Clinical aspects of medication overuse headaches.

Medication overuse headache (MOH) is a subset of chronic daily headache, occurring from overuse of 1 or more classes of migraine abortive medication. Acetaminophen, combination analgesics (caffeine combinations), opioids, barbiturates (butalbital), non-steroidal anti-inflammatory drugs, and triptans are the main classes of drugs implicated in the genesis of MOH. Migraine seems to be the most common diagnosis leading to MOH. The development of MOH is associated with both frequency of use of medication and behavioral predispositions. MOH is not a unitary concept. The distinction between simple (type 1) vs complex (type 2) forms is based on both the class of overused medication and behavioral factors, including psychopathology and psychological drug dependence. MOH is a challenging disorder causing decline in the quality of life and causing physical symptoms, such as daily and incapacitating headaches, insomnia, and non-restorative sleep, as well as psychological distress and reduced functioning. MOH is associated with biochemical, structural, and functional brain changes. Relapse after detoxification is a challenge, but can be addressed if the patient is followed over a prolonged period of time with a combination of prophylactic pharmacotherapy, use of abortive medication with minimal risk of MOH, withholding previously overused medication, and providing psychological (cognitive-behavioral) therapy.

A practice guide for continuous opioid therapy for refractory daily headache: patient selection, physician requirements, and treatment monitoring.

OBJECTIVES: To provide a guide to the use and limitations of continuous opioid therapy (COT, or daily scheduled opioids) for refractory daily headache, based on the best available evidence and expert clinical experience. BACKGROUND: There has been a dramatic increase in opioid administration over the past 25 years, with limited evidence of efficacy for either pain reduction or increased function, and increasing evidence of adverse effects, including headache chronification. To date, there has been no consensus on headache-specific guidelines for selecting patients for COT, physician requirements, and treatment monitoring. METHODS: A multidisciplinary committee of physicians and allied health professionals with extensive experience and expertise in the administration of opioids to headache patients, undertook a review of the available evidence from the research and clinical literature (using the PubMed database for articles through December 2009) to develop headache-specific treatment recommendations. This guide reflects the opinions of its authors and is not an official document of the American Headache Society. RESULTS: The guide identifies factors that would qualify or disqualify the use of COT, including, determination of intractability prior to initiating COT, requisite experience of the prescriber, and requirements for a formal monitoring system to assess appropriate use, safety, efficacy, and functional impact. An appendix reviews the available evidence for efficacy of COT in chronic headache and noncancer pain, paradoxical effects (opioid-induced hyperalgesia, medication overuse headache, opioid-related reduction in triptan and nonsteroidal anti-inflammatory drug efficacy), other adverse effects (nausea and constipation, insomnia and sleep apnea, respiratory depression and sudden cardiac death, reductions in sex hormones, issues during pregnancy, neurocognitive functioning), and issues related to comorbid psychiatric disorders. CONCLUSIONS: Only a select and very limited group (estimate of 10-20%) of refractory headache patients who meet criteria for COT respond with convincing headache reduction and functional improvement over the long-term. Conservative and empirically based guidelines will help identify those patients for whom a COT trial may be appropriate, while protecting their welfare and safety.

Comprehensive inpatient treatment of refractory chronic daily headache.

OBJECTIVE: (1) To assess outcome at discharge for a consecutive series of admissions to a comprehensive, multidisciplinary inpatient headache unit; (2) To identify outcome predictors. BACKGROUND: An evidence-based assessment (2004) concluded that many refractory headache patients appear to benefit from inpatient treatment, underscoring the need for more research, including outcome predictors. METHODS: The authors completed a retrospective chart review of 283 consecutive admissions over 6 months. The inpatient program (mean length of stay = 13.0 days) included intravenous and oral medication protocols, drug withdrawal when indicated, cognitive-behavior therapy, and other services when needed, including anesthesiological intervention. Patient-reported pain levels and consensus of medical staff determined outcome status. RESULTS: The 267 completers (94%) included 212 women and 55 men (mean age = 40.3 years, range = 13-74) from 43 states and Canada. The modal diagnosis was intractable, chronic daily headache (85%), predominantly migraine. Most (59%) had medication overuse headache (MOH), involving opioids (48%), triptans (16%), or butalbital-containing analgesics (10%). Psychiatric diagnoses included stress-related headache (82%), mood disorders (70%), anxiety disorders (49%), and personality disorders (PD, 26%). More patients with a PD (62%) had opioid-related MOH than those with no PD (38%), P < .005. Of the completers, 78% had moderate to significant pain reduction, with comparable improvement in mood, function, and behavior. Clinical factors predicting moderate-significant headache improvement were limited to MOH (84% vs 69%, P < .007) and presence of a PD (68% vs 81%, P < .03). CONCLUSIONS: Most patients (78%) improved following aggressive, comprehensive inpatient treatment. Maintenance of improvement is likely to depend on multiple post-discharge factors, including continuity of care, compliance, and home or work environment.

