CNCPS 1992.

Methods	Study design: Randomised controlled trial
Participants	Diagnosis: DSM‐III panic disorder with limited or extensive phobic avoidance (panic attacks with agoraphobia) Method of diagnosis: "patients were evaluated by Structured Clinical Interview for DSM‐III Diagnosis, Upjohn (SCID‐UP) Age: M = 34, SD not provided Sex: 62 % female, 38 % male Location: 12 centres in USA, Spain, Denmark, Germany, England, Italy, Brazil, Mexico, France, Colombia, Austria, Sweden, Canada, Belgium; setting: inpatients and outpatients Co‐morbidities: patients with psychotic disorders, dementia, bipolar disorder, alcoholism or drug abuse within the last six months or significant medical problems were excluded. Patients with current major depression were excluded unless the depression was judged to be secondary to the anxiety disorder and did not have melancholic or psychotic features. Rescue medication: Quote "patients taking CNS drugs, including benzodiazepines, were excluded from the study. During the washout period, blood was drawn for benzodiazepines screening".
Interventions	Participants were randomly assigned to either: (1) imipramine arm (n = 391) Duration: 8 weeks Treatment Protocol: flexible dosage; range = 25 ‐ 250 mg, M = 155, SD not provided (2) alprazolam arm (n = 386) Duration: 8 weeks Treatment Protocol: flexible dosage; range = 1 ‐ 10 mg, M = 5.7, SD not provided (3) placebo arm (n = 391) Duration: 8 weeks
Outcomes	Time points for assessment: baseline, weekly, endpoint Outcomes: 1. Physician's and patient's global improvement scales 2. Panic Attack Scale, patient's diary 3. Overall Phobia Scale (Marks & Matthews), Phobic Anxiety Factor of the Symptom Check List (SCL‐90) 4. anticipatory anxiety 5. Hamilton Rating Scale for Anxiety (HAMA) 6. social functioning, five‐point scale 7. Hamilton Rating Scale for Depression (HRSD) 8. Hopkins SCL‐90 patient self‐rating scale for presence and intensity of symptoms
Notes	Date of study: Data collection: 1984 ‐ 1987 Funding source: sponsored by Upjohn Company, Kalamazoo, Michigan 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: "randomly assigned"; "alprazolam, imipramine or placebo were assigned in 12 randomization blocks of the basic three cell random‐assignment, parallel treatment‐design. [...] At each center patients were blindly and randomly assigned to alprazolam, imipramine or placebo treatment, based on a table of random numbers [...]. Patients removed from the protocol before three weeks had to be replaced; after three weeks, non‐completers were not replaced."
Allocation concealment (selection bias)	Unclear risk	No information provided.
Blinding of participants and personnel (performance bias) All outcomes	Unclear risk	Quote "double‐blind design". No further details.
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	Quote "double‐blind design". No further details.
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	Quote: "of 1168 patients randomized, 1122 met criteria for ITT".
Selective reporting (reporting bias)	High risk	In the primary publication, data on Panic Attack scale are not reported; data on Physician's global Improvement scale are only partially reported, and without the number of patients evaluated; data on other continuous outcomes (HAMA, HRSD) are reported without number of patients evaluated. Other data are partially reported in secondary publication of this study.
Other bias	High risk	Sponsored by Upjohn Company, Kalamazoo, Michigan; the role of the funder in planning, conducting and writing the study is not discussed.