Occipital nerve stimulation is no more effective than placebo in cluster headache

In a randomised, placebo-controlled trial, occipital nerve stimulation (ONS) reduced the frequency of attacks in patients with chronic cluster headache (CCH), but the difference from placebo did not reach statistical significance. This suggests that the apparent preventive effect of ONS is at least partially attributable to placebo responses.

 

ONS elicits neuromodulatory effects and has shown promise in preventing attacks in CCH, said Dr. Ida Stisen Fogh-Andersen (Aarhus University Hospital, Denmark). However, evidence is limited and largely derived from open-label studies. Conventional (tonic) ONS induces paresthesia that the participants can feel, thus making blinding difficult and limiting the reliability of prior comparisons.

A new approach, paresthesia-free burst stimulation, enables double-blind testing because the participant does not feel the stimulation. Dr Fogh-Andersen and colleagues therefore conducted a double-blind, randomised, placebo-controlled clinical trial of burst ONS in participants with CCH. It comprised a 4-week baseline, a 12-week trial with transcutaneous electrical nerve stimulation (TENS). The results of which were previously published [2]; ONS implantation followed by a 2-week grace period, a 12-week randomised, double-blind burst ONS treatment period, and finally a 12-week open-label tonic ONS treatment period. The primary outcome was a ≥30% reduction in attack frequency during the randomised phase.

Dr Fogh-Andersen said all 38 participants had >15 headache attacks per month. They underwent ONS implantation and were randomly assigned to burst ONS (n=19) or placebo (n=19). The primary endpoint was met by 18.81% (95% CI: 0.28%-37.87%) in the burst ONS group and 50.02% (95% CI: 26.87%-73.09%) in the placebo group. The placebo group had a 31.20% higher chance of reaching the primary endpoint (95% CI: 1.29%-61.23%; p=0.042). After the open-label phase, a ≥30% attack reduction was observed in 42.09% (95% CI: 19.91%-64.34%) and 51.11% (95% CI: 27.32%-74.88%), respectively.

Dr Fogh-Anderson concluded: “Both burst and tonic ONS reduced attack frequency in participants with severe CCH, but neither approach proved superior to placebo. These findings highlight the need for rigorous, randomised, placebo-controlled trials in the further development of ONS therapies.”

1. Fogh-Andersen I, et al. Occipital nerve stimulation for chronic cluster headache: a double-blind, randomized, placebo-controlled study. OPR-074, EAN Congress 2025, 21-24 June 2025, Helsinki, Finland.
2. Fogh-Andersen IS, et al. Headache. 2025;65(6):973-82.

 

Medical writing support was provided by Michiel Tent.

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Posted on 26 June 20253 September 2025