Treatment algorithm

Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups: see disclaimer

ACUTE

acute attack: without cardiovascular disease, cerebrovascular disease, or uncontrolled hypertension

1st line – subcutaneous sumatriptan

Back
ACUTE
|
acute attack: without cardiovascular disease, cerebrovascular disease, or uncontrolled hypertension
1st line – 

subcutaneous sumatriptan

Triptans are contraindicated in patients with coronary artery disease, peripheral vascular disease, or cerebrovascular disease, and should not be used in patients with uncontrolled hypertension or severe hepatic impairment or within 24 hours of any other 5HT1 agonist or ergotamine-type medication.

Subcutaneous sumatriptan has been shown to be effective and is the preferred triptan for treating acute attacks.[1][26][31]​​[32][33]

Triptans are thought likely to be safe in pregnancy, but are contraindicated in patients with moderate or severe hypertension.[70][71][72] [ Cochrane Clinical Answers logo ]

Primary options

sumatriptan: 6 mg subcutaneously as a single dose, may repeat at least one hour after initial dose if required, maximum 12 mg/day

1st line – high-flow oxygen

Back
ACUTE
|
acute attack: without cardiovascular disease, cerebrovascular disease, or uncontrolled hypertension
1st line – 

high-flow oxygen

High-flow oxygen has been shown to be effective in the acute treatment of cluster attacks, decreasing both the intensity and duration of attacks.[26][29][33]​​[36]​​​​

It is safe, can be used multiple times a day, and is not contraindicated in patients with hypertension or vascular disease.

High-flow oxygen therapy is the preferred option for acute treatment of cluster headache in pregnant women.[69]

Oxygen should be given at 100% with a flow rate of 12-15 L/minute using a non-rebreathing face mask for at least 15 minutes or until the attack is terminated.

1st line – noninvasive vagus nerve stimulation (for episodic cluster headache)

Back
ACUTE
|
acute attack: without cardiovascular disease, cerebrovascular disease, or uncontrolled hypertension
1st line – 

noninvasive vagus nerve stimulation (for episodic cluster headache)

Noninvasive vagus nerve stimulation (using a handheld, patient-controlled, noninvasive vagus nerve stimulator that is applied to the skin of the neck) has been shown to be effective as an acute treatment for people with episodic cluster headache, but not those with chronic cluster headache.[1][33]​​​​[37]​​​​

There have been no reports of pregnancy-related adverse effects of noninvasive neuromodulation.[69][70]

2nd line – intranasal zolmitriptan

Back
ACUTE
|
acute attack: without cardiovascular disease, cerebrovascular disease, or uncontrolled hypertension
2nd line – 

intranasal zolmitriptan

Triptans are contraindicated in patients with coronary artery disease, peripheral vascular disease, or cerebrovascular disease, and should not be used in patients with uncontrolled hypertension or severe hepatic impairment or within 24 hours of any other 5HT1 agonist or ergotamine-type medication.

Zolmitriptan nasal spray is well tolerated and effective within 30 minutes in episodic disease.[1][26][34] [ Cochrane Clinical Answers logo ]

Used in patients in whom subcutaneous sumatriptan is ineffective and those who are intolerant due to adverse effects or have a needle phobia.

Triptans are thought likely to be safe in pregnancy, but are contraindicated in patients with moderate or severe hypertension.[70][71][72]

Primary options

zolmitriptan nasal: 5 mg (one spray) in one nostril as a single dose, may repeat at least 2 hours after initial dose if required, maximum 10 mg/day

3rd line – intranasal sumatriptan or oral zolmitriptan

Back
ACUTE
|
acute attack: without cardiovascular disease, cerebrovascular disease, or uncontrolled hypertension
3rd line – 

intranasal sumatriptan or oral zolmitriptan

Triptans are contraindicated in patients with coronary artery disease, peripheral vascular disease, or cerebrovascular disease, and should not be used in patients with uncontrolled hypertension or severe hepatic impairment or within 24 hours of any other 5HT1 agonist or ergotamine-type medication.

