Manufacturer admits increase in suicidal behaviour in patients taking paroxetine

[Micklemouse]

BMJ 2006;332:1175 (20 May), doi:10.1136/bmj.332.7551.1175

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Manufacturer admits increase in suicidal behaviour in patients taking paroxetine

New York Jeanne Lenzer

GlaxoSmithKline announced last week that they had found an increase in suicidal behaviour in adults taking paroxetine (Paxil/Seroxat) compared with placebo. The conclusion was based on an analysis of patients aged 18-64 years in clinical trials.


The researchers found that 0.32% (11/3455) of people taking paroxetine for depression attempted suicide compared with 0.05% (1/1978) of depressed patients taking placebo (odds ratio 6.7, 95% confidence interval 1.1 to 149.4; P=0.058). One person in the paroxetine group successfully killed themselves. GlaxoSmithKline said the data should be interpreted with caution and that the “overall risk-benefit of paroxetine in the treatment of adult patients with MDD [major depressive disease] remains positive.”


The Glaxo study confirms the suggested link between suicidal behaviour and antidepressants in adults. In October 2004, the US Food and Drug Administration ordered drug companies to place a “black box” warning on all antidepressants, saying that suicidal behaviour might increase in children and adolescents taking the drugs. They requested all manufacturers of antidepressants to examine their data for a similar link among adults. The FDA is undertaking its own pooled analysis of adults taking antidepressants and is expected to release its results as soon as this summer.
In 2004, the Medicines and Healthcare Regulatory Agency advised physicians not to prescribe paroxetine or any other selective serotonin reuptake inhibitor to children. In light of the recent study by Glaxo, the agency issued a reminder to physicians on 10 May stating that “careful and frequent monitoring . . . is important in the early stages of treatment with paroxetine, especially if a patient experiences worsening of symptoms or if new symptoms arise after starting treatment.”


In August 2005, researchers in Norway obtained missing and unreported data from clinical trials of paroxetine and reported that there were seven suicide attempts among 916 patients taking paroxetine compared with one attempt in 550 patients taking placebo (www.biomedcentral.com/1741-7015/3/14). The researchers concluded that, “Patients and doctors should be warned that the increased suicidal activity observed in children and adolescents taking certain antidepressant drugs may also be present in adults.”

Glaxo rebutted the study findings at the time, in part because the “analysis was based solely on early data submitted to regulatory authorities in 1989.” However, the company provided the FDA with its own pooled analysis in March 2006, in which GSK researchers concluded that, “In adults with MDD (all ages), there was a statistically significant increase in the frequency of suicidal behaviour in patients treated with paroxetine compared with placebo.”


GSK sent a letter to doctors stating, “It is difficult to conclude a causal relationship between paroxetine and suicidality in adults due to the small incidence and absolute number of events, the retrospective nature of the analyses, and potential for confounding by the fact that the events of interest are a symptom of the psychiatric illnesses themselves.”


The current finding is the most recent of a series of setbacks for the drug. In December 2005, the FDA issued an alert stating that “paroxetine increases the risk of congenital malformations” in children exposed in utero to paroxetine during the first trimester, according to preliminary results of two recent studies. The most common malformation, according to a news release by GSK, is ventricular septal defect.


Another setback came when US marshals seized lots of a sustained release form of paroxetine (Paxil CR) in early March this year because of concerns about manufacturing quality that the FDA said could “pose a significant health hazard to consumers.”



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