Problematic opioid need in chronic pain: Part 2: Complex persistent dependence and the confusing patient experience on and off opioids

Transcription

1 Problematic opioid need in chronic pain: Part 2: Complex persistent dependence and the confusing patient experience on and off opioids Ajay Manhapra, MD Advanced PACT Pain Clinic, VA Hampton Medical Center Lecturer, Department of Psychiatry, Yale School of Medicine Research Scientist, VA New England MIREC, West Haven, CT S L I D E 0

2 Cognitive narratives in opioid use for chronic pain: The analgesic narrative Chronic pain is due to persistent structural problem that could be corrected Opiates are effective analgesics with manageable side effects over long term Increasing opioid dose for uncontrolled pain involves minimal risks Recent additions to this narrative: Opioids are not as effective or as safe as we thought, and addiction is a much more common than we thought. It is scary!! Shifting balance: Side effects may on average overwhelm effectiveness Tolerance and dependence are expected and normal Need for dose increase and physical withdrawals with opioid cessation Opioids should be tapered down when side effect overcomes effectiveness. Tapering is somewhat difficult but achievable with improved safety and function Problematic opioid need, behavior or taper outcomes indicate addiction/oud S L I D E 1

3 Pain: More than a somatic sensation, an experience with complex processing Physical (somatic) Pain intensity Immediate unpleasantness Extended Negative affect Pain behavior Pain experience: Not just physical pain, but all these 4 factors Pain relief: Not just reduced somatic pain, but relief in 4 domains Adapted from Riley & Wade Model S L I D E 2

4 Why opiates are such effective pain medications?: The boon and the curse!!! Analgesics Opioids direct effect Reduced pain intensity Reduced immediate unpleasantness and extended negative affect Relief Relief from PTSD, depression, emotional dysregulation, stress, anger, anxiety, insomnia etc. S L I D E 3

5 Therapeutic Dependence Vs. OUD thru illicit use: Biologically similar, but clinically distinct Illicit means Reward: Hedonic Distinct learned behavior Increasing opioid need Typical OUD/Addiction Distinct long term psycho-social effects Opioids Intermittent to Chronic use Opioid induced neuroadaptation (learning, memory) Opioid induced systemic adaptation Long term Medical Effects OD, Opioid related morbidity & mortality Systemic morbidity & mortality Psychiatric changes Chronic disease due to behavioral changes Prescribed Reward: Pain relief Distinct learned behavior Increasing opioid need Abuse/misuse, Pain dysfunction, opioid dependence Distinct long term psycho-social effects Concept adapted from: Ballantyne et al: ARCH INTERN MED/VOL 172 (NO. 17), SEP 24, 2012 & PAIN: CLINICAL UPDATES DECEMBER 2013 S L I D E 4

6 Diagnostic convention Vs. reality for patients Clearly No OUD/Addiction Particular set of behaviors absent Clear treatment options Clear OUD/Addiction Particular set of behaviors present Clear treatment options Not black and white, but many shades of grey We talk a lot about this We talk a lot about this Early Dependence We don t talk a lot about patients in this state Complex persistent dependence Most of our problem patients are somewhere here in this grey area where treatment options are unclear S L I D E 5

7 Patient story 61 year old veteran with chronic pain due to DJD of spine maintained his business on fentanyl patches (>400 MME/day) for over a decade. Over time, pain and function worsened, insomnia, anger and depression slowly emerged, but all at manageable levels. But fentanyl continued to provide relief, and he cant understand why physicians insists that opioids are not effective for chronic pain. To him, it is the only effective thing after trying everything. He started seeking more opioids from physicians because of uncontrolled pain and worsening mental health and functional life. He thought his DJD was worsening, but radiographic investigations showed stable DJD. A slow opioid taper was started by PCP with promise of improvement. His pain, function and psychiatric symptoms worsened. He was confined to wheel chair and was relying on his family even for basic care soon after opioid taper. He reported no craving, but his pain was profoundly debilitating. S L I D E 6

8 Two faces of Janus??!! Long term opioid therapy for pain Continued on opioid Worsened pain, function and psychiatric symptoms driving opioid need Opioid tapered Worsened pain, function and psychiatric symptoms driving opioid need Whether they are on or off opioids for pain, patients appears to be experiencing similar set of symptoms that drive their opioid need How do you make sense of this? A. Manhapra MD S L I D E 7

