Bialos 1982.

Study characteristics
Methods	Design: RCT Prerandomisation phase: no Duration post randomisation: 24 weeks Aim: "what would happen to these patients taking tricyclic antidepressants for more than 24 months if the medication were discontinued under placebo‐controlled, double‐blind conditions"
Participants	Country: USA Setting: community adults (outpatients from mental hygiene clinic of West Haven Veterans Administration Medical Center) Type of AD: amitriptyline Duration of antidepressant treatment prerandomisation: 3.7 years (0.5 to 8) Duration of antidepressant treatment post stabilisation: not reported Total number of randomised participants: 19 (10 placebo, 7 antidepressant) (2 discontinued, but no further information) Primary diagnosis: major depression (research diagnostic criteria) Severity of depressive symptoms at randomisation, mean (SD) HDRS 14.1 (not reported), placebo 15.6 (8.6), antidepressant not reported Raskin 6.6 (not reported), placebo 6.8 (1.7), antidepressant not reported Note: "although clinically stable, they experienced mild to moderate continuing depressive symptoms and anticholinergic side effects. Residual depressive symptoms may either be characteristic of these patients (dysthymia) or secondary to their being at the lower end of the recommended therapeutic range of amitriptyline dosage and plasma levels" Average age of onset of depressive disorder: 44.5 years (range 24 to 60 years) Comorbidity: anxiety neurosis 47%, alcohol problems 12%, 24% alcohol abuse in the past. Only 4 patients were free of medical illness Common problems were diabetes (n = 5; 29%), arthritis (n = 4; 24%), hypertension (n = 3; 18%), and gastrointestinal disorders (n = 2; 12%) Gender distribution (F): 3 (17%) of the completers Mean age, years (SD): 57.3 years (not reported), range 41 to 71 years Definition of remission: not described Inclusion criteria Subjects were considered clinically stable with a history of major depressive disorder and duration of long‐term antidepressant greater than 24 months Exclusion criteria Not reported
Interventions	Intervention 1: placebo Tapering scheme: tapering in 3 weekly decrements to placebo Intervention 2: continuation of the same dose of amitriptyline. The night‐time daily dose was 138 mg (range 50 to 250 mg) Co‐intervention: in both groups allowed: individual or group psychosocial treatment, unchanged throughout the study
Outcomes	Completion of the 6‐month protocol or the appearance of a depressive episode as decided upon by the patient and the research clinician Depressive symptoms measured by Hamilton total score and the 6 individual items (depression; early, middle, and late insomnia; retardation, diurnal variation), Raskin assessed by research clinician Weissman Social Adjustment Scale and Profile of Mood States at baseline, assessed by participants Adverse events measured by treatment‐emergent symptoms (TESs) (insomnia, autonomic anticholinergic) Assessed every 2 weeks for the first month, then every 4 weeks up to 6 months
Notes	Funding: not described; medication was provided by pharmaceutical industry COI: not described Note: all subjects were considered clinically stable and had been taking amitriptyline for an average of 3.7 years (range 0.5 to 8 years)
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Comment: not enough information provided. Quote: "the subjects were randomly divided into two groups, active medication and placebo"
Allocation concealment (selection bias)	Unclear risk	Comment: not enough information provided Quote: "identical placebo tablets"
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Comment: study is described as double‐blinded, and blinding appeared to be maintained Quote: "double‐blind conditions"; "a final evaluation was completed, after which the code was broken to determine whether the patient was taking active medication or placebo"
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Comment: study is described as double‐blinded, and blinding appeared to be maintained Quote: "the research clinician, who was blind to the patient's medication status"
Incomplete outcome data (attrition bias) All outcomes	High risk	Comment: 2 participants (10.5%) withdrew before completion of study. Not clear what group they were randomised to. Analysis was done on 17 completing study rather than on 19 randomised Quote: "nineteen patients started the study, but 2 stopped within the first 3 weeks. One discontinued medication on his own and the other developed a serious medical illness"; "the entire group (N = 17) was ...."
Selective reporting (reporting bias)	High risk	Comment: protocol not available. Hamilton and Raskin scores reported only for total (N = 17) participants and placebo (N = 10) participants. Not reported for active (N = 7) participants. Outcomes measured by Weissman's Social Adjustment Scale and Profile of Mood States were not reported. Adverse events were measured and reported. Study authors described withdrawal symptoms among participants who discontinued the antidepressant but reported no data Quote: "at baseline and end point there were no statistically significant differences on any scale scores for subjects receiving active medication..."
Other bias	Unclear risk	Comment: funding not described