Headache Medicine 2021, 12(3):240-246 p-ISSN 2178-7468, e-ISSN 2763-6178

240

ASAA

DOI: 10.48208/HeadacheMed.2021.35

Headache Medicine

Original

Applicability of DSM-V substance use disorder (SUD) criteria in

medication overuse headache (MOH)

Thaiza Agostini Córdoba de Lima

, Mario Fernando Prieto Peres

1,2

, Stephen D Silberstein

Hospital Israelita Albert Einstein, São Paulo, SP,Brazil

Instituto de Psiquiatria do Hospital das Clínicas da FMUSP, São Paulo, SP, Brazil

Thomas Je󰀨erson University: Philadelphia, PA, USA

Abstract

Medication overuse headache (MOH) is a chronic secondary headache disorder

attributed to the frequent or regular use of analgesics or acute antimigraine drugs

in patients with a primary headache disorder. In addition, it has been linked to

substance use disorder (SUD) also known as drug addiction, a persistent use of

drugs or substances, despite substantial damage and adverse consequences,

diagnosed by DSM-V criteria. At this time, apart from opioids, acute headache

medications are not included in SUD. Despite the idea that the compulsive search

for reward in MOH is similar to that observed in substance dependence, the DSM-V

SUD criteria have never been carefully applied to MOH. We propose to discuss

each DSM-V criterion of SUD diagnosis to see whether it is appropriate to use in

MOH. We considered it was not-applicable when dealing with a situation that

could be explained both by addictive behavior and by poorly controlled primary

headache. We conclude that the SUD criteria should not be applied to patients

who meet the criteria for MOH.

Mario F P Peres; Hospital Israelita Albert

Einstein; Av. Albert Einstein, 627, Bloco A1, 1º

andar, Sala 110, Jardim Leonor; 05652-900,

São Paulo-SP, Brazil. E-mail: mariop3r3s@

gmail.com

Edited by:

Marcelo Moraes Valença

Keywords:

Medication Overuse Headache

Substance use disorder

Addiction

Dependence

Abuse

Migraine

Received: November 24, 2021

Accepted: December 6, 2021

241

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Lima TAC, Peres MFP, Silberstein SD

Applicability of DSM-V substance use disorder (SUD) criteria in medication overuse headache (MOH)

Introduction

edication overuse headache (MOH) is a common

chronic secondary headache disorder attributed to the

frequent or regular use of analgesics or acute antimigraine

drugs in patients with a primary headache disorder. It is

commonly associated with chronic migraine and chronic

tension-type headache. MOH implies the idea of a para-

doxical effect of long term, frequent use of acute medica-

tion. Although MOH is more likely to occur with opioids

use, by denition, any abortive medication is considered

to cause this condition.

The diagnosis of MOH is based

on the International Classication of Headache Disorders

3rd edition (ICHD-3) 8.2 MOH is dened as: headache

occurring for 15 or more days/month in a patient with a

pre-existing primary headache and regular overuse of acute

or symptomatic headache medication for 10 (ergotamine,

triptans, analgesic combinations and opioids) or 15 (simple

non-opioid analgesics and NSAIDs) or more days/month,

for more than 3 months.

MOH has dened diagnostic criteria, but controversy still

exists about its validity.

The duration of use, quantity and

type of medication needed to cause MOH, is arbitrary

in the absence of evidence.

Furthermore, evidence of

cause and effect is also weak. In population studies, the

link between frequent use of medications and increased

frequency of headache is well demonstrated.

However,

this causal relationship can be difcult to ascertain in

individual cases. Not all patients who use analgesic

medications excessively develop chronic headache. In

addition, overuse of medication can be a response to

chronic headaches, not the cause.

Another controversy is the management of patients with

MOH. Elimination or reduction of overuse to less than 2

days per week

with or without concomitant preventive

medication are widely debated options

Many use a

bridging therapy to prevent withdrawal symptoms.

It is also necessary to rene the meaning and establish

the differences between the terms: use, misuse, overuse,

abuse, and dependence which are not clearly dened in

headache medicine.

Only the term overuse appears in the

headache classication

, but does not appear in the latest

version of the Diagnostic and Statistical Manual of Mental

Disorders (DSM).

MOH has been linked to addictive disorders. Studies

applying DSM-IV diagnostic criteria for dependence in

MOH patients, showed 50% to 68% of dependence.

11,12

After May 2013, when DSM-V was published, signicant

changes in classication and criteria for substance use

disorder and dependence occurred. DSM-IV abuse and

dependence have been combined into one new DSM-5

diagnosis: 'Substance Use Disorder'.

Substance use disorder (SUD) is considered a persistent

use of drugs or substances, despite substantial damage

and adverse consequences. Pathophysiology is associated

with changes in the reward system, the brain circuits

involved in pleasure, learning, stress, decision making and

self-control.

