Headache Reduction Research Articles

Using Peripheral Stimulation to Reduce the Pain of C2-Mediated Occipital Headaches: A Preliminary Report

Peripheral nerve stimulation (PNS) is an accepted treatment for neuropathic pain. Recent studies have focused on its potential for relieving headache pain. To investigate the effectiveness of PNS in reducing occipital headache pain. A prospective, 12-week pilot study involving 11 patients evaluated before and after implantation of PNS systems to treat C2-mediated occipital headaches. Prior to and at 4 and 12 weeks after implantation, patients completed the Short-Form McGill Pain Questionnaire (SF-MPQ), Visual Analog Scale (VAS), and Present Pain Index (PPI). Patients also answered questionnaires and kept diaries to record stimulator use, medication consumption, and numbers of headaches. A comparison of pre- and post-implantation evaluations showed statistically significant declines in scores on the SF-MPQ (64%; p = 0.0013), VAS (67%; p < 0.0001), and PPI (68%; p = 0.0009). Most patients (91% and 64% respectively) reported reductions in medication use and numbers of headaches. Patients also reported a reduction in headache symptoms and the impact of headaches on activities. Two adverse events were encountered, one due to a loose connection and, the other caused by lead migration. PNS reduced headache pain, headache frequency and medication use.

Clinical stability of Fabry disease in 54 months’ enzyme replacement therapy – follow-up of the first Polish study

We present outcomes of 54 months' agalsidase beta enzyme replacement therapy of two 48- and 46-year-old brothers with Fabry disease. The diagnosis was confirmed in 1997, and at that moment serious damage of internal organs was observed. During enzyme replacement therapy in both brothers the following changes were observed: amelioration of gastrointestinal symptoms, gain of body weight and reduction of cardiac hypertrophy in ECG. In older brother we observed: improvement in coronary blood flow, absence of angina pectoris, dyspnea, partial remission of headache and acroparaesthesia. Reduction of proteinuria, stabilization of creatinine clearance and appearance of perspiration were also noticed. In a younger brother, with a milder form of disease, we observed: improvement of hearing and vertigo, headache reduction, as well as stabilization of kidney function (although proteinuria was slightly increased). Unfortunately, acroparaesthesia and muscle pains in the legs became more severe. Enzyme replacement therapy in Fabry disease, even started in late adulthood, is effective by stabilizing organ function and markedly improving of quality of life.

Pseudoangiitis bei beidseitiger okulärer Ischämie

The term 'frosted branch angiitis' was initially used to describe an idiopathic form of vasculitis in association with panuveitis. It has since also been used to describe the angiographic phenomenon of diffuse leakage along retinal vessels against the background of other ocular and systemic diseases. We describe a 57-year-old male patient with acute bilateral reduction of visual acuity, headaches and absence of any pulse at the temporal arteries. Fluorescence angiography showed bilateral diffuse leakage along all the retinal vessels, which resembled frosted branches. Laboratory parameters and histology were not indicative of vasculitis. Imaging showed complete occlusion of both common carotid arteries and a hypoplastic vertebral artery on the left. Ocular ischemia may imitate primarily inflammatory conditions in its angiographic appearance.

Headaches and Oral Contraceptives: Impact of Eliminating the Standard 7‐Day Placebo Interval

