Stopping antidepressants leads to complaints in 1 in 6 patients

TThe moment when someone stops taking their antidepressant is fraught. Not only may patients see their psychiatric symptoms return, but they may also experience a wide variety of new symptoms in the days and weeks immediately following the medication change.

Symptoms such as nausea and headaches can be manageable and typically begin and end within a few days of discontinuing the medication. But more disruptive effects such as insomnia, irritability and sensory disturbances, or even serious effects such as suicidal ideation or lethargy, may cause patients to reconsider their decision to stop treatment, even if these resolve relatively quickly.

A new systematic review of studies on antidepressant withdrawal, published on Tuesday in The Lancet Psychiatry provides insight into the frequency and severity of those complaints. The review, which included 79 studies involving 21,000 patients, found that about 15% experienced withdrawal symptoms after stopping antidepressants. In 2 to 3% of cases the complaints were serious.

The analysis “is an important and long-awaited contribution to the research literature,” said Awais Aftab, professor of psychiatry at Case Western Reserve University School of Medicine, who did not participate in the study. It confirms that withdrawal symptoms occur with a clinically relevant frequency and should be treated with care. But it showed a lower incidence than recent estimates based on online surveyswhich caused public alarm when they suggested that symptoms might occur in half or more of patients.

“An incidence of antidepressant withdrawal symptoms of any severity experienced by one in six patients who discontinue their medication, and severe withdrawal symptoms experienced by approximately one in 30 patients, in my opinion, has greater face validity and provides better again what happens in the clinic. ” said Aftab.

Different patients and doctors will have different opinions about which incidence of withdrawal symptoms counts as rare or not, says Christopher Baethge, senior author of the study and professor of psychiatry at the University of Cologne, Germany. But “we wanted to provide a number for advice without causing unnecessary alarm,” he said.

Doctors can share data with their patients about the likelihood of them experiencing withdrawal symptoms. This allows them to validate their experience as it occurs, and reassure them that in the vast majority of cases it will resolve within a few days to a few weeks.

The incidence of withdrawal symptoms varied by antidepressant. Imipramine, a tricyclic antidepressant, was associated with the highest occurrence of withdrawal symptoms, followed by the selective serotonin and norepinephrine reuptake inhibitors desvenlafaxine and venlafaxine. Selective serotonin reuptake inhibitors fluoxetine and sertraline were the least common. (The authors could not find any studies that looked at withdrawal symptoms from common antidepressants such as bupropion, amitriptyline, and mirtazapine.) Severe symptoms were most common with imipramine and paroxetine.

“This is also consistent with clinical practice, where most discontinuation effects are concentrated around the use of venlafaxine and paroxetine,” Aftab said.

The analysis also found that withdrawal symptoms were experienced by 17% of patients in the placebo groups (that is, they had not received any medication to begin with) and so cannot all be attributed to pharmacological causes. Instead, Baethge said, other factors may come into play, such as increased awareness of worsening anxiety and depression, anticipation of symptoms after hearing about them, or symptom fluctuations that can occur regardless of medication.

That doesn’t mean these symptoms should be dismissed. “We’re not saying it’s all in their heads,” Baethge said. “Even patients who do not have pharmacologically controlled ADS [antidepressant discontinuation syndrome] for example, you feel dizzy. If they say dizziness is the problem, they feel dizzy and should be taken seriously, regardless of the cause of that dizziness.”

Researchers emphasize that more research is needed into the effects of quitting. “There is still a significant shortage of high-quality clinical trials investigating the withdrawal effects of antidepressants,” says Aftab.

Newborns can experience withdrawal symptoms, usually within the first two days of life, if they have been exposed to antidepressants in utero, for example, but there are few standardized studies in this population, Baethge said. That could be a future research focus, he said, as well as studies to break down the incidence of each discontinuation symptom.