A commission for the Food and Drug Administration voted in favour of forcing manufacturers including Pfizer, Wyeth and GlaxoSmithKline to add the government's toughest warnings, highlighted in a black box, to the drugs' labels indicating that antidepressants caused young people to become suicidal.
The outcome signifies a major setback to manufacturers of this class of drug - the selective serotonin reuptake inhibitors - which include Pfizer's Zoloft (sertraline); Eli Lilly's Prozac (fluoxetine); GSK's Paxil (paroxetine) and Forest Laboratories' Celexa (citalopram). They all work by allowing more of a neurotransmitter called serotonin to remain in the brain. The warnings are likely to affect sales of these drugs which have long been global bestsellers.
The recommendation will be sure to cast doubts over the confidence of antidepressants which have come under recent scrutiny after practices of major pharmaceutical companies hit the headlines on both sides of the Atlantic
Drugmakers came under pressure to disclose tests suggesting a rise in suicidal behavior, which ranged from attempting suicide to telling a doctor of wanting to do so. GSK, Europe's largest drugmaker, in August settled a lawsuit filed by New York Attorney General Eliot Spitzer over the reporting of safety data on the antidepressant Paxil.
Research into a new class of antidepressant or a form of treatment with a novel mechanism of action has not been as productive as hoped since current drugs produced by the larger pharmaceutical companies essentially have a stranglehold on the market. This has made it doubly difficult for new drugs to make an impact.
Better understanding of pathophysiology of depression has lead to several truly novel pipeline concepts. The modification of neuropeptide (substance P, corticotrophin-releasing factor), nicotinic acetylcholine, dopaminergic, glucocorticoid, ä-opioid, cannabinoid and cytokine receptors, gamma-amino butyric acid (GABA) and intracellular messenger systems, transcription, neuroprotective and neurogenic factors, may provide an entirely new set of potential therapeutic targets, giving hope that further major advances might be anticipated in the treatment of depressive disorder soon.
Recently Eli Lily's antidepressant, Cymbalta (duloxetine), which works by inhibiting the reuptake of both serotonin and norepinephrine, was given FDA approval in August of this year. However, convincing physicians that it is an improvement on Wyeth's older drug Effexor (venlafaxine) - which claims a similar dual mechanism of action - may prove challenging. Lilly needs to position duloxetine as an alternative first-line therapy to SSRIs, and Datamonitor forecasts revenues of $2.1 billion by 2011.
Merck's aprepitant is expected to be the first drug from the NK receptor antagonists, a completely new class of antidepressants, to hit the market. Its launch, predicted in 2006, will precipitate an influx of similar compounds to the market, presenting a major threat to the leading position of SSRIs in first-line therapy.
Despite the looming patent expiries of several leading antidepressants by 2008, pharmaceutical companies are finding it increasingly difficult to develop novel compounds to replace these products. New strategies are needed to prevent a decline in the antidepressant market. Companies need to begin focusing on the development of compounds with new modes of action and targeting treatment resistant patients.