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1.  Clinical outcome of a headache-specific multidisciplinary treatment program and adherence to treatment recommendations in a tertiary headache center: an observational study 
The Journal of Headache and Pain  2011;12(4):475-483.
This study investigated the outcome of a 5-day headache-specific multidisciplinary treatment program (MTP) and the adherence to treatment recommendations in 295 prospectively recruited consecutive headache patients [210 migraine, 17 tension-type headache (TTH), 68 combination headache, including 56 medication-overuse headache (MOH)]. Headache frequency decreased from 13.4 (±8.8) to 8.8 (±8.0) days per month after 12–18 months. Forty-three percent of the participants fulfilled the primary outcome (reduction of headache frequency of ≥50%), which was less likely in patients with combination of migraine and TTH compared to migraine (OR = 3.136, p = 0.002) or TTH (OR = 1.029, n.s.). Increasing number of headache days per month (OR = 1.092, p ≤ 0.0001) and adherence to lifestyle modifications (OR = 1.269, p = 0.004) predicted primary outcome. 51 of 56 MOH patients were treated successfully. Thirty-five percent of the patients were adherent to pharmacological prophylaxis, 61% to relaxation therapy, and 72% to aerobic endurance sports. MTP is effective in headache treatment. Adherence to therapy was associated with better outcome.
doi:10.1007/s10194-011-0348-y
PMCID: PMC3139052  PMID: 21544647
Migraine; Headache; Multidisciplinary treatment program; Adherence
2.  Clinical outcome of a headache-specific multidisciplinary treatment program and adherence to treatment recommendations in a tertiary headache center: an observational study 
The Journal of Headache and Pain  2011;12(4):475-483.
This study investigated the outcome of a 5-day headache-specific multidisciplinary treatment program (MTP) and the adherence to treatment recommendations in 295 prospectively recruited consecutive headache patients [210 migraine, 17 tension-type headache (TTH), 68 combination headache, including 56 medication-overuse headache (MOH)]. Headache frequency decreased from 13.4 (±8.8) to 8.8 (±8.0) days per month after 12–18 months. Forty-three percent of the participants fulfilled the primary outcome (reduction of headache frequency of ≥50%), which was less likely in patients with combination of migraine and TTH compared to migraine (OR = 3.136, p = 0.002) or TTH (OR = 1.029, n.s.). Increasing number of headache days per month (OR = 1.092, p ≤ 0.0001) and adherence to lifestyle modifications (OR = 1.269, p = 0.004) predicted primary outcome. 51 of 56 MOH patients were treated successfully. Thirty-five percent of the patients were adherent to pharmacological prophylaxis, 61% to relaxation therapy, and 72% to aerobic endurance sports. MTP is effective in headache treatment. Adherence to therapy was associated with better outcome.
doi:10.1007/s10194-011-0348-y
PMCID: PMC3139052  PMID: 21544647
Migraine; Headache; Multidisciplinary treatment program; Adherence
3.  Multidisciplinary integrated headache care: a prospective 12-month follow-up observational study 
The Journal of Headache and Pain  2012;13(7):521-529.
This prospective study investigated the effectiveness of a three-tier modularized out- and inpatient multidisciplinary integrated headache care program. N = 204 patients with frequent headaches (63 migraine, 11 tension-type headache, 59 migraine + tension-type headache, 68 medication-overuse headache and 3 with other primary headaches) were enrolled. Outcome measures at baseline, 6- and 12-month follow-ups included headache frequency, Migraine Disability Assessment (MIDAS), Hospital Anxiety and Depression Scale (HADS), standardized headache diary and a medication survey. Mean reduction in headache frequency was 5.5 ± 8.5 days/month, p < 0.001 at 6 months’ follow-up and 6.9 ± 8.3 days/month, p < 0.001 after 1 year. MIDAS decreased from 53.0 ± 60.8 to 37.0 ± 52.4 points, p < 0.001 after 6 months and 34.4 ± 53.2 points, p < 0.001 at 1 year. 44.0 % patients demonstrated at baseline an increased HAD-score for anxiety and 16.7 % of patients revealed a HAD-score indicating a depression. At the end of treatment statistically significant changes could be observed for anxiety (p < 0.001) and depression (p < 0.006). The intake frequency of attack-aborting medication decreased from 10.3 ± 7.3 days/month at admission to 4.7 ± 4.1 days/month, p < 0.001 after 6 months and reached 3.8 ± 3.5 days/month, p < 0.001 after 1 year. At baseline 37.9 % of patients had experience with non-pharmacological treatments and 87.0 % at 12-month follow-up. In conclusion, an integrated headache care program was successfully established. Positive health-related outcomes could be obtained with a multidisciplinary out- and inpatient headache treatment program.
doi:10.1007/s10194-012-0469-y
PMCID: PMC3444539  PMID: 22790281
Integrated; Care; Multidisciplinary treatment program; Outcome study; Headache-related disability; Headache-related quality of life; Chronic headache
4.  Team players against headache: multidisciplinary treatment of primary headaches and medication overuse headache 
The Journal of Headache and Pain  2011;12(5):511-519.
