Caumo 2009

Methods	Randomized, double‐blind, placebo‐controlled study Location: Brazil Study design: parallel, 3‐armed
Participants	A total of 63 patients randomized, 4 did not complete 59 patients completed, 20 in melatonin group, 19 in clonidine group and 20 in placebo group Age: melatonin 43.40 ± 5.48, clonidine 45.26 ± 3.40, placebo 45.35 ± 5.67 Gender (M/F) in %: melatonin: (0/100), clonidine (0/100), placebo (0/100) ASA class: I‐III Type of surgery: abdominal hysterectomy Type af anaesthesia: general and epidural
Interventions	Melatonin: 5 mg Clonidine: 100 μg Placebo Administration route: oral Time of administration: 10:00 pm the night before surgery and 1 hour preoperatively for melatonin and placebo. For clonidine an extra dose was given 36 hours postoperatively and the melatonin and placebo group both received placebo at this time
Outcomes	1. Postoperative pain assessed by pain scores (100 mm visual analogue scale) 2. Postoperative pain assessed by analgesic consumption (morphine in patient controlled analgesia) 3. Anxiety assessed by State‐Trait Anxiety Inventory (postoperative)
Notes	Sample size calculation: described 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)	Low risk	Adequately described in the article
Allocation concealment (selection bias)	Low risk	Quote: "During the entire protocol timeline, blinding and randomization were undertaken by 2 investigators who were not involved in the patient's evaluation" (page 101) (Caumo 2009)
Incomplete outcome data (attrition bias) All outcomes	Low risk	Flow diagram (figure 1) shows the 4 patients who did not complete and reasons. Quote: "...were excluded from analysis..." (page 103)
Selective reporting (reporting bias)	Unclear risk	Study protocol not available
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Quote: "During the entire protocol timeline, blinding and randomization were undertaken by 2 investigators who were not involved in the patient's evaluation. Other individuals involved in the patient's care were unaware of the treatment group to which the patient belonged" (page 101)
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Quote: "To ensure blinding, postoperative assessment was performed by a different physician from the 1 who carried out the preoperative evaluation" (page 101)