Prophylactic drug treatments of migraine

H. Massiou ( Department of Neurology, Hopital Lariboisiere, Paris, France)

Prophylactic treatment is mainly intended to reduce the frequency of migraine attacks. It is usually proposed to patients who suffer from two or more attacks per month. It should also be considered in patients who suffer from less frequent, but prolonged, disabling attacks with a poor response to abortive treatment, and who consider that their quality of life is reduced between attacks. Excessive intake of acute medication, more than twice a week, is a strong indication for prophylactic treament. In order to obtain a good compliance to treatment, the patient must be informed of the expected efficacy of the drugs, and of their most frequent side effects. Thus, the choice of a prophylactic drug is made together with the patient. Based on the results of published controlled trials, the main prophylactic drugs are some betabloquers, methysergide, pizotifene, oxetorone, flunarizine, amitriptyline, NSAIDs, and sodium valproate.

Some less evaluated drugs such as aspirin, DHE, indoramine, verapamil, may be useful. Other substances such as riboflavin, new antiepileptic dugs, feverfew, are being evaluated. The choice of the drag to start with depends on several considerations. The first step is to make sure that there are no contra indications, and no possible interaction with the abortive medications. Then, possible side effects will be taken into account, for example, weight gain is a problem for most young women and patients who practice sports may not tolerate betabloquers. Associated pathologies have to be checked. For example, a hypertensive migraineur may benefit from betabloquers ; in a patient who suffers both from migraine and tension type headaches or from depression, amitriptyline is the first choice drug. The type of migraine should also be considered ; for instance, in frequent attacks with aura, aspirin is recommended and betabloquers avoided. In most cases, prophylaxis should be given as monotherapy, and it is often necessary to try successively several drugs before finding the most appropriate one. Doses should be increased gradually, in order to reach the recommended daily dose, only if tolerance permits. The treatment efficacy has to be assessed after 2 or 3 months, during which the patient must keep a headache diary. If the drug is judged ineffective, an overuse of symptomatic medications should be checked, as well as a bad compliance, either of which may be responsible. In case of a successful treatment, it should be continued for 6 or 12 months, and then, one should try to taper off the dose in order to stop the treatment or at least to find the minimum active dose.

Use of antiepileptics in the treatment of drug-induced headache.

Josef Effler. Jin Hovorka, Hana Fucfkova, Erik Herman. Neurologic Department, "Na Frantisku" Hospital, Prague, 110 00, Czech Republic.

Aim of investigation: Evaluation of life quality enhancement in the treatment of drug-induced headache by antiepileptics of the IIIrd generation - Gabapentin.
Methods: 8 patients were given Gabapentin , in individually chosen doses (900 - 2000 mg). According to results of treatment, the patients were divided into three groups. Distinctive improvement was experienced by 5 patients -70%, medium improvement by 1 patient - 15%, slight improvement by 1 patient - 15%. In the evaluation we assessed the frequency of headache attacks and their intensity. One patient wished to have his treatment interrupted.

Conclusions: Treatment of drug-induced headache is a serious medical problem. The use of Gabapentin significantly decreased the number of attacks of headache and their intensity. The patients' quality of life was significantly enhanced by the treatment for 85% of patients.
Acknowledgements: The results were taken from clinical practice and the study received no finantial support.

Tramadol in the treatment of migraine without aura: a controlled trial vs placebo

Q. Zanchin. F. Maggionil, M.G. Buzzi, M. lannacone, B. Amantea, V. Gallai, A. Alberti, G. Relja, G. Sandrini, G. Nappi
Centro Cefalee, Clinica Neurologica I, Univ. PD; 4RCSS, NEUROMED, Pozzilli (IS); Anest. Rian., Policlinico Mater Domini, CZ; Clin. Neurol., Policlinico Monteluce, PG;
Centro Cefalee U.0. Neurol., Osp. Maggiore, TS; 'Centro Interuniversitario Studio Cefalee, 1st. Neurol. C. Mondino, PV

