Premedication with sublingual or oral alprazolam in adults undergoing diagnostic upper gastrointestinal endoscopy

Background and study aim: Diagnostic esophagogastroduodenoscopy (EGD) is uncomfortable for most patients. We determined the efficacy of alprazolam, administered orally or sublingually, as premedication for sedation during EGD.

Patients and methods: Adult EGD candidates were randomly allocated to four groups (n = 55, each group) and received alprazolam (0.5 mg) sublingually or orally, placebo sublingually or orally at 30 minutes before EGD. Main outcome measures included procedure-related anxiety and pain/discomfort (assessed using 11-point numeric scales), patient overall tolerance (assessed using a 4-point Likert scale), need for intravenous sedation, and willingness to repeat the EGD if necessary.

Results: Patients experienced greater reduction in anxiety score after medication with sublingual alprazolam (mean 2.25, standard deviation [SD] 1.73) compared with sublingual placebo (mean 0.10, standard error [SE] 0.15]; P < 0.001) and oral alprazolam (0.63, SE 0.14; P < 0.001). Also, pain/discomfort scores were lower with sublingual alprazolam compared with sublingual placebo (3.29, SE 0.29 vs. 4.16, SD 1.86; P = 0.024), and with oral alprazolam compared with oral placebo (3.48, SD 1.69 vs. 5.13, SD 2.39; P  < 0.001). Patient overall tolerance was better with sublingual alprazolam than with sublingual placebo (P = 0.005) or with oral alprazolam (P = 0.009). Regarding intravenous sedation, there was no difference between sublingual alprazolam and sublingual placebo (10.9 % vs. 10.9 %; P = 0.619) or between oral alprazolam and oral placebo (9.0 % vs. 12.7 %; P = 0.381). Willingness to repeat the procedure was greater with sublingual alprazolam than with sublingual placebo (50.9 % vs. 30.9 %; P = 0.026).

Conclusions: Sublingual alprazolam is an effective premedication for sedation during EGD. It reduces anxiety and pain/discomfort related to EGD and increases patient tolerance and willingness to repeat the EGD if necessary.

