IV Levetiracetam For Treatment of Cluster Headachein the Clinic
John Claude Krusz PhD MD, Jane Cagle LVN, Dan Daniel RPH
CASE 4: GF, a 41 year old businessman had reonset of cluster headache episodes, leftsided, 2 months prior to being seen. He was having 3-6 episodes per day, mostly at night. 4 years prior, he had first onset of cluster headaches lasting almost 6 weeks. IV
INTRODUCTION: Levetiracetam is a unique molecule used for control of seizures
levetiracetam was given in the clinic with pulse oximetry monitoring. A total of 7200mg
and has also been shown to be useful for refractory headaches and pain, both orally and
was administered. He had total cessation of his cluster episodes for 108 hours. Very mild
intravenously1-3. We currently describe treatment of an acute or ongoing flareup of
and transient drowsiness were reported after 4800mg of levetiracetam. This ceased by the
cluster headache with IV levetiracetam, in this updated series of patients.
end of the treatment. Oral levetiracetam was started at 4500mg per day and preventedreturn of all but
milder cluster episodes. IV steroids, IV sodium valproate and oral
8 case reports are described at this point. All were males who had
topiramate were sequentially utilized and added to his regimen of oral levetiracetam.
onset of cluster headaches. 2 patients had co-existent migraines. They came to theheadache clinic; an IV was placed and levetiracetam was given IV. A 400-800mg testdose was given. Then, 800-1200 mg was given IV every 10 minutes with pulse oximetrymonitoring. Patients rated their cluster severity on a 0-10 NRS scale, at the clinic and forthe next few days after treatment.
CASE 5: BM, a 50 year old disabled salesman had sudden reonset of cluster headaches
All 8 patients reported cessation or marked amelioration of cluster
2 nights prior to office visit. He had 4 episodes per day, rated at #6/10 in severity. He
headache attacks with treatment. All were placed on oral levetiracetam for prophylaxis.
had a prior history of cluster headaches, present for 5 years and then in remission for 5
Average dose was 5625 mg (range 3400-11,200mg) over 45-75 minutes. Side effects
years. He is a smoker. IV levetiracetam was given in the office after an antecubital line
were not reported other than transient drowsiness in 2 patients.
was placed. Using pulse oximetry monitoring. A total of 4000mg was administered over90 minutes,eliminating the cluster eposide completely.
drowsiness, lasting 15 minutes. This stopped at the end of treatment. Cluster headaches
IV levetiracetam is a powerful potential option for treating acute
stopped over the next 7 days on oral levetiracetam and have not returned. This was tapered
cluster headaches, in the setting of a headache clinic.
importantly, efficacy have been well demonstrated in this and other open-label studies3treating migraines and cluster headaches. Double-blind studies are warranted forlevetiracetam IV. RATIONALE:
CASE 6: RR, a 32–year-old waiter, was treated for the third bout of biannual clusterheadaches. He was treated in the fourth week of his current upsurge of clusters, havingsix to eight episodes per day. After IV placement, 4000 mg of levetiracetam was given
Cluster headaches are quite devastating and very often difficult to treat
intravenously over about 15 minutes. This softened the cluster episodes to 1 very weak
successfully. Intravenously administered medication is considered ideal for terminating
episode in the 24 hours after treatment. He was placed on oral levetiracetam, 3000 – 4500
an ongoing attack of cluster headaches, and several options currently exist: IV steroids,
mg per day, with complete resolution of his cluster episodes. After approximately six
IV sodium valproate, SQ sumatriptan, IV DHE-45. The availability of another rapidly
acting and non-toxic IV agent would give the headache clinician more options forterminating the cluster attacks. We had demonstrated that IV levetiracetam had anexcellent efficacy and equally excellent tolerability in terminating intractable migraineheadaches3 and, for this reason, choose to treat acute or new flare-ups of cluster
CASE 7: CF, a 34-year-old salesman with a history of cluster headaches and common
headaches with this form of levetiracetam. Levetiracetam blocks high-voltage calcium
migraines, and experiencing up to 20 episodes right-sided cluster headaches per day, was
channels and was shown, for the first time, to have value in treating refractory migraines
treated with 3400 mg of intravenous levetiracteam over one hour. His #7/10 headache
dissipated to 0/10 and his cluster episodes ceased. He had an intercurrent short illness and
was started on oral levetiracetam, 3000 mg per day.
Levetiracetam, purchased commercially, was crushed (20-40gm) using a Wedgwoodmortar and pestle. 85ml of sterile water was added. The entire mixture was allowed tostand for 8 hours and then filtered through a 1micron filter. The filtrate was warmed to70 degrees C, and filtered five more times through a 1 micron filter; then, successive
CASE 8: JM, 54-year-old business owner, and left-sided clusters together with
filtrations, through a 45 millimicron filter were accomplished, for 5 more times. The
trigeminal neuralgia and a history of multiple sclerosis for over 20 years. He was far less
resulting solution was buffered to pH 6.0 with either 10% NaOH or 1 Normal HCl.
concerned with the cluster headaches although they occurred one to two times per day.
Sufficient sterile water was added to make a final volume of 100ml. The rationale behind
IV levetiracetam, 3600 mg, was given over 45 minutes. This caused his cluster headaches
this extraction process is that most of the inactive ingredients are eliminated in a cold
to cease, but did not have an effect on the left-sided trigeminal neuralgia pain. He waskept on oral levetiracetam, 4500 mg per day, pending other treatments for his trigeminal
extraction; hydroxypropylmethylcellulose is insoluble in hot water and, therefore,
eliminated with heating as described.
