intravenous lignocaine (lidocaine) infusion for the treatment of chronic daily headache with...

© Blackwell Publishing Ltd

Cephalalgia,

2003,

23

, 963–971 963

Blackwell Science, Ltd

Oxford, UKCHA

Cephalalgia

1468-2982Blackwell Publishing, 2003

23••963971

Original Article

Lignocaine treatment of chronic daily headache and medication overuseDR Williams & RJ Stark

Intravenous lignocaine (lidocaine) infusion for the treatment of chronic daily headache with substantial medication overuse

DR Williams

1

& RJ Stark

1,2

1

Alfred Hospital, Melbourne and

2

Department of Medicine, Monash University, Melbourne, Australia

Williams DR & Stark RJ. Intravenous lignocaine (lidocaine) infusion for the treat-ment of chronic daily headache with substantial medication overuse. Cephalalgia2003; 23:963–971. London. ISSN 0333-1024

Patients with chronic daily headache with medication overuse are difficult to treat,especially when the doses of analgesia are substantial. We have previously shownthat intravenous lignocaine (lidocaine) infusion is useful in maintaining paincontrol while the offending analgesic agent is withdrawn in these patients. Thepublished data on long-term efficacy of this treatment is limited. We undertook aretrospective survey of 71 consecutive patients admitted for lignocaine infusion(mean 8.7 days) for treatment of chronic daily headache, with substantial analgesicabuse. Ninety percent of patients had a history of migraine headaches. In 80% ofpatients codeine was the predominant agent implicated in the analgesic reboundheadaches (mean 1053 mg/week) and 24% used ergotamine-containing medica-tions (mean 16 mg/week). Thirty-one percent frequently used injected narcotics.At completion 90% reported that their daily headache was absent or improved,and the analgesic agent was withdrawn successfully in 97%. At six month follow-up, 70% of patients reported that their daily headache was absent or improvedand 72% of patients remained free of the offending analgesic agent. Intravenouslignocaine is a useful treatment in the management of chronic daily headache withsubstantial medication overuse. The benefits of the program last for at least sixmonths.

�

Chronic daily headache, lignocaine, lidocaine, analgesic-induced headache,rebound headache

Dr R J Stark, Department of Neurology, Alfred Hospital, Commercial Road, Melbourne, VIC 3004, Australia. Tel.

+

61 3 92762000, fax

+

61 3 92766075, e-mail [email protected] Received 14 December 2002, accepted 6 May 2003

Introduction

Chronic daily headache (CDH) is often associatedwith medication overuse. There are four major diag-nostic categories of CDH: transformed migraine(TM), chronic tension-type headache (CTTH), newdaily persistent headache (NDPH) and hemicraniacontinua. These headaches last for greater than fourhours, and occur on 15 or more days per month.CDH affects 4–5% of the population (1–3) and suf-ferers represent 35% of the patients seen in subspe-cialty headache practices (4). The most troublesomecases of CDH, requiring specialist treatment, usuallyevolve from episodic migraine (72% of cases) or lesscommonly from episodic tension-type headache

(20% of cases) (5). Less often CDH occurs abruptlyas NDPH. The transformation from an episodic to adaily pattern is associated with overuse of analge-sics, opioids, ergotamine or triptans in up to 80% ofcases (6). The syndrome is characterized by the reg-ular, dependable and predictable development of aheadache within hours of the waning therapeuticeffect of the last dose of medication, creating therefractory headache cycle. Headache patients aremore prone to be caught in this cycle than patientssuffering from other chronic pain (7).