The aim was to assess the timing and severity of self-reported headaches in patients utilizing a standard 28-day oral contraceptive (OC) cycle consisting of 21 hormone (estrogen + progestin)-containing pills and 7 placebo pills (ie, 21/7-day cycle) converted to a placebo-free extended OC regimen. An open label single-center prospective analysis of headaches recorded daily on a severity scale of 0 to 10, along with the headache item of the Penn Daily Symptom Rating (DSR17) and a weekly modified Migraine Disability Assessment (MIDAS) headache questionnaire, during standard 21/7-day cycles followed by a 168-day extended placebo-free regimen of an OC containing 3 mg of drosperinone and 30 mcg of ethinyl estradiol (DRSP/EE). Of the 114 patients who began the trial, 111 completed the 21/7-day cycle portion of the study. Based on the headaches scales, there were significant differences in headache severity among the 28 days of the standard 21/7 cycles (P < .001). Greater headache severity occurred on days 25 through 28 during the 7-day placebo interval of the 21/7 cycles (P < .05). Of the 111 patients who completed the 21/7 phase of the study, 102 (92%) completed the 168-day extended placebo-free OC regimen. During the first 28 days of the extended placebo-free regimen, daily headache scores decreased (P < .0001) compared to those of the previous 21 active/7 placebo day cycle. The difference on a daily basis was first detected on extended cycle days 25 through 28 (P < .0001) and persisted throughout the remainder of the 168-day regimen. Subjects were divided into 2 groups (severe and mild) based on the median of the total headache score during the 21/7 OC cycle. The group with higher total headache scores demonstrated a significant (P < .0001) reduction in daily headaches beginning in the first 28-day interval of the extended placebo-free regimen, persisting throughout the entire 168-day extended regimen. In contrast, the group with the lower total headache score remained unchanged (P= .79) throughout the extended regimen. Impact of headaches on work, family, and social functions also improved on the extended placebo-free regimen in 6 of 8 measures (P < .05) assessed by weekly headache questionnaires. Compared to a 21/7-day OC regimen, a 168-day extended placebo-free regimen of DRSP/EE led to a decrease in headache severity along with improvement in work productivity and involvement in activities. This is a preliminary study and results may not be widely generalizable.

Headache in patients with cervical radiculopathy: a prospective study with selective nerve root blocks in 275 patients.

Since many years we routinely use diagnostic selective nerve root blocks (SNRB) at our department when evaluating patients with cervical radiculopathy. Frequently patients who also presented with headache reported that the headache disappeared when the nerve root responsible for the radicular pain was blocked with local anaesthetics. Headache has been described as a companioning symptom related to cervical radiculopathy but has never before been evaluated with SNRB performed in the lower cervical spine. For this reason we added to our routine an evaluation of the response from the SNRB on headache in patients with cervical radiculopathy. The aim was to describe the frequency of headache in patients with cervical radiculopathy and its response to a selective nerve root block of the nerve root/roots responsible for the radiculopathy. Can nerve root compression in the lower cervical spine produce headache? In this consecutive series of 275 patients with cervical radiculopathy, 161 patients reported that they also suffered from daily or recurrent headache located most often unilaterally on the same side as the radiculopathy. All patients underwent a careful clinical examination by a neurosurgeon and a MRI of the cervical spine. The significantly compressed root/roots, according to the MRI, underwent SNRB with a local anaesthetic. The effect of the nerve root block on the radiculopathy and the headache was carefully noted and evaluated by a physiotherapist using visual analogue scales (VAS) before and after the SNRB. All patients with headache had tender points in the neck/shoulder region on the affected side. Patients with headache graded significantly more limitations in daily activities and higher pain intensity in the neck/shoulder/arm than patients without headache. After selective nerve root block, 59% of the patients with headache reported 50% or more reduction of headache and of these 69% reported total relief. A significant correlation was seen between reduced headache intensity and reduced pain in the neck, shoulder and arm. The result indicates that cervical root compression from degenerative disease in the lower cervical spine producing radiculopathy might also induce headache.

Psychological Treatment of Recurrent Headache in Children and Adolescents - A Meta-Analysis

Psychologically based interventions such as relaxation training, biofeedback and cognitive-behavioural therapy are increasingly discussed as options for the treatment of migraine and tension-type headache in children and adolescents. In order to determine the state of evidence regarding the efficacy of these treatments, a meta-analysis of randomized controlled studies was conducted. In a comprehensive literature search including data from 1966 to 2004, 23 studies were found meeting the inclusion criteria. Due to the application of the random effects model, generalization of the results is possible. Specific statistical procedures were used to account for a possible publication bias. Significantly more patients improved to a clinically relevant extent (headache reduction > or =50%) in treatment conditions compared with waiting list conditions (high effect sizes). Long-term stability was also confirmed. The analysed treatments lead to improvement (up to 1 year) in headache status in children and adolescents with primary headache. However, more well-designed studies are needed to support and consolidate the conclusions of this meta-analysis and to compare the effects of psychological treatment with those of prophylactic medical interventions (in migraine), to examine potential differences between treatments, to identify moderators of efficacy and to determine effects of treatment on other health-related variables such as quality of life.

