Migraine Disorders: Linde M

Anonymous00234, Evers S, Afra J, Frese A, Goadsby PJ, Linde M, May A, Sándor PS. · Department of Neurology, University of Münster, Germany. European Federation of NeurologicalSocieties · Eur J Neurol. · Pubmed #16796580 No free full text.

Abstract: Migraine is one of the most frequent disabling neurological conditions with a major impact on the patients' quality of life. To give evidence-based or expert recommendations for the different drug treatment procedures of the different migraine syndromes based on a literature search and an consensus in an expert panel. All available medical reference systems were screened for all kinds of clinical studies on migraine with and without aura and on migraine-like syndromes. The findings in these studies were evaluated according to the recommendations of the EFNS resulting in level A,B, or C recommendations and good practice points. For the acute treatment of migraine attacks, oral non-steroidal anti-inflammatory drugs (NSAIDs) and triptans are recommended. The administration should follow the concept of stratified treatment. Before intake of NSAIDs and triptans, oral metoclopramide or domperidon is recommended. In very severe attacks, intravenous acetylsalicylic acid or subcutaneous sumatriptan are drugs of first choice. A status migrainosus can probably be treated by steroids. For the prophylaxis of migraine, betablockers (propranolol and metoprolol), flunarizine, valproic acid, and topiramate are drugs of first choice. Drugs of second choice for migraine prophylaxis are amitriptyline, naproxen, petasites, and bisoprolol.

Linde M. · Cephalea Headache Centre and Institute of Neuroscience and Physiology, Sahlgrenska Academy, Göteborg University, Gothenburg, Sweden. · Acta Neurol Scand. · Pubmed #16867028 No free full text.

Abstract: Migraine is a chronic, neurological disorder generally manifesting itself in attacks with severe headache, nausea and an increased reactivity to sensory stimuli. A low migraine threshold is set by genetic factors, although the phenotype also modulates the manifestations. The 1-year prevalence is approximately 13% and is higher among women. Patients usually experience neuropsychological dysfunction, and sometimes also reversible focal neurological symptoms. The trajectories of the characteristic symptoms of acute migraine usually follow a similar time course, indicating a reciprocal underlying mechanism. A central nervous system hyperexcitability has been demonstrated in neurophysiological studies. The dibilitating effects of migraine are not confined to the attacks per se. Many individuals do not recover completely between the attacks and most report a negative impact on the most important life domains, and an interest in testing other treatments. Young persons have a higher frequency of attacks. Acute treatment should routinely be initiated with an analgesic plus a prokinetic anti-emetic. Triptans must not be provided early during the attack to ensure their efficacy. The natural course of attacks is commonly only temporarily altered by acute treatment. Non-pharmacological treatment and drugs may be equally viable in prophylaxis for migraine. In more complicated cases, conjoint therapy should be considered. New strategies to improve adherence with existing therapeutic regimens might yield greater benefits than will new pharmacological agents.

Linde M, May A, Limmroth V, Dahlöf C, Anonymous00332. · Gothenburg Migraine Clinic and Institute of Clinical Neuroscience, Sahlgrenska University Hospital, Göteborg, Sweden. · Cephalalgia. · Pubmed #12950373 No free full text.

Abstract: Randomized placebo-controlled clinical trials have been the 'golden standard' during the last decades in the development of new drug therapies. This scientifically valid approach has recently been questioned in the fifth revised version of the Declaration of Helsinki, which states that the use of placebo-controlled clinical trials is only acceptable when no proven treatment exists for the studied disease. The World Medical Association further claims that no national ethical, legal or regulatory requirements should be allowed to reduce or eliminate any of the statements in the declaration. In spite of this, the document is not generally accepted as the world ethical standard, as demonstrated by its lack of adoption by many professional associations. In the evaluation process for a drug to be approved in many countries today, clinical investigators at the hospitals and researchers at the pharmaceutical companies are obliged to use study protocols that would be rejected if the new declaration were to be fully adopted. Adherence to the clinical trial guidelines of the International Headache Society could also mean violation of the new Helsinki declaration of ethics. Some ethics committees have already adopted the new declaration, which has caused concern among clinical investigators, who find this document to be vastly out of the line with common practice. At the moment, the situation is unclear and debated with increasing polarity concerning the scientific and ethical issues regarding the use of placebo in clinical trials.

