Selecting the right treatment for your advanced patient
Submitted by emily.kilby on Thu, 02/11/2021 - 10:09


Selecting the right treatment for your advanced patient

Tove Henriksen MD

Movement Disorder Clinic, Department of Neurology, Bispebjerg Hospital, Copenhagen, Denmark 


When decisions are made on treatment for advanced Parkinson’s disease (PD), a number of stakeholders are involved, including the government, the neurologist, the carer and the patient.  Numerous factors are relevant to the decision-making process such as reimbursement and national tradition, local access to neurologists [1], the clinician’s experience with advanced treatments, the amount of information to be communicated to - and understood by - patients and carers, and treatment-specific data on efficacy, side effects and practical aspects.

For the neurologist, a lack of randomized control trials (RCTs) makes decision-making difficult. While not an RCT, the Euroinf study provides the largest dataset comparing the motor and nonmotor effects of the advanced PD treatments [2].  Attempts have also been made to define the course of disease progression and thereby the parameters that define advanced PD in order to help provide a timeframe for initiation of advanced device-aided treatment options; amongst these are Navigate PD [3] and the multi-country Delphi expert consensus panel [4]. The result of these efforts has been the definition of advanced PD by a rule of thumb, the so-called ‘5-2-1’ rule: 5 (5 times oral levodopa tablet taken/day) -2 (2 hours of OFF time/day) -1 (1 hour/day of troublesome dyskinesia) [4].  

Apomorphine pump therapy (continuous subcutaneous apomorphine infusion, CSAI) is the oldest advanced treatment available. Most recently, the TOLEDO study, a multicentre, double-blind RCT in PD patients with persistent motor fluctuations despite optimised oral or transdermal treatment, showed apomorphine infusion to be associated with a significant and clinically meaningful reduction in off time [5].  CSAI fits well alongside deep-brain stimulation (DBS) and levodopa-carbidopa intestinal gel (LCIG) as a treatment option for advanced PD.  The selection of the most appropriate of these treatments for your patient depends on a wide range of factors including age, comorbidities, cognitive function, postural stability and carer support.  

Algorithms have been published [6] to help choose the right treatment for the advanced PD patient, and national and international guidelines add to this guidance.

How to start apomorphine infusion
To ensure a successful trial of apomorphine, several factors are important; 
•    easy access to a skilled PD nurse, 
•    a movement disorder specialist with experience of advanced treatments, or who is willing to refer the patient to a centre that has, 
•    a solid impression of the patient, 
•    encouragement of the patient and carer to seek further information from resources outside the hospital such as the local PD association, peers, and university websites [7]


When to start apomorphine infusion
We tend to offer patients the advanced treatments quite in their disease progression, at a time when the patient has already had to leave their work [8]. The Early-pump study, recruiting adults aged ≤ 65 years, with idiopathic PD and Hoehn and Yahr stage ≤ 2.5 in the best ON, may in the future give us valuable information on the effect of starting apomorphine at an earlier stage [9].



1.    Henriksen T, Dalhoff KP, Hansen HE et al. Access and use of device-aided treatment for Parkinson’s disease in Denmark. Mov Disord Clin Pract 2020;7(6):656-63

2.    Dafsari HS, Martinez-Martin P, Rizos A et al.  EuroInf 2: Subthalamic stimulation, apomorphine, and levodopa infusion in Parkinson's disease. Mov Disord 2019;34(3):353-65

3.    Odin P, Chaudhuri KR, Slevin JT et al. Collective physician perspectives on non-oral medication approaches for the management of clinically relevant unresolved issues in Parkinson's disease: Consensus from an international survey and discussion program Parkinsonism Relat Dis 2015;21(10):1133-44

4.    Antonini A, Stoessl AJ, Kleinman LS et al. Developing consensus among movement disorder specialists on clinical indicators for identification and management of advanced Parkinson's disease: a multi-country Delphi-panel approach.  Curr Med Res Opin 2018;34(12):2063-2073

5.    Katzenschlager R, Poewe W, Rascol O et al, Apomorphine subcutaneous infusion in patients with Parkinson's disease with persistent motor fluctuations (TOLEDO): a multicentre, double-blind, randomised, placebo-controlled trial.  Lancet Neurol 2018;17(9):749-59

6.    Timpka J, Henriksen T, Odin P. Non-oral Continuous Drug Delivery Techniques in Parkinson's Disease: For Whom, When, and How? Mov Disord Clin Pract 2016;3(3):221-9

7.    Trenkwalder C, Chaudhuri KR, García Ruiz PJ et al.  Expert Consensus Group report on the use of apomorphine in the treatment of Parkinson's disease – Clinical practice recommendations.  Parkinsonism Relat Disord 2015;21(9):1023-30

8.    Schrag A, Banks P. Time of loss of employment in Parkinson's disease. Mov Disord 2006;21(11):1839-43 

9.    Apomorphine Pump in Early Stage of Parkinson’s Disease (EARLY-PUMP). identifier: NCT02864004, Rennes University Hospital.



January 2021