Defining refractory migraine: results of the RHSIS Survey of American Headache Society members.

OBJECTIVES: To gauge consensus regarding a proposed definition for refractory migraine proposed by Refractory Headache Special Interest Section, and where its use would be most appropriate. BACKGROUND: Headache experts have long recognized that a subgroup of headache sufferers remains refractory to treatment. Although different groups have proposed criteria to define refractory migraine, the definition remains controversial. The Refractory Headache Special Interest Section of the American Headache Society developed a definition through a consensus process, assisted by a literature review and initial membership survey. DESIGN: A 12-item questionnaire was distributed at the American Headache Society meeting in 2007 during a platform session and at the Refractory Headache Special Interest Section symposium. The same questionnaire was subsequently sent to all American Headache Society members via e-mail. A total of 151 responses from AHS members form the basis of this report. The survey instrument was designed using Survey Monkey. Frequencies and percentages of the survey were used to describe survey responses. RESULTS: American Headache Society members agreed that a definition for refractory migraine is needed (91%) that it should be added to the International Classification of Headache Disorders-2 (86%), and that refractory forms of non-migraine headache disorders should be defined (87%). Responders believed a refractory migraine definition would be of greatest value in selecting patients for clinical drug trials. The current refractory migraine definition requires a diagnosis of migraine, interference with function or quality of life despite modification of lifestyle factors, and adequate trials of acute and preventive medicines with established efficacy. The proposed criteria for the refractory migraine definition require failing 2 preventive medications to meet the threshold for failure. Although 42% of respondents agreed with the working definition of refractory migraine, 43% favored increasing the number to 3 (50%) or 4 (26%) preventive treatment failures. When respondents were asked if they felt that the proposed definition was appropriate to select patients for invasive procedures (patent foramen ovale repair or stimulators) only 44% agreed. CONCLUSIONS: There is a consensus for a need for a definition for refractory migraine and that it should be added to the International Classification of Headache Disorder-2. There was also general agreement by the responders that refractory forms of non-migraine headache disorders should be defined.

Headache and behavioral medicine: a 50-year retrospective.

This article reviews all behaviorally oriented articles published in Headache from 1961(1:1) through the first 3 issues of 2008 and provides an analysis of trends in categories of articles by decade. A mean of 21.6% of all articles included significant attention to behavioral variables; this percentage was relatively stable from 1980 through 2008. The top 5 categories, accounting for 64% of all behavioral articles since the inception of Headache, were: behavioral treatment (19.2%), psychiatric comorbidity (14.0%), psychophysiology (11.2%), behavioral risk factors (9.8%), and psychobiological concepts (9.8%). There is an accelerating trend toward publication of articles related to psychiatric comorbidity, behavioral risk factors, and functional performance/disability.

Continuous opioid therapy (COT) is rarely advisable for refractory chronic daily headache: limited efficacy, risks, and proposed guidelines.

