Underdiagnosis and undertreatment of migraine in Italy: a survey of patients attending for the first time 10 headache centres.

The aim of this study was to asses the clinical features, pattern of healthcare and drug utilization of migraine patients attending 10 Italian headache centres (HC). Migraine is underdiagnosed and undertreated everywhere throughout the world, despite its considerable burden. Migraine sufferers often deal with their problem alone using self-prescribing drugs, whereas triptans are used by a small proportion of patients. All patients attending for the first time 10 Italian HCs over a 3-month period were screened for migraine. Migraine patients underwent a structured direct interview about previous migraine diagnosis, comorbidity, headache treatments and their side-effects and healthcare utilization for migraine. Patient satisfaction with their usual therapy for the migraine attack was evaluated with the Migraine-Assessment of Current Therapy (ACT) questionnaire. The quality of life of migraine patients was assessed by mean of Short Form (SF)-12 and Migraine-Specific Quality of life (MSQ) version 2.1 questionnaires. Of the 2675 patients who attended HCs for the first time during the study period, 71% received a diagnosis of migraine and the first 953 subjects completed the study out of 1025 patients enrolled. Only 26.8% of migraine patients had a previous diagnosis of migraine; 62.4% of them visited their general practitioner (GP) in the last year, 38.2% saw a specialist for headache, 23% attended an Emergency Department and 4.5% were admitted to hospital for migraine; 82.8% of patients used non-specific drugs for migraine attacks, whereas 17.2% used triptans and only 4.8% used a preventive migraine medication. Triptans were used by 46.4% of patients with a previous diagnosis of migraine. About 80% of migraine patients took over-the-counter medications. The Migraine-ACT revealed that 60% of patients needed a change in their treatment of migraine attacks, 85% of whom took non-specific drugs. Both the MSQ version 2.1 and the SF-12 questionnaires indicated a poor quality of life of most patients. Migraine represents the prevalent headache diagnosis in Italian HCs. Migraine is still underdiagnosed in Italy and migraine patients receive a suboptimal medical approach in our country, despite the healthcare utilization of migraine subjects being noteworthy. A cooperative network involving GPs, neurologists and headache specialists is strongly desirable in order to improve long-term migraine management in Italy.

Efficacy of dosing and re-dosing of two oral fixed combinations of indomethacin, prochlorperazine and caffeine compared with oral sumatriptan in the acute treatment of multiple migraine attacks: a double-blind, double-dummy, randomised, parallel group, multicentre study.

AIMS AND METHODS: In this double-blind, double-dummy, randomised, parallel group, multicentre study, the efficacy of dosing and re-dosing of a fixed combination of indomethacin, prochlorperazine and caffeine (Indoprocaf) was compared with encapsulated sumatriptan in the acute treatment of two migraine attacks. Additionally, in the group taking Indoprocaf, two different oral formulations were tested: effervescent tablets and encapsulated coated tablets. RESULTS: Of 297 patients randomised (150 assigned to Indoprocaf and 147 to sumatriptan), 281 were included in the intention-to-treat efficacy analysis. The initial dosing of Indoprocaf and sumatriptan was similarly effective with pain-free rates higher than 30% (95% CI of odds-ratio: 0.57-1.28) and headache relief rates of about 60% (95% CI of odds-ratio: 0.82-1.84) with both the drugs. The efficacy of re-dosing of Indoprocaf as rescue medication was more effective than that of sumatriptan with pain-free values of 47% vs. 27% in the total attacks with a statistically significant difference in the first migraine attack in favour of Indoprocaf. The efficacy of re-dosing to treat a recurrence/relapse was very high without differences between the drugs (pain-free: 60% with Indoprocaf and 50% with sumatriptan in the total attacks). Indoprocaf and sumatriptan were well-tolerated. CONCLUSION: The study demonstrated that the efficacy of the initial dosing of Indoprocaf was not higher than that of sumatriptan, but that the strategy to use the lowest effective dose as soon as the headache occurred, followed by a second dose if the headache has not relieved or to treat a relapse, was very effective, especially with Indoprocaf.

Hypofunctionality of Gi proteins as aetiopathogenic mechanism for migraine and cluster headache.

The involvement of Gi proteins in the modulation of pain perception has been widely established, and mutations in G-proteins have already been identified as the aetiopathological cause of human diseases. The aim of the present study was to determine whether a deficiency or a hypofunctionality of the Gi proteins occurred in primary headache. The functionality and the level of expression of Gi proteins were investigated in lymphocytes from migraine without aura, migraine with aura and cluster headache sufferers. A reduced capability to inhibit forskolin-stimulated adenylyl cyclase activity in headache patients was observed. Migraine patients also showed basal adenosine cAMP levels about four times higher than controls. The reduced activity of Gi proteins seems not to be related to a reduction of protein levels since no significant reduction of the Gialpha subunits was observed. These results indicate Gi protein hypofunctionality as an aetiopathogenic mechanism in migraine and cluster headache.

Decentralization monoamine super-sensitivity of migraine and opiate abstinence: common features and different target mechanisms?

The similarity between opiate withdrawal and migraine (M) has been confirmed regarding increased monoamine sensitivity at the neuromuscular junction of the hand's dorsal vein as well as at the neuraxis where dopamine (DA) supersensitivity was observed. Similarities also included an increase in cAMP levels as a precocious sign in both M and opiate withdrawal. Particular attention has been devoted to the time-course of monoamine supersensitivity in M and in abstinence. It has been found that the maximum level of super-sensitivity occurs in M at the end of the M attack, whereas the maximum super-sensitivity is present at the very beginning of opiate abstinence. The inverse time-course of this phenomenon suggests that it could play some pathophysiological role in inducing the end of the M attack. Conversely, it can represent the expected transient result of a pharmacological denervation which ought to result in a supersensitivity of opioid-dependent neuron during withdrawal. In M, the super-sensitivity is wider, indeed, it involves more receptor types. This could be an indirect proof of the involvement of inhibitory pathways other than the opioidergic one.