Multidisciplinary approaches are gaining acceptance in headache treatment. However, there is a lack of scientific data about the efficacy of various strategies and their combinations offered by physiotherapists, physicians, psychologists and headache nurses. Therefore, an international platform for more intense collaboration between these professions and between headache centers is needed. Our aims were to establish closer collaboration and an interchange of knowledge between headache care providers and different disciplines. A scientific session focusing on multidisciplinary headache management was organised at The European Headache and Migraine Trust International Congress (EHMTIC) 2010 in Nice. A summary of the contributions and the discussion is presented. It was concluded that effective multidisciplinary headache treatment can reduce headache frequency and burden of disease, as well as the risk for medication overuse headache. The significant value of physiotherapy, education in headache schools, and implementation of strategies of cognitive behavioural therapy was highlighted and the way paved for future studies and international collaboration.
doi:10.1007/s10194-011-0364-y
PMCID: PMC3173636  PMID: 21779789
Multidisciplinary treatment; Headache school; Headache nurse; Physiotherapy
5.  Team players against headache: multidisciplinary treatment of primary headaches and medication overuse headache 
The Journal of Headache and Pain  2011;12(5):511-519.
Multidisciplinary approaches are gaining acceptance in headache treatment. However, there is a lack of scientific data about the efficacy of various strategies and their combinations offered by physiotherapists, physicians, psychologists and headache nurses. Therefore, an international platform for more intense collaboration between these professions and between headache centers is needed. Our aims were to establish closer collaboration and an interchange of knowledge between headache care providers and different disciplines. A scientific session focusing on multidisciplinary headache management was organised at The European Headache and Migraine Trust International Congress (EHMTIC) 2010 in Nice. A summary of the contributions and the discussion is presented. It was concluded that effective multidisciplinary headache treatment can reduce headache frequency and burden of disease, as well as the risk for medication overuse headache. The significant value of physiotherapy, education in headache schools, and implementation of strategies of cognitive behavioural therapy was highlighted and the way paved for future studies and international collaboration.
doi:10.1007/s10194-011-0364-y
PMCID: PMC3173636  PMID: 21779789
Multidisciplinary treatment; Headache school; Headache nurse; Physiotherapy
6.  The validity of questionnaire-based diagnoses: the third Nord-Trøndelag Health Study 2006–2008 
The Nord-Trøndelag Health Study (HUNT 3) performed in 2006–2008 is a replication of the cross-sectional survey from 1995 to 1997 (HUNT 2). The aim of the present study was to assess the sensitivity and specificity of questionnaire-based headache diagnoses using a personal interview by a neurologist as a gold standard. For the questionnaire-based status as headache sufferer, a sensitivity of 88%, a specificity of 86%, and a kappa statistic of 0.70 were found. Chronic headache, chronic tension-type headache (TTH), and medication overuse headache (MOH) were diagnosed with a specificity of ≥99%, and a kappa statistic of ≥0.73. Lower figures were found for the diagnoses of migraine and TTH. For individuals with headache ≥1 day per month, a sensitivity of 58% (migraine) and 96% (TTH), a specificity of 91 and 69%, and a kappa statistic of 0.54 and 0.44 were found, respectively. The specificity for migraine with aura was 95%. In conclusion, the HUNT 3-questionnaire is a valid tool for identifying headache sufferers, and diagnosing patients with chronic headache, including chronic TTH and MOH. The more moderate sensitivity for migraine and TTH makes the questionnaire-based diagnoses of migraine and TTH suboptimal for determining the prevalence. However, the high specificity of the questionnaire-based diagnosis of migraine, in particular for migraine with aura, makes the questionnaire a valid tool for diagnosing patients with migraine for genetic studies.
doi:10.1007/s10194-009-0174-7
PMCID: PMC3452179  PMID: 19946790
Headache; Migraine; Questionnaire; Survey; Population
7.  A CARE pathway in medication–overuse headache: the experience of the Headache Centre in Pavia 
The Journal of Headache and Pain  2005;6(4):307-309.
