Warnings about the safety of the SSRI class of antidepressants may not have been issued in a timely manner because of the drug approvals process, Professor David Healy of Cardiff University has argued in this week's issue of the British Medical Journal.
Concerns over a link between selective serotonin reuptake inhibitors and an increased risk of suicidal thoughts and behaviour first arose in 1990 after a published article spotlighted that GlaxoSmithKline's Seroxat/Paxil (paroxetine) could trigger suicidal acts. Further trials pointed to a doubling in the suicide rate between placebo and active treatment but, says Prof Healy: “It was only in a recent study reviewing over 700 trials that this difference became significant.”
The issue of SSRI safety was inadvertently pushed into the limelight by GlaxoSmithKline in 2004, after the US Attorney General, Eliot Spitzer, sued the firm saying it had withheld important data concerning the safety of Paxil - then one of the biggest drugs in its pipeline. The move not only triggered global efforts to make all data publicly available, but ensured the entire class of SSRIs came rubber-stamped with a black box warning alluding to their raised risk of suicide in both children and, later, adults. It also dealt a swift blow to the market, destabilizing the dominant position of the SSRIs, and triggering a report this week predicting contraction of the market over the next years.
Adds Prof Healy: “Trials in children conducted in the mid-1990s show a doubling of the risks of suicidal acts with SSRIs. These results have recently formed the basis of warnings about the use of SSRIs in children. Trials in adults show a similar risk ratio, yet, until May 2006, no warnings were issued for adults. This trend should have been seen by both companies and regulators as something that required investigation.”
Instead, he notes, the finding was obscured by the way in which results were presented to the regulators, as well as the regulators' “rigid interpretation” of the data, which may have delayed warnings over their use.
Prof Healy now believes that the risk posed by SSRIs on suicidal thoughts and behaviour is more than double that of placebo (2.6 times greater) and calls for new ways to evaluate the risks and benefits of compounds. This is echoed by BMJ editor, Fiona Godlee, who argues in a separate editorial that the drug industry is overpowerful and under-regulated, and suggests a radical solution to prevent drug companies from evaluating their own products.