The Parkinson's-Reversing Breakthrough

Treatment for Parkinson Disease

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There is a poor evidence base for the treatment of sleep problems in PD, and the issue is complicated by the fact that treatment of sleep problems in PD needs to take into account the multifactorial nature of sleep disturbances in PD. A review by the Movement Disorder Society Task Force reported that there were no robust trials of dopaminergic agents for the treatment of nonmotor symptoms in PD, including sleep (80). Only modafinil (for EDS) and melatonin (for insomnia) have been studied in randomized, double-blind trials in a small number of patients with PD (Table 6). Other published reports consist of case series and open-label trials with limited and inadequate evidence for treatment.

TABLE 6 Management Strategies for Symptoms Contributing to Nocturnal Disturbance in Parkinson's Disease

Insomnia-related symptoms Fragmented sleep with difficulty in sleep onset and sleep maintenance Nonpharmacologic measures Avoidance of nighttime alcohol, caffeine, tobacco Increase in daytime physical activity and ensuring exposure to daylight Psychological therapies: relaxation training, cognitive therapies, biofeedback training Pharmacologic strategies Short-acting benzodiazepines: clonazepam, temazepam, diazepam Nonbenzodiazepine hypnotics: zopiclone

Tricyclic antidepressants: amitriptyline (may help nocturia but may aggravate RLS) Motor symptoms

Fidgeting, painful cramps and posturing, tremor, sleep akinesia, RLS-type symptoms Nonpharmacologic measures Use of satin bed sheets and bed straps to help moving in bed Bed rails

Pharmacologic strategies (based on case series and open label trials) Sustained dopaminergic stimulation (nighttime dosing of) Sustained release levodopa ┬▒ COMT inhibitor, Stalevo Long-acting dopamine agonists, e.g., cabergoline Nocturnal apomorphine infusion (severe RLS/PLM/dystonia/cramps) Combination of daytime apomorphine and evening cabergoline (dual agonist therapy) Practical measures to aid bioavailability of dopaminergic medications Avoidance of high-protein meals at night Domperidone if delayed gastric emptying

REM behavior disorder

Clonazepam (usually first choice) Pramipexole

Melatonin (in double blind trial)




Neuropsychiatric symptoms Distressing dreams, hallucinations, depression Nonpharmacologic measures

Consider alternative diagnosis: MSA, LBD, PSP Pharmacologic strategies Hallucinations If Drug-induced: optimize therapy Atypical neuroleptics: quetiapine, clozapine Depression

Amitriptyline; noradrenaline reuptake inhibitors; dopamine agonists, e.g., pramipexole Panic attacks During "on" periods: alprazolam, lorazepam

During "off" periods: sustained release levodopa┬▒COMT inhibitor; cabergoline;

apomorphine infusion Any time: sertraline, fluoxetine, paroxetine


TABLE 6 Management Strategies for Symptoms Contributing to Nocturnal Disturbance in Parkinson's Disease (Continued)

Urinary symptoms Nocturia

Incontinence because of inability to move during "off" phase Nonpharmacologic measures Reduction of evening fluid intake Emptying bladder before bed Use of condom catheters/bedside commode If associated with postural hypotension, head-up tilt of bed Pharmacologic strategies Low-dose amitriptyline

Possible role for D1/D2 agonists, e.g., cabergoline, pergolide, apomorphine If associated with detrusor instability: oxybutinin, tolterodine

If associated with morning hypotension: desmopressin nasal spray, avoidance of evening diuretics, antihypertensives, vasodilators

Abbreviations: COMT, catechol O-methyl-transferase; CR, controlled-release; MSA, multiple system atrophy; LBD, Lewy body dementia; PLM, periodic limb movement; PSP, progressive supranuclear palsy; RLS, restless legs syndrome.

The use of the PDSS enables the clinician to adopt a systematic and pragmatic approach to treatment of nighttime symptoms. An example would be patients with PDSS scores, indicating nocturnal motor disabilities due to wearing off, might benefit from extending the action of levodopa, by combining levodopa with a catechol O-methyl-transferase inhibitor such as entacapone or tolcapone, or using a nighttime dose of a dopamine agonist. Scores indicating hallucinations might warrant withdrawal of nighttime dopamine agonists or treatment with clonazepam if RBD is suspected. A summary of management strategies for sleep disturbances related to PD is outlined in Table 6.

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