Prediction of headache response in migraine treatment

Triptans are efficacious for the acute treatment of migraine attacks. Yet, defining a concentration-effect relation for these compounds is difficult as the dynamics of the migraine attack are not thoroughly understood. The objective of this investigation was to develop a disease model to predict measures of headache in randomized placebo-controlled clinical trials investigating oral sumatriptan as a paradigm compound. A hidden Markov model based on the states of response (no relief, relief, and pain free) and headache scores (observed variable) was used in conjunction with population pharmacokinetics. Model parameters were capable of predicting the course of headache relief, pain-free status and headache recurrence. It was shown that sumatriptan shortens mean transit times between states by up to 5 h. The potency of sumatriptan (EC(50)) was 9 ng/ml. These findings demonstrate the value of combining pharmacokinetic and efficacy information to model disease and characterize time-independent drug properties in a population of migraineurs.     

Hypnosis and biofeedback in the treatment of migraine headache

A study was made to explore the decta of subject-hypnotizability in response to 3 treatment procedures applied to 33 migraine headache sufferers. These treatment procedures included biofeedback training for hand-warming, biofeedback training for alpha enhancement, and training for self-hypnosis. The Hypnotic Induction Profile (HIP) of Spiegel & Bridger (1970) was given to each s to determine degree of hypnotizability and the MMF'I was administered to all 8s. All 3 treatment groups showed aigdicant reductions in headache rates and there were no gignificant differences between groups. Cutting acros treatment groups, high hypnotizable Ss (N = 15) showed significant reductions in headache rates when compared with low hypnotizable Ss (N = 13). There was no correlation between HIP scores and the hysteria scale of the MMPI.     

Intranasal civamide for the acute treatment of migraine headache

The objective of this study was to investigate the safety and efficacy of intranasal civamide for the acute treatment of migraine headache with or without aura. Civamide is a vanilloid receptor agonist and neuronal calcium channel blocker that inhibits the neuronal release of excitatory neurotransmitters (e.g. calcitonin gene-related peptide (CGRP) and substance P (SP)) and depletes the neurones of the trigeminal plexus of their neurotransmitter content. Applied intranasally, the release of neurotransmitters to meningeal and dural blood vessels should be decreased, along with the resultant vasodilatation, plasma extravasation, and histamine/serotonin release. Subsequent migraine headache pain may also be diminished. Thirty-four patients were enrolled into a double-blind study of intranasal civamide, and randomized to receive a single dose of either 20 microg or 150 microg of civamide, for the treatment of a single migraine headache, with or without aura, of moderate to severe pain. At 2 h post-dose, 55.6% of patients treated with either dose had a decrease in pain severity, with 22.2% of patients being pain-free. At 4 h post-dose, 72.7% of patients treated with either dose had a decrease in pain severity, with 33.0% of patients being pain-free. Adverse events were similar for both dosages, with 91.2% of patients experiencing nasal burning and 44.1% of patients experiencing lacrimation. No systemic side-effects were observed. Based upon the results of this study, intranasal civamide may be effective in the acute treatment of migraine headache. Given civamide's proposed mechanism of action, intranasal civamide should be substantially more effective for prophylaxis than acute treatment of migraine. A study evaluating its efficacy in prophylaxis of migraine is currently planned.     

Relief from migraine headache with aripiprazole treatment

There have been many reports of the association between migraine headaches and psychiatric disorders as well as of the utility of dopamine antagonists in the treatment of migraine headache. There is increasing evidence to support the activation of dopaminergic systems as a primary component of migraine pathogenesis. This report documents 3 cases of female migraineurs who received the dopamine modulator aripiprazole for treatment of co-occurring psychiatric disorders and experienced a decrease in migraine frequency and severity. A hypothesis as to the mechanism of action of dopamine regulation in migraine treatment is discussed.     

