Kane 1982.
| Study characteristics | ||
| Methods |
Design: multi‐phase, randomised, placebo‐controlled trial Prerandomisation phase: phase 1: open continuation treatment with imipramine flexible dose and 150 mg in last 6 weeks (24 weeks) Duration post randomisation: 104 weeks Aim: to compare lithium carbonate, imipramine, lithium carbonate plus imipramine, and placebo for relapse prevention in patients with unipolar disease. Only treatment arms without lithium were relevant for this review (as the review is looking at antidepressant discontinuation; lithium is not an antidepressant) |
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| Participants |
Country: USA Setting: depression clinic Type of AD: imipramine Duration of antidepressant treatment prerandomisation: 24 weeks Duration of antidepressant treatment post stabilisation: 24 weeks Number of participants: not reported for phase 1 Total numbers of randomised participants: 11 (imipramine 5, placebo 6) Primary diagnosis: recurrent unipolar major depressive disorder (study arm bipolar disorders not relevant) Number of previous episodes: mean 7.2 (SD 6.2), 70% ≥ 4 episodes, 22.6% 3 episodes, 7.4% 2 episodes Age at first depressive episode: 21.3 placebo, 36.7 imipramine Gender distribution (female): 63% of total sample male (with bipolar treatment study arm); gender not reported by treatment group Mean age, years (SD): 53.2 imipramine (SD not reported), 38.5 placebo (SD not reported) Severity of depressive symptoms at randomisation: not reported Inclusion criteria ‐ met Research Diagnostic Criteria (RDC) for recurrent unipolar major depressive disorder or for bipolar depression with hypomania (bipolar II illness) ‐ had experienced ≥ 2 episodes of depression or mania in the previous 7 years ‐ had been euthymic for 6 months before entry into the study ‐ between the ages of 18 and 65 years ‐ free of coexisting medical illnesses that might complicate the use of lithium carbonate or imipramine ‐ signed a consent form Definition of response/remission: "euthymia"; no criteria specified Exclusion criteria ‐ not clearly defined |
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| Interventions |
Intervention 1: imipramine Intervention 2: placebo Imipramine: dosage at 100 to 150 mg/d, according to clinical judgement. Tapering scheme: not reported Each treatment group received lithium placebo (placebo tablets cancel each other out) |
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| Outcomes |
Primary outcomes ‐ relapse ‐ definition of relapse/recurrence: RDC for major depressive disorder and symptoms persisted for a week after evaluation; RDC criteria for minor depressive disorder persisted for 4 successive weeks and were removed (also RDC criteria for mania, even if symptoms had not persisted for a week) Secondary outcome ‐ mania, hypomania, and dropouts due to euthymia |
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| Notes |
Funding: supported in part by a grant from the Goldman Foundation (non‐commercial foundation) COI: not reported |
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| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Quote: ”patients were randomly assigned” Comment: insufficient information to permit judgement |
| Allocation concealment (selection bias) | Unclear risk | Comment: information insufficient to permit judgement |
| Blinding of participants and personnel (performance bias) All outcomes | Unclear risk | Quote: “double‐blind.....patients were given treatment by a physician blind to the regimen” Comment: does not state how patients were blinded; insufficient information to permit judgement |
| Blinding of outcome assessment (detection bias) All outcomes | Unclear risk | Comment: information insufficient to permit judgement |
| Incomplete outcome data (attrition bias) All outcomes | Unclear risk | Comment: although reasons for dropping out are reported, study authors do not explicitly state the numbers and reasons by treatment group (e.g. depressive relapse outcome); only 5 patients in placebo group, whereas 6 were randomised |
| Selective reporting (reporting bias) | High risk | Comment: study report fails to include results for adverse events and withdrawal symptoms that would be expected to have been reported for a discontinuation study. None of our secondary outcomes were reported |
| Other bias | Low risk | Comment: study appears to be free from other sources of bias |