Fashionable pharmaceuticals

The pharmaceuticals industry has an obsession with novelty. We want better drugs with fewer side-effects, but too often newness is correlated (wrongly) with an improvement in quality. One new drug that is twice as good at treating an illness as its predecessor is better than five drugs each offering a one per cent improvement on the first. ‘New’ drugs which appear on the market often seem to be derivatives of the well-tested substances which precede them and not genuinely novel drugs.

Consider escitalopram, a relatively new SSRI antidepressant. This is not a new drug in any meaningful way—rather, it is an enantiomerically pure form of the older, off-patent antidepressant citalopram. (In chemistry, a chemical’s connectivity—the order in which groups are bonded to one another—is referred to as its stereochemistry, and chemicals can have different forms or _enantiomers _as a result of these different ways of connecting the groups together.) Citalopram is a mixture of two enantiomers; isolate one and you’ve got escitalopram.

While escitalopram does seem to have better clinical efficacy at treating depression, it can’t really be said to be new in the way that, say, fluoxetine (Prozac) was when it hit the market in the late 1980s. Fluoxetine was seen as revolutionary when it was introduced, but its efficacy—and that of its more modern siblings—is still only barely better than placebo. Is it possible that nothing better has come along in more than twenty years?

A number of other drugs—amineptine, tianeptine, moclobemide and selegiline among them—have shown great promise in treating depression and, may indeed be suitable for general mood enhancement. Amineptine was withdrawn from the market because of its slight stimulant effects, never to be manufactured again. (Surely a substance which could genuinely and consistently improve one’s mood would be addictive by definition?)

The other three drugs have been shown to be promising antidepressants and mood enhancers but there seems little interest in comparing their efficacy with that of fluoxetine, the de facto treatment for depression in a number of countries. We are eager to test new drugs but no-one is willing to spend money testing ‘old’ drugs. Tianeptine isn’t even licenced for sale in the US, presumably because it is now off-patent and no company has any incentive to push for FDA approval.

Yohimbine is another interesting drug which languishes in scientific obscurity. Potentially quite a useful aphrodisiac and treatment for erectile dysfunction, this study into its effectiveness asks why so little data on it is available, concluding that its off-patent status is a serious disincentive for further investigation into its clinical efficacy:

Despite such a long history and encouraging activity, the drug has not yet been subjected to scientifically rigid human clinical trials. … Recent studies have been designed with a lack of insight and complete disregard of those fundamental studies. … Dose-response investigations are not available, alternative routes of administration have not been investigated… Synergistic activity with other drugs was last studied nearly four decades ago. Assessments of various populations were carried out in very limited cohorts and only in the most general terms. …

Yohimbine is an old drug. As such it does not enjoy patent protection or commercial viability. Until molecular/formulation changes can be brought about … serious investigation of the drug will remain in limbo.

If big pharma isn’t going to look into vintage pharmacotherapies, shouldn’t governments be willing to do so? If the purpose of bodies like NICE is to find the most effective treatment at the lowest cost, don’t they have an incentive to investigate other drugs; to scour the literature for candidate substances and fund studies of drugs which showed promise but were left languishing?