Intractable pain, headache or otherwise, is a devastating and life-controlling experience. The need to effectively and aggressively control pain is a fundamental tenet of clinical care. In the past several years, increasing advocacy for continuous opioid therapy has become an important, if not controversial, theme in the development of treatment guidelines and teaching programs. Ironically, the increasing willingness of physicians to prescribe scheduled opioids for their headache and pain patients has occurred in the absence of compelling data demonstrating efficacy or long-term safety. To the contrary, two meta-analyses on chronic noncancer pain (CNCP) and one long-term uncontrolled study on headache patients demonstrate a relatively small number of patients benefiting from the treatment. Recent neuroscience data on the effects of opioids on the brain raise serious concern for long-term safety and also provide the basis for the mechanism by which chronic opioid use might induce progression of headache frequency and severity. Significant adverse effects, including influence on sexual hormonal balances, physical and psychological dependence, the development of opioid-induced hyperalgesia, and cardiac arrhythmia and sudden death that can be seen with standard dosages of methadone, make a strong argument against widespread use of continuous opioid therapy (COT) in otherwise healthy young and middle-aged headache patients. We believe that COT should be used in rare circumstances for chronic headache patients, and propose initial guidelines for selecting patients and monitoring treatment. The physician should be well versed in the details of opioid prescribing, administration, and monitoring, and should be prepared to discontinue opioids when clinical justification, patient behavior, or failure to achieve therapeutic goals make discontinuance necessary.

Defining refractory migraine and refractory chronic migraine: proposed criteria from the Refractory Headache Special Interest Section of the American Headache Society.

Certain migraines are labeled as refractory, but the entity lacks a well-accepted operational definition. This article summarizes the results of a survey sent to American Headache Society members to evaluate interest in a definition for RM and what were considered necessary criteria. Review of the literature, collaborative discussions and results of the survey contributed to the proposed definition for RM. We also comment on our considerations in formulating the criteria and any issues in making the criteria operational. For the proposed definition for RM and refractory chronic migraine, patients must meet the International Classification of Headache Disorders, Second Edition criteria for migraine or chronic migraine, respectively. Headaches need to cause significant interference with function or quality of life despite modification of triggers, lifestyle factors, and adequate trials of acute and preventive medicines with established efficacy. The definition requires that patients fail adequate trials of preventive medicines, alone or in combination, from at least 2 of 4 drug classes including: beta-blockers, anticonvulsants, tricyclics, and calcium channel blockers. Patients must also fail adequate trials of abortive medicines, including both a triptan and dihydroergotamine (DHE) intranasal or injectable formulation and either nonsteroidal anti-inflammatory drugs (NSAIDs) or combination analgesic, unless contraindicated. An adequate trial is defined as a period of time during which an appropriate dose of medication is administered, typically at least 2 months at optimal or maximum-tolerated dose, unless terminated early due to adverse effects. The definition also employs modifiers for the presence or absence of medication overuse, and with or without significant disability.

Chronic headache: New advances in treatment strategies.

Chronic daily headache (CDH) affects approximately 4 to 5% of the population and encompasses a number of different diagnoses, including transformed migraine, chronic tension-type headache (TTH), new-onset daily persistent headache, and hemicrania continua. Although the pathophysiology of CDH is still poorly understood, some research has suggested that each of the various subtypes of CDH may have a different pathogenesis. The goals of prophylactic therapy are to reduce the frequency, severity, and duration of headache attacks; to improve responsiveness to treatment of acute attacks; to improve function; and to reduce disability. However, opinions differ as to exactly which are the best and most appropriate outcome measures for prophylaxis. Several pharmacologic treatment options exist, including antidepressants, anticonvulsants, muscle relaxants, serotonin agonists, ergots, serotonin antagonists, antianxiety agents, and other miscellaneous drugs. Tizanidine, an alpha(2)-adrenergic agonist, has recently emerged as a promising prophylactic adjunct for CDH, which implicates a central alpha(2)-adrenergic mechanism as an important factor in the pathophysiology of CDH.

Cluster headache pain vs. other vascular headache pain: differences revealed with two approaches to the McGill Pain Questionnaire.

We compared cluster headache pain and other vascular (migraine and mixed) headache pain on pain intensity ratings and the McGill Pain Questionnaire (MPQ). Cluster headache sufferers reported not only more intense pain and more affective distress, but also different pain qualities than did migraine and mixed headache sufferers. The pain qualities that best distinguished cluster headaches from other vascular headaches were the presence of punctate pressure and thermal sensations and the absence of dull pain. Although cluster headache sufferers and other vascular headache sufferers endorsed different sensory pain qualities, MPQ subscales proved no better than pain intensity ratings at distinguishing these two groups. This finding may have occurred because MPQ subscale scores include an intensity component and do not provide information about specific pain qualities such as that provided by MPQ sensory items. These findings provide evidence that cluster headaches are characterized by distinct pain qualities and are not simply a more intense version of the same vascular headache pain experienced by migraine and mixed headache sufferers. They further suggest than when the MPQ is used to assess specific pain qualities, sensory items and not the sensory subscale are the preferred units for analysis.