Clinical trial registration: NCT01949038 ClinicalTrials.gov

• References

• 1 Brandt LJ. Patients’ attitudes and apprehensions about endoscopy: how to calm troubled waters. Am J Gastroenterol 2001; 96: 280-284
• 2 Campo R, Brullet E, Montserrat A et al. Identification of factors that influence tolerance of upper gastrointestinal endoscopy. Eur J Gastroenterol Hepatol 1999; 11: 201-204
• 3 Lee SY, Son HJ, Lee JM et al. Identification of factors that influence conscious sedation in gastrointestinal endoscopy. J Korean Med Sci 2004; 19: 536-540
• 4 Abraham NS, Fallone CA, Mayrand S et al. Sedation versus no sedation in the performance of diagnostic upper gastrointestinal endoscopy: a Canadian randomized controlled cost-outcome study. Am J Gastroenterol 2004; 99: 1692-1699
• 5 Cohen LB, Delegge MH, Aisenberg J et al. AGA Institute review of endoscopic sedation. Gastroenterology 2007; 133: 675-701
• 6 McQuaid KR, Laine L. A systematic review and meta-analysis of randomized, controlled trials of moderate sedation for routine endoscopic procedures. Gastrointest Endosc 2008; 67: 910-923
• 7 Arrowsmith JB, Gerstman BB, Fleischer DE et al. Results from the American Society for Gastrointestinal Endoscopy/U.S. Food and Drug Administration collaborative study on complication rates and drug use during gastrointestinal endoscopy. Gastrointest Endosc 1991; 37: 421-427
• 8 Daneshmend TK, Bell GD, Logan RF. Sedation for upper gastrointestinal endoscopy: results of a nationwide survey. Gut 1991; 32: 12-15
• 9 Kuganeswaran E, Clarkston WK, Cuddy PG et al. A double-blind placebo controlled trial of oral midazolam as premedication before flexible sigmoidoscopy. Am J Gastroenterol 1999; 94: 3215-3219
• 10 Mui LM, Teoh AY, Ng EK et al. Premedication with orally administered midazolam in adults undergoing diagnostic upper endoscopy: a double-blind placebo-controlled randomized trial. Gastrointest Endosc 2005; 61: 195-200
• 11 Rafeey M, Ghojazadeh M, Feizo Allah ZH et al. Use of oral midazolam in pediatric upper gastrointestinal endoscopy. Pediatr Int 2010; 52: 191-195
• 12 Hedenbro JL, Ekelund M, Aberg T et al. Oral sedation for diagnostic upper endoscopy. Endoscopy 1991; 23: 8-10
• 13 Liacouras CA, Mascarenhas M, Poon C et al. Placebo-controlled trial assessing the use of oral midazolam as a premedication to conscious sedation for pediatric endoscopy. Gastrointest Endosc 1998; 47: 455-460
• 14 Martinez JL, Sutters KA, Waite S et al. A comparison of oral diazepam versus midazolam, administered with intravenous meperidine, as premedication to sedation for pediatric endoscopy. J Pediatr Gastroenterol Nutr 2002; 35: 51-58
• 15 de Alencar VM, Gonçalves RD, Cruz AA. Oral medication with diazepam or midazolam associated or not with clonidine for oculoplastic office surgery under local anesthesia. Ophthal Plast Reconstr Surg 2010; 26: 269-272
• 16 Ashton H. Guidelines for the rational use of benzodiazepines. When and what to use. Drugs 1994; 48: 25-40
• 17 De Witte JL, Alegret C, Sessler DI et al. Preoperative alprazolam reduces anxiety in ambulatory surgery patients: a comparison with oral midazolam. Anesth Analg 2002; 95: 1601-1606
• 18 Jonas JM, Cohon MS. A comparison of the safety and efficacy of alprazolam versus other agents in the treatment of anxiety, panic, and depression: a review of the literature. J Clin Psychiatry 1993; 54 Suppl 25-45
• 19 Kendrick DB, Strout TD. The minimum clinically significant difference in patient-assigned numeric scores for pain. Am J Emerg Med 2005; 23: 828-832
• 20 Saghaei M. Random allocation software for parallel group randomized trials. BMC Med Res Methodol 2004; 4: 26
• 21 Hjermstad MJ, Fayers PM, Haugen DF et al. Studies comparing numerical rating scales, verbal rating scales, and visual analogue scales for assessment of pain intensity in adults: a systematic literature review. J Pain Symptom Manage 2011; 46: 1073-1093
• 22 Weitz G, von Homann NJ et al. Premedication with orally administered lorazepam in adults undergoing ERCP: a randomized double-blind study. Gastrointest Endosc 2007; 66: 450-456
• 23 Driessen JJ, Smets MJ, Goey LS et al. Comparison of diazepam and midazolam as oral premedicants for bronchoscopy under local anesthesia. Acta Anaesthesiol Belg 1982; 33: 99-105
• 24 Pisalchaiyong T, Trairatvorakul C, Jirakijja J et al. Comparison of the effectiveness of oral diazepam and midazolam for the sedation of autistic patients during dental treatment. Pediatr Dent 2005; 27: 198-206
• 25 Tyagi P, Tyagi S, Jain A. Sedative effects of oral midazolam, intravenous midazolam and oral diazepam in the dental treatment of children. J Clin Pediatr Dent 2013; 37: 301-305
• 26 Pywell CA, Hung YJ, Nagelhout J. Oral midazolam versus meperidine, atropine, and diazepam: a comparison of premedicants in pediatric outpatients. AANA J 1995; 63: 124-130
• 27 Arenoso HJ, Sabban HC, Heguilen RM et al. Sublingual administration of alprazolam: a pharmacokinetic approach. Int J Pharmaceut Med 2002; 16: 218
• 28 Scavone JM, Greenblatt DJ, Shader RI. Alprazolam kinetics following sublingual and oral administration. J Clin Psychopharmacol 1987; 7: 332-334
• 29 Scavone JM, Greenblatt DJ, Friedman H et al. Enhanced bioavailability of triazolam following sublingual versus oral administration. J Clin Pharmacol 1986; 26: 208-210
• 30 Kroboth PD, McAuley JW, Kroboth FJ et al. Triazolam pharmacokinetics after intravenous, oral, and sublingual administration. J Clin Psychopharmacol 1995; 15: 259-262
• 31 Berthold CW, Dionne RA, Corey SE. Comparison of sublingually and orally administered triazolam for premedication before oral surgery. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1997; 84: 119-124
• 32 van Zuuren FJ, Grypdonck M, Crevits E et al. The effect of an information brochure on patients undergoing gastrointestinal endoscopy: a randomized controlled study. Patient Educ Couns 2006; 64: 173-182
• 33 Luck A, Pearson S, Maddern G et al. Effects of video information on precolonoscopy anxiety and knowledge: a randomised trial. Lancet 1999; 354: 2032-2035
• 34 Soma Y, Saito H, Kishibe T et al. Evaluation of topical pharyngeal anesthesia for upper endoscopy including factors associated with patient tolerance. Gastrointest Endosc 2001; 53: 14-18