Medication–overuse headache (MOH) is one of the headache forms that most frequently prompts patients to consult a specialist headache centre. The prevaence of this form in the general population is approximately 1–2%. Around 40% of patients seen at headache centres present with a chronic form of headache and 80% of this chronic headache patients make excessive use of symptomatic drugs. MOH shows a clinical improvement, accompained by a reduction in the consumption of analgesic drugs, if patients are submitted to detoxification therapy. But detoxification is only the first stage in a long and complex course of care and global approach demands adequate follow–up visit to prevent early relapses. At the Headache Centre of the C. Mondino Institute of Neurologt in Pavia, a course of care (CARE) has been developed for the complente management of patients with MOH both during Hospitalization and durimg the subsequent follow–up period. CARE IS designed to trace the clinical, psychopathological and pharmacological profile of MOH in the short–, medium– and long–term; to look for factors possibility predictive of relapse; to assess the direct costs linked to overuse–headache in the year leading up to and following detoxification; and to evaluate disability, in terms of working days lost, before and after detoxification.
doi:10.1007/s10194-005-0216-8
PMCID: PMC3452024  PMID: 16362695
Medication–overuse headache; Care pathway; Management
8.  Validation of criterion-based patient assignment and treatment effectiveness of a multidisciplinary modularized managed care program for headache 
The Journal of Headache and Pain  2012;13(5):379-387.
This prospective observational study evaluates the validity of an algorithm for assigning patients to a multidisciplinary modularized managed care headache treatment program. N = 545 chronic headache sufferers [migraine (53.8 %), migraine + tension type (30.1 %), tension type (8.3 %) or medication overuse headache (6.2 %), other primary headaches (1.5 %)] were assigned to one of four treatment modules differing with regard to the number and types of interventions entailed (e.g., medication, psychological intervention, physical therapy, etc.). A rather simple assignment algorithm based on headache frequency, medication use and psychiatric comorbidity was used. Patients in the different modules were compared with regard to the experienced burden of disease. 1-year follow-up outcome data are reported (N = 160). Headache frequency and analgesic consumption differed significantly among patients in the modules. Headache-related disability was highest in patients with high headache frequency with/without medication overuse or psychiatric comorbidity (modules 2/3) compared to patients with low headache frequency and medication (module 0). Physical functioning was lowest in patients with chronic headache regardless of additional problems (modules 1/2/3). Psychological functioning was lowest in patients with severe chronicity with/without additional problems (module 2/3) compared to headache suffers with no/moderate chronicity (module 0/1). Anxiety or depression was highest in patients with severe chronicity. In 1-year follow-up, headache frequency (minus 45.3 %), consumption of attack-aborting drugs (minus 71.4 %) and headache-related disability decreased (minus 35.9 %). Our results demonstrate the clinical effectiveness and the criterion validity of the treatment assignment algorithm based on headache frequency, medication use and psychiatric comorbidity.
doi:10.1007/s10194-012-0453-6
PMCID: PMC3381067  PMID: 22581187
Integrated care; Multidisciplinary modularized treatment program; Outcome study; Headache-related disability; Headache-related quality of life; Chronic headache
9.  Preliminary results of a withdrawal and detoxification therapeutic regimen in patients with probable chronic migraine and probable medication overuse headache 
The Journal of Headache and Pain  2005;6(4):334-337.
Chronic migraine (CM) is an invalidating condition affecting a significant population of headache sufferers, frequently associated with medication overuse headache (MOH). Controlled trials and guidelines for the treatment of MOH are currently not available. We studied the efficacy of a therapeutic regimen for the withdrawal of the overused drug and detoxification in a sample of patients suffering from probable CM and probable MOH during admission in eight hospitals of Piemonte–Liguria–Valle d’Aosta. Fifty patients, 42 females (84%) and 8 males (16%), mean age at observation 50.66±13.08 years, affected by probable CM and daily medication overuse following IHS diagnostic criteria were treated as inpatients or in a day hospital. Headache index (HI) and daily drug intake (DDI) were used for evaluating the severity of headache and medication overuse. The patients were treated by abrupt discontinuation of the overused drug and by a therapeutic protocol including i.v. hydration, dexamethasone, metoclopramide and benzodiazepines for 7–10 days. Prophylactic medication was started immediately after admission. Analgesics or triptans were used under medical control only in cases of severe rebound headache. Diagnostic protocol included routine blood tests (at admission and at discharge), dosage of B12 and folic acid. Patients underwent follow-up controls one, three and six months after discharge. The initial diagnosis was probable CM in almost all patients included in the study (41 patients); in nine patients the diagnosis was not specified (coded only as CDH). The overused medications were simple analgesics in 17 cases (34%), combination analgesics in 19 cases (38%), triptans alone or with analgesics in 13 cases (26%) and ergotamine in 2 cases (4%). We collected data from 39 patients at first follow–up (1 month), 32 after 3 months and 14 after 6 months. Mean HI was 0.91 at admission, 0.22 at discharge, 0.38 after 30 days, 0.46 after 3 months and 0.48 after 6 months. Mean DDI was 2.80 at admission, 0.39 at discharge, 0.41 after 1 month, 0.52 after 3 months and 0.59 after 6 months. These results are on average positive and tend to remain stable with time. Although preliminary and obtained on a limited number of patients at 6–month follow–up, our results seem to be encouraging about the use of the proposed therapeutic protocol.
doi:10.1007/s10194-005-0225-7
PMCID: PMC3452038  PMID: 16362704
Chronic daily headache; Chronic migraine; Medication overuse; Detoxification
10.  Medication overuse headache: a critical review of end points in recent follow-up studies 
The Journal of Headache and Pain  2010;11(5):373-377.
