Parkinson, Diagnos-kk og implikasjoner i forhold -l psykiatriske lidelser og deres behandling

Transkript

1 Parkinson, Diagnos-kk og implikasjoner i forhold -l psykiatriske lidelser og deres behandling Dag Årsland Karolinska Ins0tutet Stavanger Universitetssjukehus

2 Parkinsons sykdom- lynkurs Parkinsonisme - 2/4 kardinalsymptom: hviletremor, rigiditet, bradykinesia, s0llingsforandringer (posture) Patologisk definisjon: nevrontap dopaminerge nevroner I substan0a nigra, og Lewylegemer i gjenværende Ca 6000 i Norge, insidens 12/ /år, aldersavhengig, gene0sk Overlevelse lite påvirket i Norge Ikke- motoriske symptomer vanlig og vik0g, inkl psykiatriske PD er modell for Nevropsykiatrisk sykdom

3 Hva er vik-g for psykiatere? Vite at psykiatriske symptomer er hyppige og vik0ge ved PD Kunne diagnos0sere og behandle disse Kunne diagnos0sere PD og kjenne 0l de vik0gste an0parkinson- medisinene og deres effekt og bivirkninger

4 Parkinsons sykdom: 3 myter 1. PD is a nigro- striatal disorder Mul0ple systems are involved; neocortex, thalamus, hippocampus, amygdalae, brain stem 2. PD is a dopaminergic deficit disorder Cholinergic, noradrenergic, serotonergic, glutamatergic Psykiatriske deficits are common Symptomer 3. PD is a motor disorder Non- motor symptoms are common, occur early, and have major clinical impact 4. PD is an a- synucleinopathy Amyloid- and tau- pathology also

5 PD-related brain changes relevant for NPS Transmi(er changes: Dopamine Serotonin Noradrenaline Acetylcholine Glutamate Braak et al 2006

6 Høy forekomst av psykiatrisk sykelighet ved PD Motor hyper Irritability Disinhibition 16% had 1, 20% had 2, 25% had 3+ NPI items PD NC Apathy Euphoria Anxiety Dysphoria Agitation Hallucination Delusions Other common NPS: REM- sleep behavioural disorder- ca 30% Impulse control disorders- ca 15% NPI frequency (% )(n=139) Aarsland et al. J Neurol Neurosurg Psych 1999;67:492-6 NMSQuest: Interna0onal study Chaudhuri et al. Mov Disord 2006

7 Impulskontrollforstyrrelser (ICD) ved PD Gambling Seksuell aierd, endring Patologisk shopping Spiseforstyrrelse Hobbyism Punding Vandring Avhengighet av dopaminerge medikament

8 Årsaker -l psykiske symptomer ved Parkinsons sykdom Arv Komorbiditet Hjerneforandringer Generell psykososial belastning Psykiske symptomer Medikamenter DBS Tidligere (latent) psykisk lidelse Psykologisk reaksjon (på diagnose, symptomer, funksjonssvikt)

9 Consequences of NPS Caregiver stress (Aarsland 2001) Reduced quality of life (Herlofson 1998,1999, 2000) Progression of PD (Starkstein 1992) Psychiatric symptoms Cognitive impairment (Troster 1995) Nursing home placement (Aarsland 2000) Mortality (Marder 1991)

10 An-parkinson- medisiner og mentale bivirkninger Preparat Medisin Mental bivirkning Levo- dopa Dopamin- agonister Madopark, Sinemet Stalevo (+COMT- I) Apomorfin, pramipexole (Sifrol) ropinirol, ro0go0n pramipexole Kognisjon, psykose, delirium Kognisjon, psykose, delirium, impuls ICD, søvn- alakker An0depressiv effekt? MAO- inhibitor Rasagilin, selegilin An0- depressiv effekt? DBS Impulsivitet, depresjon, suicidalitet?

11 Psychiatric assessment in PD Unstructured interview Structured diagnos0c interview (SCID- I) Ra0ng scales Observer- based, carer- based, or self- report Spectrum (NPI, NMSS, UPDRS) or symptom- specific Aims of scales: Screening Diagnosis Severity Change

12 Management of NPS - General aspects Diagnosis: Severity and profile of neuropsychiatric symptoms Exclude other causes (drugs, physical disease, stressors) Other brain disease: DLB, AD, schizophrenia Management: General: Remove contribu0ng factors Modify an0parkinson treatment Informa0on, coping and other psychological strategies Symptoma0c drug treatment?

13 Psychotropic drugs in PD: Evidence Demen0a: level 1 Depression: level 1 Psychosis: level 1 Apathy, RBD, ICD: some evidence Anxiety: very lille evidence

14 Depresjonsbehandling - PD

15 Two key an-depressant studies Nortriptylin, paroxe0ne, PLA Venlafaxine, paroxe0ne, PLA Menza 2009 Richard 2012

16 Lancet Neurol 2010

17 Non-drug alternatives ECT increases dopaminergic activity and may improve depression and parkinsonism 1 Supportive psychotherapy/cbt, especially in early stage 2 DBS, rtms multidisciplinary rehabilitation (logopedics, physiotherapy, assessment for social services need, psychotherapy, relaxation, diet) 3 1. Kennedy et al. J Neuropsych Clin Neurosci 2003;15: Dobkin et al. Am J Psychiatry Trend P et al.: Clin Rehabil 2002; 16(7):717-25

18 Treatment of Depression in Clinical Prac-ce Suppor0ve talking, CBT Adjust an0park- drugs: Pramipexol If symptoma0c drug treatment indicated: SSRI, or venlafaxine, or nortriptyline Severe treatment resistant: consider alterna0ves including ECT, transcranial s0mula0on

19 Antipsychotics in PD: RCT Olanzapine and Risperidon: minor effects, motor worsening Clozapin: 2 positive studies, well tolerated Quetiapin: Many positive open studies, 4 RCT- 3 negative, 1 positive Possible alternatives: Rivastigmine? Memantine? Pimavanserin?

20 Quetiapine for PD-psychosis: time to discontinuation Shotbolt et al 2009

21 Pimavanserin for PD-psychosis RCT, placebo-ctr PIM (5HT2 inverse agonist) 40 mg/d fixed dose 6w (2w run-in) N=199, Age:72, MMSE: 26 Primary outcome: SAPS-PD Well tolerated Drop-out due to AE: PIV: 10 (4<10d for psychosis) PLA: 2 d=0.5 CGI-severity SAPS-PD CGI-change Cummings et al Lancet 2014

22 Treatment of psychosis in clinical practice Consider secondary factors Consider changing PD-drug treatment Information, coping strategies Consider ChEI (if cognitively impaired) Consider quetiapine or clozapine if needed (low doses, short duration) Monitor AE, incl cqt, BMI, cholesterol, glucose, BP

23 Behandling av andre psykiatriske symptomer Demens: kolinesterasehemmer, (memantin) (Level 1) Impulskontrollforstyrrelse: dose-reduksjon av DA-agonist REM-søvn atferdsforstyrrelse: melatonin, klonazepam Angst: små doser BZD, SSRI

24 Oppsummering: Psykiatriske symptomer ved Parkinson Hyppig, stor klinisk betydning Under-diagnostisert og under-behandet Generelle strategier er viktig Level-1 evidens finnes for psykose og depresjonsbehandling Risiko for bivirkninger er stor