9 Key behavioral adaptation concepts related to LTOT Opponent process (Solomon RL 1974) Every process that has an affective balance, (i.e. is pleasant or unpleasant), is followed by a secondary, "opponent process". With repeated exposure, the opponent process is strengthened A behavioral process different from OIH (a sensory phenomenon) Allostasis (Sterling & Eyer 1988): Process of maintaining stability through change Organisms actively adjust to both predictable and unpredictable events Systems adapt to range of demand with behavioral alterations whilst neural mechanisms adapt Affective dynamism: Dependence is not static phenomenon, but a dynamic process that interacts with affective balance Protracted withdrawal Persistent impairments are observed after acute withdrawal from alcohol, opiates, benzodiazepines and other substances S L I D E 8

10 Behavioral Tolerance & Opponent effect modifying patient experience Repeated opioid use and change over time Analgesic effect after each dose Pharmacological effect remains the same over time Opponent effect: Pain after each dose None Opponent effect increases over time Net Effect = Expected effect (relief) Opponent effect (pain) Relief minimal, but highly salient Diminished relief after each opioid dose Increased baseline pain before each opioid dose Allostasis: Baseline pain reset to higher levels Increasing irreversibility A. Manhapra MD Adapted from Solomon RL, American Psychologist, 1980, 35: & Koob et. al. S L I D E 9

11 Affective dynamism with complex dependence Tolerance & dependence are not static phenomena They dynamically interact with pain, stress, sleep, affective state, mood, anxiety, and other psychiatric symptoms Express as varying levels of pain and opioid need Lability or dysregulation of symptoms often leads to polypharmacy Complex dependence Opioid need A. Manhapra MD S L I D E 10

12 Allostatic reset and opioid dose reduction/cessation Allostatic reset: Finding new normal, with repeated opioid exposure, altered physiology gets used to a certain level of opioids. Increasing irreversibility When opioid dose decreased or stopped: Adapt and establish another new normal with lower dose/no drug (successful dose reduction/cessation) OR Try to reinstate the old normal through behavioral changes, if the changes are too hardwired (struggling with dose reduction/cessation) A. Manhapra MD S L I D E 11

13 Protracted withdrawal in dose reduction/cessation A shift in affective processing in protracted abstinence Anhedonia, dysphoria and anxiety often undetected by standard testing Significant sleep disturbances Insignificant challenges provoke negative affect, anger, craving and relapse Normal pleasurable events evoke decreased positive affect or none Persistent pain that does not respond to standard therapy Heilig et al S L I D E 12

14 A well established perspective S L I D E 13

15 Protracted withdrawal syndrome complex Involves following elements: 1. Specific protracted withdrawal symptoms 2. Rebound and reemergence of original symptoms 3. Rebound and reemergence of co-occurring disorders Can occur with opioid cessation and dose reduction Causes aberrancy, opioid seeking behaviors and heroin use with opioid taper Causes relapse after abstinence in SUDs A. Manhapra MD S L I D E 14

16 Protracted withdrawal with opioids for pain Worsening pain Increasing opioid need Insomnia, excessive daytime sleepiness Cessation or dose reduction Worsening physical and social functioning Depression, anxiety Emotional dysregulation, suicide, violence Concentration, memory and cognitive problems Worsening psychiatric problems S L I D E 15

17 Two faces of Janus??!! Complex persistent dependence Opponent effect and affective dynamism with continued opioids Worsened pain, function and psychiatric symptoms driving opioid need Protracted withdrawal with opioid cessation or taper Worsened pain, function and psychiatric symptoms driving opioid need Patients can experience similar set of symptoms that drive their opioid need whether they are on or off opioids for pain A. Manhapra MD S L I D E 16

18 If this not addiction, I have to call this something! This is bad!! Complex Persistent Opioid Dependence (CPOD) Insistence/Need to continue opioids or increase opioid dose for pain despite caution regarding Minimal or no efficacy Complex behavioral and social patterns around opioids (what is characterized as opioid seeking, misuse/abuse, etc.) Safety issues Increased opioid related morbidity and mortality Increased psychiatric morbidity Increased overall morbidity and mortality Screen for patients with significant CPOD DME 100 MG High psychiatric load, Prior SUD Significant pain dysfunction Aberrancies S L I D E 17