No guidelines for performing and presenting the results of studies on patients with medication overuse headache (MOH) exist. The aim of this study was to review long-term outcome measures in follow-up studies published in 2006 or later. We included MOH studies with >6 months duration presenting a minimum of one predefined end point. In total, nine studies were identified. The 1,589 MOH patients (22% men) had an overall mean frequency of 25.3 headache days/month at baseline. Headache days/month at the end of follow-up was reported in six studies (mean 13.8 days/month). The decrease was more pronounced for studies including patients with migraine only (−14.6 days/month) compared to studies with the original diagnoses of migraine and tension-type headache (−9.2 days/month). Six studies reported relapse rate (mean of 26%) and/or responder rate (mean of 28%). Medication days/month and change in headache index at the end of follow-up were reported in only one and two of nine studies, respectively. The present review demonstrated a lack of uniform end points used in recently published follow-up studies. Guidelines for presenting follow-up data on MOH are needed and we propose end points such as headache days/month, medication days/month, relapse rate and responder rate defined as ≥50% reduction of headache frequency and/or headache index from baseline.
doi:10.1007/s10194-010-0221-4
PMCID: PMC3452270  PMID: 20473701
Medication overuse headache; Follow-up; Outcome parameters; Relapse rate; Responders
11.  Botulinum toxin type-A in the prophylactic treatment of medication-overuse headache: a multicenter, double-blind, randomized, placebo-controlled, parallel group study 
The Journal of Headache and Pain  2011;12(4):427-433.
Medication-overuse headache (MOH) represents a severely disabling condition, with a low response to prophylactic treatments. Recently, consistent evidences have emerged in favor of botulinum toxin type-A (onabotulinum toxin A) as prophylactic treatment in chronic migraine. In a 12-week double-blind, parallel group, placebo-controlled study, we tested the efficacy and safety of onabotulinum toxin A as prophylactic treatment for MOH. A total of 68 patients were randomized (1:1) to onabotulinum toxin A (n = 33) or placebo (n = 35) treatment and received 16 intramuscular injections. The primary efficacy end point was mean change from baseline in the frequency of headache days for the 28-day period ending with week 12. No significant differences between onabotulinum toxin A and placebo treatment were detected in the primary (headache days) end point (12.0 vs. 15.9; p = 0.81). A significant reduction was recorded in the secondary end point, mean acute pain drug consumption at 12 weeks in onabotulinum toxin A-treated patients when compared with those with placebo (12.1 vs. 18.0; p = 0.03). When we considered the subgroup of patients with pericranial muscle tenderness, we recorded a significant improvement in those treated with onabotulinum toxin A compared to placebo treated in both primary (headache days) and secondary end points (acute pain drug consumption, days with drug consumption), as well as in pain intensity and disability measures (HIT-6 and MIDAS) at 12 weeks. Onabotulinum toxin A was safe and well tolerated, with few treatment-related adverse events. Few subjects discontinued due to adverse events. Our data identified the presence of pericranial muscle tenderness as predictor of response to onabotulinum toxin A in patients with complicated form of migraine such as MOH, the presence of pericranial muscle tenderness and support it as prophylactic treatment in these patients.
Electronic supplementary material
The online version of this article (doi:10.1007/s10194-011-0339-z) contains supplementary material, which is available to authorized users.
doi:10.1007/s10194-011-0339-z
PMCID: PMC3139089  PMID: 21499747
Botulinum toxin type-A; Medication-overuse headache; Prophylactic treatment; Migraine; Pericranial muscle tenderness
12.  Botulinum toxin type-A in the prophylactic treatment of medication-overuse headache: a multicenter, double-blind, randomized, placebo-controlled, parallel group study 
The Journal of Headache and Pain  2011;12(4):427-433.
Medication-overuse headache (MOH) represents a severely disabling condition, with a low response to prophylactic treatments. Recently, consistent evidences have emerged in favor of botulinum toxin type-A (onabotulinum toxin A) as prophylactic treatment in chronic migraine. In a 12-week double-blind, parallel group, placebo-controlled study, we tested the efficacy and safety of onabotulinum toxin A as prophylactic treatment for MOH. A total of 68 patients were randomized (1:1) to onabotulinum toxin A (n = 33) or placebo (n = 35) treatment and received 16 intramuscular injections. The primary efficacy end point was mean change from baseline in the frequency of headache days for the 28-day period ending with week 12. No significant differences between onabotulinum toxin A and placebo treatment were detected in the primary (headache days) end point (12.0 vs. 15.9; p = 0.81). A significant reduction was recorded in the secondary end point, mean acute pain drug consumption at 12 weeks in onabotulinum toxin A-treated patients when compared with those with placebo (12.1 vs. 18.0; p = 0.03). When we considered the subgroup of patients with pericranial muscle tenderness, we recorded a significant improvement in those treated with onabotulinum toxin A compared to placebo treated in both primary (headache days) and secondary end points (acute pain drug consumption, days with drug consumption), as well as in pain intensity and disability measures (HIT-6 and MIDAS) at 12 weeks. Onabotulinum toxin A was safe and well tolerated, with few treatment-related adverse events. Few subjects discontinued due to adverse events. Our data identified the presence of pericranial muscle tenderness as predictor of response to onabotulinum toxin A in patients with complicated form of migraine such as MOH, the presence of pericranial muscle tenderness and support it as prophylactic treatment in these patients.
