The IBD Patient in Pain Eva Szigethy MD, PhD Associate Professor of Psychiatry, Pediatrics and Medicine Director, Visceral Inflammation and Pain (VIP) Center Division of Gastroenterology szigethye@upmc.edu
Case Study 44 old female (Sue) with Crohn s disease x 4 years but over past 6 months abdominal pain is worse. Mild increase in pain with eating. 2-3 loose stools per day. No change in pain with defecation. This new bout of constant pain started after C-diff infection 3 months ago- treated with antibiotic Current medications: Anti-TNF No surgeries.
Acute versus Chronic Pain Pain: An unpleasant sensory and emotional experience associated with actual or potential tissue damage Acute: Cause usually understood. Often result of disease, or surgery. Treatment: short-term and curative Chronic: Lasts > 3 months constant or 6 months intermittent. May not be linked to actual physiologic event. Psychological sequelae common Treatment: goal-oriented, non-curative International Assoc. Study of Pain; NIH
Scales For Measuring Abdominal Pain Single Element Measurement (Intensity) Visual Analog Scale Multidimensional Measurement PROMIS pain instrumentswww.nihpromis.org Intensity, Interference, Behavior
PROMIS Pain Behavior Items When I was in pain I became irritable When I was in pain I grimaced When I was in pain I would lie down When I was in pain I moved extremely slowly When I was in pain I became angry When I was in pain I clenched my teeth When I was in pain I tried to stay very still Reveki, 2009
Spectrum of Pain Diagnosis in IBD Acute Gastroenteritis or IBD flare (CD > UC) Recent surgery SUE? Acute-Chronic IBD- IBS (irritable bowel syndrome)- possible postinfectious Rome III criteria for IBS Abdominal pain at least 3 days a month in the last 3 months, and also least 2 of the following: a. The pain/discomfort is relieved by defecation b. and/or the start of the pain/discomfort is associated with altered stool frequency c. and/or the start of the pain/discomfort is associated with altered stool form (appearance).
Acute versus Chronic Pain Inflammation Anatomicalstrictures/fistulas Motility Post-surgical recovery Bacterial overgrowth Menstrual cycle?anti-tnf-no Central nervous system involvement Psychological- anxiety, depression Neurobiologicalvisceral hyperalgesia Microbiome TREAT SOURCE Bielefeldt et al., Inflamm Bowel Dis 2009; Srinath et al., Ther Advances in Gastro 2012; Camilleri N Engl J Med 2012; Bharadwaj, 2015 Wang, 2015; Chichlowski & Rudoloph, 2015
Case-continued CRP normal and colonoscopy negative IBD-IBS pain from peripheral (visceral) nerve sensitization after C-diff exposure also possible. Sue not going to work due to her GI symptoms and starting to limit social functioning
IBD-IBS 30-80% of adults with inactive IBD had irritable bowel syndrome (IBS) symptoms May have unrecognized inflammation High rates of anxiety/depression Early life trauma linked to visceral hypersensitivity in IBS and IBD Increase TRPV1 (vanilloid) Minderhound et al., Dig Dis Sci 2004; Farrokhyar et al., Inflamm Bowel Dis 2006; Ansari et al., Eur J Gastro Hepatol 2008; Keohane, AJG 2010; Long, AJG 2010; Drossman AJG, 2011; Akbar 2012
Treatment of Pain in IBS Psychosocial Interventions- cognitive behavioral therapy, scripted hypnotherapy 8-12 sessions with practice over 3-4 months Low FODMAP (fermentable, oligo, di, mono saccharides and polyol) diet Henrich Journal of psychosomatic research 2014; Palsson & Whitehead, Clinical Gastro & Hep 2013; Whorwell, 2008; Szigethy Am J Clinical Hypnosis 2015; Marsh Eur J Nutr. 2015, Ford, Am J Gastro, v 109 suppl, 2014
Pain Medications in IBS Antidepressants with moderate evidence Rifaximin for IBS-D (For IBD?? Guslandi, W J Gastro, 2011) Lonaclotide and Lubiprostone for IBS-C (Contraindicated for mechanical source of pain in IBD, chronic pancreatitis, etc. and intestinal obstruction) Ford, Am J Gastro, v 109 suppl, 2014
Case Study- next 3 months Teach behavioral interventions for pain management- distraction techniques and hypnosis so brain can be less reactive to false alarm pain signals. Behavioral sleep interventions and sleep hygeine I don t want an antidepressant- this is not mental
