Consulting the Consultants: Integrated Care within HDSA Specialty Clinic

Transcription

1 Consulting the Consultants: Integrated Care within HDSA Specialty Clinic Morgan Faeder MD, PhD Darcy Moschenross MD, PhD Robin Valpey MD Neeta Shenai MD

2 APM 2017 Darcy Moschenross, MD, PhD With respect to the following presentation, there has been no relevant (direct or indirect) financial relationship between the party listed above (and/or spouse/partner) and any for-profit company which could be considered a conflict of interest.

3 APM 2017 Morgan Faeder, MD, PhD With respect to the following presentation, there has been no relevant (direct or indirect) financial relationship between the party listed above (and/or spouse/partner) and any for-profit company which could be considered a conflict of interest.

4 Objectives 1. Know the cause and presentation of Huntington s Disease 2. Describe the behavioral symptoms of HD 3. Appreciate the role of the psychiatrist in a multi-disciplinary care team for patients with HD

5 Overview of HD CAG repeat on 4p16.3 Normal: <27 Intermediate:27-35 (prone to expansion) Incomplete penetrance: Complete penetrance: % AD inheritance Age of onset and rate of progression correlated with CAG repeat number Presents at any stage of life, usually in early middle age 5

6 Overview of HD Abnormal accumulation of Huntingtin protein Loss of striatal medium spiny neurons Marked specificty: Most affected: caudate and putamen with projections to the globus pallidus cortical layers 3,5,6 CA1 region of hippocampus Substantia nigra Caudate atrophy can be seen on imaging up to 11 years prior to onset of symptoms 6

7 Movement Disorder Prediagnostic phase: Restlessness, fidgeting noted by family Diagnostic phase: Chorea Motor impersistence Incoordination Slowed saccades motor example rating scale standard 7

8 Behavioral Disorder May present with behavioral symptoms: Irritability, anxiety, mood instability Common symptoms Disinhibition Suicidal ideation (up to 25%) Apathy Depressed mood Euphoria Aggression Less common: Delusions Compulsions Rare findings Hallucinations hypersexuality Not linked to disease severity 8

9 Cognitive Disorder May show difficulty with complex tasks prior to diagnosis Deterioration in executive function Planning Organizing Learning new skills Long-term memory spared Speech deteriorates before comprehension Progressive decline correlated with disease severity 9

10 Huntington s Disease Center of Excellence University of Pittsburgh s Center of Excellence was approved in 2015 by the HDSA as a multidisciplinary clinic for patients with HD (now 42 total). Operates 1/day per month 1 large room where patient sees everyone at once 4 rooms to split off to see privately before or after if needed. Sees pts in follow up for HD and also performs genetic testing Total clinic volume ~ pts, majority come every 3-6 months 10

11 Specialists within the Specialty Clinic Abound Neurologist Psychosomatic Medicine Fellow and Attending Physical Therapy Occupational Therapy Speech therapy Dietician Genetic Testing HDSA SW (from the Western PA HDSA) 11

12 Role of the Psychiatrist Treatment of behavioral symptoms Very little evidence base Collaborate with neurologist to streamline psychotropics Tetrabenazine vs haloperidol Clonazepam for dystonia vs anxiety Distinguish cognitive dysfunction from other causes of psychiatric illness Advise families on behavioral interventions Assessment of readiness for HD testing 12

13 Psychiatric Assessment of the HD Patient Full assessment with careful attention to: Family history Who has HD and at what age did sx start What impact did growing up in a household with HD (if applicable) have Trauma Increased risk of victimization Impulsivity and poor judgement Past Psychiatric History Previous psychiatric diagnoses emphasis on early signs of HD Previous psychiatric tx and response Centrally active medications Substance use Risky behaviors Legal issues Symptoms of depression, demoralization, and/or apathy Suicidality 13

14 Psychopharmacology in HD Very little evidence of efficacy of psychiatric medications in this population Few studies, poorly done Much of the time we are treating symptoms that are a direct result of HD subcortical degeneration Apathy Impulsivity Perseveration Amotivation 14

