Survey
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
Evaluating and Treating Pain in IBD Eva Szigethy MD, PHD Associate Professor of Psychiatry, University of Pittsburgh Director, Medical Coping Clinic, Children’s Hospital of Pittsburgh Director, Visceral Inflammation and Pain (VIP) Center Division of Gastroenterology, Hepatology, and Nutrition December 12, 2013 Disclosure • Sources of Funding – – – – CCFA Senior Investigator Award NIMH R01 Grants American Psychiatric Press Inc., Book Editor Merck- Consultant, Advisory Board • All medication suggestions in this presentation are off-label uses unless noted otherwise. Abdominal pain is common in IBD Of adults with IBD, 20% consume up to 80% of medical costs. Chronic pain and depression are key factors Binion et al., 2010 Relationship between pain and telephone encounters in adults with IBD Ramos Rivers 2013 Multiple Factors to Consider for Causes of Pain in IBD • • • • • • Inflammation Anatomical- strictures/adhesions/fistulas Bacterial overgrowth- small intestine Neurobiological/Psychological Psychosocial Genetics Bielefeldt et al., Inflamm Bowel Dis 2009; Srinath et al., Ther Advances in Gastro 2012; Camilleri N Engl J Med 2012 IBD-IBS • 30-80% of adults with inactive IBD had irritable bowel syndrome (IBS) symptoms • Self-reported pain in 45%-100% pediatric patients with IBD • 10-40% with IBS • Over half depressed Simren et al., Am J Gastroent 2002 ; Minderhound et al., Dig Dis Sci 2004; Farrokhyar et al., Inflamm Bowel Dis 2006; Ansari et al., Eur J Gastro Hepatol 2008; Zimmerman et al., Inflamm Bowel Dis 2012, Crandall et al., J Ped Gastro & Nutr 2007 Greenley et al., J Ped Psychol 2012 Unrecognized inflammation in adults with quiescent IBD Crohn’s Disease Ulcerative Colitis Keohane et al., Am J Gastroenterol 2010 Influences on Visceral Sensitization Stress Abnormal inputs Repetitive bowel stimulation Acute inflammation Infection IBD (mild or in remission) Neurological trauma Operations Invasive procedures Zighelboim J, Dig Dis & Sci 1995; 40:819 Drossman DA et. al., Gastroenterology 2002 The brain can amplify the pain from the gut ● Pain involves both the gut and brain ● Acute GI pain usually results from injury to the gut (e.g., active disease or infection) ● Chronic GI pain can result from the gut (visceral hypersensitivity), brain (central hypersensitivity), or both ABDOMINAL PAIN Psychological Depression and anxiety in adult and pediatric IBD Mood disorders linked to persistent pain in quiescent IBD Increased worrying, limited coping ability, somatization Mechanisms still unclear Szigethy et al. J Am Acad Child Adolesc Psychiatry. 2004; Fuller-Thomson, Sulman. IBD 2006; Farrokhyar et al. IBD 2006; Srinath et al. DDW 2011 (Abstract); Graff et al IBD 2009 ABDOMINAL PAIN Psychosocial Life stressors ~ coping pain perception in IBD Early life trauma linked to visceral hypersensitivity Chronic stress reactivation risk Ross et al. JPGN 2011 Drossman. Am J Gastroenterol 2011 Engstrom J Am Academ Child Adolesc Psych 1991 Levenstein et al. Am J Gastroenterol 2000 Components of Pain History (Clinical Manual of Pain Management in Psychiatry, R. Leo, APPI 2007) Somatic Onset/Duration Location Quality Intensity Psychological Mood/Affect Cognitive Coping Psychiatric Illness Associated features Aggravating factors ABD Alleviating factors PAIN Social Impact on relationships Capacity for intimacy/sexuality Activities of daily living Educational Vocational Pain is a modifiable experience Psychosocial Context • • • • • • • Pain Experience Pain beliefs Cultural Expectation Conditioning Social support Stress Sleep Cognitions • Hypervigilance • Attention • Catastrophizing Neurobiological • Neurodegeneration • Maladaptive plasticity Injury Genetics • Peripheral and central sensitization • Mechanical • Mutations • Gene products Nociceptive Modulation Pain Management Education for Abdominal Pain • The goal of education is to communicate information to patients and families about abdominal pain and its connection with psychological triggers, as well as factors that may exacerbate pain, such as social reinforcement and school/work avoidance • Family therapy targets family interactions and relationships rather than the individual patient in order to change maladaptive behaviors, increase tolerance of symptoms and encourage independent coping skills. Brent M JPGN 2009; Bursch JPGN 2008; Walker Pain 2006; Chiou & Nurko, 2010 Education: Offering a Validated Explanatory Model for Pain Cognitive Behavior Therapy (CBT) for Pain • CBT has most empirical support for treating depression and anxiety in adults with IBD • CBT alters behavior, perception, and thinking to change mood and sensations • CBT helps individuals to interrupt automatic emotional processing which maintains negative cognitions and rumination about pain • CBT teaches problem-solving skills based on personal control and the ability to adjust behavior and thoughts accordingly = stress management Palsson & Whitehead, 2013 Cognitive Behavioral Therapy versus medical treatment as usual for depressed adolescents with IBD • Improved abdominal pain Changes in Somatic Symptoms: CBT vs TAU **** 50 % Change in CDI Item Scores • CBT modified to target illness perception and relaxation for pain Results • 3 month pre- post treatment: • Decreased depression • Improved quality of life 40 30 ** ** * * 20 * 10 0 Anhedonia Sleep problems PASCET-PI TAU Fatigue Poor appetite Pain CDI Items Szigethy et al., 2004,2007,2009 Definition of Clinical Hypnosis • A state of inner absorption, concentration and focused attention • An altered state of consciousness with observable brain changes. • This “trance” allows access to primitive, automatic brain mechanisms to control perception, memory and somatic function. • Utilizes the human brain’s natural tendency to dissociate. Driving and missed your exit? …… Trance Empirical Evidence for Hypnosis for IBS is growing • GI symptoms- pain, distention, motility • Rectal smooth muscle tone/sensitivity • Analgesic medicine use • Autonomic nervous system • Suffering- anxiety, depression, emotional awareness (CNS) • Quality of life • Functioning- work productivity, doctor visits Palsson & Whitehead, 2013 Hypnosis for IBD Adults • Improved IBD activity and circulating cytokines • Improved quality of life • Less corticosteroid use • Decreased rectal mucosal release of substance P, histamine • Decreased rectal blood flow • Maintaining remission in UC patients Children • Improved post-hypnosis in pain, diarrhea, inflammatory markers • Controlled for change in medical treatment Miller & Whorwell 2008, Mawdsley 2008 Shaol 2008; Keefer , 2013) Common elements in empirically tested GI hypnosis • Brief and time-limited therapy (6-12 weekly or bi-weekly sessions) • Interventions are gut-focused: Gastrointestinal suggestions and gut imagery and metaphors targeting central symptoms of each disorder, and promoting normalization of gut functioning and reduced symptom experience. • Home practice used in between therapist visits with recorded hypnosis audio exercise or self-hypnosis Examples of hypnotic language • “Your brain is now sending messages to the gut-control stations to tune down the intensity and quality of pain signals so that you feel less discomfort…” • “…your brain can easily and automatically filter out any uncomfortable sensations and allow in (warm, cool) comfortable sensations Benefits of Psychological Treatment High response rate (about 70%) Can benefit patients not responding to medical treatments Is additive to and possibly synergistic with medical treatments