Neuropathic pain in Palliative Care

Transcription

1 Neuropathic pain in Palliative Care How do we treat it and do we really know what we are doing? Dr.med. Andreas Ebneter (H-FR and University Center for Palliative Care (PZ) nselspital), Prof. Dr.med. Steffen Eychmueller (PZ, nselspital), Based on CME-Course (nternal medicine ) on Neuropathic by Dr.med. A.Ebneter (H-FR Fribourg) and Dr.med. Boris Cantin (Palliative Care H-FR)) UC Zentrum für Palliative Care / Neuropathic Pain in Palliative Care, Dr. med. A. Ebneter 2 1

2 UC Zentrum für Palliative Care / Neuropathic Pain in Palliative Care, Dr. med. A. Ebneter 3 UC Zentrum für Palliative Care / Neuropathic Pain in Palliative Care, Dr. med. A. Ebneter 4 2

3 UC Zentrum für Palliative Care / Neuropathic Pain in Palliative Care, Dr. med. A. Ebneter 5 UC Zentrum für Palliative Care / Neuropathic Pain in Palliative Care, Dr. med. A. Ebneter 6 3

4 Opioids: - Almost always present as a first line analgesic. - Experience shows that they do work for neuropathic pain, but evidence is weak: - Do they work better in Palliative Care because most pain in our patients is of mixed origin?? - What is the role of (NSR/opioids) Tapentadol/Tramadol? (Palliative Care H.FR) Calcium channel blockers (α2-δ) Gabapentine ( ) Dosage Start with 100-(300)mg 3x/j pregabaline (Lyrica ) Dosage: Start with mg b.i.d ncrease of 100 à 300mg/ q1-7d max 3600mg/j devided t.i.d. Avantages Good evidence, few interaction Disadvantages: sedation, «dizziness», peripheral edema Renal excretion.. ncrease by 2x mg q7d Max. Dose 600mg/j. Avantages: Less pills to take, few intéraction. Anxiolytic effect. Disadvantage: Sédation, «dizziness» Renal excretion (Palliative Care H.FR) H-FR Fribourg

5 Tricyclics antidepressant Amitriptyline Dosage: 1x/j 25mg evening ncrease q3-7j by 25mg; max 150mg Avantages: Cheap, good evidence, facilitate sleep and improves psychie Nortriptyline Dosage: 1x j 10 mg /soir augmenter tous les 3-5 jours de 10 mg (dose max: 50 mg) Avantages: Less side effects (anticholinergic) Disadvantages (anticholinergic effect): Sedation, dry mouth;; urinary rentention, orthostasis Precautions: Cardiovasculare diseases, structural brain lesions (seizures), glaucoma Sounds good..but..: Cochrane 2015: Non unbiased evidence for OR against effect. (Palliative Care H.FR) H-FR Fribourg NSR Antidepressant DULOXETNE (cymbalta ) Dosage Start with 30 mg -> mg/d VENLAFAXNE (Effexor ) Dosage Start with 37,5mg -> mg/d Avantages Antidepressant and anxiolytique Avantages Antidepressant Disadvantage Nausea, dizziness Precautions Renal and hepatic insufficiency nteractions (Serotonergic syndrome!) Disadvantage Nausea Precautions Hepatic insufficiency nteractions (Serotonergic syndrome!) (Palliative Care H.FR) H-FR Fribourg

6 Local treatment: Who does use what? Topical lidocaine (Neurodol): Dosage: 1-3 Patch /d for max. 12h!! Avantages - Few systemic effect - Possible synergy with pregabaline Disadvantages - Local reaction Capsaicin(Qutenza) Dosage: 1 Patch for 30 min, (q90d!!) (WTH PRE-MEDCATON!!) Avantages - Few systemic effect Disadvantages - transient, severe local reaction (Premedication necessary!! - ONYL in specialized setting. - Expensive (Palliative Care H.FR) H-FR Fribourg nvasive treatment TENS/PENS - «Gate Control», does only work it "Gate" is working - Paroxystic reactions possible! Peripherical nerf block - no RCT, works well (for approx. 2 month) (anecdotic evidence) Sympathic ganglionary block Spinal (Epidural, intrathecal) Administration (Palliative Care H.FR) H-FR Fribourg

7 NMDA Antagonists Methadone - Opioid + Antg. NMDA - Use: 3 line opioid Avantages: Dual effect, few neurotoxicity, no actif metabolites Disadvantage: - Complex pharmacology, long- QT Ketamine -NMDA-Antagonist Avantages: pure NMDA antagonist - Possible effect on depression nconvénients: - Application i.v./s.c. - Psychotropic side effects - (Possible neurotoxicity) (Palliative Care H.FR) H-FR Fribourg Methadon: Proud Chicken or Smart Cowboy? 123rft.com Deviantart.com UC Zentrum für Palliative Care / Neuropathic Pain in Palliative Care, Dr. med. A. Ebneter 14 7

