1. Adjuvant Pain Treatments Elizabeth Whiteman, M.D.

2. Goals and Objectives Understand the physiology of pain Assess for different causes of pain Pain in special populations Use of adjuvant drugs Non pharmacologic methods Non physical causes of pain

3. Adjuvant medications ▫Acetaminophen and non opioids ▫Anti-inflammatory ▫Antidepressants ▫Anti seizure medication ▫Anticholinergics ▫Local anesthetics ▫Corticosteroids ▫Other: calcitonin, bisphosphonates ▫Muscle relaxants ▫NMDA inhibitors

4. Adjuvant medications can be used alone or in conjunction with other pain medication (opioids) Medication can be titrated to pain relief and avoid side effects A patient may benefit most from adjuvants in pain symptoms more neuropathic or visceral

5. Case 1 Mary is a 60 year old female with a history of metastatic breast cancer. She has had increased pain in her Right flank, radiating around her chest. She is on Morphine SR 15mg BID. But the pain is getting worse. She describes it as sharp.

6. Differential Diagnosis? Bone metastasis spine Nerve impingement Herpes Zoster Localized bone metastasis Fracture

7. You examine her and there is no localized rash or blisters. She has hypersensitivity to touch but no localized pain. X ray is negative for rib fracture, shows osteopenic bone. MRI T spine shows Mets to her T spine and compression fracture with nerve impingement

8. Treatment options?

9. Acetaminophen Acetaminophen can be used for mild to moderate pain. 650mg-1000mg q6hr. Max dose 4000mg/24 Hr. Acetaminophen IV has been effective in immediate post op pain control. Only approved for Post op use now. Less need for narcotics.

10. Anti-inflammatories NSAIDS and Cox 2 inhibitors ▫Can be used for inflammation, bone pain and as an adjuvant to narcotics ▫Risk vs. benefit in thrombotic risk for CAD or CVA patients ▫Risk GI bleed or renal insufficiency, inhibit platelet aggregation ▫Poor choice for patients with poor PO intake and risk GI side effect. ▫Consider GI prophylaxis

11. Corticosteroids Often useful as adjuvant in pain control Bone metastasis Increased intracranial pressure Nerve impingement Acute internal inflammation (visceral pain) Also caution for GI bleed, glucose control and Altered mental status and delirium especially in elderly or patients with neurologic dysfunction

12. Antidepressants Tricyclic Antidepressants( amitryptiline, nortriptiline, desipramine) ▫For neuropathic pain ▫High side effects- Anticholinergic ▫Use with caution in elderly, often sedating SSRI’s, SNRI’s (venlafaxine, duloxetine) ▫Can be used as adjuvant medication ▫Duloxetine is approved for diabetic neuropathy (off label for post herpetic neuralgia)

13. Anticonvulsants Anti seizure medications ▫Carbamazepine, phenytoin  Monitor LFT  Monitor CBC with carbamezepine (risk aplastic anemia)  Risk for sedation ▫Pregabalin (lyrica)  Approved for diabetic neuropathy and post herpetic neuralgia  25-100mg tid dosing  Need to renal dose

14. Gabapentin Good results for neuropathic pain ▫Sharp shooting pain, numbness, burning Usual effective dose 900-3600mg/day in 3 divided doses Slow and gradual dose increase ▫100mg QD to start, increase by 100mg every 3-5 days as tolerated ▫100mg bid-100mg tid etc…

15. Anticonvulsant side effects Monitor for dizziness Altered mental status Lethargy Anorexia or nausea

16. Alpha-2 Receptor Agonists Clonidine- tablets, patch, epidural ▫Post op use showed decreased narcotic consumption ▫Increased time to next analgesic need ▫Risk of sedation and bradycardia, but no increased risk hypotension ▫Side effects dizziness, CNS depression, xerostomia ▫Rebound hypertension, withdraw gradually

17. Antispasm drugs May help in muscle spasm eg: MS, spinal cord injuries Muscle relaxants ▫May be helpful in muscle spasm  baclofen, carisoprodol, cyclobenzaprine, methocarbamol  Monitor for side effects: sedation, confusion Benzodiazepines ▫clonezepam, lorazepam, diezepam ▫Risk for sedation, confusion

18. NMDA Receptor Antagonists Methadone Ketamine ▫-Opioid sparing ▫Studies show reduced opioids need ▫Start 10-15mg q6hr PO or 0.04mg/hg/hr iv (max 0.3mg/kg/hr) ▫Side effects dizziness, hallucinations

19. Parental lidocaine  Can be an effective agent to treat severe pain especially when neuropathic and thus has potential to improve a patient’s quality of life  side effects are short lived (usually light- headedness, nausea, phlebitis at site of infusion) with no untoward long term effects  Use of opioid medications can often be reduced, minimizing their side effects  Start with a lidocaine bolus/loading dose, then start a continuous IV or SC infusion, the goal is the lowest dose possible that still controls the pain

20. Non Pharmacologic Strategies Topical anesthetics ▫Ice, heat,massage ▫Heated rubs (BenGay, icy hot etc.) ▫topical NSAID creams ▫Lidocaine Patch ▫Capsaicin cream

21. Non Pharmacologic Physical interventions ▫Heat/cold ▫Massage ▫Repositioning, bracing ▫Acupuncture/Acupressure ▫Physical therapy

22. Non pharmacologic Therapy Other ▫Relaxation Guided imagery Distraction ▫Cognitive therapy ▫Support group ▫Spiritual

23. Anticancer Therapies Radiation Chemotherapy Bisphosphonates ▫Pamidronate, zolendronate, ibandronate ▫Full benefit usually takes 7-14 days Surgery Radiopharmaceutical agents ▫Stronium 89

24. Calcitonin/ Bisphosphonates Calcitonin not recommended for pain relied in metastatic disease Bisphosphonates ▫reduce bone absorption and formation by inhibiting adhesion of tumor cells and inhibiting osteoclast function

25. Case Mary’s MRI had metastatic lesions in her ribs and t spine. Her pain is still not controlled on A PCA pump and she is very sleepy and delirious when her basal PCA is increased. Treatment options?? steroids bisphosphonates NSAIDS radiation treatment

26. After treatment with all the above Mary completes her radiation treatment in the hospital and pain is stable on MS Contin 60mg bid and Decadron 4mg po bid She is discharged to home on hospice and lives 2 more months with pain controlled.

27. References Chang VT, Jain S, Chau C, Update in cancer pain Syndromes, Journal of Palliative med 2006;9(6):1414-1434 Foley KM, Acute and Chronic cancer pain syndromes In: Doyle D, Hank GW, Cherney N et al. Oxford Textbook of Palliative medicine, 3 rd edition, New York, NY, Oxford University Press: 2005. Janjan N, Lutz S, Bedwinek J et al. Therapeutic Guidelines for the treatment of Bone Metastasis: A report from the American College of Radiology, Appropriateness Criteria Expert Panel, Journal of Palliative Medicine, 2009;12(5): 417-426.