Antiepileptic drugs for neuropathic pain and fibromyalgia - an overview of Cochrane reviews.

BACKGROUND Antiepileptic drugs have been used for treating different types of neuropathic pain, and sometimes fibromyalgia. Our understanding of quality standards in chronic pain trials has improved to include new sources of potential bias. Individual Cochrane reviews using these new standards have assessed individual antiepileptic drugs. An early review from this group, originally published in 1998, was titled 'Anticonvulsants for acute and chronic pain'. This overview now covers the neuropathic pain aspect of that original review, which was withdrawn in 2009. OBJECTIVES To provide an overview of the relative analgesic efficacy of antiepileptic drugs that have been compared with placebo in neuropathic pain and fibromyalgia, and to report on adverse events associated with their use. METHODS We included reviews published in theCochrane Database of Systematic Reviews up to August 2013 (Issue 7). We extracted information from each review on measures of efficacy and harm, and methodological details concerning the number of participants, the duration of studies, and the imputation methods used, in order to judge potential biases in available data.We analysed efficacy data for each painful condition in three tiers, according to outcome and freedom from known sources of bias. The first tier met current best standards - at least 50% pain intensity reduction over baseline (or its equivalent), without the use of last observation carried forward (LOCF) for dropouts, an intention-to-treat (ITT) analysis, in parallel group studies with at least 200 participants lasting eight weeks or more. The second tier used data from at least 200 participants where one or more of the above conditions were not met. The third tier of evidence related to data from fewer than 200 participants, or with several important methodological problems that limited interpretation. MAIN RESULTS No studies reported top tier results.For gabapentin and pregabalin only we found reasonably good second tier evidence for efficacy in painful diabetic neuropathy and postherpetic neuralgia. In addition, for pregabalin, we found evidence of efficacy in central neuropathic pain and fibromyalgia. Point estimates of numbers needed to treat for an additional beneficial effect (NNTs) were in the range of 4 to 10 for the important outcome of pain intensity reduction over baseline of 50% or more.For other antiepileptic drugs there was no evidence (clonazepam, phenytoin), so little evidence that no sensible judgement could be made about efficacy (valproic acid), low quality evidence likely to be subject to a number of biases overestimating efficacy (carbamazepine), or reasonable quality evidence indicating little or no effect (lamotrigine, oxcarbazepine, topiramate). Lacosamide recorded such a trivial statistical superiority over placebo that it was unreliable to conclude that it had any efficacy where there was possible substantial bias.Any benefits of treatment came with a high risk of adverse events and withdrawal because of adverse events, but serious adverse events were not significantly raised, except with oxcarbazepine. AUTHORS' CONCLUSIONS Clinical trial evidence supported the use of only gabapentin and pregabalin in some neuropathic pain conditions (painful diabetic neuropathy, postherpetic neuralgia, and central neuropathic pain) and fibromyalgia. Only a minority of people achieved acceptably good pain relief with either drug, but it is known that quality of life and function improved markedly with the outcome of at least 50% pain intensity reduction. For other antiepileptic drugs there was no evidence, insufficient evidence, or evidence of a lack of effect; this included carbamazepine. Evidence from clinical practice and experience is that some patients can achieve good results with antiepileptics other than gabapentin or pregabalin.There is no firm evidence to answer the important pragmatic questions about which patients should have which drug, and in which order the drugs should be used. There is a clinical effectiveness research agenda to provide evidence about strategies rather than interventions, to produce the overall best results in a population, in the shortest time, and at the lowest cost to healthcare providers.

[1]  S. Straube,et al.  The Costs and Consequences of Adequately Managed Chronic Non‐Cancer Pain and Chronic Neuropathic Pain , 2014, Pain practice : the official journal of World Institute of Pain.

[2]  A. Oaklander,et al.  Objective evidence that small-fiber polyneuropathy underlies some illnesses currently labeled as fibromyalgia , 2013, PAIN®.

[3]  N. Puri,et al.  WITHDRAWN: Topical lidocaine for the treatment of postherpetic neuralgia. , 2013, The Cochrane database of systematic reviews.

[4]  P. Wiffen,et al.  Topiramate for neuropathic pain and fibromyalgia in adults. , 2013, The Cochrane database of systematic reviews.

[5]  R. Palmer,et al.  Continuing efficacy of milnacipran following long-term treatment in fibromyalgia: a randomized trial , 2013, Arthritis Research & Therapy.

