Terra 1998.

Study characteristics
Methods	Design: multi‐phase, multi‐centre, randomised controlled trial Prerandomisation phase Phase 1: acute treatment with fluvoxamine (6 weeks) Phase 2: continuation treatment with fluvoxamine (18 weeks) Duration post randomisation: 52 weeks Aim: to test the efficacy of fluvoxamine in reducing the risk of new episodes of depression
Participants	Country: France Setting: 63 centres Type of AD: fluvoxamine Duration of antidepressant treatment prerandomisation: 24 weeks Duration of antidepressant treatment post stabilisation: 18 weeks Number of participants: 436 entered phase 1, 283 responded to phase 1 treatment, 204 maintained remission trough continuation phase 2 Total numbers of randomised participants: 204 (110 fluvoxamine, 94 placebo) Primary diagnosis: recurrent major depressive disorder Number of previous episodes, mean (SD): 3.5 (1.5) placebo, 3.5 (1.4) Gender distribution (female): placebo 78%, fluvoxamine 70% Mean age, years (SD): placebo 45 (11.4) years, fluvoxamine 44.5 (10.7) years Severity of depressive symptoms at randomisation: not reported Inclusion criteria ‐ 18 to 70 years ‐ moderate/severe episode of MDD (DSM‐III R) at entry to phase 1 ‐ no psychotic feature ‐ MADRS ≥ 25 ‐ history of ≥ 2 episodes in previous 5 years separated by symptom‐free interval ≥ 6 months ‐ "good responders" at Week 6 of acute treatment and sustained response during 18‐week open continuation treatment phase Definition of response: response to acute treatment: at Week 6, total score < 10 on MADRS and score of 1 or 2 on CGI‐S; response to continuation treatment: score < 12 for all assessments and no score higher than 1 or 2 on the CGI Severity of Illness Scale Exclusion criteria ‐ pregnant, lactating, childbearing potential and not taking adequate contraceptive measures or wishing to become pregnant during the period of the study ‐ concomitant clinically unstable disease ‐ epilepsy or history of convulsions ‐ bipolar disorder ‐ history of schizophrenia or manic episodes ‐ known hypersensitivity to fluvoxamine or previous unsuccessful treatment with fluvoxamine ‐ chronic alcoholism ‐ ECT within previous 2 weeks, requiring treatment with any non‐psychotropic drug that might interfere with the pharmacokinetics of fluvoxamine
Interventions	Intervention 1: placebo Tapering scheme: not reported Intervention 2: fluvoxamine 100 mg once a day Benzodiazepines and hypnotics for severe anxiety and insomnia were permitted during open acute and continuation treatment, provided treatment had been initiated more than 3 months before the start of the study
Outcomes	Primary outcome ‐ recurrence Definition of recurrence: reappearance of at least 5 symptoms in DSM‐III‐R criteria for major depression (2 assessments by investigator 8 days apart). Attempted or completed suicide also considered a recurrence Secondary outcome ‐ time to recurrence, depressive symptoms using MADRS score and HAM‐D score ‐ anxiety symptoms using Covi Anxiety Scale ‐ global severity of illness using CGI‐S ‐ unwanted signs and symptoms
Notes	Funding: not reported COI: not reported
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Quote: “patients were randomly assigned” 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	Quote: "double‐blind" Comment: information insufficient 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: reasons for withdrawals in phase 1 (n = 98) and in phase 2 (n = 60) Number of discontinuation was not described in the text and reason was not reported (110 fluvoxamine patients – 109 presented in Table 2); last observation carried forward analysis for MADRS, MADRS suicide score, CGI‐S, and Covi Anxiety Scale
Selective reporting (reporting bias)	High risk	Comment: no protocol available; withdrawal symptoms not an outcome; incomplete information on adverse events reported
Other bias	Unclear risk	Source of funding not reported