Summary of findings for the main comparison. Agomelatine compared to placebo for preventing seasonal affective disorder (SAD).
| Agomelatine compared to placebo for preventing seasonal affective disorder (SAD) | ||||||
| Population: adults with a history of SAD Setting: inpatient and outpatient clinics in Europe and North America Intervention: agomelatine (25 mg a day) Comparison: placebo | ||||||
| Outcomes | Anticipated absolute effects* (95% CI) | Relative effect (95% CI) | № of participants (studies) | Certainty of the evidence (GRADE) | Comments | |
| Risk with placebo | Risk with agomelatine | |||||
| Incidence of SAD (modified ITT) assessed with: SIGH‐SAD 16 or higher within a year | Low | RR 0.83 (0.51 to 1.34) | 199 (1 RCT) | ⊕⊝⊝⊝ Very lowa, b, c | Modified ITT analysis | |
| 300 per 1000 | 249 per 1000 (153 to 402) | |||||
| Moderate | ||||||
| 500 per 1000 | 415 per 1000 (255 to 670) | |||||
| High | ||||||
| 600 per 1000 | 498 per 1000 (306 to 804) | |||||
| Number of persons with at least one adverse event within a year | Study population | RR 1.06 (0.84 to 1.34) | 225 (1 RCT) | ⊕⊝⊝⊝ Very lowa, b, c | ||
| 540 per 1000 | 572 per 1000 (453 to 723) | |||||
| Severity of depression (SIGH‐SAD score) at the end of the study | The mean severity of depression (SIGH‐SAD score at end of study) was 10.1 | MD 1.80 lower (4.58 lower to 0.98 higher) | ‐ | 199 (1 RCT) | ⊕⊝⊝⊝ Very lowa, b, c | Modified ITT analysis |
| Quality of life | No evidence identified | |||||
| Quality of interpersonal and social functioning | No evidence identified | |||||
| Number of persons with at least one severe adverse event within a year | Study population | RR 0.76 (0.17 to 3.30) | 225 (1 RCT) | ⊕⊝⊝⊝ Very lowa, b, c | ||
| 35 per 1000 | 27 per 1000 (6 to 117) | |||||
| *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; ITT: intention‐to‐treat; MD: mean difference; RCT: randomised controlled trial; RR: risk ratio; SIGH‐SAD: Structured Interview Guide for the Hamilton Depression Rating Scale, Seasonal Affective Disorders | ||||||
| GRADE Working Group grades of evidence High certainty: further research is very unlikely to change our confidence in the estimate of effect. Moderate certainty: further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate. Low certainty: further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate. Very low certainty: we are very uncertain about the estimate. | ||||||
aWe downgraded one step for "high risk of bias" due to the high attrition rate (45% in agomelatine group and 52% in placebo group). bWe downgraded one step for "indirectness" because participants in this prevention study were enrolled in a study where they received open‐label treatment with agomelatine. Only those reaching stable remission were eligible for the prevention study. This may not represent a real‐world scenario of SAD prevention. cWe downgraded one step for "imprecision" because optimal information size was not reached, and the confidence interval was broad including both a potential beneficial and harmful effect.