SAN FRANCISCO – Adding melatonin to alprazolam significantly decreased preoperative anxiety, compared with either medication alone or with placebo, in a randomized, double-blind trial of 80 patients.
Adult patients undergoing laparoscopic cholecystectomy who reported a preoperative anxiety level of at least 3 cm on a 10-cm Visual Analog Scale (VAS) had average anxiety scores of 5 cm before being randomized to preoperative medication with alprazolam 0.5 mg, melatonin 3 mg, both drugs, or placebo (with 20 patients in each group).
Dr. Krishna Pokharel
After 1 hour spent in a quiet room following the premedication, VAS scores had fallen by an average of 3 cm in the two-drug group, significantly more than average 2-cm reductions with either drug alone, or a 1-cm decline on placebo, Dr. Krishna Pokharel and her associates reported.
Adding melatonin did not seem to worsen the sedative or amnesiac effects of alprazolam, she reported in a poster presentation at the annual meeting of the American Society of Anesthesiologists.
In the past, some of her patients who had been premedicated with a benzodiazepine before general anesthesia and surgery sometimes became aroused during the procedure, perhaps because benzodiazepines suppress endogenous melatonin levels, Dr. Pokharel said. She hypothesized that adding melatonin might help, and the study results have convinced her institution to routinely add melatonin to alprazolam for surgical premedication in anxious patients, said Dr. Pokharel of B.P. Koirala Institute of Health Sciences, Dharan, Nepal.
Patients were shown different pictures during assessments of anxiety and sedation at various time points before surgery. At 24 hours after surgery, 10 patients on alprazolam plus melatonin could recall the picture they saw 1 hour after taking the presurgical medication, compared with 9 patients on alprazolam alone, 18 patients on melatonin alone, and 16 patients on placebo, the poster reported.
In other results, average scores on a 5-point scale for sedation at 1 hour were 0.5 with melatonin, 1 for each group using alprazolam, and 0 with placebo, among other secondary outcomes. At 24 hours after surgery, five patients in the two-drug group could not remember being transferred to the OR, compared with four patients on alprazolam, one patient on melatonin, and none of the patients on placebo.
All groups scored 2 on a 3-point scale for orientation 1 hour after taking the premedication. The amount of propofol needed to achieve a loss of response to verbal commands at the time of general anesthesia induction averaged 66 mg in the alprazolam plus melatonin group, 59 mg after alprazolam alone, 79 mg after melatonin alone, and 76 mg on placebo.
No patients developed serious adverse events.
Dr. Pokharel reported having no financial disclosures.
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