European Federation of Neurological Societies

1. European Federation of Neurological Societies EFNS Guidelines for medical treatment of neuropathic pain. Revised 2009. G. CRUCCU EFNS Secretariat, Vienna Dept. Neurological Sciences, Rome

2. EFNS guidelines on pharmacological treatment of neuropathic pain Attal et al. Eur J Neurol 2006

3. EFNS guidelines evidence/recommendations

4. Q-o-L and comorbidities In all trials, pain relief is always the primary endpoint. But in clinical practice our goal is to give the patient a decent life. Hence we do recommend to evaluate treatments for they effect on global change, sleep, mood, functional capacity, and quality-of-life (QoL). Quality of life scales: Nottingham Health Profile and SF-36

5. Quality of Life, Mood, Sleep 8 1 2 1 4 Positive Negative 1

6. Safety Concerns TCA Antidepressant Besides the typical contraindications regarding glaucoma and prostatic hypertrophy, an association between TCA treatment and sudden cardiac death has raised concern; a recent epidemiological study found a slight increase in sudden cardiac death with high-dose TCA (Ray et al. 2004). Therefore caution is recommended for older patients, particularly those with cardiovascular risk factors.

7. Safety Concerns Opioids Although in RCTs on neuropathic pain, the side effect profile of opioids was good, less than 20 % of patients continue with opioids after one year, because of an unfavourable balance between side effects and efficacy (class I SR: Attal 2000). According to recent European recommendations, opioids should be considered for chronic non-cancer pain as second line, if other reasonable therapies fail to provide adequate analgesia (Kalso et al 2003).

8. How many patients do get a decent pain relief in the various pain conditions? Pharmacological management of neuropathic pain remains a challenge despite the availability of new treatments, while no single treatment is appropriate for all neuropathic pain conditions. Recent systematic reviews identified that only a proportion of neuropathic pain patients obtain successful pain relief (30-50%) with conventional medical management. Finnerup NB, Otto M, McQuay HJ, et al. Pain 2005; Attal N, Cruccu G, Haanpää M, et al. Eur J Neurol 2006;

9. Diagrams of Reliability / Effective Gain Low Reliability High efficacy BEST High Reliability Low efficacy WORST

10. Data from 91 double-blind RCTs across 7454 patients. Cruccu & Taylor: Pain Pract 2007

11. EFNS guidelines evidence/recommendations

12. EFNS guidelines on pharmacological treatment of neuropathic pain. Revised 2009. N Attal, R Baron, G Cruccu, M Haanpää, P Hansson, TS Jensen, T Nurmikko EFNS Panel Neuropathic Pain. Centre d'Evaluation et de Traitement de la Douleur, Hôpital Ambroise Paré, Université Versailles-Saint-Quentin, France. Division of Neurological Pain Research and Therapy, Department of Neurology, Universitatsklinikum Schleswig-Holstein, Kiel, Germany. Department of Neurological Sciences, La Sapienza University, Rome, Italy. Departments of Anaesthesiology and Neurosurgery, Pain Clinic, Helsinki University Hospital, Helsinki, Finland. Clinical Pain Research and Pain Center, Department of Neurosurgery, Karolinska Institute, University Hospital, Stockholm, Sweden. Dept. of Neurology and Danish Pain Research Center, Aarhus University Hospital, Aarhus, Denmark. Pain Research Institute, Division of Neurological Science, University of Liverpool, UK

14. Treatments are presented in alphabetical order. Drugs marked with an asterix were found effective in single center class II or III studies and are not recommended. Drugs marked with two asterixes are not (yet) available for use.

15. Treatments are presented in alphabetical order. Drugs marked with an asterix were found effective in single center class II or III studies and are not recommended. Drugs marked with two asterixes are not (yet) available for use.

16. Important questions that the new guidelines were expected to face • Opioids: yes or not? • Classic antiepileptics are really effective? • When and which polytherapy

17. Thank you for your attention

18. Oppioidi: sì o no? • L’obiezione principale (effetti a lungo termine) è stata fino ad ora affrontata in modo adeguato solo per l’ossicodone. Uno studio di registrazione di 36 mesi in 233 pazienti ha dimostrato che con ossicodone a rilascio controllato (dose media 52 mg): • la richiesta di incremento dose si stabilizzava mediamente al 10% dopo un anno • il 2.6% dei pazienti sviluppava abuso/dipendenza nel corso dei 3 anni Portenoy et al: Clin J Pain 2007

19. Antiepilettici nel dolore neuropatico • Tranne per la comprovata efficacia di carbamazepina e oxcarbazepina nella nevralgia trigeminale, • Topiramato, lamotrigina e oxcarbazepina sono risultati insufficientemente efficaci nelle polineuropatie dolorose • Una esauriente revisione Cochrane conclude che lamotrigina è inefficace nel dolore in generale Cruccu: Curr Opin Neurol 2007; Wiffen Rees: Cochrane Database Syst Rev 2007; Cruccu et al: Eur J Neurol 2008; Finnerup et al. MedGenMed 2008.

20. Politerapia • Da un lato la maggior parte dei medici che si occupa di dolore cronico ricorre alla politerapia molto spesso, dall’altro gli studi controllati sono pochissimi • Questi riguardavano solo gabapentin in associazione con morfina o venlafaxina • Fortunatamente siamo riusciti a sensibilizzare l’industria e sono iniziati una serie di studi controllati circa le principali associazioni. • Per ora sono stati pubblicati due studi controllati circa l’associazione tra ossicodone con pregabalin e con gabapentin (che ne dimostrano i vantaggi), ma altri importanti studi sono in corso (su Lancet è in pubblicazione lo studio TCA + GBP e sta per partire lo studio PGB + DUL) Hanna et al. Eur J Pain 2008; Gatti et al, Eur Neurol 2009; Gilron et al, Lancet, in press