Daily scheduled opioids for intractable head pain: long-term observations of a treatment program.

BACKGROUND: Daily scheduled opioids (DSO) have been employed in some instances to remediate intractable headache. However, long-term studies of effectiveness, sequelae over several years, predictors of long-term benefit, comparisons of pain-related outcome measures, and prevalence of problematic drug behavior are not available. METHODS: The authors evaluated the results of a treatment program at their institution designed to treat and monitor intractable headache patients administered DSO. Of 160 sequential patients participating in the program, 70 who remained on DSO for at least 3 years qualified for inclusion in an efficacy analysis. Patients completed structured questionnaires at each medical visit as part of routine clinical care. The authors assessed medical records during treatment, and during the 2 years before starting DSO. The primary clinical efficacy variable was percentage improvement in the severe headache index (frequency x severity of severe headaches/week). RESULTS: Analysis of the medical records found 41 (26%) of the original 160 patients with >50% improvement. Patients reported larger improvements on a visual analog scale (mean improvement = 70%) than shown by the medical record (mean improvement = 46%), p < 0.00001. Problem drug behavior (dose violations, lost prescriptions, multisourcing) occurred in 50% of patients, usually involving dose violations. CONCLUSIONS: 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.

Behavioral and nonpharmacologic treatments of headache.

Cognitive-behavioral analysis and the multiaxial assessment of relevant behavioral domains (headache frequency and severity, analgesic and abortive use and misuse, behavioral and stress-related risk factors, comorbid psychiatric disorders, and degree of overall functional impairment) help set the stage for CBT of headache disorders. Controlled studies of CBTs for migraine, such as biofeedback and relaxation therapy, have a prophylactic efficacy of about 50%, roughly equivalent to propranolol. Cluster headache responds poorly to behavioral treatment. The persistent overuse of symptomatic medication impedes the effectiveness of behavioral and prophylactic medical therapies. Behavioral treatment can help sustain improvement after analgesic withdrawal, however, and prevent relapse in cases of analgesic overuse. Cognitive factors (e.g., an enhanced sense of self-efficacy and internal locus of control) appear to be important mediators of successful behavioral treatment. Patients with CDH are more likely to overuse symptomatic medication (and in some cases abuse analgesics), have more psychiatric comorbidity; have more functional impairment and disability, and are at least as likely to experience stress-related intensification of headache as patients whose episodic headaches occur less than 15 days per month. Despite the significance of these behavioral factors, patients with CDH (particularly those with migrainous features) are less likely to benefit from behavioral treatment without concomitant prophylactic medication than is the case for episodic TTH and migraine sufferers. Continuous daily pain may be more refractory to behavioral treatment as a solo modality than CDH marked by at least some pain-free days or periods of time. The combination of behavioral therapies with prophylactic medication creates a synergistic effect, increasing efficacy beyond either type of treatment alone. Compliance-enhancement techniques, including behavioral contracts for patients with severe personality disorders, can increase adherence to behavioral recommendations. CBT has earned an important place in the comprehensive treatment of patients with episodic migraine/TTH and severe, treatment-resistant chronic daily headache.

Nefazodone for chronic daily headache prophylaxis: an open-label study.

OBJECTIVE: To assess effectiveness, tolerability, and safety of nefazodone as a prophylactic agent for chronic daily headache. BACKGROUND: Nefazodone is a potent, selective 5-HT2 antagonist with a distinct and atypical mechanism of action. The evolution of intermittent migraine to chronic daily headache has been linked to up-regulation of 5-HT2 receptors as well as other factors. Other effective migraine prophylactic medications are also 5-HT2 antagonists. Although research has shown nefazodone to be an effective antidepressant with a good tolerability and safety profile, its potential role in headache prophylaxis has not been tested. DESIGN: This was a two-center, open-label study with a 4-week baseline, followed by 12 weeks of treatment with nefazodone at a median dose of 300 mg (mean, 303.66 +/- 65.57 mg; range, 100 to 450 mg depending on tolerability). Potential patients were required to report more than 15 days of headache per month for at least 3 months prior to screening. Only patients with at least 15 days of recorded headache during baseline were included in the final sample (N=52). Most patients (n=48) had a history of migraine based on International Headache Society criteria; 4 had primarily chronic tension-type headache, but with more migrainous features than permitted by International Headache Society criteria for a primary chronic tension-type headache diagnosis. RESULTS: Significant improvement was demonstrated for all headache diary measures, with significance levels ranging from P<.00001 for average intensity, duration, headache index (intensity x duration), peak intensity, headache days per week, and peak impairment, to P<.0033 for severe headache days per week, and P<.0051 for rescue medication days. During the last month of treatment, 71% of the patients completing the study showed at least a 50% reduction in headache index compared to baseline, and 59% had at least a 75% improvement. Visual analog scales completed at 4-week intervals showed significant improvement in patient ratings of overall headache status, quality of life, sleep, mood (P<.00001), and sexual function (P<.00053). Significant improvements were also observed in the Pain Disability Index (P<.00007), Beck Depression Inventory-II (P<.00001), Hamilton Rating Scale for Depression (P<.0008), and Hamilton Psychiatric Rating Scale for Anxiety (P<.00007). Headache indices for patients in the top quartile on the depression and anxiety scales (clinical depression/anxiety) did not differ from the other patients during baseline. However, patients who were depressed or anxious showed significantly more improvement over the course of 12 weeks of treatment (P<.0006 or less for the depression scales, P<.026 for anxiety). Common mild to moderate adverse events reported by 10% or more of the patients included fatigue, nausea, dry mouth, dizziness, sleep disturbance, blurred vision, irritability/nervousness, and sedation. Only 5 of the 52 patients discontinued the study due to adverse events: headache (2 patients), and nausea, sleep disturbance, and a drugged feeling (1 patient each). CONCLUSIONS: These results provide preliminary support for the efficacy of nefazodone in the prophylaxis of chronic daily headache. In this sample, nefazodone was safe and generally well tolerated. Patient ratings of sexual function improved over the course of treatment, in contrast to what is generally observed with most antidepressants. Nefazodone may be particularly beneficial for patients with chronic daily headache and comorbid depression. Further research is indicated.