Aim of investigation: this multicenter, double-blind crossover, randomized, placebo controlled trial was conducted to check the efficacy of tramadol in the treatment of migraine without aura.
Methods: a total of 38 patients (9 men, 29 women) were treated with 20 drops orally whenever they had a migraine attack, they could repeat the dose (20 drops) at 30 minute intervals during the first 2 h if pain relief was insufficient. Each patient had to treat four successive migraine attacks (two pairs).
Results: the clinical evaluation was performed on 48 complete pairs of attacks in 30 patients. Rescue medications in the first two hours were required in 13 cases with placebo and 6 with tramadol. The number of migraine attacks relieved within two hours (primary efficacy) was reached by 16 patients taking tramadol and 6 with placebo, and tramadol had a useful effect regardless of whether it was given before or after placebo. During the study 15 patients treated with tramadol reported adverse events, mainly dizziness, nausea and vomiting.
Conclusions: In this first systematic trial in patients with migraine without aura tramadol showed better analgesic Йспоп than placebo in relieving pain, but to confirm these results, additional clinical trials should be performed in a larger study population.
Acknowledgements: Medical Department, Formenti -Griinenthal (Italy)

Efficacy and safety of the association of calcium carbasalate plus metoclopramide and oral sumatriptan

N Fabre, G Geraud, MA Herrmann, R Cahn
Departement of Neurology - Rangueil Hospital - 310 -Toulouse - France, Laboratoires UPSA - 92044 - La Defense - France

Objectives: The aim of this open pilot study was to evaluate the efficacy and safety of an association of calcium carbasalate (equivalent to 900 mg aspirin) plus metoclopramide (10 mg) and oral sumatriptan (100 mg) in the acute treatment of migraine attacks.
Methods: 20 patients with International Headache Society criteria for migraine were included in the study. Eighteen patients treated one, two or three migraine attacks for a total of 41 attacks. The primary efficacy criteria was the rate of pain free patients 2 hours after study drug intake during the first attack. Main secondary efficacy criteria were pain free for second, third and all attacks, the evolution of associated symptoms 1 and 2 hours after treatment and recurrence of migraine within 24 hours.
Results: For the primary criteria, 65 % of patients were pain free (95 % CI 38-86). The proportions obtained for the second, third and all attacks were 62 %, 60 % and 63 % respectively. During the first attack the proportion of pain free patients at 2 hours without rescue medication and recurrence within 24 hours was 35 %. The recurrence of headache within 24 hours was 37 % for all attacks. The study drug was considered as superior to their most effective usual treatment by 76 % of patients for all attacks.
Conclusions: This pilot study demonstrates that the essociation of aspirin, metoclopramide and sumatriptan is an effective and well tolerated treatment for acute migraine attacks. The efficacy results are better than those obtained with each of the compounds taken separately and with any of the antimigraine drags available.

Cost of migraine management : a comparative view of the economic impact of combined oral calcium carbasalate plus metoclopramide versus marketed triptans

Huttin C, Martin P, Massiou H
University Paris X - 92000 - Nanterre-France', Assessment of Medical Care Inc - 75017 - Paris and Department of Psychiatry - St Antoine Hospital - 75475 - Paris-France2, 92160-Antony-France3

Migraine is a chronic disease correlated with loss of working days and a decrease in the quality of life. In population based studies from the U.S.A and Europe, the estimated 1-year prevalence ranges from 8 to 14%.
Extrapolating the combined cost of treatment and loss of productivity in the U.S.A. the annual cost of migraine was estimated as US92$ 6 to 17 billion. In the U.K, the cost of migraine to the economy in terms of lost productivity has been valued at more than 600m per year. In France, it was estimated at around 5 billion FF.
Calcium carbasalate (equivalent to aspirin) plus metoclopramide (CM) is an important addition to the range of therapeutic strategies used to treat migraine attacks as it provides headache relief in 54 to 64% of patients. Adverse effects with CM are generally mild and transient.
The association aspirin plus metoclopramide has been shown to be as effective as oral sumatriptan for the treatment of two migraine attacks in one trial and for the first migraine attack out of three in another one. Other oral marketed triptans in France are not more effective than sumatriptan. For these reasons we have assessed the economic efficiency of CM versus triptans, using a decision analysis model based on literature analysis. We have estimated the cost-effectiveness ratios of these various strategies. Our findings indicate that CM can be the most efficient strategy as first line therapy, depending on results from the decision tree, for the treatment of migraine attacks.