Mapping Pain Generators for Surgical Treatment of Migraine Headaches

Mapping Pain Generators for Surgical Treatment of Migraine Headaches

Zonisamide Prophylaxis in Refractory Pediatric Headache

Currently, no medications are approved for pediatric headache prophylaxis in the United States. Zonisamide is an antiepileptic drug with preliminary studies suggesting some efficacy in the adult headache population. A retrospective chart review was conducted on refractory headache patients in our multidisciplinary Headache Clinic who were treated with zonisamide, an antiepileptic drug, for headache prophylaxis. Records were reviewed for pertinent data including patient history, diagnosis, prior treatment regimens, and zonisamide response, along with headache frequency. Twelve patients were identified (8 girls); mean age was 13.5 years. Eight of the 12 patients had a positive response to zonisamide with greater than 50% reduction in headaches from pretreatment values. Zonisamide had some efficacy in headache reduction. It was well tolerated with only minor side effects. Further prospective studies with zonisamide are warranted in refractory pediatric headache patients.

Pain Characteristics of the Acute Migraine Attack

This study describes the pain characteristics of the acute migraine attack, including time of onset, time to peak, duration, intensity, quality, aggravation by activity, as well as recurrence frequency and time to recurrence, in a tertiary care practice. The literature documenting the characteristics of the pain of the acute attack of migraine is sparse. A total of 1,283 migraine patients (ICHD 1.1, 1.2, 1.5.1, and ICHD 1.6 [total migraine population]) were evaluated at first visit. Headache character (throbbing, aching, pressure, stabbing scaled grade 0 to 3; 0 = none; 1 = mild; 2 = moderate; 3 = severe), intensity (for average, minimum, and maximum intensity headaches, scaled 0 to 10), lifetime duration, frequency per month, duration in minutes (for average, minimum, maximum duration headaches), time of onset of headache (morning, afternoon, evening, night, anytime), aggravation of headache with activity (scaled 0 to 3), percentage recurrence, time to recurrence, were recorded. Patients were stratified into different groups; ICHD 1.1, 1.2, and 1.5.1 (migraine) ICHD 1.1 and 1.2 (episodic migraine), ICHD 1.5.1 (chronic migraine), and ICHD 1.6 (probable migraine). Patients with unremitting daily headache were excluded. A total of 84.3% patients were female, and the mean age was 37.7, ranging from 13.0 to 80.5 years. Eight hundred seventy-four patients were classified as ICHD 1.1, 1.2, and 1.5.1 (migraine), 524 with ICHD 1.1 and 1.2 (episodic migraine), 350 with ICHD 1.5.1 (chronic migraine), and 409 with ICHD 1.6 (probable migraine). Time of onset of headache was mostly in the morning in 18.7%, afternoon 13.5%, evening 4.0%, during night 9.4%, and "anytime" 54.3%, with minor differences seen in different headache types, gender, presence of aura, and headache frequency. The median time to peak of the headache was greater in migraine than probable migraine (90 minutes vs. 60 minutes; P < .01). Headache duration medians were reported as minimum of 12 hours, maximum of 48 hours with an average of 24 hours, females being greater than males in average headache (24.0 vs. 12.0; P < .01), minimum (24.0 vs. 8; P < .05), and maximum (48.0 vs. 24.0; P < .01). Only the minimum duration differed between migraine and atypical migraine (12.0 vs. 4.0; P < .01). Headache intensity medians were as follows: average intensity 7/10, minimum 4/10, and maximum 10/10, with no differences in migraine versus probable migraine, gender, or headache frequency. Headache intensity median was consistently greater in migraine episodic than chronic migraine (average 8.0 vs. 6.5, minimum 4.5 vs. 3.0, maximum 10.0 vs. 9.0, all P < .05). Headache character (greater than grade 1) was throbbing (73.5%), aching (73.8%), pressure (75.4%), and stabbing (42.6%) with significantly more throbbing in migraine than in probable migraine (73.5% vs. 63.2%; P < .01) and more aching in chronic than in episodic migraine (65.4% vs. 63.1%; P < .05). Headache increased by activity was present in 90.2% of patients, grade 1 in 13.8%, grade 2 in 30.8%, and grade 3 in 45.5% of patients. The presence of activity aggravating headache was more likely to be associated with headache triggers, maximum headache severity, longer time to 50% reduction of headache, and longer time to absent headache with triptans, and more headache-associated symptoms, and longer postdrome duration (all P < .05). Recurrence rate was 43.8% with the median time to recurrence being 8 hours. Significantly less recurrence occurred with episodic than chronic migraine (30.0% vs. 50.0%; P < .01). This study provides an in-depth description of pain features in the acute migraine attack. It was found that a significant number of patients need to be provided with the means of treating headache rapidly in at least some of their headaches and that headache recurrence needs to be addressed in a large number of patients.

