Alternative Injectable Therapies for Trigeminal Neuralgia: A Systematic Review of Efficacy and Safety

Background:
Trigeminal neuralgia (TNN) is a disabling facial pain disorder marked by sudden unilateral paroxysms, most often in the maxillary or mandibular branches. Prevalence is 4–29 cases per 100,000 persons, with female predominance. Pharmacological therapy is a first-line treatment and microvascular decompression is the surgical standard, but both are limited by resistance, intolerance, or procedural risk. Injectable therapies have recently emerged as minimally invasive alternatives. This review systematically evaluated their efficacy and safety in TNN.

Methods:
A systematic search of PubMed (MEDLINE) and the Cochrane Library was performed for studies published between 2015 and 2025 using the terms “trigeminal neuralgia AND injection.” Eligible studies were randomized trials or cohort studies including ≥20 adults with classical TNN treated by injectable therapies and reporting pain or safety outcomes. From 363 records, 13 studies met inclusion criteria.

Results:
Thirteen studies (seven randomized trials; six cohorts; ~840 patients) were analyzed. Botulinum toxin A (BTX-A) was most studied (n = 27–152), reducing pain by 40–70% and attack frequency by up to 60%, with ≥50% responders in 55–91% and relief lasting 3–6 months. A pilot trial (n = 81) found single-dose BTX-A more durable than repeated dosing. Ozone therapy (n = 103) lowered VAS from 8.1 to 2.9 at 12 months. Calcitonin-enhanced blocks (n = 30, n = 33) prolonged analgesia up to 35 weeks and reduced drug use. Corticosteroid–anesthetic blocks (n = 72), bupivacaine adjuncts (n = 73), and guanfacine–lidocaine (n = 37) also showed significant benefits. Adverse effects were mild and transient.

Conclusions:
Injectable therapies demonstrate consistent efficacy and safety in TNN. BTX-A and calcitonin have the strongest evidence, while other modalities remain promising but less studied. They may represent a minimally invasive option for refractory patients pending validation in larger multicenter trials.