migraine in primary care advisors vienna, 25 october 2002, 2-6 pm individualising migraine care: the...

MIGRAINE IN PRIMARY CARE ADVISORS

Vienna, 25 October 2002, 2-6 pm

Individualising migraine care:The clinical relevance of providing different

modes of administration of antimigraine drugs

Introduction and objectives

Dr Andrew Dowson

Kings’ Headache Service, London

Programme

• Dr Andrew Dowson: Introduction and objectives

• Dr Trevor Rees: Modes of administration of available antimigraine drugs: a review of their strengths and weaknesses

• Dr Bruce Charlesworth: The clinical profile of the conventional tablet, orally dispersible tablet and nasal spray formulations of zolmitriptan (Zomig®)

• Break

Programme

What factors should be considered in the choice of formulation to be used for antimigraine therapies?

• Dr Andrew Dowson: Selection of initial therapy

• Dr Sue Lipscombe: Follow-up care: monitoring treatment and selection of therapy

• General discussion

Objectives of today’s meeting

• Review available formulations of antimigraine drugs– Emphasis on the triptans

• Review the clinical profile of the Zomig formulations

• Agree on concepts of individualisation of care for migraine

Objectives of today’s meeting

• Review the factors that should be evaluated in choosing the appropriate formulation for each patient

• Develop recommendations for the prescription of different triptan formulations in primary care

Outputs from the project

• Article to be published in a learned journal

• MIPCA newsletter (‘popular’ GP version)

• Slide set for educational purposes

Modes of administration of available antimigraine drugs: a review of their strengths

and weaknesses

Dr Trevor Rees

Hawthorns Surgery, Sutton Coldfield

Overview

• Available drugs and formulations in the UK

• Review of clinical profile of different triptan formulations– Relative strengths and weaknesses

Available drugs and formulations in the UK

OTC acute medications

• Simple analgesics/NSAIDs and combination medications (e.g. Solpadeine)– Conventional tablets– Dispersible tablets


Prescribed acute medications• NSAIDs

– Conventional tablets

• Analgesic-anti-emetic combinations– Tablets / dispersible tablets

• Analgesic-isometheptene combinations (Midrid)– Capsules

• Analgesic-codeine combinations (Migraleve)– Tablets


Prescribed acute medications

• Triptans– Conventional tablets (all)– Orally dispersible tablets (Zomig, Maxalt)– Nasal sprays (Imigran, Zomig)– Subcutaneous injection (Imigran)

• Ergotamine– Conventional tablets (Cafergot / Migril)


Prescribed prophylactic medications

• Beta-blockers– Conventional tablets, sustained-release

capsules, oral solutions

• Serotonin antagonists

• Anticonvulsants

• Antidepressants– All conventional tablets

Clinical profiles of the different triptan formulations

Conventional tablets

• Generally well absorbed from the intestine• Effective therapy

60% of patients with headache relief after 2 hours

• Onset of action within 30-60 min• Generally well tolerated• Differences between the triptans are

generally small and of uncertain clinical significance

Sheftell FD, Fox AW. Cephalalgia 2000;20(Suppl2):14-24

Dowson AJ, Cady RK. Rapid Reference to Migraine, 2002

Conventional tablets: Efficacy

0

10

20

30

40

50

60

70

80

90

Sum100

Sum50

Nara2.5

Zolm2.5

Riz 10 Almo12.5

Ele 40

Pat

ien

ts (

%)

Proportion of patients with headache relief after 2 hours (maximum published values)

Dowson AJ, Cady RK. Rapid Reference to Migraine, 2002

Orally dispersible tablets

• Generally well absorbed from the intestine

• Effective therapy 60% of patients with headache relief after

2 hours

• Onset of action within 30-60 min• Generally well tolerated• Similar clinical profile to conventional

tablet formulationsSheftell FD, Fox AW. Cephalalgia 2000;20(Suppl2):14-24

Dowson AJ et al. Cephalalgia 2001;21:419-20

ODT tablets: Efficacy

0

10

20

30

40

50

60

70

80

90

Zolmitriptan Rizatriptan

Tablet

ODT

Pat

ien

ts (

%)



Dowson AJ et al. Cephalalgia 2001;21:419-20

Nasal sprays

• Well absorbed from the nasal mucosa, but some also absorbed from the intestine

• Effective therapy– Up to 70% of patients with headache relief after 2

hours

• Rapid onset of action: within 15 min• Generally well tolerated, with some reports of

taste disturbances• May have superior clinical profile to oral

formulations


Purdy A et al. Cephalalgia 2001;21:418-9

Nasal sprays: Efficacy

0

10

20

30

40

50

60

70

80

Zolmitriptan Sumatriptan

Nasal spray

Oral

Pat

ien

ts (

%)



