Understanding and managing sleep and nonmotor symptoms of parkinson’s disease

1. Understanding and managing sleep and nonmotor symptoms of parkinson’s disease Jennifer Witt, MD Swedish Neuroscience Institute Medical Director of Movement Disorders

2. What is motor or nonmotor? Motor symptoms Non motor symptoms Mood Cognition Bowel and bladder function Temperature regulation Blood pressure regulation Sense of smell Sleep and energy issues Pain • Slowness/smallness of movement, or lack of movement • Tremor • Stiffness • Walking problems • Stooped posture

3. Why is it important to talk about? • These symptoms can be as disabling or more disabling than the motor symptoms • We don’t want to under-recognize or under-report, which leads to under treatment or lack of treatment • It is not always easy to know what is a non-motor symptom and what is a side effect of medication or DBS

4. How often do these occur? . * Identified as possible pre-motor symptoms Reichmann H, et al. Expert Opin. Pharmacother. 2009 10(5):773-84 Chaudhuri K, et al. Lancet Neurology. 2006, 5:235-245.

5. Mood • Depression – diagnosis may be different than in non-PD patients • Hallmark is loss of pleasure in things that are normally enjoyable. • Other features of depression in people WITHOUT PD overlap with PD symptomatology or med side effects • Feeling slow, fatigued • Difficulty with concentration or making decisions • Problems with sleep

6. Mood • Anxiety • More than expected for a situation, causing problems in day to day life • 1. Feeling wound-up, tense, or restless2. Easily becoming fatigued or worn-out3. Concentration problems4. Irritability5. Significant tension in muscles6. Difficulty with sleep

7. Mood • Apathy • Often overlaps with depression but does not have to • Loss of motivation or interest • Emotional display is flattened

8. Depression: isn’t it normal if you have an incurable disease? • is depression reactive or endogenous? • higher prevalence in PD compared with other chronic conditions w/ comparable disability • lack of clear relation between presence of depression (incidence) and severity of PD symptoms • Depressive symptoms can precede motor symptoms • Simuni and Sethi: Nonmotor manifestations of Parkinson’s Disease. annneurol 2008; 64 (suppl):S65-s80 • Rektorova et al. Pramipexole and pergolide in the treatment of depression in PD. Eur J Neurol (2003); 10:399-406

9. Pathophysiology of Depression in PD:dopaminergic, serotonergic, & noradrenergic mechanisms • What parts of the brain are involved?: • serotonergic and noradrenergic structures: raphenuclei and locus coeruleus • both involved early in the course of PD • Dopaminergic projections from the ventral tegmentum of the midbrain to the medial temporal and orbitofrontal regions have been shown to be affected • Reduced cerebrobrospinalfluid levels of the serotonin metabolite 5-hydroxyindoleacetic acid correlated with severity of depression in PD • Evidence from imaging studies: • limbic noradrenergic/dopaminergic pathways are dysfunctional in PD patients with depression compared to those without • Genetic predisposition: • first degree relatives of patients with PD are more likely to have had depression or anxiety D. Aarsland et al,.Movement Disorders, Vol. 24, No. 15, 2009

10. Mood • Treatment options • Optimize PD medications and minimize wearing off • Nonpharmacologic: counseling, bright light therapy (7500 Lux 30 min/day 1st hour of being awake 20 cm), EXERCISE, Omega-3 supplements (180 mg EPA and 120 mg DHA) • Antidepressants: no single drug has been shown to be better than the rest. Trial and error in individuals. Keep a list! • Treat other medical conditions that can contribute

11. cognition • Refers to: memory, language function, executive function, visuospatial processing/perception, attention • Very commonly affected • Can be a source of poor compliance, anxiety, frustration, difficulty in relationships

12. cognition • What is mild cognitive impairment? • When one of the domains of cognition are impaired, but not disabling (nuisance level) • What is dementia? • When more than one domain are impaired AND it is disabling • PD is one of many causes of dementia. Alzheimer’s is another separate cause. Strokes are another common cause

13. cognition • Management • Speech therapy, staying mentally active • Physical exercise • pill boxes with timers, cell phone alarms, watch alarms • Medications: (Exelon), galantamine (Razadyne), donepezil (Aricept), memantine (Namenda)

14. constipation • STAGE 1: lifestyle modifications. • drink LOTS of fluids, fruits and vegetables. • increase fiber intake (all-bran, Fiber-one cereals). • Bulk forming laxatives (Metamucil, Citrucel, Fibercon) • Heated Prune Juice. • decrease medications that result worsen constipation • Diphenhydramine (Benedryl), trihexyphenidyl (Artane), opiates (narcotic painkillers). • Get adequate exercise.

