Kocsis 1996.

Study characteristics
Methods	Design: multi‐phase double‐blind randomised placebo‐controlled trial Prerandomisation phases Phase 1: acute treatment with desipramine 20 mg to 200 mg (10 to 12 weeks) Phase 2: continuation treatment with desipramine same dose (16 weeks) Post randomisation duration: 104 weeks Aim: to compare desipramine hydrochloride and placebo for maintenance therapy of remitted patients with chronic depression
Participants	Country: USA Setting: community adults (selected from responders to advertisements for chronic depression and patients seeking treatment for depression at a psychiatric outpatient clinic) Type of AD: desipramine Duration of antidepressant prerandomisation: 26 to 28 weeks Duration of antidepressant after stabilisation: 16 weeks Number of participants: 129 entering phase 1, 105 completed phase 1, 66 entered phase 2, 54 completed phase 2 Total number of randomised participants: 53 (25 placebo, 28 desipramine) Primary diagnosis ‐ pure dysthymia ‐ double depression ‐ chronic major depression (number of participants not reported for RCT) Severity of depressive symptoms at randomisation (HMDR), mean (SD): not reported for each group at randomisation; full remission reported for 40 participants; partial remission reported for 10 participants Gender distribution (F): presented by type of depression rather than by treatment group: 51% pure dysthymia, 61% double depression, 64% chronic major depression at baseline of phase 1 Mean age: presented by type of depression rather than by treatment group: 37 (10) pure dysthymia, 37 (9) double depression, 36 (11) chronic major depression at baseline of phase 1 Inclusion criteria ‐ outpatients who met DSM‐III‐R diagnostic criteria for "pure" dysthymia, dysthymia with current major depression ("double depression"), or chronic major depression with full/partial remission after desipramine treatment (10 to 12 weeks acute and 16 weeks continuation phases) Definition remission Full remission: HAM‐D scores < 7 and GAS scores > 70 on 3 consecutive biweekly ratings Partial remission: ≥ 50% reduction from baseline HAM‐D score, HAM‐D score ranging from 7 to 12, and GAS ≥ 60 on 3 successive ratings Exclusion criteria ‐ diagnosis of schizophrenia ‐ current substance abuse or dependence ‐ history of mania or definite hypomania ‐ any severe or chronic medical illness or medical contraindication to desipramine
Interventions	Intervention 1: identical placebo at the same dose equivalent Tapering scheme: tapered by approximately 25% a week over a month, then received identical placebo for the same dose equivalence for the next 100 weeks or until relapse Intervention 2: continuation of desipramine at the same dose Tapering scheme: tapered by approximately 25% per week over the month Co‐intervention: stable long‐term psychotherapy during the study is allowed
Outcomes	‐ relapse Definition of relapse: HAM‐D > 12 and GAS < 60 on 3 successive ratings over 4 weeks, or at least 1 rating meeting these criteria and an urgent need for alternative treatment for a depressive syndrome ‐ time to relapse
Notes	Funding: study was supported by a grant from the National Institute of Mental Health and the pharmaceutical industry; matching placebo was provided by the pharmaceutical industry COI: not reported
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	Unclear risk	Comment: information insufficient to permit judgement Quote: “double‐blind”; “plasma drug level was reviewed by a non‐blind observer who was not involved in the treatment. The nonblind observer gave instructions or dummy instructions for dosage adjustments”
Blinding of outcome assessment (detection bias) All outcomes	High risk	Comment: possible bias due to absence of independent raters is reported by study authors Quote: "ratings were done by study clinicians who may have been able to guess the maintenance treatment based on side effects"
Incomplete outcome data (attrition bias) All outcomes	Low risk	Comment: 50/53 patients completed the study; number of dropouts balanced across both groups – 2/25 placebo and 1/28 desipramine
Selective reporting (reporting bias)	High risk	Comment: study protocol is not available (given age of study, might not have been a necessity then). Study does not measure safety outcomes (adverse events and withdrawal symptoms). Withdrawal symptoms were not an outcome. None of our secondary outcomes were reported.
Other bias	Unclear risk	Comment: grant from the pharmaceutical industry