Cluster Headache—Acute and Prophylactic Therapy

Avi Ashkenazi, MD; Todd Schwedt, MD

Headache. 2011;51(2):272-286.

Somatostatin and Octreotide

Sicuteri et al conducted a controlled study to examine the efficacy of intravenous somatostatin for acute CH attacks.^[29] Seventy-two attacks, experienced by 8 men, were studied. Somatostatin infusion was superior to placebo, and comparable to intramuscular ergotamine, in relieving CH pain. Matharu et al evaluated the efficacy of octreotide, a somatostatin analog that can be given subcutaneously, for acute CH.^[30] Octreotide 100 μg was significantly superior to placebo with regard to headache response rates (52% vs 36%).

An important advantage of these drugs is their lack of vasoconstrictive effect, making them a viable treatment option for patients who cannot use triptans because of vascular diseases.

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Table 1. Drugs for the Acute Treatment of Cluster Headache
Therapy	Level of Evidence (EFNS Guidelines)^42,87*	Dose	More Common AEs	Comments
Oxygen	A	7–10 L/min (higher flow rates may be needed)	None	Inhaled via a non-rebreathable mask for 15–20 minutes
Sumatriptan SC	A	6 mg	Nausea, fatigue, paresthesias, chest/throat tightness	May be taken up to twice daily during a cluster period; contraindicated in patients with CV diseases
Sumatriptan IN	A	20 mg	Nausea, fatigue, paresthesias, chest/throat tightness, unpleasant taste	Slower onset of action then sumatriptan SC; contraindicated in patients with CV diseases
Zolmitriptan IN	A	5–10 mg	Nausea, fatigue, paresthesias, chest/throat tightness, unpleasant taste	Comparable in efficacy to sumatriptan IN; contraindicated in patients with CV diseases
Octreotide SC	B	100 μg	Injection site pain, abdominal pain, nausea, hyperglycemia	Can be used in patients with CV diseases
Lidocaine IN	B	1 mL (4–10%)	none	Only moderate effect on head pain
Dihydroergotamine IV, IM, SC, or IN	Not rated	1 mg	Nausea, diarrhea, muscle cramps, chest tightness, unpleasant taste (IN)	IV probably the most effective route; contraindicated in patients with CV diseases; cannot be used with triptans

* See Appendix for detailed guidelines.
AEs = adverse effects; CV = cardiovascular; EFNS = European Federation of Neurological Societies; IM = intramuscular; IN = intranasal; IV = intravenous; L/min = liters per minute; SC = subcutaneous.

Table 2. Maintenance Prophylactic Therapy for Cluster Headache
Therapy	Level of Evidence (EFNS Guidelines)^42,87*	Target Dose per Day	Monitoring	More Common AEs
Verapamil	A	200–900 mg	EKG	Hypotension, constipation, peripheral edema
Lithium carbonate	B	600–900 mg	Lithium levels, renal function, thyroid function	Diarrhea, tremor, polyuria
Topiramate	B	50–200 mg	Serum bicarbonate	Paresthesias, weight loss, cognitive dysfunction, fatigue, dizziness, taste alteration
Valproic acid	C	500–2000 mg	CBC, liver function	Weight gain, fatigue, tremor, hair loss, nausea
Melatonin	C	10 mg	None	Fatigue, sedation
Baclofen	C	15–30 mg	None	Drowsiness, dizziness, ataxia, muscle weakness
Botulinum toxin	Not rated	50 units	None	Muscle weakness, injection site pain
Gabapentin	Not rated	800–3600 mg	CBC	Somnolence, fatigue, dizziness, weight gain, peripheral edema, ataxia
Clonidine	Not rated	0.2–0.3 mg	None	Fatigue, hypotension

* See Appendix for detailed guidelines.
AEs = adverse effects; CBC = complete blood count; EFNS = European Federation of Neurological Societies; EKG = electrocardiogram.

Appendix

European Federation of Neurological Societies (EFNS) guidelines—evidence classification scheme for a therapeutic intervention

Class I: An adequately powered prospective, randomized, controlled clinical trial with masked outcome assessment in a representative population or an adequately powered systematic review of prospective randomized controlled clinical trials with masked outcome assessment in representative populations. The following are required:

Randomization concealment.
Primary outcome(s) is/are clearly defined.
Exclusion/inclusion criteria are clearly defined.
Adequate accounting for dropouts and crossovers with numbers sufficiently low to have minimal potential for bias.
Relevant baseline characteristics are presented and substantially equivalent among treatment groups or there is appropriate statistical adjustment for differences.

Class II: Prospective matched-group cohort study in a representative population with masked outcome assessment that meets a-e or a randomized, controlled trial in a representative population that lacks 1 criteria a-e.

Class III: All other controlled trials (including well-defined natural history controls or patients serving as own controls) in a representative population, where outcome assessment is independent of patient treatment.

Class IV: Evidence from uncontrolled studies, case series, case reports, or expert opinion.

Rating of recommendations:

Level A rating (established as effective, ineffective, or harmful) requires at least 1 convincing class I study or at least 2 consistent, convincing class II studies.

Level B rating (probably effective, ineffective, or harmful) requires at least 1 convincing class II study or overwhelming class III evidence.

Level C (possibly effective, ineffective, or harmful) rating requires at least 2 convincing class III studies.

Adapted with permission from Brainin et al. Guidance for the preparation of neurological management guidelines by EFNS scientific task forces—revised recommendations 2004. Eur J Neurol 2004;11:577–581.

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