CDH associated with medication overuse is a dif-ficult form of headache to manage. The basis fortreatment is withdrawal of the offending medicationin order to break the cycle of recurrent but ineffective

964

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Cephalalgia,

2003,

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, 963–971

analgesic intake (8–11). Combinations of outpatientand inpatient withdrawal programs have beensuggested using symptomatic treatment, dietarychanges, migraine prophylaxis, biofeedback andbehavioural therapy. A number of pharmacologicalagents have been suggested to limit the symptomsof withdrawal and improve the likelihood of rever-sion back to episodic headache. These includesumatriptan (12), valproate (13), tricyclic antidepres-sants (14, 15), selective serotonin reuptake inhibitors(16, 17), methadone (18), corticosteroids (19), dihy-droergotamine (20, 21), histamine (22) andlignocaine (23). In most reported series, the successrate of medication withdrawal is greater than 75% atsix months, with at least moderate improvement ofheadache in greater than 50% of patients (Table 1).However most studies include few of the most dif-ficult patients with high dose codeine or narcoticoveruse, and some even excluded them (19).

The patient population in our headache clinic fre-quently overuses codeine. Tablets of codeine 8 or10 mg in combination with paracetamol or aspirinare available in Australia without medical prescrip-tion and tablets of codeine 30 mg in combinationwith paracetamol 500 mg, with or without doxy-lamine, are frequently prescribed by general practi-tioners for headache treatment. Many of thesepatients require inpatient withdrawal therapy. Wehave previously shown that intravenous lignocaineinfusion given for severe CDH is safe (24).Lignocaine is known as lidocaine in North America.The present study was undertaken to assess the effi-cacy of this program in patients who have CDH withsubstantial medication overuse.

Methods

Study design

This study is a retrospective survey of patientsadmitted to hospital for lignocaine infusion for treat-ment of CDH with associated medication overuse.Seventy-one consecutive patients who were referredto our headache clinic, and admitted to one of threehospitals for treatment, were included. Two hospi-tals were large suburban private hospitals and theother was a large public teaching hospital in Mel-bourne, Australia. Admission for treatment was con-sidered only in those patients who had failedoutpatient withdrawal, or were considered to be atrisk of substantial symptoms of withdrawal due tothe dose of analgesics being used. Patients with sig-nificant cardiac disease, epileptic seizures, heartblock, and allergic reactions to lignocaine were

excluded. Results were obtained from case notes ofall patients, and via structured interview in clinic orby telephone. Data were collected at discharge fromhospital, one month and six months later. Patientswere asked to compare their headaches to the timeprior to medication withdrawal. They were askedif their daily headaches were absent (

<

7 days perfortnight), improved (

>

7 days per fortnight, lesssevere), or not improved. These two-week data wereaveraged over the month to most accurately reflectthe quality and frequency of headache at the time ofthe interview. Data regarding medication use in thetwo weeks prior to interview were also obtainedfrom the patient.

Patients

Seventy-one patients, 62 women and 9 men, aged16–74 years (mean 44 years) were surveyed(Table 2). All presented with headaches that fulfilledthe criteria for CDH with medication overuse (25).The mean duration of CDH prior to treatment was66 months (range 3–480 months). Ninety percent ofpatients had transformed migraine, 4% had chronictension-type headache and 6% had new daily persis-tent headache. The mean number of headache daysper month was 29 (range 22–30 days, except for onepatient) and headache medications were used on amean of 29 days per month (again 20–30 days exceptfor the same single patient who took pethidine200 mg IM 8 times a month). Sixty-two percent ofpatients used multiple agents. Codeine was impli-cated in 80% of cases (mean 1053 mg/week), otheropioid preparations in 47% (parenteral in 31%), trip-tans in 17% (mean 3.7 doses/week) and ergotaminecontaining medications in 24% (mean 16 mg/week).

Patient management

We have previously shown that the treatment ofCDH with lignocaine infusion is safe (24) and theprotocol previously reported was used for this seriesof patients (Table 3). All patients were informed ofthe course of treatment and the importance ofcomplete withdrawal of medications implicated intheir CDH. On admission these medications wereabruptly stopped and lignocaine infusion wasstarted at 2 mg/minute. Rescue medications usedincluded nonsteroidal anti-inflammatory (NSAID)agents and paracetamol. Triptans were used only inthose patients in whom they were not implicated inthe CDH, and who had previously suffered episodicmigraine. Inpatient psychiatric assessment wasoffered to all 40 (62%) patients who were treated in

