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CHUM, Centre Hospitalier Universitaire de Montréal

Headache Treatment update, the letter

Vol.2 no1 April 2007

Medication overuse headache

Generalities: Medication overuse headache has been defined as the perpetuation or maintenance of chronic head pain in chronic headache sufferers, caused by frequent and excessive use of rescue medication. A majority of subjects (76.7%) 1 have more than 28 headache days per month and 12.9% of subjects, have 15-21 headache days per month. Over- users, may use 1 (35.1%), 2 (36.8%) or 3 (31.6%) substances1. Drugs overused are; butalbital, acetaminophen, opiates, NSAIDs, aspirin, ergot compounds and triptans. Overuse to aspirin and triptans have increased since 19951. Rebound may refer to the fluctuating headache during the period of overuse of medication (Saw teeth manifestation of daily head pain) or at other times, refer to the worsening of headache when the medications are abruptly stopped (Status migrainosus) 1. Patients with overuse may improve simply by being kept medication free for 2 months2. Not all patients improve this way; 45% improve, 48% stay unchanged, and 7% deteriorate2. The reduction in headache frequency is more significant in pure migraine compared to tension type headache, migraine and tension type headache, and other headache diagnosis2. If all patients with medication induced headache are kept off medication for 2 months, with strong encouragement, relative reduction in headache frequency within 7 months, for all headache groups is possible; with renewed effect of prophylaxis or appearance of responsiveness to pharmacological and non pharmacological therapeutic intervention2. Diagnosis: Use IHS criteria for diagnosis. Overuse is in terms of treatment days per month, on more than several days each week. The headache, within the same day, may shift from a headache with migraine like characteristics, to having those of tension type headache, or status migrainosus. The doses of overused medication are: ergot > 10days/month > 3 months, Triptans > 10 days/month >3months, and analgesics >15 days/month, opiates > 10 days/month, combination medication > 10 days/month for > 3months. Diagnosis of medication overuse is confirmed when overuse has been discontinued and the patient has shown improvement2. Principles of Treatment: · Uncomplicated medication overuse cases: Currently, there are no universally accepted standardized therapeutic protocols and no specific guidelines for medication overuse headache. In simple cases, (see below for definition of complicated cases) detoxification therapy consists in withdrawing the overused drug(s) and treatment of the withdrawal symptoms by means of a bridging programme of pharmacological or/and a non pharmacological support, designed to help the patient tolerate the withdrawal process. This is performed as an out patient. Effective education is crucial to proper management of medication overuse headache and decisive implication of the patient is mandatory. A transitional therapy may not be necessary during the acute phase of withdrawal for these patients3. An ideal time lapse for neuronal convalescence would be 2 months2. · Complicated medication overuse cases: Patients with a current diagnosis or history of coexistent, significant and complicating medical illnesses with a current diagnosis of mood disorder, anxiety disorder or addiction disorder using a structured interview for DSM-IV axis I disorders4; Overuse of agents containing opiates, barbiturates, benzodiazepines; the use of prophylactic drugs within the past 3 months; previous detoxification treatments; inability to furnish reliable information about medical history and psychiatric symptoms and contraindication to different detoxification pharmacological protocols3. Then these patients should be treated by a team in a headache clinic, ideally as out patients5, 6

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Most common treatment and recommended detoxification protocols in Canada

Table 1. Modified Raskin DHE protocol6

Dosing and timing of anti-emetic (metoclopramide), and anti-migraine (dihydroergotamine; DHE) medication. Outpatient, clinic-based Day 1: 0800­1000: metoclopramide 10­20 mg p.o. + DHE 0.5­1 mg i.v. 1600­1800: metoclopramide 10­20 mg p.o. + DHE 0.5­1 mg i.v. 2200­0000: metoclopramide 10­20 mg p.o. + DHE i.n. or DHE 0.5­1 mg s.c. Day 2: 0800­1000: metoclopramide 10­20 mg p.o. + DHE 0.5­1 mg i.v. 1600­1800: metoclopramide 10­20 mg p.o. + DHE 0.5­1 mg i.v. 2200­0000: metoclopramide 10­20 mg p.o. + DHE i.n. or DHE 0.5­1 mg s.c. Day 3: 0800­1000: metoclopramide 10­20 mg p.o. + DHE 0.5­1 mg i.v. 1600­1800: metoclopramide 10­20 mg p.o. + DHE 0.5­1 mg i.v. 2200­0000: metoclopramide 10­20 mg p.o. + DHE i.n. or DHE 0.5­1 mg s.c. Outpatient, home-based Day 4: Metoclopramide 10­20 mg p.o. bid + DHE 0.5­1 mg s.c. or DHE 1 unit i.n., bid Day 5: Metoclopramide 10­20 mg p.o. bid + DHE 0.5­1 mg s.c. or DHE 1 unit, i.n. bid Day 6: Metoclopramide 10­20 mg p.o. bid + DHE 0.5­1 mg s.c. or DHE 1 unit i.n. bid Outpatient, end of protocol Day 7: DHE 0.5­1 mg s.c. bid prn or DHE 1 unit, i.n. bid prn, 2­3 days/week + prophylaxis Or New rescue medication (triptan) 2­3 days/week + prophylaxis i.n., intranasal; i.v., intravenous; p.o., oral; s.c., subcutaneous

