The efficacy of withdrawal therapy in subjects with chronic daily headache and medication overuse following prophylaxis with topiramate and amitriptyline

Management of patients affected by chronic daily headache (CDH) with medication overuse constitutes one of the most important unresolved problems. The uncertainty regarding the classification and the prophylaxis are a remarkable part of this problem. Objectives are to: (1) to evaluate the efficacy of withdrawal therapy following prophylaxis with topiramate and amitriptyline in a population affected by CDH and medication overuse with follow-up at 1 (T1), 3 (T2) and 6 (T3) months; (2) to identify which group of the Silberstein’s CDH classification (1994) may benefit from this protocol. Inclusion criteria are patients with CDH (headache for more >15 days/month for at least 3 consecutive months) and medication overuse according with IHS second edition (8.2 group); exclusion criteria are patients with secondary headache. All patients included in the study were hospitalized for 1 week. Type of overuse: combination of medications, 38%; analgesics, 29%; triptans, 29%; opioids, 2%; ergotamines, 2%. During hospitalization the following protocol was applied: desametasone 4 mg i.v./day for 1 week, diazepam 6 mg/day for 10 days and prophylaxis with amitriptylin plus topiramate. This prophylaxis was protracted for at least 6 months. The dosages assumed ranged for amitriptylin from 10 to 20 mg/day and for topiramate from 50 to 100 mg/day. In the last 4 years 105 patients with CDH (age 24–89 years; f 96; m 9) were admitted to the hospital. The protocol was applied in 52 patients (age, 29–65 years; f 49; m 3). At T1, 89% of the patients did not fall again into medication overuse; at T2, 64%; and at T3,45% of the patients remained free from overuse. According to the Silberstein’ proposal at T1, 93% of the subjects was affected by transformed migraine; and 7% by tension-type headache. At T3, all the patients free from overuse were affected by transformed migraine. Our data suggest that the patients affected by CDH and medication overuse benefit from withdrawal therapy performed during hospitalization plus prophylaxis with amitriptyline plus topiramate. This combination seems a good pharmacological solution to reduce the risk of relapse.

     

Valproic acid in prophylaxis of refractory migraine

OBJECTIVE: The efficacy and safety of valproic acid were assessed as a prophylactic agent in migraine patients who previously derived no significant benefit from conventional prophylactic medications for migraine. PATIENTS AND METHODS: One hundred and twenty patients aged 23-58 years with the diagnosis of migraine without aura. Response to therapy was determined by using a headache calendar detailing the frequency and severity of attacks. Reduction of 50% or greater in the frequency or severity of headache was considered as improvement. RESULTS: Improvement was observed in headache frequency within 67% of patients. Headache severity had been improved in 60% of patients. The mean average dosage of valproic acid was 1,250 mg daily. Most of the side effects are mild and tolerable. CONCLUSION: These results suggest that valproic acid is effective and safe in the treatment of refractory migraine headache.     

Treatment of medication overuse headache – guideline of the EFNS headache panel

Background: Medication overuse headache is a common condition with a population‐based prevalence of more than 1–2%. Treatment is based on education, withdrawal treatment (detoxification), and prophylactic treatment. It also includes management of withdrawal headache. Aims: This guideline aims to give treatment recommendations for this headache. Materials and methods: Evaluation of the scientific literature. Results: Abrupt withdrawal or tapering down of overused medication is recommended, the type of withdrawal therapy is probably not relevant for the outcome of the patient. However, inpatient withdrawal therapy is recommended for patients overusing opioids, benzodiazepine, or barbiturates. It is further recommended to start individualized prophylactic drug treatment at the first day of withdrawal therapy or even before. The only drug with moderate evidence for the prophylactic treatment in patients with chronic migraine and medication overuse is topiramate up to 200 mg. Corticosteroids (at least 60 mg prednisone or prednisolone) and amitriptyline (up to 50 mg) are possibly effective in the treatment of withdrawal symptoms. Patients after withdrawal therapy should be followed up regularly to prevent relapse of medication overuse. Discussion and conclusion: Medication overuse headache can be treated according to evidence‐based recommendations.     

