Long-term antidepressant use may reduce risk for depression relapse
Patients in primary care practices who “felt well enough” to stop certain antidepressants — and did so — were at higher risk for relapse of depression by 52 weeks compared with those who continued therapy, researchers wrote.
“Most clinical trials of antidepressants and relapse have been done in people taking the medication for fewer than 8 months,” Gemma Lewis, PhD, a senior research fellow and lecturer in psychiatric epidemiology in the division of psychiatry at University College London, told Healio Primary Care. “Until now, we didn’t know whether antidepressant treatment was still effective when someone had been taking them for many years.”
Lewis and colleagues randomly assigned 478 patients from the United Kingdom in an approximate 1:1 ratio to remain on citalopram, fluoxetine, sertraline or mirtazapine (maintenance cohort) or to taper and ultimately stop therapy with the use of a placebo (discontinuation cohort). The average age of all patients was 54 years and 73% were women.
All patients had experienced at least two depressive episodes or had been taking antidepressants for at least 2 years and reported feeling well enough to consider discontinuing antidepressant use. It is “the first large study in primary care to focus on people who have been taking antidepressants for long periods of time,” Lewis said.
The researchers reported in The New England Journal of Medicine that 70% of the maintenance cohort and 52% of the discontinuation cohort adhered to the trial’s protocol.
Relapse by 52 weeks — the trial’s primary outcome — occurred in 39% of the maintenance cohort and 56% of the discontinuation cohort (HR = 2.06; 95% CI, 1.56-2.7).
Although secondary outcome results — depressive and anxiety symptoms, physical and withdrawal symptoms, quality of life, time to stopping medication or placebo and global mood ratings — were “generally in the same direction as the primary outcome,” patients in the discontinuation cohort experienced more symptoms of depression, anxiety and withdrawal than those in the maintenance cohort, Lewis and colleagues wrote.
The researchers reported that the study failed to identify characteristics of patients who might be more likely to discontinue medication without relapsing.
“Our findings add to evidence that for many patients, long-term treatment is appropriate, but we also found that many people were able to effectively stop taking their medication when it was tapered over 2 months,” Lewis said.
The results add another dimension to the shared decision-making process in this clinical area, she added.
“Our findings can help doctors and patients make an informed decision together on whether or not to stop their antidepressants after recovery from a depressive episode,” Lewis said. “Antidepressants are effective, but like many medications, are not ideal for everyone.”
Jeffrey Jackson, MD, MPH, a professor at the Medical College of Wisconsin, wrote in a related editorial that the study results confirm what was already widely known in the medical community and underscore “the fact that current treatment options for depressed patients are not ideal.”
Pulling from his own clinical experiences, Jackson encouraged PCPs who treat patients with depression, particularly after a life-changing event, “to consider weaning antidepressant treatment after at least 6 months of remission.”
“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.”
Jackson also recommended that, regardless of treatment track, PCPs closely monitor their patients with depression, teach them how to recognize the signs of a relapse and instruct these patients to contact them should the signs occur.
References:
Jackson JL, et al. N Engl J Med. 2021;doi:10.1056/NEJMe2111447.
Lewis G, et al. N Engl J Med. 2021;doi:10.1056/NEJMoa2106356.
Staying on long-term antidepressants reduces risk of relapse. Published Sept. 29, 2021. Accessed Sept. 29, 2021.