Premedication with Oral Alprazolam and Melatonin Combination: a Comparison with Either Alone--a Randomized Controlled Factorial Trial

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.