Headache Medicine 2021, 12(2) p-ISSN 2178-7468, e-ISSN 2763-6178

128

ASAA

DOI: 10.48208/HeadacheMed.2021.23

Headache Medicine

Original

Higher frequency of medication overuse headache in patients

attended by neurologists in Lima, Peru

María Elena Novoa

, Carlos A. Bordini

2,3

Department of Neurovascular Diseases, National Institute of Neurological Sciences, Lima, Peru

Neurologic Unit, FACEF Medical School, Brazil

Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, São Paulo, Brazil

Abstract

Background

The type of medical care received (self-medication and/or medical care provided by a

general practitioner or a neurologist) may be associated with differences in the frequency of

medication overuse headaches.

Method

This cross-sectional analytical study included 222 records of patients with chronic daily hea-

daches seen at the National Institute of Neurological Sciences Outpatient Unit in Lima, Peru.

A pre-designed questionnaire was used to assess and categorize patients with frequent and

chronic headaches.

Results

Ninety-four patients (42.34% of those with chronic daily headaches) met the criteria for

medication overuse headache. Of these, 19 (28%) self-medicated, 22 (36%) consulted with

the general practitioner, and the highest proportion of subjects, 53 (58%), consulted with a

neurologist. On bivariate analysis, subjects who had received care from a general practitio-

ner and self-medicated were 38% and 51% less likely to have MOH than the subjects who

received medical care from the neurologist (p=0.012; 95% CI 0.42-0.90 and p=0.001; 95%

CI 0.32-0.74). On multivariate analysis adjusting by sociodemographic and clinical factors,

the association remained signicant in regards to self-medication, but became marginal

(p=0.055) in regard to being seen by a general practitioner.

Conclusion

In this study, the frequency of the headache due to overuse of medication was higher in pa-

tients attending a neurologist than those attending a general practitioner or self-medicated.

This cross-sectional design cannot assess whether this reects more severe cases looking

for specialized care or more medication overuse headaches as a result of inappropriate

management.

Address all correspondence to Ma-

ría E. Novoa. National Institute of

Neurological Sciences, Jr. Ancash

1271 Lima-Perú, e-mail: maria.no-

voa.m@upch.pe

Edited by:

Marcelo Moraes Valença

Keywords:

Headaches

Medication overuse headache

(MOH)

Chronic daily headaches

Neurologists

General practitioners

Headache Disorders

Secondary

Received: May 6, 2021

Accepted: September 5, 2021

129

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Novoa ME, Bordini CA

Higher frequency of medication overuse headache in patients attended by neurologists in Lima, Peru

Introduction

eadache is a symptom associated with many medical

conditions (ICHD-3), and migraine and tension-type

headache (TTH) are the most prevalent types of headaches.

When migraine or TTH are categorized as episodic migraine

(EM) and episodic TTH (ETTH) if attacks occur less than

15 days a month. If attacks occur for 15 or more days per

month, they are dened as chronic daily headaches (CDH;

chronic migraine [CM] or chronic TTH [CTTH])

1,2

; making

up both groups CM and CTTH, the majority of patients

with chronic daily headaches CDH.

Medication overuse

headache (MOH) is a CDH, mostly underlying a pre-exist-

ing primary headache, and adding to this, the overuse of

symptomatic medication (10 to 15 days/month, depending

on the overused drug, equal to or greater than three months)

for acute episodes.

The prevalence of MOH is 1% to 2% in

the general population, predominantly in women in industri-

alized countries.

The global burden of disease lists MOH

as the 18

cause of disability. In addition to disability due

to migraine (6

cause of disability); together, they represent

the 3

leading cause of disability in the world.

4,5

Currently, the global campaign to reduce the burden of

headache (Lifting the Burden) is assessing known and

potential risk factors associated with MOH. Several

studies have determined associations with polymorphic

variants related to the susceptibility of conversion to

MOH

, psychopathological comorbidities

, within these,

post-traumatic stress events

, depression, anxiety and

insomnia

, and other sociodemographic factors, such as

low education, place of residence, limited medical contact

and type of medical care received in the development of

MOH.

10-13

Factors that, in addition to transforming EM

and ETTH into CM and CTTH

7-9,14,15

, induce patients to

seek different types of medical attention and to overuse

medication in an effort to obtain relief from their pain.

16-19

There is no clear evidence regarding the association of

MOH with the type of medical care received. A 2012

Swedish publication suggested that limited medical

care, due to reduced neurological care in rural areas,

leads to self-medication with over-the-counter medication,

increasing the likelihood of MOH development.

Factor

similar to the reality of developing countries such as

Peru, where specialists are concentrated in metropolitan

areas. This study evaluated whether there is a relationship

between MOH and the type of medical care received (self-

medication, general practitioner or neurologist) in new

patients who attended a neurological referral center.