Sumatriptan nasal spray is less effective than subcutaneous injection but appears effective compared with placebo.[1][26][35] [ Cochrane Clinical Answers logo ]

There is some evidence for effectiveness of oral zolmitriptan.[1][26][31]

Triptans are thought likely to be safe in pregnancy, but are contraindicated in patients with moderate or severe hypertension.[70][71][72]

Primary options

sumatriptan nasal: 5-20 mg in one nostril as a single dose, may repeat at least 2 hours after initial dose if required, maximum 40 mg/day

OR

zolmitriptan: 2.5 to 5 mg orally as a single dose, may repeat at least 2 hours after initial dose if required, maximum 10 mg/day

3rd line – intranasal lidocaine

Back
ACUTE
|
acute attack: without cardiovascular disease, cerebrovascular disease, or uncontrolled hypertension
3rd line – 

intranasal lidocaine

Can bring about rapid relief of cluster attacks in at least one third of patients. Application should be as close as possible to the sphenopalatine fossa.​[9][11][26]

During administration, patient should recline the head back and toward the affected side.[9]

Primary options

lidocaine: 1 mL of a 10% lidocaine solution placed with a cotton swab intranasally (ipsilaterally/bilaterally) for 5 minutes

Plus – transitional therapy

Back
ACUTE
|
acute attack: without cardiovascular disease, cerebrovascular disease, or uncontrolled hypertension
|
requiring attack suppression
Plus – 

transitional therapy

Treatment recommended for ALL patients in selected patient group

Preventive medications may take at least 2 weeks at the maximum dose to exert their full effect. Therefore, interventions that act more quickly, but are not appropriate for long-term use, are often started concurrently with standard preventive agents to suppress attacks rapidly. These interventions are referred to as transitional, short-term, or bridge therapies.[1][26]

Corticosteroids are the fastest-acting agents for inducing remission and are effective as transitional therapy.

A short tapering course of an oral corticosteroid such as prednisone is commonly used.[1][26][33]​ Prednisone was effective for the short-term prevention of episodic cluster headache in a double-blind randomized controlled trial.[38] However, corticosteroids must not be used on a regular basis (more than 2-3 times a year) due to the risk of long-term adverse effects. Patients should be screened for potential contraindications (e.g., coronary artery disease, hypertension, diabetes) before treatment with corticosteroids. Prednisone may be used with caution in pregnancy (avoided during the first trimester and dose kept as low as possible), but there is some suggestion of an increased risk of fetal abnormalities.[74]

Corticosteroids can also be delivered via greater occipital (or suboccipital) nerve blocks, which have been shown to be effective in reducing attack frequency.[33]​ A variety of corticosteroids have been used in studies, usually combined with a local anesthetic.[1][26] The mixture is injected into the greater occipital nerve on the symptomatic side; the injection point lies two-thirds of the distance on a line drawn from the center of the mastoid to the external occipital protuberance. A nerve block is often performed once at the start of a cluster period, and can be repeated on a regular basis (once every 3-4 months) for patients with chronic cluster headache. There have been no reports of pregnancy-related adverse effects of greater occipital nerve block.[69][70]

Intravenous dihydroergotamine may also be considered as transitional therapy; however, it is contraindicated in patients with cardiovascular or cerebrovascular risk factors (e.g., coronary artery disease, hypertension, or stroke) and should not be used in these patients.[1][26] Ergot preparations should not be used within 24 hours of triptans.

Primary options

prednisone: 100 mg orally once daily for 5 days, then gradually taper dose

More

Secondary options

dihydroergotamine: 1 mg intravenously as a single dose, may repeat after 60 minutes if required, maximum 2 mg/day or 6 mg/week

acute attack: with cardiovascular disease, cerebrovascular disease, or uncontrolled hypertension

1st line – high-flow oxygen

Back
ACUTE
|
acute attack: with cardiovascular disease, cerebrovascular disease, or uncontrolled hypertension
1st line – 

high-flow oxygen

Triptans are contraindicated in patients with coronary artery disease, peripheral vascular disease, or cerebrovascular disease, and should not be used in patients with uncontrolled hypertension or severe hepatic impairment or within 24 hours of any other 5HT1 agonist or ergotamine-type medication.