No side effects Benefits continue years after treatment ends Reduces health care costs 2234 Pain Management: Medications • IBD Medications- remission is goal • Antispasmodics – beware of obstruction • NSAIDS and COX-2 inhibitors- beware of worsening IBD flare • Acetaminophen- no significant anti-inflammatory, gastric or renal effects but hepatotoxicity • Opioids- beware of long-term use • Psychotropics- do they work? Srinath et al.; 2012; Grover & Drossman IBD Monitor, 2009 Rationale for Antidepressants for IBD Treatment of psychiatric co-morbidity Peripheral effects Motility / secretion Afferent Central pain modulatory effects 1252 Antidepressants: TCA, SSRI, SNRI • The neurochemicals targeted involved in visceral motility and sensation (IBS). • Unclear whether they directly impact nociception or their beneficial effects are mediated by decreasing anxiety and depression. • SSRI/SNRI: Few side effects or drug-drug interactions Mikocka-Walus BMC Gastroenterol 2007, 2009; Friedrich et. al. Clin. Ther. 2010 ; Rahimi 2009 Tricyclic Antidepressants (TCA) • Increase serotonin, endogenous opioid release, direct action on opioid receptors. Potentiate the actions of opiates requiring lower dose. • Effects on pain reduction and improved sleep more rapid than antidepressant effect (3-7 days) and at lower doses. • Anticholinergic side effects such as dry mouth, constipation, blurred vision, urinary retention, confusion, delirium. • Autonomic side effects include orthostatic hypotension, sweating, palpitations, tachycardia, increased blood pressure and prolonged QT, QRS and PR intervals and depressed ST segments requiring EKG monitoring. Overall Forest Plot of Antidepressant Studies for IBS Tricyclic Antidepressants (TCAs) Treatment Control Heefner, 1978 Myren, 1982 Ngain, 1984 Boerner, 1988 Bergmann, 1981 Vil, 1991 Drossman, 2003 Talley, 2008 Vahedi, 2008 Subtotal (95% CI) n/N n/N 10/22 5/30 14/21 16/42 5/19 14/25 60/115 0/18 8/27 319 12/22 10/31 21/21 19/41 14/16 20/25 36/37 5/16 16/27 256 0.1 0.2 RR (random) Weight RR (random) 95% CI % 95% CI 5.94 2.66 14.74 7.63 3.82 10.67 16.77 0.33 5.02 67.36 0.5 Favors treatment 1 0.83 0.52 0.67 0.82 0.30 0.70 0.83 0.08 0.50 0.68 (0.46, (0.20, (0.49, (0.30, (0.14, (0.47, (0.63, (0.00, (0.26, (0.56, 1.51) 1.33) 0.90) 1.36) 0.65) 1.04) 1.08) 1.36) 0.97) 0.83) 2 10 5 Favors control Total events: 32 treatments; 153 controls Test for heterogeneity: Chi2=10.94, df=8, (P=0.21), F=26.9% Test for overall effect: Z=3.86 (P=0.0001) Ford AC et al. Gut, Nov 2008; doi:10.1136/gut.2008.163162 2692 Antidepressant Receptor Site Effects TCAs (25-150 mg) Amitriptyline (3o) Doxepin (3o) Desipramine (2o) Nortriptyline (2o) SSRIs (1-2 pills) Citalopram Escitalopram Fluoxetine Paroxetine Sertraline SNRI’s (variable) Venlafaxine Duloxetine Milnacipran NE 5HT Histamine Ach +++ ++ +++ +++ +++ +++ +++ + ++++ ++++ + ++ ++++ ++ + ++ nil nil nil nil nil ++++ ++++ ++++ ++++ ++++ nil nil nil nil nil nil nil nil nil nil ++ +++ +++ ++ +++ ++ nil nil nil nil nil nil 1259a Antidepressant considerations TCA SSRI SNRI Potential benefits Pain Depression Pain Depression Anxiety Pain Depression Adverse effects Sedation Constipation Hypotension Dry mouth Arrhythmia Weight gain Agitation Diarrhea Night sweats Headache Sexual dysfunction Nausea Agitation Dizziness Sleep disturbance Fatigue Liver dysfunction Overdose Risk Moderate Minimal Minimal Cost/month $5-30 $40-80 $60-100 Approach to prescribing antidepressants • Address false expectations or beliefs of patients • Provide psychopathological explanation of patient’s symptoms that psychopharmacological agent would target • Provide information/rationale aligned with patient’s interests/concerns • Negotiate treatment plan – Benefit in 4-6 weeks – Most side effects decrease in 1-2 weeks – Consider