8 Methadon: Co-Analgesic or full rotation?? Co-Analgesic: - Methadon 3x mg /d as a adjuvant to an other opioid. - Evidence: - Small studies (N = 10-20) - Reduction of subjective pain intensity but not necessary total opioid dose - Expert opinion Advantages: - Outpatient titration and switch possible - Less stigma (co-analgesic) - Less reluctance to use from peers. Disavantages: - Mixture of opioids - No clear distintcion between primary opioid effect and Methadon - Complicated pharmacology Full Rotation - Edmonton Schema (Rotation over 3 days) («Chicken») - «Stop and go» («Cowboy») Advantages: - One drug = one pharmacokinetic - Stronger NMDA-Effect? Disavantages: - npatient setting often necessary - Good compliance necessary - Cardiac Side-effects? UC Zentrum für Palliative Care / Neuropathic Pain in Palliative Care, Dr. med. A. Ebneter 15 Key message Pain in Palliative Care is very often mixed Our experience is that anti-neurogenic Co- Analgesic do work but Hard- Evidence is moderate- weak UC Zentrum für Palliative Care / Neuropathic Pain in Palliative Care, Dr. med. A. Ebneter 16 8

9 Highest evidence Gabapentine Pregabalin Duoloxetine Venlafaxine Recommandation First line First line First line First line Amitryptiline (First line )? Moderate to weak evidence Capsaicin 8% patches Recommandation Second line ( peripherical pain) Lidocaine patches Tramadol (Palliative Care H.FR) H-FR Fribourg Second line ( peripherical pain) Second line Botulium Toxin A Thrid lin Adapté selon Finnerup et al, Lancet Neuro Choice of opioid is free (+/-) - Choice of co-analgesic clinical Clinical Anxiety Seizure risk Depression Abdominal pain/ ncreased secretion/ Depression (without cardiac or cerebral Comorbidities)/ Urge-bladder Well localized pain generalized, diffuse pain Mixed pain Co-Analgésique Pregabaline NSR (Duloxetine/Venlafaxine) Amitriptyline Lidocaine locale Methadon Ketamine UC Zentrum für Palliative Care / Neuropathic Pain in Palliative Care, Dr. med. A. Ebneter 18 9

10 bibliographie 1. Palliative Drugs [cited 2016; Available from: 2. Bhaskar, A. and R. Mittal, Local Therapies for Localised Neuropathic Pain. Rev Pain, (2): p Bourne, S., A.G. Machado, and S.J. Nagel, Basic anatomy and physiology of pain pathways. Neurosurg Clin N Am, (4): p Caddy, C., et al., Ketamine and other glutamate receptor modulators for depression in adults. Cochrane Database Syst Rev, 2015(9): p. Cd de Leon-Casasola, O.A. and V. Mayoral, The topical 5% lidocaine medicated plaster in localized neuropathic pain: a reappraisal of the clinical evidence. J Pain Res, : p Derry, S., et al., Nortriptyline for neuropathic pain in adults. Cochrane Database Syst Rev, : p. Cd Finnerup, N.B., et al., Pharmacotherapy for neuropathic pain in adults: a systematic review and meta-analysis. Lancet Neurol, (2): p Finnerup, N.B., et al., Neuropathic pain: an updated grading system for research and clinical practice. Pain, Gallagher, H.C., et al., Venlafaxine for neuropathic pain in adults. Cochrane Database Syst Rev, 2015(8): p. Cd Hirayama, Y., et al., Effect of duloxetine in Japanese patients with chemotherapy-induced peripheral neuropathy: a pilot randomized trial. nt J Clin Oncol, (5): p Jensen, T.S. and N.B. Finnerup, Allodynia and hyperalgesia in neuropathic pain: clinical manifestations and mechanisms. Lancet Neurol, (9): p Jensen, T.S., C.S. Madsen, and N.B. Finnerup, Pharmacology and treatment of neuropathic pains. Curr Opin Neurol, (5): p Klepstad, P., et al., Evidence of peripheral nerve blocks for cancer-related pain: a systematic review. Minerva Anestesiol, (7): p McKenna, M. and A.B. Nicholson, Use of methadone as a coanalgesic. J Pain Symptom Manage, (6): p. e McNicol, E.D., A. Midbari, and E. Eisenberg, Opioids for neuropathic pain. Cochrane Database Syst Rev, 2013(8): p. CD Moore, R.A., et al., Amitriptyline for neuropathic pain in adults. Cochrane Database Syst Rev, 2015(7): p. Cd Moore, R.A., et al., Gabapentin for chronic neuropathic pain and fibromyalgia in adults. Cochrane Database Syst Rev, 2014(4): p. Cd Murrough, J.W., et al., Antidepressant efficacy of ketamine in treatment-resistant major depression: a two-site randomized controlled trial. Am J Psychiatry, (10): p Reddy, A., S. Yennurajalingam, and E. Bruera, Dual opioid therapy using methadone as a coanalgesic. Expert Opin Drug Saf, (1): p Wallace, E., et al., Addition of methadone to another opioid in the management of moderate to severe cancer pain: a case series. J Palliat Med, (3): p Woolf, C.J. and R.J. Mannion, Neuropathic pain: aetiology, symptoms, mechanisms, and management. Lancet, (9168): p (Palliative Care H.FR) H-FR Fribourg