A randomized double-blind, placebo-controlled, cross-over trial (Vestparoxy) of the treatment of vestibular paroxysmia with oxcarbazepine

Abstract

ObjectiveVestibular paroxysmia (VP) is characterized by short, often oligosymptomatic attacks of vertigo which occur spontaneously or are sometimes provoked by turning the head. Despite the description of the disease almost 40 years ago (first termed “disabling positional vertigo”), no controlled treatment trial has been published to date. The Vestparoxy trial was designed as a randomized, placebo-controlled, double-blind cross-over trial to examine the therapeutic effect of oxcarbazepine (OXA) in patients with definite or probable VP.MethodsPatients were recruited from August 2005 to December 2011 in the outpatient Dizziness Unit of the Department of Neurology of the Munich University Hospital, and randomized to receive OXA (first week: 300 mg once per day, second week: 300 mg b.i.d., third week: 300 mg t.i.d. until the end of the third month), followed by placebo or vice versa with a 1-month wash-out period in between. The primary endpoint was the number of days with one or more attacks. Secondary endpoints were the number of attacks during the observed days, and the median (for each day) duration of attacks. All these endpoints were assessed using standardized diaries collected at the end of each treatment phase.ResultsForty-three patients were randomized, 18 patients provided usable data (2525 patient days) for at least one treatment phase and were included in the main (intention-to-treat) analysis. The most common reasons for discontinuation documented were adverse events. The risk of experiencing a day with at least one attack was 0.41 under OXA, and 0.62 under placebo treatment, yielding a relative risk of 0.67 (95% CI 0.47–0.95, p = 0.025). The number of attacks during the observed days ratio was 0.53 (95% CI 0.42–0.68, p < 0.001) under OXA compared to placebo. Median attack duration was 4 s (Q25: 2 s, Q75: 120 s) under OXA, and 3 s (Q25: 2 s, Q75: 60 s) under placebo treatment. When days with no attacks, i.e., duration = 0, were included in the analysis, these figures changed to 0 (Q25: 0, Q75: 3 s), and 2 (Q25: 0, Q75: 6 s). No serious adverse events or new safety findings were identified during the trial.ConclusionsThe Vestparoxy trial showed a significant reduction of VP attacks under OXA compared to placebo treatment, confirming the known and revealing no new side effects.

Vestibular Disorders

“…For the latter reason, MRI in this condition is indicated mainly to rule out other etiologies. A randomized, controlled trial demonstrated the significant therapeutic efficacy of oxcarbazepine at a dosage of 900 mg/day (attack frequency halved), although poor tolerability of the drug led to a 60% dropout rate (25). Lac osamide (100-200 mg/day) seems to be a welltolerated alternative, as individual cases of off-label use have shown (26).…”

Seltene Erkrankungen des vestibulären Labyrinths: von Zebras, Chamäleons und Wölfen im Schafspelz

“…or oxcarbazepine 300–900 mg p.o. per day) reduces the ephaptic transmission and thus results in a significant reduction of both attack frequency and severity within a few days or weeks 110 , as shown in a double-blind randomized controlled clinical trial for oxcarbazepine versus placebo 122 . It should, however, be noted that there was a high drop-out rate due to adverse effects in this study.…”

“…Eine Therapie mit Natriumkanalblockern (Carbamazepin 200–800 mg oder Oxcarbazepin 300–900 mg pro Tag) reduziert die ephaptischen Entladungen und führt innerhalb weniger Tage bis Wochen meist zu einer deutlichen Reduktion von Attackenfrequenz und –schwere 110 , wie in einer doppelblind randomisierten kontrollierten Studie für Oxcarbazepin gegen Placebo gezeigt wurde 122 . Allerdings brachen viele Patienten aufgrund von Nebenwirkungen die Studie vorzeitig ab.…”

Practical approach to vertigo: a synthesis of the emerging evidence

“…41 It may be triggered by exercise or heat, is associated with 'staccato' or 'type-writer' tinnitus and is often responsive to carbamazepine or oxcarbazepine. 42,43 Syndrome 4: imbalance Imbalance is the final common vestibular syndrome and can be caused by numerous conditions spanning across systems.…”