Screening and behavioral management: medication overuse headache--the complex case.

The new appendix criteria for a broader concept of chronic migraine from the International Headache Society no longer require headache resolution or return to the previous headache pattern to confirm the diagnosis of medication overuse headache (MOH). MOH can be subdivided into simple (Type I) and complex (Type II). Complex cases may involve long-term use of daily opioids or combination analgesics, multisourcing, multiple psychiatric comorbidities, and/or a history of relapse. Daily use of opioids for other medical conditions, psychiatric comorbidity including borderline personality disorder, prior history of other substance dependence or abuse, and family history of substance disorders are risk factors for MOH. Relapse for analgesic overusers can be as high as 71% at 4-year follow-up. A case illustration spans 20 years from initial presentation through multiple periods of recovery and relapse to illustrate issues in the screening and management of complex MOH patients.

Medication overuse headache: biobehavioral issues and solutions.

This article reviews current research on medication-overuse headache (MOH), and provides clinical suggestions for effective treatment programs. Epidemiological research has identified reliance on analgesics as a predictive factor in headache chronicity. MOH can be distinguished as simple (Type I) or complex (Type II). Simple cases involve relatively short-term drug overuse, relatively modest amounts of overused medications, minimal psychiatric contribution, and no history of relapse after drug withdrawal. In contrast, complex cases often present with multiple psychiatric comorbidities and a history of relapse. Although limited, current research suggests that comorbid psychiatric disorders are more prevalent in MOH than in control headache conditions, and may precede the onset of MOH. There appears to be an elevated risk of family history of substance use disorders in MOH patients, and an increased risk of MOH in patients with diagnosed personality disorders. Current studies suggest a high rate of relapse at 3 to 4 years after drug withdrawal and pharmacological treatment, with most relapse occurring during the first year of treatment. Relapse is a greater problem with analgesics than ergots or triptans. The addition of behavioral treatment to prophylactic medication may significantly reduce the risk of relapse over a period of several years. Clinical recommendations include assessment and modification of psychological factors that may underlie MOH, provision of detailed educational information, and combining behavioral treatment with the current standard of drug withdrawal and use of prophylactic pharmacotherapy.

Efficacy of intravenous diphenhydramine versus intravenous DHE-45 in the treatment of severe migraine headache.

This study was conducted to compare the efficacy of intravenous diphenhydramine with dihydroergotamine mesylate (DHE-45; Novartis International AG, Switzerland) in the treatment of severe, refractory, migraine headache. A retrospective review was conducted to include eighty randomly chosen patients who were admitted to the Michigan Head Pain & Neurological Institute's inpatient program at Chelsea Community Hospital. Patients had received nine doses of diphenhydramine or nine doses of DHE-45 during a 3-day period. Patients receiving DHE-45 also received metoclopramide (Reglan; AH Robins Company, Inc., Richmond, VA) as prophylaxis for nausea. Demographics, headache diagnosis, psychiatric discharge diagnoses, abortive medications, and adverse events were recorded and assessed.

Headache and psychiatric comorbidity: historical context, clinical implications, and research relevance.

The comorbidity of headache and psychiatric disorders is a well-recognized clinical phenomenon warranting further systematic research. Affective disorders occur with at least three-fold greater frequency among migraineurs than among the general population, and the prevalence increases in clinical populations, especially with chronic daily headache. When present, psychiatric comorbidity complicates headache management and portends a poorer prognosis for headache treatment. However, the relationship between headache and psychopathology has historically been misunderstood, and measures of psychopathology have not always met the standard of formal Diagnostic and Statistical Manual of Mental Disorders, 4th ed. (DSM-IV) criteria. In some cases, headache has been inappropriately attributed to psychological or psychiatric features, based on anecdotal observations. The challenge for future studies is to employ research methods and designs that accurately identify and classify the subset of headache patients with psychiatric disorders, evaluate their impact on headache symptoms and treatment, and identify optimal behavioral and pharmacologic treatment strategies. This article offers methodological considerations and recommendations for future research including: (i) ascribing dual-International Classification of Headache Disorders, 2nd ed. (ICHD-2) headache and DSM-IV psychiatric diagnoses according to reliable and valid diagnostic criteria, (ii) differentiating subclinical levels of depression and anxiety from major psychiatric disorders, (iii) encouraging validation studies of the recently published ICHD-2 diagnoses for "headache attributed to psychiatric disorder," (iv) expanding epidemiological research to address the range of DSM-IV Axis I and II psychiatric diagnoses among various headache populations, (v) identifying relevant psychiatric and behavioral mediator/moderator variables, and (vi) developing empirically based screening and treatment algorithms.