The Effect of Paroxetine on the Reduction of Migraine Frequency is Independent of Its Anxiolytic Effect

Background and purposeAnxiety is the most important precipitating factor of migraine attacks, and more than half of migraineurs have coexisting anxiety disorders. Paroxetine, an antidepressant, is one of the selective serotonin reuptake inhibitors (SSRIs) that has an anxiolytic effect, and is also known to be effective for migraine prophylaxis. The aim of this study was to determine the role of the anxiolytic effect of paroxetine on the prevention of migraine.MethodsThis study investigated migraineurs with a general anxiety disorder who visited the neurological clinic. The following efficacy variables were assessed at baseline and after taking paroxetine (20 for 12 weeks: headache frequency, Hamilton Anxiety Rating Scale (HAM-A), Headache Management Self-Efficacy Scale (HMSE), and Headache Disability Inventory (HDI). The correlation between the headache responsiveness to paroxetine and improvement in anxiety levels was analyzed.ResultsTwenty-four patients (aged 54.96±12.09 years, mean±SD) were included in this study. Paroxetine reduced headache frequency by 49.1% within 12 weeks (p<0.05 vs baseline). HAM-A and HMSE scores also showed an improvement, whereas there was no significant change in HDI score. The baseline HAM-A scores did not differ between paroxetine responders and nonresponders. In addition, the improvement in HAM-A score was not correlated with the reduction in headache frequency.ConclusionsParoxetine decreased the headache frequency and reduced anxiety levels. However, the anxiolytic effect of paroxetine was not correlated with the migraine prevention effect. These observation indicate that the anxiolytic effect of paroxetine does not contribute strongly to its prophylactic effect on migraine frequency in migraineurs with anxiety disorder.

Medication-Overuse Headache in Children: Is Initial Preventive Therapy Necessary?

Chronic daily headaches can be a difficult problem in children as well as adults. Over half of the cases of chronic daily headaches in adults are thought to be due to medication-overuse headache, and treatment consists of discontinuation of these analgesics. Since many patients are also treated with preventive agents at the time of analgesic withdrawal, it is difficult to determine whether discontinuation alone is the most effective treatment. A retrospective study was performed to evaluate the outcomes of 43 children (ages 6-17 years) with medication-overuse headache 1 month after withdrawal of analgesics: 20 children received daily doses of a preventive medication, and 23 received no preventive medication. Headache reduction was assessed 1 month later. There was no difference in the percentage, with 90% or greater headache reduction at 1 month between children treated by withdrawal of analgesic drugs only and those receiving preventive medications (57% vs 50%, respectively). There was no influence of age, gender, use of triptans as rescue agents, or caffeine use on outcomes. A previous duration of headaches over 2 years was negatively correlated with overall outcome. We advise discontinuation of analgesics in all children with medication-overuse headache, without the necessity for starting daily preventive agents concurrently. Should headaches persist after 1 month, such agents can be added. (J Child Neurol 2006;21:45-48).

CPD: The patient with daily headaches.

The term daily (CDH) describes a variety of headache types, of which chronic migraine is the most common. Daily headaches often are disabling and may be challenging to diagnose and treat. Medication overuse, or drug rebound headache, is the most treatable cause of refractory daily headache. A pathologic underlying cause should be considered in patients with recent-onset daily headache, a change from a previous headache pattern, or associated neurological or systemic symptoms. Treatment of CDH focuses on reduction of headache triggers and use of preventive medication, most commonly antidepressants, antiepileptic drugs, and beta blockers. Medication overuse must be treatedwith discontinuation of symptomatic medicines, a transitional therapy, and long-term prophylaxis. Anxiety and depression are common in patients with CDH and should be identified and treated. Although the condition is challenging, appropriate treatment of patients with CDH can bring about significant improvement in the patient's quality-of-life. For full text, click here: SA Fam Pract 2005;47(10).

