{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T00:26:42Z","timestamp":1792628802727,"version":"4.5.0"},"reference-count":33,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,2,21]],"date-time":"2022-02-21T00:00:00Z","timestamp":1645401600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Psychiatry"],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Promising results from a trauma reactivation study on post-traumatic stress disorder suggest that propranolol is capable of attenuating symptoms of traumatically induced mental disorders by blocking memory reconsolidation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A randomized, parallel, placebo-controlled, quadruple-blind trial was designed to determine the effectiveness of perioperative propranolol during exposure to dental extractions in reducing dental anxiety in patients with dental anxiety or dental phobia. Between November 2014 and December 2018, 52 patients with high levels of fear in anticipation of dental extractions who were referred to a department of oral and maxillofacial surgery for at least two tooth and\/or molar removals with 1 month in between were included. On the first visit participants received either 120 mg of perioperative oral propranolol (<jats:italic>n<\/jats:italic> = 19) or placebo (<jats:italic>n<\/jats:italic> = 17), and a core fear memory was reactivated 1 h preoperatively. The primary outcome was change in severity of dental anxiety from baseline to 1-month follow-up, as indexed by the short version of the dental anxiety inventory (S-DAI). Secondary outcome measures were change in intra-operative state anxiety and specific phobia diagnoses.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Linear mixed model (LMM) yielded no statistically significant difference in change of dental trait anxiety from baseline to 1-month follow-up between propranolol and placebo groups (Cohen's <jats:italic>d<\/jats:italic> = 0.23). S-DAI scores decreased in both study arms from baseline to follow-up (propranolol arm: from 32.1 [SD = 7.3] to 29.1 [SD = 8.8]; placebo arm: from 31.6 [SD = 7.5] to 27.1 [SD = 6.5]). Also, administering propranolol was not associated with a significant difference in change of intra-operative state anxiety or phobia diagnoses between groups over time.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The results do not concur with earlier findings regarding post-traumatic stress disorder, and suggest that individuals with traumatically induced fears or phobias do not benefit from the application of perioperative propranolol.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fpsyt.2022.842353","type":"journal-article","created":{"date-parts":[[2022,2,21]],"date-time":"2022-02-21T11:03:51Z","timestamp":1645441431000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["Perioperative Propranolol Against Dental Anxiety: A Randomized Controlled Trial"],"prefix":"10.3389","volume":"13","author":[{"given":"Serge A.","family":"Steenen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naichuan","family":"Su","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roos","family":"van Westrhenen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arjen J.","family":"van Wijk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dani\u00ebl S. L.","family":"Tjia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"de Lange","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ad","family":"de Jongh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,2,21]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"189","DOI":"10.1016\/S0006-3223(01)01279-3","article-title":"Pilot study of secondary prevention of posttraumatic stress disorder with propranolol","volume":"51","author":"Pitman","year":"2002","journal-title":"Biol Psychiatry."},{"key":"B2","doi-asserted-by":"publisher","first-page":"503","DOI":"10.1016\/j.jpsychires.2007.05.006","article-title":"Effect of post-retrieval propranolol on psychophysiologic responding during subsequent script-driven traumatic imagery in post-traumatic stress disorder","volume":"42","author":"Brunet","year":"2008","journal-title":"J Psychiatr Res."},{"key":"B3","doi-asserted-by":"publisher","first-page":"256","DOI":"10.1038\/nn.2271","article-title":"Beyond extinction: erasing human fear responses and preventing the return of fear","volume":"12","author":"Kindt","year":"2009","journal-title":"Nat Neurosci."