a new study shows.
The results of the Antidepressants to Prevent Relapse in Depression (ANTLER) trial also suggest that “many patients can discontinue their antidepressants safely in primary care without relapsing, when there is a tapering regime,” said lead investigator Gemma Lewis, PhD, from University College London, in an interview.
The multicenter, randomized, double-blind trial, which was published in the New England Journal of Medicine (2021;385:1257-67), included 478 patients, from 150 primary care practices in the United Kingdom.
The participants (73% female, average age 54 years) had a history of at least two depressive episodes or had been taking antidepressants (citalopram, fluoxetine, sertraline, or mirtazapine) for at least 2 years. The vast majority of patients – 70% – had been using the drugs for more than 3 years, the researchers wrote.
Study participants were randomized to either maintain their antidepressant regimen or to taper off for up to 2 months before switching to a placebo.
Over a follow-up of 52 weeks, relapse occurred in 56% of those who discontinued, compared with 39% of those who maintained their regimen (hazard ratio, 2.06; P < .001). Relapse also occurred sooner in the discontinuation group (13 weeks vs. 19 weeks).
The definition of relapse was answering yes to either of the following two questions:
- Have you had a spell of feeling sad, miserable, or depressed?
- Have you been unable to enjoy or take an interest in things as much as you usually do?
Patients also had to report that one of these experiences had lasted for 2 weeks or more, and having had at least one of the following symptoms: depressive thoughts, fatigue, loss of concentration, or sleep disturbance.
By the end of the trial, 39% of patients in the group who discontinued taking an antidepressant had returned to taking that type of drug.
“We found that remaining on antidepressants long-term does effectively reduce the risk of relapse. However, we also found that 44% of those who discontinued their antidepressants did not relapse after a full year,” Dr. Lewis said.
Who can stop medications without relapsing is unknown
“Many people can stop their medication without relapsing, though at present we cannot identify who those people are,” noted Dr. Lewis.
“Our study did not investigate who is at higher risk of relapse … but this is something we will focus on in the future,” she said.
For primary care clinicians whose patients are considering discontinuation of antidepressant medication, “current best practice is to engage with patients’ priorities and collaborate in coming to a decision,” she noted.
“For the individual patient, it is only possible to know about the average likelihood of relapse – and the severity of potential relapses will also be unpredictable. Our findings will give patients and clinicians an estimate of the likely benefits and harms of stopping long-term maintenance antidepressants to inform shared decision-making in primary care.”