Monday, October 5, 2009

Which is better, a simple drug or a complex drug?

Here is another critique of medication marketing trends in psychiatry:

I agree quite strongly that there has been a collusion between:
- psychiatrists who eagerly yearn to meaningfully apply their knowledge of psychopharmacology, pharmacokinetics, neurotransmitter receptor binding profiles, etc. (to justify all those years of study)
- and pharmaceutical company sales reps

I can think of attending many academic rounds presentations in which a new drug would be discussed, for example a newly released SSRI. During the talk, there would be boasting about how the new drug had the highest "receptor specificity", or had the lowest activity at receptors other than those for serotonin (e.g. for histamine or acetylcholine).

These facts that I was being shown, while enjoying my corporate-sponsored lunch, were true. But they were used as sales tactics, by-passing clear scientific thought. Just because something is more "receptor-specific" doesn't mean that it works better! It may in some cases be related to a difference in side effects. Yet sometimes those very side-effects may be related to the efficacy of the drug.

By way of counter-example, I would cite the most effective of all antipsychotic medications, clozapine. This drug has very little "receptor-specificity." It interacts will all sorts of different receptors. And it has loads of side effects too. Perhaps this is part of the reason it works so well. Unfortunately, this does not sit well with those of us who yearn to explain psychiatric medication effects using simple flow charts.

Similarly, the pharmacokinetic differences between different medications are often used as instruments of persuasion--yet often times they are either clinically irrelevant, of unproven clinical relevance, or even clinically inferior (e.g. newer SSRI antidepressants have short half-lives, which can be advantageous in some regards; but plain old Prozac, with its very long half-life, can be an excellent choice, because individuals taking it can safely skip a dose without a big change in the serum level, and ensuing side-effects).

I should not be too cynical here -- it is important to know the scientific facts that can be known about something. Receptor binding profiles and half-lives, etc. are important. And it can be useful to find medications that have fewer side-effects, because of fewer extraneous receptor effects. The problem is when we use facts spuriously, or allow them to persuade us as part of someone's sales tactic.

So, coming back to the question in the title, I would say it is not necessarily relevant whether a drug works in a simple or complex way. It is relevant whether it works empirically, irrespective of the complexity of its pharmacologic effects.

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