Findings are ‘important’ but ‘disappointing’
In an editorial published alongside the study (N Engl J Med. 2021;385:1327-8), Jeffrey L. Jackson, MD, MPH, from the Zablocki VA Medical Center and the Medical College of Wisconsin in Milwaukee characterized the findings as “important but disappointing.”
“They confirm what most primary care physicians already knew or intuited. The frequency of relapse after the discontinuation of treatment is high, particularly among patients with several previous depressive episodes,” he explained.
Dr. Jackson also pointed out some unknowns about the trial, including the length trial participants had been in remission for depression.
“It is unclear whether the trial results are generalizable to primary care patients with a first episode of depression,” he said, and noted that participants with three or more previous depressive episodes were more than twice as likely to relapse, compared with participants with fewer episodes.
“I encourage patients with a single bout of depression, especially episodes that are triggered by a life event, such as loss of a loved one, to consider weaning antidepressant treatment after at least 6 months of remission,” he wrote. “For those with three or more previous bouts of depression, my practice has been to recommend that they anticipate medical treatment for life or, if they wish to stop taking medication, explore nonpharmacologic approaches, such as cognitive-behavior therapy.”
Protective effect of antidepressants was clear
“This is an important paper providing an evidence base to the often-cited recommendation that after two or more episodes of depression, antidepressant medication should be continued indefinitely,” said Neil Skolnik, MD, professor of family and community medicine at the Sidney Kimmel Medical College, Thomas Jefferson University in Philadelphia, who was not involved in the study.
“The protective effect of antidepressant medication here was clear – those who discontinued antidepressant medication had a clinically and significantly higher rate of relapse at the end of a year.”
Side effects can be significant
“It is important to note, though, that in the discontinuation group, 44% of patients did not experience a relapse,” Dr. Skolnik said. “While antidepressants work without significant side effects for many patients, for others there are significant side effects that include adverse sexual side effects, effects on appetite and weight, nighttime sweats, and other side effects.”
“So, this study should not be confused to mean that all patients who have had recurrent depression should remain on antidepressants long term. The decision about whether to continue an antidepressant is influenced by many things and should be a shared decision-making process between clinician and patient, informed by the important results of this study, the current situation of the patient, and most importantly, the patient’s informed decision of what they would like to do,” he said.
The study was funded by the U.K. National Institute for Health Research
Dr. Lewis, Dr. Jackson, and Dr. Skolnik reported no conflicts of interest.