E-ISSN : 2757-7163
Materials and Methods: The study group consisted of women aged 19 to 64 years diagnosed as CM according to current International Headache Society (IHS) criteria, and OAB using the OAB-V8 (Overactive Bladder Inquiry Form - V8) and ICIQ-SF (International Consultation on Incontinence Questionnaire Short Form) forms as well as clinical evaluation in the neurology and urology clinics. 63 patients informed and agreed to enter the study were started migraine prophylaxis and evaluated after 6 months for comparison of pre-treatment and post-treatment VPS (visual pain scale), OAB-V8, and the ICIQ-SF scores. Flunarizine, topiramate, venlafaxine and propranolol were used in the treatment of patients.
Results: The mean age of 63 women included in the study was 39.15 ± 8.74 (19-64) years. The mean Body Mass Index (BMI) of the patients was determined as 25.41 ± 3.64 (16.4-35.6) kg/m2. After migraine prophylaxis, VPS, OAB-V8 and ICIQ-SF scores decreased significantly in the entire patient group (p<0.05). Statistically significant changes were found in the values of VPS, OAB-V8 and ICIQ-SF in the topiramate or propranolol treated groups. In the flunarizine group, there was a significant statistical response in the VPS and OAB-V8 scores, while there were no significant changes in the ICIQ-SF and OAB-V8 scores in the venlafaxinetreated group.
Conclusion: The beneficial effect of migraine prophylaxis on OAB symptoms support somewhat shared etiopathogenesis for both disorders. However, the series is small and considering the involvement of multifactorial factors and complex physiopathology for both disorders further studies are necessary to reveal the underlying mechanisms and clinical impacts.
This study group consisted of women aged 19 to 64 years diagnosed as CM according to the International Headache Society (IHS) criteria [4]. Patients were evaluated by urology and neurology physicians according to exclusion and inclusion criteria and participated in the study. The exclusion criteria were determined as follows: Urinary tract infection, neurogenic bladder and other etiology that can cause a neurogenic bladder (such as spinal cord injury, peripheral nerve disease), history / diagnosis of interstitial cystitis, lower urinary tract symptoms due to bladder stone and pelvic mass, symptomatic or severe pelvic organ prolapse, vaginal cancers, concomitant diseases that cause fluid shifts, such as congestive heart failure, cirrhosis, and pulmonary edema, use of diuretics and similar medicines, excessive fluid consumption (assessed by at least 3 days of voiding diary).
Questionnaires and Definitions
The individuals participating in the study were evaluated by
the neurology and urology physician with a study questionnaire
consisting of four parts; (I) Patient demographics; the gender,
age, body mass index (BMI) of the participants, (II) Migraine ID
test for the diagnosis of CM, which was any headache occurring
≥ 15 days per month for at least 3 months with migraine features
on ≥ 8 days every month, headache without excessive drug use
and non-attributable to another reason, and the visual pain scale
(VPS) scored between 0 and 10 points for qualitative evaluation
of migraine pain, (III) OAB-V8 (Overactive Bladder Inquiry
Form - V8) [5], (IV) ICIQ-SF (International Consultation on
Incontinence Questionnaire Short Form [6].
Accordingly, patients diagnosed as having both CM and OAB were identified and evaluated as reported before [3]. In this study, we aimed to investigate whether there would be any improvement in symptoms of OAB after migraine prophylaxis in patients with CM and OAB, as a follow-up. Patients informed and agreed to enter the study who were started migraine prophylaxis were evaluated after 6 months using the VPS, OAB-V8, and ICIQ-SF forms. Pre-treatment (before prophylaxis) and post-treatment (after prophylaxis) symptoms were compared. There was a total of 63 women patients included in the study. Migraine prophylaxis was made using topiramate (22 patients), venlafaxine (14 patients), propranolol (12 patients), and flunarizine (15 patients), according to doctor and patient preference and related health issues, however, drugs that would affect bladder dynamics and used in the treatment OAB were avoided. Multiple agents were used and randomly selected (if no comorbid condition necessitating the need for a particular preference was present such as depression or epilepsy) to prevent selection bias and specific drug effects. None of the patients included in the study was given any medication for the treatment of OAB as this could certainly affect the results.
