Summary of findings 1. Abrupt discontinuation compared to continuation of long‐term antidepressants for depressive and anxiety disorders in adults.
| Abrupt discontinuation compared to continuation of long‐term antidepressants for depressive and anxiety disorders in adults | ||||||
| Patient or population: participants with depressive or anxiety disorders Setting: primary care and specialist mental healthcare services Intervention: abrupt discontinuation Comparison: continuation | ||||||
| Outcomes | Anticipated absolute effects* (95% CI) | Relative effect (95% CI) | №. of participants (studies) | Certainty of the evidence (GRADE) | Comments | |
| Risk with continuation of long‐term antidepressants | Risk difference with abrupt discontinuation | |||||
| Successful discontinuation rate | None of the studies reported successful discontinuation rate | |||||
| Relapse (as defined by study authors) (HR) Follow‐up from 24 weeks to 80 weeks Studies without psychological support |
Low riska (3 studies) | HR 2.09 (1.59 to 2.74) | 1373 (10 RCTs) | ⊕⊝⊝⊝ VERY LOWb | Studies did not distinguish relapse from symptoms of withdrawal | |
| 100 per 1000 | 98 more per 1000 (from 54 more to 151 more) | |||||
| Moderate risk (4 studies) | ||||||
| 285 per 1000 | 219 more per 1000 (from 128 more to 316 more) | |||||
| High risk (3 studies) | ||||||
| 564 per 1000 | 260 more per 1000 (from 169 more to 333 more) | |||||
| Withdrawal symptoms Assessed with: proportion of participants with a withdrawal syndrome based on DESS Scale Follow‐up 2 weeks |
In one study, there was no evidence of an effect on the incidence of withdrawal symptoms between abrupt discontinuation and continuation | 182 (1 RCT) | ⊕⊝⊝⊝ VERY LOWc | Withdrawal syndrome was defined as increase of 4 or more on the DESS Scale (regardless of severity) during the first 2 weeks after discontinuation There were no differences in the proportions of participants with withdrawal syndrome based on DESS scores between the abrupt discontinuation group (31/146; 21.2%) and the continuation group (4/36; 11.1%) (P ≥ 0.06). |
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| Adverse events Follow‐up: from 4 to 100 weeks |
216 per 1000 | 18 more per 1000 (from 70 fewer to 138 more) | OR 1.11 (0.62 to 1.99) | 1012 (7 RCTs) |
VERY LOWd | Pooling possible for 7 of 10 studies that measured adverse events. Studies did not distinguish between adverse events and withdrawal symptoms |
| Depressive symptoms Assessed with: HAM‐D scale Follow‐up: range 40 to 80 weeks |
Mean HAM‐D total score at endpoint: 9.9 (1 study) | MD 0.44 higher (1.12 lower to 2 higher) | ‐ | 330 (3 RCTs) | ⊕⊝⊝⊝ VERY LOWe | Pooling possible for 3 of 7 studies that measured depressive symptoms Higher score indicates more severe depressive symptoms |
| Anxiety symptoms Assessed with 4 different scales Follow‐up: range 28 to 80 weeks |
In 2 studies (n = 235), there were no differences in anxiety symptoms between abrupt discontinuation and continuation of antidepressants A third study (n = 204) showed that antidepressant continuation improved anxiety symptoms |
‐ | 439 (3 RCTs) | ⊕⊝⊝⊝ VERY LOWf | Data could not be pooled due to variability of outcome measures One study used our prioritised outcome HAM‐D Scale |
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| Quality of life | None of the studies reported quality of life | |||||
| Social and occupational functioning | None of the studies reported social and occupational functioning | |||||
| *The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: confidence interval; DESS: Discontinuation‐Emergent Signs and Symptoms; HAM‐D: Hamilton Rating Scale for Depression; HR: hazard ratio; OR: odds ratio; RCT: randomised controlled trial. | ||||||
| GRADE Working Group grades of evidence. High certainty: we are very confident that the true effect lies close to that of the estimate of the effect. Moderate certainty: we are moderately confident in the effect estimate: the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different. Low certainty: our confidence in the effect estimate is limited: the true effect may be substantially different from the estimate of the effect. Very low certainty: we have very little confidence in the effect estimate: the true effect is likely to be substantially different from the estimate of effect. | ||||||
aAssumed risk calculated as the proportion of participants on antidepressants with the outcome (relapse) in the included studies and divided into low (cut‐off < 20%), moderate (cut‐off < 40%), and high risk (≥ 40%), multiplied by 1000.
bDowngraded by two levels for risk of bias (poor description of randomisation and blinding and withdrawal confounding bias) and by one level for indirectness (majority of participants with recurrent depression; one study included panic disorder).
cDowgraded by one level due to imprecision (single study with small number of participants), by one level for risk of bias (poor description of randomisation and blinding, severity of withdrawal symptoms not scored in the outcome; and relatively short period for observing withdrawal symptoms), and by one level for indirectness (study included participants with single or recurrent depressive disorder but did not report numbers of participants with single or recurrent disorder or previous number of episodes)
dDowngraded by one level for risk of bias (poor description of randomisation process and blinding, attrition bias and withdrawal confounding bias), by one level for imprecision (wide 95% confidence interval, which includes the null effect of no difference), and by one level for indirectness (studies included participants with recurrent depressive disorder).
eDowngraded by one level for risk of bias (poor description of randomisation and blinding, attrition bias, and withdrawal confounding bias), by one level for imprecision (wide 95% confidence interval, which includes the null effect of no difference between treatments), and by one level for indirectness (participants with recurrent disorder).
fDowngraded by one level for imprecision (no pooling and small number of participants), by one level for risk of bias (confounding withdrawal bias, poor description of randomisation and blinding), and by one level for indirectness (only one of the three studies included participants with anxiety disorder (panic disorder)).