Headache Medicine, v.1, n.1, p. 25-28, jan./fev./mar. 2010 25

Lithium-responsive headaches

Cefaleias lítio-responsivas

RESUMORESUMO

RESUMO

IntroductionIntroduction

Introduction: Lithium-responsive headaches are primary and

they have beginning nocturnal or on awakening. They are

classified in three groups: Nocturnal Migraine, Cluster

Headache, and Hypnic Headache. All three types show a

positive therapeutic response to lithium and the average dose

is from 300 to 900 mg at bedtime.

Objective:Objective:

Objective: To review the

headaches that have nocturnal or on awakening beginnings

and those which demonstrate a therapeutic response to lithium.

Method: Method:

Method: We reviewed the literature on lithium and its

historical and pharmacological aspects, and its use in the

treatment of nocturnal headaches.

Conclusion: Conclusion:

Conclusion: Lithium is

an efficient drug in the treatment of nocturnal headache and

headache on awakening.

alavrasalavras

alavras

chave:chave:

chave: Nocturnal migraine; cluster headache;

hypnic headache; lithium-responsive headaches.

ABSTRACTABSTRACT

ABSTRACT

Introdução:Introdução:

Introdução: As cefaleias lítio-responsivas são primárias e

se caracterizam por seu início noturno ou ao despertar. São

divididas em três grupos: migrânea noturna, cefaleia em

salvas e cefaleia hípnica. Todas têm boa resposta terapêutica

ao lítio e a dose varia de 300 a 900 mg/dia.

Objetivo Objetivo

Objetivo:

Revisar as cefaleias que têm início durante o sono ou ao

despertar e que respondem ao lítio.

Método:Método:

Método: Foi revisada a

literatura sobre o lítio quanto ao seu histórico, sua farmacologia

e a sua utilização clínica no tratamento das cefaleias noturnas.

Conclusão: Conclusão:

Conclusão: O lítio é uma medicação eficaz no tratamento

da cefaleia noturna e ao acordar.

Key words: Key words:

Key words: Migrânea noturna; cefaleia em salvas; cefaleia

hípnica; cefaleias lítio-responsivas.

REVIEW ARTICLEREVIEW ARTICLE

REVIEW ARTICLE

Raimundo Pereira da Silva Neto

, Kelson James Almeida

Neurologista e Membro da Sociedade Brasileira de Cefaleia

Residente de Neurologia do HC-USP

Centro de Neurologia e Cefaleia do Piauí - Teresina PI, Brasil

Silva Neto RP, Almeida KJ

Lithium-responsive Headaches. Headache Medicine. 2010;1(1):25-28

INTRODUCTION

Nocturnal headaches (Table 1) are generated during

sleep and occur either at dawn or awaken the patient

during the night.

1-7

There is a temporal relationship

between the nocturnal headache attacks and the period

of REM sleep. These headaches are divided into primary

(nocturnal migraine, cluster headache and hypnic

headache) and secondary (attributed to giant-cell arteritis,

intracranial hypertension secondary to hydrocephalus or

intracranial neoplasia and sleep apnea headache). All

primary headaches respond to therapy using lithium

carbonate and therefore are referred to as lithium-

responsive, while the treatment of secondary headaches

is based on the removal of their cause.

LITHIUM IN HEADACHES

Lithium (from the Greek lithos, stone) is a chemical

element represented by the symbol Li, discovered by Johan

August Arfwedson in 1817 through minerals derived from

a petalite mine on the island of Utö (Sweden). The

principal minerals from which lithium is extracted are

lepidolite, petalite, spodumine and amblygonite. The

name lithium was given due to the fact that it had been

found inside a mineral, even though it was later found in

plant ashes as well.

Lithium is found in diverse forms within nature, such

as: salts, chlorides, bromides, stearate, hydroxides, etc.