Table 2: Raskin protocol8

10 mg metocolpramide IV 0.5mg DHE IV (2-3min.)

nausea

Persistant pain No nausea

No pain. No nausea

Wait 8 hours, then 0.3-0.4mg DHE q8h h for 3 days + 10mg metoclopramide

DHE 0.5mg IV 1hour later No metoclopramide Then DHE 0.75- 1 mg q8h x2days

DHE 0.5mg IV q 8h For 3 days + 10mg metoclopramide

Table 3: Corticosteroids7

Oral prednisone treatment First week (7days) 1-2 mg/kg/day with a maximal dose of 100mg/day. 100 mg/day divided in 2 doses (morning and night), ten pills of 5 mg bid or one 50mg pill BID. Second week: start decrease of prednisone with the following regimen (10mg pills) Day 1 : 5 pills in the morning, 4 pills at bed time

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Day 2: 4 pills in the morning , 4 pills at bed time Day 3: 4 pills in the morning, 3 pill at bed time Day 4: 3 pills in the morning, 3 pills at bed time Day 5: 3 pills in the morning, 2 pills at bed time Day 6: 2 pills in the morning, 2 pills at bed time Day 7: 2 pills in the morning, 1 pill at bed time Day 8: 1 pill in the morning, 1pill at bed time, and stop the next day You stop all analgesics at midnight before the beginning of this treatment.

Other Corticosteroid regimen Prednisone, 6 day tapering course* 60mg/day x 2, 40mg/day x 2, 20mg/day x 2 and stop Prednisone, 5 day fixed dose** 100mg/day x 5 and stop , no tapering * 2 large open label studies, ** 1 small placebo controlled study

Table 4:Neuroleptics7

Chlorpromazine.*

* no clinical studies

Dose. 12.5- 25mg (IV,IM,PO) 3-4x/day

Maximum daily dose 150mg/24hrs

Table 5:NSAID's7

NSAID's Naproxen* Indométhacin dose Po 500mg Sup 500mg Sup 100mg Max/24hres 1,000mg 1,000mg 150mg

*providing the patient is not overusing NSAIDs

Table 6:Sodium Valproate7

Sodium Valproate

Loading dose

maintenance dose IV 5mg/kg over 15min. q8h

IV 10mg/kg over 30 minutes

Table 7:Lidocaine7

Lidocaine*

Starting dose

Escalating dose 3mg/min for 24hrs., maximun less than 4mg/min

Maximum dose 3.4mg/k/h 4mg/min

duration maximum 7days

IV 1mg/min for 6-9hrs., 2mg/min for 24hrs.,

*hospitalization is mandatory with cardiopulmonary monitoring

Recruiting in clinical trials:

Prednisolone in the treatment of withdrawal headache in probable medication overuse headache; phase III, sponsor:Sorlandet Hospital HF Medication overuse headache: withdrawal or preventive medication; sponsor: Norwegian University of science and Technology Evaluation of almotriptan and topiramate in detoxification and treatment of subjects with medication overuse headache; phase IV, sponsor :Ortho-McNeil

References: 1: Bigal Me, Papoport AM, Sheftell FD, Tepper SJ, Lipton RB. Tranformed migraine and medication overuse in a tertiary headache centre-clinical characteristics and treatment. Cephalalgia,2004,24,483-490 2: Zeeberg P, Olesen J, Jensen R. Discontinuation of medication overuse in headache patients: recovery of therapeutic responsiveness. Cephalalgia, 2006, 26, 1192-1198 3: Rossi P, Di Lorenzo C, Faroni J, Cesarino F, Nappi G. Advice alone vs. Structured detoxification programmes for medication overuse headache: a prospective, randomized, openlabel trial in transformed migraine patients with low medical needs. Cephalalgia, 2006. 26, 1097-1105 4: Lake A E, Medication overuse headache: biobehavioral issues and solutions; Headache 2006;46(suppl 3):S88-S97 5: Suhr B, Evers S, Bauer B, Gralow I, Grotemeyer KH, Husstedt IW; Drug-induced headache: long-term results of stationary versus ambulatory withdrawal therapy. Cephalagia 19 1999, 44-49 6: Boudreau G, Aghai E, Marchand L, Langlois M. Outpatient intravenous dihydroergotamine for probable medication overuse headache. Headche Care Vol 3 No 1, 2006, 45-49 7: Paemeleire K, Crevitis L, Goadsby P, Kaube H. Practical management of medication-overuse headache. Acta neurol. Belg. 2006,106,43-51 8: Raskin NH. Headache 1990;30(2):550-53. This is a peer reviewed letter. Future updates: Migraine and pregnancy, migraine and breast feeding Registered Business Number 84636 8967 www.bic.mni.mcgill.ca/users/gaby/cliniques/migraine for previous headache letters

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