Author
Michael C. Rowbotham
Other affiliations: Sutter Health, University of San Francisco, Endo International plc ...read more
Bio: Michael C. Rowbotham is an academic researcher from University of California, San Francisco. The author has contributed to research in topics: Neuropathic pain & Chronic pain. The author has an hindex of 58, co-authored 156 publications receiving 17465 citations. Previous affiliations of Michael C. Rowbotham include Sutter Health & University of San Francisco.
Papers published on a yearly basis
Papers
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Aarhus University1, French Institute of Health and Medical Research2, Washington University in St. Louis3, Tufts Medical Center4, University of Rochester5, Queen's University6, Helsinki University Central Hospital7, Karolinska Institutet8, Oslo University Hospital9, Aarhus University Hospital10, University of the Witwatersrand11, Churchill Hospital12, Johns Hopkins University13, Imperial College London14, Chelsea and Westminster Hospital NHS Foundation Trust15, California Pacific Medical Center16, Florey Institute of Neuroscience and Mental Health17, University of Edinburgh18, University of Sydney19, Greenwich Hospital20, University of Dundee21, University of California, San Diego22
TL;DR: The results support a revision of the NeuPSIG recommendations for the pharmacotherapy of neuropathic pain and allow a strong recommendation for use and proposal as first-line treatment in neuropathicPain for tricyclic antidepressants, serotonin-noradrenaline reuptake inhibitors, pregabalin, and gabapentin.
Abstract: Summary Background New drug treatments, clinical trials, and standards of quality for assessment of evidence justify an update of evidence-based recommendations for the pharmacological treatment of neuropathic pain. Using the Grading of Recommendations Assessment, Development, and E valuation (GRADE), we revised the Special Interest Group on Neuropathic Pain (NeuPSIG) recommendations for the pharmacotherapy of neuropathic pain based on the results of a systematic review and meta-analysis. Methods Between April, 2013, and January, 2014, NeuPSIG of the International Association for the Study of Pain did a systematic review and meta-analysis of randomised, double-blind studies of oral and topical pharmacotherapy for neuropathic pain, including studies published in peer-reviewed journals since January , 1966, and unpublished trials retrieved from ClinicalTrials.gov and websites of pharmaceutical companies. We used number needed to treat (NNT) for 50% pain relief as a primary measure and assessed publication bias; NNT was calculated with the fi xed-eff ects Mantel-Haenszel method. Findings 229 studies were included in the meta-analysis. Analysis of publication bias suggested a 10% overstatement of treatment eff ects. Studies published in peer-reviewed journals reported greater eff ects than did unpublished studies (r² 9·3%, p=0·009). T rial outcomes were generally modest: in particular, combined NNTs were 6·4 (95% CI 5·2–8·4) for serotonin-noradrenaline reuptake inhibitors, mainly including duloxetine (nine of 14 studies); 7·7 (6·5–9·4) for pregabalin; 7·2 (5·9–9·21) for gabapentin, including gabapentin extended release and enacarbil; and 10·6 (7·4–19·0) for capsaicin high-concentration patches. NNTs were lower for tricyclic antidepressants, strong opioids, tramadol, and botulinum toxin A, and undetermined for lidocaine patches. Based on GRADE, fi nal quality of evidence was moderate or high for all treatments apart from lidocaine patches; tolerability and safety, and values and preferences were higher for topical drugs; and cost was lower for tricyclic antidepressants and tramadol. These fi ndings permitted a strong recommendation for use and proposal as fi rst-line treatment in neuropathic pain for tricyclic antidepressants, serotonin-noradrenaline reuptake inhibitors, pregabalin, and gabapentin; a weak recommendation for use and proposal as second line for lidocaine patches, capsaicin high-concentration patches, and tramadol; and a weak recommendation for use and proposal as third line for strong opioids and botulinum toxin A. Topical agents and botulinum toxin A are recommended for peripheral neuropathic pain only. Interpretation Our results support a revision of the NeuPSIG recommendations for the pharmacotherapy of neuropathic pain. Inadequate response to drug treatments constitutes a substantial unmet need in patients with neuropathic pain. Modest effi cacy, large placebo responses, heterogeneous diagnostic criteria, and poor phenotypic profi ling probably account for moderate trial outcomes and should be taken into account in future studies. Funding NeuPSIG of the International Association for the Study of Pain.
2,512 citations
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TL;DR: Gabapentin is effective in the treatment of pain and sleep interference associated with PHN and Mood and quality of life also improve with gabapentin therapy.
