Forced Swim Tests on Animals Under Scrutiny
The results of animal studies in biomedical and behavioral research often do not translate to humans. A particular animal test used in depression research has recently been scrutinized for this reason.
While researchers have been eager to find treatments for depression, a condition affecting more than 264 million individuals around the world, they often rely on a “forced swim test” to determine whether a compound might serve as a potential antidepressant.
In the forced swim test, rodents are placed in a pool of water, usually for 5-15 minutes. During this time, the animals alternate between swimming and floating. Researchers have attributed the more passive floating posture with “despair” and depressive-like behaviors. For the purposes of this test, researchers compare how long the animal swims versus floats when given the compounds.
There have long been concerns about this test from a purely scientific standpoint, as there may be other explanations as to why the animal swims or floats. From an ethical standpoint, the test is suspect because the rodents are neither able to escape from the container of water nor provided with a place to rest. Animal researchers have defended this test, citing rodents’ ability to swim well and for extended periods of time. Some have even called this test the “gold standard” animal test for depression.
A recent study in Drug Discovery Today, however, looked into how accurate the forced swim test is as a preclinical screen for antidepressant drugs. Researchers conducted a retrospective analysis, focusing on available data from pharmaceutical companies, to see whether the forced swim test correctly informed human clinical trials.
The researchers focused on data from the 15 pharmaceutical companies with the largest generated revenue. They compared the results of the forced swim test with the results and robustness of human data to see if data from the forced swim test likely predicted human clinical efficacy.
Of the 109 compounds tested for treating antidepressant behavior using the forced swim test, only 28% were further investigated for effects on depression in people. Of those compounds, only 23% were predictive of the outcome in humans. And none of those compounds have been marketed to treat human depression.
The authors concluded that the forced swim test is not a reliable screening tool for antidepressant drugs by pharmaceutical companies and recommended that its use be suspended while more data are collected. They further recommended that this controversial test be discontinued if the collection of additional data found similar results.
We are encouraged to see researchers examining—and rethinking—the effectiveness of animal tests, because studies like this can highlight the problems of using animal research to find treatments for humans. We hope that retrospective analyses such as these will be conducted for other common animal tests, as issues with those tests are likely to be raised as well. As the evidence continues to mount regarding the inefficacy of animal tests, the impetus to move to more predictive—and humane—methods will follow.
E.R. Trunnell, E.R and Carvalho, C. “The forced swim test has poor accuracy for identifying novel antidepressants.” Drug Discovery Today, 2021.