High-flow oxygen is the preferred treatment in patients with these contraindications.

High-flow oxygen has been shown to be effective in the acute treatment of cluster attacks, decreasing both the intensity and duration of attacks.[26][29][33]​​[36]​​​​ It is safe and can be used multiple times a day.

High-flow oxygen therapy is the preferred option for acute treatment of cluster headache in pregnant women.[69]

Oxygen should be given at 100% with a flow rate of 12-15 L/minute using a non-rebreathing face mask for at least 15 minutes or until the attack is terminated.

1st line – noninvasive vagus nerve stimulation (for episodic cluster headache)

Back
ACUTE
|
acute attack: with cardiovascular disease, cerebrovascular disease, or uncontrolled hypertension
1st line – 

noninvasive vagus nerve stimulation (for episodic cluster headache)

Noninvasive vagus nerve stimulation (using a handheld, patient-controlled, noninvasive vagus nerve stimulator that is applied to the skin of the neck) has been shown to be effective as an acute treatment for people with episodic cluster headache, but not those with chronic cluster headache.[1][33]​​​​[37]​​

There have been no reports of pregnancy-related adverse effects of noninvasive neuromodulation.[69][70]

2nd line – intranasal lidocaine

Back
ACUTE
|
acute attack: with cardiovascular disease, cerebrovascular disease, or uncontrolled hypertension
2nd line – 

intranasal lidocaine

Can bring about rapid relief of cluster attacks in at least one third of patients. Application should be as close as possible to the sphenopalatine fossa.[9][11][26]

During administration, patient should recline their head back and toward the affected side.[9]

Primary options

lidocaine: 1 mL of a 10% lidocaine solution placed with a cotton swab intranasally (ipsilaterally/bilaterally) for 5 minutes

Plus – transitional therapy

Back
ACUTE
|
acute attack: with cardiovascular disease, cerebrovascular disease, or uncontrolled hypertension
|
requiring attack suppression
Plus – 

transitional therapy

Treatment recommended for ALL patients in selected patient group

Preventive medications may take at least 2 weeks at the maximum dose to exert their full effect. Therefore, interventions that act more quickly, but are not appropriate for long-term use, are often started concurrently with standard preventive agents to suppress attacks rapidly. These interventions are referred to as transitional, short-term, or bridge therapies.[1][26]

Corticosteroids are the fastest-acting agents for inducing remission and are effective as transitional therapy.

A short tapering course of an oral corticosteroid such as prednisone is commonly used.[1][26][33]​ Prednisone was effective for the short-term prevention of episodic cluster headache in a double-blind randomized controlled trial.[38] However, corticosteroids must not be used on a regular basis (more than 2-3 times a year) due to the risk of long-term adverse effects. Patients should be screened for potential contraindications (e.g., coronary artery disease, hypertension, diabetes) before treatment with corticosteroids. Prednisone may be used with caution in pregnancy (avoided during the first trimester and dose kept as low as possible), but there is some suggestion of an increased risk of fetal abnormalities.[74]

Corticosteroids can also be delivered via greater occipital (or suboccipital) nerve blocks, which have been shown to be effective in reducing attack frequency.[33]​ A variety of corticosteroids have been used in studies, usually combined with a local anesthetic.[1][26] The mixture is injected into the greater occipital nerve on the symptomatic side; the injection point lies two-thirds of the distance on a line drawn from the center of the mastoid to the external occipital protuberance. A nerve block is often performed once at the start of a cluster period, and can be repeated on a regular basis (once every 3-4 months) for patients with chronic cluster headache. There have been no reports of pregnancy-related adverse effects of greater occipital nerve block.[69][70]

Dihydroergotamine is contraindicated in patients with cardiovascular or cerebrovascular risk factors and/or established cardiovascular disease (e.g., coronary artery disease, hypertension, or stroke) and should not be used in these patients.

Primary options

prednisone: 100 mg orally once daily for 5 days, then gradually taper dose

More
ONGOING

preventive treatment for episodic cluster headache

1st line – verapamil

Back
ONGOING
|
preventive treatment for episodic cluster headache
1st line – 

verapamil

The main goal of preventive therapy is rapidly suppressing individual attacks and maintaining remission for the duration of the patient's typical cluster period.

