Gentil 1993.

Methods	Study design: Randomised controlled trial
Participants	Diagnosis: DSM‐III‐R panic disorder with or without agoraphobia Method of diagnosis: semi‐structured interview Age: for imipramine, M = 36.35 (SEM = 2.12); for clomipramine, M = 34.1 (SEM = 1.89) Sex: for imipramine, 70% women, 30% men; for clomipramine 50% women, 50% men Location: Brazil; setting: outpatients Co‐morbidities: patients with other medical condition, drug abuse, OCD, primary major depression or psychoses were excluded; major depression without melancholia, secondary to panic disorder, could still be included Rescue medication: Not stated
Interventions	Participants were randomly assigned to either: (1) imipramine arm (n = 20) Duration: 8 weeks Treatment Protocol: flexible dosage; range = 25 ‐ 200 mg, M = 113.8, SD = 9.5 (2) clomipramine arm (n = 20) Duration: 8 weeks Treatment Protocol: flexible dosage; range = 10 ‐ 80 mg, M = 50, SD = 4.2 (3) placebo arm (propantheline) (n = 20) Duration: 8 weeks Treatment Protocol: flexible dosage; M = 85.5, SD = 5.7
Outcomes	Time points for assessment: baseline, week 2, 4, 6 and 8 Outcomes: 1. Clinical Global Impression Scale (CGI) 2. Sheehan Anxiety Scales 3. Hamilton Rating Scale for Depression (HRSD) 4. Beck Depression Inventory (BDI)
Notes	Date of study: Not stated Funding source: grants from FAPESP and FINEP, donations from Rhodia SA, Metalurgica Matarazzo, Itautec, Soft Consultoria an Industrias Bardella SPA, Fundacao Zerbini and Fundacao Faculdade de Medicina Declarations of interest among the primary researchers: Not stated
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Quote: "they were randomly allocated". Dropouts before completing the fourth week of treatment were replaced (therefore we considered only data before replacing: number of dropouts at fourth week).
Allocation concealment (selection bias)	Unclear risk	No information provided.
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Quote "double‐blind treatment"; "Capsules were in the hospital pharmacy with tablets of the commercially available TCAs or propanteline (placebo) and filled up with lactose. The dose range of propanteline was selected to give mild to moderate peripheral anticholinergic effects".
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Quote "double‐blind treatment"; "Capsules were in the hospital pharmacy with tablets of the commercially available TCAs or propanteline (placebo) and filled up with lactose. The dose range of propanteline was selected to give mild to moderate peripheral anticholinergic effects".
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	15 patients left the trial before completing the first four weeks of treatment and were replaced. No information provided on incomplete outcome data management.
Selective reporting (reporting bias)	High risk	Data on the scales HAMD and BDI not reported at endpoint. Data on the scales CGI and Sheehan are reported only in graphs; number of patients evaluated not specified.
Other bias	Low risk	Quote: "this study was not supported by the manufacturers of the drugs tested".