An open-label dose-titration study of the efficacy and tolerability of tizanidine hydrochloride tablets in the prophylaxis of chronic daily headache.

OBJECTIVE: To assess effectiveness and safety of tizanidine hydrochloride tablets for the prophylaxis of chronic daily headache. BACKGROUND: Tizanidine hydrochloride is an alpha2-adrenergic agonist that inhibits the release and effectiveness of norepinephrine at both central sites (eg, the locus ceruleus) and the spinal cord. It acts as a central muscle relaxant and has antinociceptive effects. Preliminary research and retrospective analyses have suggested efficacy in treatment of both chronic tension-type headache and chronic daily headache with migrainous features. DESIGN: Thirty-nine patients with more than 15 headache days per month (33 with migraine, 5 migrainous, 1 chronic tension-type) completed a 4-week baseline, with 31 completing a planned 12 weeks of treatment with tizanidine. Dosing was titrated from 2 mg at bedtime to a median daily dose of 14 mg (mean, 13.5; SD, 4.3; range, 4 to 20, divided over three doses per day) by treatment week 4. RESULTS: The overall headache index through week 12 (headache frequency x average intensity x duration) declined significantly (P<.00000002), with a corresponding increase in mean percentage improvement from 49% for weeks 1 through 4, to 65% for weeks 5 through 8, and 64% for weeks 9 through 12 (P<.0182). During weeks 9 through 12, 67% had improved more than 50% compared to baseline. Overall headache frequency declined from 22.83 to 15.83 days per month (P<.00001), with frequency of severe headaches dropping from 7.52 to 3.58 days per month (P<.000035). Average headache intensity dropped from 1.83 to 1.07 (1-to-5 scale), peak intensity declined from 2.37 to 1.40, and mean duration was reduced from 6.96 to 4.00 hours per headache (P<.00001). Improvement also occurred on visual analog scales of overall headache status, mood, sleep, quality of life (P<.00001), and sexual function (P<.0075); as well as the Beck Depression Inventory-II (P<.00073). Mild-to-moderate adverse events reported by more than 10% of the patients included somnolence, asthenia, and dry mouth. Only 3 patients discontinued treatment due to adverse events: somnolence and dry mouth alone (n = 1), or in combination with either hyperkinesis (n = 1) or constipation (n = 1). One patient had elevated liver enzymes that returned to normal after the drug was discontinued. CONCLUSIONS: The results provide preliminary support for the efficacy, safety, and tolerability of tizanidine in the prophylaxis of chronic daily headache.

Behavioral self-management in an inpatient headache treatment unit: increasing adherence and relationship to changes in affective distress.

OBJECTIVE: To evaluate prospectively the contribution of a psychological self-management program to the amelioration of headache-related distress of patients with intractable migraine treated in a comprehensive, multidisciplinary, inpatient program. BACKGROUND: Previous research has shown the effectiveness of this overall inpatient program but did not examine the relationships between the use of relaxation and other headache-related behavioral factors. METHODS: Data from 221 admissions to a Commission on Accreditation of Rehabilitation Facilities-accredited, nationally recognized, inpatient treatment unit were analyzed for the current study. On admission and on discharge (average length of stay, 12.9 days), subjects completed a 7-day retrospective, self-report questionnaire assessing health behavior compliance and emotional factors. The intervention consisted of intensive medical therapy in addition to cognitive-behavioral treatment delivered in a group setting. RESULTS: Adherence increased significantly for relaxation practice and life-style modifications of diet, exercise, and sleep regulation for headache prevention (P<.00001). Beck Depression Inventory scores decreased significantly (P<.00001), and a greater decrease in depression by the end of the program was reported by subjects who practiced relaxation most compared with those who practiced relaxation least. CONCLUSIONS: Low baseline adherence rates for health behavior increased significantly during the final week of inpatient treatment. Behavioral self-management variables, not headache reduction, were significantly associated with patients' reduction in affective distress.