Abstract: Context.—Postherpetic neuralgia (PHN) is a syndrome
of often intractable neuropathic pain following herpes zoster
(shingles) that eludes effective treatment in many patients.Objective.—To determine the efficacy and safety of the
anticonvulsant drug gabapentin in reducing PHN pain.Design.—Multicenter, randomized, double-blind,
placebo-controlled, parallel design, 8-week trial conducted from August
1996 through July 1997.Setting.—Sixteen US outpatient clinical centers.Participants.—A total of 229 subjects were randomized.Intervention.—A 4-week titration period to a maximum dosage
of 3600 mg/d of gabapentin or matching placebo. Treatment was
maintained for another 4 weeks at the maximum tolerated dose.
Concomitant tricyclic antidepressants and/or narcotics were continued
if therapy was stabilized prior to study entry and remained constant
throughout the study.Main Outcome Measures.—The primary efficacy measure was
change in the average daily pain score based on an 11-point Likert
scale (0, no pain; 10, worst possible pain) from baseline week to the
final week of therapy. Secondary measures included average daily sleep
scores, Short-Form McGill Pain Questionnaire (SF-MPQ), Subject Global
Impression of Change and investigator-rated Clinical Global Impression
of Change, Short Form-36 (SF-36) Quality of Life Questionnaire, and
Profile of Mood States (POMS). Safety measures included the frequency
and severity of adverse events.Results.—One hundred thirteen patients received
gabapentin, and 89 (78.8%) completed the study; 116 received placebo,
and 95 (81.9%) completed the study. By intent-to-treat analysis,
subjects receiving gabapentin had a statistically significant reduction
in average daily pain score from 6.3 to 4.2 points compared with a
change from 6.5 to 6.0 points in subjects randomized to receive placebo
(P<.001). Secondary measures of pain as well as changes in
pain and sleep interference showed improvement with gabapentin
(P<.001). Many measures within the SF-36 and POMS also
significantly favored gabapentin (P≤.01). Somnolence,
dizziness, ataxia, peripheral edema, and infection were all more
frequent in the gabapentin group, but withdrawals were comparable in
the 2 groups (15 [13.3%] in the gabapentin group vs 11 [9.5%] in
the placebo group).Conclusions.—Gabapentin is effective in the
treatment of pain and sleep interference associated with PHN. Mood and
quality of life also improve with gabapentin
therapy.
1,397 citations
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TL;DR: In this article, the authors describe current approaches to the diagnosis and assessment of neuropathic pain and discuss the results of recent research on its pathophysiologic mechanisms, and provide specific recommendations for use of these medications.
Abstract: Chronic neuropathic pain, caused by lesions in the peripheral or central nervous system, comes in many forms. We describe current approaches to the diagnosis and assessment of neuropathic pain and discuss the results of recent research on its pathophysiologic mechanisms. Randomized controlled clinical trials of gabapentin, the 5% lidocaine patch, opioid analgesics, tramadol hydrochloride, and tricyclic antidepressants provide an evidence-based approach to the treatment of neuropathic pain, and specific recommendations are presented for use of these medications. Continued progress in basic and clinical research on the pathophysiologic mechanisms of neuropathic pain may make it possible to predict effective treatments for individual patients by application of a pain mechanism–based approach.
1,229 citations
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University of Helsinki1, French Institute of Health and Medical Research2, University of Wisconsin-Madison3, Lancaster University4, Sapienza University of Rome5, Karolinska University Hospital6, Johns Hopkins University7, University College London8, Aarhus University Hospital9, University of Liverpool10, Imperial College London11, University of California, San Francisco12, University of Würzburg13, University of Aberdeen14, Heidelberg University15
TL;DR: Screening questionnaires are suitable for identifying potential patients with neuropathic pain, but further validation of them is needed for epidemiological purposes and quantitative sensory testing is recommended for selected cases in clinic, including the diagnosis of small fiber neuropathies and for research purposes.
Abstract: This is a revision of guidelines, originally published in 2004, for the assessment of patients with neuropathic pain. Neuropathic pain is defined as pain arising as a direct consequence of a lesion or disease affecting the somatosensory system either at peripheral or central level. Screening questionnaires are suitable for identifying potential patients with neuropathic pain, but further validation of them is needed for epidemiological purposes. Clinical examination, including accurate sensory examination, is the basis of neuropathic pain diagnosis. For more accurate sensory profiling, quantitative sensory testing is recommended for selected cases in clinic, including the diagnosis of small fiber neuropathies and for research purposes. Measurement of trigeminal reflexes mediated by A-beta fibers can be used to differentiate symptomatic trigeminal neuralgia from classical trigeminal neuralgia. Measurement of laser-evoked potentials is useful for assessing function of the A-delta fiber pathways in patients with neuropathic pain. Functional brain imaging is not currently useful for individual patients in clinical practice, but is an interesting research tool. Skin biopsy to measure the intraepidermal nerve fiber density should be performed in patients with clinical signs of small fiber dysfunction. The intensity of pain and treatment effect (both in clinic and trials) should be assessed with numerical rating scale or visual analog scale. For future neuropathic pain trials, pain relief scales, patient and clinician global impression of change, the proportion of responders (50% and 30% pain relief), validated neuropathic pain quality measures and assessment of sleep, mood, functional capacity and quality of life are recommended.