Pathophysiology and management of transformed migraine and medication overuse headache

There is considerable overlap in the mechanisms mediating migraine headache pain and sustained opioid-induced paradoxical pain. Both involve upregulation of calcitonin gene-related peptide and increased excitability of dorsal horn neurons. Descending facilitation from the rostral ventromedial medulla may contribute to this increased excitability. Using special magnetic resonance imaging techniques, high iron levels were found in the periaqueductal gray of patients with chronic daily headache with medication overuse. The periaqueductal gray is the center of a powerful descending antinociceptive neuronal network and projects to the rostral ventromedial medulla and subsequently to the dorsal horn. The periaqueductal gray is also involved in the behavioral response to opiate withdrawal. Dysfunction in the periaqueductal gray may explain why frequent analgesic use can result in medication overuse headache in migraineurs. Management of transformed migraine with medication overuse involves patient education, biobehavioral therapy, withdrawal of overused acute medications, bridge therapy for withdrawal headache, initiation of preventive medication, and close follow-up.     

Treatment of medication overuse headache—A review

Medication overuse headache (MOH) is the most prevalent chronic headache disorder with a prevalence between 1% and 2% worldwide. The disease has been acknowledged for almost 30 years, yet experts still disagree on how best to treat MOH. By performing a search in PubMed on the terms “medication overuse headache,” “analgesics abuse headache,” “rebound headache,” “drug induced headache,” and “headache AND drug misuse” limited to human studies published in English between January 1, 2004, and November 1, 2017, we aimed to evaluate current literature concerning predictors of treatment outcome, inpatient and outpatient treatment programs, initial versus latent administration of prophylactic medications, and to review the effect of prophylactic medications. Selection criteria were prospective, comparative, or controlled trials on treatment of MOH in persons of at least 18 years of age. Several studies evaluated risk factors to predict the outcome of MOH treatment, but many studies were underpowered. Psychiatric comorbidity, high dependence score, and overuse of barbiturates, benzodiazepines, and opioids predicted a poorer outcome of withdrawal therapy. Patients with these risk factors benefit from inpatient treatment, whereas patients without risk factors benefit equally from inpatient and outpatient treatment. Some medications for migraine prophylactics have shown better effect on MOH compared with placebo, but not when combined with withdrawal. We conclude that detoxification programs are of great importance in MOH treatment. Latent administration of prophylactic medications reduces the number of patients needing prophylactic medication. Individualizing treatment according to the predictors of outcome may improve treatment outcome and thus reduce work‐related and treatment‐related costs.     

Application of ICHD-II and revised diagnostic criteria to patients with chronic daily headache

The objective of this study was to evaluate how the criteria of the second edition of the International Classification of Headache Disorders (ICHD-II) and the revised criteria fit a sample of patients with chronic daily headache (CDH). One hundred and five patients with CDH in a tertiary headache centre were included. Headache was assessed using a semi-structured interview. Patients were classified according to the ICHD-II and to the new appendix criteria of the ICHD. Using the ICHDII, 91% of patients received a combination of diagnoses and 76% received only a probable diagnosis: 47% had probable chronic migraine (CM) with probable medication overuse headache (MOH), 28% had probable chronic tension-type headache (CTTH) with probable MOH, 20% had CTTH and 3.8% had CM. Using the new appendix criteria, 88.5% of patients required one diagnosis. Seventy-six percent of patients were classified as MOH, 17% had CTTH and 6.7% had CM. The classification of CDH remains controversial. Alternative criteria for CM with and without medication overuse are discussed.     

Treatment of chronic migraine with medication overuse: is drug withdrawal crucial?

Chronic headaches have increasingly become a focus within the field of head pain. For the most part patients with frequent headaches eventually overuse their medications, and if it happens (the percentage is approximately 4%), the diagnosis of chronic migraine with medication overuse headache is clinically important, because patients rarely respond to preventive medications whilst overusing acute medications. Properly treating medication overuse with adequate strategies is an essential component for helping these patients to improve and for preventing relapses. The necessity of withdrawal performed by different treatment schedules, outcomes, and the long-term durability of treatment are discussed.     

