Letter to the Editor Cephalalgia 2015, Vol. 35(11) 1034–1035 ! International Headache Society 2015 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav DOI: 10.1177/0333102415586067 cep.sagepub.com
Response to Letter to the Editor Dear Editor-in-Chief, Cephalalgia We appreciate Dr Charleston’s interest in our study. Since occipital nerve blocks (ONBs) are widely performed in clinical practice for the preventive treatment of migraine and other headache disorders, this study was designed to determine if an ONB performed at a single point in time reduces the number of headache and migraine days at four weeks in patients fulfilling the diagnostic criteria for episodic and chronic migraine. While several open-label (1–3) case series/ studies have explored different doses of both the anesthetic and steroid with variable benefit, there is no randomized placebo-controlled evidence to guide clinicians. Injections of anesthetics typically respond quickly and faster than medications. A combination of anesthetic and steroid theoretically provides anesthetic pain relief and reduction of inflammation, respectively. The anesthetic effect is within seconds-minutes while the steroid effect presumably occurs within one to seven days, and therefore the study was designed to determine if the combination changed the frequency of headaches within four weeks of the injection as pain relief has been reported to last several days to a few months (4). Although onabotulinumtoxinA has been shown to reduce headache days after multiple injections, it has also been shown to be effective after a single injection. The patients were injected even if they did not have a headache on that day; however, patients receiving onabotulinumtoxinA or other prophylactic medications may not have a headache on the day they start therapy. Although in practice patients may have a headache on their injection day, typically the injections are used in this circumstance to acutely treat the headache. This study was not designed to look at the acute response to the injections. While the authors agree that the placebo was not inactive, in order to ensure blinding a low dose of anesthetic was used and although this small amount of anesthetic could potentially alter sensation in the occipital region, the placebo response was very similar to placebo responses in other migraine analgesic trials (5).
In fact, placebo responses to injection therapy in migraine trials are typically higher than those seen in this study (6–9). The study explored only greater ONBs for the treatment of migraine and not nerve blocks in other regions. Since ONBs are more commonly employed in practice compared to other extracranial nerves, this study was intended to address a very specific research question. Finally, the dose of the methylprednisolone (20 mg on each side) was chosen based on the clinical practice. Conflict of interest None declared.
References 1. Ashkenazi A, Matro R, Shaw JW, et al. Greater occipital nerve block using local anaesthetics alone or with triamcinolone for transformed migraine: A randomised comparative study. J Neurol Neurosurg Psychiatry 2008; 79: 415–417. 2. Afridi SK, Shields KG, Bhola R, et al. Greater occipital nerve injection in primary headache syndromes—prolonged effects from a single injection. Pain 2006; 122: 126–129. 3. Weibelt S, Andress-Rothroock D, King W, et al. Suboccipital nerve blocks for suppression of chronic migraine: Safety, efficacy, and predictors of outcome. Headache 2010; 50: 1041–1044. 4. Blumenfeld A, Ashkenazi A, Napchan U, et al. Expert consensus recommendations for the performance of peripheral nerve blocks for headaches—A narrative review. Headache 2013; 53: 437–446. 5. Bendtsen L, Mattsson P, Zwart JA, et al. Placebo response in clinical randomized trials of analgesics in migraine. Cephalalgia 2003; 23: 487–490. 6. Aurora SK, Dodick DW, Turkel CC, et al. OnabotulinumtoxinA for treatment of chronic migraine: Results from the double-blind, randomized, placebo-controlled phase of the PREEMPT 1 trial. Cephalalgia 2010; 30: 793–803. 7. Diener HC, Dodick DW, Aurora SK, et al. OnabotulinumtoxinA for treatment of chronic migraine: Results from the double-blind, randomized, placebo-controlled phase of the PREEMPT 2 trial. Cephalalgia 2010; 30: 804–814.
Dilli and Dodick 8. Dodick DW, Goadsby PJ, Silberstein SD, et al. Safety and efficacy of ALD403, an antibody to calcitonin gene-related peptide, for the prevention of frequent episodic migraine: A randomised, double-blind, placebo-controlled, exploratory phase 2 trial. Lancet Neurol 2014; 13: 1100–1107. 9. Dodick DW, Goadsby PJ, Spierings EL, et al. Safety and efficacy of LY2951742, a monoclonal antibody to calcitonin gene-related peptide, for the prevention of migraine: A phase 2, randomised, double-blind, placebo-controlled study. Lancet Neurol 2014; 13: 885–892.
