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Source: Minor DS, Harrell T. Headache disorders. In: DiPiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey L, eds. Pharmacotherapy: A Pathophysiologic Approach. 10th ed. New York, NY: McGraw-Hill; 2017. Accessed September 11, 2018.


  • Most severe of the primary headache disorders, known as trigeminal autonomic cephalalgia

  • Classified by attacks of excruciating, unilateral head pain that occurs in series lasting for weeks or months (ie, cluster periods) separated by remission periods usually lasting months or years


  • Exact prevalence is uncertain.

  • Estimated lifetime prevalence of 124 per 100,000 people or 0.12%

  • Male to female ratio is approximately 4:1 with the age onset typically in the third to fifth decade.


  • Pathophysiologic mechanisms are not completely understood.

  • Neuroimaging studies performed during acute attacks have shown activation of the ipsilateral hypothalamic gray area, implicating the hypothalamus as a modulator of cluster headaches.

    • Activation of the trigeminal-autonomic reflexes leads to ipsilateral pain and cranial autonomic features.


  • One hallmark of cluster headaches is the circadian rhythm of painful attacks.

  • Episodic cluster headaches are the most common cluster headache subtype.

    • Attacks occur daily for a week to several months, followed by pain-free intervals.

    • Average remission periods are 2 years in length.

  • Attacks occur commonly at night and more commonly in the spring and fall.

  • Attacks occur suddenly, pain peaks quickly after onset and lasts 15–180 min.

  • Pain presentation

    • Excruciating

    • Penetrating

    • Boring intensity in the orbital, supraorbital, and temporal unilateral locations

    • Auras are not present with cluster headaches.

  • Cranial autonomic symptoms

    • Conjunctival injection

    • Lacrimation

    • Nasal stuffiness

    • Rhinorrhea

    • Eyelid edema

    • Facial sweating

    • Miosis/ptosis

    • Typically resolve with resolution of the headache


  • Diagnostic criteria per International Headache Society (IHS) classification system:

    1. At least five attacks fulfilling criteria B–D

    2. Severe or very severe unilateral orbital, supraorbital and/or temporal pain lasting 15–180 min (when untreated)

    3. Either or both of the following:

      • At least one of the following symptoms or signs, ipsilateral to the headache:

        1. Conjunctival injection and/or lacrimation

        2. Nasal congestion and/or rhinorrhea

        3. Eyelid edema

        4. forehead and facial sweating

        5. miosis and/or ptosis

      • Sense of restlessness or agitation

    4. Occurring with a frequency between one every other day and eight per day

    5. Not better accounted for by another ICHD-3 diagnosis


  • Directed at managing the acute attack

  • Oxygen

    • Standard acute treatment is 100% oxygen at a rate of at least 12 L/min for 15 min

  • Triptans

    • Safe and effective due to quick onset of subcutaneous and intranasal routes

      • Subcutaneous sumatriptan (6 mg) is the most effective agent.

      • Nasal sprays are less effective but may be better tolerated in some patients.

      • Orally administered triptans have limited use in cluster attacks because of their relatively slow onset of action.


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