Can Drugs Relieve the Societal Burden of Psychopathology?

There has been much progress in psychopharmacology in recent decades. But there are some reasons to believe that medications are limited in their abilities to make society mentally healthier. One problem has to do with efficacy. Several meta-analyses have concluded that the advantage over placebo conferred by antidepressants in the treatment of depression, although statistically significant with sizeable samples, is only about 2 points on a 50-point scale. Given the dependence upon randomized controlled trials, much of what we know about efficacy of psychotropic medications is information about what happens in about 12 weeks, but psychiatric conditions tend to be chronic, and medications often need to be maintained for years to treat them; we know little about the long-term effects. However, we do know enough to recognize a problem over and above efficacy: oppositional tolerance. This refers to the tendency of biological systems to oppose the effects of medications, i.e., to downregulate the pathways drugs enhance, and to upregulate the ones they oppose. This can lead to withdrawal effects. Oppositional tolerance, which is a much bigger problem with some drugs than others, can lead to permanent changes, such as those of tardive dyskinesia and supersensitivity psychosis, and it has been hypothesized to worsen the course of psychiatric illness.