15 Psychopharmacology in HD Guiding principles: Treat diagnosable psychiatric illness as you would with any patient High potency typical antipsychotics for movement disorder and impulsivity/agitation High potency typical antipsychotics for those unable to tolerate tetrabenazine or for whom it is contraindicated SSRIs for perseveration Avoid benzodiazepines, stimulants when possible It may take several medication trials to optimize treatment Much of management will be behavioral 15

16 Behavioral interventions Collaboration with PT/OT/SLP/nutrition! Interventions can be based on symptoms (aggression, anxiety,...) or based on hypothesized cause of symptoms Unmet needs Presence of environmental irritants When a person can express their thoughts/feelings, we often treat based on a combination of these More complicated with more severe cognitive issues or lack of awareness of the link between cause and symptom

17 Behavioral interventions

18 Behavioral interventions

19 Behavioral interventions

20 Inpatient Psychiatric Care Last resort when psychiatric illness or behavioral problems cannot be managed outpatient Close collaboration of the HD team with the inpatient psychiatry team helps optimize treatment 20

21 Case Presentations Morgan Faeder MD PhD Darcy Moschenross MD PhD Robin Valpey MD Neeta Shenai MD

22 Case 1 38 year old male with Huntington s Disease who presented with chief complaint of insomnia and depression Current Psychiatric Symptoms Insomnia Depression with chronic suicidal thoughts Anxiety Intrusive thoughts about childhood Pt identified self-medicating his anxiety and insomnia with alcohol use 22

23 Case 1 Family Hx and Personal Hx with HD Father, grandmother and grandfather all diagnosed with HD Father presented when he was in late 20s, when pt was around 10 Father alive but institutionalized At this point, started to look up early signs of HD and found many symptoms that matched his own Genetic testing after 18, but felt like he knew he had HD at age 10 23

24 Case 1 Psychiatric Symptoms Depression since age 10 Childhood experiences, embarrassing moments Ruminative thoughts lead to suicidal thoughts chronically; no plan, intent or acts of furtherance One aborted suicide attempt as teenager (standing on bridge) Anxiety Racing thoughts, particularly at night Social component related to HD symptoms Insomnia Difficulty falling asleep and staying asleep Has been seeing sleep specialist, multiple med trials Diagnosed with mild OSA, but does not use dental appliance (removes it when he is intoxicated) 24

25 Case 1 Substance Use Hx Uses alcohol to help fall asleep every night Takes 3-4 shots bourbon/whiskey every night, to point of feeling tipsy/intoxicated No significant change in tolerance Abstinent for 18 months, but felt tired all the time, insomnia out of control and worsened anxiety Does not identify alcohol use as problem, as this is treatment for anxiety and insomnia 25

26 Case 1 Psychiatric Hx No previous inpatient or outpatient treatment; no individual therapy Previous Med Trials: zolpidem, Lorazepam 4 mg, Olanzapine 10 mg, Sonata 10 mg, Doxepin 10 mg, Trazodone, Sertraline 100 mg, 2-3 other antidepressant that he cannot remember Sleep aids not helpful Many taken along with alcohol Antidepressants work opposite Doesn t notice an effect while taking, feels better when stopping 26

27 Case 1 Social Hx Lives alone Never been in relationship Interested in having a partner, but inhibited by his HD diagnosis Main supports are mom and brother Both live 5 minutes away Significant conflict Trying to become less dependent on them Disability for HD and Depression 27

28 Case 1 Neurologic Exam VS: Weight 210 lbs; BMI 25.6 kg/m2 No tremor or notable psychomotor slowing CN II-XII grossly intact Strength: normal in upper/lower extremities; no cogwheeling or noted rigidity Deep tendon reflexes: Slightly brisk throughout Coordination: mildly incoordinated bilaterally with rapid alternating movements without significant slowing; no dysmetria on finger-tonose Tongue protrusion: normal No difficulty with Luria testing Gait: slightly wider-based, but steady; tandem gait with deviation 1-3 times in 10 steps 28

