry
skin, epistaxis, eruptive xanthomas, flushing, fragility of skin, hair
abnormalities, hirsutism, hyperpigmentation and hypopigmentation,
infections (including disseminated herpes simplex), nail dystrophy,
paronychia, peeling of palms and soles, photoallergic/photosensitizing
reactions, pruritus, pyogenic granuloma, rash (including facial
erythema, seborrhea, and eczema), sunburn susceptibility increased,
sweating, urticaria, vasculitis (including Wegener's granulomatosis;
see PRECAUTIONS: Hypersensitivity), abnormal wound healing (delayed
healing or exuberant granulation tissue with crusting; see
PRECAUTIONS: Information for Patients and Prescribers)."
So we can conclude that there are not only "any cases similar" to what
your friend is suffering from, but that his problems could be
attributed to "official" adverse reactions.
If we look at the contraindication and warnings section, again we are
reminded that this drug should not be administered to somebody with a
preexisting psychiatric condition:
"WARNINGS: Psychiatric Disorders: Accutane may cause depression,
psychosis and,
rarely, suicidal ideation, suicide attempts, suicide, and aggressive
and/or violent behaviors. Discontinuation of Accutane therapy may be
insufficient; further evaluation may be necessary. No mechanism of
action has been established for these events (see ADVERSE REACTIONS:
Psychiatric). Prescribers should read the brochure, Recognizing
Psychiatric Disorders in Adolescents and Young Adults: A Guide for
Prescribers of Accutane (isotretinoin)." [2]
The important statement that "no mechanism of action has been
established" seems to be confirmed by the FDA, specifically the CDER:
From "Accutane: A Letter to Consumers and Health Care Providers": [4]
"With respect to psychiatric events, our advisory committee agreed
that no clear causal link has been established. However, definitive
demonstration of causality for a rare adverse event can be difficult
to demonstrate. When there is reasonable suspicion of an association,
patients should be informed. We are working diligently with the
sponsor on this issue. We certainly agree with the need for more
scientific study of this issue, but we recognize that the design of
informative trials presents significant methodologic and ethical
challenges."
Since the drug hit the market (1982), Roche has obviously been forced
to adapt label and product information of Accutane/Roaccutane several
times. As of 1988, the product leaflet in England had to inform
consumers about "dangerous side effects such as depression, suicide
attempts and psychotic episodes." [5] After the FDA took action (see
the letter above), other revisions obviously became neccessary. A
letter from the FDA to Roche, confirming the most recent changes for
the US, is available on the CDER website. [6] One of its key
requirements is that the labelling information contain in its entirety
a brochure on "Recognizing Psychiatric Disorders". [7]
3) If you search the web, it becomes clear quickly, that this drug
really has its opponents and, possibly outweighing in numbers, its
supporters. There is one association of "individuals and families of
individuals who have suffered" called the "Accutane/Roaccutane Action
Group" [8] who have collected an extensive amount of data: among other
items scientific literature, a detailed "label history" of
(Ro)accutane and an adverse reaction database. They repetedly accuse
Roche of fraud, however, which makes their statements somewhat biased.
It seems reasonable to conclude, though, that Roche didn't/doesn't
seem to be very eager to support studies that would definitely prove
or refute especially the psychiatric reproaches brought up against
their product. They have always been stating, as has the FDA in an
letter to the New England Journal Of Medicine that the "number of
suicides reported among users of isotretinoin does not exceed the
number that would be predicted on the basis of the suicide rate in the
United States and the estimated number of patients exposed to the
drug." [9] The "Accutane/Roaccutane Action Group" site has also a page
dedicated to lawsuits and may be of assistance in case you would
consider taking legal steps against Roche.
This site features diaries of (Ro)accutane users, showing the positive
side of this medication. [10] But let's come to the most important
point of this answer, how can your friend be helped?