Electronic supplementary material
The online version of this article (doi:10.1007/s10194-011-0339-z) contains supplementary material, which is available to authorized users.
doi:10.1007/s10194-011-0339-z
PMCID: PMC3139089  PMID: 21499747
Botulinum toxin type-A; Medication-overuse headache; Prophylactic treatment; Migraine; Pericranial muscle tenderness
13.  Cerebrovascular reactivity during the Valsalva maneuver in migraine, tension-type headache and medication overuse headache  
Functional Neurology  2012;26(4): 223 - 227 .
Summary
The aim of this study was to investigate, by means of transcranial Doppler ultrasound (TCD), cerebrovascular reactivity during the Valsalva maneuver (VM) during the headache-free interval in patients with migraine (M), migraine plus tension-type headache (M+TTH), and migraine plus medication overuse headache (M+MOH). A total of 114 patients (n=60 M, n=38 M+TTH, n=16 M+MOH) and n=60 controls were investigated; diagnoses were made according to the International Headache Society criteria. All subjects underwent TCD monitoring and, simultaneously, non-invasive assessment of arterial blood pressure and end-tidal CO 2 . Two indices were determined: the cerebrovascular Valsalva ratio (CVR) was calculated as the maximum end-diastolic flow velocity acceleration during the late straining phase of the VM [cm/s 2 ] and the centroperipheral Valsalva ratio (CPVR) was defined as the quotient of CVR to the concomitant arterial blood pressure acceleration [cm/mmHg × s].
The dynamic cerebrovascular autoregulatory response to the VM, measured as CVR, was increased in patients with M and M+TTH compared to age-matched healthy subjects. By contrast, CPVR (i.e. the quotient of the cerebrovascular to the peripheral autonomic response), was increased in M patients compared to healthy subjects and all other headache conditions tested.
Cerebrovascular autoregulatory response during the VM was increased in M patients compared to age-matched normal healthy subjects, indicating a disturbed autonomic control of cerebral vasoreactivity. The CPVR seems to be a sensitive parameter for distinguishing between M patients and M+TTH or M+MOH patients.
PMCID: PMC3814561  PMID: 22364943
cerebral autoregulation ;  cerebral vasoreactivity ;  migraine ;  transcranial Doppler ;  Valsalva maneuver
14.  Nosology and treatment of primary headache in a Swiss headache clinic 
The Journal of Headache and Pain  2005;6(3):121-127.
We assessed demographics, diagnoses, course, severity, impact and treatment of primary headache outpatients from records in the Headache and Pain Clinic, Neurological Department, Zürich University Hospital. All outpatients seen from 1996 to 1998 for migraine, tension–type headache, and both, were included. Diagnoses, drug, physical and alternative treatments before and after referral were listed. Descriptive statistics were used for differences between the general population and this sample, the diagnoses, and treatments. The coexistence of migraine and tension–type headache, and the high frequencies of headache days would have excluded most migraine patients from typical drug trials: at best, only one third were eligible. The socioeconomic impact of combined and difficult syndromes calls for comprehensive management beyond simple treatment with instant relief drugs. The diagnostic and therapeutic practices of referring physicians exposed a deficit of information on headache, and a need for relevant education.
doi:10.1007/s10194-005-0166-1
PMCID: PMC3451640  PMID: 16355292
Primary headache; Tertiary care; Demographics; Epidemiology; Drug treatment
15.  Psychopathology and quality of life burden in chronic daily headache: influence of migraine symptoms 
The Journal of Headache and Pain  2010;11(3):247-253.
