Spiker 1985.

Study characteristics
Methods	Randomised, double‐blind comparison Random assignment procedure described in part Blinding adequately described
Participants	SADS and RDC criteria for major depressive disorder, primary subtype, and psychotic subtype (only with delusions); bipolar participants included Severity rating ≥ 4 on 6‐point scale in the SADS that rates severity of delusion HRSD‐17 > 14 Inpatients No data about prior treatment for current episode
Interventions	3 groups: perphenazine vs amitriptyline vs amitriptyline + perphenazine Doses: perphenazine mean 50 mg vs amitriptyline mean 218 mg vs amitriptyline mean 170 mg + perphenazine mean 54 mg Blood levels: perphenazine 19 to 113 ng/mL vs amitriptyline (+ nortriptyline) 130 to 500 ng/mL vs amitriptyline 157 to 690 ng/mL + perphenazine 18 to 128 ng/mL 7 days drug free Treatment period: 4 weeks Additional medication: benztropine mesylate 4 mg
Outcomes	Dichotomous data: study author defined: response is HRSD‐17 < 7 and delusional rating score = 1 (6‐point scale in the SADS). No remission data (definition of response is definition of remission) Continuous data: symptom reduction: no ITT data; global response: no ITT data; QOL: no data Overall dropout rate: yes Dropout due to adverse effects: amitriptyline + perphenazine 2/22, perphenazine 1/17 Mortality rate: 0
Notes	Only participants with delusions 7 drop out in ITT (in the original data, dropouts are excluded from the analysis); response data ITT 3/17 (original 3/16); 7/19 (7/17); 14/22 (14/18) 9/58 = 15.5% bipolar participants in analysis. Because of lack of data, we were not able to exclude these bipolar participants from the analysis
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	As reported: "the hospital pharmacist assigned patients randomly"
Allocation concealment (selection bias)	Low risk	Probably yes: "the hospital pharmacist assigned patients randomly"
Blinding (performance bias and detection bias) of participants	Low risk	As reported: "the hospital pharmacist assigned patients randomly. All tablets looked identical" "All raters and floor staff and the patient were blind to the patient's drug treatment and the plasma‐level data"
Blinding (performance bias and detection bias) of personnel	Low risk	As reported: "the hospital pharmacist assigned patients randomly. All tablets looked identical" "All raters and floor staff and the patient were blind to the patient's drug treatment and the plasma‐level data"
Blinding (performance bias and detection bias) of outcome assessors	Low risk	As reported: "the hospital pharmacist assigned patients randomly. All tablets looked identical" "All raters and floor staff and the patient were blind to the patient's drug treatment and the plasma‐level data"
Incomplete outcome data (attrition bias) All outcomes	Low risk	None
Selective reporting (reporting bias)	Unclear risk	No protocol available. Generally accepted outcomes have been used
Other bias	Unclear risk	Only participants with delusions are included 9/58 = 15.5% bipolar participants in analysis. Because of lack of data, we were not able to exclude these bipolar participants from the analysis We re‐analysed the data to ITT