Melatonin vs. midazolam premedication in children: a double-blind, placebo-controlled study

Eur J Anaesthesiol. 2005 Mar;22(3):189-96. doi: 10.1017/s0265021505000335.


Background and objective: Unlike midazolam, melatonin premedication is not associated with cognitive impairment in adults despite its anxiolytic properties. The use of melatonin as a premedicant in children has not been reported. This randomized, double-blind, placebo-controlled study compared the perioperative effects of different doses of melatonin and midazolam in children.

Methods: Seven groups of children (n = 15 in each) were randomly assigned to receive one of the following premedicants. Midazolam 0.1, 0.25 or 0.5 mg kg(-1) orally, melatonin 0.1, 0.25 or 0.5 mg kg(-1) orally each mixed in 15 mg kg(-1) acetaminophen, or placebo only (15 mg kg(-1) acetaminophen). Anxiety and temperament were evaluated before and after administration of the study drug, on separation from parents and on the introduction of the anaesthesia mask. At week 2 postoperatively, the behaviour of the children was measured by the Post Hospitalization Behaviour Questionnaire.

Results: Melatonin or midazolam each in doses of 0.25 or 0.5 mg kg(-1) were equally effective as premedicants in alleviating separation anxiety and anxiety associated with the introduction of the anaesthesia mask. A trend was noted for midazolam to prolong recovery times as the dosage increased. The use of melatonin was associated with a lower incidence (P = 0.049) of excitement at 10 min postoperatively, and a lower incidence (P = 0.046) of sleep disturbance at week 2 postoperatively than that observed with midazolam and control groups. No postoperative excitement was noted in the melatonin groups at 20, 30 and 45 min.

Discussion: Melatonin was not only as effective as midazolam in alleviating preoperative anxiety in children, but it was also associated with a tendency towards faster recovery, lower incidence of excitement postoperatively and a lower incidence of sleep disturbance at week 2 postoperatively.

Publication types

  • Clinical Trial
  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anesthesia Recovery Period
  • Anesthesia, Inhalation / instrumentation
  • Anesthesia, Inhalation / psychology
  • Anti-Anxiety Agents / administration & dosage*
  • Anxiety / prevention & control
  • Anxiety, Separation / prevention & control
  • Child Behavior / drug effects
  • Child, Preschool
  • Double-Blind Method
  • Female
  • Follow-Up Studies
  • Humans
  • Hypnotics and Sedatives / administration & dosage*
  • Male
  • Masks
  • Melatonin / administration & dosage*
  • Midazolam / administration & dosage*
  • Placebos
  • Preanesthetic Medication*
  • Prospective Studies
  • Psychomotor Agitation / prevention & control
  • Sleep Wake Disorders / prevention & control
  • Temperament / drug effects


  • Anti-Anxiety Agents
  • Hypnotics and Sedatives
  • Placebos
  • Melatonin
  • Midazolam