},{"key":"B4","doi-asserted-by":"publisher","first-page":"20170033","DOI":"10.1098\/rstb.2017.0033","article-title":"the surprising subtleties of changing fear memory: a challenge for translational science","volume":"373","author":"Kindt","year":"2018","journal-title":"Philos Trans R Soc Lond B Biol Sci."},{"key":"B5","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1126\/science.1231357","article-title":"Prediction error governs pharmacologically induced amnesia for learned fear","volume":"80","author":"Sevenster","year":"2013","journal-title":"Science."},{"key":"B6","doi-asserted-by":"publisher","first-page":"598","DOI":"10.1016\/j.biopsycho.2012.01.007","article-title":"The effects of noradrenergic blockade on extinction in humans","volume":"89","author":"Bos","year":"2012","journal-title":"Biol Psychol."},{"key":"B7","doi-asserted-by":"publisher","first-page":"30","DOI":"10.1016\/j.nlm.2010.03.004","article-title":"Dissociating response systems: erasing fear from memory","volume":"94","author":"Soeter","year":"2010","journal-title":"Neurobiol Learn Mem."},{"key":"B8","doi-asserted-by":"publisher","first-page":"263","DOI":"10.1016\/j.nlm.2011.05.003","article-title":"Noradrenergic enhancement of associative fear memory in humans","volume":"96","author":"Soeter","year":"2011","journal-title":"Neurobiol Learn Mem [Internet]."},{"key":"B9","doi-asserted-by":"publisher","first-page":"179","DOI":"10.1038\/s41398-020-0857-z","article-title":"Reconsolidation-based treatment for fear of public speaking: a systematic pilot study using propranolol","volume":"10","author":"Elsey","year":"2020","journal-title":"Transl Psychiatry."},{"key":"B10","doi-asserted-by":"publisher","first-page":"2422","DOI":"10.1523\/JNEUROSCI.4001-13.2014","article-title":"Reconsolidation and extinction are dissociable and mutually exclusive processes: behavioral and molecular evidence","volume":"34","author":"Merlo","year":"2014","journal-title":"J Neurosci."},{"key":"B11","doi-asserted-by":"publisher","first-page":"580","DOI":"10.1101\/lm.035493.114","article-title":"Prediction error demarcates the transition from retrieval, to reconsolidation, to new learning","volume":"21","author":"Sevenster","year":"2014","journal-title":"Learn Mem."},{"key":"B12","doi-asserted-by":"publisher","first-page":"427","DOI":"10.1176\/appi.ajp.2017.17050481","article-title":"Reduction of PTSD symptoms with pre-reactivation propranolol therapy: a randomized controlled trial","volume":"175","author":"Brunet","year":"2018","journal-title":"Am J Psychiatry."},{"key":"B13","doi-asserted-by":"publisher","first-page":"135","DOI":"10.1111\/j.1600-0722.2008.00602.x","article-title":"Prevalence of dental fear and phobia relative to other fear and phobia subtypes","volume":"117","author":"Oosterink","year":"2009","journal-title":"Eur J Oral Sci."},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1186\/s13063-015-1065-7","article-title":"Effects of propranolol on fear of dental extraction: study protocol for a randomized controlled trial","volume":"16","author":"Steenen","year":"2015","journal-title":"Trials."},{"key":"B15","doi-asserted-by":"publisher","first-page":"4","DOI":"10.1053\/joms.2000.17878","article-title":"Guidelines for anxiety control and pain management in oral and maxillofacial surgery","volume":"58","author":"Zuniga","year":"2000","journal-title":"J Oral Maxillofac Surg."},{"key":"B16","doi-asserted-by":"publisher","first-page":"52","DOI":"10.1034\/j.1600-0528.2003.00025.x","article-title":"Trauma-related phenomena in anxious dental patients","volume":"31","author":"de Jongh","year":"2003","journal-title":"Community Dent Oral Epidemiol."},{"key":"B17","doi-asserted-by":"publisher","first-page":"286","DOI":"10.1111\/j.1600-0722.2006.00384.x","article-title":"Psychological trauma exposure and trauma symptoms among individuals with high and low levels of dental anxiety","volume":"114","author":"De Jongh","year":"2006","journal-title":"Eur J Oral Sci."},{"key":"B18","doi-asserted-by":"publisher","first-page":"451","DOI":"10.1016\/j.janxdis.2008.09.002","article-title":"Negative events and their potential risk of precipitating pathological forms of dental anxiety","volume":"23","author":"Oosterink","year":"2009","journal-title":"J Anxiety Disord."},{"key":"B19","doi-asserted-by":"publisher","first-page":"515","DOI":"10.1002\/acp.3127","article-title":"Presence, content, and characteristics of memories of individuals with dental phobia","volume":"29","author":"van Houtem","year":"2015","journal-title":"Appl Cogn Psychol."