Purdy A et al. Cephalalgia 2001;21:418-9

Sumatriptan subcutaneous injections

• Very rapid absorption• Most effective therapy

– >80% of patients with headache relief after 2 hours

• Very rapid onset of action: within 10 min• Has superior efficacy profile to all other

formulations• Has more associated side effects than all

other formulations


Subcutaneous sumatriptan: Efficacy

0

10

20

30

40

50

60

70

80

90

Subcut 6 mg Nasal spray 20mg

Oral 100 mg

Pat

ient

s (%

)



Strengths and weaknesses of different triptan formulations

Strengths• Familiarity/comfort• Most drugs well

absorbed from intestine• Clinical studies show

that triptan tablets provide effective migraine relief

• Well tolerated• Relative cost

Weaknesses• Need water for use• Gastric stasis

associated with migraine

• May not be effective for some patients/ attacks

• Slower onset of action (30-60 min)

Conventional tablets

Strengths• Innovative migraine

treatment• Flexible use: No need

for water• Generally well absorbed

from intestine• Clinical studies show

that ODT triptans are effective for migraine

• As well tolerated as conventional tablets

• Relative cost

Weaknesses• Not familiar• Gastric stasis

associated with migraine

• May be no more effective than conventional tablets

• May not be effective for some patients/ attacks

• Slower onset of action• Not absorbed from

mouth

Orally dispersible tablets (ODT)



for water• Good nasal absorption • Rapid onset of action

(15 min)• May be more effective

than tablet formulations• As well tolerated as

conventional tablets

Weaknesses• Not familiar• Some absorption may

occur in the stomach• May not be effective for

some patients/ attacks• Some reports of taste

disturbances

Nasal sprays



for water • Fastest onset of action

(10 min)• More effective than all

other formulations• Non-needle injectors on

horizon

Weaknesses• Fear of injections• More side effects than

with other formulations• Some side effects may

be disturbing to the patient and restrict use

• Relative expense

Subcutaneous injection

Conclusions

• All triptan drugs and formulations are effective and well tolerated acute treatments for migraine

• Triptans are the ‘gold standard’ treatment• Different triptan formulations have their own

strengths and weaknesses• The choice of triptan formulation may not be

obvious from the outset• Guidance to help the physician choose an

appropriate formulation for each patient would be welcome

What factors should be considered in the choice of formulation to be used for

antimigraine therapies?

Selection of initial therapy

Dr Andrew DowsonKings’ Headache Service, London

New MIPCA guidelines for migraine management

Individualising care processes:Initial consultation and

treatment

Detailed history, patient education and buy-inDiagnostic screening and differential diagnosisAssess illness severity

Attack frequency and durationPain severityImpact (MIDAS or HIT questionnaires)Non-headache symptomsPatient history and preferences

Intermittentmild-to-moderate migraine

(+/- aura)

Intermittentmoderate-to severe migraine

(+/- aura)

Aspirin/NSAID (large dose)Aspirin/paracetamol plus anti-emetic

Oral triptan

Nasal spray/subcutaneous triptan

Initial consultation

Initial treatment

Rescue

Rescue

Behavioural/complementary therapies

Copyright MIPCA 2002, all rights reserved

Dowson AJ et al. Curr Med Res Opin 2002;18: in press.

Assess illness severity

• Attack frequency and duration• Pain severity• Impact on daily living

– MIDAS/HIT questionnaires

• Non-headache symptoms• Patient factors

– History, preference and other illnesses

Matchar DB et al. Neurology 2000; www.aan.com. Bedell AW et al. Primary Care Network 2000.

http://www.aan.com/

Assessment of severity

Mild-to-moderate migraine Moderate-to-severe migraine

Headaches mild-to-moderate in intensity

Headaches moderate or severe in intensity

Non-headache symptoms not severe in intensity

Significant non-headache symptoms, possibly severe

Impact not significant:

MIDAS Grade I or II

HIT Grade 1 or 2

Significant impact:

MIDAS Grade III or IV

HIT Grade 3 or 4 Matchar DB et al. Neurology 2000; www.aan.com.

