Multimodal Therapies for the Treatment of Neuropathic Pain: The Role of Lidocaine Patches in Combination Therapy: A Narrative Review

Neuropathic pain (NP) has a population presence of up to 10%. Both systemic agents and topical agents are recommended as first-line therapy for the treatment of NP but monotherapy provides adequate pain relief only in < 50% of the cases. This has created the need for multimodal combination therapy, a practice that is becoming more common. Combination therapy with multiple systemic agents has a risk for drug–drug interactions and adverse events (AEs), while add-on therapy with a topical agent such as lidocaine patches minimizes such risks. The focus of this review was to find if there is evidence from trials that combination therapy of the topical lidocaine patches with systemic agents will have better efficacy and/or less risk of AEs than the combination of two systemic agents. Since gabapentinoids are one of the most common systemic agents used in first-line NP therapy, the objective of this review was to summarize the safety and efficacy data and evaluate the benefit–risk ratio from three gabapentinoid combinations; gabapentinoid plus opioids, gabapentinoid plus antidepressants, and gabapentinoid plus topical lidocaine patches. Reviews of clinical trials of combinations of gabapentinoids plus other systemic agents (opioids or antidepressants) were associated with increased AEs and dropouts while improvement in analgesic efficacy was inconsistent. Clinical trials where the patients were provided topical lidocaine patches when their first treatment with a gabapentinoid was inadequate demonstrated improved analgesic efficacy with minimal additional AEs. This led to the conclusion that topical lidocaine patches—associated with minimal systemic adverse effects and proven benefits in various neuropathic pain (NP) conditions—can enhance the likelihood of achieving meaningful pain relief when used as adjuvant therapy for NP.