Stewart 1997.
| Study characteristics | ||
| Methods |
Design: multi‐phase double‐blind parallel 2‐arm randomised placebo‐controlled trial Prerandomisation phases Phase 1: acute treatment with imipramine or phenelzine (6 weeks) Phase 2: continuation trial with imipramine or phenelzine (24 weeks) Duration post randomisation: 24 weeks Aim: to assess the efficacy of phenelzine and imipramine for patients with chronic atypical depression |
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| Participants |
Country: USA Setting: community adults (outpatients from Depression Evaluation Service, an outpatient research clinic of the New York State Psychiatric Institute) Type of AD: imipramine or phenelzine Duration of antidepressant treatment prerandomisation: 30 weeks Duration of antidepressant treatment post stabilisation: 24 weeks Total number of randomised participants: imipramine comparison: 32 (15 placebo, 17 imipramine); phenelzine comparison: 28 (15 placebo and 13 phenelzine) Primary diagnosis: chronic atypical depression ‐ imipramine comparison: major depression (63%), dysthymia (18%) or both (18% currently dysthymic and history of major depression; 28% with depression superimposed on dysthymia) at least 2 years ‐ definite (67%) or probable (30%) atypical depression (phenelzine comparison: major depression (63%), dysthymia (18%), or both (18% currently dysthymic and history of major depression; 28% with depression superimposed on dysthymia) at least 2 years ‐ definite (67%) or probable (30%) atypical depression Severity of depressive symptoms at randomisation: CGI‐I 1 or 2 relative to depressed baseline state Mean duration of current depression, months (SD): imipramine 176 (142), phenelzine 284 (169) Percentage of adult life depressed (SD): imipramine 56% (23), phenelzine 73 (21) Age at onset, years (SD): imipramine 17 (13), phenelzine 11 (8) Gender distribution (F): imipramine 66%, phenelzine 46% Mean age, years (SD): imipramine 38 (7, range 27 to 55), phenelzine 39 (10, range 23 to 58) Comorbidity, n (%) ‐ imipramine: panic disorder 7 (12), GAD 3 (5), social phobia 18 (30), OCD 4 (7), eating disorder 6 (10), past history alcohol abuse/dependence 7 (28), past history substance abuse 9 (15) ‐ phenelzine: panic disorder 7 (12), GAD 3 (5), social phobia 18 (30), OCD 4 (7), eating disorder 6 (10), past history alcohol abuse/dependence 7 (28), past history substance abuse 9 (15) Inclusion criteria ‐ depressive symptoms ≥ 2 years at entry to phase 1 ‐ responders to acute trial of imipramine or phenelzine; maintained remission ≥ 6 months ‐ diagnosis of major depression, dysthymia, or both (DSM‐III criteria) and definite or probable atypical depression (Columbia University criteria) Definition of response: CGI‐S 1 or 2 Exclusion criteria ‐ not reported |
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| Interventions |
Study arm 1 Intervention 1: placebo Intervention 2: imipramine, continuation dose maintained from acute phase Study arm 2 Intervention 1: placebo Intervention 2: phenelzine, continuation dose maintained from acute phase Tapering scheme: tapering over 2 weeks |
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| Outcomes | ‐ recurrence Definition of recurrence: 2 consecutive weeks of CGI rating ≥ 3 (minimally improved, unchanged, or various categories of worsening compared with pretreatment baseline) ‐ survival analysis ‐ time to recurrence |
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| Notes |
COI: not reported Funding: study supported by a grant from the National Institute of Mental Health |
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| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Comment: information insufficient to permit judgement |
| Allocation concealment (selection bias) | Unclear risk | Comment: information insufficient to permit judgement |
| Blinding of participants and personnel (performance bias) All outcomes | Low risk | Comment: blinding of participants and personnel; blinding unlikely to have been broken Quote: "after randomisation and for the remainder of the study, patients and doctors were blind to treatment" |
| Blinding of outcome assessment (detection bias) All outcomes | Low risk | Comment: blinding of outcome assessors (doctors); blinding unlikely to have been broken Quote: "at each visit, the physician completed a Hamilton depression scale and CGI" |
| Incomplete outcome data (attrition bias) All outcomes | Unclear risk | Comment: although dropouts are low (2), reasons are not reported |
| Selective reporting (reporting bias) | High risk | Comment: adverse events and withdrawal symptoms are not reported; they are a fundamental outcome in drug discontinuation studies |
| Other bias | Low risk | None |