Future directions in behavioral headache research: applications for an evolving health care environment.

Three decades of research has produced effective behavioral treatments for migraine and tension-type headache, yet the full fruition of this research has not been realized. Further development and dissemination of behavioral treatments is needed to impact the large numbers of those with headache who potentially could benefit from these interventions. At the same time, an evolving health care environment challenges researchers and providers to employ greater efficiency and innovation in managing all chronic disorders. Hopefully, the recently published clinical trials guidelines for behavioral headache research will serve as a catalyst for production of quality empiricism that, in turn, will generate enhanced behavioral strategies and will optimize health care resource utilization. This article describes 10 areas of critical needs and research priorities for behavioral headache research, including: replication and extension of seminal studies using improved methodology; analysis of barriers to implementation of behavioral treatments; development of referral and treatment algorithms; behavioral compliance facilitation with medical interventions; development of a headache self-management model; integration of behavioral intervention within traditional medical practice; identification and management of comorbid psychopathology among headache patients; prevention of disease progression; analysis of behavioral therapeutic mechanisms, and development of innovative treatment formats and applications of information technologies.

Guidelines for trials of behavioral treatments for recurrent headache, first edition: American Headache Society Behavioral Clinical Trials Workgroup.

Guidelines for design of clinical trials evaluating behavioral headache treatments were developed to facilitate production of quality research evaluating behavioral therapies for management of primary headache disorders. These guidelines were produced by a Workgroup of headache researchers under auspices of the American Headache Society. The guidelines are complementary to and modeled after guidelines for pharmacological trials published by the International Headache Society, but they address methodologic considerations unique to behavioral and other nonpharmacological treatments. Explicit guidelines for evaluating behavioral headache therapies are needed as the optimal methodology for behavioral (and other nonpharmacologic) trials necessarily differs from the preferred methodology for drug trials. In addition, trials comparing and integrating drug and behavioral therapies present methodological challenges not addressed by guidelines for pharmacologic research. These guidelines address patient selection, trial design for behavioral treatments and for comparisons across multiple treatment modalities (eg, behavioral vs pharmacologic), evaluation of results, and research ethics. Although developed specifically for behavioral therapies, the guidelines may apply to the design of clinical trials evaluating many forms of nonpharmacologic therapies for headache.

Borderline personality disorder and the chronic headache patient: review and management recommendations.

BACKGROUND: Physicians and psychologists who treat headache not infrequently encounter patients with borderline personality disorder (BPD). BPD patients frequently suffer from headache, and often pose special problems in treatment. Few guidelines exist for the management of the BPD headache patient. OBJECTIVES: To provide an overview of current concepts on BPD, including comorbidity, psychopathophysiology, and treatment. To provide an explicit framework for managing borderline behavior in patients with chronic headache. METHODS: A literature review combined with clinical observations from the tertiary treatment of intractable headache in outpatient and inpatient settings. RESULTS: BPD is found in almost 2% of the general population, with increased prevalence in patients with comorbid psychopathology and substance abuse. Severe headaches and migraine appear to be more prevalent in patients with BPD than the general population. A reported history of abuse is common, but must be interpreted with caution. Recent research has found reduced hippocampal volume in women patients with BPD; hypometabolism in the premotor, prefrontal, and anterior cingulate cortex, as well as the thalamic, caudate, and lenticular nuclei; and serotonergic dysfunction. Opioid medications may have an adverse influence on certain clinical features of BPD. Some patients show at least short-term improvement in dissociative behavior when given opioid antagonists. Treatment should combine appropriate pharmacotherapy with ongoing psychotherapy. Early identification of BPD is likely to improve the course of treatment. Treatment often requires explicit contracts, consistent limit-setting, confrontation, and communication between different treating professionals to avoid "splitting." The recognition and management of the doctor's own countertransference is important to successful management. Noncompliant patients may need to be terminated from treatment. CONCLUSIONS: Specific management guidelines and the use of explicit treatment contracts can help sustain patients in treatment, reduce the risk of medication abuse, and minimize distress in the treating professional. Headaches and other symptoms in patients with BPD can be successfully managed over the course of a long-term relationship with clearly defined limits.