Address Poor sleep Regularity Subjective satisfaction/ high quality Appropriate timing Adequate duration High efficiency Sustained alertness during waking hours
Behavioral Treatment-Insomnia A set of principles taught to patients over 1 month: 1. Consistency of sleep/wake times 2. Don t go to bed unless tired 3. If not falling asleep after 20 minutes, go do something else. 4. No or brief naps. 5. Daytime activity matters GOAL: Time in bed = Actual Sleep time Szigethy @ Germain
Case Study-next 6 months Non-compliant with psychosocial interventions History of chronic recurrent depression Other pain syndromes- fibromyalgia and chronic headaches. No other medical diagnoses. Oxycodone and fentanyl patch x 1 month after ER visit Patient goes to multiple ERS to get narcotics and "fights" with staff/mds when not given drugs. Currently depressed and poor sleep
Chronic Pain Suffering: Central Pain Syndromes Central nervous system (non-nociceptive) disturbances in pain processing with diffuse hyperalgesia Behavioral factors prominent Etiology: female, genetics, early trauma/abuse Repetitive exposure to stressors lead to psychological and behavioral response to chronic pain..vicious cycles Phillips, 2011; Leserman. 1996; 2) Drossman, 1990; 3) Longstreth, 1993; 4) McCauley, 1997
Spectrum of Pain Psychopathology in IBD SUE Acute Acute-chronic Chronic Severe Brief pain related to gastroenteritis or IBD flare (CD > UC) IBD- IBS (irritable bowel syndrome)- possible postinfectious Central chronic pain +/- Multiple pain syndromes +/- Childhood trauma +/- Psychopathology +/- Narcotic use
Chronic central pain does not response well to narcotics or brief cognitive behavioral therapy We must change the lens through which we see treatment of chronic refractory pain.
Education about Brain-Gut-Pain Connection PSYCHOLOGICAL Mood Cognitions Personality Suffering Disability Suicide Peripheral nerve damage PHYSICAL Inflammation Obstruction Surgery Srinath and Szigethy 2012
Central Pain Example: Borderline Personality Disorder Borderline personality disorder (BPD) is characterized by a pervasive and persistent pattern of instability and impulsivity. Instability in mood, self-image, relationships. Disruption on emotional, cognitive, and interpersonal domains Prevalence 2-10%
Borderline Personality and Pain High rates of chronic pain syndromes (>50%) Excessive use of opioids for chronic pain Association between borderline personality disorder and narcotic use in patients with IBD Samsone & Samsone, 2010; Crowell 2009
Sue s formulation Has many characteristics of central pain prone phenotype (CNS mediated pain) Female, history of other chronic pain syndromes, catastrophizing Also assess for early life trauma Need to assess if narcotic use has evolved into substance abuse/dependence.
Managing Challenging Behaviors in Chronic Pain: Clear explanation of expectations from treatment onset Empathic listening and repeat back what you heard Setting consistent limits and clear verbal and written instructions Validate anger but redirect toward their helplessness not their helpers Re-channel entitlement into realistic expectations of good care Arrange regular appointments not based on worsening. Manage your countertransference Groves, 1978
Behavioral Interventions for Chronic Pain Meditation and mindfulness techniques reduce pain perception and suffering. Hypnosis improved acute and chronic pain across a variety of conditions. Moderate exercise Astin 2002,Knittle 2010, Glombiewski 2010; Andrasik 2007; Elkin 2007; Kok 2013; Tang 2013; Palsson & Whitehead 2014; Patterson & Jensen, 2003
Treatment Plan for Sue Build a strong therapeutic relationship to improve motivation and educate about neurobiology of pain circuits. Continue to offer behavioral interventions Begin appropriate alternative non-opioid pain medications. Explore willingness to come off opiates
