June 2025
Updated review finds modest outcomes for neuropathic pain treatments
By Rebecca Jenkins
Treatments for neuropathic pain have modest outcomes and uncertainty remains around the effectiveness of some therapies, according to an updated evidence review.
The systematic review and meta-analysis from the Neuropathic Pain Special Interest Group of the International Association for the Study of Pain was conducted to incorporate new evidence from randomised controlled trials, emerging neuromodulation techniques and advances in evidence synthesis to update a previous 2015 review.
The latest analysis, published in The Lancet Neurology, included 313 double-blind, randomised controlled trials including almost 50,000 adult patients that evaluated pharmacological and neuromodulation treatments administered for at least three weeks, or with at least three weeks of follow up.
Overall, the review authors were able to make a strong recommendation for use of tricyclic antidepressants (TCAs), α2δ-ligands, and serotonin and noradrenaline reuptake inhibitors (SNRIs) as first-line treatments.
They were also able to make a weak recommendation for capsaicin 8% patches, capsaicin cream and lidocaine 5% plasters as second-line recommendations.
Evidence for capsaicin cream was previously considered inconclusive, they noted.
There was a weak recommendation for botulinum toxin and opioids as third-line treatments for neuropathic pain.
Tramadol, which was previously a second-line treatment, was now grouped with opioids, the authors noted.
Repetitive transcranial magnetic stimulation (rTMS) was analysed for the first time, but the authors were only able to make a weak recommendation for the modality as third-line treatment.
Future research, including for neuromodulation techniques and combination therapy, was necessary to optimise outcomes and improve patient quality of life, the authors concluded.
‘Despite the inclusion of an additional 109 randomised controlled trials, the recommendations have only changed modestly since 2015,’ they noted.
‘The systematic review underscores the modest efficacy of many pharmacological treatments for neuropathic pain, possibly influenced by the heterogeneity of underlying mechanisms and participant phenotypes in clinical trials.’
Dr Charles Brooker, Clinical Associate Professor at the Northern Clinical School, The University of Sydney, said the review methodology was robust and included strategies to address reporting bias, as it was thought based on the previous 2015 study that under-reporting of negative outcomes improved the apparent benefit by about 10%.
‘However, the message from the review has not changed much and the important takeaway points include that overall treatment options for neuropathic pain are poorly effective,’ he told Medicine Today.
Dr Brooker agreed with the review authors that there was a need for more blinded trials with sham control for spinal cord stimulation, but noted trials were challenging due to the cost of the devices, the complex heterogeneous nature of the problems treated and the subjective nature of the outcome.
‘The longer-term unblinded studies do show considerable functional improvement and reduced opioid intake across the cohort, suggestive of therapeutic benefit,’ he said.
He also backed the authors’ recommendations for further research into different combinations of pharmacological options for neuropathic pain.
‘Combined therapy is commonly used clinically but it should be instituted carefully as it has not been tested,’ Dr Brooker said.
‘For example, in a patient with depression on treatment with SNRI who develops neuropathic pain, we would like to know if the addition of pregabalin or low-dose TCA is likely to help or cause too many side effects – this is a very common clinical scenario,’ he said.
Overall, Dr Brooker stressed the importance of individualised care when treating neuropathic pain and the need to consider pharmacological and nonpharmacological therapies.
‘Don’t go just on the number needed to treat when choosing treatment; consider your patient – e.g. the elderly are more at risk of side effects,’ he said.