SUPPLEMENT ARTICLE
Recommendations for the Pharmacological Management of Neuropathic Pain: An Overview and Literature Update

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The Neuropathic Pain Special Interest Group of the International Association for the Study of Pain recently sponsored the development of evidence-based guidelines for the pharmacological treatment of neuropathic pain. Tricyclic antidepressants, dual reuptake inhibitors of serotonin and norepinephrine, calcium channel α2-δ ligands (ie, gabapentin and pregabalin), and topical lidocaine were recommended as first-line treatment options on the basis of the results of randomized clinical trials. Opioid analgesics and tramadol were recommended as second-line treatments that can be considered for first-line use in certain clinical circumstances. Results of several recent clinical trials have become available since the development of these guidelines. These studies have examined botulinum toxin, high-concentration capsaicin patch, lacosamide, selective serotonin reuptake inhibitors, and combination therapies in various neuropathic pain conditions. The increasing number of negative clinical trials of pharmacological treatments for neuropathic pain and ambiguities in the interpretation of these negative trials must also be considered in developing treatment guidelines. The objectives of the current article are to review the Neuropathic Pain Special Interest Group guidelines for the pharmacological management of neuropathic pain and to provide a brief overview of these recent studies.

Section snippets

GUIDELINES FOR THE PHARMACOLOGICAL MANAGEMENT OF NP

The NeuPSIG guidelines recommend medications as first-line treatment if efficacy in NP has been established in multiple RCTs (Oxford Centre for Evidence-based Medicine grade A recommendation18), and these results are consistent with the authors' clinical experience; as second-line if efficacy in NP has been established in multiple RCTs (grade A recommendation), but there were reservations about the use of the medication relative to the first-line medications based on the authors' clinical

RECENT CLINICAL TRIALS

In this section, we briefly discuss several recent RCTs that should be considered in future efforts to revise the treatment guidelines summarized herein. These studies do not represent a comprehensive update of recent NP trials but rather have been selected because they involve novel treatments or provocative issues.

NEGATIVE TRIALS OF PHARMACOLOGICAL TREATMENTS FOR NP AND THEIR INTERPRETATION

An increasing number of RCTs have failed to show significant differences in primary efficacy analyses comparing groups treated with a medication for NP and placebo, despite previous preclinical and clinical studies suggesting that efficacy would be expected.71, 72, 73, 74, 75, 76, 77 It is unclear whether these results reflect a true lack of efficacy in the specific conditions studied or whether other factors have accounted for the lack of success in demonstrating efficacy (eg, inadequate power

CONCLUSION

Diverse pharmacological treatments of NP have become available, and interpreting the data on their efficacy and safety involves substantial complexities and ambiguities. In updating the NeuPSIG pharmacological guidelines for the management of NP, a multifactorial evaluation will be required that carefully considers the clinical importance of the improvements shown by patients and the benefits and risks of each treatment in view of the other available treatments for NP95, 96, 97 (Table 3). In

Acknowledgments

We thank Paul J. Lambiase for coordinating the meeting on which this supplement is based.

REFERENCES (113)

  • MC Rowbotham et al.

    Venlafaxine extended release in the treatment of painful diabetic neuropathy: a double-blind, placebo-controlled study

    Pain

    (2004)
  • BR Stacey et al.

    Pregabalin for postherpetic neuralgia: placebo-controlled trial of fixed and flexible dosing regimens on allodynia and time to onset of pain relief

    J Pain

    (2008)
  • J Højsted et al.

    Addiction to opioids in chronic pain patients: a literature review

    Eur J Pain

    (2007)
  • JH Vranken et al.

    Pregabalin in patients with central neuropathic pain: a randomized, double-blind, placebo-controlled trial of a flexible-dose regimen

    Pain

    (2008)
  • AB O'Connor et al.

    Pain associated with multiple sclerosis: systematic review and proposed classification

    Pain

    (2008)
  • V Tugnoli et al.

    Botulinum toxin type A reduces capsaicin-evoked pain and neurogenic vasodilatation in human skin

    Pain

    (2007)
  • M Backonja et al.

    NGX-4010, a high-concentration capsaicin patch, for the treatment of postherpetic neuralgia: a randomised, double-blind study

    Lancet Neurol

    (2008)
  • A Shaibani et al.

    Lacosamide in painful diabetic neuropathy: an 18-week double-blind placebo-controlled trial

    J Pain

    (2009)
  • A Shaibani et al.

    Long-term oral lacosamide in painful diabetic neuropathy: a two-year open-label extension trial

    Eur J Pain

    (2009)
  • SH Sindrup et al.

