Risks by Medication
Desvenlafaxine, venlafaxine, imipramine, and escitalopram were associated with higher frequency of discontinuation symptoms and imipramine, paroxetine, and either desvenlafaxine or venlafaxine were associated with a higher severity of symptoms.
Fluoxetine, sertraline, and citalopram had lower rates of discontinuation symptoms. No data were available for bupropion, mirtazapine, and amitriptyline.
As for the clinical implications of the findings, Dr. Henssler said that he does consider discontinuation symptoms when selecting a medication. “I would choose a drug with lower rate of these symptoms unless there was a specific reason to choose one with a higher rate,” he said.
Dr. Henssler added that these data raise awareness of the placebo effect.
“Considering the placebo results, approximately half of antidepressant discontinuation symptoms could be attributable to expectation or non-specific symptoms,” the researchers noted.
“This is not to say all antidepressant discontinuation symptoms are caused by patient expectations; in practice, all patients discontinuing antidepressants need to be counseled and monitored, and patients who report antidepressant discontinuation symptoms must be helped, in particular those who develop severe antidepressant discontinuation symptoms,” they concluded.
Experts Weigh In
Commenting on the study at a press briefing, Oliver Howes, MD, chair of the psychopharmacology committee at the Royal College of Psychiatrists, United Kingdom, said that he welcomed “the insight that this robust study provides.”
“If someone chooses to stop taking their antidepressants, their doctor should help them to do so slowly and in a controlled manner that limits the impact of any potential withdrawal symptoms,” Dr. Howes said.
He added that the Royal College of Psychiatrists has produced a resource for patients and carers on stopping antidepressants that offers information on tapering medication at a pace that suits individual patient needs.
Also commenting, Tony Kendrick, MD, professor of primary care, University of Southampton, United Kingdom, pointed out some limitations of the new meta-analysis — in particular, that the method of assessment of discontinuation symptoms in the included studies was very variable, with specific measurement scales of discontinuation symptoms used in only six of the studies.
“In most cases the assessment seemed to depend at least partly on the judgment of the authors of the included studies rather than being based on a systematic collection of data,” Dr. Kendrick added.
In an accompanying editorial, Glyn Lewis, PhD, and Gemma Lewis, PhD, University College London, United Kingdom, wrote that though the meta-analysis has its limitations, including the fact that many of the studies were small, often use antidepressants that are not commonly used now, and studied people who had not taken the antidepressants for a very long time, “the results here are a substantial improvement on anything that has been published before.”
They emphasize the importance of discussing the issue of a placebo effect with patients when stopping antidepressants.
The editorialists pointed out that as antidepressants are prescribed to many millions of people, the relatively uncommon severe withdrawal symptoms will still affect a substantial number of people. However, for individual clinicians, severe withdrawal symptoms will seem uncommon, and most patients will probably not be troubled by antidepressant withdrawal, especially when medication is tapered over a few weeks.
They noted that cessation of antidepressants can lead to an increase in depressive and anxious symptoms, and distinguishing between relapsing symptoms and withdrawal is difficult.
“Short-term symptoms that reduce quickly, without intervention, are best thought of as a form of withdrawal, even if those symptoms might be similar or identical to the symptoms of depression and anxiety. More serious and longer-term symptoms might best be managed by tapering more slowly, or even deciding to remain on the antidepressant,” the editorialists wrote.
There was no funding source for this study. The authors declare no competing interests. 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.
A version of this article appeared on Medscape.com.