Lignocaine treatment of chronic daily headache and medication overuse

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, 963–971

Tab

le 1

Dru

g-in

duc

ed h

ead

ache

: lon

g-te

rm f

ollo

w-u

p

Year

Aut

hor

Trea

tmen

t

n

%

cod

eine

dos

em

g/ w

eek

% narc

otic

s% er

gots

F/U

(mon

ths)

50%

d

ecre

ase

%

bett

er

1981

Tfe

lt-H

anse

n &

Kra

bbe

(28)

Sed

ativ

e40

00

100

1248

n/a

1982

Ala

-Hur

ula

(27)

Sed

ativ

e23

00

100

3–6

2674

1986

Rap

opor

t

et a

l

. (41

)W

ithd

raw

al90

n/a

n/a

n/a

4n/

a82

1990

Mat

hew

et a

l

. (42

)B

iofe

edba

ck17

240

n/a

022

3n/

a75

1991

Her

ing

& S

tein

er (

43)

Supp

orti

ve46

n/a

n/a

376

n/a

8019

91M

athe

w &

Ali

(13)

Val

proa

te30

n/a

n/a

n/a

360

93

1992

Sil

ber

stei

n &

Sil

ber

stei

n

(20

)

IV D

HE

5022

567

1422

2459

8719

93L

ake

& S

aper

(44

)

IV D

HE

100

n/a

n/a

n/a

8n

/a75

1994

Sape

r

et a

l

. (16

)Fl

uoxe

tine

64n/

an/

an/

a3

n/a

4719

94Fo

ster

& B

afal

ouko

s (1

7)Pa

roxe

tine

60n/

an/

an/

a3–

973

n/a

1995

Rob

bins

(18

)M

etha

don

e53

n/a

n/a

n/a

636

5719

96Sc

hnid

er

et a

l

. (29

)N

euro

lept

ics

380

021

6052

n/a

1998

Dru

ker

& T

eppe

r (1

2)Su

mat

ript

an26

15n/

a27

156

6977

1998

Nic

olod

i

et a

l

.

(22

)

His

tam

ine

680

n/a

n/a

n/a

267

100

1998

Pri

ngs

hei

m &

How

se

(21

)

IV D

HE

132

n/a

n/a

n/a

346

51

2000

Kry

mch

anto

wsk

i

et a

l

. (19

)Pr

edni

sone

400

00

581

0n/

a20

00L

into

n-D

ahlo

f

et a

l

. (15

)A

mit

ript

ylin

e10

114

>

350

n/a

n/a

1–3

67n/

a

2000

Lu

et a

l

.

(45

)

Pro

chlo

rper

azin

e87

n/a

18

1466

n/a

2001

War

ner

(46)

S/C

DH

E50

n/a

n/a

n/a

8n/

a78

2003

Wil

liam

s &

Sta

rk

(cu

rren

t pa

per)

Lig

noc

ain

e71

8010

5346

246

5171

Inpa

tien

t tr

ials

are

sho

wn

in B

old

. % c

odei

ne, p

erce

ntag

e of

pat

ient

s us

ing

cod

eine

; dos

e m

g/ w

eek,

dos

e of

cod

eine

per

wee

k; %

nar

coti

cs, p

erce

ntag

e of

pati

ents

usi

ng n

arco

tic

med

icat

ions

; % e

rgot

s, p

erce

ntag

e of

pat

ient

s us

ing

ergo

tam

ine

base

d m

edic

atio

ns; 5

0% d

ecre

ase,

per

cent

age

of p

atie

nts

who

se h

ead

ache

freq

uenc

y ha

d r

educ

ed b

y at

lea

st 5

0% a

t st

udy

end

; % b

ette

r, p

erce

ntag

e of

pat

ient

s w

hose

hea

dac

hes

had

im

prov

ed o

n tr

eatm

ent;

IV

DH

E, i

ntra

veno

usd

ihyd

roer

gota

min

e; S

/C

DH

E, s

ubcu

tane

ous

dih

ydro

ergo

tam

ine;

n/

a, n

ot a

vaila

ble.

