PD ExpertBriefing: Impulsive and Compulsive Behaviors in Parkinson s Disease

Transcription

1 PD ExpertBriefing: Impulsive and Compulsive Behaviors in Parkinson s Disease Presented By: Daniel Weintraub, M.D. Associate Professor of Psychiatry, University of Pennsylvania; Parkinson s Disease and Mental Illness Research, Education and Clinical Centers, Philadelphia VA Medical Center Tuesday, September 27, 2011 at 1:00 PM EDT

2 Welcoming Remarks Robin Elliott Executive Director Parkinson s Disease Foundation

3 Goals Provide overview of impulsive and compulsive behaviors in PD: Presentation Epidemiology Potential risk factors Assessment Management

4 Presentation

5 Vignettes - Gambling My father has been treated for Parkinson s since his diagnosis in his late 40 s, over 25 yrs ago. He has developed a severe compulsive gambling problem over the years such that he is now destitute and broke. He owned multiple successful automobile dealerships and has been on the board of the bank for many years His disease has required increasing amounts of multiple meds, including dopaminergic drugs The following year he (the neurologist) said it was a known effect but knew of no treatment I am concerned about suicide I am wondering from all I have read this week if there is a compulsion drug he can be treated with for this Some recommend weaning off the dopaminergic drugs. I am not sure how this would go for him.

6 Vignettes Eating and Sex During the day I can control my appetite and I have will power. Then in the evening right before bed time it starts and I feel the urge to eat. I have gained 15 lbs and I have been thin all my life so this is a shock for me. Now I am on a diet, it s slow because I keep wanting to eat When I wake up in the morning I see the number of wrappers that are at the bed side and it is a shock. It is like an urge that you just cannot satisfy. It happens at night when I am alone. I often go on the internet and look at websites that are sexual in nature. It causes me to lose a lot of sleep. The lack of sleep is causing problems at work; some people are starting to notice that I am exhausted in the afternoon I am not as productive as I was before I have let a lot of things (around the house) go because I spend my time fantasizing and on the internet.

7 Issues Highlighted by Cases Association with PD medications Behaviors atypical or excessive for individual Lack of control over behaviors Lack of pleasure associated with behaviors Needing vs. wanting Significant distress or impairment in many cases, often enduring Difficult clinical management decisions

8 Terminology Impulse control disorders (ICDs) are category of psychiatric disorders in DSM-IV Essential feature failure to resist impulse, drive, or temptation to perform act that is harmful to person or others ICDs accepted as term for major disorders reported to occur in PD Gambling Buying Sexual behaviors Eating

9 Presentation Gambling Can involve frequent low stakes (slots, scratch cards), casinos Sexual behavior Demands on spouse, internet, prostitution, changes in sexual orientation Buying Purchasing same items repeatedly Eating Cravings for certain foods (sweets), overnight eating

10 Related Disorders Dopamine dysregulation syndrome (DDS) More like addiction Misuse and escalating dose of medication Occurs with levodopa or subcutaneous apomorphine typically Appears less common in US than in Europe Punding (fascination with meaningless objects or activities) Hobbyism (more complex task preoccupation) Walkabout Other (hoarding, reckless driving)

11 Beneficial Changes in Behaviors? Increased sexual drive in patients with decreased sexual drive and performance? Increased appetite in patients that lose weight? Enhance creativity? Increased motivation in patients with apathy or avoidance? Increased enjoyment? These possibilities have not been adequately explored in Parkinson s disease.

12 Epidemiology

13 ICDs in Untreated PD Antonini et al. Movement Disorders 2011;26:

14 DOMINION Study Study of frequency and correlates of 4 ICDs in PD MAGS for gambling, MIDI for buying and sexual behavior, and DSM-IV criteria for binge-eating 46 PD centers in US and Canada 3090 patients 75 years old completed assessments 66% of patients were taking a dopamine agonist (DA) Overall, 86.8% of patients were taking levodopa Weintraub et al. Archives of Neurology 2010;67:

15 Frequency of ICDs At least one ICD identified in 14% of patients 29% of ICD patients had 2 ICDs Frequencies of individual ICDs were: Problem/pathological gambling = 5.0% Compulsive sexual behavior = 3.5% Compulsive buying = 5.7% Binge-eating disorder = 4.3%

16 Potential Risk Factors

17 Relationship to Dopamine Agonist Treatment ICD type DA treatment status Current ICD N (%) No current ICD N (%) Any ICD No dopamine agonist 72 (6.9) 978 (93.1) <.001 P value (CMH-test); odds ratio [95% CI] Dopamine agonist 348 (17.1) 1692 (82.9) 2.72 [2.08;3.54] Problem/pathological No dopamine agonist 24 (2.3) 1026 (97.7) <.001 gambling Dopamine agonist 130 (6.4) 1910 (93.6) 2.82 [1.81;4.39] Pathological gambling No dopamine agonist 17 (1.6) 1033 (98.4).004 only Dopamine agonist 72 (3.5) 1968 (96.5) 2.15 [1.26;3.66] Compulsive sexual No dopamine agonist 18 (1.7) 1032 (98.3) <.001 behaviour Dopamine agonist 90 (4.4) 1950 (95.6) 2.59 [1.55;4.33] Compulsive buying No dopamine agonist 30 (2.9) 1020 (97.1) <.001 Dopamine agonist 147 (7.2) 1893 (92.8) 2.53 [1.69;3.78] Binge-eating disorder No dopamine agonist 18 (1.7) 1032 (98.3) <.001 Dopamine agonist 114 (5.6) 1926 (94.4) 3.34 [2.01;5.53]

