P-135 Effects of venlafaxine on clinical and pupillometry mea- sures in patients with progressive supranuclear palsy

Objectives: This ongoing, monocentric, prospective, interventional trial aims to characterize the effects of venlafaxine, a serotonin-nore- pinephrine reuptake inhibitor, on 1. Clinical measures as neuropsy- chiatric and motor outcomes, 2. Evoked pupil dilation responses (PDR) and spontaneous pupil oscillations as an indirect biomarker of brainstem locus coeruleus (LC) activity in patients with progres- sive supranuclear palsy (PSP).
Background: PSP is an atypical Parkinsonian syndrome with pre- dominant brainstem dysfunction, reduced levodopa response and poor prognosis. Histopathologically, early degeneration of noradren- ergic cells in the locus coeruleus (LC) is found in PSP, which corre- lates with disease severity (Kaalund et al., 2020). The LC is involved in numerous physiological functions as arousal, attention, adaptive behavior and locomotor control. The pharmacological approach of substitution of the noradrenergic deficit with venlafax- ine might therefore improve LC related symptoms (Kaalund et al., 2020) with concomitant pupillary changes in PSP.
Methods: 12 PSP patients were assessed at baseline and after 4–6 weeks of treatment with venlafaxine. At both visits, disease-specific interviews and clinical assessments were performed (PSP rating scale, Luria sequence, three-clap test). Cognitive tests (MoCA, Trail Making Test (TMT), verbal fluency) and questionnaires (Geriatric Depression Scale (GDS), Starkstein Apathy Scale (SAS), PSP-QoL scale) were performed. Pupillometry was recorded at rest and during an auditory oddball paradigm at baseline and follow-up and com- pared to 12 healthy age-matched controls (HC), which were assessed once without venlafaxine. Baseline and follow-up outcomes were compared by ANOVA and post-hoc t-tests.
Results: Clinically, higher GDS and TMT-B interim mean values were found in PSP compared to HC indicating depression and impaired executive functions in PSP. At follow-up visit, the patients’ GDS
mean score and the time needed for the TMT-B were improved by venlafaxine. Preliminary, ongoing pupillometry analysis of PDR indi- cates that the average amplitude is reduced in PSP compared to HC and might be enhanced by venlafaxine.
Conclusions: Preliminary clinical and pupillometry findings suggest that venlafaxine might reestablish LC brainstem function resulting in improved executive functions and reduced depressiveness in PSP patients, which might be reflected by pupillary changes as an index of LC activity.