Statistical Analysis
Statistical analyses were performed using SPSS (Version 22.0,
SPSS Inc., Chicago, IL, USA Hitit University Licensed) package
program. The mean age of 63 women included in the study was
39.25 ± 9.21 (19-64) years. The mean BMI of the patients was
determined as 25.29 ± 3.61 (16.4-33.3) kg/m2. Our analyses were
performed with the SPSS 22.0 program and were studied at a 95%
confidence level. In our analysis, parametric dependent groups
t-test and ANOVA test were used. The Analysis of the pre-and
post-treatment in the group separation and the whole group was
analyzed by the dependent group"s t-test.
In the venlafaxine group; the change in VPS score is significant (p<0.05). While the average was 6.64 before treatment, it decreased to 4.50 with a decrease of 2.14 points after treatment. The change in OAB-V8 and ICIQ-SF scores is not significant (p>0.05).
In the propranolol group; the change in VPS score is significant (p<0.05). While the average was 7.00 before treatment, it decreased to 3.25 with a decrease of 3.75 points after treatment. OAB-V8 score change is significant (p<0.05). While the average was 15.58 before treatment, it decreased to 9.42 with a decrease of 6.17 points after treatment. ICIQ-SF score change is significant (p<0.05). While the average was 7.33 before the treatment, it decreased to 4.42 with a decrease of 2.92 points after treatment.
In the flunarizine group; the change in VPS score is significant (p<0.05). While the average was 6.27 before treatment, it decreased to 4.73 with a decrease of 1.53 points after treatment. OAB-V8 score change is significant (p<0.05). While the average was 14.73 before treatment, it decreased to 11.33 with a decrease of 3.40 points after treatment. ICIQ-SF score change is not significant (p>0.05).
In the whole patient group; the change in VPS score is significant (p<0.05). While the average was 6.67 before treatment, it decreased to 4.11 with a decrease of 2.56 points after treatment. OAB-V8 score change is significant (p<0.05).
While the average was 14.87 before treatment, it decreased to 10.48 with a decrease of 4.40 points after treatment. ICIQ-SF score change is significant (p<0.05). While the average was 6.22 before treatment, it decreased to 4.49 with a decrease of 1.73 points after treatment.
ANOVA test was used to examine the pre-and post-treatment questionnaires in terms of drug groups. There were no significant differences between the drug groups in terms of VAS, OAB-V8, and ICIQ-SF measurements before and after treatment (p>0.05). Table 1 summarized the investigation of pre-and post-treatment variation in the whole group and between drug groups.
Preventive therapy for migraine aims to decrease headache frequency and severity for a better quality of life and progression to CM for episodic patients. There are many agents used for migraine prophylaxis with individual benefits and drawbacks affecting the selection. Beta-blockers; metoprolol, and propranolol are beneficial in hypertensive while the antidepressants like amitriptyline and venlafaxine are preferred in patients with depression or anxiety disorders, and insomnia. Anticonvulsants; valproate acid and topiramate can be used. Especially in women of childbearing age or patients with Raynaud"s phenomenon calcium channel blockers, verapamil, and flunarizine might be prescribed. Among other agents are calcitonin gene-related peptide antagonists like erenumab, and galcanezumab [8].
OAB is a condition defined as urinary urgency, usually accompanied by frequent urination and nocturia, with or without urgency urinary incontinence, in the absence of urinary tract infection or other obvious pathology [9]. Urinary incontinence, like a migraine, negatively affects the psychological health and quality of life of women [10]. Unfortunately, few people seek help for this symptom because of embarrassment and stigma [11]. Urinary incontinence accompanying CM will worsen both the quality of life and stigmatization. Both CM and OAB are common in women over the age of 40 and their prevalence will increase over the years due to increasing awareness [12,13].
