For adults with remitted depression, gradual tapering of antidepressant medication, alongside psychological support, prevents relapse to a similar extent as continuing antidepressants at full therapeutic doses, while abrupt or fast discontinuation should be avoided, a new analysis showed.

Slow tapering with support could prevent one relapse in every five people compared with abrupt stopping or fast tapering, investigators estimated, adding that the findings point to a need for updated evidence-based guidelines that encourage regular treatment review and effective deprescribing when appropriate.

“By incorporating a substantially larger evidence base, a broader range of deprescribing strategies, and direct head-to-head comparisons, our new review clarifies the scientific evidence about the most effective way to come off antidepressants for individuals successfully treated for depression and could change how coming off antidepressants is managed globally,” lead author Giovanni Ostuzzi, MD, PhD, from the University of Verona in Verona, Italy, said in a statement.

“We encourage anyone considering coming off antidepressants to discuss the process with their doctor first to jointly find the best strategy for them,” Ostuzzi added.

The study was published online on December 10 in Lancet Psychiatry.

Filling a Research Gap

While current guidelines recommend antidepressants for moderate-to-severe depression and anxiety disorders, “they also recommend to consider discontinuation after 6-9 months of maintenance after remission of a first episode, while longer treatment periods are required for repeated episodes over time or with severe symptoms,” Ostuzzi explained in a press briefing hosted by the UK nonprofit Science Media Center.

Yet it’s been estimated that up to 40% of patients take these medications for 5 years or more, which might lead to long term adverse events, including sexual dysfunction, emotional blunting, as well as a higher risk for withdrawal symptoms once discontinuation is attempted, Ostuzzi noted.

And there has been little rigorous research into the safest and most effective approaches to discontinue antidepressant therapy.

To investigate, Ostuzzi and colleagues did a systematic review and network meta-analysis comparing the effectiveness of five different deprescribing strategies: abrupt discontinuation, fast tapering (≤ 4 weeks), slow tapering (> 4 weeks), dose reduction (≤ 50% of the minimal effective dose), or continuation, with or without psychological support.

The analysis included 76 randomized controlled trials involving 17,379 adults (mean age, 45 years; 68% women; 88% White individuals) with fully or partially remitted depressive or anxiety disorders while on antidepressant therapy.

Sixty of the 76 trials were in depression. Most patients were on selective serotonin-reuptake inhibitor or serotonin norepinephrine reuptake inhibitor therapy. Mean follow-up was around 11 months.

How to Safely Stop

The analysis found moderate-certainty evidence that in people with clinically remitted depression, slow tapering of antidepressants combined with psychological support is as effective in preventing relapse over the following year as continuing antidepressants at standard doses, with or without psychological support.

Continuing standard dose antidepressant therapy plus psychological support was “the best performing” treatment strategy, reducing the risk for relapse by 60% (relative risk [RR], 0.40), with a number needed to treat of four to prevent one relapse, Ostuzzi told in the briefing.

Continuing antidepressant therapy without psychological support reduced the risk for relapse by 49%, with a number needed to treat of five.

However, “most interestingly,” said Ostuzzi, slow tapering of antidepressant therapy plus psychological support had similar benefits in preventing relapse as continuing antidepressants, reducing the risk by about half (RR, 0.52).

Continuing the antidepressant at a reduced dose was better than abruptly stopping and fast tapering for reducing depression relapse, but the certainty of evidence was low. And fast tapering of the antidepressant was associated with a risk for relapse that was nearly identical to abrupt stopping of the medication.

Across all deprescribing strategies, tolerability and adverse events were comparable, with no major safety concerns. Withdrawal symptoms were hard to assess due to inconsistent reporting but appeared more common in those continuing antidepressants, suggesting that these events are more apt to be antidepressant side effects rather than true withdrawal phenomena, the authors said.

In a statement, study co-author Debora Zaccoletti, PsyD, from the University of Verona, said the findings “highlight the need for clinical guidelines to be updated to promote regular treatment reviews and individualized deprescribing with gradual tapering and structured psychological support for patients with depression who are feeling better and wish to come off their medication.”

Individualized Approach

Reached for comment, Joseph Goldberg, MD, clinical professor, Department of Psychiatry, Icahn School of Medicine at Mount Sinai in New York City, said tapering of antidepressant medication is not for everyone; appropriate patient selection is key when considering it.

“For someone who’s had multiple depressive episodes, stopping the antidepressant may be a bad idea,” Goldberg, who wasn’t involved in the study, told Medscape Medical News.

However, in the appropriate patient, this study shows that “if you pair a gradual tapering with psychological support, you get the best result; your chance of relapse in the coming year is actually about as steady as if you continue the medicine,” he said.

“Antidepressants should never be stopped abruptly, except in rare cases such as a serious allergic or toxic reaction,” Goldberg noted.

Also weighing in, Nina Kraguljac, MD, professor, Department of Psychiatry and Behavioral Health, Ohio State University College of Medicine in Columbus, Ohio, and chair of the American Psychiatric Association Council on Research, told Medscape Medical News that this analysis will be “very helpful clinically to inform deprescribing strategies.”

“This paper really shows that discontinuing medication has to be done very thoughtfully and carefully. It really needs to be an individual decision between a patient and physician. Nobody should rush to discontinue medications without a clear clinical reason to do so,” said Kraguljac, who also wasn’t part of the study.

An important caveat, she said, is that the studies only looked at relapse risk over about 1 year after discontinuation — meaning the results apply mainly to short-term relapse risk.

In a linked comment, Jonathan Henssler, MD, with Charité–Universitätsmedizin Berlin, Berlin, Germany, said one of the most consistent findings in this review was that adjunctive psychological support or psychotherapy resulted in improved outcomes for all the different pharmacological strategies.

“Although this might seem a trivial finding, it is of substantial clinical importance,” Henssler wrote.

The study received no specific funding. Ostuzzi, Zaccoletti, Goldberg, and Kraguljac had no relevant disclosures.