1035 Esma Dilli and David W Dodick Department of Neurology, Mayo Clinic, USA Corresponding author: Esma Dilli, University of British Columbia, 8275A, 2775 Laurel St, Vancouver, BC V5Z 1M9, Canada. Email: [email protected]
Response to Letter to the Editor Dear Editor-in-Chief, Cephalalgia We appreciate Dr Charleston’s interest in our study. Since occipital nerve blocks (ONBs) are widely performed in clinical practice for the preventive treatment of migraine and other headache disorders, this study was designed to determine if an ONB performed at a single point in time reduces the number of headache and migraine days at four weeks in patients fulfilling the diagnostic criteria for episodic and chronic migraine. While several open-label (1–3) case series/ studies have explored different doses of both the anesthetic and steroid with variable benefit, there is no randomized placebo-controlled evidence to guide clinicians. Injections of anesthetics typically respond quickly and faster than medications. A combination of anesthetic and steroid theoretically provides anesthetic pain relief and reduction of inflammation, respectively. The anesthetic effect is within seconds-minutes while the steroid effect presumably occurs within one to seven days, and therefore the study was designed to determine if the combination changed the frequency of headaches within four weeks of the injection as pain relief has been reported to last several days to a few months (4). Although onabotulinumtoxinA has been shown to reduce headache days after multiple injections, it has also been shown to be effective after a single injection. The patients were injected even if they did not have a headache on that day; however, patients receiving onabotulinumtoxinA or other prophylactic medications may not have a headache on the day they start therapy. Although in practice patients may have a headache on their injection day, typically the injections are used in this circumstance to acutely treat the headache. This study was not designed to look at the acute response to the injections. While the authors agree that the placebo was not inactive, in order to ensure blinding a low dose of anesthetic was used and although this small amount of anesthetic could potentially alter sensation in the occipital region, the placebo response was very similar to placebo responses in other migraine analgesic trials (5).
In fact, placebo responses to injection therapy in migraine trials are typically higher than those seen in this study (6–9). The study explored only greater ONBs for the treatment of migraine and not nerve blocks in other regions. Since ONBs are more commonly employed in practice compared to other extracranial nerves, this study was intended to address a very specific research question. Finally, the dose of the methylprednisolone (20 mg on each side) was chosen based on the clinical practice. Conflict of interest None declared.
References 1. Ashkenazi A, Matro R, Shaw JW, et al. Greater occipital nerve block using local anaesthetics alone or with triamcinolone for transformed migraine: A randomised comparative study. J Neurol Neurosurg Psychiatry 2008; 79: 415–417. 2. Afridi SK, Shields KG, Bhola R, et al. Greater occipital nerve injection in primary headache syndromes—prolonged effects from a single injection. Pain 2006; 122: 126–129. 3. Weibelt S, Andress-Rothroock D, King W, et al. Suboccipital nerve blocks for suppression of chronic migraine: Safety, efficacy, and predictors of outcome. Headache 2010; 50: 1041–1044. 4. Blumenfeld A, Ashkenazi A, Napchan U, et al. Expert consensus recommendations for the performance of peripheral nerve blocks for headaches—A narrative review. Headache 2013; 53: 437–446. 5. Bendtsen L, Mattsson P, Zwart JA, et al. Placebo response in clinical randomized trials of analgesics in migraine. Cephalalgia 2003; 23: 487–490. 6. Aurora SK, Dodick DW, Turkel CC, et al. OnabotulinumtoxinA for treatment of chronic migraine: Results from the double-blind, randomized, placebo-controlled phase of the PREEMPT 1 trial. Cephalalgia 2010; 30: 793–803. 7. Diener HC, Dodick DW, Aurora SK, et al. OnabotulinumtoxinA for treatment of chronic migraine: Results from the double-blind, randomized, placebo-controlled phase of the PREEMPT 2 trial. Cephalalgia 2010; 30: 804–814.
Dilli and Dodick 8. Dodick DW, Goadsby PJ, Silberstein SD, et al. Safety and efficacy of ALD403, an antibody to calcitonin gene-related peptide, for the prevention of frequent episodic migraine: A randomised, double-blind, placebo-controlled, exploratory phase 2 trial. Lancet Neurol 2014; 13: 1100–1107. 9. Dodick DW, Goadsby PJ, Spierings EL, et al. Safety and efficacy of LY2951742, a monoclonal antibody to calcitonin gene-related peptide, for the prevention of migraine: A phase 2, randomised, double-blind, placebo-controlled study. Lancet Neurol 2014; 13: 885–892.
1035 Esma Dilli and David W Dodick Department of Neurology, Mayo Clinic, USA Corresponding author: Esma Dilli, University of British Columbia, 8275A, 2775 Laurel St, Vancouver, BC V5Z 1M9, Canada. Email: [email protected]
