Psychotropic Base Rates: The Argument From Antibiotics

The obscure antiprotozoal drug suramin has the prettiest molecular structure I’ve ever seen. It also has some evidence as a potential treatment for autism based on a cell danger response model of the condition.

I’m not going to get too excited here, because there are a lot of things that can cure stuff in mice. Still, one has to ask – an antiprotozoal? Really?

Protozoa are primitive little parasites kind of like bacteria. The most famous is plasmodium, which causes malaria. There’s not much reason an antiprotozoal drug should cross-react with the brain, so if it does treat autism it’s probably just a coincidence.

But it’s a pretty common one. I’ve already noted how an antibiotic used to treat acne, minocycline, is a promising schizophrenia treatment. The news article on such is called “Scientists Shocked To Find Antibiotics Alleviate Symptoms Of Schizophrenia”, but maybe by this point they should start being less shocked.

Off the top of my head, I can think of two other antibiotics with a significant psychiatric role. Iproniazid, the first antidepressant ever discovered, was originally used as an anti-tuberculosis drug – and just by eyeballing the chemical structure it’s pretty easy to see the relationship to current-mainstay-of-tuberculosis-treatment isoniazid. There are records – amusing in retrospect – of doctors remarking on how unusually happy and excited patients were to finally be getting treatment for their tuberculosis. Eventually someone put two and two together. realized the drug itself was a mood-lifting agent, and the antidepressants were born.

Cycloserine is a totally different antitubercular drug that doesn’t even share a chemical structure or mode of action with iproniazid. Nevertheless, it seems to affect classical conditioning in interesting ways, which makes it of use to psychiatrists. The most exciting possibility is that it speeds up the extinction response, meaning it could theoretically help someone “unlearn” behavior. There’s a common use – which the evidence only ambiguously supports – where you use it to treat something like social anxiety disorder by having a patient take it in relatively safe social situations. When nothing bad happens (hopefully), the cycloserine speeds up the usual process of “unlearning” the social situation-fear link and the patient gets better more quickly than if they had to become comfortable with crowds the old fashioned way. There are also some proposed uses regarding cocaine and other drug addictions.

And these are just the ones with good psychiatric effects. Less positive psychiatric effects are a dime a dozen in antibacterials and antiprotozoals – for example, people on mefloquine do some pretty weird stuff.

There’s no really good reason why antibiotics should have psychiatric effects. As mentioned before, beyond the fact that we’re selecting for bioactive chemicals here, it’s probably just coincidence. But that itself is a very interesting finding. If we think of antibiotics as chemicals chosen at random – as far as psychiatry is concerned – that means that random chemicals will often change mental processes around in important ways.

This shouldn’t be surprising – the brain is full of stuff and pretty easy to chemically disrupt. But it’s worth remembering. A lot of skepticism about new drugs – or new toxicity claims – comes from low base rates: the expectation that most chemicals are not active medications. But in psychiatry, the base rates might be higher than we think.