Introduction: Medication overuse headache (MOH) is a secondary headache that occurs 15 or more days per month in patients with pre-existing headaches. It results from the excessive (10 or 15 days/month) use of drugs used as acute or symptomatic headache therapy. The Aim: To examine the relationship between demographic parameters, illnesses and habits of life, clinical type and length of previous headache and MOH; clinical features of MOH.

Material and methods: The study was conducted at the Clinic of Neurology, Clinical Center of Niš, and included 83 patients (11 men and 72 women) who were first diagnosed with MOH. The mean age of the study cohort was 40.5 ± 11.6 years. The study was performed in strict accordance with the Declaration of Helsinki after informed consent by each participant in the study Approved by the local Ethical Committee.

Results: In the study cohort, there were more women (86.7%), non-smokers (59%), those who did not consume alcohol (95.2%), physically inactive (90.4%), those who consumed caffeinated beverages (89.2%), with diseases of the cardiovascular (12%) and osseous joint system (10.8%). MOH was most commonly generated by the transformation of chronic migraine (64%). The duration of MOH until diagnosis was 5.1 ± 5.5 years. The following MOH characteristics were observed: moderate pain (45.8%), bilateral localization (56.6%), temporal presentation (65.1%), and neck tightness (81.9%). Common (41%) and combination analgesics (48.2%) were used most frequently, 15 to 25 days per month. The impact of MOH on daily life was assessed as significant (HIT - 65.4 ± 5.5), correlating with the duration of earlier chronic headaches (r = 0.327, p = 0.003).

Conclusion: MOH is generated by the transformation of a previous chronic headache due to overuse of analgesic therapy. MOH significantly affects all aspects of the patient’s life. MOH can be prevented by educating patients, by limiting the use of analgesic therapy, especially in the at-risk group (middleaged women with chronic migraines).

• Medication; Overuse; Headache

Todorovic S, Ljubisavljevic S (2024) Main Clinical Characteristics of Medication Overuse Headache. J Neurol Disord Stroke 11(2): 1218.

Medication overuse headache (MOH) is a secondary headache classified according to the International Headache Society as a group of headaches attributed to the use or discontinuation of various substances [1]. MOH occurs 15 or more days per month in patients with pre-existing headaches. It occurs due to regular (at least three consecutive months) overuse (10 days, or 15 days for certain medications) of medicines used as acute or symptomatic headache therapy. MOH can occur due to excessive use of ergotamine, triptans, ordinary analgesics (paracetamol, acetylsalicylic acid, nonsteroidal anti-inflammatory drugs (NSAIDs), opioids, combined analgesics, and simultaneous use of several types of drugs.

This type of headache most often occurs in the fourth decade (between 30 and 50), more common in women (female to male ratio is 3-4:1) [3]. The estimated prevalence of MOH is about 3%. The burden on the patient and his family is a consequence of the impairment of the quality of daily life. MOH represents a significant burden on the health system and society as a whole, it affects the reduction of working capacity, often missing work [1-3].

Although it can occur from any type of headache, MOS is most often caused by the chronic transformation of migraine. A complete understanding of the pathophysiological process that leads to the occurrence of this condition is not fully elucidated. It is assumed that processes of central sensitization (suppression of endogenous pain modulation, neuronal excitability due to neurotransmitter imbalances (adrenaline, serotonin), etc.) represent the pathogenetic basis of MOH [4-8].

MOH treatment involves educating patients about the necessity of limited use of analgesics, most often with the simultaneous implementation of detoxification therapy and prophylactic support of coanalgetic therapy (valproate, topiramate, amitriptyline, onabotulinum toxin A, etc.). This can be done in an outpatient or hospital setting. During the use of triptans, ergotamine, and NSAIDS is advised to abruptly stop the excessive use of these drugs. On the other hand, a gradual reduction in the dose of the drug is recommended for previous overuse of barbiturates, benzodiazepines and opioids [9,10].

Although it is considered potentially preventable, changeable and unchanging risk factors for MOH have not yet been recognized. Identifying these risk factors could benefit to identify patients with a previous headache who are at higher risk for chronification and transformation a previous headache into MOH.

The research aimed to examine:

• Association of demographic parameters, diseases and habits of life, clinical type and duration of previous headache and MOH

• Clinical features of MOH

The research was conducted as part of a project approved by the Ethics Committee of the Faculty of Medicine in Niš as an observational, cross-sectional study.

The study included all patients examined at the Headache Clinic of the Neurology Clinic, Clinical Center in Nis during 2019 (January-December) in whom the diagnosis of MOH was made for the first time in this period. Patients gave informed consent to participate in the study.

The diagnosis of MOH is made according to the current diagnostic criteria of the International Classification of Headaches [1]. In all patients, the second etiology of the headache is excluded after complete diagnostic processing (computed tomography, magnetic resonance imaging, etc.).

Data on the included patients were collected - demographic data, data from the history of personal life, the existence of other diseases, the existence of previous (primary and/or secondary) headaches (type, characteristics, duration of headache, frequency of occurrence, effectiveness of symptomatic and preventive therapy), habits and risk factors (physical activity, smoking cigarettes, use of alcohol, caffeine, etc.).

