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 Headache has been associated with psychiatric illness in the medical literature for well over a century. Unfortunately, as noted by Silberstein and colleagues, 1 the relationship between headache and psychopathology has been clinically discussed far more often than it has been systematically studied. This relationship remains probably one of the most poorly understood, while at the same time clinically important, areas for future headache research. The present article provides a brief historical context for research examining headache and psychiatric comorbidity. Despite an arguably dubious genesis emerging from psychoanalytic case reports with little evidence supporting 493

This study is the first double-blind placebo-controlled trial of fluoxetine for chronic daily headache (CDH) and migraine. After a one month single-blind baseline on placebo, subjects with CDH (n = 64) and migraine (n = 58) were randomly assigned to a three month trial of fluoxetine (20 mg) or an identical placebo. Fluoxetine and placebo were increased to 40 mg in the second month, depending on patient response. Patients kept daily headache records, and completed 100 mm visual analogue scales (VAS) of headache and mood each month. For the group of CDH patients on fluoxetine, overall headache status (VAS) after three months compared to the end of the single-blind placebo baseline improved a mean of 50% vs. 11% for those receiving the double-blind placebo (P = .029), with 47% vs. 23% improving at least 50% (P = .097, n.s.). Fluoxetine patients showed significant improvement in monthly mood ratings compared to placebo (.001 by the end of the study), and modest but significant improvement in daily records of headache frequency (P = .019) but not pain severity. Significant mood improvements preceded improvement in headache, reaching significance by the end of the second month on fluoxetine (P = .013), while headache improvement emerged only during the third month (P = .001). Double-blind investigator judgement identified more headache improvement in fluoxetine than placebo recipients (40% vs. 22%, P = .032).(ABSTRACT TRUNCATED AT 250 WORDS)

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.

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.

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.

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.

For a select group of intractable headache patients, DSO can offer significant benefit. However, 74% of those treated either failed to show significant improvement or were discontinued from the program for clinical reasons. The relatively low percentage of patients with demonstrated efficacy and unexpectedly high prevalence of misuse have clinical relevance.

Despite a mean of only 3.50 medical visits in a population of complex patients, significant improvement was demonstrated in several key economically relevant variables within 6 months of referral. If maintained over the long term, the results support the concept that matching intensity of treatment (comprehensive/tertiary care) to severity of illness (complex/refractory cases) is cost-effective.