title: Effects of propranolol on fear of dental extraction: study protocol for a randomized controlled trial.
abstract: BACKGROUND
  Undergoing an extraction has been shown to pose a significantly increased risk for the development of chronic apprehension for dental surgical procedures, disproportionate forms of dental anxiety (that is, dental phobia), and symptoms of post-traumatic stress. Evidence suggests that intrusive emotional memories of these events both induce and maintain these forms of anxiety. Addressing these problems effectively requires an intervention that durably reduces both the intrusiveness of key fear-related memories and state anxiety during surgery. Moreover, evidence suggests that propranolol is capable of inhibiting "memory reconsolidation" (that is, it blocks the process of storing a recently retrieved fear memory). Hence, the purpose of this trial is to determine the anxiolytic and fear memory reconsolidation inhibiting effects of the ß-adrenoreceptor antagonist propranolol on patients with high levels of fear in anticipation of a dental extraction.
  
  
  METHODS
  This trial is designed as a multicenter, randomized, placebo-controlled, two-group, parallel, double-blind trial of 34 participants. Consecutive patients who have been referred by their dentist to the departments of oral and maxillofacial surgery of a University hospital or a secondary referral hospital in the Netherlands for at least two tooth and/or molar removals and with self-reported high to extreme fear in anticipation of a dental extraction will be recruited. The intervention is the administration of two 40 mg propranolol capsules 1 hour prior to a dental extraction, followed by one 40 mg capsule directly postoperatively. Placebo capsules will be used as a comparator. The primary outcome will be dental trait anxiety score reduction from baseline to 4-weeks follow-up. The secondary outcomes will be 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.
  
  
  CONCLUSIONS
  This randomized trial is the first to test the efficacy of 120 mg of perioperative propranolol versus placebo in reducing short-term ("state") anxiety during dental extraction, fear memory reconsolidation, and lasting dental ("trait") anxiety in a clinical population. If the results show a reduction in anxiety, this would offer support for routinely prescribing propranolol in patients who are fearful of undergoing dental extractions.
  
  
  BACKGROUND
  ClinicalTrials.gov identifier: NCT02268357 , registered on 7 October 2014. The Netherlands National Trial Register identifier: NTR5364 , registered on 16 August 2015.
authors.affiliation: Department of Oral and Maxillofacial Surgery, Academic Medical Center of the University of Amsterdam, Meibergdreef 9, 1105, AZ, Amsterdam, The Netherlands. s.a.steenen@amc.uva.nl.
authors.forename: Serge A
authors.initials: SA
authors.lastname: Steenen
authors.affiliation: Department of Social Dentistry and Behavioral Sciences, Academic Centre for Dentistry Amsterdam, Gustav Mahlerlaan 3004, 1081, LA, Amsterdam, The Netherlands. a.vwijk@acta.nl.
authors.forename: Arjen J
authors.initials: AJ
authors.lastname: van Wijk
authors.affiliation: Department of Psychiatry, Erasmus University Medical Center, 's-Gravendijkwal 230, 3015, CE, Rotterdam, The Netherlands. r.vanwestrhenen@erasmusmc.nl.
authors.forename: Roos
authors.initials: R
authors.lastname: van Westrhenen
authors.affiliation: Department of Oral and Maxillofacial Surgery, Academic Medical Center of the University of Amsterdam, Meibergdreef 9, 1105, AZ, Amsterdam, The Netherlands. j.delange@amc.uva.nl.
authors.forename: Jan
authors.initials: J
authors.lastname: de Lange
authors.affiliation: Department of Social Dentistry and Behavioral Sciences, Academic Centre for Dentistry Amsterdam, Gustav Mahlerlaan 3004, 1081, LA, Amsterdam, The Netherlands. a.d.jongh@acta.nl.|School of Health Sciences, Salford University, Salford, UK. a.d.jongh@acta.nl.
authors.forename: Ad
authors.initials: A
authors.lastname: de Jongh
mesh_terms: D000284:Administration, Oral; D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage* / Q000009:adverse effects; D059031:Anticipation, Psychological / Q000187:drug effects; D002214:Capsules; D002985:Clinical Protocols; D016854:Dental Anxiety / Q000209:etiology / Q000517:prevention & control* / Q000523:psychology; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004644:Emotions / Q000187:drug effects; D006801:Humans; D008568:Memory / Q000187:drug effects; D009426:Netherlands; D011433:Propranolol / Q000008:administration & dosage* / Q000009:adverse effects; D012107:Research Design; D011795:Surveys and Questionnaires; D013997:Time Factors; D014081:Tooth Extraction / Q000009:adverse effects / Q000523:psychology*; D016896:Treatment Outcome
chemical_list: D000319:Adrenergic beta-Antagonists; D002214:Capsules; D011433:Propranolol