The Patient with Daily Headaches

The term “chronic daily headache” (CDH) describes a variety of headache types, of which chronic migraine is the most common. Daily headaches often are disabling and may be challenging to diagnose and treat. Medication overuse, or drug rebound headache, is the most treatable cause of refractory daily headache. A pathologic underlying cause should be considered in patients with recent-onset daily headache, a change from a previous headache pattern, or associated neurological or systemic symptoms. Treatment of CDH focuses on reduction of headache triggers and use of preventive medication, most commonly antidepressants, antiepileptic drugs, and beta blockers. Medication overuse must be treated with discontinuation of symptomatic medicines, a transitional therapy, and long-term prophylaxis. Anxiety and depression are common in patients with CDH and should be identified and treated. Although the condition is challenging, appropriate treatment of patients with CDH can bring about significant improvement in the patient's quality-of-life.

Mini-gauge epidural needles and catheters for labour analgesia

INTRODUCTION: Needle redesign revolutionized spinal anesthesia by producing large reductions in postdural puncture headache (PDPH). Epidural needles now represent the leading cause of severe PDPH after regional anesthesia. Further success in prevention is most likely to come from use of smaller gauge epidural needles. 20g epidural steroid injection has a reported PDPH incidence of 9.8% (1)compared with > 70% with larger needles. 20g epidural needles produce a 4-5 fold reduction in CSF leak compared with current needles following puncture(2) and clinical work suggests that blood patch is more successful for smaller gauge punctures (3). This trial examined the feasibility of using mini-gauge Tuohy needles and catheters for continuous epidural labour analgesia.

Predictors of Responsiveness to Physiotherapy Management of Cervicogenic Headache

A recent randomized controlled trial tested the effectiveness of therapeutic exercise and manipulative therapy on 200 subjects with cervicogenic headache. Although treatments were efficacious, 25% of patients did not achieve a clinically acceptable outcome--50% reduction in headache frequency. This study aimed to identify predictors from variables in subjects' demographics and headache history which might identify those who did or did not achieve a 50-79% or 80-100% reduction in headache immediately after the active treatments and 12 months postintervention. The results revealed no consistent pattern of predictors, although the absence of light-headedness indicated higher odds of achieving either a 50-79% [odds ratio (OR) = 5.45) or 80-100% (OR = 5.7) reduction in headache frequency in the long term. Headaches of at least moderate intensity, the patient's age and chronicity of headache did not mitigate against a successful outcome from physiotherapy intervention.

Treatment of Large and Giant Intracranial Aneurysms with Onyx. Preliminary Findings

Large and giant aneurysms account for three to seven per cent of intracranial aneurysms. They are mainly located in the carotid siphon or vertebrobasilar junction and usually give rise to mass effect, headache, haemorrhage or ischaemia. Treatment consists of surgical clipping or endovascular embolization and aims to exclude the aneurysm from the cerebral circulation to prevent haemorrhage. We describe our preliminary clinical and angiographic findings after endovascular embolization of large and giant intracranial aneurysms using Onyx and the remodelling technique. Six patients with large or giant intracranial aneurysms were treated. The maximum diameter of the aneurysmal sac varied from 15 to 33 mm, the neck measured from 5 to 10 mm and the sac-neck ratio varied from 2.14 a 4.7. Treatment (planned sessions in five patients and one in emergency) was performed in the angiography suite after detailed angiographic diagnosis including 3D formatting of the area of interest. Informed consent was obtained from the patients and their relatives. Intracranial compensation was tested angiographically and clinically before treatment. The polymer (Onyx HD 500 – 20% EVOH; 80% DMSO) was selectively injected into the lumen of the aneurysmal sac during balloon catheter occlusion of the aneurysm neck and parent vessel. Clinical and angiographic follow-up varied from three to 12 months and all patients were assessed angiographically 12 months after treatment. Complete occlusion was achieved after treatment in two aneurysms, both treated by Onyx alone. Occlusion was between 95 and 100% in two patients (one treated with Onyx alone, the other with GDCs + Onyx). Occlusion was more than 90% and less than 95% in one patient (GDCs + Onyx). Occlusion was less than 90% in the remaining patient treated with GDC + Onyx. In the four aneurysms not completely occluded, the residual part involved the neck region. Only one complication arose during treatment consisting of controlateral hemiparesis at the site of the aneurysm due to thrombus occlusion of the middle cerebral artery trifurcation, with full recovery of neurological deficit a month after treatment. Angiographic follow-up disclosed findings the same as those at the end of treatment in three patients whereas the residual aneurysm had increased by 5% in one patient. Two giant aneurysms showed a major recanalization of the aneurysmal sac. At clinical follow-up three patients reported a progressive reduction of ocular symptoms caused by compression: symptoms had slightly improved in one patient after treatment and in the remaining two with aneurysm recanalization diplopia and palpebral ptosis remained unchanged. All patients treated reported a mild progressive reduction of headache except for the patient presenting recanalization at follow-up after ten months. No major complications were found at follow-up. We plan to reserve this procedure for selected cases of large aneurysms not amenable to other treatments. Embolization should always be undertaken by physicians skilled in the remodelling technique and complete embolization of the aneurysm is crucial. The availability of new materials, easier to handle and more viscous and adhesive than Onyx, will simplify the procedure and prevent aneurysm recanalization.