Headache level during neuropsychological testing and test performance in patients with chronic posttraumatic headache.

This study addresses (1) the relationship between headache presence/intensity at time of testing and neurocognitive performance, and (2) the probability that testing triggers or intensifies pain. Subjects were 125 patients with chronic posttraumatic headache (mean = 2.67 years post injury) who completed a 4-hour test battery emphasizing memory. Comparisons of 34 individual tests/subtests and the five Wechsler Memory Scale-Revised (WMS-R) indices of relative memory impairment for 73 patients with no headache or mild headache versus 52 patients with moderate to severe pain revealed no significant differences. Testing intensified existing headaches for 55% but triggered headache for only 1 of 20 (5%; P =.00003). Results support the validity of neuropsychological test performance regardless of pain level, although testing can be painful.

Comprehensive/tertiary care for headache: a 6-month outcome study.

OBJECTIVE: To assess programwide (outpatient plus inpatient) outcome using prospective measures for the first 6 months of treatment at a comprehensive headache center. Background.-There is little published data on the overall programwide efficacy of comprehensive, multidisciplinary treatment centers for severe, refractory headache disorders. METHODS: For 1 week each month over a 2-year period, all new patients completed an initial questionnaire noting frequency/severity of headaches and other headache-relevant measures. A follow-up version mailed at 6 months was returned by 218 of 421 patients (response rate 52%). Sixteen percent were treated both in and out of the hospital, with 84% treated as outpatients only. Patients had a mean of 2.50 medical visits after the initial evaluation, and 43% met with a psychologist. RESULTS: Mean headache frequency dropped from 5.30 to 3.45 days per week (P<.00001), with severe headaches declining from 2.31 to 1.33 days per week (P<.00001). Sixty-seven percent of the patients had at least a 50% reduction in headaches, with a mean percentage improvement per patient in severe headaches of 56% (median 67%). Emergent care visits within 6 months dropped from 4.39 to 1.67 (P<.00001). Days with significant headache-related work impairment declined from 2.04 to 0.67 days per week (P<.00001), a net annualized reduction of 71.24 impaired workdays per year per patient. For full-time workers, missed work days in 6 months dropped from 5.46 to 2.68 (P<.00261). The mean percentage improvement for headache-impaired workdays was 67% (median 88%), and for work absence was 63% (median 100%). Total days incapacitated per week dropped from 1.72 to 0.89 (P<.00001), with a mean percentage improvement of 67% (median 91%). Significant treatment satisfaction was reported by 89%. A weighted Goal Attainment Scale based on the percentage of patients showing significant improvement in pain control, functioning, work performance, reliance on emergent care, depression, and satisfaction revealed an overall Goal Attainment score of 72%. CONCLUSIONS: 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.

Assessing the dimensions of pain: a multitrait-multimethod evaluation of seven measures.

A multitrait-multimethod design was used to examine the convergent and discriminant validity of seven pain measures from three widely used self-report instruments designed to assess the sensory, affective and intensity dimensions of pain. The instruments were the McGill Pain Questionnaire, the Pain Perception Profile and Numerical Ratings. Three distinct factor models, each corresponding to a different hypothesis about how these pain measures are related, were tested using confirmatory factor analysis in a sample of 419 headache sufferers. A three-factor model, postulating three correlated factors defined by the three assessment instruments best explained the correlations between the pain measures. Measures of sensory, affective and intensity dimensions from the three instruments failed to exhibit convergent or discriminant validity. Rather, instrument variance obscured the pain qualities the three pain instruments were designed to assess. These findings suggest that greater attention needs to be paid to how formal characteristics of pain assessment instruments influence patients' descriptions of their pain.

Double-blind trial of fluoxetine: chronic daily headache and migraine.

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)

Comprehensive inpatient treatment for intractable migraine: a prospective long-term outcome study.

This paper describes outcome data for 100 patients with severe, intractable, persistent migraine (chronic daily headache), who were admitted to a comprehensive inpatient Head-Pain Treatment Unit for a mean of 8.5 days. Headache, pain-related behavior, depression, sleep disturbance, functional performance, work status, and medication use were assessed at admission, post-discharge (mean = 2.3 weeks) and long-term follow-up (mean = 8.3 months). Significant improvement noted two weeks after discharge was maintained over time. Long-term results revealed a 64% reduction in the mean number of days in a 2-week period with severe to incapacitating headache (6.29 to 2.26), with a corresponding increase in pain-free days (1.03 to 5.40). At follow-up, the frequency of severe headaches was reduced by at least 50% for 75% of the patients. The mean rating of overall improvement was 74%. Patients on work-leave due to pain dropped from 24% to 4%, while the number of working patients rose from 31% to 53%. The data showed statistically significant reductions in days lost to pain, depression, sleep disturbance, and use of symptomatic medication. All the above analyses were significant at P = .000. These results demonstrate the efficacy of the inpatient headache program intervention for this group of patients.