Linde M, Elam M, Lundblad L, Olausson H, Dahlöf CG. · Gothenburg Migraine Clinic, Gothenburg, Sweden. · Cephalalgia. · Pubmed #15566420 No free full text.

Abstract: Unpleasant sensory symptoms are commonly reported in association with the use of 5-HT1B/1D-agonists, i.e. triptans. In particular, pain/pressure symptoms from the chest and neck have restricted the use of triptans in the acute treatment of migraine. The cause of these triptan induced side-effects is still unidentified. We have now tested the hypothesis that sumatriptan influences the perception of tactile and thermal stimuli in humans in a randomized, double-blind, placebo-controlled cross-over study. Two groups were tested; one consisted of 12 (mean age 41.2 years, 10 women) subjects with migraine and a history of cutaneous allodynia in association with sumatriptan treatment. Twelve healthy subjects (mean age 38.7 years, 10 women) without migraine served as control group. During pain- and medication-free intervals tactile directional sensibility, perception of dynamic touch (brush) and thermal sensory and pain thresholds were studied on the dorsal side of the left hand. Measurements were performed before, 20, and 40 min after injection of 6 mg sumatriptan or saline. Twenty minutes after injection, sumatriptan caused a significant placebo-subtracted increase in brush-evoked feeling of unpleasantness in both groups (P < 0.01), an increase in brush-evoked pain in migraineurs only (P = 0.021), a reduction of heat pain threshold in all participants pooled (P = 0.031), and a reduction of cold pain threshold in controls only (P = 0.013). At 40 min after injection, no differences remained significant. There were no changes in ratings of brush intensity, tactile directional sensibility or cold or warm sensation thresholds. Thus, sumatriptan may cause a short-lasting allodynia in response to light dynamic touch and a reduction of heat and cold pain thresholds. This could explain at least some of the temporary sensory side-effects of triptans and warrants consideration in the interpretation of studies on migraine-induced allodynia.

Dahlöf C, Linde M. · Gothenburg Migraine Clinic, Göteborg, Sweden. · Cephalalgia. · Pubmed #11531898 No free full text.

Abstract: A randomly selected sample of 1668 individuals (782 women and 886 men) aged 18-74 years was interviewed by telephone using a standardized questionnaire including the International Headache Society (IHS) criteria for migraine. The survey was performed by SIFO, the national public opinion poll agency. The results obtained demonstrate that 21% of the Swedish population had suffered from severe headaches during the past year. A majority of these headache sufferers (61%) fulfilled the IHS-criteria for migraine. The 1-year prevalence of migraine in Sweden was found to be 13.2 +/- 1.9% (16.7% among women and 9.5% among men). The prevalence of migraine in this Swedish population did not differ between the northern, middle and southern part of Sweden, or between urban and rural areas or different income groups. Only about half (49%) of the migraineurs had been diagnosed by a physician. Among the individuals who fulfilled the IHS criteria for migraine the mean attack-frequency was 1.3 per month and the mean attack-duration was 19 h. If the duration of the attack was disregarded as a strict criterion for migraine (attacks < 4 h and > 72 h were included), the prevalence increased to 17.0 +/- 1.9% without affecting the sex distribution. With this amendment, 92% of those who considered their headaches to be migraine or migraine-like in fact fulfilled the alternative criteria for migraine. However, only 76% of those who believed that they had migraine or migraine-like headaches fulfilled the strict IHS criteria for migraine. An extension of the time window from 4 to 72 h may be reasonable both from a pragmatic and from a rational clinical point of view.

Varkey E, Cider A, Carlsson J, Linde M. · Cephalea Headache Centre, Gothenburg, Sweden. · Headache. · Pubmed #18783448 No free full text.