Methods

Clinical interview - In this cross-sectional analytical study,

we selected all records with CDH from a previous study

that evaluated 419 new patients with headaches in the

outpatient clinic of the National Instituto Nacional de

Ciencias Neurológicas (INCN), Lima, Peru (a reference

tertiary center). In the previous study, the participants

were interviewed and examined by an INCN headache

specialist, after the application of a complete clinical and

demographic questionnaire.

Questionnaire - A questionnaire allowed the diagnosis of

episodic and chronic headaches according to ICHD-III-Beta

version-2013 criteria.

For the study, we included from the

primary study, data records with the diagnosis of DCH,

excluding records with missing data. The questions: (1) Do

you usually take any medication to relieve headaches?, (2)

How many times a month do you take any medication?,

and (3) How long have you been using the drug? allowed

to generate the diagnosis of MOH; while the questions

(1) Has a doctor ever treated your headache in your life?

and (2) What specialty did the treating physician have?

allowed to categorize the type of medical care received.

Ethical aspects - The primary study protocol and informed

consent form, as well as this secondary data analysis,

were approved by the research and ethics committee of

the INCN (N0523-2018-CIEI-INCN).

Data processing - Analysis was performed using Stata

14 StataCorp, (Texas, United States). Descriptive

statistics are provided with measures of central tendency,

frequencies, percentages, means and standard deviations

as appropriate. We consider signicance at p<0.05

with two-tailed test. We compared proportions using chi-

square (X

) test, after analysis of assumptions, to test the

alternative hypothesis, that lack of neurological attention

is associated with MOH. Simple and adjusted regressions

were performed using generalized linear models (GLM),

binomial family to measure prevalence ratios (PR) due to

our cross-sectional design. Due to the non-convergence of

the binomial GLM model, a robust Poisson generalized

linear model (GLM) was also run.

Results

From the primary study consisting of 419 participants

(April 2016) (Figure 1), we selected 222 data records with

130

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Novoa ME, Bordini CA

Higher frequency of medication overuse headache in patients attended by neurologists in Lima, Peru

CDH, the total population of this cross-sectional study.

Figure 1. Flowchart for the screening of medication overuse headache

patients. CEFAPERU data.

Sociodemographic and clinical variables are described in

Table 1. The average age was 46 (±17 SD) years. They were

146 (66%) women and 76 (36%) men. As in other studies,

CDH is more prevalent in women; and more patients lived in

urban areas, 124 (56%). Migraines (n=122, 55%) were the

most frequent type of headache. The order of frequency of

drug use was: drugs not remembered, (n=83, 38%), NSAIDs

(n=58, 26%), paracetamol (39, 18%), other drugs (24, 11%)

and ergotamine (18, 0.8%). Regarding the type of medical

care received, neurological care was more frequent, occurring

in 92 cases (41%), followed by self-medication in 68 (31%),

and care by a general practitioner in 62 (28%) (Figure 2).

Figure 2. Levels of type of care received by patients with chronic daily

headache who developed medication overuse headache (MOH).

While all drug categories were overused; regression adjustment

demonstrated that ergotamine were associated with a higher

proportion of MOH. Using neurological care as a category of

reference in the simple regression, we demonstrated a 38%

lower probability of MOH in patients seen by the general

practitioner (p=0.012, 95% CI 0.42-0.90), and a 51%

lower probability of developing MOH with self-medication

(p=0.001, 95% CI 0.32-0.74). Whereas, multiple regression

adjusted for other sociodemographic and clinical variables,

made the strength of association with general practitioner care

marginal (30% less probability, p = 0.053, 95% CI 0.48-

1.00), maintaining signicant for self-medication (37% less

probability, p=0.030, 95% CI 0.42-0.96) (Table 1).

Discussion

In this study, MOH was more frequent in patients seen by

neurologists, compared to subjects seen by the general

practitioner or self-medicated. In our view, the most plausible

explanation is that individuals with MOH sought specialized

care, although we cannot rule out that the higher frequency

of MOH resulted from inadequate neurological management.

Jonsson et al.

, in Sweden, reported that the high proportion

of MOH in their study was due to limited access to medical

care. However, in this series the frequency of MOH among

those who received medical attention was non-signicantly

higher with neurological care than with care performed by

other physicians. Longitudinal studies are required to conrm

this hypothesis.

Most studies report that migraine is the most common underlying

headache in MOH, followed by TTH.

18,21,22

Our data have

this trend, although there was no signicant difference. On

the other hand, although psychiatric comorbidities such as

anxiety, depression, and others, plus altered hormone levels

associated with mood swings in women over 40 years of

age

7,23

, could lead to CDH and MOH, we found no signicant

differences for MOH in this subgroup.

Shand et al.

reported that the overused drugs that led to the

development of MOH in Argentina and Chile were combined

ergotamine (70%) and NSAIDs (33.8%). Johnson et al.

however, showed a higher proportion of MOH (66%) with

overuse of psychotropic drugs. While Find et al.

, in a multicenter

study on MOH, reported that ergotamine was greatly overused

in Latin America (72% compared with 4% in Europe, p<0.001).