966



Cephalalgia,

2003,

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, 963–971

the public hospital. Twenty-four hour bedside car-diac monitoring was performed throughout theadmission in the public hospital, and continuousmonitoring by telemetry was undertaken for at leastthe first two days in the private hospitals. Except forthe method of cardiac monitoring all other aspectsof care in public and private hospitals were equiva-lent. The infusion was maintained on the ward forat least seven days and no longer than 14 days. Pro-phylactic medication for migraine was usually com-menced prior to discharge. Patients were given astrategy for headache management to avoid medica-tion overuse, and were followed-up in the headache

clinic at least one month and six months afterdischarge.

Results

Treatment was generally well tolerated, with 66(93%) patients completing the full protocol. In five(7%) patients treatment was stopped before sevendays at the patients’ request. Four patients dis-charged themselves before day five because of per-ceived lack of response. The fifth was transferred toa psychiatric institution following an episode ofacute psychosis that had started prior to admission.

Fifteen (21%) patients suffered mild side-effectsfrom the treatment. Six (8%) had painful IV sites, five(7%) had IV site infections requiring oral antibiotics.Two patients required peripherally inserted centralcatheters because of poor intravenous access. Onepatient taking antihypertensive medications hadsymptomatic hypotension. The infusion wasstopped for two hours, and oral hypotensive agentswere withheld. One patient with a past history ofsupraventricular tachycardia (SVT) had an episodeof SVT during the infusion. One patient complainedof oscillopsia, one of hot flushes and two patientshad diarrhoea. In no patients was treatment abortedbecause of side-effects.

The mean length of stay in hospital was 8.7 days(range 3–17), and the mean duration of lignocaineinfusion was 8 days (range 3–14). Narcotic with-

Table 2

Patient characteristics

Number 71

Sex (female/male) 62/9Age (years) 44 (16–74)Headache days/month 29.2Duration of CDH (months) 66 (3–480)Headache type

Transformed migraine 90%Chronic tension type headache 4%New persistent daily headache 6%

Analgesia profileMedication overuse 100%Multiple agents 62%Analgesic days/month 29 (8–30)

Table 3

Lignocaine infusion protocol

ProcedureThis inpatient procedure lasts for 7–10 days; management is by the Neurology Unit.Medical assessment and examination is required before commencing the infusion.Infusion must be delivered at a controlled rate by I.M.E.D. pump or similar device.The dose of lignocaine is 2 mg/min.

Observations during infusionA 12 lead ECG is obtained before and 30–60 minutes after starting the infusion.Vital signs are recorded prior to infusion.Pulse and blood pressure are measured every 5 minutes for the first 30 minutes of the infusion, then every 15 minutes for 3

hours, and thereafter every 2 hours while the patient is awake.The patient is attached to a bedside cardiac monitor.ECG rhythm strips are obtained every 5 minutes for the first 30 minutes of the infusion, then every 15 minutes for 3 hours,

and thereafter every 2 hours, including during sleep.

Management of breakthrough headacheNo codeine, narcotic or related medication is to be used.Headache not adequately controlled by the lignocaine alone is managed by NSAIDs unless contraindicated. Diclofenac 50mg

or naproxen 500mg is the usual choice, up to 3 times a day. Sometimes ranitidine is required to treat or prevent epigastric side effects of NSAIDs.

Patients with a history of episodic migraine, who do not overuse triptans, may be treated with triptans in the setting of severe breakthrough headache.

Treatment of nausea with prochlorperazine or metoclopromide is sometimes necessary.


967


Cephalalgia,

2003,

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, 963–971

drawal symptoms including mild to moderate agita-tion, insomnia and self limiting diarrhoea wereencountered frequently. Benzodiazepines were occa-sionally used to manage patients with moderatelysevere symptoms. Rescue medications were used totreat rebound headache in 80% of cases. Non-steroi-dal anti-inflammatory drugs (NSAIDs) were used asacute headache treatment in 70% of cases, oral trip-tans in 18% and other medications in 13%. Migraineprophylaxis was commenced in 45% patients.