Abstract: OBJECTIVES: The aim of this study was to develop and evaluate an exercise program to improve maximum oxygen uptake (VO(2 max)) in untrained patients with migraine without making their migraines worse. PATIENTS AND METHODS: Twenty-six patients were studied at a headache clinic in Sweden. The exercise program, based on indoor cycling, was performed 3 times per week during 12 weeks. VO(2 max), migraine status, side effects, and quality of life were evaluated. RESULTS: VO(2 max) increased from 32.9 mL/kg/minute to 36.2 mL/kg/minute (P = .044). Quality of life increased and significant improvements in migraine status (attack frequency, symptom intensity, and intake of medicine) were seen. During the 12 weeks of exercise, on one occasion one patient had a migraine attack, which started immediately after training. No other side effects were reported. CONCLUSIONS: The evaluated exercise program was well tolerated by the patients and improved their VO(2 max) with no deterioration of migraine status.

Varkey E, Hagen K, Zwart JA, Linde M. · Cephalea Headache Centre, Gothenburg, Sweden. · Cephalalgia. · Pubmed #18771495 No free full text.

Abstract: The aim of this study was to evaluate, using a prospective and a cross-sectional design, the relationship between level of physical activity and migraine and non-migraine headache. In the prospective part, 22,397 participants, not likely to have headache, answered questions about physical activity at baseline (1984-1986) and responded to a headache questionnaire at follow-up. In the cross-sectional part (1995-1997), 46,648 participants answered questions about headache and physical activity. Physically inactive individuals at baseline were more likely than active individuals to have non-migraine headache 11 years later (odds ratio 1.14, 95% confidence interval 1.02, 1.28). In the cross-sectional analyses, low physical activity was associated with higher prevalence of migraine and non-migraine headache. In both headache groups, there was a strong linear trend (P < 0.001) of higher prevalence of 'low physical activity' with increasing headache frequency. The result may indicate that physical inactivity among headache-free individuals is a risk factor for non-migraine headache and that individuals with headache are less physically active than those without headache.

Linde M, Jonsson P, Hedenrud T. · Cephalea Headache Centre, Gothenburg, Sweden. · Acta Neurol Scand. · Pubmed #18513346 No free full text.

Abstract: OBJECTIVES: Randomized controlled trials of prophylactic treatments for migraine focus on the effects in an ideal situation and underestimate the impact of non-adherence, which in this study was examined in a natural setting. MATERIALS AND METHODS: A sample of 174 adult migraineurs with a current prescription of pharmacological prophylaxis were consecutively recruited at a specialist clinic. Logistic regression analysis was performed to analyse the association between adherence (self-reported with the Medication Adherence Report Scale) and number of years with migraine, frequency of attacks, number of days with migraine per month, attack duration, presence of cardinal features, mean intensity of pain, and recovery between attacks. RESULTS: One third (35%) were non-adherent. Neither demographic characteristics nor any of the disease specific variables were significantly associated with adherence. CONCLUSION: Characteristics of the disease per se did not predict non-adherence which was also observed among patients with severe migraine. The full benefit of drugs cannot be realized at currently achieved levels of adherence.

Hedenrud T, Jonsson P, Linde M. · Department of Social Medicine, The Sahlgrenska Academy at Göteborg University, Göteborg, Sweden. · Ann Pharmacother. · Pubmed #18073328 No free full text.