previous drugs that works and family history of drug response Drossman 2002 Gabapentin/pregabalin • Centrally acting agents with mechanism unclear. – ?centrally acting voltage-gated calcium channel modulators. – structurally similar to γ-amino butyric acid (GABA), which is a major inhibitory neurotransmitter in the CNS. • They reduce neuropathic pain by attenuating the release of many different neurotransmitters • Has few side effects and does not require serum monitoring. Taylor 2007; Gale & Houghton, 2011; Richard 2013 Other Central Agents with GI effects Mirtazapine Serotonergic and noradrenergic drug with 5HT2 and effects – can have pain benefit Use with nausea, anorexia, weight loss, diarrhea Some sedation 5HT3 Clonidine α2-adrenergic against with central (anxiety reduction) peripheral (pain reduction via bowel compliance) Helps reduce diarrhea Prevents adrenergic effects of narcotic withdrawal and Buspirone Azapirone with anti-anxiety effects acting on non BZD GABA receptors Has 5HT1 and 5HT2 effects Potential benefit for PDS (dyspepsia) due to receptive relaxation of stomach 2061 Quetiapine Atypical antipsychotic with complex effects Dopamine (D1 and D2) and Serotonin (5HT1a and 5HT2) antagonism with some α2-adrenergic blocking effect Treatment Effects Bipolar disorder and schizophrenia (labelling) Augmentation for OCD, PTSD, depression Sleep (normal sleep architecture) Anxiety reduction Some analgesic benefit Improves painful FBD refractory to TCA or SNRI1 Side effects Sedation, somnolence, dry mouth Metabolic syndrome (weight gain, glucose intolerance, hyperlipidemia) Abnormal LFTs (rare) 1Grover M, Drossman DA. Dig Dis Sci 2009;54:1284 2062 Atypical Antipsychotic Quetiapine* in Refractory FGIDs 10/21 (48%) subjects discontinued Quetiapine 90 Significantly/somewhat better Same Worse 80 70 60 % 50 Patient response 40 30 20 10 0 Global GI symptoms Abdominal pain Bowel habits * Dopamine (D1 and D2) and Serotonin (5HT1A and 5HT2) antagonism with some a2-adrenergic blocking effect Grover M, Drossman DA, et al. Dig Dis Sci 2009; 54:1284 2787 Potential Benefits of Supplemental Psychopharmacologic Agents CENTRAL ACTING • Central pain perception— analgesia PERIPHERAL ACTING • Peripheral analgesic effects— alters visceral afferent signaling • • GI physiology (motility and secretion) via effects on neurotransmitter pathways Mood—anxiety, increased stress responsiveness • Treatment of associated psychiatric disorders— depression, PTSD, somatization • Treatment of associated sleep disturbances • Smooth muscle effects on viscera Grover & Drossman, 2011 Opioids (Narcotics) • Bind to CNS opioid receptors and inhibit release of pain neurotransmitters. • Mixed agonist/antagonists available • Many side effects –constipation, nausea, vomiting, sedation, pruritis, respiratory depression. Opioids (narcotics) • Used acutely after surgical resection of the intestinal tract and to treat pain due to inflammation in IBD. • 5–13% of patients with IBD are on chronic narcotics in the outpatient setting. • Risk factors for outpatient narcotic use in IBD include psychiatric comorbidities (anxiety and depression), history of abuse, female gender, and a high degree of clinical symptoms • 20-70% inpatients with IBD use narcotics • Risk factors for inpatient narcotic use include diagnosis of CD, substance abuse, psychiatric factors, and the presence of IBS symptoms Edwards 2001; Cross 2005; Hanson 2009; Long 2011 Concerns with Opiates • Psychological/physical dependence • Higher rates of infection/mortality • Narcotic Bowel Syndrome (NBS) Grunkmeier 2007; Lichenstein 2006; Typical Clinical Presentation for NBS Chronic or recurrent abdominal pain which is treated with narcotics Narcotics may have relieved pain initially but then stop working Shorter pain-free periods