The comorbidity between CM and OAB will also be supported by comprehensive studies. Both disorders have common factors underlying the relationship in etiopathogenesis, as well as their complex multifactorial etiopathogenesis that remains unclear.
When we examined the literature, we encountered publications that could explain similar etiopathogenesis. Activation of the trigeminovascular system results in the release of vasoactive neuropeptides particularly calcitonin gene-related peptide (CGRP) that induce vasodilation and neurogenic inflammation in leptomeningeal and extracranial vessels causing acute migraine pain. Repeated peripheral activation might sensitize central pain pathways, transforming episodic migraine into a chronic condition in predisposed patients. Similarly, women with OAB have increased density of suburothelial nerve fibers that are immune-reactive for CGRP supporting that increased, aberrant sensory afferent activity might be a factor in OAB pathophysiology [14,15].
Botulinum toxin A treatment is effective in both OAB and CM [16]. Botulinum toxin A has been shown to reduce increased CGRP levels in CM patients [17] and to inhibit CGRP release in the bladder of experimental animals [18]. Finally, central brain structures implicated in OAB and CM pathophysiology, such as the prefrontal cortex, hypothalamus, or periaqueductal grey nuclei are common [19]. The association between CM and OAB based on shared pathophysiological mechanisms should be supported by further epidemiological studies. In clinical practice, CM as well as OAB patients could be warned about possible comorbidity. In this study, we aimed to determine whether migraine prophylaxis would affect the symptom severity of OAB, and to our knowledge, this is the first study. Based on our previous "Clinical Reflection of OAB Migraine Comorbidity: Prospective Cross-sectional study" data, we compared the VPS scores and OAB symptom scores of CM patients with OAB after six months of prophylactic migraine treatment and found that patients had a regression in both VPS, ICIQ-SF scores and OAB symptoms.
Migraine and OAB are two diseases that both affect the quality of life and psychosocial health. Getting relief, the migraine pain might provide better tolerance and struggle for OAB symptoms. Thus, a psychological benefit and better selfesteem might be responsible for the beneficial effect of migraine prophylaxis on OAB symptoms. It is important not only to feel healthy but also to get rid of the psychological stress of CM and/or OAB symptoms. However, symptoms of OAB hurt the quality of life as these patients are required to identify toilet locations before leaving home and avoid collective activities. Thus, the physical and psychosocial problems of OAB might be hardly bearable in some patients themselves. Similarly, migraine attacks also cause a person to stay away from social activities.
Similar lifestyle changes are recommended in the treatment of migraine and OAB. Lifestyle changes are advised in both disease processes and found to be beneficial but usually insufficient. For OAB, adequate and appropriate fluid intake is advised. Insufficient fluid intake or fluid restriction may play a role in the development of urgency, frequent urination, and urinary tract infections by increasing urine concentration, irritating the bladder mucosa, and reducing the functional capacity of the bladder [19,20]. Studies have shown that the removal of artificial sweeteners and food such as highly spicy foods, citrus fruits, and tomato-containing products from the diet can play a role in the treatment of incontinence [21]. It is recommended to use similar dietary restrictions in migraine patients to reduce the frequency of attacks. As stated, before none of the patients included in the study was given any medication for the treatment of OAB, such as muscarinic receptor antagonists, beta-3 agonists, and desmopressin as this could certainly affect the results. Also, conservative measures specific to OAB were neglected such as timed voiding, special dietary habits (like avoidance of caffeine), and so on. Sleep adjustment, adequate fluid intake, diet, and weight control in necessary patients were recommended for migraine patients. Similar measures might be beneficial for OAB symptoms. Adequate and appropriate fluid intake serves as a quick washout of irritants from the bladder and produces diluted urine [19,20]. Nuotio et al., in their population-based study involving 1059 women and men between the ages of 60 and 89, found a relationship between smoking and urinary urgency, but it was not confirmed by others [22-24]. As studies have shown the relationship between smoking and migraine, cessation of smoking should be recommended in comorbid patients [25]. Nevertheless, lifestyle and dietary adjustments can help manage both migraine and OAB symptoms and quality of life improvement. We have recommended the above-mentioned lifestyle recommendations in addition to prophylactic treatment in CM, thus the regression in OAB symptoms might be partially influenced. In OAB clinical spectrum conservative measures are usually insufficient in most of the patients, thus attributing the benefit solely to lifestyle changes is not logical.
