Spiker 1988.

Study characteristics
Methods	Re‐analysing 2 studies (not including data from Spiker 1985) Randomised, double‐blind, placebo‐controlled Randomisation procedure not explicitly described Blinding adequately described in original studies
Participants	Re‐diagnosing by using DSM‐III criteria Major depressive disorder DSM‐III HRSD‐17 > 14 (≥ 30 based on the sum of 2 raters) Inpatients. Subgroup psychotic participants No data about prior treatment for current episode
Interventions	Amitriptyline vs placebo 3 days 50; 4 days 100; 7 days 150; 14 days 200 mg amitriptyline (at least 3 weeks ≥ 150 mg) Blood levels: unknown Extra medication: none 2 weeks' drug‐free washout period 1 week placebo (single‐blind); total period of 3 weeks drug free Treatment period: 4 weeks
Outcomes	Dichotomous data: study author defined: response is HRSD‐17 < 7 (< 14/2) + not psychotic or HRSD‐17 = 6.5 to 9.5 (13/2 to 19 /2) + not psychotic + 1/3 or less of entering score Remission data not specified Continuous data: symptom reduction: no data; global response: no data; QOL: no data Overall dropout rate: yes Dropout due to adverse effects: no data Mortality rate: 0 (no data)
Notes	20% response in 2‐week drug‐free period (psychotic + non‐psychotic); no data about psychotic vs non‐psychotic in these 2 weeks 4 weeks' treatment; only 2 weeks 200 mg; no blood levels Subgroup of 27 participants with psychotic depression. Amitriptyline 14; placebo 13 Dropouts 4 (amitriptyline) and 3 (placebo) are excluded from analysis by study authors. Responders amitriptyline 4/10 and placebo 0/10. ITT responders: amitriptyline 4/14 and placebo 0/13
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	As reported: "patients were randomly assigned"
Allocation concealment (selection bias)	Unclear risk	No data
Blinding (performance bias and detection bias) of participants	Low risk	As reported: "all patients received 4 identical capsules daily: patients and staff were blind"
Blinding (performance bias and detection bias) of personnel	Low risk	As reported: "all patients received 4 identical capsules daily: patients and staff were blind"
Blinding (performance bias and detection bias) of outcome assessors	Unclear risk	No data
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	None
Selective reporting (reporting bias)	Unclear risk	No protocol available. Generally accepted outcomes have been used
Other bias	High risk	Participants were retrospectively re‐diagnosed. Psychotic depression and non‐psychotic depression were included and randomly assigned. We used the data about psychotic participants 14 days' drug‐free period (20% remission with no further data) + 1 week placebo before random assignment could be due to low placebo response