Deprescribing Antidepressants Safely: New Evidence Supports Gradual Taper With Therapy

Gradually discontinuing antidepressants with the support of psychological therapy may be as effective as remaining on medication for preventing depression relapse, according to the largest and most comprehensive review to date on how best to stop antidepressants.¹ The findings, published in The Lancet Psychiatry, offer some of the clearest evidence yet to guide deprescribing practices amid growing concerns about long-term use and withdrawal symptoms.

“Depression is often a recurring condition, and without ongoing treatment, as many as three out of four people with recurrent depression relapse at some point,” lead author Giovanni Ostuzzi, PhD, of the University of Verona in Italy, said in a statement.² “Clinical guidelines recommend continuing antidepressants for a certain period after remission, then considering discontinuation once the person has remained well. Yet in everyday practice, treatment is often prolonged far beyond what guidelines suggest. Many people do not wish to stay on medication indefinitely, and some experience troublesome side effects. Still, there has been little rigorous research into the safest and most effective approaches to discontinue treatments.”

The systematic review and network meta-analysis analyzed 76 randomized controlled trials involving 17,379 adults who had achieved full or partial remission from depression or anxiety while taking antidepressants, most commonly selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs).¹ The majority of participants were White (88%) and had a mean age of 45 years; most were women (68%). The studies followed patients for roughly 10 to 11 months after they began tapering or continued medication.

Researchers compared 5 major strategies: abruptly stopping medication, tapering quickly over 4 weeks or fewer, tapering slowly over more than 4 weeks, reducing the dose to half or less of the minimal effective dose, and continuing antidepressants. Several strategies were also evaluated with and without psychological support.

Across approaches, slow tapering combined with structured therapy was one of the most effective strategies for preventing relapse in depression. Its protective effect was comparable to remaining on an antidepressant at a standard dose. In contrast, abrupt discontinuation and fast tapering resulted in the highest relapse rates.

Pooled analyses demonstrated that the following strategies significantly reduced the risk of relapse compared with abrupt discontinuation: continuation at standard dose plus psychological support (RR, 0.40; 95% CI, 0.26-0.61; number needed to treat [NNT], 4.3; moderate certainty), continuation at standard dose (RR, 0.51; 95% CI, 0.46-0.58; NNT, 5.3; moderate certainty), slow tapering plus psychological support (RR, 0.52; 95% CI, 0.38-0.72; NNT, 5.4; moderate certainty), and continuation at reduced dose (RR, 0.62; 95% CI, 0.42-0.92; NNT, 6.8; low certainty). These strategies also outperformed fast tapering, with point estimates for relative risk ranging from 0.39 to 0.52.

“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,” Ostuzzi stated.²

The analysis also found that reducing antidepressants to a lower dose was somewhat better than abrupt stopping or fast tapering, though the evidence supporting this approach was weaker.¹ Psychological support, when added to either fast or slow tapering, improved outcomes as well, but the certainty of that evidence was low.

For anxiety disorders, the researchers cautioned that the available data were less robust and that dedicated trials are needed to determine whether similar tapering principles apply.

No major differences across strategies emerged in terms of adverse effects or treatment discontinuation. However, information on withdrawal symptoms, a pressing concern among patients and clinicians, was limited or missing from many studies, restricting conclusions about how different tapering methods influence overall quality of life.

This systematic review and meta-analysis provides clarity and practical guidance in the complex and contested field of antidepressant discontinuation, according to Jonathan Henssler, PD, from the department of Psychiatry and Psychotherapy, at Charité at St Hedwig Hospital.³ In his linked commentary, he emphasized that adjunctive psychological support consistently improved outcomes across all pharmacological strategies, underscoring the clinical importance of combining therapy with medication management. Slow tapering without psychological support is not superior to abrupt discontinuation, he stressed, and maintaining antidepressant therapy often yields the best outcomes, reflecting the chronicity and severity of depression.

The review’s coauthor Debora Zaccoletti, PsyD, of the University of Verona, stated that “considerable healthcare resources are needed to develop and implement dedicated psychotherapy approaches in clinical practice so more cost-effective, short-term, scalable, and remotely delivered interventions should be tested and prioritised.” She also noted that these findings “highlight the need for clinical guidelines to be updated to promote regular treatment reviews and individualised deprescribing with gradual tapering and structured psychological support for patients with depression who are feeling better and wish to come off their medication.”

References

1. Zaccoletti D, Mosconi C, Gastaldon C, et al. Comparison of antidepressant deprescribing strategies in individuals with clinically remitted depression: a systematic review and network meta-analysis. Lancet Psychiatry. Published online December 10, 2025. https://www.thelancet.com/journals/lanpsy/article/PIIS2215-0366(25)00330-X/fulltext
2. Slow tapering plus therapy most effective strategy for stopping antidepressants, finds major meta-analysis. News release. Lancet Psychiatry; December 10, 2025.
3. Henssler J. More than medication. Lancet Psychiatry. Published online December 10, 2025. https://www.thelancet.com/journals/lanpsy/article/PIIS2215-0366(25)00361-X/fulltext