How Do Antidepressants Work?

This video explores the history and development of antidepressants, starting from their accidental discovery in the 1950s to the creation of SSRIs like Prozac. It discusses the chemical imbalance theory and how these drugs target neurotransmitters to alleviate depression, while also addressing the reduction of stigma around mental health.

Pause the video now if you'd like to read more about how antidepressants work. In the 1950s, the discovery of two new drugs sparked what would become a multi-billion dollar market for antidepressants. Neither drug was intended to treat depression at all. In fact, at the time, many doctors and scientists believed psychotherapy was the only approach to treating depression. The decades-long journey of discovery that followed revolutionized our understanding of depression and raised questions we hadn't considered before. One of those first two antidepressant drugs was iproniazid, which was intended to treat tuberculosis. In a 1952 trial, it not only treated tuberculosis, it also improved the moods of patients who had previously been diagnosed with depression. In 1956, a Swiss clinician observed a similar effect when running a trial for imipramine, a drug for allergic reactions. Both drugs affected a class of neurotransmitters called monoamines. The discovery of these antidepressant drugs gave rise to the chemical imbalance theory—the idea that depression is caused by having insufficient monoamines in the brain's synapses. Iproniazid, imipramine, and other drugs like them were thought to restore that balance by increasing the availability of monoamines in the brain. These drugs targeted several different monoamines, each of which acted on a wide range of receptors in the brain. This often meant a lot of side effects, including headaches, grogginess, and cognitive impairments, including difficulty with memory, thinking, and judgment. Hoping to make the drugs more targeted and reduce side effects, scientists began studying existing antidepressants to figure out which specific monoamines were most associated with improvements in depression. In the 1970s, several different researchers converged on an answer. The most effective antidepressants all seemed to act on one monoamine called serotonin. This discovery led to the production of fluoxetine, or Prozac, in 1988. It was the first of a new class of drugs called Selective Serotonin Reuptake Inhibitors, or SSRIs, which block the reabsorption of serotonin, leaving more available in the brain. Prozac worked well and had fewer side effects than older, less targeted antidepressants. The makers of Prozac also worked to market the drug by raising awareness of the dangers of depression to both the public and the medical community. More people came to see depression as a disease caused by mechanisms beyond an individual's control, which reduced the culture of blame and stigmatization surrounding depression. And more people sought help. In the 1990s, the number of people being treated for depression skyrocketed. Psychotherapy and other treatments fell by the wayside, and most people were treated safely.