In a clean room with a sterile laminar flow horizontal hood, the above solution
was further filtered through a 22 millimicron filter into a sterile serum vial. The finalsolution was clear and transparent with a very low viscosity. Initially a concentration of
An average of 5625 mg (3400-11200 mg) levetiracetam was administered IV in
200mg/ml levetiracetam was compounded in 10ml multi-dose vials; after several patients
the clinic. In all cases, cessation of cluster episodes occurred and allowed rapid
were successfully treated, a concentration of 400mg/ml was adopted for routine use in
commencement of aggressive oral levetiracetam therapy for cluster prophylaxis. In one
this study. The final levetiracetam solution was preservative-free and, therefore, any
case (#4) additional medication strategies were added to oral levetiracetam to control
medication that was administered was routinely kept in a refrigerator at 3-4 degrees F. A
90-day expiration date was assigned to all vials of levetiracetam, whether used or not. The FDC blue and yellow colors washed out with the repeated filtrations as above. DISCUSSION:
This case series of successful treatment of cluster headaches with IV
CASE 1: RC, a 34 year old male with postconcussional left-sided migraines, developed
levetiracetam complements that obtained in the treatment of refractory migraines3.This is
right sided unilateral stabbing headaches with ptosis, lacrimation, rhinorrhea, and facial
an ongoing series of patients treated with IV levetiracetam for this condition. It adds
and eyelid numbness. These headaches would wake him up from sleep and were stabbing
another pharmacologic tool to the medications available for interrupting a cycle of cluster
in nature, lasting 5-15 minutes, up to 5 times per day. He had been tried on Topiramate
headaches. It also serves as a “loading” dose type of treatment, since patients were able to
without success for his migraines. He also used droperidol, IM, at home for his
continue on oral levetiracetam for prophylaxis. Safety and tolerability were quite evident
migraines.He was on tizanidine for sleep. His other medications did not abate the right-sided cluster episodes. This was the first onset of such headaches and he was treated on
in the lack of side effects of any note, despite dosing in excess of that typically used for
the 4th day of cluster headache. After placement of an IV, he was given a test dose of
seizure management. This was also the case for treatment of intractable migraine attacks3.
400mg levetiracetam IV. Then 400mg were given IV every 4-5 minutes. A total of
Levetiracetam should be studied intravenously for its effects in a double-blind manner
11,200mg levetiracetam was given. His #9/10 headache abated totally and he did not
and the manufacturer has presented data on the pharmacokinetic profile of IV
have any right sided cluster headaches nor any left sided migraines for 2 and a half
levetiracetam after single and repeated dosing4.
weeks. He reported no side effects to the medication. He was started on orallevetiracetam, 4500mg per day, but discontinued it when the headaches did not return. Six months after initial IV treatment, he had re-onset of right-sided cluster headaches andwas again treated with the same IV dose of levetiracetam, again with 3 weeks ofheadache-free time.He moved out of state and is lost to followup. CONCLUSIONS:
CASE 2: LM, a 58 year old man, had onset of left-sided headaches which woke him up
? Levetiracetam, given intravenously, is a powerful addition to the
from a sound sleep 6 weeks before his visit to the headache clinic. No prior history of any
medications that are useful in treating cluster headache flare-ups. It acts
type of headache. He was a smoker and had a history of CAD, with a coronary stent
rapidly to eliminate ongoing cluster headaches.
placement. He had a history of right-sided trigeminal neuralgia. Cluster episodes wereabout 4 to 5 per day. After IV placement, 5200mg of IV levetiracetam were given over 90
? It has excellent efficacy and tolerability for treating cluster headaches. An
minutes. No side effects other than mild drowsiness were reported. He reported no
average of 5625 mg was administered with almost no side effects.
headaches whatsoever for 3 days after treatment. He was placed on up to 5500mg per day
Cessation of cluster episodes occurred in each case.
of oral levetiracetam, with 2500mg at bedtime. After 2 months, he was tapered down to3500mg and after he felt the cluster episodes were gone, he was tapered off oral
? IV Levetiracetam can be the starting point for aggressive oral therapy with
the same medication for suppression of cluster headaches, without theneed for dosage titration.
CASE 3: MK, a 51 year old attorney, had right sided cluster headaches for nine years. These were daily and unremitting, but responded to DHE-45 injections, nalbuphineinjection and nasal spray. A host of prophylaxis medications were tried, includingzonisamide, oxcarbazepine, lamotrigine, gabapentin, topiramate, methadone andolanzapine. He came to the clinic with #10/10 headache, right sided, with ptosis andlacrimation. After IV placement, a total of 8800mg of IV levetiracetam was given over 90
minutes. Headaches ceased (0/10). No side effects were reported. MK was placed on oral
) Krusz, JC, Levetiracetam: novel agent for refractory chronic neuropathic pain, J of the Neurologic Sciences, 187 (Suppl 1):S474, 2001
levetiracteam, 5250mg per day. He has maintained a much better pattern on oral
2) Krusz, JC, Levetiracetam as prophylaxis for resistant headaches, Headache Quarterly, 12:54, 2001
3) Krusz, JC, Daniel, D., Intravenous levetiracetam for acute intractable migraines, Poster abstract: presented at the 14th Migraine Trust
International Symposium, Sept 2002, London, United Kingdom
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