2026 ECNP Congress

PS03-3145

Real-world duration of rivastigmine therapy in dementia: oral versus transdermal patch

Bandar Alaqeel — M. Alsubaie, A. Rokon, A. Alshehri · King Abdulaziz Medical City, Mental Health, Riyadh, Saudi Arabia

2026 ECNP Congress

Introduction

Rivastigmine, a cholinesterase inhibitor used in mild-to-moderate dementia [1], is available as an oral capsule and a transdermal patch. The patch was developed to improve tolerability and permit higher doses, and trials have shown more consistent plasma concentrations and fewer gastrointestinal adverse events with the patch [2,3]. Whether this advantage translates into longer real-world treatment persistence has been variable across observational cohorts [4].

Aims

To compare real-world treatment persistence between oral and transdermal patch rivastigmine in patients with dementia at a Saudi tertiary center, where rivastigmine is the only cholinesterase inhibitor on the institutional formulary.

Methods

Retrospective cohort study at King Abdul-Aziz Medical City, Riyadh, using de-identified electronic health record data. All patients aged ≥60 years initiating rivastigmine for clinical dementia between 2015 and 2026 with ≥6 months of follow-up were eligible. Discontinuation was defined as a gap of ≥6 months between the last rivastigmine prescription and the patient’s most recent prescription of any medication, with no restart; discontinuation date was set to last refill plus 90 days (institutional dispensing supply). Patients with shorter gaps were censored. Persistence was estimated by the Kaplan–Meier method and compared using the log-rank test. A multivariable Cox model adjusted for age, sex and concomitant antidepressant use, with the proportional hazards assumption verified. Pre-specified sensitivity analyses applied a 12-month gap rule and restricted the cohort to patients initiating in 2020 or later. Therapeutic-target attainment (oral ≥6 mg BID; patch ≥9.5 mg/24h) was reported descriptively, not modelled. Dementia subtype was assigned by propagating any specific subtype ever recorded for a patient.

Results

Of 904 patients receiving rivastigmine, 634 met eligibility criteria (191 oral, 443 patch). Median age at initiation was 76 years (IQR 71–81), and 55.0% were male. Patch users were significantly more likely than oral users to reach the therapeutic target dose (73.1% versus 38.2%, p<0.001). The Kaplan–Meier median time on rivastigmine was 51.0 months in the oral group (95% CI 38.4–65.6) and 49.8 months in the patch group (41.0–64.1). Twelve-month persistence was 88.0% (oral) versus 87.3% (patch); twenty-four-month persistence was 71.6% versus 70.4%. The two survival curves overlapped throughout follow-up, and the log-rank test demonstrated no significant difference between formulations (χ²=0.02, p=0.88). The null finding was robust to all sensitivity analyses. In the multivariable Cox model the adjusted hazard ratio for patch versus oral was 1.01 (95% CI 0.78–1.31, p=0.95). Concomitant antidepressant use was the only independent predictor of discontinuation (adjusted hazard ratio 1.33, 95% CI 1.02–1.75, p=0.036), with non-significant trends for older age and female sex.

Conclusions

In a real-world cohort, oral and transdermal rivastigmine produced equivalent treatment persistence over a median of approximately three years of follow-up, despite the patch’s clear advantage in achieving therapeutic dose. The patch’s pharmacological benefit did not translate into longer therapy. Concomitant antidepressant use, but not formulation, predicted earlier discontinuation, identifying a subgroup at increased risk of attenuated benefit. These findings argue against routinely preferring the patch on persistence grounds and support patient-individualized choice.

References

  1. Birks, J., Grimley Evans, J., Iakovidou, V., Tsolaki, M., 2009. Rivastigmine for Alzheimer’s disease. Cochrane Database Syst. Rev. (2), CD001191.
  2. Winblad, B., Cummings, J., Andreasen, N., Grossberg, G., Onofrj, M., Sadowsky, C., Zechner, S., Nagel, J., Lane, R., 2007. A six-month double-blind, randomized, placebo-controlled study of a transdermal patch in Alzheimer’s disease — rivastigmine patch versus capsule. Int. J. Geriatr. Psychiatry 22 (5), 456–467.
  3. Grossberg, G.T., Sadowsky, C., Frostl, H., Frolich, L., Nagel, J., Tekin, S., Zechner, S., Lane, R., Cummings, J.L., 2009. Safety and tolerability of the rivastigmine patch: results of a 28-week open-label extension. Alzheimer Dis. Assoc. Disord. 23 (2), 158–164.
  4. Karaman, Y., Erdogan, F., Koseoglu, E., Turan, T., Ersoy, A., 2005. A 12-month study of the efficacy of rivastigmine in patients with advanced moderate Alzheimer’s disease. Dement. Geriatr. Cogn. Disord. 19 (1), 51–56.