26 Headache Medicine, v.1, n.1, p. 25-28, jan./fev./mar. 2010

RAIMUNDO PEREIRA DA SILVA NETO E COLABORADOR

Only the lithium salts are used in medicine, particularly

lithium carbonate (Li

). Initially classified as an anti-

psychotic, but today it is used for its regulating effects on

mood, anti-mania and, secondarily, as an anti-

depressant.

The activating mechanism of lithium is not well

elucidated, however it is known to be effective in

pathologies of clinical evolution, inhibiting the synthesis

of prostaglandin and the action of the prolactin, acting

on the monoamine, the cyclic AMP, the platelet and sleep.

Lithium establishes and increases the serotoninergic

transmission in the central nervous system, particularly in

the hippocampus. Due to this, it has been used in the

treatment of nocturnal headaches. According to Silva Neto

et al.,

lithium is an effective medication in the treatment

of nocturnal and awakening headaches as well as

nightmares.

Lithium is rapidly absorbed by the gastrointestinal tract

and the plasmatic concentration reaches its peak within

two to four hours after ingestion. Lithium slowly crosses

the blood-brain barrier. Ninety-five percent (95%) of the

drug is excreted via urine in a rapid phase and in another

slower phase, which may take as long as 14 days. Lithium

should not be used concurrently with a hyposodic diet or

with diuretics that induce the loss of sodium, given that the

depletion of sodium provokes intracellular retention of

lithium.

The average dose is from 300 mg two to three times

daily, taken orally, aiming to maintain a plasmatic

concentration between 0.4 and 0.8 mEq/l. The periodic

control of the serum level should be given.

There are diverse collateral effects to various organs,

some of them quite worrisome:

1. Neurotoxicity: drowsiness, mental confusion,

lethargy, clouded vision, shaking of the extremities,

cramping, dizziness, nystagmus, ataxia, extrapyramidal

signs, and convulsions;

2. Thyroid: hypothyroidism (10 times more frequent

in women) in 5% of the cases and painless increase in the

thyroid (reversible with the suspension of the use of the

drug). Doses of TSH, T3 and T4 should be given every

six months;

3. Renal: edema and sodium retention in the initial

phase of treatment, polyuria, polydipsia, and insipid

diabetes by hormonal anti-diuretic blockage at the renal

tube level;

4. Hematological: leukocytosis for polymorpho-

nuclears;

5. Cardiac: tachycardia and narrowing of the T wave

and dysfunction of the sinus nodule;

6. Dermatalogical: cutaneous ulcers, psoriasis, hair

loss, and acne-like eruptions;

7. Gastrointestinal: nausea, vomiting, diarrhea, and

abdominal pains;

8. Pregnancy: there are registered occurrences of

new-borns of mothers using lithium that acquire depression

of the central nervous system, hypotonia, neonatal goiter,

and cardiac malformations, especially Ebstein's anomaly.

THE PRIMARY NOCTURNAL HEADACHES

Nocturnal MigraineNocturnal Migraine

Nocturnal Migraine

A migraine without aura where all of the attacks begin

during the night or upon awakening.

Still has not been

sufficiently validated by scientific studies. Overall, the

experience of specialists suggests the existence of a primary

headache that arises either during sleep or upon awakening

and fulfills the diagnostic criteria for migraine and not for

other primary headaches. Additional scientific evidence is

required in order to formally accept and include in the

next international classification of headaches.

According to Edgard Raffaelli (personal

conversation), similar to the menstrual headache, nocturnal

migraine do not respond to habitual prophylactic

treatments for migraine, suggesting the existence of at least

three different neurotransmission systems.

Due to the use of lithium in pathologies having a

cyclical evolution, testing was begun on nocturnal

migraine. These patients have had an absolute therapeutic

response to lithium carbonate, at a daily dosage of 300

to 900 mg/day in the form of a singular night-time

dosage.

