Antidepressant withdrawal symptoms are much less common than you might think

The incidence of antidepressant withdrawal symptoms appears to be much lower than previously thought, according to a new meta-analysis of studies evaluating the issue.

After taking into account the placebo effect, results showed that true discontinuation symptoms occurred in approximately 15% of patients who discontinued antidepressant therapy, and serious symptoms occurred in approximately 2% of patients.

“Taking into account all available data, we conservatively estimate that one in six to seven patients actually has a pharmacologically-caused antidepressant discontinuation symptom. This may still be an overestimate, due to the difficulty of taking into account residual or recurrent antidepressant symptoms. depression or anxiety,” the researchers concluded.

This study Publish online On June 5th Lancet.

More reliable data

“We are not saying that all the symptoms associated with stopping antidepressants are placebo effects – this is a real phenomenon – and we are not saying that stopping antidepressants is problem-free – but our findings suggest that there are fewer true symptoms associated with stopping antidepressants than previous studies have suggested,” study investigator Christopher Bethge, MD, of the University of Cologne in Germany, said at a news conference at the Science Media Centre.

“Our data should de-emotionalize the debate on this issue. Antidepressant discontinuation symptoms are a problem, but they should not cause undue anxiety to patients or physicians,” Bethge added.

“Previous studies on this issue included studies with selection bias in that they were more likely to include people with symptoms that caused them to stop taking antidepressants,” said lead researcher Jonathan Henssler, MD, of Charité University Medicine Berlin in Germany. “This study included a broader range of studies and excluded studies, so we believe the results are more reliable.”

Controversial Issues

The researchers found that antidepressant withdrawal symptoms were highly variable and nonspecific, with the most frequently reported symptoms being dizziness, headache,nausea, insomniaThese symptoms usually occur within a few days and are usually temporary, but may last for weeks or months.

In explaining the mechanism behind this phenomenon, Bethge noted that antidepressants, which are selective serotonin reuptake inhibitors, increase available serotonin in the brain, but the body responds by reducing the number of serotonin receptors. The reduced amount of available serotonin after stopping the medication can lead to withdrawal symptoms.

However, the incidence and severity of these symptoms remain controversial, the researchers noted, noting that antidepressant withdrawal symptoms are estimated to occur in the majority of patients (56%), with almost half of cases classified as severe.

Previous evaluation attempts have been questioned from a methodological perspective, particularly as they involved online surveys and other studies prone to selection and dissatisfaction bias.

“Medical professionals remain polarized about the incidence and severity of symptoms associated with antidepressant discontinuation, and the debate continues in the public media,” the researchers wrote.

This is the first publication of a larger project on antidepressant discontinuation symptoms.

In this study, researchers conducted a meta-analysis of 44 controlled trials and 35 observational studies evaluating the incidence of antidepressant discontinuation symptoms, involving a total of 21,002 patients, of which 16,532 patients discontinued antidepressant treatment and 4,470 patients discontinued placebo.

At least one antidepressant discontinuation symptom occurred in 31% of patients who discontinued antidepressant treatment and in 17% after placebo discontinuation, giving a true incidence of pharmacologically induced antidepressant discontinuation symptoms of 14% to 15%.

The study showed that 2.8% of people who stopped taking antidepressants experienced severe discontinuation symptoms, and 0.6% of people who stopped taking a placebo experienced severe discontinuation symptoms, meaning the actual incidence of severe symptoms in people who stopped taking antidepressants was about 2%.

There was no association with duration of treatment or pharmaceutical company funding, and various statistical analyses produced similar results, suggesting the findings are robust, Bethge reported.

Drug-related risks

Desvenlafaxinevenlafaxine, Imipramineand Escitalopram Discontinuation symptoms are frequent, imipramine, ParoxetineEither desvenlafaxine or venlafaxine was associated with greater symptom severity.

Fluoxetine, Sertralinecitalopram was associated with a low incidence of discontinuation symptoms. Bupropion, Mirtazapineand Amitriptyline.

Regarding the clinical implications of the study's findings, Hensler said that patients would consider the symptoms associated with discontinuation when choosing a medication. “Unless there is a specific reason to choose a drug with a higher incidence of these symptoms, I would choose the drug with a lower incidence of these symptoms,” he said.

Henssler added that these data raise awareness of the placebo effect.

“Taking placebo results into account, approximately half of antidepressant discontinuation symptoms could be attributed to expectancy or nonspecific symptoms,” the researchers noted.

“This is not to say that all antidepressant discontinuation symptoms are caused by patient expectations. Indeed, all patients who discontinue antidepressants should receive counselling and supervision, and patients who report antidepressant discontinuation symptoms should be supported, especially those who develop severe antidepressant discontinuation symptoms,” the researchers concluded.

Expert opinion

Commenting on the study at a press conference, Dr Oliver Howes, Chair of the Royal College of Psychiatrists' Committee on Psychopharmacology, said he welcomed the “insights that this powerful study provides”.

“If you choose to stop taking your antidepressant, your doctor should help you do so slowly and in a controlled way that minimises the effects of potential withdrawal symptoms,” Howes said.

He added that the Royal College of Psychiatrists has produced material for patients and carers about stopping antidepressants, providing information on gradually tapering medication at a pace that suits each individual patient's needs.

Tony Kendrick, MD, professor of primary care at the University of Southampton in the UK, also pointed out several limitations of the new meta-analysis, notably that the ways in which withdrawal symptoms were assessed in the included studies were highly variable, and specific measurement scales of withdrawal symptoms were used in only six of the studies.

“In most cases, the assessments are not based on systematic data collection but rather appear to rely, at least in part, on the judgment of the authors of the studies included,” Kendrick added.

In an accompanying editorial, Dr Glyn Lewis and Dr Gemma Lewis of University College London, UK, wrote that while the meta-analysis has limitations, including the fact that many of the studies were small, they used antidepressants that are no longer in common use, and they included people who had not taken antidepressants for a long time, “these results represent a significant improvement over those previously published.”

They stress the importance of discussing the issue of placebo effects with patients when discontinuing antidepressants.

The editorialists noted that because antidepressants are prescribed to millions of people, relatively rare severe withdrawal symptoms will still affect a significant number of people, but to individual clinicians, severe withdrawal symptoms will be perceived as rare, and most patients will not suffer from antidepressant withdrawal symptoms, especially if the medication is tapered over a period of several weeks.

The researchers noted that stopping antidepressants can make depression and anxiety symptoms worse, making it difficult to distinguish between a return of symptoms and withdrawal symptoms.

“Short-term symptoms that quickly relieve without intervention are best thought of as a form of withdrawal, even if the symptoms are similar or identical to those of depression or anxiety disorders. More severe, long-term symptoms may be best managed by gradually tapering the medication or by a decision to continue taking the antidepressant,” the editorialists wrote.

This study had no funding sources. The authors declare that they have no conflicts of interest. Dr. Jauhar has received honoraria for educational talks on antipsychotics and psychosis from Sunovian, Jannsen and Boehringer-Ingelheim and is a consultant for LB Pharmaceuticals. Dr. Kendrick led the NIHR REDUCE trial of internet and telephone support for antidepressant discontinuation and was a member of the guideline committee for the NICE 2022 depression guideline..