Antidepressants are some of the most commonly prescribed medicationsin rich countries, including the United States, Canada, the United Kingdom and much of western Europe.

The question of what happens when a person stops taking these drugs, which are typically not prescribed for long-term use, has been controversial since they were identified in the 1950s.

Now, a new study published Wednesday in the journal The Lancet Psychiatry, has found that 14% of people — roughly one in six — who discontinued antidepressants experienced withdrawal symptoms such as dizziness, headaches, nausea, insomnia and irritability.

The one-in-six figure is lower than some researchers who study antidepressants say they expected.

"It will be gratifying to know rates of withdrawal are nowhere near as high as reported [at around 50%]," Sameer Jauhar, a psychiatrist at King's College London who specializes in affective disorders, said in a press statement. Jauhar was not part of the study.

Nonetheless, for those who experience them, withdrawal symptoms "are real and patients need to be informed, monitored and helped if [they] occur," lead author Christopher Baethge, a psychiatrist at the University of Cologne in Germany, stressed in a press statement.

Low incidence of severe symptoms

The meta-analysis, which is the most comprehensive to assess the prevalence of antidepressant discontinuation symptoms to date, included 79 scientific studies featuring a total of 21,002 adult participants.

The studies included 44 randomized control trials and 35 observational studies related to antidepressant discontinuation symptoms published between 1961 and 2019.

The authors estimate that around one in seven people reported experiencing at least one symptom after stopping antidepressants, while a small number — around one in 35 — reported severe symptoms.

"Severe discontinuation symptoms occur much less, but should be taken seriously, and are important as many millions of patients take antidepressants. Unclear is which patients will suffer from (severe) discontinuation symptoms," said Eric Ruhé, a psychiatrist at Radboud University Medical Center in the Netherlands, who was not involved in the study.

It was also unclear from the study how long withdrawal symptoms might last after cessation of antidepressants, but Baethge said research indicates "they often resolve after two to six weeks, or when antidepressants are resumed."

The authors found that the medications desvenlafaxine, venlafaxine, imipramine and escitalopram were most often linked to withdrawal symptoms. Fluoxetine and sertraline had the lowest rates of discontinuation symptoms.

What causes antidepressant discontinuation symptoms?

Most antidepressants belong to a group of drugs known as selective serotonin reuptake inhibitors (SSRIs).

SSRIs work by blocking serotonin reuptake in the brain, meaning more serotonin is around to act on brain cells.

Scientists don't fully understand how withdrawal symptoms arise, but one theory is that "if you take away the increased serotonin by stopping SSRIs, this leads to the withdrawal symptoms," said Baethge.

Fluctuations in the level of serotonin signaling in the brain can impact a range of brain states, like sensory perception, emotional states and sleep-wake states. But how withdrawal of SSRIs relates to specific symptoms like dizziness, headaches or insomnia remains unclear.

Some theories related to a link between serotonin and depression have been criticized as oversimplified by researchers. Scientists are now developing more comprehensive theories of depression. 

'Background noise' of symptoms

The study also found that nearly one in five people in the studies' placebo groups described symptoms similar to those reported by the participants in the group that had discontinued antidepressants. 

Baethge said this was likely down to a "nocebo" effect, in which "the expectation of bad things to happen once you take or stop taking a drug creates a heightened awareness of worsening anxiety or depression after taking helpful medication. This effect might be amplified in patients whose doctors told them to expect symptoms."

Baethge said the findings suggest there is a general "background noise" of non-specific symptoms in normal life for many people, akin to normal fluctuations in sensory perception.

"We are not saying it's all in their heads. It's tempting to think if something occurs under placebo, it's all imagination. The point is the patients do truly feel dizzy, for example, and it needs to be taken seriously, no matter what causes it," said Baethge.

Edited by: Clare Roth

Sources:

Henssler J, et al., Incidence of antidepressant discontinuation symptoms: a systematic review and meta-analysis. Lancet Psychiatry 2024 https://doi.org/10.1016/S2215-0366(24)00133-0