A Meta‑analysis Exploring the Efficacy of Neuropathic Pain Medication for Low Back Pain or Spine‑Related Leg Pain: Is Efficacy Dependent on the Presence of Neuropathic Pain?

TY - JOUR

T1 - A Meta‑analysis Exploring the Efficacy of Neuropathic Pain Medication for Low Back Pain or Spine‑Related Leg Pain: Is Efficacy Dependent on the Presence of Neuropathic Pain?

AU - Jennifer, Ward

AU - Grinstead, Anthony

AU - Kemp, Amy

AU - Kersten, Paula

AU - Schmid, Annina

AU - Ridehalgh, Colette

N1 - Publisher Copyright: © The Author(s), under exclusive licence to Springer Nature Switzerland AG 2024.

PY - 2024/10/26

Y1 - 2024/10/26

N2 - Background and Objective: Highly variable pain mechanisms in people with low back pain or spine-related leg pain might contribute to inefficacy of neuropathic pain medication. This meta-analysis aimed to determine how neuropathic pain is identified in clinical trials for people taking neuropathic pain medication for low back pain or spine-related leg pain and whether subgrouping based on the presence of neuropathic pain influences efficacy. Methods: EMBASE, MEDLINE, Cochrane Central, CINAHL [EBSCO], APA PsycINFO, ClinicalTrials.gov, and the World Health Organization International Clinical Trials Registry were searched from inception to 14 May, 2024. Randomized and crossover trials comparing first-line neuropathic pain medication for people with low back pain or spine-related leg pain to placebo or usual care were included. Two independent authors extracted data. Random-effects meta-analyses of all studies combined, and pre-planned subgroup meta-analyses based on the certainty of neuropathic pain (according to the neuropathic pain Special Interest Group [NeuPSIG] neuropathic pain grading criteria) were completed. Certainty of evidence was judged using the grading of recommendations assessment development and evaluation [GRADE] framework. Results: Twenty-seven included studies reported on 3619 participants. Overall, 33% of studies were judged unlikely to include people with neuropathic pain, 26% remained unclear. Only 41% identified people with possible, probable, or definite neuropathic pain. For pain, general analyses revealed only small effects at short term (mean difference [MD] − 9.30 [95% confidence interval [CI] − 13.71, − 4.88], I2 = 87%) and medium term (MD − 5.49 [95% CI − 7.24, − 3.74], I2 = 0%). Subgrouping at short term revealed studies including people with definite or probable neuropathic pain showed larger effects on pain (definite; MD − 16.65 [95% CI − 35.95, 2.65], I2 = 84%; probable; MD − 10.45 [95% CI − 14.79, − 6.12], I2 = 20%) than studies including people with possible (MD − 5.50 [95% CI − 20.52, 9.52], I2 = 78%), unlikely (MD − 6.67 [95% CI − 10.58, 2.76], I2 = 0%), or unclear neuropathic pain (MD − 8.93 [95% CI − 20.57, 2.71], I2 = 96%). Similarly, general analyses revealed negligible effects on disability at short term (MD − 3.35 [95% CI − 9.00, 2.29], I2 = 93%) and medium term (MD − 4.06 [95% CI − 5.63, − 2.48], I2 = 0%). Sub-grouping at short term revealed larger effects in studies including people with definite/probable neuropathic pain (MD − 9.25 [95% CI − 12.59, − 5.90], I2 = 2%) compared with those with possible/unclear/unlikely neuropathic pain (MD −1.57 [95% CI − 8.96, 5.82] I2 = 95%). Medium-term outcomes showed a similar trend, but were limited by low numbers of studies. Certainty of evidence was low to very low for all outcomes. Conclusions: Most studies using neuropathic pain medication for low back pain or spine-related leg pain fail to adequately consider the presence of neuropathic pain. Meta-analyses suggest neuropathic pain medication may be most effective in people with low back pain or spine-related leg pain with a definite/probable neuropathic pain component. However, the low to very low certainty of evidence and poor identification of neuropathic pain in most studies prevent firm recommendations.

AB - Background and Objective: Highly variable pain mechanisms in people with low back pain or spine-related leg pain might contribute to inefficacy of neuropathic pain medication. This meta-analysis aimed to determine how neuropathic pain is identified in clinical trials for people taking neuropathic pain medication for low back pain or spine-related leg pain and whether subgrouping based on the presence of neuropathic pain influences efficacy. Methods: EMBASE, MEDLINE, Cochrane Central, CINAHL [EBSCO], APA PsycINFO, ClinicalTrials.gov, and the World Health Organization International Clinical Trials Registry were searched from inception to 14 May, 2024. Randomized and crossover trials comparing first-line neuropathic pain medication for people with low back pain or spine-related leg pain to placebo or usual care were included. Two independent authors extracted data. Random-effects meta-analyses of all studies combined, and pre-planned subgroup meta-analyses based on the certainty of neuropathic pain (according to the neuropathic pain Special Interest Group [NeuPSIG] neuropathic pain grading criteria) were completed. Certainty of evidence was judged using the grading of recommendations assessment development and evaluation [GRADE] framework. Results: Twenty-seven included studies reported on 3619 participants. Overall, 33% of studies were judged unlikely to include people with neuropathic pain, 26% remained unclear. Only 41% identified people with possible, probable, or definite neuropathic pain. For pain, general analyses revealed only small effects at short term (mean difference [MD] − 9.30 [95% confidence interval [CI] − 13.71, − 4.88], I2 = 87%) and medium term (MD − 5.49 [95% CI − 7.24, − 3.74], I2 = 0%). Subgrouping at short term revealed studies including people with definite or probable neuropathic pain showed larger effects on pain (definite; MD − 16.65 [95% CI − 35.95, 2.65], I2 = 84%; probable; MD − 10.45 [95% CI − 14.79, − 6.12], I2 = 20%) than studies including people with possible (MD − 5.50 [95% CI − 20.52, 9.52], I2 = 78%), unlikely (MD − 6.67 [95% CI − 10.58, 2.76], I2 = 0%), or unclear neuropathic pain (MD − 8.93 [95% CI − 20.57, 2.71], I2 = 96%). Similarly, general analyses revealed negligible effects on disability at short term (MD − 3.35 [95% CI − 9.00, 2.29], I2 = 93%) and medium term (MD − 4.06 [95% CI − 5.63, − 2.48], I2 = 0%). Sub-grouping at short term revealed larger effects in studies including people with definite/probable neuropathic pain (MD − 9.25 [95% CI − 12.59, − 5.90], I2 = 2%) compared with those with possible/unclear/unlikely neuropathic pain (MD −1.57 [95% CI − 8.96, 5.82] I2 = 95%). Medium-term outcomes showed a similar trend, but were limited by low numbers of studies. Certainty of evidence was low to very low for all outcomes. Conclusions: Most studies using neuropathic pain medication for low back pain or spine-related leg pain fail to adequately consider the presence of neuropathic pain. Meta-analyses suggest neuropathic pain medication may be most effective in people with low back pain or spine-related leg pain with a definite/probable neuropathic pain component. However, the low to very low certainty of evidence and poor identification of neuropathic pain in most studies prevent firm recommendations.

UR - http://www.scopus.com/inward/record.url?scp=85207345320&partnerID=8YFLogxK

U2 - 10.1007/s40265-024-02085-6

DO - 10.1007/s40265-024-02085-6

M3 - Article

SN - 0012-6667

JO - Drugs

JF - Drugs

ER -