Acute Pain Management: Migraine Headaches 2020-05-03آ  Acute Migraine Headache Treatment Algorithm 10

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  • Acute Pain Management:

    Migraine Headaches

    October 26, 2019

    Arezou Teimouri & Dr. Maureen Allen

    Choosing Wisely Academic Detailing Conference

  • Disclosures

    ▰ Arezou Teimouri, RPh

    ▻ BPharm, MPharmSci

    ▻ Drug Evaluation Unit

    ▻ No conflicts of interest

    ▰ Dr. Maureen Allen

    ▻ MD, CCFP-EM(PC), FCFP

    ▻ Family and Emergency Medicine

    ▻ No conflicts of interest

    2

  • Objectives

    Review the evidence for:

    ▰ Acetaminophen ▰ Acetaminophen with codeine combination

    ▰ Non-steroidal anti-inflammatory drugs (NSAIDs) for classic migraine headache treatment in outpatient settings.

    3

  • Patient Case: JP

    4

  • JP

    ▰ 44 year old male ▰ PMH: Classic Migraine Headaches (without aura) x 2

    years

    ▰ Has occasional migraines (~7/year, started after getting a new job)

    ▰ Current medication: acetaminophen 500 mg prn with minimal relief

    ▰ He recently heard of a new powdered drug that is mixed with water, that’s supposedly better for migraines

    ▰ Wants to know if that would be the best option

    5 PMH: past medical history; PRN: as needed/as required

  • Background

    Classic Migraine Headaches

    6

  • Classic Migraine Headache: Without Aura

    International Headache Society Criteria

    7

    Worthington I et al. Can J Neurol Sci. 2013; 40(5), Suppl.3 – S5

  • Classic Migraine Headache: With Aura

    8

    International Headache Society Criteria

    Worthington I et al. Can J Neurol Sci. 2013; 40(5), Suppl.3 – S5

  • Goals of Pharmacotherapy

    Relieve:

    ▰ Pain rapidly and consistently

    ▻ Pain-free within two hours ▰ Associated symptoms (e.g., nausea,

    vomiting, photophobia, phonophobia)

    ▰ Migraine-related disability (return to normal function)

    Minimal or no adverse events.

    9

    Worthington I et al. Can J Neurol Sci. 2013; 40(5), Suppl.3 – S6

  • Acute Migraine Headache Treatment Algorithm

    10

    Mild- Moderate

    • Acetaminophen

    • NSAIDs

    Moderate- Severe

    • NSAIDs + triptan rescue

    • Triptans

    Refractory • Triptan + NSAID combination

    ± rescue therapy

    • Dihydroergotamine

    ± metoclopramide

    prn for

    nausea/vomiting *Opioid (i.e., codeine)-

    containing medications

    and tramadol-containing

    medications are not

    recommended for routine

    use

    Worthington I et al. Can J Neurol Sci. 2013; 40(5), Suppl.3 – S33-62

  • EVIDENCE REVIEW 11

  • Important Terminology

    ▰ Pain-free Outcome

    ▻ Moderate or severe pain to none

    ▻ Pre-specified time interval (e.g. 2 hours)

    ▻ Desired by International Headache

    Society (IHS)

    ▰ Headache Response

    ▻ “Pain relief”

    ▻ “Headache relief”

    ▻ Decrease in headache intensity from moderate or

    severe to mild or none

    ▻ Pre-specified time intervals (1, 2, or 4 hours)

    12

    Worthington I et al. Can J Neurol Sci. 2013; 40(5), Suppl.3 – S11

  • Important Terminology Continued…

    ▰ Sustained pain-free

    ▻ The number (%) of patients pain-free at

    2 hours (h) + over

    the next 22 h

    (without rescue)

    ▰ Headache recurrence

    ▻ re-emergence of moderate-severe

    headache (within 24 h)

    after initial response

    13

    Worthington I et al. Can J Neurol Sci. 2013; 40(5), Suppl.3 – S11

  • Acetaminophen

    Evidence Review for Migraines

    14

  • “ Derry S, Moore R. Paracetamol (acetaminophen) with or without an antiemetic for acute migraine headaches in

    adults. Cochrane Database Syst Rev.

    2013, Issue 4. Art. No.: CD008040. DOI:

    10.1002/14651858.CD008040.pub3

    1515

  • Cochrane Review: Acetaminophen

    16

    Patients Adults ≥18 years of age Migraine diagnosis based on International Headache Society Criteria

    Intervention Paracetamol (acetaminophen) 1000 mg ± an antiemetic (self-administered)

    Comparator(s) Placebo, active-treatments

    Outcome(s)

    Primary outcomes:

     Pain-free at 2 h, without the use of rescue medication

     Reduction in headache pain (‘headache relief’) at 2 h

    Derry S, Moore R. Cochrane Database Syst Rev. 2013 (4).