Bedell AW et al. Primary Care Network 2000.

http://www.aan.com/

Selection of initial therapy

Evidence-based medicine (Duke database) suggests:

• Behavioural therapy recommended for all• Acute therapy recommended for all• Prophylactic therapy recommended for

certain patients• Complementary therapies may be useful as

adjunctive therapy

Headache Consortium. Neurology 2000; www.aan.com. Bedell AW et al. Primary Care Network 2000.

http://www.aan.com/

Goals of therapy

• Acute medications: to rapidly relieve the headache and other symptoms, and permit the return to normal activities (within 2 hours?)

• Prophylactic medications: to reduce headache frequency by >50%

Matchar DB et al. Neurology 2000; www.aan.com.Bedell AW et al. Primary Care Network 2000.

Ramadan NM etal. Neurology 2000; www.aan.com.

http://www.aan.com/

http://www.aan.com/

Strategy for providing initial acute therapy in individualised care

Migrainediagnosis

Severityassessment

Mild to moderate migraine Moderate to severe migraine

Initial therapy Initial therapy

Rescue Rescue

If unsuccessful

Migraine attack

Dowson AJ et al. Curr Med Res Opin 2002;18: in press

Stratified care

Staged care

Recommended initial acute treatments

Mild-to-moderate migraine

• Aspirin or NSAIDs (high doses)

• Aspirin/paracetamol plus anti-emetics

• Paracetamol plus isometheptene– Use if possible before headache starts

• Rescue medications– Oral triptans– Use for any headache severity

Matchar DB et al. Neurology 2000; www.aan.com.

http://www.aan.com/

Recommended initial acute treatments

Moderate-to-severe migraine

• Oral triptans (tablet/ODT)– Use after the headache starts, if possible

when it is mild in intensity

• Rescue medications– Nasal spray or subcutaneous triptans– Symptom control


http://www.aan.com/

Who should receive a triptan as initial therapy?

• Patients with moderate-to-severe migraine

• Patients with any severity migraine who have failed on other acute medications


http://www.aan.com/

What formulation of triptan should be used as initial therapy?

• Is a conventional tablet always the best choice?

• Would ODT formulations be more appropriate?

• Should any patients receive nasal spray or subcutaneous formulations from the outset?

Circumstances where ODT or non-oral formulations may be appropriate

• ODT / nasal– Unpredictable attacks– Need for greater convenience– Patient preference

• Nasal / subcutaneous– Severe / fast onset attacks– Need for rapid response– Severe nausea– Vomiting– Patient preference


What formulation of triptan should be used as rescue therapy?

• Second dose of initial medication?

• Alternative oral triptan?

• ODT formulation?

• Nasal spray?

• Subcutaneous injection?

Factors affecting the choice of rescue medication

• Impact

• Work / lifestyle pressures

• Severity of attack

• Length of attack

• Vomiting / severe nausea

• Patient preference

Patient preference factors: What do patients experience?

• Headache relief too slow

• Inadequate overall relief

• Inconsistency of response

• Headache returns after initial relief

• Too many side effects

Lipton RB, Stewart WF. Headache 1999;39(Suppl2):20-6

What do patients want? How do they express their preferences?

• Greater speed of action

• Enhanced overall effectiveness

• Restored ability to function

• Fewer side effects

• Satisfaction with therapy

• Greater convenience

Dowson AJ, manuscript in preparation

Strategy for providing prophylactic medications in individualised care

• Prophylactic medications should be provided:– For patients with frequent, high-impact migraine

attacks (4/month?)– Where acute medications are ineffective or

precluded by safety concerns– For patients who overuse acute medications

and/or have CDH– For patients with the rare migraine variants

• However: acute medications should also be provided for breakthrough attacks

Ramadan NM et al. Neurology 2000; www.aan.com. Bedell AW et al. Primary Care Network 2000.

Dowson AJ et al. MIPCA 2000.

http://www.aan.com/

Recommended initial prophylactic treatments

• First-line medications:– Beta-blockers (propranolol, metoprolol,

timolol, nadolol)– Anticonvulsants* (sodium valproate)– Antidepressants* (amitriptyline)

• Second-line medications– Serotonin antagonists (pizotifen,

methysergide, cyproheptadine)

* Not licensed for migraine in the UK

Ramadan NM et al. Neurology 2000; www.aan.com.

http://www.aan.com/

Factors influencing the choice of initial prophylactic medication

• Side effects mean that certain patients are not able to take specific drugs– Beta-blockers may not be suitable for

sportspeople• Weight gain experienced with many drugs

may limit compliance in a largely female population

• Anticonvulsants and antidepressants may be used for patients with concurrent conditions

• Anticonvulsants and antidepressants are also effective if CDH is suspected

Conclusions

• The choice of initial drug can be individualised for each patient’s needs

• Oral triptans are suitable acute medications for most patients

• ODT, nasal spray and subcutaneous triptans are suitable initial medications for certain patients and/or as rescue medication

Follow-up care: monitoring treatment and selection of therapy

Dr Sue LipscombePark Crescent New Surgery, Brighton

New MIPCA guidelines for migraine management

Follow-up treatment


Oral triptan

Initial treatment

Follow-up treatment

Oral triptanAlternative oral triptan


Rescue

If unsuccessful

Consider prophylaxis +acute treatment for

breakthrough migraineattacks

Frequent headache(i.e. 4 attacks per month)

Consider referralChronic daily

Headache (CDH)?