It is believed to be a subset of brain and

behavioral disorders, similar to the spectrum of obsessive-

compulsive disorder.

The classes of substances include:

alcohol, cannabis, hallucinogens, inhalants, opioids,

sedatives, hypnotics, anxiolytics, stimulants, tobacco,

and other or unknown substances.

Apart from opioids

and barbiturates, acute headache medications are

not included. But compulsive reward seeking in MOH

similar to that seen in substance dependence has been

discussed.

16-18

ICHD-3 suggests the similarity between patient’s behavior

with MOH and SUD and recommends the use of the

Severity of Dependence Scale (SDS) score to predict MOH

among headache patients. However, the criteria do not

allow us to distinguish these conditions, nor to understand

the complex relationship between patient behavior and

medication intake. DSM-V substance Use Disorder (SUD)

criteria has never been validated in MOH and other

headache disorders. We aim analyze the SUD in order

to discuss it’s appropriateness in headache medicine. We

also reviewed the denitions of: overuse, misuse, abuse,

dependence, addiction, tolerance and withdrawal, and

suggest a new classication system for patients with

frequent acute headache medication use.

Terms and Denitions

In 1988 headache was associated with painkillers

medications. Since then, there have been changes in

nomenclature. ‘‘Drug-induced headache” was rst used,

then “headache induced by chronic substance use or

exposure” and now, “medication overuse headache”, was

dened in 2004.

2,19

Although widely used, there is no clear denition

of “overuse”, “misuse” and “abuse”, often used

interchangeably. Other related terms can also be

confusing, such as drug addiction, addiction, tolerance,

242

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Lima TAC, Peres MFP, Silberstein SD

Applicability of DSM-V substance use disorder (SUD) criteria in medication overuse headache (MOH)

and withdrawal. All these terms need to have a clear and

universal meaning to avoid misunderstandings in medical

practice.

The inappropriate use of those terms is not exclusivity

the eld of neurology. These terms are often used

interchangeably in articles related to laxatives, nasal

decongestants, tranquilizers, sleeping aids, analgesics

for indications other than headache, and over-the-counter

medications.

20-23

According to recent medical literature, the denitions

based on health-related use are as follows

10,24,25

Use

: Correct use of dose, administration interval and

indication.

Overuse

: Excessive use related to the frequency or duration

of treatment. No behavior pattern of intake is attached.

Misuse

: Taking the medication inappropriately, not

respecting the prescription. Incorrect use of dose,

administration interval and indication. For example,

skipping or doubling doses or using for a purpose not

consistent with legal or medical guidelines. It has a negative

impact on psychological or physical health, but does not

fulll the DSM-V criteria for substance use disorder.

Abuse and Dependence

: The most recent classication

combines the two terms into a single unied category,

named as substance use disorder (SUD). Both terms are

related to the harmful use a drug or medication for a non-

medical reason, the diagnosis is based on DSM-5 criteria

which will be discussed later.

Addiction

: The DSM-5 did not include the term addiction

to avoid using a word with a strong stigma, to describe a

disorder with a wide spectrum, as SUD can be classied

as mild, moderate and severe. There is a potential negative

connotation.

Tolerance

: It is a neuropharmacological phenomenon.

There is a change in the dose and effect correlation. The

individual needs a larger dose to obtain the desired effect

or a reduced effect is obtained after consuming the usual

dose. Tolerance is extremely variable depending on the

individual, the substance and the delivery of the substance.

Withdrawal

: It is a substance-specic syndrome that occurs

when concentrations of a substance in the blood or tissues

decrease in an individual with chronic use. The symptoms

are class dependant; therefore, there are distinct diagnostic

criteria for different classes of substances. No tolerance or

withdrawal is required for the diagnosis of substance use

disorder (SUD).

Intoxication

: It is a substance-specic reversible syndrome

due to its recent ingestion. Intoxication can be acute or

chronic, symptoms vary depending on the time of exposure.

SUD criteria applicability in MOH

context

Our proposal is to discuss each SUD DSM-V criterion in

order to assess whether it is applicable or if adaptation is

necessary, to chronic headache and frequent medication

use. We considered the criterion as non-applicable when

dealing with a situation that could be explained by

both addictive behavior and poorly controlled primary

headache. For example, how to differentiate whether the

use of medication was motivated for pain reduction or

represents dependence behavior? How to assess whether

damage in professional and personal life is caused by

poorly controlled primary headache or by a psychiatric

disorder related to substance use?

MOH is associated with barbiturates, analgesic

combinations, metamizole (dipyrone), acetaminofen,

acetylsalicylic acid, caffeine, opioids, ergot, non-

steroidal anti-inammatory drugs (NSAIDs), and triptans.

