Pfizer Zoloft Warnings to Canadian Doctors Contrast to US - FDA Caves In to Pharma lobbying
Thu, 10 Feb 2005
The FDA has, once again, quietly colluded with industry, compromising the safety of children's lives to maintain drug manufacturers' cash flow.
After two FDA advisory committee hearings (Feb 2-3 and Sept 13-14, 2004) and independent analyses of the data from 24 clinical trials in which children were exposed to an SSRI antidepressant, the FDA was convinced that a causal relationship had been scientifically established between SSRIs and suicidality (suicide attempts) in children and adolescents.
On October 15, 2004 the FDA issued label warnings to reflect the scientific evidence, stating:
"A causal role for antidepressants in inducing suicidality has been established in pediatric patients." http://www.fda.gov/cder/drug/antidepressants/SSRIlabelChange.htm
However, under pressure from the manufacturers of SSRI antidepressants whose $17 billion dollars in sales began to suffer, the FDA caved in, and changed the wording. Once again, the FDA is instrumental in hiding from physicians, parents, the scientifically established fact that the drugs - not the underlying condition--pose a suicide risk for children. The omission of this vital information from SSRI drug labels deliberately misleads the courts as well. [CNN report below]
Below, is Pfizer's letter to Canadian physicians acknowledging that the use of SSRI antidepressants has generated reports - in clinical trials and post-marketing reports - "in both pediatrics and adults, of severe agitation-type adverse events coupled with self-harm or harm to others. The agitation-type events include: akathisia, agitation, disinhibition, emotional lability, hostility, aggression, depersonalization. In some cases, the events occurred within several weeks of starting treatment."
Why has the FDA failed to ensure that US physicians and parents are as well informed about the hazards of widely advertised drugs as their Canadian neighbors are?
Contact: Vera Hassner Sharav
Health Canada Endorsed Important Safety Information on ZOLOFT (sertraline hydrochloride)
May 26, 2004
Subject: Stronger WARNING for SSRIs and other newer antidepressants regarding the potential for behavioural and emotional changes, including risk of self- harm
Dear Health Care Professional,
Pfizer Canada Inc., following discussions with Health Canada, would like to inform you of important safety information regarding the possibility that SSRIs (selective serotonin reuptake inhibitors) and other newer antidepressants may be associated with behavioural and emotional changes, including risk of self-harm.
The new Class warning incorporated in the Product Monograph of ZOLOFT* (sertraline hydrochloride) capsules is provided below.
POTENTIAL ASSOCIATION WITH THE OCCURRENCE OF BEHAVIOURAL AND EMOTIONAL CHANGES, INCLUDING SELF-HARM
Pediatrics: Placebo-Controlled Clinical Trial Data
Recent analyses of placebo-controlled clinical trial safety databases from SSRIs and other newer antidepressants suggest that use of these drugs in patients under the age of 18 may be associated with behavioural and emotional changes, including an increased risk of suicidal ideation and behaviour over that of placebo. The small denominators in the clinical trial database, as well as the variability in placebo rates, preclude reliable conclusions on the relative safety profiles among these drugs.
Adult and Pediatrics: Additional data
There are clinical trial and post-marketing reports with SSRIs and other newer antidepressants, in both pediatrics and adults, of severe agitation-type adverse events coupled with self-harm or harm to others. The agitation-type events include: akathisia, agitation, disinhibition, emotional lability, hostility, aggression, depersonalization. In some cases, the events occurred within several weeks of starting treatment.
Rigorous clinical monitoring for suicidal ideation or other indicators of potential for suicidal behavior is advised in patients of all ages. This includes monitoring for agitation-type emotional and behavioural changes.
Patients currently taking sertraline hydrochloride should NOT be discontinued abruptly, due to risk of discontinuation symptoms. At the time that a medical decision is made to discontinue an SSRI or other newer antidepressant drug, a gradual reduction in the dose rather than an abrupt cessation is recommended.
IIt should be noted that a causal role for SSRIs and other newer antidepressants in inducing self-harm or harm to others has not been established. The possibility of a suicide attempt is inherent in depression and other psychiatric disorders, and may persist until remission occurs. Therefore, high-risk patients should be closely supervised throughout therapy with appropriate consideration to the possible need for hospitalization. The updated warning informs practitioners that all patients being treated with SSRIs and other newer antidepressants should be rigorously monitored for clinical worsening, or onset/ worsening of agitation-type adverse events, or other indicators of potential for suicidal behaviour.
Sertraline hydrochloride is not indicated for use in the pediatric population.
New Information Added to the Consumer Information Section
The Consumer Information Section of the Product Monograph has been updated to reflect this new Class warning, and to advise patients that treatment with SSRIs and other newer antidepressants is most safe and effective when there is good communication with the treating physician about how the patient is feeling.
