FDA Requires Black Box Warnings For Antidepressant Serzone
Posted By Glenn Johnston
9-8-2005
In 1994, the antidepressant drug Serzone was approved by the Food and Drug Administration (FDA). Also known as nefazodone HCl, Serzone was first introduced by Bristol-Myers Squibb Co. with the claimed benefit of reduced sexual side effects commonly associated with antidepressants. However, after 2000, Serzone began to face increased criticism for contributing to liver failure. Later, Serzone was once again targeted, along with 10 other antidepressants, for possibly having a role in worsening the symptoms of depression and increasing the risks of suicide.
Black Box Warning for Risk of Liver Failure
In 2000-2001, experts, in conjunction with the FDA, estimated that individuals who use Serzone to battle depression or anxiety are three to four times more likely to suffer liver failure. As a result, in December 2001, the FDA required Bristol-Myers Squibb to put a "Black Box Warning" on all Serzone labeling prior to distribution. A Black Box Warning is reserved only for the most serious drug side effects and acts as an automatic indicator instructing physicians to prescribe the drug only as a last resort (e.g., in life threatening cases). In January 2002, Bristol-Myers Squibb issued a drug warning letter to all health care providers informing them of life threatening liver failures occurring in patients treated with Serzone.
Serzone Pulled From Other Markets
In February 2003, Bristol-Myers Squibb pulled Serzone from the European markets after many countries banned the drug due to links with liver failure. Later that year, Serzone was also withdrawn from Canadian pharmacies for the same reason. However, the FDA permitted Bristol-Myers Squibb to continue marketing Serzone in the U.S. as long as the drug was labeled with the appropriate Black Box Warning.
Worsened Symptoms of Depression and Suicide Risks in Youths
Later, the focus shifted from liver failure to new adverse health implications associated with Serzone. Along with 10 newer-generation antidepressant drugs, Serzone was linked to the possibility of causing worsened symptoms of depression and increased suicidal tendencies in children and teens.
The 10 antidepressants targeted by the FDA include:
- Prozac
- Zoloft
- Paxil
- Luvox
- Celexa
- Lexapro
- Wellbutrin
- Effexor
- Serzone
- Remeron
In March 2004, the FDA issued a public health advisory outlining the new developments. The FDA also instructed manufacturers of the above antidepressants to "strengthen their labeling" to include a warning recommending close observation of young patients taking the antidepressants, but did not expressly link any of the drugs to suicidality. In June 2004, Bristol-Myers Squibb issued another warning letter to health care providers informing them of the latest information.
New Serzone Warning Label
Together with the FDA, Bristol-Myers Squibb created a new label to advise prescribing physicians and the public about the risks associated with Serzone treatment. Warnings of liver failure remained in a "boxed warning" in acknowledgment of the fact that Serzone has been linked to that risk. A new warning, regarding antidepressants generally, is placed in a separate revised "WARNINGS" section of the label. The second warning states, in part, that while there are concerns that antidepressants "may have a role in inducing worsening of depression and the emergence of suicidality," a causal role has yet to be established.
Further Testing
At the FDA's direction, Columbia University assembled an international panel of pediatric suicidality experts to analyze several studies testing links between antidepressants, including Serzone, and increased suicide rates in children and adolescents. FDA officials indicated that there appears to be such a link.
Serzone Pulled from U.S. Market but Generic Forms Remain
Citing declining sales, Bristol-Myers Squibb announced that it would stop selling Serzone in the U.S. as of June 2004. However, Serzone is not "banned" by the FDA and is still listed with a marketing status as being "available by prescription." Thus, although Serzone may not be sold in the U.S., it might still be available to fill or refill prescriptions for several months. Also, generic forms of nefazodone remain available in the U.S.