Ninety seven percent of patients who completedthe protocol had successfully withdrawn from theimplicated medication, and 90% noticed animprovement in their headaches (Fig. 1). The dis-charge plan for managing episodic migraineincluded NSAIDs for 65% of patients and triptansfor 51%; 65% were discharged on migraine prophy-

laxis, 51% on antidepressants and 23% on sedatives(Table 4).

One month after discharge 88% of patientsremained free of the offending medication. The dailyheadache improved in 76% of patients. The meannumber of headache days per month had fallen from29.2 to 18.3 days.

Six months after discharge 71% of patientsremained free of the offending medication. The dailyheadache was absent in 51% of patients, and a fur-ther 20% of patients rated their daily headache asimproved. The mean number of headache days haddecreased to 15.4 days per month. The number ofpatients using codeine based medications decreasedby 76% (from 57 to 12,

P

<

0.001). Of those who werestill using codeine based medications the meanweekly dose decreased by 22%, to 825 mg (median420 mg; interquartile range 300–1120 mg) (Table 4).The number of patients using ergotamine basedmedications decreased by 71% (from 15 to 4,

P

=

0.01). Of those who were still using ergotaminebased medications the mean weekly dose decreasedby 77%, to 4 mg (Table 4).

Forty-eight patients have been surveyed beyond6 months, a mean of 16 months (range 8–34 months)after leaving hospital. Of these patients 58%remained free of the offending medication, adecrease of 16% from interview at six months. How-ever the mean weekly dose of analgesic and thenumber of headache days per month were less than

Figure 1

Headache outcome.

0102030405060708090

100

0 6 16

Time (months)

1

No

. of

pat

ien

ts (

%)

Daily headache not improved

Daily headache improved

Daily headache absent

Free from offending agent

Table 4

Headache frequency and medication use before and after lignocaine infusion

Patients atadmission

1 month afterinfusion

6 months afterinfusion

>

6 months afterinfusion

Number 71 66 62 48Headache (days/month) 29.2 18.3 15.4 15.1Medications usedCodeine 80% 20% 31%

P

-value

<

0.0001

<

0.0001(mean dose mg/week) (1053 mg) (825 mg) (690 mg)

Ergotamine 24% 6% 2%

P

-value 0.01 0.002(mean dose mg/week) (16 mg) (4 mg) (6 mg)

Triptans 17% 44% 38%

P

-value 0.001 0.02(mean no. tablets/week) (4) (2) (2)

Other narcotics 47% 11% 10%

P

-value 0.0001 0.0001Injectable narcotics 31% 8% 12%

P

-value 0.002 0.03Antidepressants 45% 55%Sedatives 25% 27%Headache prophylaxis 20% 65%

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had been the case at 6 months. The daily headachewas absent or improved in the same number ofpatients as at six months (Fig. 1).

In the group of patients with transformedmigraine, the results were better than thoseobserved for other headache types. At most recentreview daily headache was absent in 63% ofpatients, a mean of 15 months after treatment,compared with 17% in patients with other headachetypes. The number of patients free from the offend-ing medication at that time was substantiallydifferent between the two groups (65% and 33%,respectively).

We assessed whether reversion to use of theoffending medication was associated with poorercontrol of daily headache. At six-month review, 29%of patients were again using the medication impli-cated in their CDH. Of this group of patients 72%said that their headache was not improved, and only6% had no CDH (i.e. had headaches less than15 days per month) (Fig. 2). By contrast, in the groupwho remained free from the offending agent only13% had no improvement, and 69% had no CDH(Fig. 3).

In the six months following admission severalpatients were offered other therapies as part oftheir on-going management. Two were treatedwith buprenorphine for opiate withdrawal follow-ing a return to medication overuse, one wassuccessfully prescribed an angiotensin convertingenzyme inhibitor by her local doctor for migraineprophylaxis and five started antidepressantmedication.

