Acil 2004

Methods	Randomized, double‐blind, placebo‐controlled study Location: Turkey Study design: parallel, 3‐armed (melatonin, midazolam, placebo)
Participants	A total of 66 patients, 22 patients in each arm Age: melatonin 39.9 ± 7.5, midazolam 37.3 ± 7.8, placebo 39.2 ± 6.8 Gender: not described ASA class: I‐II Type of surgery: laparoscopic cholecystectomy Type of anaesthesia: general Baseline (anxiety, pain) described: yes, no
Interventions	Melatonin: 5 mg Midazolam: 15 mg Placebo Administration route: sublingual Time of administration: 90 min preoperatively
Outcomes	1. Anxiety measured by visual analogue scale (pre‐ and postoperative) 2. Sedation score 1 to 4 3. Orientation score 0 to 2 4. Psychomotor performance measured with Trail Making A and B tests and the Word Fluency test All outcomes were evaluated before (baseline), and 10, 30, 60 and 90 min after premedication had been given, and after the operation at 15, 30, 60 and 90 min in the recovery room 5. Pain measured by visual analogue scale 6. Satisfaction score (yes or no)
Notes	Sample size calculation: not described Author (Karagöz) contacted by e‐mail on 4 July 2013 to clarify unspecified issues: no answer Author (Acil) contacted by telephone on 9, 14, 17 October 2013 to clarify unspecified issues: no answer
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	No information provided. Described as randomized
Allocation concealment (selection bias)	Unclear risk	No information provided
Incomplete outcome data (attrition bias) All outcomes	Low risk	No reported dropouts or missing data
Selective reporting (reporting bias)	Unclear risk	Study protocol not available
Blinding of participants and personnel (performance bias) All outcomes	Unclear risk	Information not provided for taste of study drug
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Quote: "a doctor blinded to the group assignment performed all tests" (page 554) (Acil 2004)