Comprehensive Surgical Treatment of Migraine Headaches

The purpose of this study was to investigate the efficacy of surgical deactivation of migraine headache trigger sites. Of 125 patients diagnosed with migraine headaches, 100 were randomly assigned to the treatment group and 25 served as controls, with 4:1 allocation. Patients in the treatment group were injected with botulinum toxin A for identification of trigger sites. Eighty-nine patients who noted improvement in their migraine headaches for 4 weeks underwent surgery. Eighty-two of the 89 patients (92 percent) in the treatment group who completed the study demonstrated at least 50 percent reduction in migraine headache frequency, duration, or intensity compared with the baseline data; 31 (35 percent) reported elimination and 51 (57 percent) experienced improvement over a mean follow-up period of 396 days. In comparison, three of 19 control patients (15.8 percent) recorded reduction in migraine headaches during the 1-year follow-up (p < 0.001), and no patients observed elimination. All variables for the treatment group improved significantly when compared with the baseline data and the control group, including the Migraine-Specific Questionnaire, the Migraine Disability Assessment score, and the Short Form-36 Health Survey. The mean annualized cost of migraine care for the treatment group (925 dollars) was reduced significantly compared with the baseline expense (7612 dollars) and the control group (5530 dollars) (p < 0.001). The mean monthly number of days lost from work for the treatment group (1.2) was reduced significantly compared with the baseline data (4.41) and the control group (4.4) (p = 0.003). The common adverse effects related to injection of botulinum toxin A included discomfort at the injection site in 27 patients after 227 injections (12 percent), temple hollowing in 19 of 82 patients (23 percent), neck weakness in 15 of 55 patients (27 percent), and eyelid ptosis in nine patients (10 percent). The common complications of surgical treatment were temporary dryness of the nose in 12 of 62 patients who underwent septum and turbinate surgery (19.4 percent), rhinorrhea in 11 (17.7 percent), intense scalp itching in seven of 80 patients who underwent forehead surgery (8.8 percent), and minor hair loss in five (6.3 percent). Surgical deactivation of migraine trigger sites can eliminate or significantly reduce migraine symptoms. Additional studies are necessary to clarify the mechanism of action and to determine the long-term results.

The Effect of Propranolol on Glyceryltrinitrate-Induced Headache and Arterial Response

Prophylactic drug trials in migraine are long-lasting and expensive and require long-term toxicology information. A human migraine model would therefore be helpful in testing new drugs. Immediate headache and delayed migraine after glyceryltrinitrate (GTN) has been well characterized. We have recently shown that sodium valproate has prophylactic effect in the GTN model. Here we report our experience with propranolol in this model. Nineteen subjects with migraine without aura and 16 sex- and aged-matched healthy subjects were included in a two-centre randomized double-blind cross-over study. Fourteen migraine subjects and 14 healthy subjects completed the study and results from comparison of the 28 subjects are reported. Randomly propranolol 160 mg or placebo were each given daily for 14 days to both migraine and healthy subjects. A 20-min intravenous infusion of GTN 0.25 microg/kg per min was administered on a study day at the end of both pretreatment periods. Headache was registered for 12 h after GTN infusions. Its intensity was scored on a numerical verbal rating scale from 0 to 10. Fulfilment of International Headache Society (HIS) criteria was recorded for 24 h. Radial and superficial temporal artery diameters and blood velocity of both middle cerebral arteries were measured. All migraine subjects developed headache after GTN. No reduction of overall peak headache was found after propranolol (median 5, range 0-7) compared with placebo (median 5, range 0-10) (P = 0.441). Eight of the 14 completing migraine subject developed IHS 1.1 migraine after GTN, two subjects on both days, three subjects only after placebo, and three subjects only after propranolol. No reduction of GTN-induced migraine was found after propranolol compared with placebo (5 vs. 5, P = 1.000). All healthy subjects developed headache after GTN. No reduction of overall peak headache was found after propranolol (median 2, range 1-5) compared with placebo (median 1, range 1-7) (P = 0.315). Two subjects fulfilled IHS criteria 1.1 for migraine without aura after propranolol but not after placebo. The fulfilment was short lasting and did not require rescue medication. Headache after GTN was more pronounced in migraine subjects than in healthy subjects both with (P = 0.003) and without pretreatment with propranolol (P = 0.017). We found that 2 weeks of propranolol constricted the radial artery in healthy subjects but not in migraine subjects. GTN-induced vasodilatation abolished this difference. Mean maximum blood flow velocity in the middle cerebral artery was higher in healthy subjects than in migraine patients (P = 0.003-0.033) and unaffected by propranolol. We observed no effect of propranolol on GTN-induced headache and migraine. This could indicate that GTN induces migraine at a deeper level of the pathophysiological cascade of migraine than the prophylactic effect of propranolol. Propranolol does not constrict cerebral arteries, which therefore cannot be part of its mechanism of action in migraine.

