Falls and Fractures in Patients with Parkinson's Disease-Related Psychosis Treated with Pimavanserin vs Atypical Antipsychotics: A Cohort Study

Abstract

Background: Parkinson's disease-related psychosis increases patients' risk of falls. Pimavanserin is an atypical antipsychotic approved in the USA in 2016 for the treatment of hallucinations and delusions associated with Parkinson's disease-related psychosis.

Objective: We aimed to compare the risk of falls/fractures among patients with Parkinson's disease-related psychosis treated with pimavanserin vs other atypical antipsychotics.

Patients and methods: We identified a cohort of patients with Parkinson's disease-related psychosis aged ≥ 40 years initiating either pimavanserin or a comparator antipsychotic (clozapine, quetiapine, risperidone, olanzapine, aripiprazole, brexpiprazole) in US commercial insurance and supplementary Medicare claims (2015-2019). Comparators were propensity score matched 2:1 with pimavanserin initiators; incidence rates of falls/fractures were compared using incidence rate ratios (IRRs) and 95% confidence intervals (CIs).

Results: We identified 112 eligible pimavanserin initiators and 982 comparators. Pimavanserin initiators were younger and had fewer severe comorbidities, indicators of impairment, and healthcare encounters, though they had higher Parkinson's disease medication use. The crude incidence rates [cases/100 person-years] (95% CI) for composite falls/fractures were 17.8 (7.7-35.0) for pimavanserin and 40.8 (35.0-47.4) for comparators. Matching retained 108 pimavanserin initiators and 216 comparators-all characteristics were well balanced after matching-with a matched IRR (pimavanserin vs comparator) of 0.71 (95% CI 0.27-1.67). Sensitivity analysis IRR estimates were consistently below 1.00, with a sensitivity analysis not requiring a diagnosis of psychosis resulting in an IRR estimate of 0.55 (95% CI 0.34-0.86).

Conclusions: The results of this study do not suggest an increase in the risk of falls or fractures associated with pimavanserin compared with other antipsychotics in patients with Parkinson's disease-related psychosis. Sensitivity analyses suggest a decreased risk.

Fig. 1

Identification of eligible pimavanserin or comparator atypical antipsychotic initiators for inclusion in the study cohort. Note: The duration of each assessment window is given in days relative to the cohort entry date (day 0). Square brackets indicate the window is inclusive of the stated date. Similar sets of criteria (e.g., washout windows, exclusion assessment windows, covariate assessment windows, follow-up windows) are shown in the same color. Figure template available at www.repeatinitiative.org. PD Parkinson’s disease. ^a Comorbid conditions that were exclusion criteria were bipolar disorder, schizophrenic disorders, Huntington’s disease, and pathologic fracture. ^b Baseline conditions included wheelchair use, ambulance transport or life support, bladder dysfunction, coagulopathy, home oxygen, paralysis, dementia, cancer screening, heart failure, lipid abnormality, vertigo, difficulty walking, podiatric care, rehabilitation services, arthritis, skin ulcer, sepsis, stroke/brain injury, weakness, diabetes mellitus complications, home hospital bed, myocardial infarction, peripheral vascular disease, chronic obstructive pulmonary disease, peptic ulcer disease, liver disease, diabetes mellitus, hemiplegia, chronic kidney disease, tumor, leukemia, lymphoma, human immunodeficiency virus/acquired immune deficiency syndrome, delirium, osteoporosis, multiple sclerosis, celiac disease, Crohn’s disease, ulcerative colitis, ankylosing spondylitis, depression, hyperthyroidism, Cushing’s syndrome, hyperparathyroidism, vitamin D deficiency, malnutrition, impaired vision, and orthostatic hypotension. ^c Baseline comedications included osteoporosis treatment, androgen deprivation therapy, nonsteroidal anti-inflammatory drugs, cyclooxygenase-2 inhibitors, systemic glucocorticoids, enzyme-inducing anticonvulsants, thiazolidinediones, benzodiazepines, sedatives, digoxin, diuretics, anticholinesterase inhibitors, antidepressants, and Parkinson’s disease drugs (levodopa-carbidopa, anticholinergics, dopamine agonists, monoamine oxidase B inhibitors, catechol-O-methyltransferase inhibitors, amantadine, and istradefylline). ^d Baseline healthcare utilization included number of hospitalizations and number of emergency department visits. ^e Earliest occurrence of administrative study end (31 December 2019); disenrollment from the MarketScan databases; pathological fracture that may have resulted from conditions such as cancer, infection, osteomalacia, and Paget’s disease; diagnosis of bipolar disorder, schizophrenic disorders, or Huntington’s disease; discontinuation of index medication; and initiation of a different study antipsychotic other than the index treatment

Fig. 2

Attrition of the study cohort by application of eligibility criteria

Fig. 3

Relative balance of patient characteristics between the pimavanserin and comparator atypical antipsychotic treatment groups among patients with Parkinson’s disease (PD) psychosis, before and after matching

Fig. 4

Propensity score distributions of the pimavanserin and comparator atypical antipsychotic treatment groups among patients with Parkinson’s disease psychosis