29 Case 1 What pharmacologic treatments would you consider for his symptoms? Insomnia? Anxiety? Depression? 29

30 The Importance of Considering Substance Use Smoking associated with increased risk for and earlier onset of Alzheimer s Disease (AD), increased risk for dementia in general, and increased risk and more severe progression of Multiple Sclerosis (MS) Heavy alcohol use associated with earlier onset of AD and increased risk for dementia in general Other substances (particularly dopaminergic) associated with structural brain changes and cognitive deficits While substance abuse is not a proven causative risk factor for neurodegenerative disorders, the evidence suggests that it may influence neurodegenerative processes 30

31 Prevalence Mixed data regarding prevalence of substance use disorders in HD population Challenge with temporal relation: substance use often starts at younger age than is typical for HD onset Rates of alcohol use disorder appear comparable to general population King 1985, Jensen et al 1993, Ehret et al 2007 Rates of nicotine use may be higher than general population Ehret et al 2007: 40% compared to 26.5% Other drug use No studies 31

32 Risk Factors Risk Factors in General Population Family hx of substance use disorder, depression, anxiety, personality traits, hx of physical, sexual or emotional trauma, witnessing substance abuse in childhood, early age of first use Gender Ehret et al 2007: 1976 subjects grouped into low vs high alcohol and low vs high cigarette, analyzed various demographic factors Men more likely than women to have high alcohol use (39% sampled men compared to 18% sampled women) and high cigarette use (52% men compared to 28% women) 32

33 Risk Factors continued Psychiatric symptoms HD Ehret et al 2007: Assessed pathologic psychiatric rating based on 10 negatively valenced affective symptoms (ex: sadness, irritability). Alcohol: Increased use significantly associated with higher score Nicotine: Similar trend noted, but not significant. Jensen et al 1993: Higher rates of alcohol use in HD patients compared to their healthy first and second degree relatives Alcohol use occurred after symptom onset possible consequence of the disease than a risk factor for it 33

34 Possible Mechanisms for SUD in HD Impulsivity Depression and Anxiety Self medication (movements, psychiatric symptoms, insomnia) Neurobiologic mechanisms Progressive atrophy and neuronal loss in cortical-striatal circuits also implicated in development of substance use disorders Possible direct toxic effect via brain-derived neurotrophic factor and calcium signaling 34

35 Association with Movements Tobacco Acts on nicotinic cholinergic system Shown to reduce symptoms in dyskinesias, ataxia and Tourette s syndrome Alcohol Shown to improve some primary movements disorders (essential tremor and myoclonic dystonia) Anecdotally helps with movements in HD Stimulants Action primarily mediated through dopaminergic and noradrenergic mechanisms Use associated with worsened movements in tic disorders, Tourette s syndrome and tardive dyskinesia 35

36 Association with Psychiatric Conditions Psychiatric symptoms seen in substance intoxication and withdrawal, can be induced by substances or exist outside of substance use disorder Substance use associated with increased rates of comorbid psychiatric diagnoses: Depressive disorders, Bipolar disorder, Anxiety disorders, PTSD, Eating Disorders, Schizophrenia and ADHD HD also associated with higher rates of psych dx: Major Depressive Disorders (22% lifetime prevalence), Bipolar Disorder (5-10%), Anxiety Disorders (GAD 9%, Panic D/O 8%) Other psychiatric symptoms of HD may also contribute to substance use Demoralization, Impulsivity/Disinhibition, Irritability 36

37 SUD and Age of Movement Onset Schultz et al 2017: ENROLL-HD data 1849 participants: 566 tobacco abuse, 374 alcohol abuse, 217 other drugs, 692 control Assessed age of motor onset (AMO), controlled for CAG repeats Alcohol: 1.0 years earlier than control (female: 1.3 years earlier; male: 0.9 years earlier) Tobacco: 2.3 years earlier than control group (stronger effect size for females) Drugs: 3.3 years earlier than control (female: 4.6 years earlier, male: 2.5 years earlier) Proposed mechanisms: increased dopamine activity via substance abuse (cocaine/amphetamines>nicotine>alcohol) Conclusion: Given the substantial effect size (particularly for women), interventions in SUD could reduce HD AMO 37