Psychological and neuropsychological integration in multidisciplinary pain management after TBI.

The intersection of traumatic brain injury and posttraumatic chronic pain poses a significant challenge for the health practitioner. Effective intervention requires psychological and neuropsychological evaluation, multidisciplinary teamwork, and an understanding of a wide range of pain disorders and their relationship to traumatic brain injury. Assessment must include documentation of both current functioning and premorbid history. Pain interacts with cognitive impairment, mood and anxiety disorders, dysinhibition syndromes, and personality disorders, posing significant diagnostic dilemmas and treatment challenges. Coordinated care requires multiple, ongoing interventions from a variety of specialists. Patient involvement, focusing on internal locus of control, mediates successful treatment.

Chronic daily headache prophylaxis with tizanidine: a double-blind, placebo-controlled, multicenter outcome study.

OBJECTIVE: To assess the efficacy of tizanidine hydrochloride versus placebo as adjunctive prophylactic therapy for chronic daily headache (chronic migraine, migrainous headache, or tension-type headache). BACKGROUND: Tizanidine is an alpha2-adrenergic agonist that inhibits the release of norepinephrine at both the spinal cord and brain, with antinociceptive effects that are independent of the endogenous opioid system. Previous open-label studies have suggested the drug may be effective for treatment of chronic daily headache. METHODS: Two hundred patients completed a 4-week, single-blind, placebo baseline period, with 134 fulfilling selection criteria and then randomized to tizanidine or placebo. Ninety-two patients completed at least 8 weeks of treatment (tizanidine, n = 45; placebo, n = 47), and 85 patients completed 12 weeks of treatment (tizanidine, n = 44; placebo, n = 41). Most patients (77%) met the diagnostic criteria for migraine of the International Headache Society; 23% had either chronic migrainous headache or chronic tension-type headache. Tizanidine was slowly titrated over 4 weeks to 24 mg or the maximum dose tolerated (mean, 18 mg; SD, 6.4; median, 20.0; range, 2 to 24), divided equally over three dose intervals per day. Overall headache index ([headache days x average intensity x duration in hours]/28 days) was the primary end point. RESULTS: Tizanidine was shown to be superior to placebo in reducing the overall headache index (P =.0025), as well as mean headache days per week (P =.0193), severe headache days per week (P =.0211), average headache intensity (P =.0108), peak headache intensity (P =.0020), and mean headache duration (P =.0127). The mean percentage improvement during the last 4 weeks of treatment with tizanidine versus placebo was 54% versus 19% for the headache index (P =.0144), 55% versus 21% for severe headache days (P =.0331), 35% versus 19% for headache duration (P =.0142), 35% versus 20% for peak headache intensity (P =.0106), 33% versus 20% for average headache intensity (P =.0281), and 30% versus 22% for total headache days (P =.0593). Patients receiving tizanidine also scored higher ratings of overall headache improvement on a visual analog scale (P =.0069). There was no statistically significant difference in outcome for patients with chronic migraine versus those with only migrainous or tension-type headache. Adverse effects reported by more than 10% of the patients included somnolence (47%), dizziness (24%), dry mouth (23%), and asthenia (19%). Dropouts due to adverse events did not differ significantly between tizanidine and placebo. CONCLUSIONS: The results support tizanidine as an effective prophylactic adjunct for chronic daily headache, including migraine, migrainous headache, and tension-type headache. These results also suggest the possible importance of an alpha2-adrenergic mechanism underlying the pathophysiology of this spectrum of headache disorders.