194 Headache Medicine, v.2, n.4, p.194-199, Oct/ Nov/Dec. 2011

Hospital management of intractable headaches.

The Instituto de Neurologia de Curitiba approach

Manejo hospitalar das dores de cabeça intratáveis. Abordagem do

Instituto de Neurologia de Curitiba

ABSTRACTABSTRACT

ABSTRACT

Intractable headaches, also called refractory headaches, are

usually unresponsive to standard therapies and comprise

clinical conditions that represent a clinical management

problem regarding therapy. Thereby, many approaches to

manage "intractable headaches" have been proposed;

meanwhile many aspects remain unclear and open to debate.

Accordingly, these patients often require special care and

customized management, such as inpatient treatment.

Hospitalization aims to enhance management of the patients

as a whole and thus improve their quality of life. This paper

summarizes the Instituto de Neurologia de Curitiba (INC)

approach, which comprises withdrawal of the overused

medication, management of abstinence symptoms,

management of rebound headache, introduction of effective

prophylactic therapy, general counseling and education of

the patient, and other aspects of management. The inpatient

approach used at the INC is presented and a small sample of

patients treated according to this approach is described and

discussed.

Keywords:Keywords:

Keywords: Intractable headaches; Refractory headaches;

Inpatient treatment.

ORIGINAL ARTICLEORIGINAL ARTICLE

ORIGINAL ARTICLE

RESUMORESUMO

RESUMO

As dores de cabeça intratáveis, também chamadas de

"cefaleias refratárias", geralmente não respondem aos trata-

mentos habituais e compreendem diversas clínicas as quais

representam um problema de manejo terapêutico. Muitos

esquemas para abordar as "dores de cabeça intratáveis" têm

sido propostos, porém diversos aspectos referentes ao seu

manejo permanecem obscuros e abertos ao debate. Frequen-

temente, estes pacientes necessitam de cuidados especiais e

personalizados de tratamento, tais como o manejo hospitalar.

A hospitalização visa propiciar o manejo destes pacientes de

uma forma abrangente, e, assim, melhorar sua qualidade de

vida. Este artigo resume a abordagem do Instituto de Neuro-

logia de Curitiba (INC), a qual compreende a retirada da

medicação em demasia, o manejo de sintomas de abstinência,

o tratamento da dor de cabeça rebote, a introdução de terapia

profilática eficaz, o aconselhamento geral e a educação do

paciente, assim como outros aspectos envolvidos. A abor-

dagem de internação usada no INC é apresentada e uma

pequena casuística de pacientes tratados de acordo com esta

abordagem é descrita e discutida.

alavrasalavras

alavras

chave:chave:

chave: Dores de cabeça intratáveis; Dores de

cabeça refratárias; Tratamento hospitalar.

Rowe A, Iachinski R, Rizelio V, Sato HK, Nascimento MT, Souza RK, Kowacs PA

Hospital management of intractable headaches. The Instituto de Neurologia de Curitiba approach.

Headache Medicine. 2011;2(4):194-9

Adriel Rowe

, Renato Iachinski

, Vanessa Rizelio

, Henry Koiti Sato

, Maria Tereza de Moraes Souza Nascimento

Ricardo Krause Martinez de Souza

, Pedro André Kowacs

Fundação Universidade Regional de Blumenau, PR

Serviço de Neurologia do Instituto de Neurologia de Curitiba, PR

Headache Medicine, v.2, n.4, p.194-199, Oct/ Nov/Dec. 2011 195

INTRODUCTION

Intractable headaches

(1-3)

(also called "refractory

headaches") represent a clinical management problem

regarding therapy. The problem stems from its definition:

previous treatments in adequate doses have failed to control

the symptoms. Table 1 summarizes a proposed classification

for refractoriness of a headache to prophylactic therapy.

Most patients presenting "intractable headaches" have

probable chronic migraine and probable headache

secondary to the overuse of excessive symptomatic

medication. There are several approaches to managing

"intractable headaches", some of them not tested with

adequate methods. In this paper, the inpatient approach

used at the Instituto de Neurologia de Curitiba (INC) for

treating chronic headaches intractable to prophylactic

therapy is presented and a small sample of patients treated

according to this approach is described and discussed.