38 Treatment Considerations Withdrawal considerations Particularly important for benzodiazepines and alcohol Symptoms of withdrawal may be masked by or confused with symptoms of HD Level of Care Assess need for inpatient, intensive outpatient, outpatient, detox Consider pt s willingness to engage in treatment modality (ex: group environment) Medications Include: Naltrexone, Acamprosate, Disulfiram, Buprenorphine, Methadone No specific studies looking within HD population Consider contraindications/cautions (ex: hepatic/renal impairment) Psychiatric medications for comorbid conditions 38

39 Collaborative Care Coordination of Care with HD Team Neurologist: address non-psychiatric symptoms (particularly movement symptoms) Physical/Occupational Therapist: improve functionality (could be contributing to psychiatric symptoms) Social Workers: connecting with support group, engagement in therapy Family/Friends: improve support and engagement Other specialists outside of team Medical sub-specialties (ex: sleep specialists) Addiction specialists (ex: buprenorphine/methadone) Psychologists (individual, family, marital therapy) 39

40 Case 1 Reviewed Insomnia Encouraged ongoing work with sleep specialist Trial of suvorexant Encouraged oral appliance for sleep apnea Sleep hygiene techniques Anxiety/Depression Referral for individual therapy Added Propranolol, titrated to 30mg BID Added Mirtazapine, titrated to 30mg QHS Substance Use Discussed AA/12-step groups Encouraged dual diagnosis work in therapy 40

41 Summary While substance abuse is not a proven causative risk factor for neurodegenerative disorders, the evidence suggests that it may influence neurodegenerative processes Patients with HD may be more at risk for substance use disorder Substance use may lead to earlier age of symptom onset in HD 41

42 Case 2 27 yo woman with Huntington s disease akinetic-rigid type who presented with chief complaint of aspiration from a domestic violence shelter. She has current psychiatric symptoms of depression, PTSD, impulsivity, and disinhibition.

43 Case 2 Past Psychiatric History: Inpatient Psychiatric Hospitalizations: 2 prior in 2007 and 2013 Prior Suicide Attempts: once in 2014 Outpatient treatment: previously seen by therapist Prior medication trials: None Current Psychiatric Medications: None 43

44 Case 2 Family History: Mother and all of mother s siblings with HD and deceased Social History: Living situation: Was living with father, but was neglectful so moved in with uncle; uncle physically abusive Financial situation: concern for financial abuse from father Legal: police custody several occasions for concern for alcohol use disorder 44

45 Case 2 Current Medications: Carbidopa/levodopa 25mg/100 mg PO BID for Parkinsonian symptoms Dronabinol 5 mg PO TID for appetite stimulation Famotidine 20 mg PO daily for GERD 45

46 Case 2 Neurological Examination: VS: Weight 123 lbs; BMI 21.1 kg/m2 Moderate bradykinesia and psychomotor slowing CN II-XII grossly intact except for saccades Strength: normal in upper/lower extremities; cogwheeling in LUE Coordination: dysmetria with FTN, moderate slowing of rapid alternating movements Tongue protrusion: approximately 8-10 seconds Difficulty with Luria testing Gait: wide-based, rigid, retropulsion 46

47 Safety Assessment Abuse Report to adult protective services Report to Social Security that father wrongfully accessing finances Charges filed against uncle Living Situation Police Not able to live in domestic violence shelter due to medical needs Placed in a personal care home then apartment with 24/7 nursing supervision Targeted multiple times as she reports I walk like I m drunk Medical documentation sent to county police of diagnosis of HD 47

48 Case 2: Lethality Risk Intermittent suicidal ideation with thoughts to cut her wrist Reported thoughts to her aide, who convinced her to abort the attempt Chronic passive death wish 48

49 Suicide Risk in HD Rates estimated between 5-10% Risk highest period prior to diagnosis and immediately after Risk factors: Presence of depression/anxiety Irritability/aggression Substance use disorder Cognitive deficits Impulsivity Medication side effect (tetrabenazine) 49 (Epping E, 2011)

