Efficacy and Safety of Inhaled and Sublingual Apomorphine for On‑Demand Treatment of OFF Episodes in Parkinson Disease: A Systematic Review and Meta-Analysis With Exploratory Network Comparison.

Authors

Jamir Pitton Rissardo, Jorge Luis Vargas Rojas, Juan Aristizabal Marin, Ana Leticia Fornari Caprara

Published in

Clinical neuropharmacology. Sep 17, 2026. Epub Sep 17, 2026.

Abstract

OFF episodes are a major source of disability in Parkinson disease (PD). Noninjectable apomorphine formulations, including inhaled (INH) and sublingual (SL) delivery systems, provide rapid dopaminergic stimulation for on-demand symptom relief. However, their efficacy and safety remain incompletely characterized.
We conducted a systematic review and meta-analysis of randomized parallel-group and crossover trials evaluating inhaled or sublingual apomorphine for OFF episodes in PD. The primary outcome was change from baseline in MDS-UPDRS III scores at 30 and 60 minutes post-dose, pooled as mean differences (MD). Safety outcomes were summarized as risk ratios (RR). Random-effects models were applied when substantial heterogeneity was present. PROSPERO (CRD420261440116).
Four randomized controlled trials (n=406) were included. At 30 minutes, noninjectable apomorphine significantly improved motor function compared with control interventions (MD: -11.66 points, 95% CI: -17.56 to -5.76; I2= 92%). A similar effect was observed at 60 minutes (MD: -13.03 points, 95% CI: -20.75 to -5.31; I2=87%). Formulation type was not a significant moderator of treatment effect, although subgroup analyses suggested greater persistence of benefit with SL formulations at 60 minutes. Somnolence/fatigue (RR: 2.19, 95% CI: 1.11-4.31) and yawning (RR: 3.90, 95% CI: 1.06-14.00) were more frequent with apomorphine. Certainty of evidence for motor outcomes was moderate according to GRADE.
INH and SL apomorphine provide clinically meaningful short-term motor improvement during OFF episodes in PD. Despite substantial heterogeneity, these findings support their use as effective on-demand therapies and highlight the need for individualized treatment strategies and further comparative-effectiveness research.

PMID:
42757652
Bibliographic data and abstract were imported from PubMed on 18 Sep 2026.

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