medwireNews: Intranasal oxytocin administered every third day for 6 weeks to patients with frontotemporal dementia is associated with a small improvement in Neuropsychiatric Inventory (NPI) apathy score, suggest findings from the Intranasal Oxytocin for Frontotemporal Dementia (FOXY) study.
Elizabeth Finger (University of Western Ontario, London, Canada) and colleagues write in The Lancet Neurology that “this trial is the largest in participants with frontotemporal dementia to show efficacy for any symptom, and the first to show a small benefit of a medication for apathy.”
The FOXY study was a multicenter, randomized, double-blind, placebo-controlled, adaptive, crossover, phase 2a/2b superiority trial carried out at clinics in Canada and the USA.
The study participants (60% men) were aged 30–80 years (mean 66 years) with a diagnosis of probable frontotemporal dementia and had an NPI apathy score of at least 2 points (mean 8.1 points), a study partner who interacted with them for at least 3 hours per day, and 30 days of stable cognitive and behavioral medications.
Stage 1 of the study was designed to select the optimal dosing schedule and involved 60 patients who were randomly assigned to receive 72 IU of intranasal oxytocin or placebo twice every 1, 2, or 3 days, for 6 weeks, followed by a 6-week washout and then crossover to the other intervention.
Treatment every third day was selected as the best dosing schedule, based on Bayesian posterior probabilities, and was used in stage 2 of the study, which involved 34 individuals not involved in stage 1 who received intranasal oxytocin or placebo according to this schedule in the same crossover design as in stage 1.
During treatment with intranasal oxytocin every third day across stages 1 or 2 there was a significant reduction, or improvement, in mean NPI apathy score of 1.29 points, whereas there was no change during treatment with placebo. This translated to an estimated 1.32-point greater reduction in the NPI apathy score with oxytocin treatment relative to placebo in the per-protocol population of 49 people.
Prespecified subgroup analyses showed greater reductions in NPI apathy score relative to placebo for men (1.47 points); people with mild disease severity (1.42 points), based on a Clinical Dementia Rating global score of 0–1 versus 2 points; patients younger than 67 years (1.89 points); and people with the behavioral variant frontotemporal dementia clinical subtype (1.53 points).
The researchers note that “reductions in apathy were not associated with worsening of other disruptive behaviors,” and “[c]ompliance with the intranasal sprays was high [97.1%].”
Upper respiratory tract infection and headache were the most common adverse events, occurring in a respective 5% and 4% of patients during oxytocin treatment, and 6% and 3% of patients during placebo treatment, but no cases were attributed to treatment.
This “shows that intranasal oxytocin up to 72 IU twice daily is safe and well tolerated over a 6-week period,” say Finger et al.
In an accompanying comment, Muireann Irish and Rebekah Ahmed, both from The University of Sydney in New South Wales, Australia, caution that interpreting the “relatively small” treatment effect “in terms of clinical relevance, and its effect on an individual living with frontotemporal dementia are unclear.”
They highlight that “carers did not report a substantial reduction in their level of distress experienced due to apathy symptoms, again suggesting that the treatment effect of oxytocin is relatively circumscribed.”
Finger et al conclude that the improvement in apathy with intermittent oxytocin “is a promising indicator of likely usefulness over longer durations, which could be explored in future phase 3 or pragmatic trial designs.” In response, Irish and Ahmed suggest that “the utility of oxytocin might lie in a multipronged approach rather than as a standalone treatment for apathy.”
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