Olanzapine in the treatment of refractory migraine and chronic daily headache

BACKGROUND: Olanzapine, a thienobenzodiazepine, is a new "atypical" antipsychotic drug. Olanzapine's pharmacologic properties suggest it would be effective for headaches, and its propensity for inducing acute extrapyramidal reactions or tardive dyskinesia is relatively low. We thus decided to assess the value of olanzapine in the treatment of chronic refractory headache. METHODS: We reviewed the records of 50 patients with refractory headache who were treated with olanzapine for at least 3 months. All previously had failed treatment with at least four preventative medications. The daily dose of olanzapine varied from 2.5 to 35 mg; most patients (n = 19) received 5 mg or 10 mg (n = 17) a day. RESULTS: Treatment resulted in a statistically significant decrease in headache days relative to baseline, from 27.5 +/- 4.9 before treatment to 21.1+/-10.7 after treatment (P <.001, Student t test). The difference in headache severity (0 to 10 scale) before treatment (8.7+/-1.6) and after treatment (2.2 +/- 2.1) was also statistically significant (P <.001). CONCLUSION: Olanzapine may be effective for patients with refractory headache, including those who have failed a number of other prophylactic agents. Olanzapine should receive particular consideration for patients with refractory headache who have mania, bipolar disorder, or psychotic depression or whose headaches previously responded to other neuroleptic medications.     

Amitriptyline in the prophylactic treatment of migraine and chronic daily headache

(Headache 2011;51:33‐51) Objective and Background.— Amitriptyline is one of the most commonly used medications in migraine prophylaxis. There have been relatively few placebo‐controlled studies of amitriptyline in migraine prophylaxis or in treatment of chronic daily headache (CDH). This report deals with a large placebo‐controlled trial of amitriptyline vs placebo of 20 weeks duration that included subjects with intermittent migraine (IM) as well as CDH. The study was carried out between 1976 and 1979; however, results have never been fully reported. Methods.— Patients with a history of migraine as defined by the 1962 Ad Hoc Committee report were recruited for this study. Subjects had at least 2 headaches per month, and no limit was placed on the number of headaches per month that could be experienced. The study format included a 4‐week baseline period (Period A) in which all subjects received placebo in a dose of 2 pills per day for one week, 3 pills per day for one week and then 4 pills per day for 2 weeks. Subjects with at least 2 migraine headaches in this period were then entered into Period B and randomized into either amitriptyline or placebo tracks. Medication consisted of identical tablets containing either 25 mg amitriptyline or placebo. Period B was 4 weeks in duration with dose titration identical to Period A. The dose could be reduced if necessary to reduce side effects. The minimum dose was one pill per day. Period C was a 12‐week maintenance or stabilization period in which the patient continued the dose established by week 8 with visits at weeks 12, 16, and 20. Patients kept a headache calendar that was used for data collection. Headache frequency (per month), severity, and duration (hours) were the primary measurement parameters employed for data analysis. Results.— For the entire group, 391 subjects were entered into Period A, 338 were randomized into Period B, 317 (81%) subjects completed the first post‐randomization visit (8 weeks), 255 (65%) completed week 12, 210 (54%) completed week 16, and 186 (48%) completed week 20. Using headache frequency and evaluating parameters of (a) improvement, (b) no change, or (c) worsening relative to baseline, there was a significant improvement in headache frequency for amitriptyline over placebo at 8 weeks (P = .018) but not at 12, 16, or 20 weeks. When amitriptyline and placebo patients were compared for headache frequency at 8, 12, 16, and 20 weeks to their own placebo stabilization period at 4 weeks, statistically significant improvement vs worsening was seen in headache frequency at each evaluation point for both amitriptyline and placebo groups (P ≤ .01) reaching 50% reporting a decrease in frequency in each group and approximately 10% reporting worsening by week 20. There were no significant differences in headache severity or duration between amitriptyline and placebo groups at anytime during the study. Within the study sample, there were 36 amitriptyline and 22 placebo subjects who had headaches ≥17 days/month that fit the current definition of CDH by the Silberstein‐Lipton criteria. These were analyzed separately as a subgroup for comparison of amitriptyline vs placebo using a metric of (1) no change or worsening; (2) up to a 50% improvement; and (3) ≥50% improvement in headache frequency. Amitriptyline was superior to placebo in number with improvement in frequency of ≥50% at 8 weeks (25% vs 5% [P = .031]) and at 16 weeks (46% vs 9% [P = .043]). There was a trend for amitriptyline to be superior to placebo at 12 and 20 weeks but this did not reach significance. Conclusions.— In this study, using headache frequency as the primary metric, for the entire group, amitriptyline was superior to placebo in migraine prophylaxis at 8 weeks but, because of a robust placebo response, not at subsequent time points. For the subgroup with CDH, amitriptyline was statistically significantly superior to placebo at 8 weeks and 16 weeks with a similar but nonsignificant trend at 12 and 20 weeks. Compared with placebo amitriptyline is effective in CDH. Amitriptyline was also significantly effective in IM compared intragroup to its own baseline; however, placebo was equally effective in the same analysis. The reason for the robust placebo response in the IM group is not clear, but has been occasionally reported.     