The aim of this study is to compare the psychopathology and the quality of life of chronic daily headache patients between those with migraine headache and those with tension-type headache. We enrolled 106 adults with chronic daily headache (CDH) who consulted for the first time in specialised centres. The patients were classified according to the IHS 2004 criteria and the propositions of the Headache Classification Committee (2006) with a computed algorithm: 8 had chronic migraine (without medication overuse), 18 had chronic tension-type headache (without medication overuse), 80 had medication overuse headache and among them, 43 fulfilled the criteria for the sub-group of migraine (m) MOH, and 37 the subgroup for tension-type (tt) MOH. We tested five variables: MADRS global score, HAMA psychic and somatic sub-scales, SF-36 psychic, and somatic summary components. We compared patients with migraine symptoms (CM and mMOH) to those with tension-type symptoms (CTTH and ttMOH) and neutralised pain intensity with an ANCOVA which is a priori higher in the migraine group. We failed to find any difference between migraine and tension-type groups in the MADRS global score, the HAMA psychological sub-score and the SF36 physical component summary. The HAMA somatic anxiety subscale was higher in the migraine group than in the tension-type group (F(1,103) = 10.10, p = 0.001). The SF36 mental component summary was significantly worse in the migraine as compared with the tension-type subgroup (F(1,103) = 5.758, p = 0.018). In the four CDH subgroups, all the SF36 dimension scores except one (Physical Functioning) showed a more than 20 point difference from those seen in the adjusted historical controls. Furthermore, two sub-scores were significantly more affected in the migraine group as compared to the tension-type group, the physical health bodily pain (F(1,103) = 4.51, p = 0.036) and the mental health (F(1,103) = 8.17, p = 0.005). Considering that the statistic procedure neutralises the pain intensity factor, our data suggest a particular vulnerability to somatic symptoms and a special predisposition to develop negative pain affect in migraine patients in comparison to tension-type patients.
doi:10.1007/s10194-010-0208-1
PMCID: PMC3451907  PMID: 20383733
Psychopathology; Quality of life; Chronic daily headache; Migraine symptoms; Tension type headache symptoms
16.  Diagnosis and management of the primary headache disorders in the emergency department setting 
Headache continues to be a frequent cause of emergency department (ED) use, accounting for 2% of all visits. The majority of these headaches prove to be benign but painful exacerbations of chronic headache disorders, such as migraine, tension-type, and cluster. The goal of ED management is to provide rapid and quick relief of benign headache, without causing undue side effects, as well as recognizing headaches with malignant course. Though these headaches have distinct epidemiologies and clinical phenotypes, there is overlapping response to therapy: non-steroidals, triptans, dihydroergotamine, and the anti-emetic dopamine-antagonists may play a therapeutic role for each of these acute headaches. Because these headaches often recur over the days and months following ED discharge, the responsibility of the emergency physician includes identifying as yet unmet treatment needs and ensuring successful transition of care of these patients to an outpatient healthcare provider. Herein, we review the diagnostic criteria and management strategies for the primary headache disorders.
doi:10.1016/j.emc.2008.09.005
PMCID: PMC2676687  PMID: 19218020
headache; migraine; emergency department
17.  Economic impact of primary headaches in Turkey: a university hospital based study: part II 
This study was planned to investigate the economic impact of headache on Turkish headache sufferers attending a tertiary care outpatient headache clinic.
A total of 937 headache patients were included in this study and questioned using a questionnaire for the profile of patients and headache, quality of life of patients and economic impact of headache. The median total direct cost was found to be 88.0 USD and the median total cost was 160.7 USD. The drug treatment cost was the highest item followed by the specialist outpatient care cost. The average lost and inefficient work/school days was 1.5 (0–45) and 8.4 (0–100) days for one year.
It was shown that loss of productivity was higher for migraine without aura group when compared with the episodic and chronic tension–type headache groups. The results of this nationwide university hospital based study methshowed that headache, especially migraine, has considerable economic impact on patients.
doi:10.1007/s10194-006-0273-7
PMCID: PMC3451708  PMID: 16538424
Headache; Tensiontype headache; Migraine; Economic impact; Loss of work days
18.  Chronic migraine plus medication overuse headache: two entities or not? 
The Journal of Headache and Pain  2011;12(6):593-601.
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.
doi:10.1007/s10194-011-0388-3
PMCID: PMC3208042  PMID: 21938457
Chronic migraine; Refractory chronic migraine; Medication overuse headache; Detoxification; Rehabilitation; OnabotulinumtoxinA
19.  Chronic migraine plus medication overuse headache: two entities or not? 
The Journal of Headache and Pain  2011;12(6):593-601.
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.
doi:10.1007/s10194-011-0388-3
PMCID: PMC3208042  PMID: 21938457
Chronic migraine; Refractory chronic migraine; Medication overuse headache; Detoxification; Rehabilitation; OnabotulinumtoxinA
20.  Nabilone for the treatment of medication overuse headache: results of a preliminary double-blind, active-controlled, randomized trial 
The Journal of Headache and Pain  2012;13(8):677-684.
Medication overuse headache (MOH) is a severe burden to sufferers and its treatment has few evidence-based indications. The aim of this study is to evaluate efficacy and safety of nabilone in reducing pain and frequency of headache, the number of analgesic intake and in increasing the quality of life on patients with long-standing intractable MOH. Thirty MOH patients were enrolled at the University of Modena’s Interdepartmental Centre for Research on Headache and Drug Abuse (Italy) in a randomized, double-blind, active-controlled, crossover study comparing nabilone 0.5 mg/day and ibuprofen 400 mg. The patients received each treatment orally for 8 weeks (before nabilone and then ibuprofen or vice versa), with 1 week wash-out between them. Randomization and allocation (ratio 1:1) were carried out by an independent pharmacy through a central computer system. Participants, care givers, and those assessing the outcomes were blinded to treatment sequence. Twenty-six subjects completed the study. Improvements from baseline were observed with both treatments. However, nabilone was more effective than ibuprofen in reducing pain intensity and daily analgesic intake (p < 0.05); moreover, nabilone was the only drug able to reduce the level of medication dependence (−41 %, p < 0.01) and to improve the quality of life (p < 0.05). Side effects were uncommon, mild and disappeared when nabilone was discontinued. This is the first randomized controlled trial demonstrating the benefits of nabilone on headache, analgesic consumption and the quality of life in patients with intractable MOH. This drug also appears to be safe and well-tolerated. Larger scale studies are needed to confirm these preliminary findings.
doi:10.1007/s10194-012-0490-1
PMCID: PMC3484259  PMID: 23070400
Medication overuse headache (MOH); Treatment; Nabilone; Cannabinoid; Migraine
21.  Acupuncture for tension-type headache: a multicentre, sham-controlled, patient-and observer-blinded, randomised trial 
The Journal of Headache and Pain  2007;8(5):306-314.
Acupuncture treatment is frequently sought for tension-type headache (TTH), but there is conflicting evidence as to its effectiveness. This randomised, controlled, multicentre, patient-and observer-blinded trial was carried out in 122 outpatient practices in Germany on 409 patients with TTH, defined as ≥0 headache days per month of which ≤1 included migraine symptoms. Interventions were verum acupuncture according to the practice of traditional Chinese medicine or sham acupuncture consisting of superficial needling at nonacupuncture points. Acupuncture was administered by physicians with specialist acupuncture training. Ten 30-min sessions were given over a six-week period, with additional sessions available for partial response. Response was defined as >50% reduction in headache days/month at six months and no use of excluded concomitant medication or other therapies. In the intent-to-treat analysis (all 409 patients), 33% of verum patients and 27% of sham controls (p=0.18) were classed as responders. Verum was superior to sham for most secondary endpoints, including headache days (1.8 fewer; 95% CI 0.6, 3.0; p=0.004) and the International Headache Society response criterion (66% vs. 55% response, risk difference 12%, 95% CI: 2%-21%; p=0.024).). The relative risk on the primary and secondary response criterion was very similar (∼0.8); the difference in statistical significance may be due to differences in event rate. TTH improves after acupuncture treatment. However, the degree to which treatment benefits depend on psychological compared to physiological effects and the degree to which any physiological effects depend on needle placement and insertion depth are unclear.
doi:10.1007/s10194-007-0416-5
PMCID: PMC3476149  PMID: 17955168
Episodic tension-type headache; Chronic tension-type headache; Verum acupuncture; Sham acupuncture; Randomised controlled trial
22.  Headache: a ‘suitable case’ for behavioural treatment in primary care? 
Headache is a health problem with considerable impact at personal, social, and financial levels in terms of distress, disability, and cost. In the past, many studies have investigated the use of various behavioural treatment modalities for headache. Literature reviews consistently support the effectiveness of behavioural therapeutic approaches for the treatment of the most common primary headaches, namely migraine and tension-type headache. This article recommends that behavioural headache therapies should be developed, tested, and integrated into primary care practice, where most patients with headache are seen and treated. The large population seen in general practice, most of whom have uncomplicated primary headaches, could represent the ideal target for testing behavioural therapies.
PMCID: PMC2042573  PMID: 17359612
behaviour; headache; migraine; primary care; tensiontype headache; therapy
23.  Tricyclic antidepressants and headaches: systematic review and meta-analysis 
Objective To evaluate the efficacy and relative adverse effects of tricyclic antidepressants in the treatment of migraine, tension-type, and mixed headaches.
Design Meta-analysis.
Data sources Medline, Embase, the Cochrane Trials Registry, and PsycLIT.
Studies reviewed Randomised trials of adults receiving tricyclics as only treatment for a minimum of four weeks.
Data extraction Frequency of headaches (number of headache attacks for migraine and number of days with headache for tension-type headaches), intensity of headache, and headache index.