},{"key":"B20","doi-asserted-by":"publisher","first-page":"44","DOI":"10.1111\/j.1600-0722.2007.00500.x","article-title":"What are people afraid of during dental treatment? anxiety-provoking capacity of 67 stimuli characteristic of the dental setting","volume":"116","author":"Oosterink","year":"2008","journal-title":"Eur J Oral Sci."},{"key":"B21","doi-asserted-by":"publisher","first-page":"5722","DOI":"10.1002\/jcp.27441","article-title":"Between an ugly truth and a perfect lie: wiping off fearful memories using beta-adrenergic receptors antagonists","volume":"234","author":"AlOkda","year":"2019","journal-title":"J Cell Physiol."},{"key":"B22","doi-asserted-by":"publisher","first-page":"E75239","DOI":"10.1371\/journal.pone.0075239","article-title":"High trait anxiety: a challenge for disrupting fear memory reconsolidation","volume":"8","author":"Soeter","year":"2013","journal-title":"PLoS One."},{"key":"B23","doi-asserted-by":"publisher","first-page":"1306","DOI":"10.1177\/00220345910700091401","article-title":"Effect of a beta-adrenergic blocking agent on dental anxiety","volume":"70","author":"Liu","year":"1991","journal-title":"J Dent Res."},{"key":"B24","doi-asserted-by":"publisher","first-page":"350","DOI":"10.1111\/j.1600-0528.1998.tb01972.x","article-title":"Reliability and validity of the short version of the dental anxiety inventory","volume":"12","author":"Iha","year":"1998","journal-title":"PLoS One"},{"key":"B25","doi-asserted-by":"publisher","first-page":"1026","DOI":"10.1002\/da.22168","article-title":"Is dental phobia a blood-injection-injury phobia?","volume":"31","author":"van Houtem","year":"2014","journal-title":"Depress Anxiety."},{"key":"B26","doi-asserted-by":"publisher","first-page":"209","DOI":"10.1097\/00006842-197905000-00004","article-title":"Impact of event scale: a measure of subjective stress","volume":"41","author":"Horowitz","year":"1979","journal-title":"Psychosom Med."},{"key":"B27","volume-title":"Coping With Trauma: Theory, Prevention and Treatment","author":"Kleber","year":"1992"},{"key":"B28","unstructured":"ThalheimerW\n            CookS\n          How to Calculate Effect Sizes From Published Research: A Simplified Methodology [Internet].2002"},{"key":"B29","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1016\/j.psychres.2014.09.005","article-title":"Pharmacological blockade of memory reconsolidation in posttraumatic stress disorder: three negative psychophysiological studies","volume":"225","author":"Wood","year":"2015","journal-title":"Psychiatry Res [Internet]."},{"key":"B30","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3389\/fpsyt.2021.775770","article-title":"Placebo and non-specific effects in reconsolidation-based treatment for arachnophobia","volume":"12","author":"Elsey","year":"2021","journal-title":"Front Psychiatry."},{"key":"B31","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1038\/S41386-021-00984-W","article-title":"Traumatic memory reactivation with or without propranolol for PTSD and Comorbid MD symptoms: a randomised clinical trial","volume":"20","author":"Roullet","year":"2021","journal-title":"Neuropsychopharmacology [Internet]."},{"key":"B32","doi-asserted-by":"publisher","first-page":"1316","DOI":"10.1038\/s41467-018-03659-1","article-title":"Pharmacologically induced amnesia for learned fear is time and sleep dependent","volume":"9","author":"Kindt","year":"2018","journal-title":"Nat Commun."},{"key":"B33","doi-asserted-by":"publisher","first-page":"222","DOI":"10.1503\/jpn.120111","article-title":"Propranolol's effects on the consolidation and reconsolidation of long-term emotional memory in healthy participants: a meta-analysis","volume":"38","author":"Lonergan","year":"2013","journal-title":"J Psychiatry Neurosci."}],"container-title":["Frontiers in Psychiatry"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fpsyt.2022.842353\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,2,21]],"date-time":"2022-02-21T11:03:54Z","timestamp":1645441434000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fpsyt.2022.842353\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,2,21]]},"references-count":33,"alternative-id":["10.3389\/fpsyt.2022.842353"],"URL":"https:\/\/doi.org\/10.3389\/fpsyt.2022.842353","relation":{},"ISSN":["1664-0640"],"issn-type":[{"value":"1664-0640","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,2,21]]},"article-number":"842353"}}