Gilaberte 2001.

Study characteristics
Methods	Design: multi‐phase double‐blind randomised placebo‐controlled trial Prerandomisation phases Phase 0: washout phase (1 week) Phase 1: acute treatment with fluoxetine 20 mg of 40 mg (8 weeks) Phase 2: continuation treatment with fluoxetine 20 mg of 40 mg (24 weeks) Duration post randomisation: 48 weeks Aim: to evaluate the efficacy and safety of fluoxetine 20 mg/d for relapse prevention and for extending the time free of symptoms among patients with recurrent unipolar major depression
Participants	Country: Spain Setting: community adults (10 centres) Type of antidepressant: fluoxetine 20 mg Duration antidepressant treatment prerandomisation: 32 weeks Duration antidepressant treatment post stabilisation: 24 weeks Primary diagnosis: recurrent depression Number of participants: 253 entered phase 1, 145 achieved recovery at end of phase 2 Total number of randomised participants: 140 (70 placebo, 70 fluoxetine) Severity of depressive symptoms at randomisation (HAM‐D 17) (SD): 3.1 (2.7) placebo, 2.8 (2.0) fluoxetine Number of previous episodes: 2.6 (1.5) placebo, 2.3 (1.2) antidepressant Gender (female %): 78.6 in both groups Age, years: 43.8 placebo, 44.4 fluoxetine Inclusion criteria ‐ 18 to 65 years ‐ ≥ 1 previous major depressive episode in the last 5 years (DSM‐III‐R criteria) ‐ ≥ 18 on the HAM‐D 17 and ≥ 4 on the CGI Severity Scale in the index episode of depression ‐ received no pharmacological treatment during index depressive episode ‐ responded to acute treatment and remained in response during continuation period Definition of response/remission: no longer met the diagnostic criteria for major depression per DSM‐III‐R, and had HAM‐D 17 scores ≤ 8 and CGI severity scores ≤ 2) Exclusion criteria ‐ patients with other Axis I diagnoses ‐ organic mental disorders ‐ history of drug abuse or severe physical illness ‐ at risk for suicide ‐ pregnant or breast‐feeding women and women of childbearing potential not using adequate contraceptive measures ‐ resistant to pharmacological treatment during previous depressive episodes
Interventions	Intervention 1: placebo Intervention 2: fluoxetine 20 mg per day Tapering scheme: not reported
Outcomes	Recurrence Definition of relapse/recurrence: meeting DSM‐III‐R criteria for major depression and HAM‐D 17 score ≥ 18 and CGI‐S score ≥ 4, or both of these, for at least 2 weeks HAM‐D 17, CGI‐S, CGI‐I, and Hamilton Rating Scale for Anxiety Treatment‐emergent adverse events, reasons for discontinuations, changes in blood pressure, ECG, weight Adverse events were collected by non‐probing inquiry and were recorded without regard to causality
Notes	Funding: study was supported by a grant from pharmaceutical companies COI: not reported; first author is a member of European Product Team Physicians of the pharmaceutical company
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Comment: no information
Allocation concealment (selection bias)	Unclear risk	Comment: method of concealment not described
Blinding of participants and personnel (performance bias) All outcomes	Unclear risk	Comment: insufficient information to permit judgement Quote: "double‐blind"
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	Comment: insufficient information to permit judgement Quote: " ...patients were evaluated monthly by psychiatrists for recurrence of depression..."
Incomplete outcome data (attrition bias) All outcomes	High risk	Comment: much higher dropout rate in discontinuation group (41/70) than in antidepressant group (21/70)
Selective reporting (reporting bias)	High risk	Comment: protocol was not available; outcomes were not clearly pre‐specified, nor were the time points at which they were to be measured. Adverse events were reported. Withdrawal symptoms were not an outcome. None of our secondary outcomes were reported
Other bias	Unclear risk	Comment: grant from pharmaceutical industry