Comorbidity between idiopathic overactive bladder and chronic migraine

Abstract

Objective

We tested whether overactive bladder (OAB) and chronic migraine (CM) could be comorbid.

Patients and methods

CM women, aged 40–69 years, answered a validated OAB questionnaire. Prevalence data were compared with those reported in our country in the general population (GP) using the same questionnaire.

Results

We interviewed 231 CM women. Eighty-four met OAB criteria. OAB prevalence in CM patients was significantly higher than that found in the GP (36.4% vs. 21.8% in the GP; p = 0.0001). There were 34 CM women aged 40–49 years (34.3% vs. 15.2%; p = 0.001), 35 aged 50–59 years (38.9% vs. 21.7%; p = 0.004) and 15 aged 60–69 years (35.7% vs. 24.5%; p = 0.15) meeting OAB criteria. Seventy-seven (33% vs. 9.9%; p = 0.002) needed more than eight micturitions/24 h, 61 (26.4% vs. 8.1%, p = 0.002) experienced nocturia and 43 (18.6% vs. 8.1%; p = 0.001) urinary incontinence.

Conclusion

In this exploratory study, at least in women, OAB and CM are comorbid, which suggests shared mechanisms.

Introduction

The International Headache Society (IHS) Classification defines CM as ≥15 headaches days per month for at least three months, with ≥eight days per month fulfilling migraine criteria, in the absence of medication overuse and that cannot be attributed to another causative disorder (1). CM is much more frequent in middle-aged women (2).

According to the Standardization Subcommittee of the International Continence Society, idiopathic overactive bladder (OAB) is now defined as denoting urgency with or without urge incontinence, usually with frequency and nocturia (3). These symptoms can occur either singly or in combination and cannot be explained by systemic or local pathological factors. OAB is a chronic condition defined urodynamically as detrusor overactivity and characterized by involuntary bladder contractions during the filling phase of the micturition cycle. OAB is a frequent condition in adults, especially in women after 40 (4–7). Its prevalence in Europe in subjects aged ≥40 years has been shown to be around 17% (5,6). Female predominance is clear, mainly between 40 and 60 years.

The fundamental cause of OAB remains to be discovered, but there is accumulating evidence that, as happens in CM, hyperactivity in afferent nerves plays an important role (8,9). Moreover, brain structures involved in both OAB and CM development are almost identical (9) and both conditions respond to onabotulinumtoxinA treatment (10). In summary, OAB and CM share high prevalence, patient profile, (conceptually) pathophysiological mechanisms and response to onabotulinumtoxinA treatment. Our aim here was to examine the hypothesis that OAB and CM could be comorbid conditions.

Patients and methods

Women aged 40 to 69 years attending four headache clinics in Spain, who had been diagnosed by us as having CM according to current IHS criteria (1), were included in this study between May and October, 2015. The study was approved by the institutional ethics review board and complied with the Declaration of Helsinki. All participants gave their informed consent for this study. We excluded women who were pregnant, suffered from serious, active psychiatric or somatic diseases, overused alcohol, took diuretics or referred to a history of neurologic, urologic or obstetric/gynaecological diseases, which could induce or predispose to urinary urgency or incontinence. We excluded women with very severe depression (>23) or anxiety (>30) based on the Hamilton Depression and Anxiety Scales.

CM women were first asked the screening OAB question, taken literally from the validated questionnaire used in the previous OAB epidemiological study in Spain: “Do you feel an irrepressible urge to urinate on a regular basis, dash to the bathroom and eventually manage to get to the toilet on time? CM women responding “yes” to this question answered the remaining 16 items of the OAB questionnaire to characterize the nature of the urinary condition (3,11)”.

OAB prevalence data obtained here in CM patients were compared to those coming from the OAB prevalence study in our country carried out in 1669 subjects from the general population (GP). Details of this study have been fully published (11). Data analysis was performed using the software Statistical Package for the Social Sciences (SPSS) version 20.0 package for Windows. Demographics were summarized using descriptive statistics. Dichotomous and categorical variables were compared with the chi-squared test, and continuous variables were compared with the unpaired t-test. Categorical variables were presented as percentages and frequency, and continuous variables as mean and standard deviation (SD). Statistical significance was accepted if the p-value was <0.05.

Results

We interviewed 231 CM women. Eighty-four CM women aged 40–69 years also met OAB criteria. This OAB prevalence in CM patients was significantly higher than that found in the GP in Spain (36.4% vs. 21.8%; p = 0.0001) (Figure 1). When analysed by decades, there were 34 CM women aged 40–49 years (34.3% vs. 15.2% in the GP; p = 0.001), 35 aged 50–59 years (38.9% vs. 21.7% in the GP; p = 0.004) and 15 aged 60–69 years (35.7% vs. 24.5% in the GP; p = 0.15) meeting OAB criteria. These results did not differ among the four hospitals. There were 125 (54.1%) and 69 (29.8%) CM patients meeting criteria for anxiety and depression, respectively. A total of 104 CM women (45%) took antidepressants. The prevalence of OAB was similar in CM patients with and without anxiety, with and without depression, and with and without consumption of antidepressants (p ≤ 0.10).