Migraine

If unsuccessful

If unsuccessful

Initial treatmentCopyright MIPCA 2002, all rights reserved

If management unsuccessful



Oral triptan

Initial treatment

Follow-up treatment

Oral triptanAlternative oral triptan


Rescue

If unsuccessful

Consider prophylaxis +acute treatment for

breakthrough migraineattacks

Frequent headache(i.e. 4 attacks per month)

Consider referralChronic daily

Headache (CDH)?

Migraine

If unsuccessful

If unsuccessful

Copyright MIPCA 2002, all rights reserved

If management unsuccessful


Recommended follow-up procedures

• Instigate proactive long-term follow-up procedures

• Monitor the outcome of therapy– Headache diaries– Impact questionnaires (MIDAS/HIT)

• Make appropriate treatment decisions


Who are the diaries for?

• The patient

• The doctor

• Both

What is the diary for?

• Recording data– Triggers, patterns, results of medication,

frequency of medication taken

• To make the patient feel the doctor is interested

• To help the doctor make lifestyle and medication suggestions

Headache diaries

• Beneficial for the prospective management of migraine

• Two types of diary can be used– Patient-held long-term diary for continual use,

containing basic information on patterns of headache

– Short-term diary used over a specific timescale for intense monitoring

• The two diaries can be used in tandem• Data from the diaries can be used to

individualise follow-up treatment decisions

Follow-up treatment decisions

• Acute medications– Patients effectively treated should

continue with the original therapy• Analgesic-based medications• Triptans

– Patients who fail on original therapy should be offered other therapies, based on clinical issues and patient preference

• Analgesic-based medications oral triptan• Triptan alternative triptan

Dowson AJ, Cady RC. Rapid Reference to Migraine 2002.

Individual treatment for individual attacks

• Doctor and patients may be able to identify different severities and types of attacks

• The patient may choose to have a range of treatments to hand to treat each attack with the medication they feel most appropriate

• If this is the case, then several prescriptions may be necessary

Switching between triptans

• If one oral triptan fails, an alternative oral triptan may be effective– ODT triptan may be suitable for patients

who cannot predict their attacks easily and/or require greater convenience of use

• Patients needing rapid onset of action and greater convenience of use may benefit from nasal spray and injection formulations

Switching between triptans

• Patients needing greater overall relief and/or experiencing significant impact may benefit from nasal spray or subcutaneous formulations

• Patients reporting bothersome side effects may require a triptan with a better tolerability profile

• ODT, nasal spray and subcutaneous formulations may also be suitable as rescue medications


• Prophylactic medications– Initial dose can be titrated up as necessary

to achieve an effective dose– Medication needs to be provided for an

adequate time period (up to 3 months)– If effective, treatment can continue for 6

months, after which it may be stopped– If ineffective, another prophylactic

medication may be tried– Monitor closely for side effects and

patients’ subjective impressionsDowson AJ et al. Curr Med Res Opn 2002;18: in press


• Specialist referral – Migraine patients refractory to repeated

acute and prophylactic medications– Patients who have developed CDH during

treatment– Patients suspected of having sinister

headaches, rare migraine variants, cluster headache and other refractory non-migraine headaches

– Patient request

Specialist referrals

• Worrying migraine – are they TIAs or hemiplegic migraine?

• Worrying times – pregnancy, breast feeding, menopause

• For specialist treatment only, e.g. methysergide, botox, off-licence drugs.

• For special investigations – CT, MRI

Conclusions

• Follow-up should be available for migraine patients– Headache diaries– Impact questionnaires

• Acute and prophylactic medications can be changed to maximise therapeutic effect and patient satisfaction

• The different triptan formulations provide flexible therapy that can be targeted to each patient’s needs and desires

migraine in primary care advisors vienna, 25 october 2002, 2-6 pm individualising migraine care: the...

Documents

migraine slide

london slide

primary care slide

zomig formulations

available antimigraine

dispersible tablets

overview available drugs

sutton coldfield slide