The European perch (Image: Wikipedia Commons)

Benzodiazepines are some of the most heavily prescribed drugs worldwide. They include blockbusters like Xanax and Valium. Billions of benzodiazepine antidepressants, anxiolytics, hypnotics, sedatives and antipsychotics are doled out by doctors every year. They treat a variety of disorders ranging from insomnia to schizophrenia; they also commonly cause deaths from overdosing. But if you think all of them end up inside patients, it's worth looking at other places, especially since these drugs target proteins called GABA receptors which are found in a variety of other organisms.

The distribution of pharmaceuticals on such a large scale combined with imperfect filtration and chemical treatment systems inevitably means that some of them are going to end up in the environment, and over the years scientists have studied the effects of a variety of industrial and pharmaceutical entities on ecosystems and animal behavior. Now here's a group from Umea University in Sweden that found traces of an anxiety drug named oxepezam (marketed as Serax) in European perch fish from the River Fyris. And they observe some odd and potentially concerning effects.

They start by looking at the concentration of the drug in the water and inside the muscles of the fish. After confirming that the drug accumulates in the muscles of the fish to a significant extent (as do many greasy organic molecules), they exposed the fish to two concentrations of oxazepam; 1.8 microgram/L and 910 microgram/L. Given that the solubility of oxazepam in water is about 180 milligrams/L, this is a pretty dilute concentration which is confirmed by previous studies of other water bodies. The researchers studied the effects of the low and high concentrations on three kinds of fish behavior; activity (measured as number of swimming bouts), boldness (measured by tendency to enter a novel tank area) and sociability (measured by affinity of an individual fish to its fellow fishes).

The authors find that both concentrations of oxazepam affect the fish; they become bolder, more active and less social in case of the higher concentration whereas the lower concentration does not seem to affect boldness. To look at more direct behavioral effects of the drug, the authors looked at a dominant behavioral trait - feeding. The fish were exposed to 20 zooplankton before and after exposure to oxazepam and it was found that the fish exposed to the higher drug levels essentially engorged themselves on the zooplankton, a behavior you would expect from bolder and more active animals. On a larger scale this could mean that fish foraging in river waters with high concentrations of oxazepam would consume a food source much faster. Since the population of zooplankton would presumably remain unchanged, this could translate to a lot of hungry, bold, asocial fish competing for a limited food source. It's a situation I would try to avoid if I were a perch.

It's not clear what the large-scale implications of these observations are but the results warrant further investigation. Fish are part of an intricate ecosystem with multiple checks and balances, acting as both prey and predator. Just as more active and bolder fish consume zooplankton faster, so might they also appear more visible and attractive to predators. Their behavior could thus in turn affect the behavior and populations of predators which could further influence other organisms through a ripple effect.

There are caveats to be remembered when drawing conclusions from this study. This was a laboratory experiment so we don't know what the effects on real fish in the wild would be; although the authors also found oxazepam in the muscles of wild fish, real ecosystem would present hundreds, maybe thousands of other chemical compounds that could reinforce or counteract the observed behavioral tics. Seasonal changes and the rise and ebb of water levels would also affect drug levels and fish populations. Real ecosystems also contain many other diverse symbionts, predators and prey and it's hard to predict the behavior of one species in the presence of so many others. Finally, this study was limited to perch and we don't know how it affects the behavior and populations of other fish which are staples of human diets around the world, but this is something that does need to be investigated.

This paper does serve the important purpose of alerting us to the central fact that by targeting biological mechanisms which are common to the bodies of thousands of species, the drugs we design, market and overprescribe have very real - and unintended - effects on a wide distribution of living creatures. It's a paradigm that certainly deserves more attention. At the very least it indicates that we can never be too responsible in limiting the exposure of our favorite anxiety drugs to the environment.