OAB results in a decrease in the quality of life and an increase in both sensory and affective qualities of pain [26]. The severity of pain is increased in parallel with the severity of symptoms in OAB patients. This result, independent of the effect of OAB on emotional state, supports the hypothesis that central sensitization predisposes to pain syndromes in the pathophysiology of OAB. According to these results, it can be emphasized that patients with OAB may be predisposed to pain syndromes as well as lower urinary tract symptoms and that clinicians should consider this during the evaluation of patients [27].
A study in the literature found that about 30% of OAB patients were accompanied by depression, and these patients complained of more severe OAB symptoms [28]. Some of the agents used in migraine prophylaxis are antidepressants and serve dual benefits, especially in these cases. Tricyclic antidepressants are competitive antagonists of muscarinic acetylcholine receptors, the predominant class of acetylcholine receptors in the brain. However, these agents also block muscarinic receptors in other sites of the body producing symptoms such as blurred vision, dry mouth, and urinary retention. Antidepressants particularly amitriptyline are used in migraine prophylaxis and avoided in this study because of marked anticholinergic properties that are beneficial for OAB patients. Topiramate is an antiepileptic and carbonic anhydrase inhibitor used to treat chronic migraines and does not affect the bladder. Antidepressants, venlafaxine is a serotoninnorepinephrine reuptake inhibitor and receptor data state anticholinergic effects are minimal. However anticholinergic side effects including dry mouth and constipation might be encountered. It is not expected to be beneficial for symptoms of OAB in its therapeutic range. Flunarizine is a calcium antagonist and does not affect the bladder. As stated before drugs that would affect bladder dynamics and be used in the treatment of OAB were excluded and multiple agents were used and randomly selected to prevent selection bias and specific drug effects. None of the patients included in the study was given any medication for the treatment of OAB as this could certainly affect the results. Although the small number of cases in our study is considered a limitation, statistically we obtained significant results in all drug subgroups. We could not obtain statistically significant results in OAB-V8 and ICIQ-SF in the venlafaxine group and ICIQS total scores in the flunarizine group. We think that we will shed light on studies aimed at etiopathogenesis with extensive studies involving more cases.
Ethics Committee Approval: The study was a cross-sectional prospective study approved by the Hitit University School of Medicine Ethics Committee (ethics committee approval date and number: 06.01.2021/349).
Informed Consent: An informed consent was obtained from all the patients.
Publication: The results of the study were not published in full or in part in form of abstracts.
Peer-review: Externally peer-reviewed.
Authorship Contributions: Any contribution was not made by any individual not listed as an author. Concept – S.E., A.B., F.U.T.; Design – S.E., A.B., F.U.T.; Supervision – S.E., A.B., F.U.T.; Resources – S.E., A.B., F.U.T.; Materials – S.E., A.B., F.U.T.; Data Collection and/or Processing – S.E., A.B., F.U.T.; Analysis and/or Interpretation – S.E., A.B., F.U.T.; Literature Search – S.E., A.B., F.U.T.; Writing Manuscript – S.E., A.B., F.U.T.; Critical Review – S.E., A.B., F.U.T.
Conflict of Interest: The authors declare that they have no conflicts of interest.
Financial Disclosure: The authors declare that this study received no financial support.
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