Cook 1986.

Study characteristics
Methods	Design: double‐blind randomised placebo‐controlled trial Prerandomisation phase: no Duration post randomisation: 28 weeks Aim: to evaluate the rate of relapse following discontinuation of antidepressant therapy in elderly depressives
Participants	Country: USA Setting: community adults (outpatients from Iowa City VA Geriatric Psychiatry Clinic) Type of antidepressant: TCA (desipramine, amitriptyline, doxepine, imipramine) Duration of antidepressant treatment prerandomisation: from 12 months to 192 months Duration of antidepressant treatment post stabilisation: from 12 months to 96 months Total number of randomised participants: 18 (9 placebo, 6 antidepressant) Primary diagnosis: major depression disorder with at least 1 previous episode Number of previous depressive episodes: from 1 to "too many to count" placebo, from 1 to "too many to count" antidepressants Severity of depressive symptoms at randomisation (HDRS score), mean (SD): 5.1 (3.9) placebo, 4.8 (3.5) antidepressant (at week 4, before discontinuation) Gender distribution (F): 0% Mean age, years: 63.2 Inclusion criteria ‐ chart diagnosis of major depressive disorder (Research Diagnostic Criteria) ‐ had been treated with a TCA for a year or longer without evidence of recurrence of depressive symptoms warranting a change in therapy ‐ patients interviewed using SADS‐L and only those who met Research Diagnostic Criteria for unipolar depression were included Definition of remission: use of AD without evidence of recurrence of depressive symptoms warranting a change in therapy Exclusion criteria ‐ not reported
Interventions	Intervention 1: tapering to placebo Tapering scheme: gradually over either 4 (4 persons) or 8 (5 persons) weeks. Intervention 2: continuation of the same dose of active medication
Outcomes	Recurrence, monthly measured or until recurrence Definition of relapse/recurrence: investigator’s clinical assessment that change in pharmacological treatment was indicated Change from baseline in depressive symptoms, measured by Hamilton Depression Rating Scale (HDRS), Montgomery Asberg Depression Rating Scale (MADRS), Carroll Depression Scale (Carroll) Adverse events, measured by Treatment‐Emergent Symptoms Scale (TESS)
Notes	Funding: not described COI: not described
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Comment: insufficient information to judge Quote: “randomly assigned”
Allocation concealment (selection bias)	Unclear risk	Comment: not described
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Comment: blinding of participants and key study personnel ensured; unlikely that blinding could have been broken Quote: “the study was conducted under double‐ blind conditions”; " ... identical appearing placebo or active medication..."; "...reoccurrence was assessed by the psychiatrist (B.L.C.) blind to whether the patient was on placebo or active medication"
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Comment: blinding of outcome assessment ensured; unlikely that blinding could have been broken Quote: "reoccurrence was defined as the blind investigator’s clinical assessment that change in pharmacologic treatment was indicated"
Incomplete outcome data (attrition bias) All outcomes	Low risk	Comment: 3/18 withdrew before randomisation but reasons clearly stated
Selective reporting (reporting bias)	High risk	Comment: study protocol not available, although given the age of this study, protocols might not have been standard practice at that time. Study authors report that they assessed participants on the Treatment‐Emergent Symptoms Scale, yet adverse events were reported incompletely. Withdrawal symptoms were not an outcome
Other bias	Unclear risk	Source of funding not reported