Two US Congressional hearings were held in the House of Representatives
were held on the 5th December 2000 ('Accutane - Is this
Acne Drug Treatment Linked to Depression and Suicide?' Read Transcript) and 12th
December 2002( 'Issues relating to the Safety of Accutane/Roaccutane
(Isotretinoin/cis-13-retinoic acid) Read Transcript'.
At both hearings there were a panel of represenatives from
- FDA representatives; Read Dr.
Woodcock's Statement & Dr
Jonica Bull's Statement (Includes History of Drug, Label Warnings, ADRs etc.) |
Both hearings provided a large amount of information on Accutane/Roaccutane
and new information on adverse reactions, clinical trials and studies
were presented. In addition questions were asked raised regarding
scientific studies, clinical trials and the internet sale of the
drug.
The following links contain the transcripts of both hearings and to important information revealed at the hearings.
- 'Issues Relating to the Safety of Accutane' - 5th December 2000
- 'Accutane - Is this Acne Drug Treatment Linked to Depression and Suicide?' - 12th December 2002
Amanda Callais was prescribed Accutane as a 14 year-old in September 1997. By November she was seriously depressed and attempted suicide. The psychiatrist treating her for depression was not aware of the connection between Accutane and depression and did not suspend her use of the drug after her suicide attempt. She remained seriously depressed. In February 1998, Amanda’s mother, Lori learned of the FDA’s warning and stopped Amanda’s treatment. Amanda quickly made a full recovery. Mother and daughter are here today to share their experience.
Stacy and Mike Baumann of Mundelein Illinois lost their son Daniel to suicide in December 1999. Daniel began Accutane treatment in July 1999. He suffered many adverse effects - chapped lips, dry skin and itching, joint and muscle pain, headaches, nausea, loss of appetite, mood swings, and insomnia. The physician thought his depression was school-related and never mentioned the FDA warning.
Mr. Charles Jackson of Lubbock, Texas lost his 17 year-old son, Clay, in January 2000. Clay had been on Accutane for about three months. The family was provided no information by the physician regarding the FDA warning.
Panel of Experts
Dr. David Pariser of Norfolk, Virginia, testified on the behalf of the American Academy of Dermatology and provided an overview of the types of acne and when Accutane is recommended.
Dr. Douglas Jacobs, on faculty at Harvard, and a Roche consultant, presented his evaluation of the adverse drug events regarding psychosis, depression, and suicide and Accutane.
Dr. James O'Donnell, Assistant Professor of Pharmacology, Rush Medical School presented information regarding the connection between Accutane and other vitamin A derivatives and depression and suicide.
Dr. Jonca Bull testified on behalf of the Food and Drug Administration (FDA). Accompanied by Dr. Phyllis Huene.
Rep. Burton's Opening Statement
Four main questions were addressed:
- When did the issue of depression and suicide first arise regarding Accutane?
- What actions did Roche and the FDA take to determine if there was a causal link?
- When and how was the public notified?
- Was that public notification adequate?
The drug was licensed by the Food and Drug Administration (FDA) in 1982 as an oral prescription drug for the treatment of severe acne. However, he raised serious concerns that many individuals have been prescribed this drug for less severe forms of acne.
He highlighted that a significant number of psychiatric events, mostly severe depression, have been reported through post-marketing surveillance and that the FDA have received reports of sixty-six suicides and one thousand three hundred seventy three psychiatric adverse events other than suicide related to Accutane.He explained how they learned through their investigation that the first report of depression in patients taking Accutane occurred in September 1982. Two patients in a clinical trial with 523 patients reported depression. Roche received five adverse experience reports of depression in 1983. November 1983, Roche received its first report of attempted suicide. November 1984, Roche received its first report of suicide. In May 1986 Roche received reports of five or six positive rechallenges in patients who experienced depression during Accutane therapy. In these patients, the depression went away when they stopped taking Accutane and began again after starting Accutane therapy again. Positive rechallenge is a significant indicator of a causal link between a drug and the adverse event.
