Objective: To evaluate the efficacy and safety of inhaled (INH) and sublingual (SL) film apomorphine formulations for on-demand treatment of OFF episodes in Parkinson’s disease (PD).

Background: OFF episodes contribute substantially to disability in PD. Non‑injectable apomorphine formulations offer fast dopaminergic stimulation for on-demand symptom relief. Although INH and SL apomorphine exhibit rapid pharmacokinetics, comparative data on the magnitude,  durability, and tolerability of motor response remain limited.

Method: A systematic PubMed search identified randomized, placebo‑controlled parallel or crossover trials evaluating INH or SL apomorphine for OFF episodes in PD. The primary outcome was the change from baseline in MDS UPDRS-III scores at 30 and 60 minutes post‑dose, pooled as the mean difference (MD). Safety outcomes were summarized using risk ratios (RR). Between‑study heterogeneity was assessed with I². Random‑effects models with REML were used when heterogeneity was substantial.

Results: Four trials were included (n = 406). At 30 minutes, pooled analyses showed a greater improvement in MDS UPDRS‑III score with active treatment compared with placebo (MD −11.66 points, 95% CI −17.56 to –5.76; I² = 92%) [Figure 1]. Similar effects were observed at 60 minutes,  (MD −13.03 points, 95% CI −20.75 to –5.31; I² = 87%) [Figure 2], indicating sustained short-term motor benefit despite substantial heterogeneity. Dopaminergic adverse events occurred more frequently with active therapy, including somnolence/fatigue (RR 2.19, 95% CI 1.11–4.31) and yawning (RR 3.90, 95% CI 1.06–14.40) [Figure 3]. In contrast, nausea (RR 2.41, 95% CI 0.57–10.23) and dizziness (RR 2.71, 95% CI 0.89–8.27) did not reach statistical significance.

Conclusion: INH and SL apomorphine provide statistically significant short-term motor improvement during OFF episodes in Parkinson’s disease; however, treatment effects are highly heterogeneous, with wide prediction intervals indicating variable clinical response. Adverse events reflect expected dopaminergic effects. These findings support on-demand apomorphine as an effective option for selected patients while highlighting the need for individualized treatment selection and further comparative studies to clarify durability and tolerability.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/efficacy-and-safety-of-inhaled-and-sublingual-apomorphine-for-on-demand-treatment-of-off-episodes-in-parkinsons-disease-a-meta-analysis-of-randomized-placebo-controlled-trial/