{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T17:07:53Z","timestamp":1780506473902,"version":"3.54.1"},"reference-count":8,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T00:00:00Z","timestamp":1780444800000},"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. Neurol."],"abstract":"\n Background and objective<\/jats:title>\n First-line serotonergic antidepressants achieve clinical response in approximately 60\u201365% of patients with persistent postural-perceptual dizziness (PPPD), leaving a substantial refractory population. Aripiprazole, a serotonin-dopamine modulator with partial D2 and 5-HT1A agonism and 5-HT2A antagonism, may address dopaminergic and emotional dysregulation insufficiently controlled by serotonergic agents alone. This study evaluated the preliminary efficacy and tolerability of aripiprazole as second-line pharmacotherapy in patients with refractory functional dizziness disorders, including PPPD.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n We retrospectively reviewed 16 patients (6 men, 10 women; mean age 50 \u00b1 16.1 years) with refractory dizziness disorders, including PPPD (\n n<\/jats:italic>\n = 9), psychogenic dizziness (\n n<\/jats:italic>\n = 4), vestibular migraine (\n n<\/jats:italic>\n = 2), and M\u00e9ni\u00e8re's disease (\n n<\/jats:italic>\n = 1), who received aripiprazole (1.5\u20133.0 mg\/day) after insufficient response to first-line antidepressants. The primary outcome was treatment response based on the Clinical Global Impression-Improvement scale (CGI-I; score 1\u20133 defined as improvement). Secondary outcomes included changes in Dizziness Handicap Inventory (DHI), Niigata PPPD Questionnaire (NPQ), and foam posturography in evaluable patients.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n CGI-I response was observed in 12 of 16 patients (75.0%). Four patients were non-responders, and one discontinued treatment because of extrapyramidal adverse effects. In patients with available questionnaire data (\n n<\/jats:italic>\n =4\u20135), DHI and NPQ scores improved after treatment. Foam posturography showed no significant changes.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n In this pilot retrospective series, aripiprazole demonstrated promising preliminary efficacy as a second-line treatment for refractory functional dizziness disorders. Its multimodal serotonin-dopamine mechanism may target symptoms insufficiently controlled by serotonergic agents alone. Given the small sample size and uncontrolled design, these findings should be considered hypothesis-generating. Prospective controlled studies are warranted.<\/jats:p>\n <\/jats:sec>","DOI":"10.3389\/fneur.2026.1858965","type":"journal-article","created":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T16:22:56Z","timestamp":1780503776000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Aripiprazole as second-line pharmacotherapy for a heterogeneous cohort of refractory functional dizziness disorders: a pilot preliminary retrospective study"],"prefix":"10.3389","volume":"17","author":[{"given":"Fumiyuki","family":"Goto","sequence":"first","affiliation":[{"name":"Department of Otolaryngology-Head and Neck Surgery, Tokai University School of Medicine","place":["Isehara, Kanagawa, Japan"]},{"name":"Goto ENT & Dizziness Clinic","place":["Machida, Tokyo, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koichiro","family":"Wasano","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology-Head and Neck Surgery, Tokai University School of Medicine","place":["Isehara, Kanagawa, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,6,3]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"191","DOI":"10.3233\/VES-170622","article-title":"Diagnostic criteria for persistent postural-perceptual dizziness (PPPD): consensus document of the committee for the classification of vestibular disorders of the Barany Society","volume":"27","author":"Staab","year":"2017","journal-title":"J Vestib Res."},{"key":"B2","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1136\/practneurol-2017-001809","article-title":"Persistent postural-perceptual dizziness (PPPD): a common, characteristic and treatable cause of chronic dizziness","volume":"18","author":"Popkirov","year":"2018","journal-title":"Pract Neurol."},{"key":"B3","doi-asserted-by":"publisher","first-page":"2523","DOI":"10.1007\/s00415-021-10427-7","article-title":"Predictors of treatment response to pharmacotherapy in patients with persistent postural-perceptual dizziness","volume":"268","author":"Min","year":"2021","journal-title":"J Neurol."},{"key":"B4","doi-asserted-by":"publisher","first-page":"1566898","DOI":"10.3389\/fneur.2025.1566898","article-title":"Long-term outcomes of pharmacotherapy in patients with persistent postural-perceptual dizziness","volume":"16","author":"Yagi","year":"2025","journal-title":"Front Neurol."},{"key":"B5","doi-asserted-by":"publisher","first-page":"923","DOI":"10.4088\/JCP.v62n1201","article-title":"Dopamine system stabilizers, aripiprazole, and the next generation of antipsychotics, part 2: illustrating their mechanism of action","volume":"62","author":"Stahl","year":"2001","journal-title":"J Clin Psychiatry."},{"key":"B6","doi-asserted-by":"publisher","first-page":"100657","DOI":"10.1016\/j.xocr.2025.100657","article-title":"A case of refractory dizziness effectively treated with the addition of aripiprazole to antidepressant therapy","volume":"34","author":"Goto","year":"2025","journal-title":"Otolaryngol Case Rep."},{"key":"B7","doi-asserted-by":"publisher","first-page":"100664","DOI":"10.1016\/j.xocr.2025.100664","article-title":"Brexpiprazole augmentation in antidepressant therapy for persistent postural-perceptual dizziness (PPPD): a case report","volume":"35","author":"Goto","year":"2025","journal-title":"Otolaryngol Case Rep."},{"key":"B8","doi-asserted-by":"publisher","first-page":"e747","DOI":"10.1097\/MAO.0000000000002325","article-title":"A validated questionnaire to assess the severity of persistent postural-perceptual dizziness (PPPD): the Niigata PPPD Questionnaire (NPQ)","volume":"40","author":"Yagi","year":"2019","journal-title":"Otol Neurotol."}],"container-title":["Frontiers in Neurology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fneur.2026.1858965\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T16:22:57Z","timestamp":1780503777000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fneur.2026.1858965\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,3]]},"references-count":8,"alternative-id":["10.3389\/fneur.2026.1858965"],"URL":"https:\/\/doi.org\/10.3389\/fneur.2026.1858965","relation":{},"ISSN":["1664-2295"],"issn-type":[{"value":"1664-2295","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,3]]},"article-number":"1858965"}}