50 Case 2: Lethality Assessment Risk Factors Executive dysfunction Impulsivity Depression Aborted suicide attempt History of trauma Protective Factors 24/7 supervision Demonstration of discussing with support system Positive relationship with care providers Challenges to Assessment: Use of formal diagnostic criteria to define depression in HD criticized Frequent co-occurrence of physical symptoms (sleep and weight loss) Cognitive deficits 50

51 Case 2: Treatment Options What pharmacological treatment would you consider to target her symptoms? Depression/irritability/SI? Impulsivity/aggression? PTSD? 51

52 Case 2: Treatment of Depression No randomized controlled trials to evaluate depression Animal models with SSRI treatment slowing progression of HD One randomized controlled trial with fluoxetine and HD examining effect on cognition CIT-HD randomized controlled trial with citalopram and HD examine effect on executive function Case reports of Lithium reducing suicide risk 52 Beglinger, 2014

53 Case 2: Treatment No randomized controlled trials of PTSD in HD One case report of combat-related trauma treated with olanzapine Citalopram initiated and titrated to 40 mg PO daily Presented to clinic with symptoms of: Mood lability Increase in disinhibition/hypersexuality Increase in impulsivity/aggression 53

54 Case 2: Treatment Most commonly secondary to dopaminergic agents Treatment options: Lower caribopa/levodopa Addition of antipsychotic Initiation/increase of SSRI Initiation of mood stabilizer (valproic acid) Valproic acid DR 250 mg PO qhs initiated 54

55 Case 2: Valproic Acid Animal models shown improvement in behavioral and motor components Reduce neuronal death from glutamate excitotoxicity Enhance clearance of protein aggregate accumulation Conflicting evidence in reduction in chorea 55

56 Case 2: Valproic Acid Drug Duration Dose Subjects (N) VPA 4 weeks MG TID VPA weeks mg/day VPA 9 weeks mg/day VPA + Olanzapine 8 weeks BID; 5-10 mg/day Major FInding 3 No effect on involuntary movements 14 Ineffective reduction in chorea 6 Reduced awakenings 2 Improved motor function VPA? mg/day 8 Improved basic motor coordination tasks 56

57 Case 2: Collaborative Care Social Worker Reported to adult protective services Filed report to police on documentation of diagnosis Physical Therapist Assessment of wide based gait Nutritionist 123 lbs; BMI 21.1 Reviewed diet, how to increase calorie intake, use of supplements Neurologist Adjusted carbidopa/levodopa Psychiatrist Evaluated lethality and mood 57

58 Case 2: Summary Patients with HD are a vulnerable population and important to screen for abuse No randomized studies of treatment of depression and PTSD in HD Pharmacologic treatment based on symptom presentation 58

59 References Byars JA, Beglinger LJ, Moser KJ, Gonzalez-Alegre P, Nopoulos P. Substance abuse may be a risk factor for earlier onset of Huntington disease. Journal of Neurology 2012;259: Ehret JC, Day PC, Weigand R, Wojcieszek J, Chambers RA. Huntington disease as a dual diagnosis disorder: Data from the national research roster for Huntington disease patients and families. Drug and Alcohol Dependence 2007; 86: Jensen P, Sorensen SA, Fenger K, Bolwig TG. A study of psychiatric morbidity in patients with Huntington's disease, their relatives, and controls. Admissions to psychiatric hospitals in Denmark from 1969 to British Journal of Psychiatry 1993;163: King M. Alcohol abuse in Huntington s disease. Psychological Medicine 1985;15(4): Lopez W, Jeste DV. Movement disorders and substance abuse. Psychiatric Services 1997;48(5): Quik M, Zhang D, Perez XA, Bordia T. Role for the nicotinic cholinergic system in movement disorders; therapeutic implications. Pharmacology & Therapeutics 2014;144: Schultz JL, Kamholz JA, Moser DJ, Feely SME, Paulsen JS, Nopoulos PC. Substance abuse may hasten motor onset of Huntington disease. American Academy of Neurology 2017; 88: