Antianxiety treatment in PD improves motor function

Presenter: Nabila Dahodwala, MD, MS, University of Pennsylvania, Philadelphia, PA.

The impact of anxiety symptoms and treatment on Parkinson’s disease-related disability: Findings from the Parkinson’s Progression Markers Initiative. Abstract 549.

Initiating antianxiety treatment in patients with Parkinson disease (PD) reduced their scores on the Movement Disorders Society–Unified Parkinson's Disease Rating Scale (MDS-UPDRS) and their use of PD medication, based on cohort data from the Parkinson’s Progression Markers Initiative (PPMI), a large multicenter, longitudinal, observational study. Assessment of the dataset revealed that anxiety contributes to ongoing functional decline in PD and is a treatable symptom that may improve outcomes, according to presenter Nabila Dahodwala, MD, MS, and colleagues from the University of Pennsylvania, Philadelphia, PA.

Anxiety is common among people with PD,1 even early in disease, and its presence is associated with short-term adverse outcomes such as decreased health-related quality of life and increased caregiver burden.2,3 Despite numerous treatment options, however, anxiety treatment in PD in real-world clinical practice is underused, possibly as a result of disabling side effects and overall limited efficacy, Dahodwala said.

Further, the impact of suboptimal treatment of anxiety in PD remains unknown. The functional consequences of baseline anxiety symptoms and the longer-term impact of initiating anxiety treatment in PD were therefore explored among a cohort of participants in the PPMI with newly diagnosed, untreated (at baseline) PD. As a part of PPMI, motor, cognitive, and psychiatric assessments are conducted annually for up to 7 years. Outcomes measures include the MDS-UPDRS parts 1, 2, 3, and total scores, levodopa equivalent daily doses, and the Schwab and England Activities of Daily Living (ADL) scale.

The presence of potentially significant anxiety symptoms was determined using the State Trait Anxiety Inventory state subscale, with a score of 40 or greater considered a positive screen. Self-reported use of antidepressants or anxiolytics and/or sedatives was also assessed.

The effect of anxiety and anxiety treatment on motor and nonmotor outcomes was assessed using marginal mean regression models controlling for age, sex, race and/or ethnicity, and education and depression scores. The effect of anxiety on time to initiation of dopaminergic therapy was analyzed using Cox proportional hazards models.

A total of 493 participants with de novo PD were identified, 111 (22.5%) of whom screened positive for anxiety at baseline, but about two thirds (N = 71; 64.0%) were untreated for anxiety. At baseline, those with anxiety had significantly lower scores on the MDS-UPDRS part 1 (P < 0.001), MDS-UPDRS part 2 (P = 0.02), MDS-UPDRS total (P < 0.001), and the Schwab and England ADL scale (P = 0.04). The percentage with cognitive impairment was significantly greater in participants with anxiety than in those without anxiety (23.5% vs 13.4%; P = 0.02).4

Anxiety at baseline and longitudinally was associated with worse motor scores and functional ability after adjusting for age, sex, race, and education. “The presence of anxiety led to faster time to initiation of PD therapy, which may reflect the direct influence of anxiety on personal preference for starting treatment or a faster disease progression,” the researchers wrote in their poster presentation.

A total of 16 of 71 (22.5%) participants with anxiety who were not treated for anxiety at baseline initiated anxiety treatment during the study. Initiation of anxiety treatment was associated with a reduction in MDS-UPDRS total scores (effect size prior to treatment: 5.45, P < 0.001; change after treatment: minus 3.11, P = 0.038) and lower levodopa daily dose equivalent (effect size prior to treatment: 142.7, P < 0.001; change after treatment: minus 85.6; P = 0.022).

The improvement in the trajectory of motor scores and in the amount of dopamine replacement therapy with the treatment of anxiety suggests that management of nonmotor symptoms such as anxiety also benefits motor symptoms, they concluded.

References

  1. Simunt T, Caspell-Garcia C, Coffey CS, et al. Baseline prevalence and longitudinal evolution of non-motor symptoms in early Parkinson’s disease: the PPMI cohort. J Neurol Neurosurg Psychiatry 2018; 89(1):78-88. doi: 10.1136/jnnp-2017-316213.
  2. Ray S, Agarwal P. Depression and anxiety in Parkinson disease. Clin Geriatr Med 2020; 36(1):93-104. doi: 10.1016/j.cger.2019.09.012.
  3. Leiknes I, Tysnes O-B, Aarsland D, Larsen JP. Caregiver distress associated with neuropsychiatric problems in patients with early Parkinson’s disease: the Norwegian ParkWest study. Act Neurol Scand 2010; 122(6):418-424. doi: 10.1111/j.1600-0404.2010.01332.x.
  4. Dahodwala N, Weintraub D, Bock M, et al. The impact of anxiety symptoms and treatment on Parkinson’s disease-related disability: findings from the Parkinson’s Progression Markers Initiative [abstract]. Mov Disord 2023; 38 (suppl 1). https://www.mdsabstracts.org/abstract/the-impact-of-anxiety-symptoms-and-treatment-on-parkinsons-disease-related-disability-findings-from-the-parkinsons-progression-markers-initiative/. Accessed Aug 28, 2023.

 

The Parkinson’s Progression Markers Initiative (PPMI), a public-private partnership, is funded by the Michael J. Fox Foundation for Parkinson's Research. Funding partners include 4D Pharma, Abbie, AcureX, Allergan, Amathus Therapeutics, Aligning Science Across Parkinson's, AskBio, Avid Radiopharmaceuticals, BIAL, Biogen, Biohaven, BioLegend, BlueRock Therapeutics, Bristol-Myers Squibb, Calico Labs, Celgene, Cerevel Therapeutics, Cave Therapeutics, DaCapo Brainscience, Denali, Edmond J. Safra Foundation, Eil Lilly, GE HealthCare, Genentech, GSK, Golub Capital, Gain Therapeutics, Hand Therapeutics, Insitro, Jansen Neuroscience, Lundbeck, Merck, Meso Scale Discovery, Mission Therapeutics, Neurocrine Biosciences, Pfizer, Piramal, Prevail Therapeutics, Roche, Sanofi, Servier, Sun Pharma Advanced Research Company, Takeda, Teva, UCB, Vanqua Bio, Verily, Voyager Therapeutics, the Weston Family Foundation, and Yumanity Therapeutics.

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