Discussion

Chronic daily headache with medication overuse ismost effectively treated by the complete discontinu-

ation of the offending medication. This strategymay be thwarted by substantial and intolerablesymptoms of withdrawal (26) and the coexistence ofpsychiatric conditions often adds to the complexityof the situation (11). The results of this study sug-gest that CDH with substantial medication overuse,including the overuse of opioids such as codeinein high doses, can be successfully treated usinglignocaine infusion as part of a comprehensiveinpatient withdrawal program. After six monthsCDH was absent in 51%, and the mean frequency ofheadache was reduced from 29.2 to 15.4 days permonth. Total medication use was reduced and con-tinued to decline during six-month follow up.Patients with TM tended to do better than thosewith CTTH or NPDH with medication overuse, butsmall numbers in the latter two groups did notallow statistical analysis. A reduction in headachefrequency and intensity persists for more than oneyear after treatment.

Treatment of chronic daily headaches with medication overuse

Lignocaine infusion for the treatment of CDH withmedication overuse is offered to a minority ofpatients in our headache clinic. Published inpatientwithdrawal programs have generally been reservedfor those who have failed outpatient therapy, or areat risk of significant side-effects of withdrawal (12,20, 27–29). A recent review of prophylactic phar-macological treatments for chronic daily headache(30) recommends antidepressants, either tricyclicsor SSRIs, as first line therapy. If these prove ineffec-tive antiepileptics are recommended as add-ontherapy. Third line therapy includes muscle relax-ants, if pericranial muscle involvement is part ofthe CDH syndrome, and antianxiety agents, if anx-

Figure 2

Headache outcome: patients on medication at 6 months.

0

10

20

30

40

50

60

70

80

90

100

0 6 16

Time (months)1

No

. of

pat

ien

ts (

%)




Off medications

Figure 3

Headache outcome: patients off medication at 6 months.

0

10

20

30

40

50

60

70

80

90

100

0 16

Time (months)61

No

. of

pat

ien

ts (

%)




Off medications


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iety is a coexistent factor. Short-term parenteraltherapy is recommended when outpatient therapyfails.

The degree of analgesic and ergotamine overusein the current study is substantially more than inother studies (Table 1). Codeine doses and theamount of opioid medication set this populationapart from those in previous reports. Studies of thelong-term efficacy of parenteral dihydroergotamine(DHE) (20, 21) and histamine (22), in patients withlesser degrees of analgesic overuse, have demon-strated overall positive treatment effects. A reduc-tion in headache frequency to less than 15 days permonth is reported in around two-thirds of thesepatients. Global assessment of long-term improve-ment was documented in around three-quarters(Table 1). The current study achieved similar reduc-tions in headache frequency and quality over at leastsix months.

Side-effects were seen in 21% of patients duringthe lignocaine infusion. They were mainly trivial,and none resulted in the termination of treatment.This compares favourably to the frequency of side-effects seen in patients receiving IV DHE, where 50%of patients suffered from side-effects, mainly nausea,diarrhoea and vomiting, resulting in a small numberof treatment failures (20, 21).

In this study exposure to all classes of analgesicsexcept triptans decreased in the first six months fol-lowing inpatient treatment (Fig. 4). To decrease therisk of returning to a pattern of analgesic abusepatients were encouraged to avoid even one-offdoses of the medication implicated in their CDH.Coincident with this significant reduction of expo-sure to analgesics is a reduction of mean headachedays per month (Table 4). The increased exposure ofpatients to triptans over the first six months reflectsthe usual treatment of those who previously sufferedfrom episodic migraine. It is our practice to use trip-

tans in these patients when they were not implicatedin the development of CDH.

The natural history of withdrawal headaches hasrecently been reported (26). The mean duration ofwithdrawal headache in those who overuseanalgesic medications is 9.5 days. It is somewhatless in those who overuse ergots (6.7 days) andtriptans (4.1 days). The duration of infusion in ourprotocol should therefore be sufficient to treat mostpatients. A briefer infusion may not adequatelytreat those who overuse analgesics. In our study84% of patients overused codeine containing medi-cations and the mean length of stay was 8.7 days(range 4–13).