Verapamil is considered the first-line preventive therapy.[1][26][29][33]​​[39]​​

An ECG must be performed before verapamil is prescribed to exclude bradycardia and other conduction abnormalities, specifically PR interval prolongation. ECGs are then repeated before each dose increase to check for signs of developing heart block.[40]

Adverse effects include constipation, dizziness, and lower extremity swelling.

Evidence for the safety of verapamil in pregnancy is limited, but calcium-channel blockers are generally thought to be safe, and nifedipine is used widely as an antihypertensive treatment in pregnancy, with limited adverse effects and established safety.[69][70][72]

For patients with episodic cluster headache, once the patient has been headache-free for at least 2 weeks, the preventive therapy is gradually tapered off. Upon entering the next cluster period, the patient should start at the previous maximum efficacious dose of verapamil, as long as the baseline ECG is normal.

Primary options

verapamil: 80 mg orally (immediate-release) three times daily initially, increase gradually according to response, maximum 480 mg/day; some specialists may recommend higher doses

1st line – galcanezumab

Back
ONGOING
|
preventive treatment for episodic cluster headache
1st line – 

galcanezumab

The main goal of preventive therapy is rapidly suppressing individual attacks and maintaining remission for the duration of the patient's typical cluster period.

Galcanezumab, a humanized monoclonal antibody against calcitonin gene-related peptide, was reported to reduce the weekly frequency of episodic cluster headache attacks measured in the 3-week period after the initial injection, compared with placebo.[1][41]

Galcanezumab is approved in the US for the treatment of episodic cluster headache. Galcanezumab is recommended in European guidelines as an off-label treatment option for patients with intractable episodic cluster headache (it is only approved for the treatment of migraine in Europe).[33]

There is no safety information about galcanezumab in pregnancy, and it is not currently recommended for pregnant women; patients should stop taking it 6 months before trying to become pregnant.[70]

For patients with episodic cluster headache, once the patient has been headache-free for at least 2 weeks, the interval between doses may be extended and the treatment ultimately stopped.

Primary options

galcanezumab: 300 mg subcutaneously once monthly

2nd line – lithium

Back
ONGOING
|
preventive treatment for episodic cluster headache
2nd line – 

lithium

The main goal of preventive therapy is rapidly suppressing individual attacks and maintaining remission for the duration of the patient's typical cluster period.

Lithium was reported to be effective as prophylaxis, although evidence is contradictory.[1][9][26][32][33]​​

Lithium levels should be monitored to prevent toxicity due to a narrow therapeutic range.[9] Although no therapeutic level for lithium has been established for cluster headache, clinical experience suggests that patients respond best when at the higher end of the therapeutic range. Lithium toxicity can result in nausea, vomiting, tremors, confusion, and vision changes. Hypothyroidism and kidney dysfunction are potential long-term adverse effects. Once a patient's clinical state and lithium levels are stable, the dose can be maintained.

Lithium is usually contraindicated in pregnancy, especially in the first trimester during organ development, because of the risk of major congenital malformations.[72][73] However, it has been suggested that it may be considered in the second and third trimesters for pregnant patients with severe cluster headache when other treatments are ineffective, if the benefit to the mother clearly exceeds the possible risk to the fetus.[74]

For patients with episodic cluster headache, once the patient has been headache-free for at least 2 weeks, the preventive therapy is gradually tapered off.

Primary options

lithium: consult specialist for guidance on dose

2nd line – melatonin

Back
ONGOING
|
preventive treatment for episodic cluster headache
2nd line – 

melatonin

The main goal of preventive therapy is rapidly suppressing individual attacks and maintaining remission for the duration of the patient's typical cluster period.

Melatonin has been reported to be effective, but evidence is largely anecdotal.[1][26][44]

Given its safety profile, some have suggested melatonin as first-line therapy in all patients requiring short-term prevention.[11][45] However, better-quality evidence for effectiveness is available for other therapies.

