DHE For Migraines 2023
DHE For Migraines
Migraine is present in 12% of the world’s population and is a common cause of disability. For women, Migraine is their most common medical problem and they have it three times more common than men. Migraine headaches come with one-sided throbbing moderate or severe pain, sensitivity to light and sound, and nausea and vomiting.
Subcutaneous, intramuscular, and nasal DHE are effective acute outpatient treatment for Migraine, severe Medication Overuse Headache (MOH), and Status Migrainosus. Hospital treatment with IV DHE works for sicker persons.
Headache doctors instruct their patients to either quickly or slowly stop over treating with their previous medications and switch over to DHE which will usually cover the headache but not cause Medication Overuse Headache.
This is an article by Britt Talley Daniel MD, member of the American Academy of Neurology, the American Headache Society, migraine textbook author, and blogger.
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Frequency of MOH
The most common new patient diagnosis for headache specialists is medication overuse headache, a syndrome caused by overtreatment with Migraine medications. Regular Migraine therapeutic drugs will not help these migraineurs.
History of Ergotamine
Ergotamine blocks serotonin receptors and causes constriction of arteries—vasoconstriction. It was first used in the sixteenth century to induce childbirth by causing constriction of smooth muscle in the uterus and then later for migraine in 1925.
Ergotamine for acute therapy of migraine had its heyday from the sixties until the nineties when Imitrex 6 mg sc injectable first came out but is rarely used for acute migraine treatment now.
A progeny of ergotamine is dihydroergotamine (DHE) which was first produced in the US in 1946. DHE blocks serotonin receptors and causes constriction of cranial blood vessels, but mainly veins. It has a long half-life of 9 hours.
MOH patients need a drug that can be given acutely to help their Migraine suffering that does not continue the Migraine inflammatory process or cause medication overuse headache.
DHE is a drug that will do this.
DHE has been used as the go to acute migraine medication for patients taking too much headache medicine—medication overuse headache.
All across America major hospitals have headache neurologists who admit patients with Chronic Migraine for IV DHE treatment. DHE can be given IV, IM, SC, and as a Nasal Spray but it is not available orally.
How is DHE given?
For Acute migraine and cluster headache treatment in adults it may be given 1mg SC/IM/Iv once with a max of 3 mg /24 hours SC/IM up to 6 mg/week;2 mg/24 h IV up to 6 mg/wk, may repeat the dose every 1 hour.
Parental (injectable) treatment is usually given at the hospital and there is a program for 5 days of hospital admission with IV DHE treatment that may be given to certain patients. Intravenous DHE injection is usually very effective for severe, frequent migraine headaches or what is called “status migrainosus.”
Pediatric dosing is currently unavailable or not applicable for this drug.
DHE can also be given by a nasal spray called Migranal which is about 1/6th as strong as parenteral treatment above (IV, IM, SC). However, it is usually effective and a great relief to those who can’t learn to give themselves a shot.
However, if a patient doesn’t respond well to NS DHE, they may respond to DHE IM because it is stronger.
One study found that 61 % of Migranal patients experienced relief by 2 hours and 86% of responders had no recurrence for 24 hours.
A new drug utilizing a new nasal dispenser mechanism of DHE is Trudhesa which is designed to be self-administered. Once assembled, Trudhesa should be primed before initial use by releasing 4 sprays. A patient should use Trudhesa immediately after priming. The recommended dose of Trudhesa is 1.45 mg administered as two metered sprays into the nose (one spray of 0.725 mg into each nostril).
The dose may be repeated, if needed, a minimum of 1 hour after the first dose. A patient should not use more than 2 doses of Trudhesa within a 24-hour period or 3 doses within a 7-day period. A patient should use or discard Trudhesa within 8 hours once the vial has been opened or the product has been assembled. A consumer assembly video is available on www.TRUDHESA.com.
Do not use DHE within 24 hours of triptan use.
An important point is that DHE should not be used within 24 hours of triptan use. Patients may use Migranal NS, Trudhesa, and IM DHE at home and usually don’t need to be admitted to hospital for further treatment.