In our analysis, the criteria applicability to opioids

and barbiturate use was excluded, since OUD and

barbiturates dependence are widely described conditions

in the literature with diagnostic criteria well dened by the

DSM-5. The applicability for analgesic combination with

caffeine acting as adjuvants was considered in this study

since caffeine is not listed as a substance included in SUD

criteria. Caffeine is the only substance listed in DSM-V that

is not included in the category for SUD.

SUD diagnosis is made when two or more criterion are

present within a 12-month period. In contrast the period for

the diagnostic criteria of MOH is 3 months.

The following is a critical analysis of the DSM-V SUD criteria

in patients that fulll criteria for MOH. DSM-5 diagnostic

criteria for SUD are based on eleven topics. Each topic

represents a manifestation of a problematic pattern of use

leading to clinically signicant impairment or distress.

Item 1. Often taken in larger amounts or over a longer

period than was intended.

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Lima TAC, Peres MFP, Silberstein SD

Applicability of DSM-V substance use disorder (SUD) criteria in medication overuse headache (MOH)

In the context of chronic pain medications use, the

denition of "large amounts" and "longer period" can be

subjective. Is this criterion about misuse or overuse? Doubt

shows how differentiating between overuse and misuse can

be challenging. Our suggestion is rst to identify whether

it is a prescription or an over-the-counter medication. The

use of doses higher than those prescribed or motivated by

a situation other than indicated classies the situation as

misuse. When the patient is actually taking medication more

frequently then prescribed, it should not be considered

as overuse because it could be a consequence of a poor

headache control.

We suggest not considering the criterion based only on a

simplistic analysis of days of the months that medication

was used, as it is done in the classication of MOH.

Item 2. A persistent desire or unsuccessful efforts to cut

down or control use.

This is clearly appropriate for illicit drugs and alcohol, but

its applicability for excessive acute headache medication

use is challenging. Since the use of an acute medication is

for a medical reason and not recreation, this item should

not be applicable in headache medicine.

Patients often want to decrease their medication, but if the

medication has been taken to control a headache disorder,

and the headache is controlled by preventive measures,

acute medications are often no longer necessary. Efforts

or desire to cut down or control analgesic by headache

sufferers is dependent on headache control not just patients

desire to not take acute medication.

Item 3. A great deal of time is spent in activities necessary

to obtain, use, or recover from the substance’s effects.

Analgesics are easily obtained over-the-counter, and if

a prescription is needed, from medical practitioners and

pharmacies. Thus, no considerable effort is necessary to

obtain the medication. As in item 2, this item ts the context

of drug dependence, such as opioids but not for other

analgesics, or headache attack abortives. In our analysis

we have also considered this criterion as non-applicable.

Item 4. Craving or a strong desire or urge to use the

substance.

Patients with inadequately treated pain might exhibit drug-

seeking behaviour similar to that of true dependence.

Opioid-based studies suggest that, to differentiate the two

situations, the dose of medication should be increased.

The search behavior is resolved if the pain is controlled

with a higher dose, while it remains the same or worsens

in the actual addictive behavior.

We excluded opioids

from our analysis and there is no recommendation to infer

the same approach to other drug classes. Furthermore, the

strong desire or urge to use the medication should not be

considered a pathological behavior pattern if the patient

is in pain, and has a strong desire or urge to alleviate

pain is perfectly legitimate, should not be considered as

unhealthy.

Item 5. Recurrent use resulting in a failure to fulll major

role obligations at work, school, or home.

Recurrent use of acute headache medication may

result in a failure to fulll major role obligations, but it

unrelated to addiction behaviours. Migraine burden

on social and professional life is widely known, several

studies have documented migraine’s impact on functional

ability. If acute medication is causing side effects such as

nausea, drowsiness or cognitive impairment, leading to

a dysfunction then it is just an undesired side effect, not

addiction behaviour.

Item 6. Continued use despite having persistent or recurrent

social or interpersonal problems caused or exacerbated

by its effects.

Item 7. Important social, occupational, or recreational

activities are given up or reduced because of use.

Both criteria 6 and 7 were analyzed simultaneously, as we

consider them redundant in the current context.

According to the explanation of criterion 5, migraine

impacts on interpersonal relationships and activities of

social life. The burden of migraine needs to be differentiated

from the consequences of the effects of medications. Thus,

we consider that this criterion requires adaptation, in order

to emphasize the need to seek additional effects due to the

use of medications.

Item 8. Recurrent use in situations in which it is physically

hazardous.

Item 9. Continued use despite knowledge of having a

persistent or recurrent physical or psychological problem

that is likely to have been caused or exacerbated by the

substance.