For patients with episodic cluster headache, once the patient has been headache-free for at least 2 weeks, the preventive therapy is gradually tapered off.

Primary options

melatonin: consult specialist for guidance on dose

2nd line – topiramate

Back
ONGOING
|
preventive treatment for episodic cluster headache
2nd line – 

topiramate

The main goal of preventive therapy is rapidly suppressing individual attacks and maintaining remission for the duration of the patient's typical cluster period.

Topiramate appears to be relatively effective in clinical practice in the preventive treatment of cluster headache.[1][9][26][33]​​ Potential adverse effects include paresthesias, weight loss, cognitive slowing, hypohidrosis, nephrolithiasis, and acute angle-closure glaucoma. 

Topiramate is usually contraindicated in pregnancy, especially in the first trimester during organ development, because of the risk of major congenital malformations (cleft lip or palate).[72][73]​ However, it has been suggested that it may be considered in the second and third trimesters for pregnant patients with severe cluster headache when other treatments are ineffective, if the benefit to the mother clearly exceeds the possible risk to the fetus.[74]​ In some countries, topiramate is contraindicated in women of childbearing age unless the conditions of a pregnancy prevention program are fulfilled to ensure that women of childbearing potential: are using highly effective contraception; have a pregnancy test to exclude pregnancy before starting topiramate; and are aware of the risks associated with use of the drug.

For patients with episodic cluster headache, once the patient has been headache-free for at least 2 weeks, the preventive therapy is gradually tapered off.

Primary options

topiramate: 25 mg orally once daily for 7 days, increase by 25 mg/day increments once weekly to 100-200 mg/day given in 2 divided doses

2nd line – gabapentin

Back
ONGOING
|
preventive treatment for episodic cluster headache
2nd line – 

gabapentin

The main goal of preventive therapy is rapidly suppressing individual attacks and maintaining remission for the duration of the patient's typical cluster period.

Evidence for gabapentin is scarce and clinical experience is not always as dramatic as that reported in the literature.[1][26][49]

Gabapentin may be used with caution in pregnancy (avoided during the first trimester and dose kept as low as possible), but there is some suggestion of an increased risk of fetal abnormalities.[74]

For patients with episodic cluster headache, once the patient has been headache-free for at least 2 weeks, the preventive therapy is gradually tapered off.

Primary options

gabapentin: consult specialist for guidance on dose

3rd line – divalproex sodium

Back
ONGOING
|
preventive treatment for episodic cluster headache
3rd line – 

divalproex sodium

The main goal of preventive therapy is rapidly suppressing individual attacks and maintaining remission for the duration of the patient's typical cluster period.

Divalproex sodium (equimolar amounts of valproic acid and sodium valproate) has been deemed as "probably ineffective", but it may be considered in circumstances where all other treatments have failed.[26]

Valproic acid and its derivatives may cause major congenital malformations, including neurodevelopmental disorders and neural tube defects, after in utero exposure. These drugs are contraindicated in pregnancy; however, if it is not possible to stop them, treatment may be continued with appropriate specialist care. These agents must not be used in female patients of childbearing potential unless other options are unsuitable, there is a pregnancy prevention program in place, and certain conditions are met. Precautionary measures may also be required in male patients owing to a potential risk that use in the 3 months leading up to conception may increase the likelihood of neurodevelopmental disorders in their children. Regulations and precautionary measures for female and male patients may vary between countries, with some countries taking a more heightened precautionary stance, and you should consult your local guidance for more information.

For patients with episodic cluster headache, preventive therapy is gradually tapered off once the patient has been headache-free for at least 2 weeks.

Primary options

divalproex sodium: 250-500 mg orally (delayed-release) twice daily; some specialists may recommend higher doses

preventive treatment for chronic cluster headache

1st line – verapamil

Back
ONGOING
|
preventive treatment for chronic cluster headache
1st line – 

verapamil

The main goal of preventive therapy is rapidly suppressing individual attacks and maintaining remission.

