Naguib 2000

Methods	Randomized, double‐blind, placebo‐controlled study Location: Saudi Arabia Study design: parallel, 3‐armed, comparative, dose‐response study
Participants	A total of 84 patients randomized 84 patients completed: 36 (12, 12, 12) in melatonin group, 12 in placebo group, 36 (12, 12, 12) in midazolam group Age: melatonin 0.05 mg/kg (30.3 ± 5.6), 0.1 mg/kg (28.4 ± 6.1), 0.2 mg/kg (28.2 ± 6.1) Midazolam: 0.05 mg/kg (23.4 ± 3.9), 0.1 mg/kg (26.2 ± 6.6), 0.2 mg/kg (28.9 ± 6.0) Placebo 29.8 ± 6.1 Gender (M/F) in %: melatonin (0/100), placebo (0/100), midazolam (0/100) ASA class: I Type of surgery: gynaecological laparoscopic procedures Type of anaesthesia: general Baseline (anxiety, pain) described: yes, no
Interventions	Melatonin: 0.05 mg/kg, 0.1 mg/kg, 0.2 mg/kg Placebo: saline Midazolam: 0.05 mg/kg, 0.1 mg/kg, 0.2 mg/kg Administration route: sublingual Time of administration: approximately 100 min preoperatively
Outcomes	1. Anxiety assessed by Visual Analogue Scale (0 to 100) (pre‐ and postoperative) 2. Orientation score (0 to 2) 3. Sedation score (0 to 4) 4. Psychomotor activity measured by The Digit‐symbol Substitution Test and Trieger dot test 5. Amnesia by showing line diagrams 6. Postoperative pain assessed by Visual Analogue Scale (0 to 100) and morphine consumption (mg)
Notes	Sample size calculation: described Author contacted by e‐mail on 9 August 2013 to clarify unspecified issues ‐ e‐mail returned = delivery failure
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Quote: "...randomly allocated..." (page 473) (Naguib 2000)
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: "... marked only with a coded label to maintain the double‐blind nature of the study" (page 474) "The contents of the syringe was given sublingually...by a resident not involved in the management of the patient or in the data collection" (page 474)
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Quote: "The same psychologist blinded to group assignment performed all test scoring and calculations" (page 474)