Borson 1992.

Methods	Study design: Randomised, placebo‐controlled, double‐blind trial Country: USA
Participants	Sample size: N = 36 randomised, but only 30 participants completed the trial and were included in the analysis Mean age: Intervention group: 58.7 years (SD ± 9.9); placebo group: 63.2 years (SD ± 8.3) Gender: N = 22 male, N = 14 female in total Inclusion criteria: Primary diagnosis of moderate to severe COPD (FEV1 and FEV1/FVC < 60% of predicted) and a coexisting depressive disorder determined by psychiatric assessment (structured clinical interview) based on DSM‐III Exclusion criteria: Other medical illness more disabling than COPD, severe cognitive impairment, recent stroke or myocardial infarction, current alcohol abuse, or other psychotropics that could not be discontinued before the trial commenced. Individuals taking more than 40 g prednisone daily and those on home oxygen were also excluded.
Interventions	Intervention: Tricyclic antidepressant (nortriptyline) Control: Placebo Duration: 12 weeks Dose: Started at 1/4 of 1 mg/kg of body weight, which was increased weekly until target reached (usually by 4th week), maintained for 8 weeks Number of participants randomised to intervention: N = 18; participants who completed the trial: N = 13 Number of participants randomised to the control group: N = 18; participants who completed the trial: N = 17
Outcomes	Primary outcomes reported: Mood change: CGI, HAM‐D, PRAS Dyspnoea: PFSI, VAS Distressing physical symptoms: PRAS Functional status: PFSI, Sickness Impact Profile, spirometry, blood gasses, 12‐minute walk test Time frame: All outcomes were measured at baseline and at end of the study.
Notes	One participant had been treated with doxepin prior to the trial entry. This participant experienced marked improvement in mood and functional status. Also, 3 participants were dysthymic (mild but chronic depression) when entering the study. The study was supported by the Medical Research Service of the Department of Veterans Affairs and approved by the University of Washington Human Research Committee.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Assignment to treatment condition was performed by a pharmacist blinded to the study questions using a table of random numbers.
Allocation concealment (selection bias)	Unclear risk	All study personnel were blind to medication assignment until completion of all evaluations; no further details provided to permit judgement on allocation concealment.
Blinding of participants and personnel (performance bias) All outcomes	Low risk	All study personnel were blind to medication assignment until completion of all evaluations.
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Double‐blind, placebo‐controlled trial
Incomplete outcome data (attrition bias) All outcomes	High risk	Dropout mentioned, but not reported per group. Only participants who completed the trial from the intervention group were taken into account. However, dropout in the intervention group was much higher than in the control group (5:1).
Selective reporting (reporting bias)	Unclear risk	Insufficient information to permit judgement. Prespecified study protocol was not published or available.
Other bias	Low risk	No other bias identified.