Oral bioavailability is poor, and it is not available in oral form in the US.
Migraine attacks should be treated quickly at onset.
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Are there any serious side effects of the drug?
DHE has a black box warning for causing serious and/or life-threatening peripheral ischemia of limbs or cerebral ischemia. Nausea is a common side effect of IV administration and less common in other modes.
Antiemetics can be given prior to DHE to counteract the nausea. Risks and contraindications are similar to the triptans. DHE and triptans should never be taken within 24 hours of each other due to the potential for coronary artery vasospasm. DHE produces no dependence.
Rare milder side effects may be nausea and leg cramping.
What are the typical uses of DHE/Migranal?
Migranal nasal spray may be used for out-patients with medication overuse headache, where they may need it for several weeks while they detox from all the pain killers they have been taking and they need something for episodes of acute headache that won’t worsen their situation.
It may also be used for patients who get into trouble taking triptans more than 2 days a week and develop short term medication overuse headache. The International Classification of Headache Disorders V 3 requires overtreating for 3 months to make a precise diagnosis of Medication Overuse Headache, but many patients have problems with shorter times of overtreatment, like several weeks or a month.
Some patients are helped by limiting triptan use to 2 days only (all migraine patients are supposed to do this) and then take DHE for a third headache day in a week, as long as it is 24 hours since they have taken a triptan.
Patients like this need to be doing the migraine lifestyle and consider getting on a preventive drug.
After they get back into episodic migraine, some patients prefer DHE NS over triptans and they just stay on that treatment.
Using DHE this way, I very rarely have to admit patients with headache but can manage most of them in the office. They need a drug that can be given acutely to help their Migraine suffering that does not continue the Migraine inflammatory process or cause medication overuse headache.
DHE is a drug that will do this.
A good question is “What type or clinical make up of persons get MOH?”
DHE Mechanism of action
DHE's antimigraine activity is due to its action as an agonist to the serotonin (5-HT) 1B,1D, and 1F receptors. It also interacts with other serotonin, adrenergic and dopamine receptors.
Contraindications of DHE:
Pregnancy
Breastfeeding
Severe renal or hepatic impairment
Ischemic heart disease
Uncontrolled hypertension
Peripheral arterial disease
Basilar or hemiplegic migraine
DHE Availability
DHE is available as a nasal spray and in ampules for subcutaneous, intramuscular and intravenous injection. Efficacy is variable in the nasal spray form with bioavailability 32% of injectable administration.
Medical articles on use of DHE for Migraine
Andrew Josephson, M.D., Medscape March 18, 2020. “A Long Course of Intravenous Dihydroergotamine Likely Effective for Refractory Headaches.”
For nearly three decades, IV dihydroergotamine (DHE) has been an option for treatment of refractory migraine in both emergency and inpatient settings.
Nagy and colleagues (2011) examined a large series of cases using IV DHE for a variety of headache conditions and in a more prolonged dosing schedule in order to report a contemporary experience with this drug.
The authors retrospectively interviewed a subpopulation of 163 of the 446 patients treated with IV DHE over a 5-year period at a single institution in London. A total of 110 women and 52 men with an average age of 45 years were included.
Diagnoses included chronic migraine in 114 (70%), cluster in 38 (23%), and new daily persistent headache in 11 (7%). One patient had both migraine with aura and new daily persistent headache.
Patients were treated with an IV DHE inpatient protocol that included 5 days of treatment with a goal cumulative dosage of 11.25 mg (range, 8.25–11.25 mg). Severe nausea, a known side effect, was treated with a variety of antiemetic medications.
A total of 74% of the patients with migraine reported benefit, half of which was rated as moderate or excellent. A total of 67% reported headache freedom during treatment, and 75% percent achieved freedom within 1 month of therapy.
The effect of this therapy on these patients with medically refractory migraine lasted an average of 28 days. All of the treated patients halted their medication overuse, including that of narcotics—a primary reason why some have advocated admission for IV DHE therapy in the past.
In terms of disability, 25% reported less time off work following treatment and 50% reported increased activity. Patients who had migraine with aura (n=42) had no appreciable differences in their results compared to those without aura.
