Premedication with Oral Alprazolam and Melatonin Combination: A Comparison with Either Alone—A Randomized Controlled Factorial Trial
What this study found
The alprazolam plus melatonin combination was more effective for preoperative anxiolysis than either agent alone or placebo. At 60 minutes, anxiety reduction from baseline in the combination arm was 3 (1.0-4.3) cm versus 0 (0-1.7) cm with placebo (P = 0.008). Sedation at 60 minutes was also greater with the combination than placebo, 1 (1.0-1.75) versus 0 (0-1) (P = 0.008), and greater than melatonin alone, 1 (1.0-1.75) versus 0.5 (0-1) (P = 0.001). Amnesia for the picture task at 60 minutes favored the combination and alprazolam alone over melatonin and placebo, and 19 of 20 participants in…
- Study & population
- Randomized controlled factorial trial with four parallel groups in adults 18 to 65 years old, ASA I-II, with preoperative anxiety (VAS score >=3) undergoing elective laparoscopic cholecystectomy.
- Intervention
- Oral premedication given 90 minutes before surgery.
- Key limitation
- Small per-arm sample size and short perioperative follow-up limit precision and longer-term interpretation.
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Open PDFOriginal abstract
We assessed if the addition of melatonin to alprazolam has superior premedication effects compared to either drug alone. A prospective, double blind placebo controlled trial randomly assigned 80 adult patients (ASA 1&2) with a Visual Analogue Score (VAS) for anxiety ≥3 to receive a tablet containing a combination of alprazolam 0.5 mg and melatonin 3 mg, alprazolam 0.5 mg, melatonin 3 mg, or placebo orally 90 min before a standard anesthetic. Primary end points were change in anxiety and sedation score at 15, 30, and 60 min after premedication, and number of patients with loss of memory for the five pictures shown at various time points when assessed after 24 h. One-way ANOVA, Friedman repeated measures analysis of variance, Kruskal Wallis and chi square tests were used as relevant. Combination drug produced the maximum reduction in anxiety VAS (3 (1.0–4.3)) from baseline at 60 min (P < 0.05). Sedation scores at various time points and number of patients not recognizing the picture shown at 60 min after premedication were comparable between combination drug and alprazolam alone. Addition of melatonin to alprazolam had superior anxiolysis compared with either drugs alone or placebo. Adding melatonin neither worsened sedation score nor the amnesic effect of alprazolam alone. This study was registered, approved, and released from ClinicalTrials.gov. Identifier number: NCT01486615.