Addressing the Opioid Epidemic by Maximizing Behavioral Treatment in Chronic Non-Cancer Pain

Transcription

1 Addressing the Opioid Epidemic by Maximizing Behavioral Treatment in Chronic Non-Cancer Pain Aleksandra Zgierska, MD PhD University of Wisconsin-Madison Robert Edwards, PhD Brigham and Women s Hospital Eric Garland, PhD, LCSW University of Utah

2 Disclosures The presenters have no conflict of interest to disclose.

3 Objectives: Behavioral treatments for improving outcomes and reducing opioid use in chronic non-cancer pain Promising evidence for Mindfulness Meditation (MM) and Cognitive Behavioral Therapy (CBT) Aleksandra Zgierska Mechanisms underlying the CBT effects Robert Edwards Mechanisms underlying the MM effects Eric Garland

4 Chronic non-cancer pain Common, with rising prevalence Care-refractory Costly $ billion annually Co-occurring mental health disorders / addiction make treatment more challenging and worsen outcomes Crisis of opioid abuse, overdose deaths Institute of Medicine, Relieving Pain in America [Report], 2011

5 Intertwined challenges of pain management and the opioid crisis Chronic pain Long-term opioid use How to safely manage chronic pain? Opioid harms How to reduce opioid use and related harm? Adapted from Krebs EE, 2017 PCORI Annual Meeting

6 JAMA 2018 RCT (N=240), patients with chronic pain, randomized into opioid vs. non-opioid analgesics At 12 months, patients treated with opioids, compared to those without opioids: similar function worse pain (p<0.05) more medication side effects (p<0.05) Krebs EE et al. JAMA 2018; 319(9):

7 Eccleston C et al Based on the available evidence, we do not know the best method of reducing opioids in adults with chronic pain conditions. We found mixed results from a small number of studies [ ].

8 Traditional treatments for chronic pain Adapted from DeBar L, PCORI 2017 Annual Meeting

9 Interdisciplinary pain programs and behavioral interventions may be effective for opioid dose. Pain, function, quality of life may improve with opioid dose. Limited evidence, more research is needed Frank JW et al. Ann Intern Med 2017; 167:

10 Mental training can lead to changes in brain function and structure, and improve health. WikiCommons, Ajifo A: Synapse in Brain.

11 Wiki Commons, Hokusai: The Great Wave off Kanagawa

12 MM and CBT offer different skills for pain coping and chronic pain management Mindfulness Meditation (MM) Nonjudgmental, accepting awareness of presentmoment experiences to change one s relationship with these experiences Cognitive Behavior Therapy (CBT) Focus on modifying unhealthy thoughts, emotions and behaviors to change the experience and control symptoms.

13 Mindfulness Meditation for Chronic Pain Creative Commons, Spirit-Fire: Meditation

14 38 heterogenous RCTs; low-quality evidence: it is safe pain (p<0.05) depression (p<0.05) quality of life (p<0.05) function (NS) may opioid use Ann Behav Med 2017; 51:

15 Hilton L et al. Ann Behav Med RCTs reported on analgesic use: CLBP (N=25), 12 weeks: analgesics (p<0.05) Esmer G et al. J Am Osteopath Assoc Nov;110(11): Opioid-treated CLBP (N=35), 26 weeks: 10 morphine-equivalent mg/day (NS) Zgierska AE et al. Pain Med 2016; 17(10): CLBP (N=342), 52 weeks: analgesics (NS) Cherkin DC et al. JAMA 2016; 315(12): Opioid-treated chronic pain, 8 weeks: opioid desire (p<0.05) & use disorder diagnosis (p 0.05) Garland EL et al. Ann Behav Med 2017; 51:

16 CBT for Chronic Pain Wiki Commons, Zahy1412: CBT

17 35 heterogenous RCTs, limited evidence: CBT vs. inactive controls: pain, function (moderate; p<0.05) CBT vs. active controls: disability (small; p<0.05) Short-term effect only on pain, disability 6 months: small effect on depression only Safe Williams AC et al. Cochrane, 2012

18 MM vs. CBT vs. control for chronic pain CLBP (N=342), 10% using opioids 26 weeks: MM and CBT were better than usual care function pain bothersomeness 52 weeks: only MM was better than usual care function pain bothersomeness exercise Cherkin DC et al. JAMA 2016; 315(12):

19 MM vs. CBT for chronic pain 3-arm RCT (N=342), CLBP MM and CBT at 52 weeks: similar effects on catastrophizing, self-efficacy, acceptance Turner JA et al. Pain 2016; 157(11): arm RCT (N=143), Rheumatoid Arthritis MM vs. CBT at 8 weeks (post-treatment): more favorable effects on catastrophizing, disability, fatigue and anxiety than CBT Davis MC et al. J Consult Clin Psychol, 2015; 83(1):24-35

20 Ongoing Study: Strategies To Assist with Management of Pain (STAMP) MM vs. CBT for opioid-treated CLBP Patient-Centered Outcomes Research Institute (# OPD )

21 STAMP Study 766 patients with opioid-treated CLBP Mindfulness meditation (MM) Cognitive behavior therapy (CBT) eight weekly two-hour sessions; daily home practice Patient-reported outcomes at 12 months: pain, function, quality of life, daily opioid dose Patient-Centered Outcomes Research Institute (# OPD )

