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

Abstract

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review of randomised double-blind studies of oral and topical pharmacotherapy for neuropathic pain, including unpublished trials (retrieved from clinicaltrials.gov and pharmaceutical websites).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.

An update and systematic review on drug therapies for the treatment of refractory chronic cough

“…Thirteen from 15 (87%) patients in the amitriptyline group had ≥50% cough improvement compared to one from 13 (8%) patients in the codeine/guaifenesin group [meta-analysis, Figure 4], number needed to treat (NNT) = 1.3. Combined NNT for 15 studies assessing amitriptyline (25–150 mg/day) for neuropathic pain is 3.6 (95% CI 3.0–4.4) [52]. There were no adverse effects of amitriptyline reported for this study (Table 4) but there was high risk of bias (Figure 2).…”

“…This corresponds to a NNT of 3.6. The combined NNT for 14 RCTs of gabapentin (900–3600 mg/day) for neuropathic pain is 6.3 (95% CI 5.0–8.3) [52]. …”

“…Allodynia and hyperalgesia are akin to the clinical characteristics of allotussia and hypertussia found in refractory CC. Unfortunately, NMDA antagonists have variable outcomes in their treatment of neuropathic pain [52] but maybe worth investigating further in refractory CC. In a guinea pig study by Canning and Mori [53], a predominant role for NMDA receptor activation during cough and a modulatory role for non-NMDA receptors was found.…”

Capsaicin 8% patch versus oral pregabalin in patients with peripheral neuropathic pain

“…Randomized controlled studies have demonstrated efficacy and safety of the capsaicin patch in the treatment of PNP (Backonja et al., 2008; Simpson et al., 2008; Irving et al., 2011; Mou et al., 2013), and it is recommended as a second‐line treatment option for the condition, (Finnerup, Attal et al., 2015). …”

“…Managing patients with PNP is challenging (Dworkin et al., 2007, 2010; Finnerup et al., 2010; Finnerup, Attal et al ., 2015); it often becomes chronic, with marked long‐term reductions in health‐related quality of life (HRQOL) (O'Connor, 2009), decreased individual productivity and increased patient and healthcare expenditure (Rodríguez et al., 2007; Navarro et al., 2011). Aetiologies range from mechanical and inflammatory diseases to injury and nerve compression (Hall et al., 2006).…”