909 citations
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University of Rochester1, University of Bristol2, Queen Mary University of London3, Veterans Health Administration4, University of Alabama at Birmingham5, University of Colorado Denver6, University of Wisconsin-Madison7, Columbia University8, University of Helsinki9, University of Liverpool10, Harvard University11, University of California, San Diego12, University of California, San Francisco13, Duke University14, University of Texas Health Science Center at Houston15, Utrecht University16
TL;DR: The results of controlled trials and the clinical experience of the authors support the use of acyclovir, brivudin (where available), famciclovir, and valacy Clovir as first-line antiviral therapy for the treatment of patients with HZ.
Abstract: The objective of this article is to provide evidence-based recommendations for the management of patients with herpes zoster (HZ) that take into account clinical efficacy, adverse effects, impact on quality of life, and costs of treatment. Systematic literature reviews, published randomized clinical trials, existing guidelines, and the authors' clinical and research experience relevant to the management of patients with HZ were reviewed at a consensus meeting. The results of controlled trials and the clinical experience of the authors support the use of acyclovir, brivudin (where available), famciclovir, and valacyclovir as first-line antiviral therapy for the treatment of patients with HZ. Specific recommendations for the use of these medications are provided. In addition, suggestions are made for treatments that, when used in combination with antiviral therapy, may further reduce pain and other complications of HZ.
699 citations
Cited by
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University of Washington1, University of Rochester2, AstraZeneca3, University of Queensland4, Pfizer5, Tufts University6, University of Pennsylvania7, Endo International plc8, University Health Network9, Harvard University10, Purdue Pharma11, Novartis12, National Institutes of Health13, Dalhousie University14, GlaxoSmithKline15, Food and Drug Administration16, Élan17, Abbott Laboratories18, University of California, San Diego19, United States Department of Veterans Affairs20
TL;DR: In this article, the authors provide recommendations for the core outcome domains that should be considered by investigators conducting clinical trials of the efficacy and effectiveness of treatments for chronic pain, and develop a core set of outcome domains would facilitate comparison and pooling of d
Abstract: Objective. To provide recommendations for the core outcome domains that should be considered by investigators conducting clinical trials of the efficacy and effectiveness of treatments for chronic pain. Development of a core set of outcome domains would facilitate comparison and pooling of d
3,476 citations
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University of Rochester1, University of Washington2, Saint Louis University3, University of Toronto4, University of Texas MD Anderson Cancer Center5, University of Pennsylvania6, Johns Hopkins University7, Yale University8, National Institutes of Health9, Pfizer10, Food and Drug Administration11, NorthShore University HealthSystem12, Merck & Co.13, Allergan14, University of Copenhagen15, Purdue Pharma16, Celgene17, University of Oxford18, Élan19, GlaxoSmithKline20, Johnson & Johnson21, Duke University22, Oregon Health & Science University23, Endo International plc24, AstraZeneca25
TL;DR: A consensus meeting was convened by the Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT) to provide recommendations for interpreting clinical importance of treatment outcomes in clinical trials of the efficacy and effectiveness of chronic pain treatments as discussed by the authors.
2,581 citations
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Aarhus University1, French Institute of Health and Medical Research2, Washington University in St. Louis3, Tufts Medical Center4, University of Rochester5, Queen's University6, Helsinki University Central Hospital7, Karolinska Institutet8, Oslo University Hospital9, Aarhus University Hospital10, University of the Witwatersrand11, Churchill Hospital12, Johns Hopkins University13, Imperial College London14, Chelsea and Westminster Hospital NHS Foundation Trust15, California Pacific Medical Center16, University of Edinburgh17, Florey Institute of Neuroscience and Mental Health18, Greenwich Hospital19, University of Sydney20, University of Dundee21, University of California, San Diego22
TL;DR: The results support a revision of the NeuPSIG recommendations for the pharmacotherapy of neuropathic pain and allow a strong recommendation for use and proposal as first-line treatment in neuropathicPain for tricyclic antidepressants, serotonin-noradrenaline reuptake inhibitors, pregabalin, and gabapentin.