Verapamil is considered the first-line preventive therapy for both episodic and chronic cluster headache.[1][26][29][33]​​[39]​​

An ECG must be performed before verapamil is prescribed to exclude bradycardia and other conduction abnormalities, specifically PR interval prolongation. ECGs are then repeated before each dose increase to check for signs of developing heart block.[40]

Adverse effects include constipation, dizziness, and lower extremity swelling.

Evidence for the safety of verapamil in pregnancy is limited, but calcium-channel blockers are generally thought to be safe, and nifedipine is used widely as an antihypertensive treatment in pregnancy, with limited adverse effects and established safety.[69][70][72]

For patients with chronic cluster headache, preventive therapy is continued indefinitely; however, if the patient remains headache-free, reducing the dose may be periodically attempted.

Primary options

verapamil: 80 mg orally (immediate-release) three times daily initially, increase gradually according to response, maximum 480 mg/day; some specialists may recommend higher doses

Consider – noninvasive vagus nerve stimulation

Back
ONGOING
|
preventive treatment for chronic cluster headache
Consider – 

noninvasive vagus nerve stimulation

Treatment recommended for SOME patients in selected patient group

In patients with chronic cluster headache, noninvasive vagus nerve stimulation as an adjunct to standard of care was shown to significantly reduce cluster headache attack frequency compared with standard of care alone.[1][33]​​[50][51]​​

There have been no reports of pregnancy-related adverse effects of noninvasive neuromodulation.[69][70]

2nd line – lithium

Back
ONGOING
|
preventive treatment for chronic cluster headache
2nd line – 

lithium

The main goal of preventive therapy is rapidly suppressing individual attacks and maintaining remission.

Lithium is reported as being effective as prophylaxis, although evidence is contradictory.[1][9][26][32][33]​​

Lithium levels should be monitored to prevent toxicity due to a narrow therapeutic range.[9] Although no therapeutic level for lithium has been established for cluster headache, clinical experience suggests that patients respond best when at the higher end of the therapeutic range. Lithium toxicity can result in nausea, vomiting, tremors, confusion, and vision changes. Hypothyroidism and kidney dysfunction are potential long-term adverse effects. Once a patient's clinical state and lithium levels are stable, the dose can be maintained.

Lithium is usually contraindicated in pregnancy, especially in the first trimester during organ development, because of the risk of major congenital malformations.[72][73] However, it has been suggested that it may be considered in the second and third trimesters for pregnant patients with severe cluster headache when other treatments are ineffective, if the benefit to the mother clearly exceeds the possible risk to the fetus.[74]

For patients with chronic cluster headache, preventive therapy is continued indefinitely; however, if the patient remains headache-free, reducing the dose is periodically attempted.

Primary options

lithium: consult specialist for guidance on dose

Consider – noninvasive vagus nerve stimulation

Back
ONGOING
|
preventive treatment for chronic cluster headache
Consider – 

noninvasive vagus nerve stimulation

Treatment recommended for SOME patients in selected patient group

In patients with chronic cluster headache, noninvasive vagus nerve stimulation as an adjunct to standard of care was shown to significantly reduce cluster headache attack frequency compared with standard of care alone.[1][33]​​[50][51]​​

There have been no reports of pregnancy-related adverse effects of noninvasive neuromodulation.[69][70]

2nd line – melatonin

Back
ONGOING
|
preventive treatment for chronic cluster headache
2nd line – 

melatonin

The main goal of preventive therapy is rapidly suppressing individual attacks and maintaining remission.

Melatonin has been reported to be effective, but evidence is largely anecdotal.[1][26][44]

Given its safety profile, some have suggested melatonin as first-line therapy in all patients requiring short-term prevention.[11][45] However, better-quality evidence for effectiveness is available for other therapies.

For patients with chronic cluster headache, preventive therapy is continued indefinitely; however, if the patient remains headache-free, reducing the dose is periodically attempted.

Primary options

melatonin: consult specialist for guidance on dose

Consider – noninvasive vagus nerve stimulation

Back
ONGOING
|
preventive treatment for chronic cluster headache
Consider – 

noninvasive vagus nerve stimulation

Treatment recommended for SOME patients in selected patient group

In patients with chronic cluster headache, noninvasive vagus nerve stimulation as an adjunct to standard of care was shown to significantly reduce cluster headache attack frequency compared with standard of care alone.[1][33]​​[50][51]​​

There have been no reports of pregnancy-related adverse effects of noninvasive neuromodulation.[69][70]

2nd line – topiramate

Back
ONGOING
|
preventive treatment for chronic cluster headache
2nd line – 

topiramate

The main goal of preventive therapy is rapidly suppressing individual attacks and maintaining remission.

