In recent years, antidepressants have faced growing criticism. Some argue these drugs don’t work, claim pharmaceutical companies have misled the public, and say antidepressants are prescribed too often simply to generate profit.
This controversy escalated after a 2023 review by Moncrieff and colleagues questioned the “serotonin hypothesis.” This long-held theory suggests that depression is caused by low levels of serotonin in the brain. The review found little convincing evidence to support this idea.
This raises an important question. If SSRIs, the most common antidepressants, are designed to raise serotonin levels, does this mean the medications are built on a flawed theory?
The answer is no. Antidepressants are not a scam, and they still help many people.
The discovery of antidepressants is a story of medical luck. In the 1950s, Swiss psychiatrist Roland Kuhn was testing a drug called imipramine on patients with schizophrenia. The drug didn’t help with schizophrenia, but surprisingly, it improved symptoms in patients who were also depressed. Imipramine had originally been created as an allergy medication.
This accidental discovery led researchers to investigate how the drug worked. They found that it increased the levels of several neurotransmitters, especially dopamine, noradrenaline, and serotonin, by stopping them from being reabsorbed into brain cells.
Drug companies then worked to refine this effect. In the 1970s, Eli Lilly developed fluoxetine, the first selective serotonin reuptake inhibitor (SSRI). It became known as Prozac and quickly became a widely used treatment for depression.
Importantly, scientists did not first assume that low serotonin caused depression. Instead, the theory came after they noticed that these drugs, which increased serotonin, helped improve mood. This led to the idea that serotonin might play a role in depression.
However, just because boosting serotonin can help some patients feel better doesn’t mean that low serotonin is the original cause of depression. Depression is a complex illness with many contributing factors.
Some studies, such as a 2024 paper by Arnone and colleagues, do show a link between serotonin and depression. But the connection is not strong enough to serve as a complete explanation. The serotonin hypothesis is now seen as an oversimplified way to explain depression and how SSRIs work.
This shift in thinking does not mean antidepressants are useless. The medications continue to help people with depression, even if the original explanation of how they work was too simple.
Researchers are now exploring other causes of depression, including brain inflammation, imbalances in other neurotransmitters, and brain cell growth. Some of these ideas were inspired by drugs like ketamine and psilocybin, which also produce antidepressant effects in unexpected ways.
Despite the ongoing search for better explanations, serotonin still appears to play an important role. It affects many processes in the brain, including sleep, appetite, stress, memory, and movement. Because of this, SSRIs influence more than just mood.
Depression remains one of the hardest mental illnesses to treat, especially with medications that interact with many systems in the brain. It’s not surprising that a simple explanation like “too little serotonin” doesn’t hold up to scientific scrutiny.
Scientific theories are meant to be tested and revised. The fact that the serotonin theory has been challenged is not a sign of failure. It shows that research is progressing.
Even if the original theory was flawed, antidepressants continue to help many people. They may not work for everyone, and they do have side effects. But for millions of patients, they remain a valuable and effective treatment.
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