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. 2001 Jun 16;322(7300):1446.

Jury finds drug 80% responsible for killings

Deborah Josefson
PMCID: PMC1173337

A US jury in Wyoming has found the British based pharmaceutical company GlaxoSmithKline responsible for a spate of family murders and a suicide committed by a patient taking the antidepressant paroxetine, which is marketed as Paxil in the United States and Seroxat in the United Kingdom.

The jury awarded $6.4m (£4.6m) to the surviving family of Donald Schell, a 60 year old man who killed his wife, daughter, and granddaughter before killing himself.

Mr Schell reportedly suffered from episodic depression but had not expressed suicidal or homicidal ideation or violent behaviour before being prescribed paroxetine, an antidepressant of the selective serotonin reuptake inhibitor class. Several years earlier he had been prescribed fluoxetine (Prozac), a related drug, but he was taken off that because he became extremely agitated.

In February 1998 he was prescribed paroxetine for mild depression and within weeks went on a murderous rampage. The jury found that the drug was 80% responsible for the four deaths.

The Wyoming decision was the first to find a drug company liable for the suicidal or homicidal actions of an individual taking its antidepressant. The jury's verdict re-ignites concerns over the safety of selective serotonin reuptake inhibitors and their possible association with violence.

It deals a serious blow to manufacturers of this popular class of antidepressants, which also includes fluoxetine and sertraline (Lustral in the United Kingdom and Zoloft in the United States).

Serotonin reuptake inhibitors were introduced in the late 1980s and early 1990s, and they quickly supplanted tricyclic antidepressants and monoamine oxidase inhibitors as the antidepressants of choice.

However, soon after they were introduced, a handful of reports of paradoxical reactions surfaced, including mania, psychosis, restlessness, and increased suicidal ideation.

Fluoxetine, the first selective serotonin reuptake inhibitor, received a lot of negative reviews in the popular press. In the early 1990s a few lawsuits were brought against Eli Lilly, the maker of fluoxetine, charging that the medication caused aggressive behaviour in a subset of patients, but the suits were settled out of court, dismissed, or won by the pharmaceutical company.

The negative publicity caused Eli Lilly to issue a "Dear Doctor" letter on 31 August 1990 to reassure physicians that no causal relation existed between increased suicidal tendencies and fluoxetine.

Selective serotonin reuptake inhibitors are generally considered to be safe and effective, but they can cause akathisia, or excessive internal restlessness, in a subset of patients. This akathisia is believed to contribute to subsequent violence.

In reaching its decision, the jury took into account literature on selective serotonin reuptake inhibitors and the testimony of David Healy, director of psychological medicine in Bangor, North Wales. Dr Healy served as an expert witness for the plaintiffs and testified that both his own research and that of GlaxoSmithKline showed that up to 25% of previously healthy volunteers who took selective serotonin reuptake inhibitors became extremely agitated.

In his own small studies of this class of antidepressants, conducted with volunteers who were not depressed and who were given sertraline, Dr Healy found that 33% felt better on the drug, 33% felt worse, and 33% didn't respond at all. Two previously non-suicidal and non-depressed volunteers became suicidal and depressed while on the drug.

A spokesman for GlaxoSmithKline, Alan Chandler, said: "We were surprised at the verdict. This is a tragedy caused by severe depression and not its treatment. There is no reliable scientific evidence linking the use of paroxetine to the events in this case or to violence generally."

He added that over 70 million patients had been treated with paroxetine without apparent problems. Indeed, it may be difficult to untangle causes and effects in cases of suicide and antidepressants.

GlaxoSmithKline plans to appeal against the verdict.

Historically, patients in the early stages of recovery from depression, especially "vegetative depression," have a slightly increased risk of suicide because the antidepressants give them more energy to carry out suicidal plans.


Articles from BMJ : British Medical Journal are provided here courtesy of BMJ Publishing Group

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