Ionescu 2008

Methods	Randomized, double‐blind, placebo‐controlled study Location: Romania Study design: parallel, 3‐armed
Participants	A total of 53 patients randomized 53 patients completed: 18 in melatonin group, 17 in midazolam group, and 18 in placebo group Age: melatonin 43.05 ± 11.40, midazolam 48.76 ± 12.61, placebo 48.38 ± 10.11 Gender (M/F) in %: not adequately described ASA class: I‐II Type of surgery: laparoscopic cholecystectomy Type of anaesthesia: general Baseline (anxiety, pain) described: no, no
Interventions	Melatonin: 3 mg Midazolam: 3.75 mg Placebo Administration route: sublingual Time of administration: the night before surgery and 90 min preoperatively
Outcomes	1. Sedation assessed by score 1 to 4 2. Anxiety assessed by CD Spielberger's questionnaire, State‐Trait Anxiety Inventory (STAI‐S) (pre‐ and postoperative) 3. Quality of postoperative sleep (good sleep, insomnia, nightmares) 4. Amnesia after recovery from anaesthesia (5 pictures) 5. Postoperative pain assessed by a visual analogue scale ‐ verbal rating (1 to 5) 6. Intraoperative fentanyl requirements
Notes	Sample size calculation: described but not adequately Author contacted by e‐mail on 5 July 2013 to clarify unspecified issues: no answer
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Quote: "...randomly allocated..." (page 9) (Ionescu 2008)
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	Low risk	Quote: "To maintain the double‐blind nature of the study, the syringes were unmarked." (page 9)
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Quote: "A registrar blinded to the group assignment performed all the tests" (page 9)