He pointed to the fact that as early as November 1984, Roche began including information on the package insert about reports of depression. Even thought French authorities required a label change to include “suicide attempt” in March 1997, the FDA did not require Roche to make a label change until February 1998.
Rep. Waxman made several comments on the research that Roche have agreed to conduct with the FDA and NIH. He said it is critical and long overdue and wanted the design of the research to be agreed as soon as possible. He commended Rep. Bart Stupak on his work in getting the word out to patients via media and website. He said the number of serious psychiatric adverse drug reaction reports seemed to suggest a link between accutane and psychiatric side-effects and that is unacceptable that it is unanswered. He stressed the problem that old boxes with old labels were sold. He also wanted answers as to why France and Europe acted quicker to changing the label warning on Accutane/Roaccutane.
The following are points of interest and/or new revelations which were discussed at the Hearing
- ADR's: -
- There were 47 suicides on the FDA database in October 2000 - there are 173 suicides on the FDA database in December 2002. Rep. Stupak forwarded to the FDA a further 37 cases which were reported to his office - Stupak. [Note since the introduction of suicide as a labeled event, suicide, suicide attempt or suicide ideation do not have to be reported to the FDA outside the USA]
- In the last quater of 1999, there were 2381 ADR reports for Accutane, 313 were serious - of these 89 were psychiatric, 44 were self injury, 5 attempted suicide, 5 completed suicide and 5 cases of psychosis. - Stupak
- Suicide and depression as possible side effects of the drug
came to the attention of the FDA as early as February 1985
in which there was a case of a suicide reported where the
patient had no history of depression.
- Prescriptions::
- 49% of prescriptions are going to mild to moderate acne
cases - Brown; Email from FDA revealed which showed that 3%
of Accutane prescribers prescribe nearly 20% of Accutane scripts
in the US.
- 49% of prescriptions are going to mild to moderate acne
cases - Brown; Email from FDA revealed which showed that 3%
of Accutane prescribers prescribe nearly 20% of Accutane scripts
in the US.
- Clinical Trials:
- In the clinical trials for the New Formulation Accutane product (which is not yet licensed), there were 11 times more psychiatric injuries with the New Formulation Product -Stupak
- Accutane was rushed on the market and approved in less that one year, while other drugs at that time [1982] took three to four years to be approved
- The clinical trial submitted to the FDA consisted of 523
patients, of which 89 were young. Of these 89 only 6 had acne,
the severity of which is unknown - Stupak. Most of the patients
had keratinizing defects that were not acne - Woodcock.
- Studies:
- An article published in 1989 entitled "Accutane: An Update for Dermatology Nurses", presented at the Congressional Hearing stated that "CNS symptoms need to be reported to the dermatologist at once. Unusual changes your patient should be aware of are insomnia, fatigue, headaches, and double vision or decreased night vision. Depression has been reported, and this tends to be seen in the adolescent patients. Parents or adults need to understand the possibility of Accutane-induced depression and not brush it off as age related or stress induced." The paper was submitted to the FDA by Roche and the information in the journal was based on Roche data - Stupak
- A 1981 document entitled "Internal Reserach Report"
was sent to the FDA by Roche in January 2002. It showed that
a study was conducted on the central nervous system of mice.
Increased irritability, hyperactivity and touch response were
found in some of the mice - the report was never submitted
to the FDA - Stupak.
- Birth Defects:
- Slone Survey - a postmarketing survey to monitor the number of pregnancies and abortions which took place while women were on Accutane. Memorandum by FDA in 1989 stated that "the sponsor has not submitted a scientifically acceptable study proposal. Rather, they have proceeded with a survey proposal rejected twice by the Division of Epidemiology and Surveillance as well as by two internationally recognised authorties in the field..The results [of the survey] cannot be trusted and should be ignored in decision making about the future of Accutane
- Memorandum dated 7 May 1990 by FDA stated that "the magnitude of fetal injury and death has been great and permanent, with 11,000 to 13,000 Accutane-related abortions and 900 to 1,100 Accutane related birth defects."
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