Non-motor Aspects of Non-motor Aspects of Parkinson’s DiseaseParkinson’s Disease

a Psychiatrist’s a Psychiatrist’s PerspectivePerspective

Geriatrics Day 2009

Ronald Bailyn, M.D.

Non-Motor SymptomsNon-Motor Symptoms

Cognitive impairment/Dementia

Psychosis

Depression

Apathy

Anxiety

Fatigue

Sleep Disturbance

Neurotransmitters-pathwaysNeurotransmitters-pathways

Dopamine/serotonin

Deep Brain Stimulation Deep Brain Stimulation

Deep Brain Stimulation – Affective Events

depression (up to 25%) J Neurol Neurosurg Psychiatry

2008;79:952-954 hypomania

agitation

apathy

DepressionDepression

DepressionDepression

Depression Prevalence in Parkinson’s Disease

Depression -- major and minor

o ~ 5-10% major depressiono ~ 20-30% minor depression

DepressionDepression

Depression

Depression is associated with reduced cognition, faster progression of physical symptoms and decreased treatment adherence

Retrospective studies suggest higher incidence as long as 20 years before diagnosis

Some indication of greater depression risk with early onset, for women and with right predominant

motor symptoms

Depression in ParkinsonsDepression in Parkinsons

From Daniel Weintraub, M.D.University of Pennsylvania

Depression TreatmentDepression Treatment

Serotonin, norepinephrine and dopaminergic neurotransmitter changes in Parkinson’s provide

a theories for treatment, but little clinical research to guide treatment

Limited evidence for specific medications (3 trials -- Cochrane 2007)

o Substantial use of SSRIs (Zoloft, Prozac, Celexa/Lexapro) possibility of aggravating motor sx

o Nortriptyline (tricyclic – has best data)

o ECT

Nortriptyline &Nortriptyline &Paroxetine StudyParoxetine Study

Menza M, Dobkin RD et al: Neurology 2008; (online Ahead of Print Dec. 17, 2008)

Trial Design:

Nortriptyline 25, 50, 75 mg Paroxetine CR 12.5, 25, 37.5 mg Placebo 1, 2, 3 pills

8 week randomized, double blind, Ham D Assessed 2, 4 and 8 weeks 52 patients Age 35-80 (mean 62)

Nortriptyline &Nortriptyline &Paroxetine StudyParoxetine Study

Results

Nortriptyline › placebo (0.002) Nortriptyline › paroxetine N.S. (0.08)

Response (= 50% improvement Ham D) 53% nortriptyline 11% paroxetine

24% placebo

Remission (= Ham D of 7 or less) 41% nortriptyline 17% paroxetine 12 % placebo 

Depression &Depression &PsychotherapyPsychotherapy

Cognitive Behavioral Therapy (CBT)

Supported in limited trials/clinical experience

Antidepressant Choices Antidepressant Choices

Class Med Avg dose(mg/day)

Start Comments

SSRI EcitalopramParoxetineSertraline

10 2050-100

101025

Also used for anxiety – often at higher doses.Can worsen motor Sx.

SNRI VenlafaxineDuloxetine

37.5 – 15020-30

37.520-30

Useful for anxiety and depression

TCA Nortriptyline 50-150 25 Blood levels can be helpful.Usually night dosing.

Other BupropionMirtazapine

100-30015-45

10015

Bupropion can be activatingMirtazapine can be sedating – usually night dosing

Adapted from: Dialogues inClinical Neuroscience – Parkinson’sDisease; 2004: Vol. 6 No. 3 p324

AnxietyAnxiety

Anxiety Disorders Anxiety Disorders

Anxiety

20-30% frequency of anxiety disorders

General anxiety, panic attacks, obsessive-compulsive

problems can present in Parkinson’s Disease

Impulse control disorders (gambling, sex, buying)o dopamine agonist association o ~ 4% prevalence (Weintraub)

 

Anxiety Disorder Anxiety Disorder TreatmentTreatment

Anxiety Treatment

Very little study or even case report literature

o Significant use of SSRIs and other antidepressant medications

o Low dose benzodiazepine medications (lorazepam, clonazepam)

(monitor sedation & balance)

o Cognitive Behavioral Treatment

ApathyApathy

ApathyApathy

Apathy

10-20% frequency – loss of goal directed behavior, life interest

Little treatment information – trials of norepinephrine and dopaminergic agents Wellbutrin, stimulants (ex. Ritalin, Strattera) Education (family) Environmental stimulation

   

SleepSleep

Sleep disordersSleep disorders& Treatment& Treatment

Various and frequent sleep disorders

Insomnia o sleep behavioral efforts o sleep medications (Tandberg 1999 study ~ 40% pts taking)

Parkinson’s motor symptomso night dose Sinemet CR

Restless legs o dopaminergic medications

Sleep disordersSleep disorders& Treatment& Treatment

More sleep disorders

REM behavior disorder o benzodiazepine (clonazepam)

Excessive daytime sleepiness (EDS)o thought to be direct symptom of Parkinson’s o review effects of Parkinson’s medicationso Provigil study negative

Behavioral/cognitive approaches to depression and Behavioral/cognitive approaches to depression and sleep problemssleep problems

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