Treatment of chronic migraine with medication overuse: is drug withdrawal crucial?

Chronic headaches have increasingly become a focus within the field of head pain. For the most part patients with frequent headaches eventually overuse their medications, and if it happens (the percentage is approximately 4%), the diagnosis of chronic migraine with medication overuse headache is clinically important, because patients rarely respond to preventive medications whilst overusing acute medications. Properly treating medication overuse with adequate strategies is an essential component for helping these patients to improve and for preventing relapses. The necessity of withdrawal performed by different treatment schedules, outcomes, and the long-term durability of treatment are discussed.     

Chronic daily headache: a rational approach to a challenging problem

Chronic daily headache (CDH) is a significant public health problem with 3 to 5% of the population worldwide experiencing daily or near-daily headaches. Patients with CDH can be particularly challenging, and clinicians require a systematic approach to help guide investigations and management. The revised 2004 International Headache Society Classification Criteria introduces formalized criteria for several CDH disorders including chronic migraine and medication overuse headache as well as new daily persistent headache, hemicrania continua, hypnic headache, and SUNCT syndrome. Medication overuse is common in patients with CDH who present to physicians. Familiarity and comfort with drug-withdrawal and detoxification strategies is therefore essential. Patients with chronic migraine and chronic cluster experience significant disability and diminished quality of life. The ability to manage these patients effectively is a rewarding clinical experience.     

In-patient vs. day-hospital withdrawal treatment for chronic migraine with medication overuse and disability assessment: results at one-year follow-up

Chronic headaches have increasingly become a focus within the field of head pain. Most patients with frequent headache eventually overuse their medications. The diagnosis of medication-overuse headache is clinically important, because patients rarely respond to preventive medications whilst overusing acute medications. Properly treating medication overuse and preventing relapse require specific therapeutic strategies and the recognition of the different factors that contribute to its development and perpetuation, including some behaviours and psychological elements that are important in sustaining the overuse of medication. Abrupt withdrawal is considered the first step for helping these patients to stop medication overuse. The possibility of withdrawal within a day-hospital setting is considered a therapeutic alternative for these patients and compared to in-patient withdrawal. Long-term results are discussed.

     

What future for treatment of chronic migraine with medication overuse?

Chronic headaches have increasingly become a focus within the field of head pain. Most of the patients with frequent headache eventually overuse their medications, and if it happens [the percentage is approximately 4%], the diagnosis of chronic migraine with medication-overuse headache is clinically important, because patients rarely respond to preventive medications while overusing acute medications. This kind of headache is recognized as a biobehavioral disorder, a complex condition wherein emotion and pain are intermingled. Properly treating medication overuse with adequate strategies by different and specific steps are essential components for helping these patients to improve and for preventing relapses. The clinical experience performed at our Headache Unit, the necessity of withdrawal, different treatment schedules, and different treatment strategies of our center were discussed.     

SPARTACUS: underdiagnosis of chronic daily headache in primary care

Despite the burden of chronic daily headache (CDH), general practitioners' (GPs) ability to recognize it is unknown. This work is a sub-study of a population-based study investigating GPs' knowledge on their CDH patients. Patients diagnosed with CDH through the screening questionnaire were interviewed by their GPs who indicated if subjects were known as patients suffering from CDH with medication overuse (MO), CDH without MO, episodic headache (EH) or non-headache sufferers. Our study showed that 64.37 % of CDH sufferers are misdiagnosed by their GPs. However, overusers are better known to GPs.     

Prise en charge des céphalées chroniques quotidiennes chez l’enfant et l’adolescent

Chronic daily headache (CDH) affects 2 to 4% of adolescent females and 0,8 to 2% of adolescent males. CDH is diagnosed when headaches occur more than 4 hours a day, for greater than or equal to 15 headache days per month, over a period of 3 consecutive months, without an underlying pathology. It is manifested by severe intermittent headaches, that are migraine-like, as well as a chronic baseline headache. Silberstein and Lipton divided patients into four diagnostic categories: transformed migraine, chronic tension-type headache, new daily-persistent headache, and hemicrania continua. The second edition of the International Classification of Headache Disorders did not comprise any CDH category as such, but provided criteria for all four types of CDH: chronic migraine, chronic tension-type headache, new daily-persistent headache, and hemicrania continua. Evaluation of CDH needs to include a complete history and physical examination to identify any possibility of the headache representing secondary headaches. Children and adolescents with CDH frequently have sleep disturbance, pain at other sites, dizziness, medication-overuse headache and a psychiatric comorbidity (anxiety and mood disorders). CDH frequently results in school absence. CDH management plan is dictated by CDH subtype, the presence or absence of medication overuse, functional disability and presence of attacks of full-migraine superimposed. Reassuring, explaining, and educating the patient and family, starting prophylactic therapy and limiting aborting medications are the mainstay of treatment. It includes pharmacologic (acute and prophylactic therapy) and nonpharmacologic measures (biobehavioral management, biofeedback-assisted relaxation therapy, and psychologic or psychiatric intervention). Part of the teaching process must incorporate life-style changes, such as regulation of sleep and eating habits, regular exercise, avoidance of identified triggering factors and stress management. Emphasis must be placed on preventive measures rather than on analgesic or abortive strategies. Stressing the reintegration of the patient into school and family activities and assessing prognosis are other issues to address during the first visit. There are limited data evaluating the outcome of CDH in children and adolescents.     

Preventive treatment of migraine

Migraine preventive therapy, even in the absence of a headache, is given in an attempt to reduce the frequency, duration, or severity of attacks. Circumstances that might warrant preventive treatment include disabling migraine attacks, the overuse of acute medications or failure of or contraindication to acute medications, troublesome side effects from medication, hemiplegic migraine, or very frequent headaches (more than 2 a week). The major medication groups for preventive treatment include anticonvulsants, antidepressants, b-adrenergic blockers, calcium channel antagonists, serotonin antagonists, neurotoxins, nonsteroidal anti-inflammatory drugs, and others. If preventive medication is indicated, the agent preferentially should be chosen from one of the first-line categories, based on the drug's side-effect profile and the patient's coexistent and comorbid conditions.     

Frequency and clinical characteristics of chronic daily headache in an outpatient clinic setting

Background and purposeChronic daily headache (CDH) is not a diagnosis but a category that includes many disorders representing primary and secondary headaches. According to the International Classification of Headache Disorders, 2^nd edition (ICHD-II), CDH is defined as headache which occurs more often than 15 days per month for at least 3 months.Material and methodsWe assessed 1154 headache sufferers diagnosed in our headache outpatient clinic. Clinical history, physical and neurological examination, and laboratory tests were performed to make a diagnosis.ResultsCDH was diagnosed according to ICHD-II in 185 (16%) patients; their mean age was 41 ± 17 years (80% were women). Chronic migraine was a cause of CDH in 49% (91/185) of patients, chronic tension-type headache in 18% (33/185), secondary headache in 25% (46/185) and unclassified pain in 8%. Medication overuse headache occurred in 15%. The most effective therapy in our patients was treatment with tricyclic antidepressants and selective serotonin reuptake inhibitors.ConclusionsThe most frequent cause of CDH in our cohort was chronic migraine. Women suffered more frequently than men. Antidepressants were the most effective preventive medications for all types of CDH, which may suggest that serotoninergic mechanisms can be an important factor in the pathophysiology of chronic pain syndromes.     

Clinical features of withdrawal headache following overuse of triptans and other headache drugs

BACKGROUND: Complete withdrawal from headache medication is the treatment of choice for medication-overuse headache. Discontinuation of the overused headache medication, however, results in the development of withdrawal headache, often associated with nausea, vomiting, and sleep disturbances. METHOD: In a prospective study of 95 patients, the authors investigated the duration and severity of withdrawal headache after overuse of various headache drugs, including single and combination analgesics, ergots, and triptans. All patients underwent standard inpatient withdrawal therapy for 14 days. RESULTS: The duration of withdrawal headache was shorter in patients overusing triptans (4.1 days) than in patients overusing ergots (6.7 days) or analgesics (9.5 days; p < 0.002). The mean headache intensity on the first day of withdrawal did not differ between the groups (p = 0.821). By day 14, however, it was lower in patients overusing triptans (0.08) than in patients overusing ergots (0.4) or analgesics (0.9; p < 0.005). Rescue medication was requested less by patients undergoing triptan withdrawal (0.25 requests) than by patients undergoing ergot withdrawal (1.25) or analgesic withdrawal (1.85; p < 0.05). Similar to findings in the entire patient population, withdrawal headache was shorter and less severe in migraineurs overusing triptans than in those overusing ergots or analgesics. Because only patients with migraine, but no patient with tension-type headache, overused triptans, withdrawal headache was shorter in the group of patients with migraine alone (6.7 days versus 9.6 days for patients with tension-type headache and 8.5 days for patients with combination headache, p < 0.02). CONCLUSION: The duration and severity of withdrawal clearly depend on the type of overused headache drug only.     

Practical strategies for treating chronic migraine with medication overuse: case examples and role play demonstrations

Patients with chronic migraine headaches complicated by medication overuse (MO) present some of the most difficult treatment challenges for headache practitioners. Recent research has identified a variety of risk factors (including MO) that appear to be associated with the escalation of the frequency and severity of migraine headache. Management of such patients with medication overuse headaches (MOH) may become more problematic due to co-morbid psychiatric issues common with migraine patients and the patient’s reluctance to limit/eliminate “overused” abortive medications. Medication adherence becomes an important treatment concern. The present article will highlight treatment issues that must be considered in the assessment and treatment of patients with chronic migraine and MOH. Case examples will be offered to illustrate the process of the implementation of these strategies.

     

Documento de revisión y actualización de la cefalea por uso excesivo de medicación (CUEM)

IntroductionMedication overuse headache is a secondary headache in which the regular or frequent use of analgesics can increase the frequency of the episodes, causing the transition from episodic to chronic headache. The prevalence of medication overuse headache is approximately 1-2%, with higher rates among women aged 30-50 years and with comorbid psychiatric disorders such as depression or anxiety, or other chronic pain disorders. It is important to be familiar with the management of this disease. To this end, the Spanish Society of Neurology's Headache Study Group has prepared a consensus document addressing this disorder.DevelopmentThese guidelines were prepared by a group of neurologists specialising in headache after a systematic literature review and provides consensus recommendations on the proper management and treatment of medication overuse headache. The treatment of medication overuse headache is often complex, and is based on 4 fundamental pillars: education and information about the condition, preventive treatment, discontinuation of the drug being overused, and treatment for withdrawal symptoms. Follow-up of patients at risk of recurrence is important.ConclusionsWe hope that this document will be useful in daily clinical practice and that it will update and improve understanding of medication overuse headache management.     

Emotional problems and prevalence of medication overuse in pediatric chronic daily headache

Chronic daily headaches are an increasingly recognized neurologic issue in children. Frequent headaches can be a source of significant disability and family discord with work/school absenteeism. Medication overuse and emotional disorder would significantly impact treatment and progression. This study examined the frequency of emotional and behavioral problems in children and adolescents with chronic daily headache compared with age-related healthy controls. Prevalence of medication overuse in this chronic daily headache group was evaluated. Otherwise healthy children and adolescents with chronic daily headache (according to International Classification of Headache Disorders-II criteria) were enrolled from the Headache Clinic. Healthy controls were prospectively enrolled from physician offices. Multiple psychological rating scales, headache diaries, presence of medication overuse, and disability surveys (Pediatric Migraine Disability Assessment Survey) were completed. A total of 57 healthy controls and 70 patients were studied. The sample consisted largely of females, many of whom (60%) had medication overuse before medical treatment. Headache patients had significantly more symptoms of anxiety, depression, and somatization compared with controls. Patients with chronic daily headache were at higher risk for emotional disorders, and medication overuse was a significant occurrence, suggesting a need for multisystem treatment approach.