Sometimes you’ll hear people argue that doctors don’t know how psych meds work, and therefore they shouldn’t be used. However, there’s a lack of clarity to these statements that, at least in my opinion, casts psychotropic meds in an unfair light.
What is the mechanism of action?
If we’re going to about how medications work, that incorporates a couple of distinct concepts.
Part A is what the drug does in the body. What receptors, enzymes, etc. does it interact with, and what is the nature of that interaction?
Part B is how that produces the therapeutic effect. Say we know drug A binds to receptor X – so what? How does that interaction with receptor X lead to a therapeutic benefit?
For most psychiatric medications, science has done a pretty good job of establishing Part A, i.e. what receptors they act at and what they do while they’re there. So to say we don’t know how they work, full stop, is misleading.
What we may be missing is the Part B, the so what.
Let’s look at ketamine as an example. It’s been around for a while as an anesthetic, and it’s known to work on NMDA and AMPA receptors, affecting the activity of the neurotransmitters glutamate and GABA. Great, so what? Well, it appears to boost levels of the protein brain-derived neurotrophic factor (BDNF), which promotes the creation of new synaptic connections in the brain.
Okay, but what’s the connection to ketamine’s antidepressant effect? That’s where things get more iffy, especially since other drugs that act the same way at NMDA receptors don’t have the same therapeutic effect as ketamine.
Another medication where there’s an element of mystery is lithium. Lithium does a lot of different things: it affects the enzyme inositol monophosphatase, it affects G-proteins that move substances in and out of cells, it regulates gene expression for growth factors, it affects downstream signal transduction cascades, and it affects the neurotransmitter GABA.
So, lithium gets around. Is it known exactly what part of its activity in the human body produces the therapeutic benefits? Nope. Does that make it a sketchy medication? No. Sure, it has side effects, but like any other medication, there needs to be an individual weighing of pros and cons.
How does this matter?
The key point here is that the medical field isn’t throwing meds at us without having any clue what they do in the body. And sometimes, the mechanism of action of the side effects is actually better understood than the therapeutic effects.
From a pragmatic perspective, what matters is whether or not a given individual gets the desired therapeutic effect from a given drug. When ketamine finally gets Health Canada approval I’m certainly not going to be waiting around for science to figure out which component of its activity is responsible for the therapeutic effect. I just want to feel better.
For more posts on psychiatric medications, the Psych Meds 101 series covers: