Obsessive-Compulsive Disorder and Migraine With Medication-Overuse Headache

Objective.— A strong association has been demonstrated between migraine, particularly in the chronic form and with medication overuse, and either major depression or various anxiety disorders. However, there has been less systematic research on the links between migraine with medication-overuse headache (MOH) and obsessive-compulsive disorder (OCD). A drug-seeking behavior shares with OCD the compulsive quality of the behavior. We investigated the relationship between OCD and MOH in migraineurs.
Methods.— A structured questionnaire was administered to subjects with: episodic migraine (EM) (n = 30), chronic migraine (CM) (n = 24), and MOH with a previous history of EM (n = 33) and 29 control subjects. Psychiatric diagnoses were made by a senior psychiatrist blinded to the diagnosis of migraine. Psychiatric assessment of OCD illness was evaluated by means of The Yale-Brown Obsessive Compulsive Scale (Y-BOCS).
Results.— In the subgroup of patients with MOH, psychiatric comorbidity (anxiety and mood disorders) was prevalent compared with CM, EM, and controls ( P  < .0001). Subclinical OCD was significantly prevalent in MOH patients with respect to other groups ( P  < .0002). Higher scores in Y-BOCS, as a measure of severity of obsessive-compulsive symptoms, were found in both MOH and CM compared with controls and EM.
Conclusions.— The excess of psychiatric comorbidity in patients with MOH can be related either to medication overuse or to chronification of headache. Among anxiety disorders, we observed a high rate of subclinical OCD. However, a direct link between compulsive behavior and medication overuse cannot be established yet. OCD in MOH might be underdiagnosed and undertreated.     

Sympathetic skin response in migraineurs and patients with medication overuse headache

BACKGROUND: Autonomic dysfunction has been reported in patients with migraine, and it may play a role in promoting attacks. OBJECTIVE: To investigate changes in the autonomic function of migraineurs and patients with medication overuse headache via sympathetic skin response, and to determine whether psychiatric comorbidity is related to any changes recorded. METHODS: A consecutive series of patients with migraine (n = 45) and medication overuse headache (n = 53) were studied. Patients with other chronic diseases requiring medication were excluded. Sympathetic skin response latencies and amplitudes from the patients with headache (N = 98) and 40 healthy controls were compared statistically. RESULTS: Sympathetic skin response latencies in patients with medication overuse headache and in migraineurs were significantly longer than in controls. To analyze the effect of psychiatric comorbidity, patients with medication overuse headache and migraineurs were each divided into 2 groups: those with psychiatric comorbidity and those without comorbidity. When the sympathetic skin response results of these 4 groups were compared with controls, the only statistically significant difference was between the sympathetic skin response latencies of controls and the latencies of patients with psychiatric comorbidity. We could not find any difference between the results from patients without psychiatric comorbidity and those of controls. CONCLUSION: Psychiatric disease may affect the results of autonomic function testing in migraineurs and patients with medication overuse headache. Consideration should be given to excluding patients with psychiatric comorbidity from studies investigating autonomic dysfunction in patients with headache.     

Utility of topiramate for the treatment of patients with chronic migraine in the presence or absence of acute medication overuse

Chronic migraine has been linked to the excessive use of acute headache medications. Medication overuse (MO) is commonly considered the most significant risk factor for the progression of migraine from an episodic to a chronic condition. Managing MO is a challenge. Discontinuation of the acute medication can result in withdrawal headache, nausea, vomiting and sleep disturbances. This review summarizes the results from two similarly designed, randomized, placebo-controlled, multicentre studies of chronic migraine conducted in the USA and European Union. Both studies demonstrate the efficacy and safety of the migraine preventive medication, topiramate, for the treatment of chronic migraine in patient populations both with and without MO. These studies may have important implications for the future of chronic migraine management, suggesting that detoxification prior to initiating prophylactic therapy may not be required in all patients if MO is present.     

Epidemiology, risk factors, and treatment of chronic migraine: a focus on topiramate

The term chronic daily headache refers to a heterogeneous group of headache disorders characterized by a frequency of headaches on ≥15 days per month. Chronic migraine is a subtype of chronic daily headache. The prevalence of chronic migraine is ∼1%. Baseline attack frequency and acute medication overuse have been identified as potential risk factors for the progression of migraine from an episodic disorder to a chronic condition. There is an unmet patient need for effective and safe treatments for patients with chronic migraine, but data from rigorous controlled trials are limited. Previous studies have demonstrated that topiramate is an effective and safe preventive treatment for episodic migraine. In addition, pilot studies have suggested the utility of topiramate for the prevention of chronic migraine. Two randomized, double-blind, placebo-controlled, multicenter trials investigating the efficacy and safety of topiramate in the treatment of patients with chronic migraine have recently been completed. This review presents comparative data from these 2 clinical trials, which suggest that topiramate at a dose of 100 mg daily is effective and generally well tolerated in chronic migraine.     

Disability in chronic migraine patients with medication overuse: treatment effects at 1-year follow-up

OBJECTIVE: To determine (1) the clinical course of a sample of chronic migraine patients with drug overuse 6 and 12 months following in-patient treatment and (2) whether functional impairment, assessed by the Migraine Disability Assessment (MIDAS) questionnaire, improved upon treatment. BACKGROUND: Patients with chronic migraine and medication overuse are particularly difficult to treat (prophylactic medications that otherwise are effective become ineffective; discontinuation of the offending medication can lead to withdrawal headache; physical and emotional dependence can be present, as well as increased psychological involvement; initial treatment gains can be difficult to maintain). METHODS: Of the 106 patients meeting criteria for chronic migraine with medication overuse, 84 went on to complete a structured in-patient treatment, consisting of medication withdrawal and then prophylactic treatment. RESULTS: As a group, the patients were improved at both 6- and 12-month follow-up, with respect to two headache parameters (frequency and medication use) and three measures of functional impact extracted from the MIDAS questionnaire (Total Score, Headache Frequency, and Headache Intensity). CONCLUSION: Chronic migraine accompanied with medication overuse led to the considerable disability prior to treatment. However, notable improvement occurred coincident with the treatment. This suggests that successful treatment has more wide-ranging positive benefits beyond mere symptom reduction. To our knowledge, this is the first investigation where the MIDAS questionnaire has been used prospectively as an outcome measure in patients with chronic migraine and medication overuse to assess disability subsequent to a semi-standardized treatment program.     

Frequent analgesics consumption in migraineurs: comparison between chronic and episodic migraineurs

Abstract To assess the frequent consumption of symptomatic medications in migraineurs, we consecutively recruited 536 migraineurs from a headache clinic. Among them, 194 (36.2%) had chronic migraine and 342 had episodic migraine. When grouped according to duration of headache, the proportion of patients with chronic migraine increased from 25.5% to 50.9% as headache history increased from <1 to >20 years. The percentage of patients with frequent analgesics consumption also increased with the duration of headache, in patients with both chronic migraine (from 25.0% to 85.7%) and episodic migraine (from 20.0% to 59.3%). Nonetheless, patients with chronic migraine had a higher prevalence of frequent consumption of abortive medications than patients with episodic migraine regardless of duration of headache history, and the common odds ratio across strata of headache duration was 2.8 (95% confidence interval, 1.9–4.1). However, we found that a long headache history is an important risk factor for frequent consumption of symptomatic medications in migraineurs in patients with both episodic migraine and chronic migraine.     

Endocrine function is altered in chronic migraine patients with medication-overuse

OBJECTIVE: To evaluate the effects of analgesic overuse on endocrine function in patients with chronic migraine and medication-overuse headache (CM-MOH). BACKGROUND: Chronic migraine is frequently associated with an overuse of symptomatic medications. Drugs currently used in acute migraine attacks are associated with several endocrine effects. At present, the endocrine effects of medication overuse in chronic migraine patients are unknown. METHODS: Eighteen patients with CM-MOH, diagnosed according to the ICHD-II criteria, and 18 healthy controls received an intravenous administration of GHRH, hCRH, and TRH. Plasma concentrations of GH, TSH, ACTH, and cortisol were measured for a 90-minute period after administration of the specific releasing hormones. RESULTS: Hormonal basal concentrations were similar in both groups. GH response to GHRH was significantly reduced in patients with CM-MOH in comparison with controls. TRH induced a reduction of TSH concentrations only at the end of the test. After hCRH administration, ACTH and cortisol concentrations were significantly higher in cases than in controls. A significant correlation between duration of the disease and altered hormonal response was found. CONCLUSIONS: Our study shows that both corticotropic and somatotropic functions are significantly impaired in CM-MOH patients and suggests a role for hormones in the development of chronic migraine.     

Voxel-based morphometry reveals gray matter abnormalities in migraine

BACKGROUND: Migraine is generally considered a functional brain disorder lacking structural abnormalities. Recent magnetic resonance imaging (MRI) studies, however, suggested that migraine may be associated with subtle brain lesions. OBJECTIVE: We evaluated the presence of global or focal gray or white matter alterations in migraine patients using voxel-based morphometry (VBM), a fully automated method of analyzing changes in brain structure. VBM data also were used to evaluate possible differences between episodic and chronic migraine. METHODS: Twenty-seven migraine right-handed patients and 27 healthy controls were selected for the study. Sixteen patients fulfilled the International Headache Society criteria for episodic migraine and 11 for chronic migraine. MRI scans were analyzed with MATLAB 6.5 and SPM2 software, using VBM method. RESULTS: In comparison with controls, migraineurs presented a significant focal gray matter reduction in the Right Superior Temporal Gyrus, Right Inferior Frontal Gyrus, and Left Precentral Gyrus. Chronic migraine patients, compared to episodic, showed a focal gray matter decrease in the bilateral Anterior Cingulate Cortex, Left Amygdala, Left Parietal Operculum, Left Middle and Inferior Frontal Gyrus, Right Inferior Frontal Gyrus, and bilateral Insula. Considering all the migraine patients, a significant correlation between gray matter reduction in anterior cingulate cortex and frequency of migraine attacks was found. CONCLUSIONS: Our study shows that migraine is associated with a significant gray matter reduction in several of the cortical areas involved in pain circuitry. In addition, we found a significant correlation between frequency of migraine attacks and signal alteration in the Anterior Cingulate Cortex. Our data provide new insight into migraine pathophysiology and support the concept that migraine may be a progressive disorder.     

Field testing alternative criteria for chronic migraine

The criteria for chronic migraine (CM), as proposed by the Second Edition of the International Classification of Headache Disorders (ICHD-2) is very restrictive, excluding most patients that evolve from episodic migraine. In this study we empirically tested three recent proposals for revised criteria for CM. We included individuals with transformed migraine (TM) with or without medication overuse, according to the criteria proposed by Silberstein and Lipton. All individuals had headache calendars for at least three consecutive months. We assessed the proportion of subjects that fulfilled ICHD-2 criteria for CM or probable chronic migraine with probable medication overuse (CM+). We also tested three proposals for making the CM criteria more inclusive. In proposal 1, CM/CM + would require at least 15 days of migraine or probable migraine per month. Proposal 2 suggests that CM/CM + would be classified in those with >or= 15 days of headache per month, where at least 50% of these days are migraine or probable migraine. Proposal 3 suggests that CM/CM + would be classified in those with chronic daily headache and at least 8 days of migraine or probable migraine per month. Among TM sufferers, 399 (62.5%) had TM with medication overuse, and just 10.2% were classified as CM+ 158 (37.5%) had TM without medication overuse; just nine (5.6%) met current ICHD-2 criteria for CM. Using the alternative criteria, proposal 1 included 48.7% of patients with TM without medication overuse; proposal 2 captured 88%, and proposal 3 classified 94.9% of these patients. For TM with medication overuse, the proportions for proposals 1-3 were, respectively, 37%, 81% and 91%. The differences were statistically significant, favouring proposal 3. Consistently, criteria for CM and CM+ should be revised to require at least 8 days of migraine or probable migraine per month, in individuals with 15 or more days of headache per month.     

Panic Disorder and Migraine: Comorbidity,Mechanisms, and Clinical Implications

A growing body of literature suggests that comorbid anxiety disorders are more common and more prognostically relevant among migraine sufferers than comorbid depression. Panic disorder (PD) appears to be more strongly associated with migraine than most other anxiety disorders. PD and migraine are both chronic diseases with episodic manifestations, involving significant functional impairment and shared symptoms during attacks, interictal anxiety concerning future attacks, and an absence of identifiable secondary pathology. A meta‐analysis of high‐quality epidemiologic study data from 1990 to 2012 indicates that the odds of PD are 3.76 times greater among individuals with migraine than those without. This association remains significant even after controlling for demographic variables and comorbid depression. Other less‐rigorous community and clinical studies confirm these findings. The highest rates of PD are found among migraine with aura patients and those presenting to specialty clinics. Presence of PD is associated with greater negative impact of migraine, including more frequent attacks, increased disability, and risk for chronification and medication overuse. The mechanisms underlying this common comorbidity are poorly understood, but both pathophysiological (eg, serotonergic dysfunction, hormonal influences, dysregulation of the hypothalamic–pituitary–adrenal axis) and psychological (eg, interoceptive conditioning, fear of pain, anxiety sensitivity, avoidance behavior) factors are implicated. Means of assessing comorbid PD among treatment‐seeking migraineurs are reviewed, including verbal screening for core PD symptoms, ruling out medical conditions with panic‐like features, and administering validated self‐report measures. Finally, evidence‐based strategies for both pharmacologic and behavioral management are outlined. The first‐line migraine prophylactics are not indicated for PD, and the selective serotonin re‐uptake inhibitors used to treat PD are not efficacious for migraine; thus, separate agents are often required to address each condition. Core components of behavioral treatments for PD are reviewed, and their integration into clinical headache practice is discussed.     

Topiramate in patients with episodic migraine: reducing the risk for chronic forms of headache

OBJECTIVE: The aim was to evaluate whether preventive treatment with topiramate in patients with episodic migraine reduces the risk of developing chronic forms of headache. BACKGROUND: Chronic forms of headache, including chronic migraine or medication overuse headache (MOH), are characterized by 15 or more headache days per month. Acute medication overuse has been shown to be a risk factor for developing chronic headache, but it is not known whether preventive treatment can reduce the risk of developing chronic forms of headache or the development of MOH. METHODS: Pooled data from 3 trials in patients with episodic migraine randomized either to treatment with 100 mg topiramate per day (n = 384) or with placebo (n = 372) were analyzed with regard to the number of headache days during a prospective 4-week baseline period and the individual final 4 weeks of each patient's treatment during the planned 26-week double-blind treatment period. RESULTS: The number of headache days per month in the topiramate versus the placebo-treated groups was 7.3 +/- 3.0 versus 7.3 +/- 3.1 during baseline and 4.1 +/- 4.2 versus 5.6 +/- 4.9 during the final 4 weeks, respectively (P < .001). At the end of the study, 8 versus 16 patients fulfilled International Headache Society criteria of chronic headache (odds ratio: 2.11, P= .082). Moreover, a significantly lower number of patients receiving topiramate treatment reported an increase in headache days per month by the end of the study when compared to placebo (66 vs 88 patients, respectively; odds ratio: 1.49, P < .05). Finally, the number of days with usage of acute medication was significantly lower in the topiramate arm compared with placebo (3.3 +/- 3.7 vs 4.3 +/- 3.6, respectively; P < .001). CONCLUSION: Preventive treatment with topiramate in patients with episodic migraine may reduce the risk of developing chronic forms of headache.     

A case-control study on excessive daytime sleepiness in episodic migraine

Migraine patients often complain of sleepiness, a problem that manifests both during and outside an attack, may impair the quality of life and can lead to potentially harmful situations. Findings from an uncontrolled study suggest that a high percentage of migraineurs experience excessive daytime sleepiness (EDS). We investigated EDS in a case-control study on 100 patients with episodic migraine and 100 age- and sex-matched healthy controls and also assessed sleep quality, anxiety and depression. Although it was found that EDS was more frequent in migraineurs than in controls (14% vs. 5%; odds ratio 3.1; 95% confidence interval 1.1-8.9), the frequency was lower than previously reported. EDS correlated with migraine disability, sleep problems and anxiety. EDS in patients with migraine probably stems from the full constellation of headache-sleep-affective symptoms resulting from the complex clinical burden of the disease.     

Acute and interictal allodynia in patients with different headache forms: an Italian pilot study

OBJECTIVE: To investigate allodynia in patients with different primary headaches. BACKGROUND: Many migraineurs have allodynia during headache attacks; some may have allodynia outside attacks; allodynia may also be associated with other primary headaches. METHODS: A total of 260 consecutive primary headache patients presenting for the first time at a headache center, and 23 nonheadache controls answered written questions (subsequently repeated verbally) to determine the presence of acute and interictal allodynia. RESULTS: We divided the patients into: episodic migraine (N = 177), subdivided into only migraine without aura (N = 114) and those sometimes or always reporting migraine with aura (N = 63); episodic tension-type headache (N = 28); chronic headaches (headache > or = 15 days/month, N = 52), including chronic migraine, chronic tension-type headache, and medication-overuse headache; and other headache forms (N = 3). Acute allodynia was present in 132 (50.7%), significantly more often in patients sometimes or always suffering migraine with aura, and those with chronic headache forms, compared to patients with migraine without aura and episodic tension-type headache. Interictal allodynia was present in 63 (24.2%) patients, with significantly higher frequency in those having migraine with aura attacks than controls and common migraine patients. CONCLUSIONS: Allodynia is not specific to migraine but is frequent in all headache patients: acute allodynia was reported in half those interviewed and in over a third of patients in each headache category; interictal allodynia was reported by nearly 25%.     

From migraine to chronic daily headache: the biological basis of headache transformation

Migraine headache carries the potential of transforming into chronic daily headache (CDH) over a period of time. Although several risk factors for migraine progression to CDH have been identified, the biological basis of this transformation is unknown. In this review, the consequences of stressful life events and medication overuse, 2 risk factors associated with the development of CDH, on brain processes involved in headache are examined. The extensive overlap in both neural circuitry and cellular events that occur with stress, medication overuse, and migraine provide insight into potential mechanisms that may lead to CDH. Particular attention is devoted to the effect of stress and medication overuse on peripheral and central neuroimmune interactions that can facilitate pain signaling. These interactions include the degranulation of mast cells in the dura, causing the sensitization of primary afferent neurons, as well as the activation of glial cells in the brain that can lead to central sensitization. It is hypothesized that the biological processes involved in migraine headache are directly impacted by stress, medication overuse, and other risk factors, resulting in a reduced threshold for induction of headache and transformation of episodic migraine to CDH.     

Daily sumatriptan for detoxification from rebound

Medications which provide symptomatic relief from headache can transform episodic migraine into chronic daily headache by propagating the daily headache, causing "rebound." It is possible to restore the episodic migraine pattern by using an inpatient course of intravenous dihydroergotamine. This study was undertaken to explore whether it was possible to use oral sumatriptan in the outpatient setting as a bridge to detoxification for patients with chronic daily headache due to medication overuse. All patients had previously met International Headache Society (IHS) criteria for episodic migraine and currently had greater than 15 days of headache per month for greater than 1 month. These patients were advised to take 25 mg sumatriptan by mouth three times a day for 10 days or until they were headache-free for 24 hours. Results reveal that of the 26 patients who started the protocol, 58% had reverted to an episodic migraine pattern at 1 month, and 69% were no longer having chronic daily headache at 6 months. This study demonstrates that it is possible to detoxify patients with rebound headaches using oral sumatriptan during the withdrawal period in an outpatient setting.     

Chronic migraine plus medication overuse headache: two entities or not?

Chronic migraine (CM) represents migraine natural evolution from its episodic form. It is realized through a chronicization phase that may require months or years and varies from patient to patient. The transition to more frequent attacks pattern is influenced by lifestyle, life events, comorbid conditions and personal genetic terrain, and it often leads to acute drugs overuse. Medication overuse headache (MOH) may complicate every type of headache and all the drugs employed for headache treatment can cause MOH. The first step in the management of CM complicated by medication overuse must be the withdrawal of the overused drugs and a detoxification treatment. The goal is not only to detoxify the patient and stop the chronic headache but also to improve responsiveness to acute or prophylactic drugs. Different methods have been suggested: gradual or abrupt withdrawal; home treatment, hospitalization, or a day-hospital setting; re-prophylaxes performed immediately or at the end of the wash-out period. Up to now, only topiramate and local injection of onabotulinumtoxinA have shown efficacy as therapeutic agents for re-prophylaxis after detoxification in patients with CM with and without medication overuse. Although the two treatments showed similar efficacy, onabotulinumtoxinA is associated with a better adverse events profile. Recently, the Phase III Research Evaluating Migraine Prophylaxis Therapy (PREEMPT) clinical program proved that patients with CM, even those with MOH, are the ones most likely to benefit from onabotulinumtoxinA treatment. Furthermore, it provided an injection paradigm that can be used as a guide for a correct administration of onabotulinumtoxinA.     