[6]  P. Wiffen,et al.  Challenges in design and interpretation of chronic pain trials. , 2013, British journal of anaesthesia.

[7]  C. Cooper,et al.  Neuropathic features of joint pain: a community-based study. , 2013, Arthritis and rheumatism.

[8]  D. Aldington,et al.  Amitriptyline for neuropathic pain and fibromyalgia in adults. , 2013, The Cochrane database of systematic reviews.

[9]  T. Tölle,et al.  Duloxetine use in chronic painful conditions – individual patient data responder analysis , 2013, European journal of pain.

[10]  Daniel Zeller,et al.  Small fibre pathology in patients with fibromyalgia syndrome. , 2013, Brain : a journal of neurology.

[11]  E. Kalso,et al.  Expect analgesic failure; pursue analgesic success , 2013, BMJ.

[12]  S. Straube,et al.  Pain measures and cut‐offs – ‘no worse than mild pain’ as a simple, universal outcome , 2013, Anaesthesia.

[13]  Z. Gabriel,et al.  An observational descriptive study of the epidemiology and treatment of neuropathic pain in a UK general population , 2013, BMC Family Practice.

[14]  R. Moore,et al.  Topical capsaicin (low concentration) for chronic neuropathic pain in adults. , 2012, The Cochrane database of systematic reviews.

[15]  P. Wiffen,et al.  COMBINATION PHARMACOTHERAPY FOR THE TREATMENT OF NEUROPATHIC PAIN IN ADULTS , 2012, The Cochrane database of systematic reviews.

[16]  R. Moore,et al.  Phenytoin for neuropathic pain and fibromyalgia in adults. , 2012, The Cochrane database of systematic reviews.

[17]  P. Wiffen CLONAZEPAM FOR NEUROPATHIC PAIN AND FIBROMYALGIA IN ADULTS , 2012, The Cochrane database of systematic reviews.

[18]  R. Dworkin,et al.  Is treatment of postherpetic neuralgia in the community consistent with evidence-based recommendations? , 2012, PAIN®.

[19]  A. Bhigjee,et al.  Clinical practice guidelines for management of neuropathic pain: expert panel recommendations for South Africa , 2012, South African medical journal = Suid-Afrikaanse tydskrif vir geneeskunde.

[20]  R. Moore,et al.  SUMATRIPTAN (ORAL ROUTE OF ADMINISTRATION) FOR ACUTE MIGRAINE ATTACKS IN ADULTS , 2012, The Cochrane database of systematic reviews.

[21]  C. Eccleston,et al.  Estimate at your peril: Imputation methods for patient withdrawal can bias efficacy outcomes in chronic pain trials using responder analyses , 2012, PAIN.

[22]  P. Wiffen,et al.  Valproic acid and sodium valproate for neuropathic pain and fibromyalgia in adults. , 2011, The Cochrane database of systematic reviews.

[23]  E. Kalso,et al.  A new definition of neuropathic pain , 2011, PAIN®.

[24]  M. Perloff,et al.  Anorgasmia with gabapentin may be common in older patients. , 2011, The American journal of geriatric pharmacotherapy.

[25]  R. Baron,et al.  Fibromyalgia and neuropathic pain - differences and similarities. A comparison of 3057 patients with diabetic painful neuropathy and fibromyalgia , 2011, BMC neurology.

[26]  G. Zaccara,et al.  The adverse event profile of pregabalin: A systematic review and meta‐analysis of randomized controlled trials , 2011, Epilepsia.

[27]  P. Wiffen,et al.  Gabapentin for chronic neuropathic pain and fibromyalgia in adults. , 2011, The Cochrane database of systematic reviews.

[28]  P. Wiffen,et al.  Lamotrigine for acute and chronic pain. , 2011, The Cochrane database of systematic reviews.

[29]  P. Wiffen,et al.  Carbamazepine for acute and chronic pain in adults. , 2011, The Cochrane database of systematic reviews.

[30]  A. Rice,et al.  Pharmacological Treatment of Painful HIV-Associated Sensory Neuropathy: A Systematic Review and Meta-Analysis of Randomised Controlled Trials , 2010, PloS one.

[31]  G. Zlateva,et al.  Evaluation of the safety and efficacy of pregabalin in older patients with neuropathic pain: results from a pooled analysis of 11 clinical studies , 2010, BMC family practice.

