Background: Antidepressants are recommended for moderate-to-severe depression and anxiety, but concerns exist around overprescribing, long-term use, and paucity of evidence-based deprescribing strategies. We aimed to compare the effectiveness of different deprescribing approaches in individuals with clinically remitted depression or anxiety. Methods: For this systematic review and network meta-analysis, we searched PubMed, PsycINFO, Web of Science, CENTRAL, CINAHL, and online trial registries from inception to April 6, 2025, for randomised controlled trials comparing 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 in adults with fully or partially remitted depressive or anxiety disorders on antidepressant treatment. The primary outcome was relapse rate by trial end. For each study, we extracted summary-level data on study characteristics, participant demographics, intervention details, and outcome measures. We did random-effects pairwise meta-analysis, and random-effects frequentist network meta-analysis to obtain relative risks (RRs) and standardised mean differences with 95% CIs. We assessed risk of bias using the Cochrane Risk-of-Bias-2 tool and the certainty of pooled estimates using the Confidence in Network Meta-Analysis approach. Individuals with lived experiences contributed to the interpretation of results. The study was registered with Open Science Framework, https://osf.io/9bsxz/. Findings: Of 13 011 records, we included 76 trials comprising 17 379 participants. The mean age of individuals was 45·2 years (SD 15·2, IQR 34·9-55·5); 11 731 (67·5%) were female and 5648 (32·5%) male; the mean follow-up was 45·9 weeks (SD 29·7). Individuals were predominantly White (mean 87·9% [SD 8·1]). 60 (79%) of 76 studies investigated depression and 16 (21%) investigated anxiety. Separate analyses by diagnosis showed consistent baseline characteristics or treatment effects, although most comparisons were informed primarily by studies of participants with depression. After pooling data across conditions, the following strategies outperformed abrupt discontinuation for relapse prevention: 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 (0·51, 0·46-0·58; NNT 5·3; moderate certainty), slow tapering plus psychological support (0·52, 0·38-0·72; NNT 5·4; moderate certainty), and continuation at reduced dose (0·62, 0·42-0·92; NNT 6·8; low certainty). These strategies also outperformed fast tapering (point estimates ranging from 0·39 to 0·52; the first three supported by moderate certainty, the last by low certainty). Compared with abrupt discontinuation, the following strategies made no difference in relapse prevention: fast tapering plus psychological support (0·52, 0·27-1·01; low certainty), abrupt stopping plus psychological support (0·73, 0·30-1·78; very low certainty), and slow tapering alone (0·81, 0·56-1·18; low certainty). Moderate heterogeneity emerged (τ2=0·07), without evidence of inconsistency. Sensitivity, subgroup, and secondary outcomes provided consistent results. Tolerability was comparable across strategies. Interpretation: In remitted depression, slow tapering plus psychological support is as effective as antidepressant continuation in preventing relapse and superior to abrupt or rapid discontinuation. In remitted anxiety, despite consistent population characteristics and effect estimates, limited evidence warrants cautious generalisation. Guidelines should promote individualised deprescribing with gradual tapering and structured psychological support. Funding: None.
Comparison of antidepressant deprescribing strategies in individuals with clinically remitted depression: a systematic review and network meta-analysis
Zaccoletti, Debora;Mosconi, Carlotta;Gastaldon, Chiara;Benedetti, Lorenzo;Gottardi, Carolina;Papola, Davide;Purgato, Marianna;Barbui, Corrado;Ostuzzi, Giovanni
2026-01-01
Abstract
Background: Antidepressants are recommended for moderate-to-severe depression and anxiety, but concerns exist around overprescribing, long-term use, and paucity of evidence-based deprescribing strategies. We aimed to compare the effectiveness of different deprescribing approaches in individuals with clinically remitted depression or anxiety. Methods: For this systematic review and network meta-analysis, we searched PubMed, PsycINFO, Web of Science, CENTRAL, CINAHL, and online trial registries from inception to April 6, 2025, for randomised controlled trials comparing 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 in adults with fully or partially remitted depressive or anxiety disorders on antidepressant treatment. The primary outcome was relapse rate by trial end. For each study, we extracted summary-level data on study characteristics, participant demographics, intervention details, and outcome measures. We did random-effects pairwise meta-analysis, and random-effects frequentist network meta-analysis to obtain relative risks (RRs) and standardised mean differences with 95% CIs. We assessed risk of bias using the Cochrane Risk-of-Bias-2 tool and the certainty of pooled estimates using the Confidence in Network Meta-Analysis approach. Individuals with lived experiences contributed to the interpretation of results. The study was registered with Open Science Framework, https://osf.io/9bsxz/. Findings: Of 13 011 records, we included 76 trials comprising 17 379 participants. The mean age of individuals was 45·2 years (SD 15·2, IQR 34·9-55·5); 11 731 (67·5%) were female and 5648 (32·5%) male; the mean follow-up was 45·9 weeks (SD 29·7). Individuals were predominantly White (mean 87·9% [SD 8·1]). 60 (79%) of 76 studies investigated depression and 16 (21%) investigated anxiety. Separate analyses by diagnosis showed consistent baseline characteristics or treatment effects, although most comparisons were informed primarily by studies of participants with depression. After pooling data across conditions, the following strategies outperformed abrupt discontinuation for relapse prevention: 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 (0·51, 0·46-0·58; NNT 5·3; moderate certainty), slow tapering plus psychological support (0·52, 0·38-0·72; NNT 5·4; moderate certainty), and continuation at reduced dose (0·62, 0·42-0·92; NNT 6·8; low certainty). These strategies also outperformed fast tapering (point estimates ranging from 0·39 to 0·52; the first three supported by moderate certainty, the last by low certainty). Compared with abrupt discontinuation, the following strategies made no difference in relapse prevention: fast tapering plus psychological support (0·52, 0·27-1·01; low certainty), abrupt stopping plus psychological support (0·73, 0·30-1·78; very low certainty), and slow tapering alone (0·81, 0·56-1·18; low certainty). Moderate heterogeneity emerged (τ2=0·07), without evidence of inconsistency. Sensitivity, subgroup, and secondary outcomes provided consistent results. Tolerability was comparable across strategies. Interpretation: In remitted depression, slow tapering plus psychological support is as effective as antidepressant continuation in preventing relapse and superior to abrupt or rapid discontinuation. In remitted anxiety, despite consistent population characteristics and effect estimates, limited evidence warrants cautious generalisation. Guidelines should promote individualised deprescribing with gradual tapering and structured psychological support. Funding: None.
I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
