**6. Primary cephalea treatment overuse and abuse statistics worldwide**

Once a patient receives the diagnosis of migraine or any other primary headache, treatments usually become supervised by a medical team and patients are directed on what to do and what not to do regarding pharmacological therapy and although this group of patients carries a certain risk for medication abuse or overuse, usually there are no major concerns unless the patient abandons regular control and supervised treatment. Unfortunately, up to 50% of migraine patients remain undiagnosed [81] and even worst, up to 82% of patients with a diagnosis of nonmigraine headache actually meet the major migraine criteria [82] leading to improper handling and medication.

Regarding chronic tension-type headaches, up to 40% of patients have not received a formal diagnosis and are not aware of what disease they are suffering from [83]; they often think they have a benign condition causing the self-medication of migraine rescue drugs (OTC painkillers and analgesics) to become a trend, leading to the worsening of their underlying disorder.

On the other hand, a group of patients with a formal diagnosis of a primary headache disorder abandon follow-up due to lack of insurance, discouraging results or moving away to an area with no specialists with experience on headache treatment, keeping their treatment as something they do on their own, usually increasing dosing and dose intervals, leading to preventive and abortive medication overuse [84]. Aside from the above mentioned, there is another group of existing patients suffering from *chronic daily headache* affecting up to 5% of the general population [85], self-medicating with over-the-counter painkillers and analgesics to deal with pain crisis, increasing the risk of evolution toward chronic headache [86] due to central nervous system sensitization [87].

Even when not included in the International Headache Society Classification of Headache, chronic daily headache is a common disorder defined by some authors as "*a disorder where patients suffer very frequent headaches (15 or more days/month), including those headaches", furthermore, "Chronic Daily Headache (CDH) may be divided into two main groups; Primary CDH is not related to any structural or systemic illness. Population based studies suggest that Chronic Tension Type Headache is the leading cause of primary CDH, on the other hand, Secondary CDH occurs 15 or more times a month or has some identifiable underlying cause* [88]" (secondary CDH is summarized in **Table 7**).


*Abbreviations*: EBV, Epstein-Barr virus; HIV, human immunodeficiency virus. Table reproduced and adapted from the original source [89].

**Table 7.** Chronic daily headache causes.

**6. Primary cephalea treatment overuse and abuse statistics worldwide**

**Drug name Symptoms relieved Precautions and possible side effects**

Aspirin Relief of fever and pain Do not use in children under 14 years

Acetaminophen Relief of fever and pain Few side effects, if taken as directed,

Naproxen Sodium Headache pain relief Side effects may include GI upset, GI

inflammation

of age due to the potential for Reye's

Side effects may include: heartburn, gastrointestinal (GI) bleeding, bronchospasm or constriction that causes narrowing of the airways, anaphylaxis and peptic ulcer

although they may include: changes in blood counts and liver functions

gastrointestinal upset, GI bleeding, nausea, vomiting, rash and changes

bleeding, nausea, vomiting, rash and

Side effects may include

changes in liver function

in liver function

Syndrome

improper handling and medication.

**Over-the-counter medications for symptomatic relief**

156 Pain Relief - From Analgesics to Alternative Therapies

Ibuprofen Relief of fever, pain and

Table reproduced and adapted from the original source [80].

**Table 6.** Side effects of main migraine rescue drugs.

**Nonsteroidal anti-inflammatories**

Once a patient receives the diagnosis of migraine or any other primary headache, treatments usually become supervised by a medical team and patients are directed on what to do and what not to do regarding pharmacological therapy and although this group of patients carries a certain risk for medication abuse or overuse, usually there are no major concerns unless the patient abandons regular control and supervised treatment. Unfortunately, up to 50% of migraine patients remain undiagnosed [81] and even worst, up to 82% of patients with a diagnosis of nonmigraine headache actually meet the major migraine criteria [82] leading to

Regarding chronic tension-type headaches, up to 40% of patients have not received a formal diagnosis and are not aware of what disease they are suffering from [83]; they often think they have a benign condition causing the self-medication of migraine rescue drugs (OTC painkillers and analgesics) to become a trend, leading to the worsening of their underlying disorder. On the other hand, a group of patients with a formal diagnosis of a primary headache disorder abandon follow-up due to lack of insurance, discouraging results or moving away to an area with no specialists with experience on headache treatment, keeping their treatment as something they do on their own, usually increasing dosing and dose intervals, leading to preventive and abortive medication overuse [84]. Aside from the above mentioned, there is another group of existing patients suffering from *chronic daily headache* affecting up to 5% of

Among all these patients "*thirty-five percent overused simple analgesics, 22% ergotics, 12.5% opioids, and 2.7% triptans; the remaining 27.8% have overused different combinations*" [28]. The major concern about these statistics is that although treatments may be helpful in the initial stages, their chronic, unsupervised use and abuse tends to lead toward pain chronification; increasing the number of pain crises, intensity of pain, and resistance to regular analgesic dosing. Moreover, relapsing after medication withdrawal is still a major issue regarding both preventive and rescue primary headache treatments [90]. How many patients progress toward chronification will vary depending on the abused medication, according to Bigal "*available data suggest that opioids induce migraine chronification (progression), and the effect is dose dependent (critical dose around 8 days of exposure per month) and more pronounced in men. Barbiturates also induce migraine progression, and the effect is dose dependent (critical dose around 5 days of exposure per month) and more pronounced in women. Triptans induce migraine progression only in those with high migraine frequency at baseline (10–14 days per month), but not overall. NSAIDs protect against migraine progression unless individuals have 10 or more headache days per month (when they become inducers, rather than protective). Finally, caffeine-containing over-thecounter products increase risk of progression*" [91], thus each available drug used must be monitored individually in order to avoid overuse and abuse-related complications. Why and how primary headaches progress to chronification because of treatment abuse is still partially unknown and a field of very active research.
