Hanlon 1964.

Methods	Allocation: randomised. Blindness: double. Duration: 12 weeks, preceded by 2 weeks wash‐out. Setting: multi‐centre.
Participants	Diagnosis: 115 anergic, withdrawn psychotic patients of which at least 99 with schizophrenia. N = 115 (n = 58 relevant). Age: range 21 to 74 years, mean 54±10.5 years. Sex: 115 F. History: inpatient. Included: no details. Excluded: over 75 years of age, diagnosed with one of the chronic brain disorders, manifested complicated physical condition. Consent: not stated.
Interventions	1. Perphenazine: 4 mg three times daily for two weeks, then 8 mg three times daily for 10 weeks, N = 29. 2. Placebo: one tablet three times daily for two weeks, then two tablets three times daily for 10 weeks, N = 29. [3. Amitriptyline: 25 mg three times daily for two weeks, then 50 mg three times daily for 10 weeks, N = 29.] [4. Amitriptyline ‐ perphenazine: 25 mg and 4 mg three times daily for two weeks, then 50 mg and 8 mg three times daily for 10 weeks, N = 28.]
Outcomes	Leaving the study early – any reason/ adverse events. Adverse events: hypotension; dry mouth; nausea; body pains; dizziness; drowsiness; insomnia; weakness; oedema; tremors; tenseness; agitation; severe regression. Unable to use ‐ Mental state: IMPS, PRP (no SD/P value). Behaviour: MACC (no SD/P value). Laboratory tests (no data).
Notes
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Randomised – no further details.
Allocation concealment (selection bias)	Unclear risk	Not stated. Quote: “ultimate medical responsibility for the patients remained in the hands of the ward physicians, who were aware of the design and study‐drugs” (p53).
Blinding (performance bias and detection bias) All outcomes	Unclear risk	Stated double blind; quote, “medication, administered in a double blind fashion, was dispensed to the wards from the pharmacy in containers identified only by the patient name and number” (p53). However, see above (allocation concealment).
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	11% (n = 13) dropped‐out of the study. Quote, "n = 5 placebo patients were discontinued and transferred to the infirmary for medical reasons unrelated to treatment; the remaining three patients were described as either overactive, restless or agitated. One perphenazine patient was dropped because of hypotension and elevated temperature, and another because of nausea and weakness" (p55). Another n = 5 participants were lost in the two other treatment arms.
Selective reporting (reporting bias)	High risk	No SD or P values reported for scale data.
Other bias	High risk	Funding: supported in part by Merck Sharp and Dohme Research Laboratories, West Point, Philadelphia (US). Raters: not independent of treatment.