[32]  F. Barrantes,et al.  The Anticonvulsive Drug Lamotrigine Blocks Neuronal α4β2 Nicotinic Acetylcholine Receptors , 2010, Journal of Pharmacology and Experimental Therapeutics.

[33]  C. Eccleston,et al.  “Evidence” in chronic pain – establishing best practice in the reporting of systematic reviews , 2010, PAIN.

[34]  T. Nurmikko,et al.  EFNS guidelines on the pharmacological treatment of neuropathic pain: 2010 revision , 2010, European journal of neurology.

[35]  Douglas G Altman,et al.  Small study effects in meta-analyses of osteoarthritis trials: meta-epidemiological study , 2010, BMJ : British Medical Journal.

[36]  S. Straube,et al.  Pregabalin in fibromyalgia - responder analysis from individual patient data , 2010, BMC musculoskeletal disorders.

[37]  S. Straube,et al.  Fibromyalgia: Moderate and substantial pain intensity reduction predicts improvement in other outcomes and substantial quality of life gain , 2010, PAIN®.

[38]  M. Rowbotham,et al.  Clinical effectiveness: An approach to clinical trial design more relevant to clinical practice, acknowledging the importance of individual differences , 2010, PAIN®.

[39]  F. Wolfe,et al.  The American College of Rheumatology Preliminary Diagnostic Criteria for Fibromyalgia and Measurement of Symptom Severity , 2010, Arthritis care & research.

[40]  Jose Alvir,et al.  How do changes in pain severity levels correspond to changes in health status and function in patients with painful diabetic peripheral neuropathy? , 2010, PAIN®.

[41]  T. Alsaadi,et al.  Guidelines for the Pharmacological Treatment of Peripheral Neuropathic Pain: Expert Panel Recommendations for the Middle East Region , 2010, The Journal of international medical research.

[42]  A. Jadad,et al.  Anticonvulsant drugs for acute and chronic pain. , 2010, The Cochrane database of systematic reviews.

[43]  A. Jadad,et al.  Anticonvulsant drugs for acute and chronic pain. , 2010, The Cochrane database of systematic reviews.

[44]  Yuan-Tsong Chen,et al.  Genetic predisposition of life-threatening antiepileptic-induced skin reactions , 2010, Expert opinion on drug safety.

[45]  J. Dieleman,et al.  Incidence of facial pain in the general population , 2009, PAIN®.

[46]  Stephen J. Smith,et al.  Gabapentin Receptor α2δ-1 Is a Neuronal Thrombospondin Receptor Responsible for Excitatory CNS Synaptogenesis , 2009, Cell.

[47]  R. Hughes,et al.  Duloxetine for treating painful neuropathy or chronic pain. , 2009, The Cochrane database of systematic reviews.

[48]  R. Dworkin,et al.  Treatment of neuropathic pain: an overview of recent guidelines. , 2009, The American journal of medicine.

[49]  P. Wiffen,et al.  Pregabalin for acute and chronic pain in adults. , 2009, The Cochrane database of systematic reviews.

[50]  A. Beydoun,et al.  Lacosamide: pharmacology, mechanisms of action and pooled efficacy and safety data in partial-onset seizures , 2009, Expert review of neurotherapeutics.

[51]  S. Straube,et al.  Enriched enrollment: definition and effects of enrichment and dose in trials of pregabalin and gabapentin in neuropathic pain. A systematic review. , 2008, British journal of clinical pharmacology.

[52]  R. Moore,et al.  Duloxetine for painful diabetic neuropathy and fibromyalgia pain: systematic review of randomised trials , 2008, BMC neurology.

[53]  B. Laurent,et al.  Prevalence of chronic pain with neuropathic characteristics in the general population , 2008, PAIN.

[54]  F. Petzke,et al.  Medikamentöse Therapie des Fibromyalgiesyndroms , 2008, Der Schmerz.

[55]  D. Carroll,et al.  Primary care incidence and treatment of four neuropathic pain conditions: A descriptive study, 2002–2005 , 2008, BMC family practice.

[56]  J. Dostrovsky,et al.  Neuropathic pain , 2008, Neurology.

[57]  R. Moore,et al.  Enriched enrolment with randomised withdrawal (EERW): Time for a new look at clinical trial design in chronic pain , 2008, PAIN.