Behavioral interventions for tension-type headache: Overview of current therapies and recommendation for a self-management model for chronic headache

Behavioral treatments (relaxation, biofeedback, cognitive-behavioral therapy) have been empirically validated for migraine and tension-type headaches, with recent meta-analyses yielding 37% to 50% reductions in tension-type headache, comparing favorably with 33% reduction from medication prophylaxis (amitriptyline). Research has moved toward increasing availability and cost effectiveness through alternative delivery formats and combining and comparing them with standard medications. Further modifications would make standard behavioral treatments available and conducive to primary care settings where most patients receive treatment. Beyond the current behavioral and drug treatments, we propose a fundamental shift in conceptualization and treatment for headache.

TENSION‐TYPE HEADACHE

The tricyclic antidepressant amitriptyline is the only documented and most widely used prophylactic drug for chronic tension‐type headache (CTTH). However, it is not fully clarified whether the serotonin (5‐HT) reuptake inhibition plays a major role for the analgesic effect of amitriptyline. To explore the importance of 5‐HT reuptake inhibition for mechanism of action of the analgesic effect of amitriptyline, we investigated platelet 5‐HT levels during preventive treatment of CTTH with amitriptyline, the selective serotonin reuptake inhibitor citalopram, and placebo. Thirty‐four patients with CTTH were given preventive treatment with amitriptyline 75 mg/day, the selective 5‐HT reuptake inhibitor citalopram 20 mg/day, and placebo in a 32‐week, double‐blind, placebo‐controlled, three‐way crossover trial. Blood samples were collected in the last week of each treatment period. Platelet 5‐HT was used as a measure of 5‐HT reuptake inhibition and determined by high performance liquid chromatography. The area under the headache curve was 308 (157‐715) (median with quartiles in parentheses) with amitriptyline, and significantly lower than 377 (158‐1121) with citalopram (P= 0.04), and 441 (178‐1408) with placebo (P= 0.002). There was no difference between citalopram and placebo (P= 0.23). Platelet 5‐HT was 0.4 (0.3‐0.7) × 10−18 mol/platelet with citalopram, which was significantly lower than 1.7 (1.2‐2.4) × 10‐18 mol/platelet with amitriptyline (P &lt; 0.001), and 3.5 (2.8‐4.3) × 10‐18 mol/platelet with placebo (P &lt; 0.001). The lower platelet 5‐HT during treatment with citalopram than amitriptyline indicates that 5‐HT reuptake was most effectively inhibited by citalopram. In contrast, amitriptyline was most effective in reduction of headache. This suggests that the analgesic effect of amitriptyline in CTTH is not solely due to 5‐HT reuptake inhibition and that other mechanisms such as norepinephrine reuptake inhibition, NMDA receptor antagonism, blockade of muscarinic receptors and ion channels should be addressed in the future research. Comment: This paper uses indirect measures of serotonin uptake to suggest a lack of effect for amitriptiline via this mechanism versus citalopram. Amitriptiline is a highly active pharmacological agent with many actions. It may be that combinations of pharmacodynamic effects are required for efficacy. Hence this study does not rule out serotonin reuptake, it just makes it less likely. —David S. Millson