19 A new cognitive narrative? Chronic pain is driven more by the neuroplasticity in pain perception circuits and less so by local structural reasons. Opiates can provide effective analgesia and relief, but has significant undesired effects that are often intolerable over long term. Serial escalation of opioid dose for uncontrolled chronic pain involves significant risks and questionable sustained efficacy. When adverse effects overcomes effectiveness, opioid tapering should be considered, and done carefully if patient agrees. Long term opioid use can result in complex persistent dependence that can Worsen experienced pain, increase opioid need and induce lability of pain and other symptoms with continued use of opioids And protracted withdrawals when opioids are withdrawn. After being on opioids for a few years, opioid taper will be difficult for many and some will suffer significant harms if not carefully monitored. S L I D E 18

20 Management of patients with pain and complex tolerance & dependence Complex Persistent Dependence Poor pain Opioid need Functional relief patterns status Improved Stabilized Improved Management of dependence and tolerance Management focused on pain Management focused on use patterns Management focused on functional status A. Manhapra MD S L I D E 19

21 CPOD in patients on long term opioids for pain: What works!!! Primary focus on dependence (dependence is the main driver of pain) Abstinence oriented treatment (taper) often worsens the situation Medication treatment of dependence Buprenorphine preferable to methadone because of lower level of dependence (what drives pain is often dependence) If buprenorphine not available, stabilize dependence with full agonist, preferably long acting May not do well with usual structured OUD oriented psychotherapy Physician counselling often suffices Education of chronic pain, dependence and their interaction Motivational enhancement techniques Multimodal pain management after stabilization of dependence Not a substitute for treatment of dependence Manage comorbid SUD and psychiatric disorders aggressively Manage poly-psychopharmacology aggressively Manage comorbid medical illnesses aggressively S L I D E 20

22 Opioid Full agonist Vs. Partial agonist (Bup) Full agonist Morphine, heroin, methadone, oxycodone, hydromorphone, hydrocodone, fentanyl, codeine, tramadol Partial agonist (buprenorphine) At low doses have a similar dosedependent activity profile as full agonists At higher doses, receptor activation does not increase proportionally with dose Ceiling effect for adverse effects Dependence, sedation, overdose, euphoria, constipation No ceiling effect on analgesia OME = 1: (Buprenorphine) Median Lethal Dose in experimental rats (mg/kg) Morphine Methadone Buprenorphine Barron et al 2002 S L I D E 21

23 What is a successful opioid taper? Successful if the risk improvement can be balanced with the degree of achievement of following goals: Stability or improvement of pain and function Avoids medical and psychiatric/psychological instability Avoids hazardous medical or psychological consequences Experiences minimal physical or psychological stress Patient is treated with dignity and respect Patient is involved in decision process Patient remains engaged in continued treatment Avoids significant protracted withdrawal symptoms Adapted from VA/DoD guideline 2010 S L I D E 22

24 Patient centered taper plan from addiction perspective Opioid risk/benefit unfavorable <100 MME/day Psychiatric and SUD morbidity low or none 100 MME/day Psychiatric and SUD morbidity high Full agonist taper Slow Partial agonist taper with buprenorphine Slow/fast A. Manhapra MD Success Off/reduced opioids Pain controlled Better function Failure Failure Buprenorphine /opioid maintenance S L I D E 23

25 POATS Study: Success with buprenorphine taper in prescription OUD Prescription opioid OUD (no heroin use) Willing to be detoxed Most had pain as the reason for opioid initiation Most receiving opioids from physicians Patients on long term opioids for chronic non-cancer pain Simple dependence Complex dependence Clear OUD 6.6% 49.2% 8.6% N=653 1-month taper N=360 3-month taper Weiss et al Arch Gen Psych 2011; Weiss et al. JSAT 2014 S L I D E 24

26 POATS Study: Long term follow up after Buprenorphine taper in prescription OUD 18 months after baseline (N=252/653) 49.6% abstinent in past 30 days 65.9% engaged in treatment and 48.8% on OAT 9 patients initiated heroin; 17 initiated opioid injection 42 month after baseline (306/653) 31.7% abstinent from opioids and not on agonist therapy 29.4% on opioid agonist therapy 31.4% were using opioids without agonist 8% initiated heroin use Take home message: Early results disappointing However, on long term follow up, treatment engagement appears to result in: Complete abstinence in about a third Continued opioid agonist treatment in about another third Potter et al JSAT 2015; Weiss et al. DAD 2015 S L I D E 25