Nitrous oxide for the treatment of acute migraine headache.

The objective of this study was to determine the efficacy of nitrous oxide in the therapy of acute migraine symptoms in emergency department (ED) patients. This was a prospective, randomized, double blind study of patients presenting to an ED. All eligible patients had a prior diagnosis and symptoms consistent with migraine headache and a normal neurological examination. Patients were randomized to receive either 50% nitrous oxide and 50% oxygen or 100% oxygen over 20 minutes. All patients completed a visual analog pain scale before and immediately after intervention. Initial pain scores and change in pain scores between the two groups were compared. There were 22 patients enrolled, 10 in the nitrous oxide group and 12 in the oxygen group. The groups were similar in age, gender, duration of headache, and initial pain scores. Pain scores decreased significantly in the nitrous oxide group (median change, 69 to 21 mm, P = .02). The oxygen group did not show significant change in pain scores (median change, 78.5 to 72, P = .09). Eighty percent of patients receiving nitrous oxide required no rescue medication at the completion of the intervention, compared with 17% of those receiving 100% oxygen (P = .008). Twenty minutes after termination of intervention, 60% of patients who had received nitrous oxide still required no rescue medication, compared with 8% of those who had received 100% oxygen (P = .02). Nitrous oxide shows efficacy in ED short-term treatment of acute migraine headache.     

Pacing as a treatment modality in migraine and tension-type headache

Purpose: To review the pacing literature; describe the use of pacing in a specialty headache clinic; and provide client feedback regarding the effectiveness of pacing in headache self-management. Method: The evidence for this report was derived from a structured literature review, an established pacing intervention program for patients with headache, and patient self-report questionnaire. Results: There are frequent references to pacing in the chronic pain and rheumatic disease literature, but no universal definition and, until recently, few outcome studies. References to pacing in the headache literature are limited. For a small sub-group of clients at a specialty headache clinic (n?=?20), pacing principles taught by occupational therapists were reported to prevent increases in headache intensity (70%); decrease headache intensity (65%), and shorten the duration of a headache (40%). Additionally, 70% of respondents used pacing to prevent headache onset. Pacing was seen to contribute to increased quality of life, headache self-efficacy, function, and independence. There were a variety of opinions regarding the most helpful pacing components. The most frequently endorsed were identify and prioritize responsibilities; balance activity and rest; schedule regular rest breaks; and delegate or eliminate tasks. Conclusions: Pacing appears to play an important role in headache self-management. More pacing research is required in both headache and chronic pain populations.

Implications for Rehabilitation

• Migraine and tension-type headaches are associated with significant pain and disability.

• Overexertion and stress are commonly reported headache triggers.

• Activity pacing allows individuals with migraine and tension-type headache to self-regulate tasks and activities so they may manage physical exertion and mental stress levels.

• Pacing may help decrease headache intensity and duration, as well as increase quality of life, function, and self-efficacy.

     

Pathophysiology of migraine headache

The underlying mechanism of migraine and pain has been unraveled recently with the advent of neuroimaging. In this article mechanism of migraine aura and the pain of migraine are discussed. In addition, interictal studies demonstrating hyperexcitability in migraine are reviewed.     

