Placebo Response Changes Depending on the Neuropathic Pain Syndrome: Results of a Systematic Review and Meta-Analysis

Cepeda, M. Soledad; Berlin, Jesse A.; Gao, Chaoqing; Wiegand, Frank; Wada, Daisuke

doi:10.1111/j.1526-4637.2012.01340.x

Cited by 62 publications

(37 citation statements)

References 158 publications

(159 reference statements)

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“…44 Pain due to HIV-related painful polyneuropathy and radiculopathy seems more refractory than other pain conditions in our meta-analysis. This may be due to large placebo responses in HIV-related neuropathy trials, 45 a distinct clinical phenotype in subgroups of patients with radiculopathy, 46 or psychological/psychosocial comorbidites, often neglected in large trials. Topical agents have no known relevance for use in central neuropathic pain, and this is clearly stated in our recommendations.…”

Section: Discussionmentioning

confidence: 99%

“…One major issue is the placebo response which seems to have increased in recent trials of neuropathic pain and may lead to an underestimation of drug effects. 51 Placebo response has been found to be higher in HIV-related neuropathies, 45 and in patients with low or variable pain scores at inclusion. 52 Conversely it seems to be lower in postherpetic neuralgia.…”

Section: Discussionmentioning

confidence: 99%

“…52 Conversely it seems to be lower in postherpetic neuralgia. 45 Another issue concerns the lack of adequate diagnostic criteria for neuropathic pain (available on request for individual trials) . The use of diagnostic algorithms for neuropathic pain 53 and screening tools 54 should contribute to reducing diagnostic heterogeneity (Table 4).…”

Section: Discussionmentioning

confidence: 99%

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Pharmacotherapy for neuropathic pain in adults: a systematic review and meta-analysis

Finnerup

Attal

Haroutounian

et al. 2015

The Lancet Neurology

2,983

2,119

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Summary Background Neuropathic pain is difficult to treat. New treatments, clinical trials and standards of quality for assessing evidence justify an update of evidence-based recommendations for its pharmacological treatment. Methods The Neuropathic Pain Special Interest Group (NeuPSIG) of the International Association for the Study of Pain conducted a systematic review of randomised double-blind studies of oral and topical pharmacotherapy for neuropathic pain, including unpublished trials (retrieved from clinicaltrials.gov and pharmaceutical websites). Meta-analysis used Numbers Needed to Treat (NNT) for 50 % pain relief as primary measure and assessed publication bias. Recommendations used the Grading of Recommendations Assessment, Development, and Evaluation (GRADE). Findings In total 229 studies were included. Analysis of publication bias suggested a 10% overstatement of treatment effects. Studies published in peer-review journals reported greater effects than online studies (R2=9·3%, p<0·01). Trial outcomes were generally modest even for effective drugs : in particular NNTs were 3·6 (95 % CI 3·0–4·4) for tricyclic antidepressants (TCAs), 6·4 (95 % CI 5·2–8·4) for serotonin- noradrenaline reuptake inbibitor (SNRI) antidepressants duloxetine and venlafaxine, 7·7 (95 % CI 6·5–9·4) for pregabalin and 6·3 (95 % CI 5·0–8·3) for gabapentin. NNTs were higher for gabapentin ER/enacarbil and capsaicin high concentration patches, lower for opioids and botulinum toxin A (BTX-A) and undetermined for lidocaine patches. Final quality of evidence was lower for lidocaine patches and BTX-A. Tolerability/safety and values/preferences were high for lidocaine patches and lower for opioids and TCAs. This permitted a strong GRADE recommendation for use and proposal as first line for TCAs, SNRIs, pregabalin, gabapentin and gabapentin ER/enacarbil in neuropathic pain, a weak recommendation for use and proposal as second line for lidocaine patches, capsaicin patches and tramadol, and a weak recommendations for use and proposal as third line for strong opioids (particularly oxycodone and morphine) and BTX-A. Data for cannabinoids, tapentadol, drug combinations, and several other antiepileptics, antidepressants and topical drugs were inconclusive. Interpretation Limited efficacy, large placebo responses, inadequate diagnostic criteria and poor phenotypic profiling probably account for modest trial outcomes and should be taken into account in future studies. Funding This study was funded by NeuPSIG.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Pharmacotherapy for neuropathic pain in adults: a systematic review and meta-analysis