  • Paracetamol 1000 mg vs. Placebo

    17

    Outcome Event rate

    RR

    95% CI

    NNT/NNH

    95% CIParacetamol 1000 mg

    Placebo

    Pain-free response at 2 h 19% 10%

    1.8

    (1.2-2.6)

    12

    (7.5-32)

    Headache relief at 2 h 56% 36%

    1.6

    (1.3-1.8)

    5.0

    (3.7-7.7)

    At least one AE 18% 23%

    0.78

    (0.64-0.95)

    21

    (11-300)

    Serious AE Insufficient Data

    Derry S, Moore R. Cochrane Database Syst Rev. 2013 (4).

    AE: adverse event; NNH: number needed to harm; NNT: number needed to treat; RR: risk ratio

  • Paracetamol 1000 mg vs. Placebo

    18

    NNH 21 At least one AE

    NNT 12 Pain-free response at 2 h

    NNT 5.0 Headache relief at 2 h

    Derry S, Moore R. Cochrane Database Syst Rev. 2013 (4).

    Quality of

    Evidence

    (GRADE) =

    Low

    3 studies (n=717)

    4 studies (n=1293)

    3 studies (n=717)

  • What about acetaminophen with codeine?

    19

  • “ Boureau F, Joubert JM, Lasserre V, Prum B, Delecoeuillerie G. Double- blind comparison of an acetaminophen

    400 mg-codeine 25 mg combination

    versus aspirin 1000 mg and placebo in

    acute migraine attack. Cephalalgia

    1994 04/01;14(2):156-161.

    20

  • RCT: Acetaminophen + Codeine

    21

    Boureau F, Joubert JM, Lasserre V, et al. Cephalalgia. 1994 04/01;14(2):156-161.

    P 18-65 years of age, migraine without aura based on International Headache Society

    criteria with onset before age 50

    (n=247)

    I Acetaminophen 400 mg combined with codeine 25 mg (ACC)

    C Aspirin 1000 mg, Placebo

    (Randomized, double-blind, double-dummy trial with cross-over during three periods).

    O Primary efficacy measure: complete or near-complete relief of pain after 2 h (score of 0 or 1

    on a four-point verbal scale)

  • Acetaminophen + Codeine vs. Aspirin vs.

    Placebo

    22

    Boureau F, Joubert JM, Lasserre V, et al. Cephalalgia. 1994 04/01;14(2):156-161.

    Outcome Event rate Statistical Significance

    Placebo Aspirin

    1000 mg

    ACC

    400/25 mg

    Complete or almost

    complete relief of

    headache after 2 h 29.8% 52.3% 49.7%

    NSS between aspirin vs. ACC

    Both aspirin and ACC significantly

    different from placebo (p=0.0003

    and p=0.0002)

    Complete relief after 2 h 11.1% 22.0% 18.4%

    NSS between the three groups

    (p=0.08)

    At least one AE 13.7% 14.7% 18.4% NSS difference between the

    three groups (p=0.99)

    Serious AE None

    ACC: acetaminophen 400 mg + codeine 25 mg; AE: adverse event; NNS: not statistically significant

  • Canadian Guidelines

    Canadian guideline on acute drug therapy for

    migraine headaches (2013)1:

    ▰ codeine-containing combinations: a last line/alternative option if no response or

    contraindications to first-line options

    Canadian review/guideline for primary care

    management of headache in adults (2015)2:

    ▰ fixed-dose combination analgesics that include codeine = a last line option

    23

    1Worthington I et al. Can J Neurol Sci. 2013; 40(5), Suppl.3 – S33-62; 2Becker WJ et al. Can Fam Physician. 2015; 61(8):670-9.

    Weak Recommendation –

    Low-quality evidence

    (Not for routine use)1

  • RxTx Algorithm for Management of Acute Migraine 24

    Purdy, R.A. Headache in Adults. RxTx, Compendium of Therapeutic Choices, Canadian Pharmacists Association. 2019.

  • Choosing Wisely

    25

    American Headache Society and American Academy of Neurology: Five Things Physicians and Patients Should Question Handouts. Choosing Wisely.

  • NSAIDs

    Evidence Review for Migraines

    26

  • NSAIDs: Mechanism of Action

    27

     Non-selective

    NSAIDs

     Aspirin

     COX-2 Inhibitors

     Non-selective

    NSAIDs

     Aspirin (irreversible

    inhibition – slightly

    more selective)

    Attribution-NonCommercial 3.0 Unported (CC BY-NC 3.0) - https://www.dovepress.com/risk-of-stroke-associated-with-nonsteroidal-anti-inflammatory-drugs-peer-reviewed-fulltext-article-VHRM

    CPhA Monograph. Nonsteroidal Anti-inflammatory Drugs (NSAIDs). 2014.

    https://www.dovepress.com/risk-of-stroke-associated-with-nonsteroidal-anti-inflammatory-drugs-peer-reviewed-fulltext-article-VHRM

  • NSAIDs with Evidence: Cochrane Reviews

    28

    (Derry et al., 201

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