A total of 84% of the patients with cluster headache reported headache freedom during the hospitalization for IV DHE treatment; the mean time to return of attacks was 17 days. Of the 11 patients with new daily persistent headache, only 2 (18%) reported a mild benefit with the treatment.
In the entire cohort, the largest predictor of achieving a pain-free state in a logistic model was increasing DHE dose (p = .001); greater amounts of nausea despite treatment with antiemetics was a predictor of failure to become pain free (p = .002).
The most common adverse event was nausea, which was reported in 94 patients (58%) and led to cessation of IV DHE treatment in 6. Other common adverse events were leg cramps and the need for replacement of the peripheral IV. Other side effects included limb pain with infusion in 26 and chest tightness during the infusion in 5. No cardiac effects including electrocardiographic changes were found in the cohort.
This report certainly suffers from limitations inherent in a retrospective analysis of an uncontrolled study. However, a few important points emerge in this modern snapshot of DHE use that may be useful to clinicians.
First, DHE is an effective therapy that can be considered in patients with refractory headache disorders including cluster headache. Interestingly, some of the patients achieved their pain-free state in a delayed fashion following discharge; this suggests that physicians should counsel their patients that the goal of IV DHE therapy is not to achieve a pain-free state during the actual admission but rather that some effects will be achieved only well after discharge and may be long-lasting.
Nausea is a common side effect and, if not controlled aggressively, can lead to treatment failure. Finally, the successful response to a longer course and cumulative dose of DHE, often 5 days and 11.25 mg, should drive protocol changes in hospitals considering this treatment. For clinicians and their patients with refractory migraine or cluster headache, IV DHE should be considered, although the cost-benefit analysis of a potentially 5-day hospitalization is an extremely important consideration meriting future investigation.
Ford, RG, Ford KT. Headache. 1997 Mar;37(3):129-36. “Continuous intravenous dihydroergotamine in the treatment of intractable headache.”
Abstract
We reviewed data on 171 patients with refractory headache treated by continuous intravenous dihydroergotamine mesylate (I.V. DHE 45) and repetitive I.V. DHE and compared the efficacy of continuous I.V. DHE to repetitive I.V. DHE. One hundred (58.5%) patients had refractory chronic daily headache. Seventy-one (42%) had drug rebound headache.
One hundred thirty-eight (81%) had refractory migraine without aura, and 28 (16%) had migraine with aura.
Treatment consisted of either continuous I.V. DHE by infusion pump or repetitive I.V. DHE and withdrawal of excessively used analgesics, analgesic narcotics, ergotamines, or benzodiazepines. Eighty-nine (92.5%) patients treated with continuous I.V. DHE became headache-free; the majority, 62 (64.5%), within 3 days. Sixty-five (86.5%) patients treated by repetitive I.V. DHE became headache-free, 50 (66.5%) within three days.
The average hospital stay for both treatment groups was 4 days. Twelve (12.5%) of the continuous group and 12 (16%) of the repetitive group were headache-free within 24 hours. The average length of time to become headache-free was similar for the two groups, 3.06 days for continuous I.V. DHE and 2.94 days for repetitive I.V. DHE.
The most common side effect was nausea, followed by diarrhea, vomiting, and leg cramps. We conclude that DHE can be accurately and easily administered by continuous I.V. infusion pump, and that continuous I.V. DHE is a safe and efficacious mode of treatment producing results similar to repetitive I.V. DHE.
Summary Comment.
It would be hard to practice headache medicine without using DHE. In the U.S. starting about 2016 and through 2018 it was unavailable for doctors to use. No reason was ever given for this.
That’s when we had to use Timolol eye drops, promethazine, quetiapine, and olanzapine, drugs indicated for psychiatric treatment because of their effect as dopamine antagonists. Timolol is a betablocker eye drop that is indicted for glaucoma.
Remember that 80-90% of visits to a headache practice are patients with medication overuse headache. Even though medication overuse headache is only about 3% of headache worldwide, it is great to have such a drug as DHE to treat these difficult patients.
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Britt Talley Daniel MD