The Use of Benzodiazepines as an Adjuvant in Pain Management: A Narrative Review with Systematic Search

Background/objectives: Benzodiazepines are widely prescribed as adjuvants in pain management, particularly for musculoskeletal conditions, with prescription rates for back and chronic pain more than doubling between 2003 and 2015. Yet, the evidence supporting this practice remains poorly defined. This study evaluates the efficacy of benzodiazepines in pain management, analyzing comparative data, pharmacological mechanisms, and global clinical guidelines. Methods: Narrative review informed by a predefined systematic search of PubMed, Scopus, Cochrane Library and Web of Science. We searched for direct comparative studies between diazepam, alprazolam, and lorazepam in pain management identified no eligible studies, revealing a significant evidence gap despite decades of clinical use. This absence of comparative evidence prompted a broader narrative examination of the evidence base for benzodiazepines across pain conditions. Results: The available literature consistently fails to support benzodiazepine analgesia. Across 111 chronic pain conditions, analgesic benefit has been demonstrated for only two rare conditions: burning mouth syndrome (evidence primarily for topical clonazepam) and stiff person syndrome (primarily case series and clinical experience). In low back pain, the condition most associated with benzodiazepine prescribing, recent randomized trials show no benefit or even harm compared to placebo, and the only positive pooled evidence derived from trials of tetrazepam, a drug withdrawn from the European market in 2013. In rheumatoid arthritis, pooled data from six small trials show no benefit over placebo at any time point. The pharmacological basis for this clinical failure is now well characterized: conventional non-selective benzodiazepines produce dose-limiting sedation before achieving sufficient receptor occupancy at the α2/α3 GABA-A subtypes responsible for antihyperalgesic effects. Despite the lack of demonstrated efficacy, prescribing persists, likely driven by clinical inertia and patient expectations reflecting anxiolytic rather than analgesic properties. Guidelines from the WHO, NICE, the VA/DoD, the American College of Physicians, the American Academy of Family Physicians, and the Wilderness Medical Society uniformly recommend against benzodiazepine use for pain. This convergence of absent efficacy, well-documented harm, and unanimous guideline opposition supports the conclusion that benzodiazepines should not be prescribed as analgesic adjuvants. Conclusions: Although the focused search targeted head-to-head trials, a broader narrative synthesis and prior comprehensive reviews likewise demonstrate a paucity of high-quality evidence for benzodiazepine analgesia. Future research should focus on subtype-selective GABA-A modulators and on strategies to align clinical practice with the existing evidence, including structured deprescribing interventions.