The Effects of Propranolol on Fear of Tooth or Molar Extraction

Effects of Propranolol on Fear of Dental Extraction: Study Protocol for a Randomized Placebo-controlled Trial.

Randomized, placebo-controlled, double-blind, parallel group clinical trial evaluating the anxiolytic effects of propranolol on fear of wisdom tooth removal. It is hypothesized that, compared to placebo, perioperative oral propranolol reduces dental trait anxiety at 1 month follow-up after wisdom tooth removal.

Study Overview

• Status: Completed
• Conditions: Dental Anxiety
• Intervention / Treatment: Drug: Propranolol

Detailed Description

RATIONALE Tooth and molar removals are among the most feared interventions in dentistry and oral and maxillofacial surgery (OMFS). Anxiety for these procedures not only produces discomfort to the patient, but may also induce patient behavior that impedes surgery, thereby increasing operative time and complicating postoperative recovery. In addition, it has been found that having undergone an extraction poses a significantly increased risk for developing chronic apprehension for dental surgical procedures, disproportionate forms of dental anxiety (i.e., dental phobia), and symptoms of post-traumatic stress. Addressing these problems effectively requires an intervention that reduces both state anxiety during surgery and dental trait anxiety in the long term.

OBJECTIVE The purpose of this trial is to determine the anxiolytic effects of the ß-adrenoreceptor antagonist propranolol on patients with high levels of fear in anticipation of dental extraction.

METHODS Trial design: Randomized, placebo-controlled, two-group, parallel, double-blind, single center trial of 34 participants. Population and recruitment: Consecutive patients, referred by their dentist to the department of Oral and Maxillofacial Surgery of the Academic Medical Center of the University Amsterdam, for at least two tooth and/or molar removals, with self-reported high to extreme fear in anticipation of dental extraction. Intervention: Two 40 mg propranolol capsules one hour prior to dental extraction, followed by one 40 mg capsule directly postoperatively. Comparator: Placebo capsules. Primary outcome: Dental trait anxiety score reduction from baseline to 4-weeks follow-up. Secondary outcomes: Self-reported anxiety during surgery; physiological parameters (heart rate and blood pressure) during recall of the crucial fear-related memory; self-reported vividness and emotional charge of the crucial fear-related memory.

RISKS AND BENEFITS ASSOCIATED WITH PARTICIPATION Participants of the trial will undergo regular dental extraction procedures (treatment as usual), with an additional potentially anxiolytic pharmacological intervention (propranolol) or placebo. The most important known side-effects of propranolol are mild and self-limiting.

• Study Type: Interventional
• Enrollment (Actual): 36
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Netherlands
  • Amsterdam, Netherlands, 1105 AZ
    • Dept. of Oral and Maxillofacial Surgery, Academic Medical Center, University of Amsterdam

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion criteria

1. Signed written informed consent
2. ≥ 18 Years of age on entry to the study
3. Self-reported high to extreme fear of tooth or molar removal
4. Dutch or English-speaking

Exclusion criteria

1. Asthma or other obstructive pulmonary disease
2. Cardiac failure
3. Cardiac arrhythmia
4. Renal failure
5. Insulin-dependent diabetes mellitus
6. Pregnant or breast-feeding
7. Current use of another ß-adrenoreceptor antagonist
8. Current use of anxiolytic or antidepressant medication
9. Currently in psychotherapy for dental anxiety
10. Systolic blood pressure < 100 mmHg

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Propranolol; capsules PROPRANOLOL (study medication); 80 mg 1 hour preoperative; 40 mg directly postoperative	Drug: Propranolol; Oral propranolol capsules; Other Names: propranolol hydrochloride; propranolol HCl
Placebo Comparator: Placebo; capsules MICROCRYSTALLINE CELLULOSE (study medication); 80 mg 1 hour preoperative; 40 mg directly postoperative	Drug: Propranolol; Oral propranolol capsules; Other Names: propranolol hydrochloride; propranolol HCl

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline at 1 month follow-up in Short version of the Dental Anxiety Inventory (S-DAI)	dental trait anxiety	Change from baseline at 1 month follow-up

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline at 1 month follow-up in Self-reported vividness and emotional charge of the crucial fear-related memory	Visual analogue scale	Change from Baseline at 1 month follow-up
Change from baseline at 1 month follow-up in State anxiety during treatment	Visual analogue scale	Change from Baseline at 1 month follow-up
Change from baseline at 1 month follow-up in Physiological parameters (heart rate and blood pressure) during recall of the crucial fear-related memory		Change from Baseline at 1 month follow-up

Collaborators and Investigators

• Sponsor: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
• Investigators: Principal Investigator: prof. dr. J. de Lange, MD, DDS, PhD, Academic Medical Center (AMC) of Amsterdam; Study Director: prof. dr. A. de Jongh, DDS, PhD, Academic Center for Dentistry Amsterdam (ACTA), University of Amsterdam

Publications and helpful links

General Publications

• Brunet A, Orr SP, Tremblay J, Robertson K, Nader K, Pitman RK. Effect of post-retrieval propranolol on psychophysiologic responding during subsequent script-driven traumatic imagery in post-traumatic stress disorder. J Psychiatr Res. 2008 May;42(6):503-6. doi: 10.1016/j.jpsychires.2007.05.006. Epub 2007 Jun 22.
• Liu HH, Milgrom P, Fiset L. Effect of a beta-adrenergic blocking agent on dental anxiety. J Dent Res. 1991 Sep;70(9):1306-8. doi: 10.1177/00220345910700091401.
• Lonergan MH, Olivera-Figueroa LA, Pitman RK, Brunet A. Propranolol's effects on the consolidation and reconsolidation of long-term emotional memory in healthy participants: a meta-analysis. J Psychiatry Neurosci. 2013 Jul;38(4):222-31. doi: 10.1503/jpn.120111.
• Steenen SA, van Wijk AJ, van Westrhenen R, de Lange J, de Jongh A. Effects of propranolol on fear of dental extraction: study protocol for a randomized controlled trial. Trials. 2015 Nov 25;16:536. doi: 10.1186/s13063-015-1065-7.

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2014
• Primary Completion (Actual): December 1, 2018
• Study Completion (Actual): December 1, 2018

Study Registration Dates

• First Submitted: October 7, 2014
• First Submitted That Met QC Criteria: October 17, 2014
• First Posted (Estimate): October 20, 2014

Study Record Updates

• Last Update Posted (Actual): April 17, 2020
• Last Update Submitted That Met QC Criteria: April 16, 2020
• Last Verified: April 1, 2020

More Information

Terms related to this study

• Keywords: Propranolol; Dental Anxiety; Tooth Extraction
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Adrenergic beta-Antagonists; Adrenergic Antagonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Antihypertensive Agents; Vasodilator Agents; Propranolol
• Other Study ID Numbers: NL42210.018.13

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided