para>Triptans are contraindicated in ischemic cardiac disease, stroke, uncontrolled hypertension, prinzmetal angina, basilar migraine, hemiplegic migraine, ischemic bowel disease, and peripheral vascular disease.
- Prophylaxis: used at start of cluster period to prevent and shorten further attacks. Start as soon as possible:
- Verapamil
- Can start at 240 mg/day and increase by 40 to 80 mg every 10 to 14 days. Short- or long-acting equivalent. Most patients respond to daily dose of 200 to 480 mg but up to 960 mg/day may be needed. NNT = 1.2 (3)[A]
- ECG monitoring for doses/increments >480 mg/day required because of risk of bradycardia (q3mo used as a guideline)
- Similar efficacy to lithium, but fewer adverse effects and faster onset make it the preferred choice.
- Often used in conjunction with another agent
Second Line
- Acute attack
- Lidocaine/cocaine: 10 mg (1 mL) of lidocaine or 40 to 50 mg of 10% cocaine intranasal. No well well-controlled randomized controlled trials (RCTs) done. Most common side effects are nasal congestion, unpleasant taste (4)[B].
- Octreotide: SC 100 μg. Can be considered in patients when triptans are contraindicated. Main side effect is GI upset (5)[A].
- Ergotamine/dihydroergotamine (DHE): original treatments for CH. Now rarely used because of significant side effects. No controlled trials done. Still used for transitional prophylaxis (see below)
- Prophylaxis
- Lithium: Start 300 mg BID, titrate to therapeutic range of 0.8 to 1.1 mEq/L. Most patients benefit from 600 to 1,200 mg/day. Widely used without formal evidence of efficacy. Retrospective case series show that lithium led to >50% reduction in attack frequency within 2 weeks in 77% of the patients with episodic CH. Must monitor levels, liver, renal, and thyroid function. Caution with nephrotoxic drugs, diuretics. Inferior to verapamil (6)[B]
- Melatonin: 10 mg in the evening showed reduction in headache frequency versus placebo in small RCT. No side effects were reported.
- Antiepileptics: topiramate, sodium valproate, gabapentin: Open studies showed reduction of cluster duration and frequency of headache, but RCT did not show superiority to placebo. Significant adverse effects
- Civamide: 100 μL of 0.025% into each nostril daily. Only studied in episodic CH in one trial of 28 patients. Not available in the United States. Most common side effects were nasal burning, lacrimation, pharyngitis, and rhinorrhea.
- Capsaicin: 0.025% ipsilateral nostril for 7 days shows benefit in small RCT.
- Methysergide: No studies available to confirm efficacy. Has serious adverse effects, including pulmonary and retroperitoneal fibrosis. Cannot be given with triptans and ergots
- Pizotifen: Modest benefit limited by fatigue and weight gain
ADDITIONAL THERAPIES
Transitional preventive treatment are as follows:
- Used until longer-term preventive treatment becomes effective. Longer term maintenance agents are started concurrently:
- Steroids: Several open studies suggested benefit, but no rigorous trials to prove efficacy. Studies support at least 40 mg/day (up to 80 mg/day) prednisone with a 10- to 30-day taper provides benefit to 60-90% patients. Adverse effects for short-term use: insomnia, psychosis, hyponatremia, edema, hyperglycemia, peptic ulcer
ALERT
Ergots are contraindicated in patients with cardiovascular disease and cannot be used with triptans.
Pregnancy Considerations
Collaboration between headache specialist, obstetrician, and pediatrician strongly encouraged. Patient should be informed of treatment benefits and risks as well as drug's potential teratogenic effect. For abortive treatment, oxygen is most appropriate first-line therapy. Nasal lidocaine (pregnancy Category B) can be used as second-line therapy. As preventive therapy, verapamil (pregnancy Category C) and steroids (pregnancy Category C) remain the preferred options. Use of SC or intranasal sumatriptan (pregnancy Category C) should be limited as much as possible. Avoid ergotamines (pregnancy Category X).
ISSUES FOR REFERRAL
Consider a neurology or headache center referral for refractory or complicated patients.
SURGERY/OTHER PROCEDURES
- Surgery may be considered only for patients who are refractory to, or have contraindications to, medical therapy.
- Various techniques focus on stimulation or ablation of segments of trigeminal nerve root and sphenopalatine ganglion. Other techniques are aimed at decreasing pain and inflammation surrounding the greater occipital nerve.