[58]  G. Lees,et al.  The Investigational Anticonvulsant Lacosamide Selectively Enhances Slow Inactivation of Voltage-Gated Sodium Channels , 2008, Molecular Pharmacology.

[59]  D. Bouhassira,et al.  Brain imaging of neuropathic pain , 2007, NeuroImage.

[60]  J. Farrar,et al.  Pharmacologic management of neuropathic pain: Evidence-based recommendations , 2007, PAIN.

[61]  T. Dorner,et al.  Prevalence of self‐reported neuropathic pain and impact on quality of life: a prospective representative survey , 2007, Acta anaesthesiologica Scandinavica.

[62]  P. Tugwell,et al.  Development of AMSTAR: a measurement tool to assess the methodological quality of systematic reviews , 2007, BMC medical research methodology.

[63]  Blair H. Smith,et al.  The epidemiology of chronic pain of predominantly neuropathic origin. Results from a general population survey. , 2006, The journal of pain : official journal of the American Pain Society.

[64]  H. J. McQuay,et al.  Algorithm for neuropathic pain treatment: An evidence based proposal , 2005, Pain.

[65]  D G Altman,et al.  Indirect comparisons of competing interventions. , 2005, Health technology assessment.

[66]  M. Smaldone,et al.  Epilepsy and erectile dysfunction: a review , 2004, Seizure.

[67]  Douglas G Altman,et al.  Validity of indirect comparison for estimating efficacy of competing interventions: empirical evidence from published meta-analyses , 2003, BMJ : British Medical Journal.

[68]  S. Libretto,et al.  The Rationale and Use of Topiramate for Treating Neuropathic Pain , 2003, The Clinical journal of pain.

[69]  E A Harvey,et al.  The teratogenicity of anticonvulsant drugs. , 2001, The New England journal of medicine.

[70]  G. McCleane Lamotrigine in the management of neuropathic pain: a review of the literature. , 2000, The Clinical journal of pain.

[71]  P. Lee,et al.  Publication bias in meta-analysis: its causes and consequences. , 2000, Journal of clinical epidemiology.

[72]  C. Woolf,et al.  Neuropathic pain: aetiology, symptoms, mechanisms, and management , 1999, The Lancet.

[73]  Sean C. Sweetman Martindale: The Complete Drug Reference , 1999 .

[74]  Dawn Carroll,et al.  Anticonvulsant drugs for management of pain: a systematic review , 1995, BMJ.

[75]  M. Devor,et al.  Trigeminal neuralgia: The role of self-sustaining discharge in the trigeminal ganglion , 1994, Pain.

[76]  Denise Kendrick,et al.  Health care needs assessment , 1993 .

[77]  P. Tugwell,et al.  The American College of Rheumatology 1990 Criteria for the Classification of Fibromyalgia. Report of the Multicenter Criteria Committee. , 1990, Arthritis and rheumatism.

[78]  J. Aronson,et al.  Oxford Textbook of Clinical Pharmacology and Drug Therapy , 1985 .

[79]  A. Webb,et al.  Torulopsis glabrata septicaemia treated with 5-fluorocytosine. , 1970, Lancet.

[80]  S. Blom Trigeminal neuralgia: its treatment with a new anticonvulsant drug (G-32883). , 1962, Lancet.

[81]  J. Rowlingson,et al.  Textbook of Pain , 2015 .

[82]  A. Dickenson,et al.  Anti-convulsants and anti-depressants. , 2007, Handbook of experimental pharmacology.

[83]  J. Stinson,et al.  Pharmacological management of chronic neuropathic pain - consensus statement and guidelines from the Canadian Pain Society. , 2007, Pain research & management.

[84]  McNally Jd,et al.  The epidemiology of self-reported fibromyalgia in Canada. , 2006 .

[85]  M. Tóth The epsilon theory: a novel synthesis of the underlying molecular and electrophysiological mechanisms of primary generalized epilepsy and the possible mechanism of action of valproate. , 2005, Medical hypotheses.

[86]  F. Song,et al.  In collaboration with the International Stroke Trial Collaborative Group. Indirect comparisons of competing interventions , 2005 .

[87]  E. Bergstralh,et al.  Epidemiology and clinical features of idiopathic trigeminal neuralgia and glossopharyngeal neuralgia: similarities and differences, Rochester, Minnesota, 1945-1984. , 1991, Neuroepidemiology.

[88]  Tw. Rall,et al.  Drugs effective in the therapy of the epilepsies , 1985 .