Even clinicians call for an approach to alleviating depression that does not rely on antidepressants, which research has found to have questionable effectiveness and increased risks of serious side effects.
Deeply depressed patients who do not get symptom relief after trying two or more antidepressants at the recommended dose and length of time are typically considered in psychiatry as having “treatment-resistant depression,” but research indicates the drugs themselves may be to blame for the treatment failure.
A new study sheds light on the extent to which antidepressants failed to relieve symptoms in patients experiencing deep depression. Researchers at the University of Birmingham in the U.K. found that half (48%) of 5,136 seriously depressed adults were considered treatment-resistant, with four out of 10 (37%) of them having tried four or more antidepressants without relief. What’s more, the researchers noted that each failed treatment compounded patients’ depression severity.

Even clinicians interviewed as part of the study called for a different strategy for treating depression. The researchers described that new strategy as “a holistic, patient-centered treatment approach, as the ‘one size fits all’ approach, typically characterized by an overreliance on pharmacological solutions, [is] inadequate.”
Other research has indicated that antidepressants have limited, if any, benefit over dummy pills (placebos). In 2023, researchers re-evaluated data from an influential study on antidepressants, funded by the National Institute on Mental Health and conducted from 2000-2004, which had found a 67% remission rate after the use of up to four antidepressants. The recent re-analysis of the data, however, corrected methodology used in the earlier study and found that the remission rate was just 35%, meaning only one in three people using antidepressants achieved remission of their symptoms.
Another recent study found even less benefit to patients from antidepressants. A 2020 review of evidence on the effectiveness of the drugs concluded not only that “antidepressants seem to have minimal beneficial effects on depressive symptoms” in patients with deep depression, but that the drugs also “increase the risk of both serious and non-serious adverse events.”
“Antidepressants should not be used for adults with major depressive disorder before valid evidence has shown that the potential beneficial effects outweigh the harmful effects,” the researchers in that study advised.
Adverse effects of antidepressants include weight gain, nausea, insomnia, agitation, emotional blunting, sexual dysfunction, suicide and violence. An analysis of the FDA’s Adverse Event Reporting System in 2010 found that 31 out of 484 prescription drugs were disproportionately associated with violence, and 11 of those 31 were antidepressants.
On discontinuing antidepressants, patients may experience withdrawal symptoms that can be severe and long-lasting. One study found that more than half (56%) of the people who attempt to come off antidepressants experience withdrawal effects, with nearly half (46%) of them describing the symptoms as severe. It is not uncommon for the withdrawal effects to last for weeks, months, or even longer.
In 2018, a citizen petition from medical researchers was delivered to the U.S. Food and Drug Administration (FDA), calling on the agency to strengthen the warning on antidepressants’ labeling to adequately convey the serious risk of persistent, even permanent sexual dysfunction after the use of antidepressants is stopped.
Antidepressants are the most widely prescribed class of psychiatric drugs. Currently, over 11% of U.S. adults – one in nine – are prescribed medication for depression, with twice as many women (15%) as men (7%) using the drugs, according to a new report from the Centers for Disease Control and Prevention (CDC).
Antidepressants are prescribed for nearly 6 million young people aged 0- 24, for whom the U.S. Food and Drug Administration (FDA) has required a warning in the drugs’ prescribing information about the increased risk of suicide from using the drugs.
A landmark 2022 study found that, despite decades of brain research into the widely promoted theory of a chemical imbalance in the brain causing depression, there is no conclusive evidence of a chemical imbalance or other brain abnormality causing depression. This finding calls into question the prescribing of antidepressants, the researchers who conducted that study wrote, as antidepressants have been prescribed to fix a supposed chemical imbalance.
For years, psychiatrists were complicit in promoting the chemical-imbalance theory, a 2022 study concluded, referencing the considerable coverage the theory received in psychiatric and psychopharmaceutical journals.
“The FDA, which is responsible for ensuring pharmaceutical drugs are safe, must take immediate action due to the growing body of research indicating that adverse effects when using or attempting to stop using antidepressants are more widely experienced and potentially more severe than current prescribing information and medication guides indicate,” said Anne Goedeke, president of the CCHR National Affairs Office. “FDA action is long overdue on this urgent public health issue.”
The content on this site is for informational purposes only and is not intended to substitute for personal medical advice given by a licensed physician. Anyone wishing to discontinue or change the dose of an antidepressant is cautioned to do so only under the supervision of a physician because of potentially dangerous withdrawal symptoms or other complications.