TRANSITIONAL THERAPY

Withdrawal of the medication overusedWithdrawal of the medication overused

Withdrawal of the medication overused

Medication previously overused is withdrawn

abruptly

(4-7)

and is never administered again during

hospitalization.

Management of the abstinence symptomsManagement of the abstinence symptoms

Management of the abstinence symptoms

Abstinence symptoms are managed accordingly to

their occurrence. Nausea is managed either with

metoclopramide or with bromopride. Previously to their

prescription, the staff performs a detailed anamnesis

directed towards detecting previous adverse events to

these compounds such as somnolence, akathisia and/

or other extrapyramidal reactions.

(8)

If some of these

symptoms are detected, preference is given for

domperidone, trimebutine, ondasentron or similar

drugs.

(9)

Insomnia is usually managed with a

benzodiazepine such as midazolam. Anxiety might be

treated with other benzodiazepines such as alprazolam,

cloxazolam, and bromazepam. Risperidone or

quetiapine might be prescribed instead, in case of

extreme anxiety or in case bipolar disorder is associated

or suspected.

(10,11)

A sensitive point is hydration.

(4)

It is

important to remind that these patients may present with

vomiting, become drowsy and lessen their water intake.

In this setting, if drugs that may lead to hypotension such

as chlorpromazine are needed, vigorous hydration with

saline is desired, unless in the case of a clear

contraindication such as heart failure or uncontrolled

hypertension.

Management of rebound headacheManagement of rebound headache

Management of rebound headache

Although rebound headache is considered to be an

abstinence symptom, it will be considered separately due

to its complexity. The first step used in the INC is to place

the patient on an intravenous NSAID, usually ketoprofen

100 mg t.i.d.

(12)

– an approach avoided if the overused

medication was ketoprofen or another NSAID. Besides

ketoprofen, intravenous chlorpromazine is given,

(4,13)

except for patients bearing a low systolic blood pressure

or bringing a history of intolerance to chlorpromazine or

to other dopamine receptor antagonist. Chlorpromazine

may be given at doses ranging from 0.2 mg/kg up to

0.7 mg/kg.

(13)

Although some authors advocate it to be

given in bolus, we prefer to dilute it in 100 ml of saline

THE INC APPROACH

The INC approach combines several lines of therapy,

to know: a) withdrawal of the overused medication, b)

management of the abstinence symptoms, c) management

of rebound headache, d) introduction of effective

prophylactic therapy, e) general counseling and education

of the patient, d) other aspects of management. All these

aspects of management are not new and will be discussed

below. Although the items a, b and c are usually coined

as "bridge therapy", we prefer the expression "transitional

therapy", akin to its use for the treatment of cluster

headache.

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196

Headache Medicine, v.2, n.4, p.19

4-199, Oct/ Nov/Dec. 2011

ROWE A, IACHINSKI R, RIZELIO V, SATO HK, NASCIMENTO MT, SOUZA RK, ET AL

and infuse it in about 30-60 minutes. We start with a fixed

dose of 25 mg + 100 ml of saline, stopping infusion

whenever headache is controlled. The dose is gradually

increased if this does not happen. It is important to

remember that adverse effects like nasal congestion, mild

akathisia and severe hypotension may occur.

(13)

While

nasal congestion and mild akathisia may be cumbersome,

orthostatic hypotension may be severe, thus both the nursing

staff and the patient must be warned that he should avoid

standing and walking unattended. As reported by Monzillo

et al., haloperidol may be given as well.

(14)

Metamizole

(dipyrone) is not used frequently at the INC emergency

room, but 1 gram intravenously is reported to be

effective.

(15)

Metamizole potential to cause hypotension

must be also kept in mind, and respective care should be

taken. Until the year of 2010 we used intravenous

dihydroergotamine (DHE),

(4)

except for those patients

overusing ergots or with cardiovascular disorders or risk

factors. About 30 minutes prior to the administration of

DHE, we used to prescribe an intravenous antiemetic. DHE

was given in the dose of 0.5 mg diluted in 50 ml of isotonic

saline, given in 30 minutes or until the resolution of pain.

