Intermittent Apomorphine Use for off Period Rescue in Parkinson's Disease: A Pragmatic Review of over Three Decades of Clinical Experience

Abstract

Background Although proven very efficacious as treatment for Parkinson's disease by Schwab as far back as the 1950s, and later confirmed by Cotzias and colleagues in the early 1970s, use of intermittent subcutaneous injections of the dopamine agonist apomorphine remains limited worldwide. Objectives To review evidence regarding use of intermittent, on‐demand apomorphine as a treatment for off‐period disability in Parkinson's disease. Methods A PRISMA‐compliant structured literature search was carried out with a focus on clinical effect (motor improvement, daily off time decrease; latency, duration), antiemetic prophylaxis, and adverse events. Results Fifty‐eight studies were evaluated. Apomorphine administration route was subcutaneous in 29 (50%), sublingual in 14 (24.1%), intranasal in 6 (10.3%), inhaled in 5 (8.6%), rectal in 3 (5.2%) and transdermal in 1 (1.7%). Irrespective of the route, motor disability improved 19% to 74% and daily off time decreased 3% to 68%, with subcutaneous having the fastest onset of action ranging from 6 to 24 minutes and lasting 28 to 96 minutes. Antiemetic prophylaxis was used in almost all studies. Systemic side effects like nausea and yawning were mild and well tolerated, but sedation led to discontinuation of subcutaneous apomorphine in 5.5%. Local side effects to subcutaneous administration did not result in discontinuation. Stomatitis with the early sublingual formulations led to discontinuation in nearly half of patients and was reduced to 16.7% with novel film strips. Conclusions Intermittent subcutaneous injections remain the most reliable and safest route of apomorphine administration, with an efficacy for off period treatment supported by nearly four decades of clinical experience.

Apomorphine at the End‐of‐Life—A Role to Play

“…Cognitive decline did not figure among the most frequent side effects reported by Castillo-Torres et al, 1 indicating that the impact of apomorphine on cognition is probably overrated, with benefits justifying the risks to some extent. As our patient had a history of hallucinations, apomorphine dosage was carefully titrated, although these complications have rarely been reported, because of apomorphine's antagonism of 5-HT2A receptors.…”

“…We read with interest the recently published systematic review by Castillo-Torres and colleagues 1 on the last 30-years of use of intermittent subcutaneous apomorphine (SCA) for off-period rescue in patients with Parkinson's disease (PD). The authors described great motor improvement and remarkable reduction in daily off-periods.…”

“…As our patient had a history of hallucinations, apomorphine dosage was carefully titrated, although these complications have rarely been reported, because of apomorphine's antagonism of 5-HT2A receptors. 1 Despite the growing emphasis recently being given to the role of palliative care in advanced PD, there is still much to be done, especially with regard to chronic pain, mood swings, or dysphagia, because there are few therapeutic options available for these patients. 4,5 Early palliative care focuses on minimizing dyskinesia and decreasing occurrence of off-periods in an effort to maximize independent motor function.…”

Expert Consensus on the Use of On‐Demand Treatments for OFF Episodes in Parkinson's Disease: A Modified Delphi Panel

“…Recent reviews of these on ‐demand treatments have discussed their development, use, advantages, and disadvantages. 14 , 15 , 16 In this study, we used a validated and reproducible method to develop guidance on when it may be appropriate to prescribe on ‐demand treatments for patients experiencing OFF episodes.…”

“…Three non‐GI administered medications are used for on ‐demand treatment of OFF episodes when oral l ‐dopa formulations fail to reliably and/or rapidly restore ON benefit of symptoms: subcutaneous apomorphine injection, sublingual apomorphine film, and inhaled l ‐dopa. Recent reviews of these on ‐demand treatments have discussed their development, use, advantages, and disadvantages 14–16 . In this study, we used a validated and reproducible method to develop guidance on when it may be appropriate to prescribe on ‐demand treatments for patients experiencing OFF episodes.…”