Management of the acute migraine headache

As many as 30 million Americans have migraine headaches. The impact on patients and their families can be tremendous, and treatment of migraines can present diagnostic and therapeutic challenges for family physicians. Abortive treatment options include nonspecific and migraine-specific therapy. Nonspecific therapies include analgesics (aspirin, nonsteroidal anti-inflammatory drugs, and opiates), adjunctive therapies (antiemetics and sedatives), and other nonspecific medications (intranasal lidocaine or steroids). Migraine-specific abortive therapies include ergotamine and its derivatives, and triptans. Complementary and alternative therapies can also be used to abort the headache or enhance the efficacy of another therapeutic modality. Treatment choices for acute migraine should be based on headache severity, migraine frequency, associated symptoms, and comorbidities.     

How to pick optimal acute treatment for migraine headache

Drug selection for the acute treatment of migraine is based on comorbid disorders, coexistent diseases, and the patient’s pain profile and specific needs and expectations. Patients should be instructed to tailor their treatment strategy to meet their specific needs by varying their medications according to pain intensity. This will aid in successful headache management, by increasing compliance and decreasing disability and cost.     

Aspirin is first-line treatment for migraine and episodic tension-type headache regardless of headache intensity

Objectives.— (1) To establish whether pre‐treatment headache intensity in migraine or episodic tension‐type headache (ETTH) predicts success or failure of treatment with aspirin; and (2) to reflect, accordingly, on the place of aspirin in the management of these disorders. Background.— Stepped care in migraine management uses symptomatic treatments as first‐line, reserving triptans for those in whom this proves ineffective. Stratified care chooses between symptomatic therapy and triptans as first‐line on an individual basis according to perceived illness severity. We questioned the 2 assumptions underpinning stratified care in migraine that greater illness severity: (1) reflects greater need; and (2) is a risk factor for failure of symptomatic treatment but not of triptans. Methods.— With regard to the first assumption, we developed a rhetorical argument that need for treatment is underpinned by expectation of benefit, not by illness severity. To address the second, we reviewed individual patient data from 6 clinical trials of aspirin 1000 mg in migraine (N = 2079; 1165 moderate headache, 914 severe) and one of aspirin 500 and 1000 mg in ETTH (N = 325; 180 moderate, 145 severe), relating outcome to pre‐treatment headache intensity. Results.— In migraine, for headache relief at 2 hours, a small (4.7%) and non‐significant risk difference (RD) in therapeutic gain favored moderate pain; for pain freedom at 2 hours, therapeutic gains were almost identical (RD: ?0.2%). In ETTH, for headache relief at 2 hours, RDs for both aspirin 500 mg (?4.2%) and aspirin 1000 mg (?9.7%) favored severe pain, although neither significantly; for pain freedom at 2 hours, RDs (?14.2 and ?3.6) again favored severe pain. Conclusion.— In neither migraine nor ETTH does pre‐treatment headache intensity predict success or failure of aspirin. This is not an arguable basis for stratified care in migraine. In both disorders, aspirin is first‐line treatment regardless of headache intensity.     

Anti-epileptic drugs in the preventive treatment of migraine headache: a brief review

Anti-epileptic drugs are employed for the prophylactic treatment of migraine. Valproic acid and its sodium salt (divalproex) have been shown to be effective in preventing migraine in double-blind placebo-controlled studies. Gabapentin and lamotrigine have also been proposed for migraine prophylaxis, but more extensive studies are needed to confirm their efficacies. The main mechanism of action of anti-epileptic drugs in the inhibition of the sodium channel to induce a depolarization, preventing the high, frequent action potentials typically excited by convulsive attacks. Moreover, valproate and gabapentin increase brain concentrations of GABA and, probably, inhibit the degradation of GABA. Other proposed mechanisms of action for valproate are a direct effect on neuronal membranes and a reduction of excitatory transmission by aspartate. Valproate, at the recommended dose of 500 mg twice daily, is well tolerated. The more frequent unwanted effects associated with almost all drugs of this class are weight gain, drowsiness, dizziness and tremor. Topiramate has recently been proposed for the treatment of unresponsive, high frequency migraine, taking into account both the GABA and glutamatergic mechanisms of action. Received: 13 November 2000 / Accepted in revised form: 5 April 2001