Parkinson, Diagnostikk og implikasjoner i forhold til psykiatriske
Parkinson, Diagnos-kk og implikasjoner i forhold -l psykiatriske lidelser og deres behandling Dag Årsland Karolinska Ins0tutet Stavanger Universitetssjukehus 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 12/100 000/år, aldersavhengig, gene0sk • Overlevelse lite påvirket i Norge • Ikke-‐motoriske symptomer vanlig og vik0g, inkl psykiatriske • PD er modell for “Nevropsykiatrisk sykdom” Dopamine functions Dopaminergic systems • movement • memory • pleasurable reward • behavior and cognition • attention • inhibit prolactin production • sleep • mood • learning Dopamine transporter SPECT: Imaging the presynap0c dopaminergic nigro-‐striatal system 13-‐03-‐15 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 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 3. PD is a motor disorder Symptomer • Non-‐motor symptoms are common, occur early, and have major clinical impact 4. PD is an a-‐synucleinopathy • Amyloid-‐ and tau-‐pathology also PD-related brain changes relevant for NPS Transmi(er changes: Dopamine Serotonin Noradrenaline Acetylcholine Glutamate Braak et al 2006 Høy forekomst av psykiatrisk sykelighet ved PD 16% had 1, 20% had 2, 25% had 3+ NPI items Motor hyper Irritability Disinhibition 60 PD 50 NC 40 30 20 Apathy 10 Euphoria 0 Anxiety Dysphoria Agitation Other common NPS: REM-‐sleep behavioural disorder-‐ca 30% Impulse control disorders-‐ ca 15% Hallucination Delusions 0 5 10 15 20 NPI frequency (% )(n=139) Aarsland et al. J Neurol Neurosurg Psych 1999;67:492-6 25 30 35 40 NMSQuest: Interna0onal study Chaudhuri et al. Mov Disord 2006 Impulskontrollforstyrrelser (ICD) ved PD • Gambling • Seksuell aierd, endring • Patologisk shopping • Spiseforstyrrelse • Hobbyism • Punding • Vandring • Avhengighet av dopaminerge medikament Årsaker -l psykiske symptomer ved Parkinsons sykdom Komorbiditet Arv Generell psykososial belastning Psykiske symptomer Tidligere (latent) psykisk lidelse Hjerneforandringer Medikamenter DBS Psykologisk reaksjon (på diagnose, symptomer, funksjonssvikt) Consequences of NPS Reduced quality of life Caregiver stress (Herlofson 1998,1999, 2000) (Aarsland 2001) Progression of PD (Starkstein 1992) Nursing home placement (Aarsland 2000) Psychiatric symptoms Cognitive impairment (Troster 1995) Mortality (Marder 1991) An-parkinson-‐medisiner og mentale bivirkninger Preparat Medisin Mental bivirkning Levo-‐dopa Madopark, Sinemet Stalevo (+COMT-‐I) Kognisjon, psykose, delirium Dopamin-‐agonister Apomorfin, pramipexole (Sifrol) ropinirol, ro0go0n pramipexole Kognisjon, psykose, delirium, impuls ICD, søvn-‐alakker An0depressiv effekt? MAO-‐ inhibitor Rasagilin, selegilin An0-‐depressiv effekt? DBS Impulsivitet, depresjon, suicidalitet? 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 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? Psychotropic drugs in PD: Evidence • Demen0a: level 1 • Depression: level 1 • Psychosis: level 1 • Apathy, RBD, ICD: some evidence • Anxiety: very lille evidence Depresjonsbehandling -‐ PD Two key an-depressant studies Nortriptylin, paroxe0ne, PLA Menza 2009 Venlafaxine, paroxe0ne, PLA Richard 2012 Lancet Neurol 2010 Non-drug alternatives • • • • 1. 2. 3. ECT increases dopaminergic activity and may improve depression and parkinsonism 1 Supportive psychotherapy/CBT, especially in early stage2 DBS, rTMS multidisciplinary rehabilitation (logopedics, physiotherapy, assessment for social services need, psychotherapy, relaxation, diet) 3 Kennedy et al. J Neuropsych Clin Neurosci 2003;15:407-‐21. Dobkin et al. Am J Psychiatry 2011 Trend P et al.: Clin Rehabil 2002; 16(7):717-‐25 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 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? Quetiapine for PD-psychosis: time to discontinuation Shotbolt et al 2009 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 Cummings et al Lancet 2014 SAPS-PD d=0.5 CGI-severity CGI-change 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 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 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
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