- Greater occipital nerve steroid injection: A retrospective analysis showed ~80% of patients with partial or complete response. Effect lasted 3.5 weeks; 21 mg of betamethasone and 2 mL of 2% lidocaine were used. One class I RCT showed benefit within 72 hours in 85% of lidocaine/betamethasone group compared with none in lidocaine/saline group. Cortivazol injection reduced severity and frequency of headache compared with placebo in an RCT (7)[A].
- No evidence for Botox or hyperbaric oxygen treatment
- Neurostimulation
- Occipital nerve stimulation (ONS) was shown to reduce severity and attack frequency in chronic CH patients.
- Deep brain stimulation (DBS) of the posterior inferior hypothalamus shows moderate therapeutic effect.
- Currently investigating sphenopalatine ganglion stimulation
INPATIENT CONSIDERATIONS
Suicidal ideation, unwilling to contract for safety
ONGOING CARE
FOLLOW-UP RECOMMENDATIONS
Patient Monitoring
- Anticipate cluster bouts and initiate early prophylaxis.
- Monitor for depression.
- Watch for adverse medication response and side effects, such as unmasking of underlying cardiovascular disorder when using medications to treat CH.
PROGNOSIS
- Unpredictable course. With aging, attack frequency often decreases.
- Poor prognosis associated with older age of onset, male gender, disease duration of >20 years for episodic form
- Possibility of transformation of episodic cluster to chronic cluster and occasionally chronic cluster to episodic cluster
COMPLICATIONS
- Depression and suicide
- Side effects of medication, including unmasking of coronary artery disease
- Potential for drug abuse/misuse
REFERENCES
11 Cohen AS, Burns B, Goadsby PJ. High-flow oxygen for treatment of cluster headache: a randomized trial. JAMA. 2009;302(22):2451-2457.22 Law S, Derry S, Moore RA. Triptans for acute cluster headache. Cochrane Database Syst Rev. 2010;(4):CD008042.33 Leone M, D'Amico D, Frediani F, et al. Verapamil in the prophylaxis of episodic cluster headache: a double-blind study versus placebo. Neurology. 2000;54(6):1382-1385.44 Costa A, Pucci E, Antonaci F, et al. The effect of intranasal cocaine and lidocaine on nitroglycerin-induced attacks in cluster headache. Cephalalgia. 2000;20(2):85-91.55 Matharu MS, Levy MJ, Meeran K, et al. Subcutaneous octreotide in cluster headache: randomized placebo-controlled double-blind crossover study. Ann Neurol. 2004;56(4):488-494.66 Stochino ME, Deidda A, Asuni C, et al. Evaluation of lithium response in episodic cluster headache: a retrospective case series. Headache. 2012;52(7):1171-1175.77 Leroux E, Valade D, Taifas I, et al. Suboccipital steroid injections for transitional treatment of patients with more than two cluster headache attacks per day: a randomised, double-blind, placebo-controlled trial. Lancet Neurol. 2011;10(10):891-897.
ADDITIONAL READING
- Ashkenazi A, Schwedt T. Cluster headache-acute and prophylactic therapy. Headache. 2011;51(2):272-286.
- Beck E, Sieber WJ, Trejo R. Management of cluster headache. Am Fam Physician. 2005;71(4):717-724.
- Fontaine D, Lanteri-Minet M, Ouchchane L, et al. Anatomical location of effective deep brain stimulation electrodes in chronic cluster headache. Brain. 2010;133(Pt 4):1214-1223.
- Hainer BL, Matheson EM. Approach to acute headache in adults. Am Fam Physician. 2013;87(10):682-687.
- International Headache Society: http://www.ihs-headache.org
SEE ALSO
Algorithm: Headache, Chronic
CODES
ICD10
- G44.009 Cluster headache syndrome, unspecified, not intractable
- G44.019 Episodic cluster headache, not intractable
- G44.029 Chronic cluster headache, not intractable
- G44.001 Cluster headache syndrome, unspecified, intractable
- G44.021 Chronic cluster headache, intractable
- G44.011 Episodic cluster headache, intractable
ICD9
- 339.00 Cluster headache syndrome, unspecified
- 339.01 Episodic cluster headache
- 339.02 Chronic cluster headache
SNOMED
- 193031009 Cluster headache syndrome (disorder)
- 230472004 Episodic cluster headache
- 230473009 Chronic cluster headache
- 230476001 Atypical cluster headache
CLINICAL PEARLS
- CHs are rare but disabling. Patients are often agitated and restless during the attack.
- Oxygen and triptans, not narcotics, are first-line therapy for acute attacks.
- Abortive, transitional, and prophylaxic treatment must all be considered.