{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T10:09:56Z","timestamp":1764583796848,"version":"3.46.0"},"reference-count":0,"publisher":"Ideggyogyaszati Szemle Journal","issue":"11-12","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Ideggy\u00f3gy\u00e1szati szemle"],"published-print":{"date-parts":[[2025]]},"abstract":"<jats:p>Background and purpose \u2013 Akathisia is a\ncommon side effect of aripiprazole treatment, which is associated with subjective distress for patients, and represents a frequent\ncause of treatment discontinuation. Propranolol and other beta-receptor blockers are\ncommonly used for treatment of akathisia.\nCytochrome P450 2D6 (CYP2D6) enzyme\nplays a major role in the metabolism of aripiprazole. Our previous study has shown that\nCYP2D6 inhibitory activity of beta-blockers\n(metoprolol and propranolol) may result in\nelevated aripiprazole plasma concentrations.\nThe objective of the present retrospective study was to assess the prevalence of\nakathisia in patients receiving propranolol or\nmetoprolol comedication, as well as in those\nnot receiving any CYP2D6 inhibitors such as\npropranolol, metoprolol, risperidone.\nMethods \u2013 Using the data of our previous\npharmacogenetic study involving 67 patients\ndiagnosed with schizophrenia or schizoaffective disorder and receiving aripiprazole\ntreatment, we retrospectively investigated the\nemergence of akathisia within 6 months following aripiprazole initiation. Information on\nthe onset of akathisia was obtained from patients\u2019 medical records. The effects of CYP2D6\ngenotype, aripiprazole plasma concentration,\npropranolol and metoprolol comedication on\nthe development of akathisia were analysed.\nThe included patients had already been taking\npropranolol and metoprolol comedication\nprior to the initiation of aripiprazole and not\nfor the treatment of akathisia.\nResults \u2013 Schizophrenia and schizoaffective\ndisorder patients treated with propranolol had a significantly higher incidence of\ndocumented akathisia (38,5%) compared to\nthe group not receiving CYP2D6 inhibitors\n(5.9%), and the group treated with metoprolol comedication (7.1%). Among the CYP2D6\ninhibitors, only the administration of propranolol increased the risk of akathisia (Wald\nChi2=5.5, p=0.02, OR=7.6 [95% CI=1.4-41.4]).\nThe polymorphic CYP2D6 alleles resulting\nin low CYP2D6 function showed a statistical\ntrend-level association with the occurrence\nof akathisia (Wald Chi2=2.6, p=0.11, OR=4.7\n[95% CI=0.7-30.8]). In a subsequent analysis,\nwe investigated the possible interaction of\npropranolol and CYP2D6 genotypes on the\ndevelopment of akathisia. The interaction\nmodel showed that the effect of propranolol\nwas not dependent on CYP2D6 genotype\n(Wald Chi2=0.1, p=0.92), however, its independent effect remained significant (Wald\nChi2=4.4, p=0.04).\nConclusion \u2013 Our findings suggest that\npropranolol comedication increases the\nrisk of the development of akathisia during\naripiprazole treatment. It is of paramount\nimportance to avoid propranolol comedication during aripiprazole treatment. However,\ntwo major limitations should be considered:\nakathisia was not assessed using a standardized clinical rating scale, and the majority of\npatients (80.6%) received antipsychotic combination therapy, which may have influenced\nthe findings. Further prospective studies\nare needed to confirm these findings based\non retrospective, naturalistic analysis about\nthe development of aripiprazole-induced\nakathisia.<\/jats:p>","DOI":"10.18071\/isz.78.0395","type":"journal-article","created":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T09:39:56Z","timestamp":1764581996000},"page":"395-404","source":"Crossref","is-referenced-by-count":0,"title":["Association of propranolol with treatment-emergent akathisia during aripiprazole treatment"],"prefix":"10.18071","volume":"78","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2436-543X","authenticated-orcid":false,"given":"\u00c1d\u00e1m","family":"Menus","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6579-6976","authenticated-orcid":false,"given":"\u00c1d\u00e1m","family":"Kiss","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5006-9407","authenticated-orcid":false,"given":"G\u00e1bor","family":"Csukly","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9464-4709","authenticated-orcid":false,"given":"Istv\u00e1n","family":"Bitter","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0861-1450","authenticated-orcid":false,"given":"Katalin","family":"Monostory","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3641-012X","authenticated-orcid":false,"given":"J\u00e1nos M.","family":"R\u00e9thely","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"7411","published-online":{"date-parts":[[2025]]},"container-title":["Ideggy\u00f3gy\u00e1szati szemle"],"original-title":[],"link":[{"URL":"https:\/\/elitmed.hu\/en\/publications\/clinical-neuroscience\/association-of-propranolol-with-treatment-emergent-akathisia-during-aripiprazole-treatment\/pdf-open","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T10:08:31Z","timestamp":1764583711000},"score":1,"resource":{"primary":{"URL":"https:\/\/elitmed.hu\/en\/publications\/clinical-neuroscience\/association-of-propranolol-with-treatment-emergent-akathisia-during-aripiprazole-treatment"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025]]},"references-count":0,"journal-issue":{"issue":"11-12","published-online":{"date-parts":[[2025]]},"published-print":{"date-parts":[[2025]]}},"URL":"https:\/\/doi.org\/10.18071\/isz.78.0395","relation":{},"ISSN":["0019-1442","2498-6208"],"issn-type":[{"type":"print","value":"0019-1442"},{"type":"electronic","value":"2498-6208"}],"subject":[],"published":{"date-parts":[[2025]]}}}