Abstract: BACKGROUND: The problem of low adherence to drug therapy is as prevalent in migraine as in any other disorder, with important consequences for the patient, such as impaired quality of life and absence from work. Beliefs about medicines have been identified as one of the most significant factors for adherence. OBJECTIVE: To analyze whether beliefs about medicines and medication-related factors are associated with adherence to prophylactic drug therapy among migraineurs at a Swedish tertiary care clinic. METHODS: A questionnaire was distributed to migraineurs visiting a tertiary care clinic in Sweden. All participants had recently been prescribed prophylactic medicine. The questionnaire was comprised of background questions, questions about disease characteristics, perceived effects, and adverse effects of migraine medications used, the Beliefs about Medicines questionnaire, and the Medication Adherence Report Scale. Medication-related variables, collected from patients' records with consent, were also included. Logistic regression analysis was performed to analyze the association between beliefs about medicines, medication-related variables, and adherence to prophylactic drugs. RESULTS: Of the 174 participants in the study, 64% were considered to be adherent to their prescribed prophylactic medicine. Users of beta-blockers were significantly more adherent compared with patients using other drugs (eg, tricyclic antidepressants [TCAs] or antiepileptics); the reverse was true for patients taking TCAs. Respondents with the lowest level of education (<or=9 y) expressed less concern about drugs and had a higher necessity-concerns differential compared with respondents with a higher educational level. In the final regression model, no variable was significantly associated with adherence. CONCLUSIONS: About one-third of the migraineurs did not adhere to their prophylactic drugs. Beliefs about medicines and medication-related factors could not predict nonadherence. We recommend further research on medication-related variables in relation to adherence among migraineurs.

Linde M, Nordlander E, Carlsson J. · · Lakartidningen. · Pubmed #17655030 No free full text.

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Linde M, Mellberg A, Dahlöf C. · Gothenburg Migraine Clinic, Gothenberg, Sweden. · Cephalalgia. · Pubmed #16686911 No free full text.

Abstract: This study was designed to document prospectively and explore scientifically the natural course of untreated migraine attacks in detail. A new, integrated, time-intensity method for self-assessment of the intensity of symptoms was tested on 18 adult International Headache Society migraineurs who volunteered to refrain from treatment during one attack. The area under the curves (AUC) during 72 h of untreated attacks was compared with attacks treated with a triptan. Migraine attacks are heterogeneous both inter- and intra-individually. In untreated attacks, the pain can stabilize and fluctuate around a plateau with a wavelength of hours. In general, the symptoms of each separate migraine attack follow a similar temporal course, with only moderate deviations. In some cases photo- and/or phonophobia (hyperexcitability) were not experienced at all, despite severe pain and nausea. Moreover, there was sometimes no nausea despite severe pain and hyperexcitability. Vomiting does not always correlate to the intensity of nausea and is not always followed by decreased headache intensity. Treatment with a triptan usually only temporarily distorts the basic pattern of attacks. Hyperexcitability can respond before pain to treatment. These genuine findings of the classic symptoms of migraine attacks support the notion of a mutual underlying pathophysiological mechanism.

Linde M, Mellberg A, Dahlöf C. · Gothenburg Migraine Clinic, and Institute of Clinical Neuroscience, Sahlgrenska Academy, Göteborg University, Gothenburg, Sweden. · Cephalalgia. · Pubmed #16426264 No free full text.

Abstract: Over the years the paradigm of treating early during the migraine attack has become well established in clinical practice. It is also recommended that the 5-HT(1B/1D) agonists be administered early during the migraine attack for efficacy. This is because it has been proposed that most migraineurs are less responsive to delayed treatment, owing to the development of central sensitization of the pain transmission. The main objective of this prospective, cross-over study at a specialist clinic was to evaluate if these recommendations should also apply to the subcutaneous formulation of sumatriptan. Results are based on 20 adult International Headache Society migraineurs. Two attacks (n=40) were treated with 6 mg subcutaneous sumatriptan as early as possible after the onset of migraine headache and two attacks (n=40) as late as the patients could bear. The median intra-individual difference between the two strategies in time from first occurrence of pain to injection was 5.7 h and the median intra-individual difference in pain intensity at the time of injection was 29 visual analogue units. No significant differences were found in time to freedom from pain, pain severity at 1 and 2 h, area under the curves from injection to pain free or in headache recurrence after injection. At the end of the study, most of the patients claimed that their medication was as effective when given early as when given late in the course of the attack. The discrepancy between our present findings and retrospective analyses of trials on oral triptans probably has more to do with the less disturbed pharmacokinetics early during the migraine attack than with central sensitization. Consequently, we recommend nonoral formulations of triptans, which do not necessarily have to be administered early during the migraine attack to provide efficacy. In conclusion, it is reassuring for migraineurs that it is worthwhile taking their medication in an appropriate formulation even if they have not been able to do so early in the course of the attack.