Results 37 studies met the inclusion criteria. Tricyclics significantly reduced the number of days with tension-type headache and number of headache attacks from migraine than placebo (average standardised mean difference −1.29, 95% confidence interval −2.18 to −0.39 and −0.70, −0.93 to −0.48) but not compared with selective serotonin reuptake inhibitors (−0.80, −2.63 to 0.02 and −0.20, −0.60 to 0.19). The effect of tricyclics increased with longer duration of treatment (β=−0.11, 95% confidence interval −0.63 to −0.15; P<0.0005). Tricyclics were also more likely to reduce the intensity of headaches by at least 50% than either placebo (tension-type: relative risk 1.41, 95% confidence interval 1.02 to 1.89; migraine: 1.80, 1.24 to 2.62) or selective serotonin reuptake inhibitors (1.73, 1.34 to 2.22 and 1.72, 1.15 to 2.55). Tricyclics were more likely to cause adverse effects than placebo (1.53, 95% confidence interval 1.11 to 2.12) and selective serotonin reuptake inhibitors (2.22, 1.52 to 3.32), including dry mouth (P<0.0005 for both), drowsiness (P<0.0005 for both), and weight gain (P<0.001 for both), but did not increase dropout rates (placebo: 1.22, 0.83 to 1.80, selective serotonin reuptake inhibitors: 1.16, 0.81 to 2.97).
Conclusions Tricyclic antidepressants are effective in preventing migraine and tension-type headaches and are more effective than selective serotonin reuptake inhibitors, although with greater adverse effects. The effectiveness of tricyclics seems to increase over time.
doi:10.1136/bmj.c5222
PMCID: PMC2958257  PMID: 20961988
24.  Basal cutaneous pain threshold in headache patients 
The Journal of Headache and Pain  2011;12-12(3):303-310.
The aim of this study was to analyze cutaneous pain threshold (CPT) during the interictal phase in headache patients, and the relationships between headache frequency and analgesic use. A consecutive series of 98 headache patients and 26 sex- and age-balanced controls were evaluated. Acute allodynia (AA) was assessed by Jakubowski questionnaire, and interictal allodynia (IA) by a skin test with calibrated monofilaments. AA is widely known as a symptom more present in migraine than in TTH spectrum: in our study this was confirmed only in cases of episodic attacks. When headache index rises towards chronicization, the prevalence of AA increases in both headache spectrums (χ2 13.55; p < 0.01). AA was associated with IA only in cases of chronic headache. When headache becomes chronic, mostly in presence of medication overuse, interictal CPT decreases and IA prevalence increases (χ2 20.44; p < 0.01), with closer association than AA. In MOH patients there were no significant differences depending on the diagnosis of starting headache (migraine or tension type headache) and, in both groups, we found the overuse of analgesics plays an important role: intake of more than one daily drug dramatically reduces the CPT (p < 0.05). Thus, when acute allodynia increases frequency, worsens or appears for the first time in patients with a long-standing history of chronic headache, it could reasonably suggest that the reduction of CPT had started, without using a specific practical skin test but simply by questioning clinical headache history. In conclusion, these results indicate that the role of medication overuse is more important than chronicization in lowering CPT, and suggest that prolonged periods of medication overuse can interfere with pain perception by a reduction of the pain threshold that facilitates the onset of every new attack leading to chronicization.
doi:10.1007/s10194-011-0313-9
PMCID: PMC3094665  PMID: 21336562
Headache; Pain threshold; Allodynia; Central sensitization; Medicine overuse
25.  Basal cutaneous pain threshold in headache patients 
The Journal of Headache and Pain  2011;12(3):303-310.
The aim of this study was to analyze cutaneous pain threshold (CPT) during the interictal phase in headache patients, and the relationships between headache frequency and analgesic use. A consecutive series of 98 headache patients and 26 sex- and age-balanced controls were evaluated. Acute allodynia (AA) was assessed by Jakubowski questionnaire, and interictal allodynia (IA) by a skin test with calibrated monofilaments. AA is widely known as a symptom more present in migraine than in TTH spectrum: in our study this was confirmed only in cases of episodic attacks. When headache index rises towards chronicization, the prevalence of AA increases in both headache spectrums (χ2 13.55; p < 0.01). AA was associated with IA only in cases of chronic headache. When headache becomes chronic, mostly in presence of medication overuse, interictal CPT decreases and IA prevalence increases (χ2 20.44; p < 0.01), with closer association than AA. In MOH patients there were no significant differences depending on the diagnosis of starting headache (migraine or tension type headache) and, in both groups, we found the overuse of analgesics plays an important role: intake of more than one daily drug dramatically reduces the CPT (p < 0.05). Thus, when acute allodynia increases frequency, worsens or appears for the first time in patients with a long-standing history of chronic headache, it could reasonably suggest that the reduction of CPT had started, without using a specific practical skin test but simply by questioning clinical headache history. In conclusion, these results indicate that the role of medication overuse is more important than chronicization in lowering CPT, and suggest that prolonged periods of medication overuse can interfere with pain perception by a reduction of the pain threshold that facilitates the onset of every new attack leading to chronicization.
doi:10.1007/s10194-011-0313-9
PMCID: PMC3094665  PMID: 21336562
Headache; Pain threshold; Allodynia; Central sensitization; Medicine overuse

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