Unfortunately, the lack of registration on the local

regulatory board (ANVISA) halted the administration of

DHE. Resort to the use of propofol is our last therapeutic

frontier.

(16)

Propofol is quite easy to administer, but great

attention must be paid in case of previous administration

of chlorpromazine or another sedating drug. Before starting

propofol infusion, even the most experienced physician

should take care to have the resuscitating material close

by.

(16)

Administration should start with a bolus injection of

3 mg, followed by sequential injections of 2 mg, always

letting the patient to regain consciousness before the

administration of the next dose. If there is any improvement,

doses are given repeatedly up to a total dose of 300 mg.

However, if the patient headache fails to improve in the first

three doses, the procedure is stopped.

(16)

Several trials have

failed to show steroids as an effective transitional therapy

or in solving rebound headache.

(6,17)

However, in selected

cases especially those in which other approaches have

failed, the administration of steroids should be considered

as an option.

(5,6)

Responders must be warned about the

dangers of prolonged use of steroids, since steroid

dependence may occur.

Introduction of effective prophylactic therapyIntroduction of effective prophylactic therapy

Introduction of effective prophylactic therapy

Patients that seek for hospital management of their

chronic and refractory headaches usually have been

submitted previously to several prophylactic therapies.

That is why a detailed past medication history is a key

point in choosing the prophylactic drug to be introduced.

Not only the kind of medication previously used, but also

its dosage, efficacy and tolerability must be surveyed to

draw a clear picture of the patient's background. The

prophylactic drug usually introduced is methysergide, a

drug with a strong effect on 5HT2A, 5HT2B and 5HT2C

receptors.

(18)

Methysergide has a clear-cut advantage of

an early prophylactic effect, and has also been strongly

recommended in the literature for the treatment of resistant

cases of migraine with a high attack frequency.

(18)

But it

is never enough to remind that, as methysergide has some

vasoconstrictive effect, the prescriber must exert great

caution – or even avoid – recommending other vaso-

constrictive drugs such as ergotics or triptans. Another

key point is that methysergide prescription should follow

the rule "start low, go slow", usually beginning at 1 mg

at bedtime and increasing the dose at 1 mg a day until

1 mg tid or 2 mg bid. Among other traditional migraine

prophylactic drugs, one most formally tested for chronic

migraine is topiramate. However, topiramate prophylactic

effect may take longer to ensue.

(5,19,20)

Valproate is

another useful prophylactic drug, especially for patients

with concomitant bipolar disorder, in whom the daily

dose must be raised above the usual 1 g/day.

(21)

As beta-

blockers, amitriptyline is a useful migraine prophylactic

drug

(22)

and was also shown to be effective for chronic

tension-type headache.

(23)

Patients responding to

intravenous chlorpromazine may be switched to oral

chlorpromazine. Chlorpromazine may be useful in

anxious patients, in those presenting with manic

symptoms or with a family history of psychiatric

disorders.

(13)

Most chronic headache patients have used

several prophylactic drugs and associations of them.

Choice of the prophylactics to be introduced during

hospitalization and at the time of hospital discharge

involve several, factors, such as efficacy, tolerability,

previous response, and the combination of different

mechanisms of action.

(24)

General counseling and education of the patientGeneral counseling and education of the patient

General counseling and education of the patient

Further than just giving medicines to the refractory

headache patient, the hospitalization is an excellent

opportunity for counseling the patient against medication

overuse behavior and to detect and treat anticipatory

anxiety.

(25)

Patients are advised for aerobic physical

activity.

(25-27)

Patients are also advised to promote changes

Headache Medicine, v.2, n.4, p.194-199, Oct/ Nov/Dec. 2011 197

in their lifestyle, if deemed necessary, and taught to have

realistic expectations regarding their headache control,

which may not be absolute.

Other aspects of managementOther aspects of management

Other aspects of management

Other therapeutic approaches can be undertaken

according to the patients needs. Rheumatologic,

psychiatric or psychological consultations are asked for

when needed.

