A systematic review and meta-analysis of randomized controlled head-to-head trials of recommended drugs for neuropathic pain.

Neuropathic pain is a challenging chronic pain condition. Limited knowledge exists regarding the relative effectiveness of pharmacological treatments, and differences in trial design and impact of the placebo response preclude indirect comparisons of efficacy between drug classes. The purpose of this systematic review and meta-analysis of head-to-head trials was to compare the efficacy and tolerability of drugs recommended for neuropathic pain. We conducted a systematic review and meta-analysis of direct-comparison double-blind randomized trials. Primary outcomes were mean change in pain intensity and number of responders with a 50% reduction in pain intensity. Secondary outcomes encompassed quality of life, sleep, emotional functioning, and number of dropouts because of adverse events. We included 30 trials (4087 patients), comprising 16 crossover and 14 parallel-group design studies. All studies were conducted in adults, and the majority were investigator-initiated trials. We found moderate-quality evidence for equivalence (no clinically relevant difference) between tricyclic antidepressants (TCA) and gabapentin/pregabalin with a combined mean difference in pain score of 0.10 (95% CI -0.13 to 0.32). We could not document differences between TCA and serotonin-noradrenaline reuptake inhibitors (SNRI), between SNRI and gabapentin/pregabalin, or between opioids and TCA (low quality of evidence). We found more dropouts because of adverse events with SNRI and opioids compared with TCA (low quality of evidence). We did not identify any studies that included topical treatments. This systematic review of direct-comparison studies found evidence for equivalence between TCA and gabapentin/pregabalin and fewer dropouts with TCA than SNRI and opioids.
Competing Interests: Outside the submitted word, N.B.F. has received consultancy fees from Vertex, Novartis Pharma, NeuroPN, Nanobiotix, Neurvati, and Samiona and has undertaken consultancy work for Aarhus University with remunerated work for Biogen, Merz, and Confo Therapeutics. She has received grants from IMI2PainCare an EU IMI 2 (Innovative Medicines Initiative) public-private consortium, and the companies involved are Grunenthal, Bayer, Eli Lilly, Esteve, and Teva, outside the submitted work. A.A.S. and N.L.G. declare no conflicts of interest.
(Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The International Association for the Study of Pain.)