Topiramate appears to be relatively effective in clinical practice in the preventive treatment of cluster headache.[1][9][33]​​​[75]​​​ Potential adverse effects include paresthesias, weight loss, cognitive slowing, hypohidrosis, nephrolithiasis, and acute angle-closure glaucoma. 

Topiramate is usually contraindicated in pregnancy, especially in the first trimester during organ development, because of the risk of major congenital malformations (cleft lip or palate).[72][73]​ However, it has been suggested that it may be considered in the second and third trimesters for pregnant patients with severe cluster headache when other treatments are ineffective, if the benefit to the mother clearly exceeds the possible risk to the fetus.[74]​ In some countries, topiramate is contraindicated in women of childbearing age unless the conditions of a pregnancy prevention program are fulfilled to ensure that women of childbearing potential: are using highly effective contraception; have a pregnancy test to exclude pregnancy before starting topiramate; and are aware of the risks associated with use of the drug.

For patients with chronic cluster headache, preventive therapy is continued indefinitely; however, if the patient remains headache-free, reducing the dose is periodically attempted.

Primary options

topiramate: 25 mg orally once daily for 7 days, increase by 25 mg/day increments once weekly to 100-200 mg/day given in 2 divided doses

Consider – noninvasive vagus nerve stimulation

Back
ONGOING
|
preventive treatment for chronic cluster headache
Consider – 

noninvasive vagus nerve stimulation

Treatment recommended for SOME patients in selected patient group

In patients with chronic cluster headache, noninvasive vagus nerve stimulation as an adjunct to standard of care was shown to significantly reduce cluster headache attack frequency compared with standard of care alone.[1][33]​​[50][51]​​

There have been no reports of pregnancy-related adverse effects of noninvasive neuromodulation.[69][70]

2nd line – gabapentin

Back
ONGOING
|
preventive treatment for chronic cluster headache
2nd line – 

gabapentin

The main goal of preventive therapy is rapidly suppressing individual attacks and maintaining remission.

Evidence for gabapentin is scarce and clinical experience is not always as dramatic as that reported in the literature.[1][26][49]

Gabapentin may be used with caution in pregnancy (avoided during the first trimester and dose kept as low as possible), but there is some suggestion of an increased risk of fetal abnormalities.[74]

For patients with chronic cluster headache, preventive therapy is continued indefinitely; however, if the patient remains headache-free, reducing the dose is periodically attempted.

Primary options

gabapentin: consult specialist for guidance on dose

Consider – noninvasive vagus nerve stimulation

Back
ONGOING
|
preventive treatment for chronic cluster headache
Consider – 

noninvasive vagus nerve stimulation

Treatment recommended for SOME patients in selected patient group

In patients with chronic cluster headache, noninvasive vagus nerve stimulation as an adjunct to standard of care was shown to significantly reduce cluster headache attack frequency compared with standard of care alone.[1][33]​​[50][51]​​

There have been no reports of pregnancy-related adverse effects of noninvasive neuromodulation.[69][70]

2nd line – galcanezumab

Back
ONGOING
|
preventive treatment for chronic cluster headache
2nd line – 

galcanezumab

The main goal of preventive therapy is rapidly suppressing individual attacks and maintaining remission.

Efficacy of galcanezumab in preventing chronic cluster headache was not demonstrated in a randomized, placebo-controlled study, but a retrospective real-world study suggested benefit for some patients.[42][43]

Galcanezumab is approved in the US for episodic cluster headache; use in chronic cluster headache is off-label. Galcanezumab is recommended in European guidelines as an off-label treatment option for patients with intractable episodic cluster headache (it is only approved for the treatment of migraine in Europe).[33]

There is no safety information about galcanezumab in pregnancy, and it is not currently recommended for pregnant women; patients should stop taking it 6 months before trying to become pregnant.[70]

For patients with chronic cluster headache, preventive therapy is usually continued indefinitely; however, if the patient remains headache-free, the interval between doses may be extended.