22 Multicenter randomized controlled trial (Investigators: A. Zgierska, R. Edwards, E. Garland) Madison, WI Boston, MA Salt Lake, UT

23 CBT: Outcomes & Mechanisms Robert Edwards, PhD The term CBT varies widely and may include self-management instructions relaxation or biofeedback, developing coping strategies, changing maladaptive beliefs about pain, and goal setting... Gatchel et al. Psychol Bull 2007

24 The primary goal of CBT for pain is to promote the adoption of an active problemsolving approach to tackling the many challenges associated with chronic pain. Specific Objectives: 1) Change patients views of their problems from totally overwhelming to manageable. 2) Learn to iteratively set and modify behavioral goals. 3) Develop and apply techniques to monitor and challenge maladaptive thoughts and beliefs. 4) Demonstrate how/when to employ pain-coping skills. 5) Re-conceptualize personal views from passive to competent and resourceful.

25 2014 Review Data Synthesis: We found good evidence that cognitive-behavioral therapy... is moderately effective for chronic or subacute LBP. Benefits over placebo, sham therapy, or no treatment averaged 10 to 20 points on a 100-point VAS pain scale...

26 Opioids

27 Opioid Use 8 weeks of group CBT + 4 months of phone-based booster calls: modest but significant reduction in opioid doses in patients with chronic pain:

28 BWH Trial: Opioid Misuse 6 month trial of 63 LBP subjects: 1) High Risk Controls, 2) High Risk Experimental, 3) Low Risk Controls. High Risk Experimental Group: a) Individual CBT-oriented motivational counseling b) Group CBT-oriented educational counseling c) Monthly Monitoring

29 Putative CBT Mechanisms

30 CBT and Negative Affect

31 Negative Affect and Opioid Outcomes In multiple studies, high level of negative affect and catastrophizing have been associated with less µ-opioid agonist analgesia and elevated rates of opioid misuse.

32 Cognitive Mechanisms: Catastrophizing A set of negative I feel I can't cognitions, stand emotions, the attitudes, pain anymore and beliefs related to pain I worry all the time about whether the pain will end I wonder whether something serious may happen Rumination Magnification Helplessness

33 Catastrophizing Score Effects on Outcomes Catastrophizing Score

34 CBT and Catastrophizing Effects at 6- to 12-months post-treatment: Significant, moderate-sized effects of CBT on reduction in catastrophizing Some evidence that effects are largest in those with the highest baseline PCS scores.

35 BPI Pain Interference CBT: Largest Effects in High Catastrophizers Ongoing BWH Trial % reduction in Pain Interference is almost twice as large in the high PCS group Pre-Treatment Post-Treatment 0 Low PCS High PCS

36 Physical Activity as a Mediator Increases in activity are the most significant mediator of CBT benefits:

37 CNS Mechanisms Prefrontal Cortex Slide courtesy of Jordan Karp Limbic Cortex Insula Most sites within the Pain Matrix process Anterior cingulate cortex information about pain AND affective states Hypothalamus & Mid-brain centers Similar changes in neurotransmitters in both pain and affective illness: GABA, Glutamate, Substance P, NMDA activation, perturbation of NE and 5HT.

38 CNS Mechanisms What Does A Catastrophizing Brain Look Like? Functional magnetic resonance imaging (fmri) measures brain activity by detecting changes associated with blood flow. This technique relies on the fact that cerebral blood flow and neuronal activation are coupled. When an area of the brain is in use, blood flow to that region also increases. We use a 3T scanner, and blood-oxygen-level dependent (BOLD) contrast, to image changes in blood flow (reflecting changes in neural activity) over time. This allows us to create activation maps of increased or decreased activity in specific brain regions.

39 Functional Connectivity: Use as a Potential Biomarker

40 Salience Network The salience network has key nodes in the insular cortex & dorsal prefrontal regions, and is critical for detecting behaviorallyrelevant stimuli, and for coordinating the brain's neural resources in response to these stimuli.

41 Default Mode Network Task-Negative network that is deactivated during tasks but activated during self-referential cognition, daydreaming, rumination, etc.

42 Catastrophizing: Associations Between Salience and DM Networks

43 Dysfunctional Connectivity in Chronic Pain

44 Dysfunctional Connectivity in Addiction Disrupted Default Mode Network and Basal Craving in Male Heroin-Dependent Individuals: A Resting-State fmri Study. Qiang Li et al, Journal of Clinical Psychiatry, 2017

45 PCS Score CBT Reduces Catastrophizing and Normalizes Brain Connectivity Fibromyalgia with high PCS scores were enrolled in a treatment study and randomized to 4 sessions of CBT (n=8) or 4 sessions of an educational control treatment (n=8). -Lazaridou et al., Pre-Tx CBT * EDU Post-Tx

46 Patients in the CBT group show reductions in functional connectivity between S1 and anterior/medial insula at post-treatment: * And those who exhibit the largest reductions in catastrophizing also have the most substantial decreases in that connectivity...

47 Overlap of Many CBT Mechanisms, with Unclear Temporal Order Depression Anxiety Fear of Pain Life Stress Etc. Catastrophizing Attention to Pain Expectations Self-Efficacy Etc. Adherence Exercise Sleep Muscle Relaxation Etc. Sensitization Brain Connectivity Pain Modulation Neuroendocrine Fx. Etc.