Treatment of sleep disorders in Parkinson s s disease (PD) K. Ray Chaudhuri London, UK GPSRC CNS 176 0709 RTG 1
Managing insomnia in PD Onset/initiation Adjustment of anti-pd treatment Sleep hygiene Hypnotics Points ts Poin Maintenance Cabergoline (CBG; ergot) po Apomorphine (Apo) sc infusion over 24 hours Rotigotine patch Ropinirole XP Subthalamic nucleus/pallidal stimulation Duodopa CR, controlled release levodopa Chaudhuri et al. Eur J Neurol 1999;6(suppl5):S11 15;Reuter et al. Acta Neurol Scand 1999;100:163 7. To view abstract, click Abstracts link above GPSRC CNS 176 0709 RTG 2
Dopamine agoinsts (DA)-induced sleep-onset insomnia Avoid high dose Use hypnotic/sedative (low dose) Avoid pulsatile therapy Sleep hygiene GPSRC CNS 176 0709 RTG 3
Duodenal levodopa improves sleep-related symptoms Score 140 120 100 80 60 40 20 P=0.002 Baseline Post duodenal levodopa % P=0.001 0 PDSS % change Sleep NMS % change Honig et al. Mov Disord 2009;24:1468 74. PDSS Parkinson's s disease sleep scale NMS Non-motor symptoms scale Higher scores indicate less severe symptoms To view abstract, click Abstracts link above GPSRC CNS 176 0709 RTG 4
Restless legs syndrome (RLS) like syndrome in PD RLS may be twice as common in PD RLS like syndrome Partially satisfies International Restless Legs Syndrome Study Group criteria RLS like syndrome type 1 Relatively unresponsive to DA Pain dominant Therapy with gabapentin in RLS like syndrome type 1 RLS like syndrome type 2 Fluctuation related Responsive to longer acting DA (ropirinole XL, rotigotine, Duodopa) Higher in autosomal recessive phenotype in PD May need polysomnography (PSG) to elucidate Reddy et al. Characterisation of restless legs (RLS) like syndrome in Parkinson s disease. Abstract. Meeting of Movement Disorder Society. 2009, Paris, France. GPSRC CNS 176 0709 RTG 5
Excessive daytime sleepiness (EDS) narcolepsy without cataplexy in PD (10% of PD population) Secondary narcolepsy phenotype Clinical PSG criteria No cataplexy Reported in preprohypocretin p polymorphism p and Taq 1A D2-receptor gene polymorphism Possibly related to hypocretin deficiency Reported while driving high risk factor for road traffic accidents Sensitivity to DA (non-ergot) GPSRC CNS 176 0709 RTG 6
Practical management of excessive daytime sleepiness Frauscher & Poewe. Chapter 16. In: Chaudhuri et al., eds. Non-Motor Symptoms of Parkinson s Disease. Oxford: Oxford University Press, 2009. GPSRC CNS 176 0709 RTG 7
EDS in PD: The future Adenosine A1 stimulation: inhibit hypocretin and Aden antagonists increase wakefulness Implications for A2a receptor antagonists Caffeine: non-selective adenosine antagonist Phase II study ongoing (clinical trial reference NCT00459420) Histamine: tonically active in wakefulness BF 2.649 H3 inverse agonist: phase II study ongoing g (clinical trial reference NCT00642928 ) GPSRC CNS 176 0709 RTG 8
REM sleep behaviour disorder (RBD) treatment Clonazepam 12 1,2 Pramipexole 3,4 Levodopa 5,6 Melatonin 7,8 Gabapentin (no published data in RBD) Donepezil 9 Duodopa (unpublished observations) No controlled trials have been carried out 1 Schenck. Sleep 2002;25:120 38; 2 Boeve et al. Brain 2007;130: 2770 88; 3 Fantini et al. Neurology 2003;61:1418 20; 4 Schimdt et al. Sleep Med 2006;7:418 23; 5 Tan et al. Mov Disord 1996;11:214 6; 6 Yamauchi et al. Gen Hosp Psychiatry 2003;25:140 2; 7 Kunz et al. Mov Disord 1999;14:507 11; 8 Boeve et al. Sleep Med 2003;4:281 4; 9 Ringman et al. Neurology 2000;55:870 1. GPSRC CNS 176 0709 RTG 9
Sleepy PD Review drugs + sleep hygiene Identify cause PDSS/EDS Treatment algorithm Nocturia RLS /akathisia/ PLMS, RLS-L Parasomnia REM/Non-REM Akinesia Insomnia Pain Evening dose of DA Gabapentin Avoid Acetylcholine/diuretic/va sodilator Try Tolterodine/Oxybutinin?Amitriptyline?DA (D1/D2 agonist) Desmopressin PSG if sleepiness persists Clonazepam/?melatonin/ DA PLMS Obstructive sleep apnoea 2 o Narcolepsy Night-time dosing of longacting DA Day-time alertness promoting agents (e.g. modafinil, caffeine) DA therapy Opiates BTX Sleep maintenance: DA Sleep onset: BDZ Adapted from Chaudhuri & Nieder. Pahwa & Lyons, eds. Oxford:Taylor & Francis Group, 2006 BDZ, short-acting benzodiazepine; BTX botulinum toxin; PLMS periodic limb movements during sleep. GPSRC CNS 176 0709 RTG 10
Question 1. High doses of dopamine agonists can: A) Make patients with PD feel sleepy B) Have no effect on their sleep C) Can cause insomnia Correct - Click anywhere to continue Incorrect, please try again Incorrect, You must please answer try again the question before continuing Submit Clear GPSRC CNS 176 0709 RTG 11
Question 2. When first giving dopaminergic agents such as pramipexole to patients with PD it is wise to recommend that they: A) Avoid strenuous exercise B) Avoid grapefruit products Correct: ~ 25% of patients experienced l h the drug dose was being escalated. Click anywhere to continue. C) Avoid driving somnolence when Correct - Click anywhere to continue Incorrect, please try again Incorrect, You must please answer try again the question before continuing Submit Clear GPSRC CNS 176 0709 RTG 12
Copyright statements Slide 2 Slide 9 Slide 12 1999, reproduced with permission from Wiley- Blackwell 2009, reproduced with permission from Oxford University it Press 2006, reproduced with permission from Informa Healthcare 13