18 Specific Dopamine Agonists ICD type Specific DA Current ICD N (%) No current ICD N (%) Any ICD Ropinirole 101 (15.5) 550 (84.5).14 P value (CMH-test); odds ratio [95% CI] Pramipexole 228 (17.7) 1058 (82.3) 1.22 [0.94;1.57] Problem/pathological Ropinirole 37 (5.7) 614 (94.3).44 gambling Pramipexole 83 (6.5) 1203 (93.5) 1.17 [0.78;1.76] Pathological gambling Ropinirole 24 (3.7) 627 (96.3).69 only Pramipexole 42 (3.3) 1244 (96.7) 0.90 [0.54;1.51] Compulsive sexual Ropinirole 28 (4.3) 623 (95.7).75 behaviour Pramipexole 58 (4.5) 1228 (95.5) 1.08 [0.68;1.71] Compulsive buying Ropinirole 51 (7.8) 600 (92.2).58 Pramipexole 87 (6.8) 1199 (93.2) 0.90 [0.63;1.30] Binge-eating disorder Ropinirole 28 (4.3) 623 (95.7).06 Pramipexole 80 (6.2) 1206 (93.8) 1.53 [0.98;2.39]

19 Other Factors Associated with ICDs Variable * Entire Study Population (N=3090) Odds ratio [95% CI] P value PAR% & Age ( 65 years vs. >65 years) 2.50 [1.98; 3.15] < % Marital status (not married vs. married) 1.48 [1.16; 1.89] % Country (living in United States) 1.62 [1.25; 2.10] < % Current smoking (yes vs. no) 1.70 [1.07; 2.70] % Family history gambling problems (yes vs. no) 2.08 [1.33; 3.25] % DA treatment (yes vs. no) 2.72 [2.07; 3.57] < % Levodopa treatment (yes vs. no) 1.51 [1.09; 2.09] %

20 Dose Effects Examining patients on a DA (N=2040) No DA dosage effect There was levodopa dosage effect (P=0.008) Examining patients on levodopa only (N=991) Higher levodopa dosage was associated with current ICD (P=0.002)

21 Other Factors Associated with ICDs ICDs more common in US (15.0%) than Canada (9.8%) Specifically compulsive gambling and buying Even controlling for differences in medication exposure No sex differences in ICDs overall, but Sexual behaviors far more common in men Buying and binge-eating more common in women Family history of gambling problems more common in three of the four ICDs (all except sexual behaviors)

22 DOMINION Study - Amantadine Data Weintraub et al. Annals of Neurology 2010;68:

23 Assessment

24 Questionnaire for Impulsive-Compulsive Disorders in Parkinson s Disease (QUIP) Valid as screening instrument for ICDs and related disorders Simple and short (<5 minutes) Clinical interview needed for screen + patients Interview should focus on all ICDs and related behaviors

25 QUIP-Rating Scale Weintraub et al. (under review).

26 Patient vs. Informant Reporting of ICD Symptoms Using QUIP Papay et al. Parkinsonism and Related Disorders 2011;17:

27 Management

28 Current Management Options Do nothing Assess clinical significance Some patients unable or reluctant to make adjustments to PD pharmacotherapy Alterations to PD pharmacotherapy Changes to DA therapy with increase in levodopa to help motor symptom management Consider deep brain stimulation (DBS) Psychopharmacology Antidepressants, antipsychotics

29 Amantadine for Gambling in PD Symptom Assessment Scale (SAS) and Yale- Brown Obsessive- Compulsive Scale (Y- BOCS) score changes. Both scores reduced by amantadine (p < compared to baseline). A = amantadine P = placebo Thomas et al. Annals of Neurology 2010;68:

30 Ongoing Clinical Trial Michael J. Fox Foundation grant Randomized, double-blind, placebo-controlled clinical trial of naltrexone for all ICDs Naltrexone is an opioid receptor anatagonist FDAapproved for the treatment of alcoholism Modulatory role for opioid peptides in the nigrostriatal dopaminergic pathway 48 subjects with 1 of 4 common ICDs Contact Information: Kim Papay kimberly.papay@uphs.upenn.edu

31 Conclusions - Epidemiology ICDs in PD are Relatively common A range occur Often co-morbid Psychiatric co-morbidity common Associated with DA use as a class Associated with levodopa and amantadine use to lesser extent Dose effects for levodopa May have other pre-morbid risk factors

32 Conclusions Assessment and Management Must ask about a range of symptoms Agreement fair between patients and informed others Screening instruments and rating scales available for clinical use Range of management strategies available Need for psychopharmacological options with established efficacy and good tolerability

33 Acknowledgements Patients, colleagues, and research staff at PD Centers at University of Pennsylvania Philadelphia Veterans Affairs Medical Center Grant support from NIMH, NINDS, State of PA, VA, and Fox Foundation for Parkinson s Research

34 Questions and Answers