4) Let me start off with something you say at the beginning of your
question: your friend was prescribed the drug for "moderate acne". I
think we can conclude by now, that (Ro)accutane is a powerful, widely
prescribed drug that does help a lot of people. Its opponents claim
that it's "overprescribed", though. [11] So my first idea would of
course be to maybe get your friend off (Ro)accutane and see how this
affects his mood as well as his acne. It seems especially worth the
try because he is experiencing skin symptoms, which seem to be
difficult to tolerate, even with the medication. Your friend should
discuss this with his doctor. If he feels that his concerns are not
addressed properly, he maybe should consider changing his
dermatologist. It may also be a good idea to consult a psychiatrist,
in case you haven't done that already, as he may be able to assess the
situation better in this context.
As to your question of how acne and psyche may interrelate, this is a
difficult field. Especially in adolescents, acne can cause severe
"embarrassment, frustration, anger, and depression" , so that it may
be "virtually impossible to separate acne from psychiatric
disturbances" [12]. Of course, your friend should have built up some
self-esteem by now, but it is clear that it may still be a major
source of discomfort. Stress is of course known to trigger acne.
[e.g., 13] However, other studies have failed to see a clear link:
"The role of stressful events in vitiligo, lichen planus, acne,
pemphigus and seborrhoeic dermatitis was either controversial or
insufficiently explored." [14]
To sum it all up, it seems recommendable to try to get off
(Ro)accutane for a while for your friend, in collaboration with his
doctor, of course, and to see how he feels. If things don't improve,
I'd suggest you go see a psychiatrist. There obviously are other
treatment options, but with all the evidence linking Isotretinoine and
depression, abstinence from it seems the first logical step.
I hope this answer was what you were looking for and helped you
understand your friend and his situation better. If you want me to do
further research on specific aspects, please do not hesitate to ask
for a clarification. I'd also be interested to learn how things turn
out for your friend.
Best wishes,
searchbot
Additional links:
Another anti-Roaccutane site:
http://www.roaccutanesurvivors.com/
Pretty well balanced article on Roaccutane by a dermatologist who
suffered from acne herself:
http://www.dermadoctor.com/pages/newsletter96.asp?WID=%7bAB739E68-E606-11D5-9175-0002B330452B%7d
CDER/FDA Roaccutane overview:
http://www.fda.gov/cder/drug/infopage/accutane/default.htm
A Yahoogroups discussion forum:
http://groups.yahoo.com/group/Accutane_and_Acne
-----------------------------------
Sources:
[1] South African Electronic Package Inserts:
http://home.intekom.com/pharm/roche/roaccuta.html
[2] Roche Accutane(R) = Roaccutane product information:
http://www.rocheusa.com/products/accutane/pi.pdf
[3] Roche Germany:
http://www.roche.de/pharma/products/fachinfo/roaccutan.pdf (Note:
document not publicly accessible, very similar to US product
information cited above.)
[4] Center for Drug Evaluation and Research (Food and Drug
Administration):
http://www.fda.gov/cder/drug/infopage/accutane/accutane-ltr.htm
[5] BBC News:
http://news.bbc.co.uk/1/hi/health/218028.stm
[6] FDA -- Roche correspndence:
http://www.fda.gov/cder/foi/appletter/2002/18662s046ltr.pdf
[7] Brochure "Recognizing Psychiatric Disorders in Adolescents and
Young Adults: A Guide for Prescribers of Accutane (insotretinoin)"
http://www.fda.gov/cder/drug/infopage/accutane/accutane_psychdisorders.htm
[8] Accutane/Roaccutane Action Group:
http://www.roaccutaneaction.com
[9] FDA letter to NEJM, 344:460, 2001
http://content.nejm.org/cgi/content/full/344/6/460 (not accessible
without a subscription)
[10] General Accutane Information and Users' Diaries:
http://accutaneeverything.cjb.net/
[11]Reuters: Action Group Urges Britain to Withdraw Acne Drug
http://www.yourlawyer.com/practice/news.htm?story_id=628&topic=Accutane
[12] Cutis 2002 Aug;70(2):133-9: The interaction between acne vulgaris
and the psyche.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12234161&dopt=Abstract
[13] Curr Psychiatry Rep 2001 Jun;3(3):219-25: Psychocutaneous
disorders
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11353586&dopt=Abstract
[14] Psychother Psychosom 2001 May-Jun;70(3):118-36: Stressful life
events and skin diseases: disentangling evidence from myth.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11340413&dopt=Abstract
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Search strategy:
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