Both criteria 8 and 9 were analyzed simultaneously. These

criteria can be considered when the patient persist with

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Lima TAC, Peres MFP, Silberstein SD

Applicability of DSM-V substance use disorder (SUD) criteria in medication overuse headache (MOH)

the medication use even when he is aware of damage

in physical and mental health and another treatment

alternative have been offered. For example, continue

use despite medical contraindication for presenting side

effects, such as: renal failure or gastritis caused by non-

steroidal anti-inammatory drugs or harmful sleepiness

secondary to medications.

Item 10. Tolerance.

We consider this criterion as non-applicable for two main

reasons. First, the tolerance and withdrawal syndrome was

excluded from the DSM-5 criteria for substance use disorder

when use is prescribed and treatment is under adequate

medical supervision. The justication for this consideration

is that the symptoms are likely to be iatrogenic and not

pathological.

Second, in order to assess the possibility of tolerance,

the following situations should be excluded: change in

the medication formulation or brand, drug interactions,

disabsorptive disorders, and occurrence of a new disease

justifying the symptoms. However, in the context of chronic

pain, there is one more differential diagnosis of drug

tolerance, called “pseudotolerance”, in which the need

for higher doses is due to the progression or exacerbation

of the underlying primary headache. Therefore, tolerance

criterion is not applicable in the context of MOH.

Item 11. Withdrawal.

The fundamental requirement for withdrawal syndrome is

the development of a behavior problem associated with

physical symptoms due to the interruption or reduction of

prolonged substance use. According to the DSM-V criteria,

there are specic withdrawal symptoms for each substance,

but what is common to all substances is that the symptoms

must cause suffering and damage to social or professional

life, and the symptoms cannot associated or explained

by another medical condition. Furthermore, the diagnosis

cannot be made for any substance, but only for substances

with a described withdrawal syndrome. For example, there

are no described withdrawal syndrome for phencyclidine

and other hallucinogens, although these substances can

cause dependence. Moreover, as with the tolerance

criterion, the abstinence syndrome was excluded from the

DSM-5 criteria for medication-prescribed use disorder.

With the above information, the question arises: Apart

from opioids and caffeine, is there withdrawal syndrome

described for medications that cause MOH? This is a

question that divides opinions between authors.

The term "withdrawal headache" has been widely used

in the context of medication discontinuation in patients

with MOH. Stopping the acute medication may result

in symptoms such as increase of headache, nausea,

vomiting, arterial hypotension, tachycardia, insomnia and

anxiety. The duration and severity of withdrawal seems to

depend on the type of overused headache drug, shorter

in patients overusing triptans than in patients overusing

ergots or analgesics. The use of corticosteroid bridge

therapy signicantly reduced the duration and intensity of

these symptoms, as the use of rescue medications. There is

debate as to whether headache rebound and associated

symptoms are drug-related withdrawal syndrome or

whether it occurs due to worsening primary headache.

Thus, we consider that this criterion is not applicable

until further studies clarify the pathophysiology of these

symptoms.

In summary, all of the eleven criteria for SUD need

adaptation or have no applicability in MOH. Therefore,

we conclude that the SUD criteria should not be applied to

the patient who meets the criteria for MOH.

Conclusion

DSM-V SUD criteria is not applicable in the context of acute

headache medication other than opioids and barbiturates.

ICHD-3 MOH criteria do not adequately address the

spectrum of addiction. Therefore, the criteria are not an

appropriate diagnosis method in this subject. Studies are

needed to develop and validate new diagnostic criteria.

In addition, this paper highlight some gaps in the MOH

criteria, such as the absence of denition of overuse and

misuse, and the need for withdrawal syndrome criteria

related to MOH non-opioids medications. Clinical trials

are needed to overcome the failures of the current criteria.

Author’s contribution: TACL -Conception or design of the

work; Data collection; Data analysis and interpretation;

Drafting the article; Critical revision of the article; Final

approval of the version to be published. MFPP - Conception

or design of the work; Data collection; Data analysis and

interpretation; Drafting the article; Critical revision of the

article; Final approval of the version to be published. SDS

- Drafting the article; Critical revision of the article; Final

approval of the version to be published.

Conflict of interest: The authors declare that there is no

conict of interest.

Funding: The authors declare that there is no funding

245

ASAA

Lima TAC, Peres MFP, Silberstein SD

Applicability of DSM-V substance use disorder (SUD) criteria in medication overuse headache (MOH)

Thaiza Agostini Córdoba de Lima

https://orcid.org/0000-0001-6694-5259,

Mario Fernando Prieto Peres

https://orcid.org/0000-0002-0068-1905

Stephen D Silberstein

https://orcid.org/0000-0001-9467-5567

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