ANODYNE study: A double-blind randomized trial of greater occipital nerve block of methylprednisolone and lignocaine versus placebo as a transitional preventive treatment for episodic cluster headache.

Abstract

Background: There is inadequate evidence of the efficacy of greater occipital nerve block (GONB) for the preventive treatment of cluster headaches. We assessed the efficacy and tolerability of GONB injections as a transitional preventive treatment for episodic cluster headaches (ECH).

Methods: This randomized, double-blind, placebo-controlled, parallel-group trial conducted at GB Pant Institute of Postgraduate Medical Education and Research, New Delhi, India, included ECH patients diagnosed by ICHD-3 criteria, aged 18-65, with one or more attacks per 24 h for seven days before randomization (baseline). ECH patients were either not on preventive medications or on stable doses for at least three months. ECH patients were randomized to receive active GONB (2 ml methylprednisolone (80 mg) and 2 ml lignocaine (2%)) and placebo (4 ml saline injections). Before giving GONB, lignocaine jelly was applied topically to mask the effect of numbness following the GONB. The primary efficacy endpoint was the mean change in weekly attack frequency from baseline to Week 4. Efficacy analyses were performed in a modified intention-to-treat population that included all patients who received at least one injection of GONB and had a follow-up for one week following GONB. The safety analysis included treatment-emergent adverse effects (TEAE) in all patients who received at least one dose of investigational product. The trial was registered with the Clinical Trials Registry of India (CTRI/2021/21/038397).

Results: Forty ECH patients were randomized between December 2021 and January 2023. Thirty-nine patients (19 in the active and 20 in the placebo groups) were available for efficacy analysis. The change in weekly attack frequency from baseline to Week 4 was -11.1 (95% CI: -8.5 to -4.4) for the active group compared to -7.7 (95% CI: -11.8 to -9.8) for placebo (mean difference -3.4 (95% CI: -5.2 to -1.7, p < 0.001). We noted TEAE in 18 (90%) of 20 patients who received the active drug and in 18 (90%) of 20 patients who received a placebo (p = 0.38). The common TEAE were local site bleeding and pain, which were mild and transient. No serious adverse events were reported.

Conclusion: This study found that GONB with methylprednisolone and lignocaine significantly reduced the weekly attack frequency from baseline to Week 1 through Week 4 in ECH patients compared to a placebo. GONB was well tolerated.