    The selective serotonin reuptake inhibitor paroxetine is effective in the treatment of diabetic neuropathy symptoms

    Pain

    (1990)
  • M Otto et al.

    Escitalopram in painful polyneuropathy: a randomized, placebo-controlled, cross-over trial

    Pain

    (2008)
  • M Hanna et al.

    Prolonged-release oxycodone enhances the effects of existing gabapentin therapy in painful diabetic neuropathy patients

    Eur J Pain

    (2008)
  • I Gilron et al.

    Nortriptyline and gabapentin, alone and in combination for neuropathic pain: a double-blind, randomised controlled crossover trial

    Lancet

    (2009)
  • RP Agrawal et al.

    Management of diabetic neuropathy by sodium valproate and glyceryl trinitrate spray: a prospective double-blind randomized placebo-controlled study

    Diabetes Res Clin Pract

    (2009)
  • S Khoromi et al.

    Morphine, nortriptyline and their combination vs. placebo in patients with chronic lumbar root pain

    Pain

    (2007)
  • B Breuer et al.

    A randomized, double-blind, placebo-controlled, two-period, crossover, pilot trial of lamotrigine in patients with central pain due to multiple sclerosis

    Clin Ther

    (2007)
  • M Silver et al.

    Double-blind, placebo-controlled trial of lamotrigine in combination with other medications for neuropathic pain

    J Pain Symptom Manage

    (2007)
  • AI Vinik et al.

    Lamotrigine for treatment of pain associated with diabetic neuropathy: results of two randomized double-blind, placebo-controlled studies

    Pain

    (2007)
  • ASC Rice et al.

    Animal models and the prediction of efficacy in clinical trials of analgesic drugs: a critical appraisal and call for uniform reporting standards

    Pain

    (2008)
  • PT Hansson et al.

    Pharmacological treatment of peripheral neuropathic conditions based on shared commonalities despite multiple etiologies

    Pain

    (2005)
  • JE Hammack et al.

    Phase III evaluation of nortriptyline for alleviation of symptoms of cis-platinum-induced peripheral neuropathy

    Pain

    (2002)
  • AL Kautio et al.

    Amitriptyline in the treatment of chemotherapy-induced neuropathic symptoms

    J Pain Symptom Manage

    (2008)
  • S Khoromi et al.

    Topiramate in chronic lumbar radicular pain

    J Pain

    (2005)
  • SN Quessy et al.

    Placebo response in neuropathic pain trials

    Pain

    (2008)
  • RH Dworkin et al.

    Interpreting the clinical importance of treatment outcomes in chronic pain clinical trials: IMMPACT recommendations

    J Pain

    (2008)
  • RH Dworkin et al.

    Interpreting the clinical importance of group differences in chronic pain clinical trials: IMMPACT recommendations

    Pain

    (2009)
  • RD Treede et al.

    Neuropathic pain: redefinition and a grading system for clinical research purposes

    Neurology

    (2008)
  • MP Jensen et al.

    The impact of neuropathic pain on health-related quality of life: review and implications

    Neurology

    (2007)
  • AB O'Connor

    Neuropathic pain: a review of the quality of life impact, costs, and cost-effectiveness of therapy

    Pharmacoeconomics

    (2009)
  • RH Dworkin et al.

    Health care costs of acute and chronic pain associated with a diagnosis of herpes zoster

    J Am Geriatr Soc

    (2007)
  • Dworkin RH, Malone DC, Panarites CJ, Armstrong EP, Pham SV. Impact of postherpetic neuralgia and painful diabetic...
  • L Donaldson Sir

    The 2008 report of the Chief Medical Officer:150 years of the Annual Report of the Chief Medical Officer: on the state of public health 2008

    (2009)
  • N Attal et al.

    EFNS guidelines on pharmacological treatment of neuropathic pain

    Eur J Neurol

    (2006)
  • DE Moulin et al.

    Pharmacological management of chronic neuropathic pain—consensus statement and guidelines from the Canadian Pain Society

    Pain Res Manag

    (2007)
  • CEBM Centre for Evidence-based Medicine

    CEBM Web site. Levels of evidence and grades of recommendation

  • G Cruccu et al.

    AAN-EFNS guidelines on trigeminal neuralgia management

    Eur J Neurol

    (2008)
  • G Gronseth et al.

    Practice parameter: the diagnostic evaluation and treatment of trigeminal neuralgia (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology and the European Federation of Neurological Societies

    Neurology

    (2008)
  • MB Max et al.

    Amitriptyline relieves diabetic neuropathy pain in patients with normal or depressed mood

    Neurology

    (1987)
  • J Raskin et al.

    Duloxetine versus routine care in the long-term management of diabetic peripheral neuropathic pain

    J Palliat Med

    (2006)
  • J Wernicke et al.