Linde M, Dahlöf C. · Gothenburg Migraine Clinic, Gothenburg, Sweden. · Cephalalgia. · Pubmed #15154855 No free full text.

Abstract: The authors have earlier reported a 1-year prevalence of 13.2 +/- 1.9% for migraine in Sweden. This is a subsequent extensive postal survey of the burden of disease and attitudes among migraineurs in a sample (n = 423, 23% men and 77% women, aged 18-74 years) randomly recruited from all main regions of the country, representative of adults in the general Swedish population with self-considered migraine. Results are presented only from participants who after analysis of symptoms were found to fulfil the International Headache Society's migraine criteria. In order to assess headache duration open-mindedly, the strict time criterion 4-72 h was deliberately disregarded as an inclusion criterion. Individuals who did not consider themselves to have migraine were excluded. Less than half of the group (45%) had received a diagnosis of migraine from a physician. Accordingly, a large number of individuals that would not have come to attention in a clinic-based study have been included. The mean attack frequency was 1.3 per month, and the number of attacks per year in Swedish adults is approximately 10 million. A minority (27%) of sufferers have a majority (68%) of all attacks. The mean attack duration was 19 h. A considerable number of individuals reported attacks < 4 h (15.8%) or > 72 h (6.4%). Less than half of the individuals recovered completely between the attacks. Despite this, only every fourth (27%) participant was currently consulting a physician (6% regularly; 21% occasionally). Most of the migraineurs reported absence from school or work, a negative influence of migraine on the most important aspects of life, and an interest in testing other treatments for migraine during the last year. Of those (n = 231) migraineurs who had consulted a physician, about 60% were satisfied with information given or treatment offered. This implies, however, that there is still room for improvement in the management of migraine in Sweden.

Linton-Dahlöf P, Linde M, Dahlöf C. · Sahlgrenska Universitetssjukhuset/Sahlgrenska, Göteborg. · Lakartidningen. · Pubmed #11478207 No free full text.

Abstract: Chronic daily headache is a commonly encountered syndrome. Typically affected are persons who as a result of recurrent attacks of migraine or tension-type headache have used medications regularly during an earlier stage. Based on clinical experience it is concluded that outpatient drug-withdrawal should be a first-line treatment for patients with chronic daily headache and frequent long-term drug-use. If there is no improvement treatment with a tricyclic drug is recommended.

Linton-Dahlöf P, Linde M, Dahlöf C. · Gothenburg Migraine Clinic, Göteborg, Sweden. · Cephalalgia. · Pubmed #11128824 No free full text.

Abstract: Chronic daily headache (CDH) associated with long-term misuse of headache medication is a common clinical problem which is refractory to most treatments. The present study is a retrospective analysis of the effect of drug withdrawal therapy in patients with CDH and frequent long-term use of headache symptomatic medication. One hundred and one adult patients (74 women and 27 men, aged between 16 and 72 years, mean age 43 years) were evaluated 1-3 months after drug withdrawal therapy had been initiated. The mean headache frequency at baseline was 26.9+/-4.0 days per month. Fifty-seven (56%) patients were significantly improved (defined as at least 50% reduction in number of headache days) after a period of drug withdrawal therapy. Based on the outcome of the drug withdrawal therapy, the patients were divided into three categories: group I, those who had between 0 and 10 headache days per month (n = 41), group II, those who had 11-20 days (n = 37), and group III, those who had 21-30 days (n = 23). The mean headache frequencies in groups I, II and III were 5.6+/-2.8 days, 15.7+/-2.5 days and 28.7+/-2.4 days, respectively. Treatment with amitriptyline was offered to patients in whom no improvement had been achieved. Ten of those 22 patients (36%) experienced a significant (> or = 50%) reduction of headache days. It is concluded that out-patient drug withdrawal therapy is the treatment of choice in patients with CDH and frequent long-term use of headache symptomatic medication, and that about one quarter of these CDH patients do not respond to drug withdrawal therapy only.