result in increasing narcotic doses Increasing doses further alter motility and aggravate pain Can occur with in patients IBS, organic disease or otherwise health subjects (e.g., post operative) Grover & Drossman 2009; Long & Drossman; 2010 Risk of long-term opioid therapy • Loss of efficacy over time • Cognitive impairment • Abnormal pain sensitivity (opioid • induced hyperalgesia) • • Aberrant drug-related behavior • • Addiction, abuse and diversion Constipation Abnormal immune function Alterations of the reproductive system (opioid-induced testosterone deficiency) • Increased risk of fracture Grunkenheimer 2007 Drossman Center There are safe ways to taper narcotics under appropriate medical care Narcotic Withdrawal Protocol Accept pain as real and treatable Elicit patients concerns/expectations Provide information through a dialog Present the withdrawal program Gauge the patient’s response Clonidine 0.1mg PO q 6 hrs. Lorazepam 1mg PO q 6hrs. TCA or SNRI Morphine equiv. Dose (mg) 220 200 180 160 140 120 100 80 60 40 20 0 PEG 3350 17g PO BID Physician – Patient Relationship Day of taper -3 -2 -1 0 1 2 3 4 5 6 7 Grunkemeier, DMS et al., Clin Gastroenterology and Hepatology 2007; 5:1126 8 9 10 . . . 21 1887 Abdominal Pain Scores 60 50 40 VAS (0-100) 30 20 10 0 Pre-detoxification Post-detoxification Stayed off narcotics Went back on narcotics n=39 n=37 n=13 n=10 Drossman DA et al. Am J Gastro 2012;107:1426 3 month follow-up 2574 Relationship of COMM Scores* to Detoxification and Responder Status 2 1.5 Successful Successful Detoxification detoxification p<0.06 Responder Responder p<0.02 Score 1 0.5 29 4 Yes No No. of subjects 20 12 Yes No 0 * = Higher COMM scores indicates greater drug abuse potential Drossman DA et al. Am J Gastro 2012;107:1426 2591 Pain Management: Other therapies • Exercise • Complimentary alternative medicine (CAM) – Acupuncture – Yoga – Massage – Meditation • Support groups Acupuncture • Postulated to have effects on acid secretion, GI motility and pain sensation via release of opiates in brain and body • Adults with IBS- no difference to sham procedure • Children with IBS or IBD- no support • Greater impact than placebo in children with chronic constipation Schneider Gut 2006; Lembo Am J Gastroenterol 2009; Broide Dig Dis Sci 2001 Summary Points • IBD is associated with psychopathology, functional pain, and maladaptive stress responses that increase morbidity, suffering, and costs. • Maximize treatment of underlying inflammation. • Integrated, personalized behavioral interventions to improve coping and decrease psychopathology can impact medical outcomes. • Pain medications as second line therapy • Better identification of risk factors for psychological stress can lead to prevention strategies. The Drossman Center for the Education and Practice of Biopsychosocial Care Focused on improving healthcare by improving doctor-patient communications. With the DrossmanCare training, healthcare providers learn how to better communicate with patients to improve satisfaction and clinical outcomes. www.drossmancenter.com drossmangastroenterology.com Augumentation Therapy ● Two different antidepressants ● Antidepressant + non-pharmacological Rx ● Antidepressant + atypical antipsychotic ● Antidepressant + anticholinergic ● Antidepressant + Pregabalin or Gabapentin Dynamicinterpersonal psycho Rx Cognitive behavioral Rx Hypnosis Antidepressants Nonpharmacologic Rx Symptomatic Rx Pharmacologic Rx Patient-physician Therapeutic relationship Sperber A and Drossman D, Alim Pharm Ther 2011;33:514 2458 Graded Multi-Component Treatment + Narcotic withdrawal Multidisciplinary approach Psychological treatments Central treatments Manage stress Gut treatments + Diet, lifestyle advice Positive diagnosis Explain, reassure Severe Moderate Mild T52