Elsevier

The Lancet Neurology

Volume 10, Issue 10, October 2011, Pages 891-897
The Lancet Neurology

Articles
Suboccipital steroid injections for transitional treatment of patients with more than two cluster headache attacks per day: a randomised, double-blind, placebo-controlled trial

https://doi.org/10.1016/S1474-4422(11)70186-7Get rights and content

Summary

Background

Suboccipital steroid injections can be used for preventive treatment of cluster headache but few data are available for the efficacy of this approach in clinical trials. We aimed to assess efficacy and safety of repeated suboccipital injections with cortivazol compared with placebo as add-on therapy in patients having frequent daily attacks.

Methods

In our randomised, double-blind, placebo-controlled trial at the Emergency Headache Centre in Paris, France, we enrolled adults aged 18–65 years with more than two cluster headache attacks per day. We randomly allocated patients to receive three suboccipital injections (48–72 h apart) of cortivazol 3·75 mg or placebo, as add-on treatment to oral verapamil in patients with episodic cluster headache and as add-on prophylaxis for those with chronic cluster headache, on the basis of a computer-generated list (blocks of four for each stratum). Injections were done by physicians who were aware of treatment allocation, but patients and the evaluating physician were masked to allocation. The primary outcome was reduction of the number of daily attacks to a mean of two or fewer in the 72 h period 2–4 days after the third injection. We assessed all patients who received at least one dose of study drug in the intention-to-treat analysis. This study is registered with ClinicalTrials.gov, number NCT00804895.

Findings

Between November, 2008, and July, 2009, we randomly allocated 43 patients (15 with chronic and 28 with episodic cluster headache) to receive cortivazol or placebo. 20 of 21 patients who received cortivazol had a mean of two or fewer daily attacks after injections compared with 12 of 22 controls (odds ratio 14·5, 95% CI 1·8–116·9; p=0·012). Patients who received cortivazol also had fewer attacks (mean 10·6, 95% CI 1·4–19·9) in the first 15 days of study than did controls (30·3, 21·4–39·3; mean difference 19·7, 6·8–32·6; p=0·004). We noted no serious adverse events, and 32 (74%) of 43 patients had other adverse events (18 of 21 patients who received cortivazol and 14 of 22 controls; p=0·162); the most common adverse events were injection-site neck pain and non-cluster headache.

Interpretation

Suboccipital cortivazol injections can relieve cluster headaches rapidly in patients having frequent daily attacks, irrespective of type (chronic or episodic). Safety and tolerability need to be confirmed in larger studies.

Funding

None.

Introduction

Cluster headache is probably the most severe primary headache disorder1 and is characterised by attacks of strong periorbital pain with ipsilateral autonomic signs, recurring at intervals ranging from once every 2 days to eight times a day.2 In episodic cluster headache, attacks occur in phases for weeks or months separated by remissions.3 About 10% of patients develop chronic cluster headache and have ongoing attacks.3

Management of cluster headache usually necessitates a combination of acute and prophylactic treatments.2, 4 The mainstay of acute treatment is subcutaneous sumatriptan5 or oxygen inhalation.6 Most patients respond to treatment, but sumatriptan is restricted to two injections a day to avoid overmedication, and an oxygen cylinder is difficult to carry around. Prophylactic drugs, mainly verapamil7, 8, 9 and lithium,2 are used to reduce the frequency of attacks and sustain improvement. Transitional or add-on prophylaxis might be useful to suppress attacks rapidly at the beginning of a cluster while waiting for the delayed efficacy of long-term preventative drugs (ie, verapamil and lithium), or for patients presenting with frequent daily attacks. Although no randomised trials have been undertaken, oral steroids are considered to be efficient5, 10, 11 and are widely used, but they might induce rebound attacks on weaning off12 and have potential serious side-effects even with short-term use.13 Suboccipital steroid injections (SSI) targeting the greater occipital nerve have been proposed as an alternative to oral steroids.14, 15, 16, 17, 18 Only one randomised, controlled trial of SSI for cluster headache has been published,19 with highly positive results, but 15 of the 23 patients included had fewer than two attacks a day at baseline. SSI are not included in the European guidelines for the treatment of cluster headache.5

We have used SSI with cortivazol20 for more than 10 years in our clinic for the transitional treatment of cluster headache. Cortivazol has a powerful affinity for the glucocorticoid receptor and a long half-life.21 We aimed to assess the efficacy and safety of SSI with cortivazol in addition to usual care in patients with frequent daily attacks, stratified by type of cluster headache (episodic or chronic).

Section snippets

Study design and patients

We did a 90 day, single-centre, double-blinded, randomised, add-on, placebo-controlled trial. We screened all patients who presented with cluster headache to the Emergency Headache Centre in Paris, France, between November, 2008, and July, 2009. We enrolled adults aged 18–65 years who met the international classification of headache disorders (ICHD-II) diagnostic criteria for episodic (3.1.1) or chronic (3.2.1) cluster headache3 and had a mean of more than two attacks per 24 h in the 3 days

Results

Figure 2 shows the trial profile. We enrolled 28 patients with episodic cluster headache and 15 with chronic cluster headache (table 1). All 43 patients received at least one dose of study drug and were included in the intention-to-treat analysis.

The treatment groups were well matched (table 1). The mean number of daily attacks at baseline was 3·7 (SD 1·3) for patients in the cortivazol group and 4·3 (1·8) for controls. There was no difference between the groups in duration of the phase of

Discussion

We show that repeated SSI with cortivazol is effective compared with placebo for transitional treatment of cluster headache in patients who have frequent daily attacks. Although patients injected with cortivazol had fewer attacks per day during the first 15 days of the study, by day 30 both groups had similar results. A potential explanation for this outcome is that concomitant treatment with verapamil became efficacious and patients with episodic cluster headache in both groups entered

References (33)

  • AS Cohen et al.

    High-flow oxygen for treatment of cluster headache: a randomized trial

    JAMA

    (2009)
  • IJ Gabai et al.

    Prophylactic treatment of cluster headache with verapamil

    Headache

    (1989)
  • G Bussone et al.

    Double blind comparison of lithium and verapamil in cluster headache prophylaxis

    Headache

    (1990)
  • M Leone et al.

    Verapamil in the prophylaxis of episodic cluster headache: a double-blind study versus placebo

    Neurology

    (2000)
  • JL Jammes

    The treatment of cluster headaches with prednisone

    Dis Nerv Syst

    (1975)
  • JR Couch et al.

    Prednisone therapy for cluster headache

    Headache

    (1978)
  • Cited by (163)

    • Diagnostic protocols and newer treatment modalities for cluster headache

      2022, Disease-a-Month
      Citation Excerpt :

      All patients were headache-free by the 5th day while 90% of patients were headache-free by the 3rd day itself68. Multiple studies have been done to demonstrate the benefit of greater occipital nerve stimulation (GON)with a combination of local anesthetic and corticosteroids in the therapy of cluster headache69–76. Afridi et al. suggested that the time taken for obtaining a response well exceeded the local anesthetic effect hence it was more likely to be functioning via altering the brain nociceptive pathways76.

    • Migraine

      2022, Comprehensive Pharmacology
    View all citing articles on Scopus
    View full text