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The Food and Drug Administration (FDA) and dermatology
organizations need to do a better job of warning consumers about the link
between Accutane, a commonly
prescribed acne drug, and depression or suicide, members of a US Congressional
committee have said. Their comments come following a recent congressional
hearing exploring the link.
"The FDA is supposed
to guarantee the efficacy of drugs for the people of this country,"
said Rep. Dan Burton (R-Ill.), chairman of the House
Committee on Government Reform. "To say that it's too difficult
to do it is kind of a cop-out."
Rep. Burton also blasted the American Academy of Dermatology
for not notifying all of its members of Accutane's mental health risks.
"Why not send a fax out to all your members saying,
'This is a risk, and we want to make sure you know about it'? If
the academy doesn't do it, give me a list of all your members and I'll
send the darned thing out."
Since 1982, when Accutane was first introduced, the
government has received 66 reports of patients who committed suicide while
taking the drug. Of course, underreporting of incidents in almost certain.
Patients who take the drug will soon get special warning
brochures outlining side effects - including the possible, but not proven,
link to suicide. Patients must then sign a paper certifying they understand
those risks, Dr. Jonca Bull, the FDA's deputy drug chief told Congress.
Also, the FDA is developing tougher restrictions on
who can take Accutane and which doctors can prescribe it, Dr. Bull told
the committee. This so-called registry is an attempt to counter another
Accutane problem: 2,000 women have gotten pregnant while taking Accutane
since the drug began selling in 1982. Accutane causes
severe birth defects. The registry could be in place ``as early
as next summer,'' Bull said.
The committee heard from several families about their
experiences with Accutane. Seventeen-year-old Amanda Calais of Denham
Springs, Louisiana, described how she began feeling depressed only a few
weeks after starting the drug. "I found myself feeling sad, and I
often cried for no reason," she said. Calais later attempted suicide.
She claims her depression lifted after she stopped using the drug.
The committee also heard from several other parents
whose children had committed suicide while taking Accutane. All of the
parents said they had received no warnings about a possible link between
Accutane and depression either from their physician or their pharmacist.
James O'Donnell PharmD, Assistant Professor of Pharmacology,
Rush Medical College, Chicago testified about the pharmacological aspects
of the drug and possible mechanisms by which Accutane may have adverse
psychological effects. He states:
"it is associated with a long list of
side-effects which are frequent, varied and at times severe. The most
commonly occurring adverse reactions are those involving the skin and
mucous membranes, which occur in all patients treated with Accutane. Other
side effects reported include skin fragility,
pyogenic granuloma-like lesions and epidermal
blistering, paronychia and alopecia
(Bigby, 1988). Gastrointestinal intolerance
occurs in 20% of patients treated (Bigby, 1988). Muscular or joint pain,
are quite common with Accutane use. Myalgia and arthralgias
occur in 16% of patients treated, which usually abate when the medication
is discontinued (Orfanos, 1997).
Blepharitis
and conjunctivitis associated with Accutane
use were recognized well before its marketing. Corneal
opacities and acute myopia have
been reported in government publications and in the ophthalmologic literature.
Other ocular reactions include optic neuritis, cataracts,
decreased night vision, blurred vision and
photosensitivity. Pseudotumor cerebri (PTC) and
headaches are also associated with the drug. In common with
other retinoids at pharmacological doses, Accutane causes elevation of
serum lipids particularly triglycerides.
Chronic hypervitaminosis A is more common
than the acute form and results from continued ingestion of high doses
[of vitamin A] for months or even years. Symptoms include anorexia, dry
itchy skin, alopecia, increased intracranial pressure, fatigue, irritability,
somnolence pronounced craniotabes and occipital edema, skin desquamation,
fissuring of the lips, pain in the legs and forearms, neurologic disturbances
and lethargy. Elevated blood lipids are also common.(Wilson, 1996 ) This
reads just like the Accutane package insert.
Concerning the possible effects of Accutane on psychiatric
function, Dr. O'Donnell states:
Vitamin A intoxication resulting in generalized
as well as Central Nervous System (CNS) symptoms, was first alluded
to in 1856 by Elisha Kane (Kane, 1856), the arctic explorer. He recorded
symptoms of vertigo, headache, drowsiness and irritability
following ingestion of polar bear liver, which was later found to contain
a high concentration of vitamin A. Over the succeeding 140 years, case
reports of the occurrence of acute schizophrenia or remitting psychosis
associated with either hypervitaminosis A (Halter, 1991; Haupt, 1977;
Landy, 1985) or vitamin A deficiency (Oliver, 1986) have appeared in
the literature. These provide literature precedent
and biologic plausibility to the causation analysis.
In 1972, Restak reported a case of toxic psychosis
in a patient following vitamin A treatment (50,000 IU 2/3 times daily)
for acne, which required hospitalization. About six months after initiating
vitamin A therapy, the patient experienced the onset of prolonged depression,
bouts of elation alternated with despondency, disturbed sleep, insomnia
and loss of appetite.
Twelve months later, while on holidays, she became
more agitated and depressed, and lost weight. She also developed blurred
vision, hyperacusis, vertigo, strong feelings of ego alienation, and
lethargy. Following psychiatric referral, total remission occurred over
6 months of close observation and anti-depressant therapy. The authors
cautioned against the use of the vitamins as preventatives for such
benign entities as acne. (Middelkoop, 2000)
In 1992, a case report described a patient, with
no previous psychiatric history, who presented with a 1-year history
of depressed mood and poor concentration (McCance-Katz, 1992). Medication
included only a multivitamin preparation of 25,000 IU of vitamin A per
day, for 2 years. Hamilton Depression Ratings confirmed full cessation
of depressive symptoms after stopping treatment.
Other reports of
lethargy, loss of interest in surroundings, insomnia, listlessness,
profound daily fatigue, anorexia and
irritability, in association with vitamin A, have been documented
(Stimson, 1961; Shaw, 1953; Oliver, 1958; Bifulco, 1957; Elliot, 1965).
Depression has been listed as a possible side effect
on Accutane's label since 1986, and the FDA in 1998 strengthened the warning
to say suicide, too, was possible. The suicide link gained wide attention
in October when a Michigan congressman, Democrat Bart Stupak, blamed his
17-year-old son's suicide on Accutane - and charged that patients and
families aren't warned about the risk, which appears in the fine print
of drug labels that many consumers never receive.
To read the testimony presented at the Accutane congressional hearings CLICK
HERE
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