Finnerup

Attal

Haroutounian

et al. 2015

The Lancet Neurology

2,983

2,119

View full text Add to dashboard Cite

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“…62 In contrast, placebo response seems to be lower in postherpetic neuralgia. 26 Several analyses from recent trials in NP have reported that the placebo response was also higher in patients with low or variable pain scores at inclusion. 34,39 Other studies are needed to further explore the potential reasons for such a high placebo response in NP.…”

Section: High Placebo Responsementioning

confidence: 98%

Pharmacotherapy of neuropathic pain

Attal¹,

Bouhassira²

2015

Pain

144

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Neuropathic pain (NP) is a significant medical and socioeconomic burden. Epidemiological surveys have indicated that many patients with NP do not receive appropriate treatment for their pain. A number of pharmacological agents have been found to be effective in NP on the basis of randomized controlled trials including, in particular, tricyclic antidepressants, serotonin and norepinephrine reuptake inhibitor antidepressants, pregabalin, gabapentin, opioids, lidocaine patches, and capsaicin high-concentration patches. Evidence-based recommendations for the pharmacotherapy of NP have recently been updated. However, meta-analyses indicate that only a minority of patients with NP have an adequate response to drug therapy. Several reasons may account for these findings, including a modest efficacy of the active drugs, a high placebo response, the heterogeneity of diagnostic criteria for NP, and an inadequate classification of patients in clinical trials. Improving the current way of conducting clinical trials in NP could contribute to reduce therapeutic failures and may have an impact on future therapeutic algorithms.

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“…A variety of factors including patient expectation, emotions such as anxiety and mood all have significant effects on the complex neurobiological process that lies behind placebo analgesia 79 80. Different types of neuropathic pain are affected in different ways by the placebo effect 81. While different treatments may have hugely differing strengths of placebo effect depending on multiple complex patient and treatment factors, it has been argued that the placebo effect of sham surgery is likely to be particularly strong 82.…”

Section: Considering Drivers Of Pain In the Diagnosis And Management mentioning

confidence: 99%

Why does my shoulder hurt? A review of the neuroanatomical and biochemical basis of shoulder pain

2013

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If a patient asks 'why does my shoulder hurt?' the conversation will quickly turn to scientific theory and sometimes unsubstantiated conjecture. Frequently, the clinician becomes aware of the limits of the scientific basis of their explanation, demonstrating the incompleteness of our understanding of the nature of shoulder pain. This review takes a systematic approach to help answer fundamental questions relating to shoulder pain, with a view to providing insights into future research and novel methods for treating shoulder pain. We shall explore the roles of (1) the peripheral receptors, (2) peripheral pain processing or 'nociception', (3) the spinal cord, (4) the brain, (5) the location of receptors in the shoulder and (6) the neural anatomy of the shoulder. We also consider how these factors might contribute to the variability in the clinical presentation, the diagnosis and the treatment of shoulder pain. In this way we aim to provide an overview of the component parts of the peripheral pain detection system and central pain processing mechanisms in shoulder pain that interact to produce clinical pain.

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Placebo Response Changes Depending on the Neuropathic Pain Syndrome: Results of a Systematic Review and Meta-Analysis

Abstract: Placebo response is influenced by the pain syndrome evaluated. These differences should be considered when evaluating novel compounds for the treatment of neuropathic pain conditions.

Cited by 62 publications

References 158 publications

Pharmacotherapy for neuropathic pain in adults: a systematic review and meta-analysis

Pharmacotherapy for neuropathic pain in adults: a systematic review and meta-analysis

Pharmacotherapy of neuropathic pain

Why does my shoulder hurt? A review of the neuroanatomical and biochemical basis of shoulder pain

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