Primary options

galcanezumab: 300 mg subcutaneously once monthly

Consider – noninvasive vagus nerve stimulation

Back
ONGOING
|
preventive treatment for chronic cluster headache
Consider – 

noninvasive vagus nerve stimulation

Treatment recommended for SOME patients in selected patient group

In patients with chronic cluster headache, noninvasive vagus nerve stimulation as an adjunct to standard of care was shown to significantly reduce cluster headache attack frequency compared with standard of care alone.[1][33]​​[50][51]​​

There have been no reports of pregnancy-related adverse effects of noninvasive neuromodulation.[69][70]

3rd line – divalproex sodium

Back
ONGOING
|
preventive treatment for chronic cluster headache
3rd line – 

divalproex sodium

The main goal of preventive therapy is rapidly suppressing individual attacks and maintaining remission.

Divalproex sodium (equimolar amounts of valproic acid and sodium valproate) has been deemed as "probably ineffective", but it may be considered in circumstances where all other treatments have failed.[26]

Valproic acid and its derivatives may cause major congenital malformations, including neurodevelopmental disorders and neural tube defects, after in utero exposure. These drugs are contraindicated in pregnancy; however, if it is not possible to stop them, treatment may be continued with appropriate specialist care. These agents must not be used in female patients of childbearing potential unless other options are unsuitable, there is a pregnancy prevention program in place, and certain conditions are met. Precautionary measures may also be required in male patients owing to a potential risk that use in the 3 months leading up to conception may increase the likelihood of neurodevelopmental disorders in their children. Regulations and precautionary measures for female and male patients may vary between countries, with some countries taking a more heightened precautionary stance, and you should consult your local guidance for more information.

For patients with chronic cluster headache, preventive therapy is continued indefinitely; however, if the patient remains headache-free, reducing the dose is periodically attempted.

Primary options

divalproex sodium: 250-500 mg orally (delayed-release) twice daily; some specialists may recommend higher doses

Consider – noninvasive vagus nerve stimulation

Back
ONGOING
|
preventive treatment for chronic cluster headache
Consider – 

noninvasive vagus nerve stimulation

Treatment recommended for SOME patients in selected patient group

In patients with chronic cluster headache, noninvasive vagus nerve stimulation as an adjunct to standard of care was shown to significantly reduce cluster headache attack frequency compared with standard of care alone.[1][33]​​[50][51]​​

There have been no reports of pregnancy-related adverse effects of noninvasive neuromodulation.[69][70]

4th line – surgery for refractory chronic cluster headache

Back
ONGOING
|
preventive treatment for chronic cluster headache
4th line – 

surgery for refractory chronic cluster headache

Surgery should only be considered for refractory chronic cluster headache once all other options have been tried, as procedures carry risks of serious adverse events.[33]

Occipital nerve stimulation (ONS) was shown in cohort studies to be a promising therapeutic option for intractable chronic cluster headache, with over two-thirds of patients showing a good response.[26][54][55][56][57]​​ There is evidence that ONS is effective even in the longer-term treatment of chronic cluster headache.[58][59] Adverse effects or complications include infection, lead breakage and migration requiring replacement, battery depletion and replacement, skin discomfort, and painful overstimulation.

Invasive sphenopalatine ganglion stimulation involves implantation of a miniaturized device. Evidence shows that the device is useful both in the treatment of acute attacks and potentially as a preventive treatment.[60][61][62] There is no evidence available on its long-term effectiveness.

Deep brain stimulation (DBS) of the posterior hypothalamic region can relieve intractable cluster headaches, with over two-thirds of patients reporting over a 50% improvement in attack.​[64][65][66]​​​​[67][68]

The potential adverse-effect profile of DBS includes intracerebral bleed, stroke, death, infection, and seizure (although all are very rare), and so it should only be considered for patients in whom all other options, including peripheral neurostimulation with ONS, have failed.

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