Figure 1.

Prevalence of OAB in CM patients compared to the GP data.

Among the 84 CM with OAB, 77 (33% vs. 9.9% in the GP; p = 0.002) needed more than eight micturitions/24 h, 61 (26.4% vs. 8.1% in the GP; p = 0.0001) experienced nocturia and 43 (18.6% vs. 8.1% in the GP; p = 0.001) suffered from urinary incontinence (Figure 2).

Figure 2.

Prevalence of other urinary behaviour symptoms in CM patients also meeting OAB criteria compared to the GP data.

Discussion

We found that OAB was significantly more common in women diagnosed as CM when compared to the GP in our country. This association between OAB and CM was seen for the whole group of CM women aged 40–69 years, and remained significant in the 40s and 50s. In CM women aged 60–69, numerical difference was clear but did not reach significance. This is explained by the lower numbers of CM patients in their 60s in this series and by the increased prevalence of OAB symptoms in the GP after the 60s due to a higher prevalence of local conditions (for instance, pelvic floor dysfunction in women or prostate hypertrophy in men), which makes it difficult to be sure of an OAB diagnosis in elderly people (4–7).

One of the limitations of this study is that we only interviewed CM women, which implies that our results are only applicable to females. We decided not to include men here for two main reasons. First, as in both conditions, OAB and especially in CM, there is a clear female predominance and second, as pointed out above, because due to the beginning of symptoms of prostate hypertrophy, the OAB symptoms’ prevalence ratio changes and becomes higher after the 60s in men. A further potential limitation of our work is that we compared our OAB prevalence results in headache clinics with those coming from just one GP OAB epidemiological study, which makes it difficult to adjust for potential confounders (11). We are aware that a GP study analysing both conditions would be ideal, but taking into account the prevalence of CM it would not be easy to carry out such study and we think that, at least as an exploratory test, it is fair to compare our data with those coming from the OAB epidemiological study. First, the big OAB study was carried out in our country and we strictly followed the same methodological process. Second, the OAB prevalence found in the study performed in Spain (11) was even higher than that found in other OAB prevalence studies (4–7), which reinforces the conclusion of OAB and CM comorbidity. Finally, results coming from the four headache clinics participating in this study were totally in agreement in terms of OAB prevalence, which gives consistency to our data.

Our results indicate that OAB and CM, two conditions only defined in the previous decade, could be comorbid. There are several arguments making this potential link between OAB and CM plausible. First, CM and OAB seem to share a patient profile, that is, women over the age of 40. CM is a rather frequent condition affecting around 2% of the general adult population (2). Its prevalence increases with age and in females; in fact, between 40 and 69 years CM prevalence was shown to be 3.6% for both sexes in our country and reaches 6% in women (2). OAB is also a frequent and chronic condition in adults, especially in women after the age of 40, and often profoundly compromises quality of life (7). Second, conceptually, OAB and CM also share pathophysiological mechanisms. Acute migraine pain occurs due to the release, by an activated trigeminovascular system, of vasoactive neuropeptides, most especially calcitonin gene-related peptide (CGRP), which induces vasodilation and neurogenic inflammation in leptomeningeal and extracranial vessels. In predisposed patients, this repeated peripheral activation is able to sensitize central pain pathways, transforming episodic migraine in a chronic condition. Increased, aberrant sensory afferent activity also seems to play a key role in OAB pathophysiology. Women with OAB have increased density of suburothelial nerve fibres that are immunoreactive for CGRP (9). A further link between OAB and CM pathophysiological mechanisms is their response to onabotulinumtoxinA treatment (10). The therapeutic effects of onabotulinumtoxinA in both conditions are not explained by their actions on motor nerve terminals, as illustrated by its absence of efficacy in chronic tension-type headache or its unexpected duration of action in OAB. OnabotulinumtoxinA has been shown to reduce increased CGRP levels in CM patients (12) and to inhibit CGRP release in the bladder of experimental animals (13). Finally, and reinforcing their pathophysiological similarities, central brain structures implicated in OAB and CM development, such as the prefrontal cortex, hypothalamus or periaqueductal gray nuclei are superimposable (9) .

In conclusion, our finding linking CM and OAB suggests shared pathophysiological mechanisms and justifies further epidemiological studies. In clinical practice, we should ask our CM patients about the presence of OAB symptoms (and vice versa).

Clinical implications

OAB and CM seem to be comorbid conditions.

Both may share pathophysiological mechanisms.

In clinical practice, we should ask CM patients about OAB symptoms (and vice versa).