Non-opioid pharmacotherapy for Sue SSRIs (citalopram) can help anxiety and depression but rarely help pain directly. Add a tricyclic antidepressant at night. Start low and go slow. Usual dose range between 50-150 mg/day Analgesia starts to occur after a week and can take 3 weeks to reach max efficacy. Amitriptyline (3 ) more sedating Nortriptyline (2 ) less sedating Desipramine (2 ) least sedating Drossman 2009; Dekel 2013; Ford, 2008; Drossman 2002; Taylor 2007; Houghton 2011; Grover 2009; Szigethy and Drossman, 2014
Potential benefits Antidepressant considerations TCA SSRI SNRI Pain Depression Anxiety Adverse effects Sedation Constipation Hypotension Dry mouth Arrhythmia Weight gain Depression Anxiety Agitation Diarrhea Night sweats Headache Sexual dysfunction Pain Depression Nausea Agitation Dizziness Sleep disturbance Fatigue Liver dysfunction Overdose Risk Moderate Minimal Minimal
PNS Mechanistic Approach to Treatment Descending Inhibition NE/5HT Opioid R Peripheral Sensitization BRAIN TCAs SSRIs SNRIs Opioids Central Sensitization Ca ++ Gabapentin /PGB Oxycarbazepine (OXC) Lamotrigine Na ++ Carbamazepine/OXC TCA Topiramate Lamotrigine SPINAL CORD NMDA Ketamine, Memantine Dextromethorphan Beydoun 2002
FDA-Approved Treatments for Neuropathic Chronic Pain Carbamazepine (Trigeminal neuralgia) Gabapentin (PHN-herpes) Lidocaine patch 5% (PHN) Duloxetine (PDN-diabetic), PHN, Fibromyalgia) Pregabalin (PHN, PDN, Fibromyalgia) Milnacipram (Fibromyalgia) Capsaicin 8% (PHN)
Other Mood Stabilizers Oxcarbazepine: Comparable analgesic effect in both new and refractory trigeminal neuralgia to CBZ Dose range (900-2100mg/day) Much more tolerated than CBZ Lamotrigine (200-400mg/day): Better than placebo in trigeminal neuralgia and diabetic neuropathy but no difference for neuropathic pain Topiramate (400mg/day): Better than placebo in one trial but not in 3 trials. Lindstrom 1987; Beydoun 2002; Zakrewska 1997; McCleane 1999; Eisenberg 2001; Edwards 1999
Concerns with Opiates in IBD No evidence of efficacy for chronic abdominal pain Psychological/physical dependence Higher rates of infection/mortality Narcotic Bowel Syndrome (NBS) versus Tolerance Grunkmeier 2007; Lichenstein 2006;
Edwards 2001; Cross 2005; Hanson 2009; Long 2011; Szigethy 2014 Opioid Use in IBD Used acutely after surgical resection of the intestinal tract and to treat pain due to inflammation/obstruction in IBD. 5 21% of patients with IBD are on chronic narcotics in the outpatient setting. 20-70% inpatients with IBD use narcotics Risk factors: CD, substance abuse, psychiatric diagnoses, IBS, history of trauma, female gender
Opioid Detoxification for Sue Attempt outpatient taper but inpatient medical hospitalization if necessary 10-33% daily reduction of i.v. morphine or hydromorphine equivalent Continue non-opioid pain medications Appropriate management of bowel motility (constipation or diarrhea) Continue behavioral interventions
Abdominal pain scores improve but high recidivism (Phase 2 only) 60 50 Visual Analog Scale (0-100) 40 30 20 10 0 Pre-detoxification n=39 Post-detoxification n=37 Stayed off narcotics n=13 Went back on narcotics n=10 Drossman DA et al. Am J Gastro 2012;107:1426 3 month follow-up
Opioid risk management if do prescribe acutely: State rules and regulations Random toxicology screens and pill counts Opioid treatment agreements Communication with PCPs and pharmacies Ongoing review and documentation of pain relief, functional status Risk assessment instruments: SOAPP-R (Screener and Opioid Assessment for Patients w/pain), COMM (Current opioid misuse measure), ABC (Addiction behaviors checklist) Take home message- have a risk management plan
Rational Approach to Chronic Pain Titrate one medication at a time Start new medications at lowest possible dose Slowly titrate (every 3-7 days) until end point of maximal significant pain relief (>50%) or intolerable side effects. Continue chronic use only if significant pain relief, tolerable side effects and increased patient functioning occur. Polypharmacy only if partial response with first med. Supplement medication with psychosocial interventions.
Personalized Psychosocial Management Pathways for Pain Active IBD Inactive IBD IBD Meds Coping therapy Cognitive behavioral therapy Hypnosis Psychotropic medication Psychotropic medication Exercise