Aripiprazole as second-line pharmacotherapy for a heterogeneous cohort of refractory functional dizziness disorders:...

First-line serotonergic antidepressants achieve clinical response in approximately 60-65% 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.

We retrospectively reviewed 16 patients (6 men, 10 women; mean age 50 ± 16.1 years) with refractory dizziness disorders, including PPPD (n = 9), psychogenic dizziness (n = 4), vestibular migraine (n = 2), and Ménière's disease (n = 1), who received aripiprazole (1.5-3.0 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 1-3 defined as improvement). Secondary outcomes included changes in Dizziness Handicap Inventory (DHI), Niigata PPPD Questionnaire (NPQ), and foam posturography in evaluable patients.

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=4-5), DHI and NPQ scores improved after treatment. Foam posturography showed no significant changes.

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.