8,9

Cluster HeadacheCluster Headache

Cluster Headache

A primary headache from the trigeminal autonomic

cephalalgias group that presents certain peculiarities such

Headache Medicine, v.1, n.1, p. 25-28, jan./fev./mar. 2010 27

LITHIUM-RESPONSIVE HEADACHES

as: excruciating pain, short-term attacks, evident circadian

rhythm, regularity, and autonomic disturbances.

The classification of headaches of the International

Headache Society (IHS-2004)

describes the cluster

headache as attacks of intense pain, strictly unilateral,

located in the orbital, supraorbital or temporal region,

lasting from 15 to 180 minutes and occurring from once

every other day to eight times daily. This headache occurs

in association with one or more of the following aspects,

all of which are ipsilateral to the pain: conjunctival

injection, lacrimation, nasal congestion, rhinorrhoea,

facial and forehead sweating, miosis, ptosis, and eyelid

edema.

Some nuances not described in the classification of

headaches are observed in clinical practice such as the

time at which the attacks occur. It has been observed that

the attacks consistently occur at the same time of day in a

significant number of patients. According to Lance, the

occurrence of a circadian rhythm will be present in 80%-

85% of the cases and the nocturnal attacks will be more

frequent, in the range of 50-60% of the crises,

approximately 90 minutes after the patient falls asleep.

Dexter and Riley

reference their findings that seven in

nine crises of cluster headaches occur during REM sleep.

Polysomnographic study shows that awakening with a

headache occurs more frequently during the period of

REM sleep, during the third and fourth stages.

Lithium was indicated as the treatment for cluster

headache by Ekbon in 1974. It is used in the treatment of

episodic nocturnal cluster headache attacks at the dosage

of 300 to 600 mg/day given orally at night in a single

dose. For chronic cases a dosage of 300 mg two-three

times daily is recommended.

Hypnic HeadacheHypnic Headache

Hypnic Headache

A primary headache that awakens the patient, also

known as an "alarm clock headache" or "clockwise

headache" and characteristically affecting the middle-

aged and elderly.

A primary headache that awakens the patient, also

known as an "alarm clock headache" and characteristically

affecting the middle-aged and elderly.

The hypnic headache was described originally by

Raskin in 1988 through a study of six subjects (5 men and

one woman), with ranging from 65-77 years of age, with

headache attacks that awakened them (in two of them

always after dream) and lasted from 30 to 60 minutes. In

three of the patients the pain was pulsing. Only two of

those studied reported cases of migraine in the past, one

with and the other without aura. None of the patients

presented autonomic disturbances that suggest cluster

headache and all of them reported bilateral pain.

Through the initial description by Raskin, various cases

were described in literature,

14,15

culminating in its inclusion

in the International Classification of Headaches

Hypnic headache is defined by the International

Headache Society

as a dull headache that always

awakens the patient and that fulfills the following diagnostic

criteria: appears only during sleep and awakens the

patient, happens more than 15 times per month, last 15

minutes or more after awakening and occurs for the first

time after 50 years of age. There is an absence of

autonomic signs and there will be no more than one of

the following symptoms: nausea, vomiting, photophobia

or phonophobia. It is not attributed to any other disturbance

or disorder.

Various studies have demonstrated that lithium

carbonate was the most effective treatment in a variety of

related cases.

4,14,15

The dosage used varied from 300 to

600 mg/day in a single dose, always at night upon going

to bed.

CONCLUSION

Lithium has been shown to be a good therapeutic

response to all primary headaches that present themselves

during the night or upon awakening.

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Correspondência

DrDr

. R. R

. R

aimundo Paimundo P

aimundo P

ereira da Silva Netoereira da Silva Neto

ereira da Silva Neto

Centro de Neurologia e Cefaleia do Piauí

Rua São Pedro, 2071 - Centro

Ed. Raimundo Martins - Salas 303/304

64001-260 - Teresina-PI - Brasil

Tel./fax: + 55 86 3221.9000

E-mail: neurocefaleia@terra.com.br

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