VA/DoD CLINICAL PRACTICE GUIDELINES MayMay 2021 2021

The Management of Chronic Sidebar 1: Case Definition of CMI * Recommended interventions are not rank- ordered; consider interventions Multisymptom Illness (CMI) based on individual patient needs, goals, and preferences 1 Chronic Multisymptom Illness (CMI) is characterized by † There has been no new evidence since the 2014 CMI CPG to suggest any Patient presents with a spectrum of chronic symptoms not fully multiple, persistent symptoms (e.g., fatigue, headache, arthralgias, myalgias, concentration and attention problems, benefit for steroids, antivirals, or antibiotics. As such, the Work Group explained by other disorders and meeting the criteria for CMI recommends against using these agents to treat CMI and symptoms and gastrointestinal disorders) across more than one body (see Sidebar 1) consistent with ME/CFS. system. The symptoms must be present or frequently recur for 2 more than six months and should be severe enough to interfere Abbreviations: CBT: cognitive behavioral therapy; CIH: complementary and Build and maintain a therapeutic patient-provider alliance while with daily functioning. integrative health; CMI: chronic multisymptom illness; CPG: clinical practice conducting a thorough evaluation of symptoms and assess for guideline; DoD: Department of Defense; FMS: fibromyalgia; FODMAP: comorbid conditions (see Sidebar 2) ↑ Indicates a “Weak for” recommendation strength fermentable oligo- , di- , mono - saccharides, and polyols; IBS: irritable bowel ↓ Indicates a “Weak against” recommendation strength syndrome; ME/CFS: myalgic encephalomyelitis/chronic fatigue syndrome; 3 ↓↓ Indicates a “Strong against” recommendation strength Does CMI co-exist with another NSAID: nonsteroidal anti- inflammatory drug; PGB: pregabalin; QoL: quality of Yes ↔ Indicates a “Neither for nor against” recommendation strength diagnosis that may partially life; SNRI: serotonin- norepinephrine reuptake inhibitor; SSRI: selective # Indicates the treatment was not included in the CPG’s evidence review contribute to the symptoms? serotonin reuptake inhibitor; TCA: tricyclic antidepressant; VA: Department of Veterans Affairs No 4 5 Refer or treat co-occurring conditions as indicated using appropriate • Provide education on CMI and discuss the findings, evidence-based VA/DoD CPGs 10 impression, and evidence In addition to the treatments in Box 6: • Develop an individualized treatment plan based on patient’s • Consider emotion-focused therapy↑ needs, goals, and preferences (see Sidebar 3) • Consider psychodynamic therapies↔ ↔ 9 • Consider trial of TCAs or antispasmodics 6 Does patient present with • Consider trial of rifaximin for patients without significant constipation↑ Yes Initial treatments may include:* CMI and symptoms • Consider linaclotide or plecanatide for patients with constipation- ↑ • Offer CBT or mindfulness-based therapy consistent with IBS?* predominant IBS and who are not responsive to osmotic laxatives↑; ↓↓ • Avoid use of opioid medications for pain related to CMI for women only, consider lubiprostone↔ ↓↓ No • Avoid use of mifepristone • Consider trial of eluxadoline for patients with significant diarrhea who do not respond to a trial of anti-diarrheals or low-FODMAP diet↔ 7 Does patient present with CMI and No • Avoid alosetron and SSRIs for IBS symptoms↔ symptoms consistent with FMS?* Yes 8 11 12 In addition to the treatments in Box 6: Does patient present with In addition to the treatments in Box 6: Yes • Consider emotion-focused therapy↑ CMI and symptoms • Avoid corticosteroids, antivirals, or antibiotics • Consider yoga, tai chi, manual acupuncture, or physical consistent with ME/CFS?* • Avoid stimulants for fatigue symptoms↓↓ exercise↑ No • Consider a trial of SNRIs or PGB↑ • Avoid NSAIDs for chronic pain related to CMI↓ 13 Have symptoms, QoL, or 14 No Yes Continue individualized treatment plan and update function improved to patient as needed (see Sidebar 3) satisfaction? VA/DoD CLINICAL PRACTICE GUIDELINES MayMay 2021 2021

Sidebar 2: Elements of Assessment Non-pharmacologic Treatments for CMI Pharmacologic Agents for CMI • Obtain medical history and military/deployment history Treatment of CMI Agent Predominant Symptom • Conduct psychosocial assessment including psychological ↑ ↔ trauma history Cognitive behavioral therapy Escitalopram Global • Conduct physical examination • Acceptance- based behavior therapy Fluoxetine↔ Global, Pain • Consider diagnostic studies, as indicated, for rule - out of • Traditional cognitive behavioral therapy Sertraline↔ Global alternative diagnoses only; avoid any tests for which there may Mindfulness-based therapies↑ Paroxetine↔ Pain be limited additional benefit • Meditation awareness training Citalopram↔ Pain • Consider additional and/or longer duration encounters • Mindfulness- based cognitive therapy Venlafaxine Immediate-release↑ Global • Mindfulness-based stress reduction Venlafaxine Extended-release↑ Global ↔ Sidebar 3: Individualized Treatment Plan Treatment of CMI and symptoms consistent with IBS or FMS Mirtazapine Global Duloxetine↔ Pain • Using a whole/holistic health approach, identify individual Emotion-focused therapy↑ Duloxetine↑ Fatigue treatment goals (e.g., return to work, improved QoL, resumption • Attachment- based compassion therapy of recreational activities) Milnacipran↑ Pain, Fatigue • Emotional awareness and expression therapy • Describe treatment options and engage in shared decision Amitriptyline↔ Pain, Fatigue making discussion and shared goal setting in support of the Treatment of CMI and symptoms consistent with IBS Pregabalin↑ Pain individual’s aspiration and purpose for health and well - being Psychodynamic therapy↔ IBS, moderate to severe • Maximize use of non- pharmacologic therapies (e.g., CBT, CIH Rifaximin↑ Low-FODMAP diet# without constipation interventions, ‡ aerobic exercise) IBS with constipation in • Develop personal health plan and timeline for follow - up and Treatment of CMI and symptoms consistent with FMS Lubiprostone↔ women >18 years old monitor progress toward personal goals Aerobic exercise↑ • Maintain continuity and caring relationship via in - person and/or Linaclotide↑ IBS with constipation Manual acupuncture↑ virtual modalities Plecanatide↑ IBS with constipation Tai chi↑ • Provide education (both for improved health literacy and Eluxadoline↔ IBS with diarrhea whole/holistic health self- care) and engage Yoga↑ families/caregiver/support person, if available • Refer to CPG and algorithm for relative usage and timing of • Based on patient needs, consider referral to case manager and • Refer to CPG for descriptions of behavioral health interventions. therapies establish interprofessional care team • Refer to current product information for additional prescribing ↑ Indicates a “Weak for” recommendation strength information ‡ See https://www.va.gov/wholehealth/ ↓ Indicates a “Weak against” recommendation strength ↓↓ Indicates a “Strong against” recommendation strength ↔ Indicates a “Neither for nor against” recommendation strength Access to the full guideline and additional resources # Indicates the treatment was not included in the CPG’s evidence review are available at the following link: https://www.healthquality.va.gov/guidelines/mr/cmi/