The effect of the association of calcium carbasalate plus metoclopramide on the quality of life of migraineurs

G Geraud, M Dujardin, F Cajfinger, M Jogeix, MA Herrmann
Department of Neurology - Rangueil Hospital - 3100 -Toulouse - France', 27000 - Evreux - France, 78380 -Vemeuil Sur Seine - France, 33000 - Bordeaux - France, Laboratoires UPSA - 92044 - Paris La Defense - France

Objective: This open-label, multicentre study was designed to evaluate the effects of the association of calcium carbasalate (equivalent to 900 mg of aspirin) plus metoclopramide (10 mg) (CM) on the health-related quality of life and clinical parameters of patients with migraine attacks.
Methods: Patients fulfilling the IBS criteria were treated with CM for all their migraine attacks for 4 months. The validated questionnaire "Qualite de vie et migraine" (QVM)* was filled in by the patients at baseline (МО), assessing their quality of life over the previous month, a period during which the patients treated their migraine attacks with their usual therapy (all except triptans and the association aspirin plus metoclopramide). The patients also filled in the QVM, 2 and 4 months (M2 and M4) after inclusion in the study. The primary efficacy criterion was the evolution of the global score on QVM between МО and endpoint. Main secondary efficacy criterion was complete pain relief 2 hours after study drug intake for each migraine attack.
229 patients were included in the study. The global score of QVM improved significantly at the endpoint (n=228) compared with baseline (p=0.0001). In total 226 patients treated 1957 migraine attacks. For all attacks, the percentage of attacks with complete pain relief, 2 hours after study drug intake was 21 %. Sixty three percent of patients and 66 % of physicians considered the efficacy of CM as good or excellent.
Conclusion: This study demonstrates that CM improves the quality of life, measured by QVM Questionnaire.

Withdrawal un drug-induced headaches: clinical aspects, relationship with drug abuse and outcome of the headaches


Unite de traitement de la douleur chronique, Hopital Pellegrin, Pace Amelie Raba-Leon, 33 076 Bordeaux cedex

Aims of investigation:
- To describe precisely the clinical aspects of the withdrawal
- To study the relationship between the drug abuse and the intensity of withdrawal symptoms
- To study the relationship between intensity of the withdrawal and its prognosis
- Intensity of headaches, nausea, vomitings and sleep disturbances are studied in 80 patients admitted for a withdrawal between 1998 and 2000.
- Intensity of headaches is quantified by a daily V.A.S.
- Nauseas, vomitings and sleep disturbances are daily estimated.
Results: Correlational analysis, linear regression analysis and ANOVA are in progress.

Tramadol in the treatment of tension headache: a controlled trial vs placebo

G. Sandrini, G. Nappi, G. Bussone, L. Grazzi, F. Puca, S. Genco, E. Stemieri, A. Pini
Centro Interuniversitario Studio Cefalee, Istituto Neurologico C. Mondino, PV, Istituto Neurologico C. Besta, MI; Servizio Cefalee di Interesse Neurologico, Policlinico, BA;
Centro per lo Studio delle Cefalee, Policlinico, МО

Aim of investigation: the trial was conducted in four Italian headache centres to compare the activity of tramadol in patients with a diagnosis of tension headache according to the IHS classification.
Methods: thirty-seven patients (11 male, 26 female), mean (SD) age 33.1 ± 10.8 years were treated with tramadol or placebo with 20 drops that should be repeated every 30 minutes in the first 2 h if pain relief was insufficient. A double blind cross-over, experimental design was employed. Each patient had to treat six successive tension headache attacks (three pairs), with a 48-hour wash out between one attack and the next.
Results: the clinical evaluation was performed on 41 complete pairs of attacks in 23 patients. Tramadol limited the severity of the attacks in 41% of patients at 2 h, compared to 19.4% with placebo (p=0.0171) and the number of tension headache attacks resolved within 2 h was reached by more patients taking tramadol than placebo (16 vs 6). During the trial 14 patients treated with tramadol complained adverse events, mainly dizziness, pruritus and vomiting.
Conclusions: tramadol in this first controlled trial in patients with tension headache showed better analgesic action than placebo. To support these results should be performed additional trials in a larger study population.
Acknowledgements: Medical Department, Formenti-Grunenthal (Italy).

