Serzone: New safety concerns ensures continued focus on antidepressants

Public Citizen, the US consumer group, has again called for the FDA to ban Bristol-Myers Squibb's Serzone, citing serious safety concerns. Serzone is not the first antidepressant treatment to have had its safety profile questioned. The case involving BMS has simply added controversy to an existing problem. The pharmaceutical companies involved are however, quick to point out the massive patient population benefiting from the use of such drugs.

Antidepressant treatments make up some of the most profitable products in the healthcare industry. Many of these high-profile drugs have nevertheless had to deal with separate attacks on their safety at some point or another. Whilst certain products have been linked to cases of suicide, the group as a whole have been alleged to be unsafe for use in children. Only Eli Lilly's Prozac has gained US approval for this indication.

The link between antidepressant drugs and suicidal tendencies has however, never been fully established. The leading pharmaceutical companies involved have sought to defend their respective treatments. But even with considerable data supporting their case the issue could end up being taken out of their hands.

Serzone pressure

Public Citizen first petitioned the US drug regulatory body in March 2003, presenting reports of 53 incidents of liver injury and 11 deaths among patients taking Serzone from December 1994 through March 31, 2002. The group's new appeal highlighted nine further cases of deaths related to liver failure in patients taking Serzone during the period from April 1, 2002 to May 12, 2003.

The controversy regarding Serzone's availability in the US is particularly significant because the drug has already been withdrawn in Europe and is about to be pulled from the Canadian market. Public Citizen has therefore asked why the FDA is apparently lagging behind other countries in drug safety.

The group's concerns have also increased due to last month's approval of several generic versions of Serzone. Public Citizen however, was careful in attacking only Serzone. It explained that the World Health Organization and Health Canada recently compared a number of popular antidepressants and found only Serzone linked to an increased risk for serious liver injury.

Other antidepressant drugs have therefore sought to distance themselves from Serzone. Although the Bristol-Myers drug is a member of the serotonergic group of antidepressants it is not a selective serotonin reuptake inhibitor (SSRI), like the market leaders, Paxil, Zoloft and Prozac.

The safety of the SSRIs

Despite this distinction however, Bristol-Myers has not been the only company to come under fire. Although regarded as having a superior side effect profile to older antidepressants such as the tricyclic antidepressants, the issue of withdrawal symptoms, possible dependence and suicidality has overshadowed the SSRIs and been the subject of much media attention.

GSK's Paxil, worth $3.1 billion, has been at the center of this controversy and faces several lawsuits alleging it can cause severe withdrawal reactions. GSK maintains that the medicine is safe, effective and non-addictive.

Over the last ten years Eli Lilly has faced over 300 lawsuits based on the supposed side-affect problems of Prozac. The most recent case to be brought against Prozac alleged that the drug can cause suicide in those patients who are unable to break down Prozac's main ingredient, fluoxetine. The Indianapolis drug manufacturer also stands accused of failing to properly warn the public about the potential side-affects of Prozac. As with the other cases, Lilly has firmly denied any such claims regarding Prozac.

Patient advocacy groups have also fought against the use of SSRIs in children. This level of pressure led to the decision by GlaxoSmithKline and Wyeth to add labeling to their respective drugs, Paxil and Effexor, warning against their use in children under 18.

Experts to decide?

Lilly's Prozac has been approved for use in adolescents however. This has added to the uncertainty surrounding the use of SSRIs and a definitive conclusion still appears some time away.

The FDA is currently reviewing study data on eight antidepressant drugs although the agency appears to have softened its recent stance against using GlaxoSmithKline's Paxil in children. The FDA is now said to be convening a panel slated to meet in February, to examine the possible relationship of the drugs to suicide.

Regulators in the UK have found it no easier to come to a decision on the safety of antidepressant drugs. At the beginning of 2003 it was announced that the Department of Health (DoH) had assembled an expert panel to review the safety of SSRIs. By April however, this panel had been dissolved following claims of potential bias.

The DoH was left with little choice but to begin planning to appoint a new expert panel. The decision means further delays for the completion of the review and ongoing questions as to the safety of the SSRIs.

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