In February 2004, a scientific advisory panel set up by Health Canada was asked to provide the clinical practice perspective on the pediatric clinical trial safety data, and the spontaneous post-marketing reports for SSRIs and other newer antidepressants. The panel agreed that a contraindication was not warranted for these medications, and supported Health Canada's recommendation for stronger warnings, while providing suggestions and comments. The record of proceedings, and other information about the panel, can be found on Health Canada's website at : http://www.hc-sc.gc.ca/hpfb-dgpsa/tpd-dpt/sap_ssri_2004-02-20_rop_e.html .
Pfizer Canada Inc. continues to work closely with Health Canada to monitor adverse event reporting and to ensure that up-to-date information regarding the use of ZOLOFT (sertraline hydrochloride) is available.
The identification, characterization and management of drug-related adverse events are dependent on the active participation of healthcare professionals in adverse drug reaction reporting programs. Healthcare professionals are asked to report any suspected adverse reactions in patients receiving ZOLOFT (sertraline hydrochloride) directly to Pfizer Canada Inc. or Health Canada at the following addresses:
Pfizer Canada Inc.
P.O. Box 800
1 800 463-6001
Any suspected adverse reaction can also be reported to:
Canadian Adverse Drug Reaction Monitoring Program (CADRMP)
Marketed Health Products Directorate
Address Locator: 0701C
OTTAWA, Ontario, K1A 0K9
Tel: (613) 957-0337 or Fax: (613) 957-0335
To report an Adverse Reaction, consumers and health professionals may call toll free:
Tel: 866 234-2345
Fax: 866 678-6789
For other inquiries: please refer to contact information.
The http://www.hc-sc.gc.ca/hpfb-dgpsa/tpd-dpt/adverse_e.html AR Reporting Form and the http://www.hc-sc.gc.ca/hpfb-dgpsa/tpd-dpt/adr_guideline_e.html AR Guidelines can be found on the Health Canada web site or in The Canadian Compendium of Pharmaceuticals and Specialties.
Your professional commitment in this regard has an important role in protecting the well-being of your patients by contributing to early signal detection and informed drug use.
Any questions from healthcare professionals may be directed to the Pfizer Medical Information Group at Tel: 1 800 463-6001.
original signed by
Bernard Prigent, M.D.
Vice President & Medical Director
Pfizer Canada Inc.
*Trademark Pfizer Inc.
Pfizer Canada Inc. Licensee
FDA backs away from antidepressant warning
Change comes to light during murder trial of teen blaming Zoloft
By Jim Polk
Wednesday, February 9, 2005 Posted: 4:14 PM EST (2114 GMT)
CHARLESTON, South Carolina (CNN) -- The Food and Drug Administration has backed off its warning that antidepressants such as Zoloft, Paxil and Prozac can cause suicidal actions among children and teens taking those prescription drugs.
Instead, the FDA, in a revised warning posted last week on its Web site, changed the wording to say only that the drugs "increased the risk of suicidal thinking and behavior in short-term studies of adolescents and children" with depression and other psychiatric disorders.
News of the FDA's warning change surfaced Wednesday in testimony here in the murder trial of 15-year-old Christopher Pittman. The defense contends Zoloft drove him to kill his grandparents when he was 12.
Dr. Steve Romano, a psychiatrist and a vice president of Pfizer, which makes Zoloft, mentioned the FDA change at Pittman's trial while being questioned about the company's own clinical trials for Zoloft.
Limiting the warning language to a risk seen in studies, rather than saying the drugs actually could cause suicidal behavior in younger patients, is a significant retreat for the FDA and came after several months of lobbying by the pharmaceutical industry.
The agency has never approved Zoloft, Paxil or most similar drugs for use by younger patients with depression. Even so, many doctors prescribe them for children and teens. Prozac is the only such antidepressant approved to treat depression in children.
The version of the warning that the agency posted on its Web site in October included this sentence: "A causal role for antidepressants in inducing suicidality has been established in pediatric patients."
The latest version omits that sentence.
The sentence was not part of the boldface black-box warning placed at the start of the insert that accompanies any prescription, but instead appeared in the first paragraph of a separate section on "Suicide Risk" which appeared just below that black box.
The replacement sentence, however, appears as the first sentence inside the black box. That first sentence was broader in the original version, saying: "Antidepressants increase the risk of suicidal thinking and behavior in children." The new version qualifies that by inserting the phrase "in short-term studies."
Romano acknowledged that the wording change was preceded by an extended "dialogue" between his drug company and others, and the FDA.
Romano was called by the defense in the Pittman case to testify about suicide-related warnings issued both in Canada and the United States.
The FDA never has suggested there is any link between these drugs and violence against others -- the issue in the Pittman murder trial.
The trial is in its eighth day and appears likely to spill over into a third week, rather than go to the jury by this weekend, as originally predicted.