During a US House Oversight and Investigation Subcommittee hearing on the Safety Issues Relating to Accutane, on December 11, 2002, internal documents from the nation's regulatory agencies were entered into the record that revealed that public health officials had been voicing concerns about patients committing suicide while on Accutane for well over a decade.
For instance, a 1998 memo from the FDA's medical officer in charge of Accutane states: "Given all the pieces of evidence available, it is difficult to avoid the conclusion that Accutane can adversely affect the adult human brain in clinically significant ways and that Accutane use is associated with severe psychiatric disease in some patients."
The memo recommends "active consideration of removal of Accutane from the market."
But instead of removing the drug from the market, on February 25, 1998, the FDA required Roche to add the following bold-face warning to drug's physician package insert:
"WARNINGS - Psychiatric Disorders: Accutane may cause depression, psychosis and, rarely, suicidal ideation, suicide attempts and suicide. Discontinuation of Accutane therapy may be insufficient; further evaluation may be necessary. No mechanism of action has been established for these events."
"ADVERSE REACTIONS - In the postmarketing period, a number of patients treated with Accutane have reported depression, psychosis and rarely, suicidal, ideation, suicide attempts and suicide. Of the patients reporting depression, some reported that the depression subsided with discontinuation of therapy and recurred with reinstitution of therapy."
In perverse twist of logic, in the same year, Roche began actively marketing Accutane as a treatment for depression, under the theory that it could help people who were suffering from depression due to poor self-image as a result of acne.
On March 5, 1998, Roche received a letter from the FDA stating that such promotion was false and misleading, and that Accutane had never been approved for the treatment of depression, and that in fact, just the opposite was true. The letter stated in relevant part:
"Roche ... has not systematically studied the ability of Accutane to modify or prevent such illnesses as depression and has presented no basis for asserting that Accutane is effective in improving the psychosocial and emotional well-being of such patients.
"This claim is particularly troublesome in light of information recently presented in a Dear Doctor letter, that Accutane may cause depression, psychosis, and rarely, suicidal ideation, suicide attempts and suicide."
The FDA also instructed Roche to "prominently disclose information about the psychiatric disorders described in the warnings section of the revised labeling" in Accutane advertisements.
In September 1998, the FDA presented an Advisory Panel with 37 cases of suicide attributed to Accutane since 1983. However, the number was later changed to 44 suicides after Roche corrected its calculations.
The Adverse Event Reporting System (AERS) is a computerized database of post-marketing adverse events, designed to support the FDA's post-marketing surveillance program of all approved drugs.
The reports in AERS are evaluated by agency reviewers in the Center for Drug Evaluation and Research (CDER) and the Center for Biologics Evaluation and Research (CBER) to detect safety signals and to monitor drug safety.
The results of a review of AERS by congressional staffers working on behalf of Congressman, Bart Stupak (D-MI), revealed during an October 5, 2000, hearing, reported 54 more suicides by persons on Accutane after the FDA issued its MedWatch in 1998.
In 2004, the Alliance for Human Research Protection, asked Keith Altman, an Adverse Drug Reaction Statistics Analyst, to analyze the FDA's Medwatch database for drug-linked suicides by children under the age of 18. The analysis found that between 1989 and June 2003, there were 216 reports of drug-linked suicides, and 72 were associated with Accutane.
For instance, a 1998 memo from the FDA's medical officer in charge of Accutane states: "Given all the pieces of evidence available, it is difficult to avoid the conclusion that Accutane can adversely affect the adult human brain in clinically significant ways and that Accutane use is associated with severe psychiatric disease in some patients."
The memo recommends "active consideration of removal of Accutane from the market."
But instead of removing the drug from the market, on February 25, 1998, the FDA required Roche to add the following bold-face warning to drug's physician package insert:
"ADVERSE REACTIONS - In the postmarketing period, a number of patients treated with Accutane have reported depression, psychosis and rarely, suicidal, ideation, suicide attempts and suicide. Of the patients reporting depression, some reported that the depression subsided with discontinuation of therapy and recurred with reinstitution of therapy."
In perverse twist of logic, in the same year, Roche began actively marketing Accutane as a treatment for depression, under the theory that it could help people who were suffering from depression due to poor self-image as a result of acne.
On March 5, 1998, Roche received a letter from the FDA stating that such promotion was false and misleading, and that Accutane had never been approved for the treatment of depression, and that in fact, just the opposite was true. The letter stated in relevant part:
"Roche ... has not systematically studied the ability of Accutane to modify or prevent such illnesses as depression and has presented no basis for asserting that Accutane is effective in improving the psychosocial and emotional well-being of such patients.
"This claim is particularly troublesome in light of information recently presented in a Dear Doctor letter, that Accutane may cause depression, psychosis, and rarely, suicidal ideation, suicide attempts and suicide."
The FDA also instructed Roche to "prominently disclose information about the psychiatric disorders described in the warnings section of the revised labeling" in Accutane advertisements.
In September 1998, the FDA presented an Advisory Panel with 37 cases of suicide attributed to Accutane since 1983. However, the number was later changed to 44 suicides after Roche corrected its calculations.
The Adverse Event Reporting System (AERS) is a computerized database of post-marketing adverse events, designed to support the FDA's post-marketing surveillance program of all approved drugs.
The reports in AERS are evaluated by agency reviewers in the Center for Drug Evaluation and Research (CDER) and the Center for Biologics Evaluation and Research (CBER) to detect safety signals and to monitor drug safety.
The results of a review of AERS by congressional staffers working on behalf of Congressman, Bart Stupak (D-MI), revealed during an October 5, 2000, hearing, reported 54 more suicides by persons on Accutane after the FDA issued its MedWatch in 1998.
In 2004, the Alliance for Human Research Protection, asked Keith Altman, an Adverse Drug Reaction Statistics Analyst, to analyze the FDA's Medwatch database for drug-linked suicides by children under the age of 18. The analysis found that between 1989 and June 2003, there were 216 reports of drug-linked suicides, and 72 were associated with Accutane.
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