Abstract: Summary Background New drug treatments, clinical trials, and standards of quality for assessment of evidence justify an update of evidence-based recommendations for the pharmacological treatment of neuropathic pain. Using the Grading of Recommendations Assessment, Development, and E valuation (GRADE), we revised the Special Interest Group on Neuropathic Pain (NeuPSIG) recommendations for the pharmacotherapy of neuropathic pain based on the results of a systematic review and meta-analysis. Methods Between April, 2013, and January, 2014, NeuPSIG of the International Association for the Study of Pain did a systematic review and meta-analysis of randomised, double-blind studies of oral and topical pharmacotherapy for neuropathic pain, including studies published in peer-reviewed journals since January , 1966, and unpublished trials retrieved from ClinicalTrials.gov and websites of pharmaceutical companies. We used number needed to treat (NNT) for 50% pain relief as a primary measure and assessed publication bias; NNT was calculated with the fi xed-eff ects Mantel-Haenszel method. Findings 229 studies were included in the meta-analysis. Analysis of publication bias suggested a 10% overstatement of treatment eff ects. Studies published in peer-reviewed journals reported greater eff ects than did unpublished studies (r² 9·3%, p=0·009). T rial outcomes were generally modest: in particular, combined NNTs were 6·4 (95% CI 5·2–8·4) for serotonin-noradrenaline reuptake inhibitors, mainly including duloxetine (nine of 14 studies); 7·7 (6·5–9·4) for pregabalin; 7·2 (5·9–9·21) for gabapentin, including gabapentin extended release and enacarbil; and 10·6 (7·4–19·0) for capsaicin high-concentration patches. NNTs were lower for tricyclic antidepressants, strong opioids, tramadol, and botulinum toxin A, and undetermined for lidocaine patches. Based on GRADE, fi nal quality of evidence was moderate or high for all treatments apart from lidocaine patches; tolerability and safety, and values and preferences were higher for topical drugs; and cost was lower for tricyclic antidepressants and tramadol. These fi ndings permitted a strong recommendation for use and proposal as fi rst-line treatment in neuropathic pain for tricyclic antidepressants, serotonin-noradrenaline reuptake inhibitors, pregabalin, and gabapentin; a weak recommendation for use and proposal as second line for lidocaine patches, capsaicin high-concentration patches, and tramadol; and a weak recommendation for use and proposal as third line for strong opioids and botulinum toxin A. Topical agents and botulinum toxin A are recommended for peripheral neuropathic pain only. Interpretation Our results support a revision of the NeuPSIG recommendations for the pharmacotherapy of neuropathic pain. Inadequate response to drug treatments constitutes a substantial unmet need in patients with neuropathic pain. Modest effi cacy, large placebo responses, heterogeneous diagnostic criteria, and poor phenotypic profi ling probably account for moderate trial outcomes and should be taken into account in future studies. Funding NeuPSIG of the International Association for the Study of Pain.
2,512 citations
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University of Rochester1, University of Washington2, University of Pennsylvania3, Johns Hopkins University4, Harvard University5, Yale University6, Ludwig Maximilian University of Munich7, AstraZeneca8, University of Queensland9, Tufts University10, Merck & Co.11, National Institutes of Health12, Endo International plc13, Food and Drug Administration14, University of Toronto15, Purdue Pharma16
2,441 citations
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TL;DR: A grading system of definite, probable, and possible neuropathic pain is proposed, which includes the grade possible, which can only be regarded as a working hypothesis, and the grades probable and definite, which require confirmatory evidence from a neurologic examination.
Abstract: Pain usually results from activation of nociceptive afferents by actually or potentially tissue-damaging stimuli. Pain may also arise by activity generated within the nervous system without adequate stimulation of its peripheral sensory endings. For this type of pain, the International Association for the Study of Pain introduced the term neuropathic pain, defined as "pain initiated or caused by a primary lesion or dysfunction in the nervous system." While this definition has been useful in distinguishing some characteristics of neuropathic and nociceptive types of pain, it lacks defined boundaries. Since the sensitivity of the nociceptive system is modulated by its adequate activation (e.g., by central sensitization), it has been difficult to distinguish neuropathic dysfunction from physiologic neuroplasticity. We present a more precise definition developed by a group of experts from the neurologic and pain community: pain arising as a direct consequence of a lesion or disease affecting the somatosensory system. This revised definition fits into the nosology of neurologic disorders. The reference to the somatosensory system was derived from a wide range of neuropathic pain conditions ranging from painful neuropathy to central poststroke pain. Because of the lack of a specific diagnostic tool for neuropathic pain, a grading system of definite, probable, and possible neuropathic pain is proposed. The grade possible can only be regarded as a working hypothesis, which does not exclude but does not diagnose neuropathic pain. The grades probable and definite require confirmatory evidence from a neurologic examination. This grading system is proposed for clinical and research purposes.
2,342 citations