Efficiency of the physical programme in the complex rehabilitation of the posterior algo-functional syndromes of the cervical spine

Elena - Luminita Sidenco, Carmen Toma, Violeta Scheau, Luminita Bellu
Clinic of Physical Medicine and Rehabilitation -Universitary Hospital Bucharest - 169 Splaiul Independentei str., 76251 Bucharest 5, Romania

Aim of investigation: To investigate the implication of the physical complex adapted treatment at the patients with different algo-functional syndromes at the cervical spine.
Methods and Results: We studied a group of 47patients with algo-functional muscular-ligamentar cervical syndromes based on complex static disorders, diagnosticaly excluding cervical discal hernia. We propose a clinical -functional score for an unitary evaluation of these cases. We applied an initial kinetic programme for two weeks; we propose a complex of stretching-strengthening- coordination exercises for the cervical muscular contraction, supported by thermo-electro-massotherapy. Efficiency of the initial kinetic programme was good, the following clinical parameters increased over 63,7%.The second stage of rehabilitation was applied a month later; we used a kinetic programme analogous to the first stage, for two weeks again, insisting on the strengthening- co-ordination exercises for the cervical muscles.The kinetic programme of the second stage of rehabilitation was supported by thermo-massotherapy. The results were superior to the first stage, the improvement of the clinical parameters was over 83,4%.The third therapeutic stage was applied 3-6 months later, after a new consultation.We used the same kinetic programme of strengthening- co-ordination exercises daily, for another two weeks, thermo-massotherapic supported.The improvement after the third stage of the kinetic programme was superior, clinical parameters increased over 90% confronted with initial values.
Conclusions: We prove the necessity of an unitary score of valuation and the efficiency of a staggered kinetic programme in the complex rehabilitation of the algo-functional muscular-ligamentar cervical syndromes, as the only efficient therapeutic alternative in the functional deficiencies compensation and for prevention of complications.

The part of the kinetic programme in the complex rehabilitationof the algo-functional soft tissues belts sufferings at the old patients

Elena - Luminita Sidenco, Anca Chendea, Violeta Scheau, Cristian Paraschivescu
Clinic of Physical Medicine and Rehabilitation -Universitary Hospital Bucharest -169 Splaiul Independentei str., 76251 Bucharest 5, Romania

Aim of investigation: We tried to prove that kinetic programme physically supported is the only way for the rehabilitation at the old patients with algo-functional soft tissues belts sufferings.
Methods: We studied a group of 40 old patients with soft tissues sufferings (periarthritis) at the shoulder or hip. Patients accused pain and limited mobility, and at the clinical examination we found muscular hypotrophy and limitation of function in the shoulder or hip. .We applied an associated kinetic programme of stretching-strengthening-control and co-ordination exercises in two different periods of 15 days, supported by electro-thermo-massotherapy. The valuations were made at the beginning and the end of the programme, on a clinical score of valuation obtained by the clinical parameters. The results were statistically processing
Results: We find from the beginning a large incidence of the periarthritis at the old patients (25,37%) and the preference for the women, larger in comparison with other ages (27 cases from the group of 40). Application of the kinetic programme, physically supported, significantly improved the pain ( completely for the spontaneous and nocturnal pain, and over 70% for the pain at the motion).Limitation of mobility increased over 63,6%, even the functional remaining is limited at the old patient and the real possibilities of the kinetic programme display can be limited by the associated pathologies. Muscular hypotrophy had a medium response (improvement under 33,7%), because of the limited biological capital and also the associated pathologies which imposed the adaptation of the kinetic programme to the real effort's possibilities. Global function of the upper limb increased over 77,5%.
Conclusions: We consider the soft tissues sufferings of the old patient indicated for the kinetic programme, adequately supported by physical proceedings; the associated cardiovascular diseases do not forbid the rehabilitation, kinetic programme specially, if the patients are well medically treated and the kinetic programme is well adapted at the real effort's possibilities of the patients.

Pain in Europe III. EFIC 2000, Nice, France, September 26-29, 2000. Abstracts book, p. 127, 245, 257, 259, 269, 273, 308, 333.