(25,28)

If deemed appropriate, biofeedback

sessions are prescribed.

(25,29,30)

SERIES PRESENTATION

We retrospectively gathered data from the INC

hospital files dated from 2006 to 2007. Nineteen records

were retrieved. Of these, 18 were female and one male.

Fifteen suffered from chronic migraine or probable chronic

migraine – since associated medication-overuse headache

was not ruled out –, one from post craniotomy headache

and one from sustained hydrocephalus-related headache.

Most patients had associated probable medication-

overuse headache and all had a class II or a class III

intractability to prophylactic therapy.

(3,31)

Regarding

comorbidities and associated conditions, one suffered from

somatoform disorder, two from major depression, four

from bipolar mood disorder and two from generalized

anxiety, as diagnosed either by the consulting psychiatrist

or by the neurologist in charge based in the DSM-IV

criteria. Most of the patients were using multiple

prophylactic drugs. As an example, 17 of the patients

were using two or more preventive drugs. Intravenous

dihydroergotamine was given for 17 of the 19 patients,

usually in a tid. dose regimen or as needed, for periods

ranging from one to 12 days. Thirteen of the patients

responded completely to dihydroergotamine, one had a

partial response and three did not respond at all. Four

patients needed intravenous propofol, and all of them

were responders. Methysergide was given for eight of the

19 patients.

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198

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ROWE A, IACHINSKI R, RIZELIO V, SATO HK, NASCIMENTO MT, SOUZA RK, ET AL

DISCUSSION

Hospitalization aims to control or to reduce the

intractable headache, to restore functionality to the patients

by reducing the incapacity, and to treat the associated

comorbidities, thus improving the patients' quality of life.

While abrupt withdrawal of the medication overused is

perhaps the greater unanimity in the management of

refractory chronic headaches associated with medication

overuse, all the other aspects are open to challenge and

debate. Aspects regarding management of analgesics

abstinence symptoms and rebound headache, transitional

(bridge) therapy, timing and type of prophylaxis are all

less clear and amenable to be challenged.

(32)

The

aggressive analgesic/antimigraine approach that we have

described probably would not be enough without the

concomitant changes in prophylactic therapy. Even the

issue of hospitalization is not a consensus.

(25)

Although it is

still possible in Brazil, in many countries it has been

substituted by day-hospital approaches, because of lack

of acceptance by the insurers. From the scientific

standpoint, hospitalization is not associated with better

outcomes in the management of chronic headaches

regarding withdrawal of the overused drug or adherence

to prophylactic therapy.

(32)

As advantages we list a better

monitoring of the drug withdrawal at its first days, earlier

rescue therapy for rebound headache and optimal facilities

for continuous medication and/or procedures needing to

be monitored.

(32)

Besides, taking the patient away from its

environment is an excellent opportunity for reviewing all

the aspects exposed above, and it allows a comprehensive

approach. Since patients to be hospitalized usually belong

to a more complex group of patients, they frequently have

associated fibromyalgia, psychiatric symptoms and/or

sleep disorders.

(25)

As posed before, psychiatric

consultation, or rheumatologic consultation as well, may

enhance patient care as a whole. Saper et al

(28)

and Freitag

et al

(25)

also share this view in favor of using hospitalization

to treat these patients. As there are no rules that fit all

patients, each patient must be individually evaluated and

his/her physician must weight the decision about how and

where to treat him/her. Although the series presented in

this paper is merely illustrative and did not aimed to justify

the approach, it gives an idea of the profile of the patients

that were submitted to this approach at our neurology

service. Based in the arguments above-mentioned, the

INC staff feels quite well acquainted in using the inpatient

approach for treating complex chronic headache and/or

intractable headache patients. However, unexpected

pitfalls may impair the INC's approach such as the recent

repetitive shortages on the supply of methysergide and

the comments about the supplier's discontinuation of the

sale of this prophylactic medication.

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Received: 9/ 8/ 2011

Accepted: 12/ 3/ 2011

HOSPITAL MANAGEMENT OF INTRACTABLE HEADACHES. THE INSTITUTO DE NEUROLOGIA DE CURITIBA APPROACH