Because researchers have had limited ability to measure how potential psychiatric drugs affect the biology of lab animals, they've "concocted" tests based on the way existing drugs affect animal behavior, says Steven Hyman, director of the Stanley Center for Psychiatric Research at the Broad Institute of Harvard and MIT.
One conventional assay for antidepressants, for example, is called the "forced swim test.
When rats given the commonly used drug imipramine, which was invented in the 1950s and is still considered one of the most effective medicines for depression, are dropped in a bucket of cold water, they swim longer before giving up.
The animals' propensity to stop struggling has been rationalized as a measure of "behavioral despair," Hyman
says, but there's actually no proof that the behavior in the test reflects human depression.
Though the swim test has been used for 50 years to test antidepressants and is still widely used, all it probably does is select for drugs that mimic the effects of imipramine in allowing a rodent to swim longer, he
That has led to a series of "me-too drugs."
The discovery of new psychiatric drugs is "dangerously stalled," Hyman
says: in terms of efficacy, antidepressants "maxed out" in the 1950s and antipsychotics in the 1960s.
So far, researchers have identified hundreds of genetic variants associated with increased risk for schizophrenia, and Hyman
guesses the number could go as high as a thousand.