15. constipation • STAGE 2: used on a daily basis in many Parkinson’s disease patients. • Senokot and Docusate—starting dose is one senna and two docusate daily. These can be increased as necessary up to three and sometimes more of each. • Magnesium supplements 250-500 mg/day • STAGE 3: if you have gone more than two to three days without a bowel movement. • Bisacodyl (dulcolax)- one to two tablets at bedtime • Lactulose (one to two tablespoons in a cup of juice daily as necessary). This is not available without prescription. • Miralax (polyethylene glycol)- one heaping tablespoon into 8oz of water daily as needed.

16. constipation • STAGE 4:if you have not had a bowel movement for several days- • Bisacodyl (Dulcolax) suppository—this is effective much sooner than the oral form so do not take at bedtime. Note that these are often rapidly effective. • Fleets Enema—this is effective if there is not a large volume of stool impacted. • STAGE 5:IMPACTION • sometimes, even an enema is not sufficient at low volumes to remove a large amount of impacted stool and patients must come into the E&A

17. Bladder or erectile dysfunction • Urinary control problems can be from other conditions associated with aging or from bladder spasms related to PD • Medical work up to rule out other causes (diabetes, prostate enlargment/cancer, gynecologic disorders, medications, infection) • Behavioral management – timed voiding, pelvic floor exercises, bedside urinal/toilet, caffeine/alcohol avoidance • Medications: antispasmodics (e.gtolteridine, oxybutynin) • Botulinum Toxin injections to detrussor (done by a urologist) • Sildenafil (Viagra) or Tadalafil (Cialis) for Erectile Dysfunction

18. Insomnia • Difficulty falling asleep • Difficulty staying asleep (Early morning awakening) • Both can be a symptom of anxiety, or not • Abnormal circadian rhythm • Napping too much or too late in the day • Delayed sleep phase disorder • Wearing off symptom • Medication side effect • Behavioral conditioning can reinforce

19. Insomnia management • Identify any triggers • Optimize “sleep hygiene” • Routine before bed – “sleep Ritual” • Associate your bed only with sleep • Avoid stimulating (or substances) activities before bed or if you get up during the night • Avoid naps in the late afternoon or evening • Exercise and get plenty of light exposure in the morning hours

20. Insomnia management • Pharmacologic • Address PD wearing off symptoms with night time meds • Address bladder issues • Melatonin 4-6 mg, usually (comes 1-10 mg) • 3 hours before bedtime (for trouble falling asleep) • At bedtime (for trouble staying asleep) • Antidepressants with sedative qualities • Mirtazepine • Trazodone • Sleeping medications • Clonazepam • Ambien • Lunesta • Sonata

21. REM sleep behavior disorder (RBD) • REM (rapid eye movement) is a stage of sleep in which dreaming occurs. It happens several times per night, but longest in the early morning. • Normally, everything but eye muscles and diaphragm are paralyzed during REM sleep • In RBD, this normal paralysis is impaired, so people with RBD will “act out the dream” • If anyone is at risk of getting injured, the most effective treatment is clonazepam

22. Excessive daytime sleepiness/fatigue • Can be a symptom of the disease or a side effect of medications • Obstructive sleep apnea is more common in PD than general population • Other sleep disorders such as RLS, and/or PLMS can reduce nighttime sleep • “sleep attacks” more common with the dopamine agonists • modafinil, armodafinil, ritalin, selegiline, rasagiline

23. Orthostatic Hypotension • Normally, when we sit up from a lying position, or stand up, our blood vessels contract to maintain blood pressure to the brain when gravity is pulling the blood volume downward • This reflex can be impaired in PD, so sitting up or standing quickly can lead to lightheadedness or even falling/fainting • Dehydration can trigger or make this worse • Some PD medications can make this worse

24. Orthostatic Hypotension • Management: • Hydration, especially in the morning • Liberal salt intake • Support stockings, keeping feet elevated when sedentary • Head of bed elevation • Staged rising • Smaller doses at a time of PD meds • Fludrocortisone, midodrine, pyridostigmine

25. Summary • Nonmotor symptoms are widely varied and can be just as important as the motor symptoms • Sometimes nonmotor symptoms can be caused by medication side effects • Many of these symptoms can be addressed with non-pharmacologic therapies, but often need specific medical treatment • If you are unsure if a symptom is a nonmotor symptom of PD or not, pay attention to the timing and talk to your provider.

26. Thank you! Questions?