Our ndings support these data, MOH was 2.5 times more

frequent in patients with ergotamine overuse compared to those

who overused drugs that they did not remember (reference

category). In Peru, as in other Latin America countries ergotamine

is extremely cheap and available over the counter.

Our study has several limitations. Self-report could create

inaccuracies in the estimation of the exposure to the studied

factors, affecting the reliability. However, a study on the

validity of the self-report on MOH dependency severity

131

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Novoa ME, Bordini CA

Higher frequency of medication overuse headache in patients attended by neurologists in Lima, Peru

Table 1. Analysis of the association between medication overuse headache and (MOH) sociodemographic and clinical characteristics.

Variables N (%)

Without MOH

(n = 128)

With MOH

(n = 94)

p-value

Simple model PR

(95% CI)

p-value

Adjusted model PR

(95% CI)

p-value

Sex

0.533

Male 76 (34.2) 46 (60.5%) 30 (39.5%) Ref. Ref.

Female 146 (65.8) 82 (56.2%) 64 (43.8%) 1.11 (0.79-1.55) 0.539 1.01(0.72-1.38) 0.955

Age 45.7±17.0 - - - - -

Categorized age (years)

0.905

18-40 87 (39.19) 51(58.6%) 36(41.4%) Ref. Ref.

41-60 86 (38.74) 48(55.8%) 38(44.2%) 1.11 (0.79-1.57) 0.554 1.21(0.87-1.68) 0.251

61-93 49 (22.07) 29(59.2%) 20(40.8%) 1.00 (0.66-1.53) 0.986 1.31(0.87-1.97) 0.204

Residence

0.219

Rural 98 (44.14) 61 (62.2%) 37 (37.8%) Ref. Ref.

Urban 124 (55.9) 67 (54.0%) 57 (46.1%) 1.22 (0.89-1.67) 0.226 1.16(0.86-1.57) 0.324

Types of Headache

0.192

Tension-type headache 49 (22.1) 30 (61.2%) 19 (38.8%) Ref. Ref.

Indeterminate headache 51 (22.6) 34 (66.7%) 17 (33.3%) 0.86 (0.51-1.45) 0.572 0.79 (0.48-1.31) 0.355

Migraine 122 (55.0) 64 (52.5%) 58 (47.5%) 1.23 (0.82-1.83) 0.317 1.15 (0.79-1.67) 0.459

Overused drugs

<0.001

Forgotten drug 83 (37.4) 67 (80.7%) 16 (19.3%) Ref. Ref.

Paracetamol 39 (17.6) 23 (59.1%) 16 (41.0%) 2.13 (1.19-3.80) 0.011 2.21 (1.21-4.03) 0.010

Other drugs 24 (10.8) 11 (45.8%) 13 (54.2%) 2.81 (1.58-4.99) <0.001 2.78(1.54-5.00) 0.001

NSAIDs 58 (26.1) 21 (36.2%) 37 (63.8%) 3.31 (2.04-5.36) <0.001 3.08(1.88-5.04) <0.001

Ergotamine 18 (8.1) 6 (33.3%) 12 (66.7%) 3.46 (1.99-5.99) <0.001 2.76(1.58-4.84) <0.001

Type medical care received

0.001

Neurologist 92 (41.4) 39 (42.4%) 53 (57.6%) Ref. Ref.

General practitioner 62 (27.9) 40 (64.5%) 22 (35.5%) 0.62 (0.42-0.90) 0.012 0.70 (0.48-1.00) 0.053

Self-medication 68 (30.6) 49 (72.1%) 19 (27.9%) 0.49 (0.32-0.74) 0.001 0.63 (0.42-0.96) 0.030

scales suggests that a self-reported version provides valuable

information as a screening tool after a headache consultation.

There are studies that provide greater security in this context,

reporting concordance between what is reported by patients

and medical prescription and diagnosis records, using

telephone lines or online platforms for interviews. The cross-

sectional design of this study limits the estimation of causality,

as well as the fact that this study was carried out in a tertiary

referral center, where the most serious cases arrive, limiting the

representativeness of MOH in the population.

We determined that subjects who arrived at this third-level

center, with a higher proportion of MOH, had already been

seen by neurologists. These results could reect that headaches

as severe as MOH, came in search of more specialized care

than they received and are the result of improper prior, non-

specialized management. However, we cannot prove this

from our data; longitudinal studies are required to clarify this

and complement our ndings. However, the high frequency

of occurrence of MOH attended by neurologists, should lead

to awareness regarding its diagnosis and management, as

well as the prompt and adequate training of specialists in its

diagnosis and management.

Conflict of interest: None

Author Contributions: MEN, Study conception and design,

Data acquisition and interpretation, Revised the manuscript

and nal approval; CAB, Critically revised the manuscript and

nal approval.

María Elena Novoa

https://orcid.org/0000-0002-7545-9217

Carlos A. Bordini

https://orcid.org/0000-0002-1249-5202

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