Iron deposition in pain-regulatory nuclei in episodic migraine and chronic daily headache by MRI

Background.— Progression of migraine toward a more disabling chronic form of at least 15 days/month is linked with frequency of attacks. Magnetic resonance imaging (MRI) findings of iron accumulation in the brain, especially in periaqueductal gray and red nucleus, have been correlated with both duration of illness and frequency of attacks. Methods.— This study therefore evaluated iron deposition as measured with MRI in basal ganglia and pain regulatory nuclei in neurologically healthy control volunteers and in patients with various migraine subtypes: episodic migraine (n = 10) with (n = 4) or without aura (n = 6), and chronic daily headache (n = 11), including medication overuse headache (MOH, n = 8), chronic tension‐type headache (n = 1), and primary chronic migraine (n = 2). The goal was to assess differences in iron deposition among migraine subtypes and controls in the hopes of linking the by‐products of frequent attacks or long duration of illness with these changes. Results.— The study sought to evaluate the tradeoff between sensitivity and specificity in T2 imaging of patients with migraine, and found that only T2 imaging in the globus pallidus was able to distinguish between episodic and chronic migraine, suggesting that this technique may be the most appropriate to assess migraine frequency. Patients with MOH did not demonstrate T2′ shortening. Conclusions.— Because iron accumulation should cause shortening of both T2 and T2′, although the lack of significance in observed T2′ difference could be due to increased variance in T2′ the measurement, these results suggest that a mechanism other than increased iron deposition may play a role in the genesis or pathophysiology of MOH.     

Topiramate in migraine progression

Increasing evidence shows that migraine, typically considered as an episodic disease, is a chronic and, in some patients, progressive disorder. Among neuromodulators used for migraine prevention, topiramate has a high level of evidence-based efficacy. Through its wide range of mechanisms of action topiramate increases the activation threshold resulting in neuronal stabilization and thereby reducing cortical neurons hyperexcitability, which is believed to be an important electrophysiological feature underlying the pathogenesis of epilepsy and migraine. Recent studies show that migraineurs have subclinical structural brain changes and persistent alteration of pain perception, in some cases correlated with the duration of the disease and the frequency of attacks that might play a role in the transformation of episodic migraine to chronic forms. An early and prolonged preventive treatment might reduce the risk of such transformation. Recent evidence suggests that topiramate, by reducing migraine frequency and use of acute medication, may prevent the negative progression of migraine. Furthermore, two recently completed multicenter, randomised, placebo-controlled trials have shown that treatment with topiramate 100 mg/day is effective and well tolerated in patients already progressed to chronic migraine and difficult to treat conditions associated with medication-overuse. Topiramate seems to be a preventive treatment, which might be able to act at different levels of the migraine cycle: reduction of frequency in episodic migraine, prevention, and treatment of chronic migraine.     

The course of migraine—a diary study in unselected patients

The course of disease and the predictive value of depression and anxiety in patients with migraine were prospectively examined. We recruited 393 migraineurs through articles in newspapers and performed a follow-up examination 30 months later. At baseline and follow-up, patients underwent a semistructured interview, filled out the Headache Impact Test (HIT-6), Self-rating Depression Scale (SDS) and Self-rating Anxiety Scale (SAS) and they kept a headache diary for 30 days. One hundred and fifty-one patients (38.6%) were seen at follow-up. The baseline data of patients with and without follow-up were comparable. At follow-up the number of headache days per month had decreased from 9.6 ± 5.8 to 8.1 ± 6.3 ( P  < 0.001) and the proportion of patients with chronic headache (15.4%) and medication overuse (13%) had remained stable. SDS and SAS scores were associated with a high migraine frequency and high initial SDS scores predicted high migraine frequency at follow-up. This longitudinal study in unselected patients with migraine not excluding subjects with chronic headache, medication overuse, depression or anxiety does not point towards migraine as a progressive disease in the vast majority of patients and confirms the importance of psychiatric comorbidity.