Summary of findings 2. Selective serotonin reuptake inhibitor compared to placebo for the treatment of depression in chronic obstructive pulmonary disease.
| Selective serotonin reuptake inhibitor (SSRI) compared to placebo for the treatment of depression in chronic obstructive pulmonary disease (COPD) | ||||||
| Patient or population: chronic obstructive pulmonary disease (COPD) with depression Setting: clinical Intervention: SSRI: paroxetine, sertraline Comparison: placebo | ||||||
| Outcomes | Anticipated absolute effects* (95% CI) | Relative effect (95% CI) | № of participants (studies) | Quality of evidence (GRADE) | Comments | |
| Risk with placebo | Risk with SSRI | |||||
|
Mean difference in depressive symptoms (from baseline to end of follow‐up) assessed with BDI, HAMD‐17 and GDS; range of possible scores: 0 to 40 (higher scores = worse symptoms); follow‐up: 6 to 12 weeks |
The standardised mean difference in depressive symptoms for placebo compared to SSRIs was 0.75 (‐1.14 lower to 2.64 higher), showing no significant difference between groups. | ‐ | 148 (2 RCTs) | ⊕⊝⊝⊝ VERY LOW 1 2 3 5 | ||
|
Adverse events (nausea, dizziness) |
While it was not possible to meta‐analyse the total adverse events rates across the studies, it was possible to meta‐analyse the results found for 2 types of medication‐specific adverse effects: nausea and dizziness. There were no significant differences between participants receiving SSRIs and those receiving placebo for nausea (OR 2.32, 95% CI 0.66 to 8.12; 171 participants; 3 studies; P = 0.19) or for dizziness (OR 0.61, 95% CI 0.09 to 4.06; 143 participants; 2 studies; P = 0.61). | ‐ | 171 (3 RCTs) |
⊕⊝⊝⊝ VERY LOW 1 4 5 | ||
|
Change in quality of life assessed with CAT and SGRQ; range of possible scores: 0 to 100 (higher scores = greater dysfunction); follow‐up: 6 weeks |
The standardised mean difference in quality of life for placebo compared to SSRIs was 1.17 (0.80 lower to 3.15 higher), showing no significant difference between groups. | ‐ | 148 (2 RCTs) | ⊕⊝⊝⊝ VERY LOW 1 2 3 5 | ||
| Change in dyspnoea | The authors indicate that dyspnoea improved post‐treatment without reaching statistical significance, but do not report post‐treatment data for this outcome. | ‐ | 23 (1 RCT) | ⊕⊝⊝⊝ VERY LOW 6 7 8 | ||
|
Change in FEV1 (l) follow‐up: 6 weeks |
The mean difference FEV1 for placebo compared to SSRIs was 0.01 litre (0.03 lower to 0.05 higher), showing no significant difference between groups. | ‐ | 148 (2 RCTs) | ⊕⊝⊝⊝ VERY LOW1 2 5 | ||
|
Change in exercise tolerance measured using a 6‐minute walk test; follow‐up: 6 weeks |
The mean difference walked on the 6‐minute walk test for placebo compared to SSRIs was 13.88 metres (11.73 higher to 16.03 higher), showing no significant difference in exercise tolerance between groups. | ‐ | 148 (2 RCTs) | ⊕⊝⊝⊝ VERY LOW1 2 5 | ||
| Change in hospital utilisation ‐ not measured | ‐ | ‐ | ‐ | ‐ | ‐ | |
| *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). BDI: Beck Depression Inventory; CAT: COPD Assessment Test; CI: confidence interval; FEV1: forced expiratory volume in 1 second; GDS: Geriatric Depression Scale; HAM‐D‐17: 17‐item Hamilton Depression Rating Scale; OR: odds ratio; RCT: randomised controlled trial; SGRQ: St George's Respiratory Questionnaire | ||||||
| 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. | ||||||
1Downgraded two levels due to risk of bias: neither of the two studies provided information regarding allocation concealment or selective reporting (Eiser 2005; He 2016). The smaller study did not describe methods of randomisation ("patients received either paroxetine 20 mg daily for 6 weeks or matched placebo in a randomised and double‐blind fashion") or blinding of outcome assessment (Eiser 2005). 2Downgraded one level: low sample size: one small study with 28 participants (Eiser 2005), and one study with 120 participants (He 2016). 3Downgraded one level: considerable heterogeneity, I² = 95%. 4Downgraded one level: low sample size: 23 participants (Lacasse 2004), 28 participants (Eiser 2005), 120 participants (He 2016). 5Downgraded one level: a small study with 28 participants was assessed at high risk of other potential sources of bias due to four out of 14 participants receiving a tricyclic antidepressant (lofepramine) instead of the SSRI paroxetine due to paroxetine‐related side effects (Eiser 2005). 6Downgraded one level: very low sample size (N = 23). 7Downgraded one level: limited data provided to verify reported non‐significant result. 8Downgraded one level: the process of allocation concealment and blinding of outcome assessment was not described.