Intravenous fosphenytoin (fPHT) demonstrated rapid and significant pain relief for patients experiencing acute exacerbations of trigeminal neuralgia (TN), according to late-breaking results from the IFT Study presented at the 2025 American Academy of Neurology (AAN) Annual Meeting in San Diego.
Acute TN flares can persist despite first-line oral therapy, often leaving patients with few non-invasive treatment options aside from surgery. The IFT Study (jRCT: 2011220043) is the first Phase III, multicenter, randomized, double-blind, placebo-controlled clinical trial to evaluate the efficacy and safety of IV fosphenytoin in this setting.
Between April 2023 and April 2024, 21 patients with TN and a baseline numerical rating scale (NRS) pain score of 5 or higher were randomized 1:1 to receive either IV fosphenytoin or placebo. Treatment involved an initial dose of 18 mg/kg followed by daily maintenance doses of 7.5 mg/kg for up to 5 days.
The primary endpoint, change in NRS pain score at 120 minutes post-initial dose, significantly favored the fosphenytoin group (p=0.008). Additionally, 90.9% of patients in the fPHT arm achieved ≥50% reduction in NRS score, compared with 40.0% in the placebo arm (p=0.040). The number of TN attacks also decreased significantly in the treatment group within 24 hours of the first dose.
Adverse events in the fPHT group were predominantly mild to moderate and included somnolence, transient blood pressure decreases, and nausea. Overall, treatment was well tolerated.
These findings suggest that IV fosphenytoin may offer an effective and well-tolerated non-surgical alternative for patients with difficult-to-control TN pain, especially in emergency settings or while awaiting surgical interventions such as microvascular decompression or radiosurgery.
The IFT Study highlights the potential of fosphenytoin as a fast-acting therapy for acute TN, addressing a long-standing treatment gap and offering clinicians a new tool for rapid pain control.
Reference: Noro S A et al. Intravenous Fosphenytoin Therapy for Acute Trigeminal Neuralgia: A Phase 3 Randomized Clinical Trial (IFT Study). 2025 American Academy of Neurology (AAN) Annual Meeting, April 5-9, 2025, San Diego, California, USA.
