No more relapses for patients who have stopped antidepressants

Adults on antidepressants for a prolonged period were significantly less likely to relapse from a depressive episode if they continued their treatment, according to a British randomized trial.

The study assigned nearly 500 patients to primary care practices who were feeling well enough to stop taking placebo (stopping) or continuing antidepressant treatment (maintenance). After 52 weeks, the primary endpoint – relapse of depression – occurred in 56% of patients in the discontinuation group and 39% of patients in the maintenance group (HR 2.06, 95% CI 1.56-2.70, P

The percentage of patients who reported feeling worse at 12 weeks than at 6 weeks was 44% in the discontinuation group and 21% in the maintenance group (OR 2.88, 95% CI 1 , 90-4.38), noted the authors in the New England Journal of Medicine.

Secondary outcomes followed a similar trend; the researchers used the 9-item version of the Patient Health Questionnaire (PHQ-9) to assess depressive symptoms, the 7-item version of the Generalized Anxiety Disorder Assessment (GAD-7) for symptoms of depression. Anxiety, the 14-item modified version of Signs and Symptoms of Interruption of Activity (DESS) for withdrawal symptoms and the 12-point Abridged Health Survey (SF-12) to assess quality of life.

At 12 weeks, the mean score for depressive symptoms was 4.1 ± 3.8 in the maintenance group and 6.3 ± 5.1 in the discontinuation group, for an estimated difference of 2.2 points (95 CI % 1.5-2.8). The mean score for anxiety symptoms at the same 12 week point was 3.1 ± 3.3 in the maintenance group and 5.3 ± 4.6 in the stop group, for a difference of 2.4 points (95% CI 1.8-3.0).

The mean score for withdrawal symptoms at 12 weeks was 1.3 ± 2.4 in the maintenance group and 3.1 ± 3.5 in the discontinuation group, for an estimated difference of 1.9 points (CI at 95% 1.5-2.3), and the mean score for mental health – the associated quality of life was 46 ± 10 in the maintenance group and 41 ± 11 in the discontinuation group, for an estimated difference of – 4.9 points (95% CI -6.4 to -3.3).

For Jeffrey Jackson, MD, MPH, of the Medical College of Wisconsin, the results of this study were significant, disappointing and unsurprising.

“They confirm what most primary care physicians already knew or had a hunch,” he wrote in an accompanying editorial. “The frequency of relapses after stopping treatment is high, especially in patients who have already had several depressive episodes.”

Jackson also pointed out that patients who had three or more previous depressive episodes were more than twice as likely to relapse as those who had fewer episodes. This, he said, places a limit on the generalization of these findings for patients who have only had one depressive episode.

After searching for participants treated in 150 GP practices in the UK, 478 eligible people were randomized to the Antidepressants to Prevent Relapse in Depression (ANTLER) trial: 238 in the maintenance group and 240 in the d group. ‘stop.

Eligible participants were adults aged 18 to 74 who had been taking antidepressants for more than 2 years or had reported at least two previous episodes of depression. All patients were on a daily antidepressant regimen – 20 mg citalopram (Celexa), 100 mg sertraline (Zoloft), 20 mg fluoxetine (Prozac) or 30 mg mirtazapine (Remeron) – for at least 9 months, were remitted recent depressive episode and reported feeling well enough to consider stopping treatment. At baseline, the two groups had similar characteristics: 73% were female, the average age was 54, and 95% were Caucasian.

In the maintenance group, 70% of patients adhered to the trial design versus 52% of the discontinuation group.

There were 17 serious adverse events during the study, nine in the maintenance group and eight in the discontinuation group. There were no deaths or suicide attempts.

Lewis and colleagues noted that other important limitations of their study were the trial’s lack of racial and ethnic diversity, and that only patients who felt ready to discontinue treatment were included in the research.

Last updated on 01 October 2021

  • Kara Grant joined the Enterprise & Investigative Reporting team at MedPage Today in February 2021. She covers psychiatry, mental health and medical education. To follow


This study was supported by the National Institute for Health Research.

Lewis did not report any disclosure. A co-author has revealed to have been a consultant for various pharmaceutical companies.

Jackson did not report any conflicts of interest.

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