Data related to MOH - location of pain (frontal, temporal, parietal, occipital), lateralization (unilateral, diffuse), character (dull, pulsating pain) intensity of the pain (using a numerical scale to assess pain), the existence of associated symptoms and signs (nausea/vomiting, photophobia, phonophobia, diplopia, neck and shoulder tightness: blurred vision, ringing in the ears: hyperacusis), type of analgesic therapy used, preventive therapy, frequency of use of this therapy (number of days/month), the effectiveness of the therapy, and the effect of headaches on the activities of everyday life (headache impact test - HIT).

For the statistical processing of data, a single database was formed to which the methods of descriptive and analytical statistics were applied. All statistical analyses were carried out in the SPSS 16.0 software package.

The study included 83 patients with MOH, 11 men and 72 women. The mean age of these patients was 40.5±11.6 years (range: 18 to 71 years) (Table 1).

Table 1: Lifestyle habits, risk factors, comorbidities

* Hi square test, p<0.05

By analyzing the frequency of the parameters studied, it was observed that in the cohort of patients with MOH there were more women, non-smokers, non-drinkers (daily use/use a greater number of days per week), physically inactive (daily/ greater number of days per week), patients with comorbidities in the form of cardiovascular and bone and joint diseases, (Table 1).

MOH was more common in migraine patients (64%), compared to tension-type headache (25%) and symptomatic headache (11%). The duration of the primary headache was 6.5 ± 3.2 years, (Graphic 1).

Graph 1: Frequency of nodules; clinical types of previous headaches.

* Hi square test, p<0.05

In the study group, the average duration of MOH (up to the time of diagnosis) was more than 5 years; more than half a month was affected by headache; the duration of individual headache attacks was more than 10 hours per day. Patients described the pain as moderate to severe (45.8%), bilateral localization (56.6%), mostly temporal presentation (65.1%), and most often with accompanying complaints in the form of neck tightness (81.9%). Most patients used ordinary analgesics (NSAIDs) (41%). and combined analgesics (48.2%), averaging 15 to 25 days per month. This treatment was ineffective in the largest percentage of patients (78.3%).

A large number of patients used prophylactic therapy and antidepressant drugs (83.1%). The effect of headaches on activities of daily living has been assessed as significant (HIT - 65.4±5.5), (Table 2).

Table 2: Clinical features of MOH

*Hi square test, p<0.05

The correlation analysis showed only the association between the duration of the previous headache and the effect of MOH on daily life activities (HIT), r=0.327, p=0.003.

The results of our research confirm the results of earlier studies [1,3,11-14] that MOH occurs mainly in middle age, more often in women. Interestingly, the largest percentage of patients in our study did not smoke or consume alcohol, while the majority of them were physically inactive and regularly used caffeinated beverages. In the literature reviewed, no significant studies were observed, the results of which could be useful for comparison with the results obtained here. A study examining at various risk factors for MOH found a correlation between physical inactivity and smoking with MOH onset [14]. Our results are partially consistent with those findings. Studies that examined at the characteristics of patients who have never had a headache in their lives found that they were men, of younger ages who regularly consumed alcoholic beverages (unpublished results). Our results on the inverse relationship between alcohol consumption and the occurrence of MOH are consistent with these findings. Although most patients with MOH did not have comorbidities, the incidence of cardiovascular and bone and joint diseases was significantly higher than other comorbid conditions. The reasons for this finding should be sought in the fact that arterial hypertension and spondylosis of the cervical spine (the most common diagnoses in these patients) are the most common causes of secondary chronic headaches [1]. This headache due to its chronic course poses a risk of developing MOH. Previous studies have found an association between diseases of the osseous joint system with the occurrence of MOH [14].

Although it can arise from all primary headaches, MOH is most often caused by the transformation of chronic migraine [1]. The results of our study found that the highest percentage of patients with MOH previously had chronic migraines.

Our research has shown that MOH is most often caused by excessive use of combined and ordinary analgesics (NSAIDs). The risk of MOH has previously been shown to be lower with triptans and ergotamine use compared to NSAIDs [15-17]. Although they used prophylactic therapy, for the most part, patients with MOH did not achieve satisfactory therapeutic efficacy.

The high values obtained here on the scale of assessment of the impact of headaches on daily life activities are in agreement with the results of previous studies [13].

Research devoted to examining the pathophysiological mechanisms of MOH finds morphometric and functional changes in regions crucial for the modulation of nociception (periaqueductal grey matter, posterior cingular cortex, hippocampus, thalamus, orbitofrontal cortex, anterior cingular gyrus, insula, precuneus) [15,16]. These structures are involved in nociception modulation, cognition, affective and addictive behavior. The mechanisms of central sensitization (hyperexcitability of pain modulation pathways) are considered crucial in the pathophysiology of MOH [1]. Bilateral, moderately severe pain accompanied by tightness in the neck and shoulders and the absence of so-called migraine features of MOH in our study (even though it is largely due to the transformation of previous chronic migraine) support the previously assumed mechanisms of central sensitization.

MOH results from the transformation of a previous chronic headache due to overuse of analgesic therapy.

It affects the middle-aged population, mostly women, affecting all aspects of the patient’s life.

Despite defined therapeutic strategies for treatment, prevention of MOH is considered inviolable (patient education, limiting the use of analgesic therapy especially in the at-risk group of patients (middle-aged women with chronic migraine)). Further investigations of other potentially modifiable risk factors for the development of MOH, its course and outcome after certain therapeutic interventions are necessary.

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