Long-term outcomes

The long-term effect of lignocaine infusion for treat-ment of CDH cannot be interpreted in isolation.Admission to hospital and infusion are part of acomprehensive, ongoing treatment program thatincludes psychiatric assessment and outpatient fol-low-up. Avoidance of medication overuse remainsthe cornerstone of long-term treatment, and isreflected in the results of this study. Despite a 97%success rate of inpatient withdrawal of medicationsin those completing the protocol, 29% of patients hadreverted to using the medication implicated in theirCDH at six-month review. This group of patientswas much less likely to be free of daily headachethan those who remained free from the offendingagent (Figs 2, 3).

Of the patients who were followed for morethan six months there was no significant changein headache frequency or quality (Fig. 1), how-ever, there was a trend for increased use of medi-cations implicated in their CDH. Only 58% ofpatients remained free of the offending medica-tion, compared to 71% at six months. The increasein medication use was mainly in the group whowere off the agent at six month follow-up (Figs 2,3). These figures include any use of the medica-tion, even one-off doses. The mean weekly doseof all medications used continued to decreaseover that time (Table 4), suggesting that one-offdoses contributed to the increased percentage ofpatients using offending agents. This implies amore rational approach to medication use andsuggests that limited reversion to use of theoffending agent after 6 months may be less dan-gerous than reversion before 6 months. Despitethis, we encourage our patients to remain offthese agents indefinitely.

Figure 4

Medication use.

0

20

40

60

80

100

0 16

Time (months)

6

No

. of

pat

ien

ts (

%)

% using codeine

% using ergots

% using triptans

% using narcotics

% using injectable narcotics

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, 963–971

Lignocaine infusion as a treatment for CDH

Only few previous studies have investigated theeffect of lignocaine infusion for treatment of CDH. Ithas been shown to have, at best, a modest effectwhen used briefly in the treatment of acute migraine(31). One limited study found that lignocaine infu-sion over a two day period was effective (23). Wehave previously used prolonged lignocaine infusionfor treatment of patients with severe CDH associatedwith the use of high doses of codeine and ergota-mine containing medications (24) because we havefound outpatient withdrawal protocols ineffective inthis patient population. Lignocaine is frequentlyused for the treatment of peripheral neuropathicpain (32).

The pathophysiology of CDH associated withmedication overuse is incompletely understood (33).Central sensitization (34), cutaneous allodynia andintracranial hypersensitivity (35) are likely to playa role. Some of these effects may be mediatedby sodium channel-related ectopic discharges inspinothalamic pathways (36). There is mounting evi-dence demonstrating abnormal cellular adaptationin the serotonin-pain control system in patients withCDH who overuse medications (37, 38). Animalmodels of craniovascular nociception have beenused to investigate possible mechanisms oflignocaine’s effect on this pain (23, 39). They suggestthat lignocaine may act to interrupt part of the noci-ceptive pathway, but is unlikely to act at the centralgenerator of the disorder (23). It is speculated thatprolonged lignocaine infusion in CDH acts to resetthis central sensitization, by modulation of periph-eral nociceptor dysfunction and/or intracranialhypersensitivity, through effects on sodium chan-nels. This is likely to be particularly useful inpatients who also have abnormal cellular adaptationin opiate-dependent nociceptor pathways due tochronic opioid use (40).

Summary

We believe that prolonged intravenous infusion oflignocaine is a practical means of treating the partic-ularly difficult group of patients with CDH associ-ated with abuse of large quantities of analgesics,including codeine. It seems to have a better side-effect profile than other parenteral therapies such asDHE and requires a similar length of stay in hospital.As part of an integrated treatment program, includ-ing long-term follow up and psychiatric assessment,long-term improvement in headache frequency andintensity is seen past six months. Improvement is

most likely if the medications implicated in CDH areavoided completely.

Acknowledgements

We thank the patients who participated in this survey andthose who referred them. We also thank other members of theneurology unit at the Alfred Hospital who assisted in the careof these patients, and Dr David Lowenstern who performedthe psychiatric assessments.

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