    An evaluation of the cardiovascular safety profile of duloxetine: findings from 42 placebo-controlled studies

    Drug Saf

    (2007)
  • Cited by (0)

    Support for the meeting on which this article is based and article preparation was provided by an unrestricted grant from Endo Pharmaceuticals to the University of Rochester Office of Continuing Professional Education, from which all authors received honoraria for their participation. Individual disclosures can be found on page S11.

    Individual Disclosures for Authors: Dr Dworkin has received in the past 12 months research support from Arcion, Montel Williams Foundation, and NeurogesX and consulting fees from Allergan, Astellas, AstraZeneca, Boehringer Ingelheim, Durect, Eisai, Endo Pharmaceuticals, Epicept, Forest, Genzyme, Johnson & Johnson, Eli Lilly, Michael J. Fox Foundation for Parkinson's Research, NeurogesX, Nuvo, Pfizer, PainReform, Philips Respironics, Sanofi Aventis, Solace, Solvay, Spinifex, UCB Pharma, US Department of Veterans Affairs, US National Institutes of Health, Wyeth, and Xenon; Dr O'Connor has no financial arrangement or affiliation with a corporate organization or a manfacturer of a product discussed in this supplement; Dr Audette has served on the speakers' bureau for Allergan, Endo Pharmaceuticals, and Johnson & Johnson; Dr Baron has received grant/research support from Pfizer Pharma, Genzyme, and Grünenthal and has served on the speakers' bureau and as a consultant for Pfizer Pharma, Genzyme, Grünenthal, Mundipharma, Allergan, Sanofi Pasteur, Astellas, Eisai, Medtronic, USB, and Eli Lilly; Dr. Gourlay has no financial arrangement or affiliation with a corporate organization or a manfacturer of a product discussed in this supplement; Dr Haanpää has served as consultant for Boehringer Ingelheim, GlaxoSmithKline, Eli Lilly, Medtronic, MSD, Mundipharma, Orion, Pfizer, and Sanofi Pasteur and is a permanent assessor of EMEA; Dr Kent has received grant/research support from GlaxoSmithKline and has served on the speakers' bureau for Medtronic; Dr Krane has no financial arrangement or affiliation with a corporate organization or a manfacturer of a product discussed in this supplement; Dr LeBel has no financial arrangement or affiliation with a corporate organization or a manfacturer of a product discussed in this supplement; Dr Levy has received grant/research support from St. Jude Medical Neuromodulation, has served as a consultant for Bioness, Codman, Medtronic, St Jude Medical Neuromodulation, and Stryker; Dr Mackey has no financial arrangement or affiliation with a corporate organization or a manfacturer of a product discussed in this supplement; Dr Mayer has received grant/research support from Johnson & Johnson and is on the Clinical Advisory Board for Palladian Health; Dr Miaskowski has no financial arrangement or affiliation with a corporate organization or a manfacturer of a product discussed in this supplement; Dr Raja has received grant/research support from Allergan and Medtronic and served as a consultant for Allergan, Alpharma (King), Schering-Plough, and Solvay; Dr Rice has received grant/research support from Pfizer and Spinifex and has served as a consultant for Pfizer, Allergen, Astellas, Daiichi Sankyo, GlaxoSmithKline, NeurogesX, Spinifex, and Eisia; Dr Schmader has received grant/research support from Merck and Wyeth and has served as a consultant for Merck and GlaxoSmithKline; Dr Stacey has received grant/research support from AstraZeneca and has served as a consultant for GlaxoSmithKline, Boehringer Ingelheim, Boston Scientific, Eli Lilly, Niktar, QRX Pharma, Pfizer, AstraZeneca, and Xenon; Dr Stanos has received grant/research support from Ortho-McNeil; has served as a consultant for Abbott Labs, Eli Lilly, Endo Pharmaceuticals, King, and Ortho-McNeil; and is on the speakers' bureau for Endo Pharmaceuticals, Eli Lilly, Ortho-McNeil, Pfizer, King, and Forest; Dr Treede has received grant/research support from Kade and Boehringer Ingelheim and has served as a consultant for Grünenthal, UCB, AWD pharma, GmbH & Co, and Kade; Dr Turk has received grant/research support from Endo Pharmaceuticals, Johnson & Johnson, and Philips Respironics and has served as a consultant for Eli Lilly, Johnson & Johnson, Philips Respironics, and SK Lifescience; Dr Walco has served as a consultant for Neuromed, Pfizer, and Purdue Pharma; Dr Wells has served as a consultant for Prostrachan and is on the speakers' bureau for Grünenthal, Napp (Purdue in the United States), and Pfizer.

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