Video assessment of yawning induced by sublingual apomorphine in migraine.

A double-blind, placebo-controlled study was carried out in 14 migraineous outpatients and 8 control subjects to assess yawning response to 0.25 mg of sublingual apomorphine, a dopamine receptor agonist, by means of an audiovisual technique. Apomorphine induced a significantly higher number of yawns than placebo in both groups of subjects, but the effect was significantly greater in migraine sufferers than in controls. The result seems to confirm the previous reported hyper-responsiveness to pharmacological dopaminergic stimulation in migraine sufferers. Moreover, the audiovisual technique seems to be an appropriate tool to study yawning response in man.

Intramuscular treatment of migraine attacks using diclofenac sodium: a crossover clinical trial.

This was a double-blind clinical trial, with a crossover design, to compare the efficacy of a non-steroidal anti-inflammatory drug, diclofenac sodium, intramuscularly administered, and placebo in the treatment of migraine attacks. The drug was administered to 40 patients once a day in three consecutive migraine attacks. If pain still remained after 6 h following administration the patient was given a 100 mg diclofenac sodium suppository, in open condition. Evaluation was by a complete medical examination performed by the physician and by the patient completing a specially designed self-assessment card. A total of eight patients dropped out of the trial (all during placebo administration): three due to poor compliance, four for refusal to continue and one because no further migraine attacks developed. Results were analysed after having checked the absence of both period and carry-over effects. In all cases diclofenac sodium was more effective than placebo (P less than 0.01). This was also confirmed by data obtained from the patient self-assessment cards (P less than 0.001) and by preferences expressed by patients at the end of the trial (P less than 0.001). Tolerance to the drug was similar to that of placebo.

Personality patterns of headache sufferers.

One hundred and sixty-seven subjects (91 females and 76 males) aged 18 to 55 and suffering from recurrent headache, daily headache, and cluster headache, were studied. In order to collect detailed information about their clinical as well as social and environmental conditions, a multi-page card was used which had been specially prepared for this purpose. The patients' personality patterns were assessed by the following methods: MMPI (the Hs, Hy, D, and Ma scales, in particular); EPQ (Eysenck Personality Questionnaire); and AS IPAT (Cattel's Anxiety Scale). The statistical analysis of the data obtained made it possible to define the personality patterns of both male and female subjects and then to differentiate between them in relation to the various types of headache. Furthermore, possible relationships between personality traits and headache suffering were investigated. If the personality patterns of females seem to have existed prior to the disease, those of males raise some questions. In cluster patients, in particular, the age of onset seems to be related to certain personality traits; in patients with daily headache, by contrast the association between the duration and severity of the disorder appears to play a major trigger role. Some of these correlations do not have a linear character and suggest new working hypotheses that go beyond the limits of standard correlations.

Lisuride as a migraine prophylactic in children: an open clinical trial.

Lisuride is an ergot derivative which acts on serotonin and dopamine receptors at both peripheral and central levels. According to the central theory of headache, lisuride is an active prophylactic drug in adult headache sufferers. Because of its activity on dopamine receptors, a hypotensive action has been observed after acute and chronic administration of high doses of the drug in adults. An open trial on 45 migrainous children was carried out, to compare lisuride with pizotiphene treatment. Some 23 children were treated with lisuride and 22 with pizotiphene for 42 days. No statistically significant difference in therapeutic results between the two groups was found. Eight migrainous children were treated with a single oral dose of lisuride (0.0250 mg) and arterial blood pressure was measured before and after the drug. No significant change in either supine or orthostatic blood pressure was recorded in pre-drug and post-drug values. This study shows that lisuride is an effective and well-tolerated prophylactic drug in migrainous children.

Multiple aspects of headache risk in children.

Both epidemiological and pharmacoclinical research have been carried out on children suffering from headache. Two epidemiological trials were performed. In the first, 562 migrainous children were questioned about several clinical symptoms that affect child headache suffers, and the incidence of these symptoms was recorded. In the second, we divided 504 nonselected school children into three groups: headache sufferers and nonheadache sufferers with or without family headache history. The same clinical symptoms were studied. Statistical analysis showed that motion sickness, recurrent abdominal pain, sleeping troubles, hyperactivity, cyclic vomiting, dizzines, and limb pain have different incidences in the three groups. These clinical symptoms and family headache history may be considered HR factors and indicate a predisposition to headache in children. The pharmacoclinical study was carried out on 15 migrainous children, five hyperactive and 10 controls. An increased sensitivity of iris adrenergic receptor in both migrainous and hyperactive children was evidenced by measuring phenylephrine-induced mydriasis. The possible etiopathogenetic correlations among headache, hyperactivity, and other HR factors are discussed in accordance with the central theory of headache.

Sexuality and headache.

Ten percent of 362 headache sufferers reported sexual arousal during migraine attack. Clinical investigations on sexuality in 16 headache sufferers, according to some studies showing correlations between idiopathic headache and sexual behavior, were performed. Patients responding by questionnaire listed each sexual experience, headache attack, and number of sleeping hours every day for 1 month. In both men and women, the number of coiti, erotic dreams, and sleeping hours were similar in headache sufferers and controls, while the frequency of masturbation was significantly reduced in the former. Sexual excitement and fantasies appeared more often in female headache sufferers than in controls, while the opposite occurred in the male group. Among the clinical analogies between the crises of migraine and morphine abstinence, sexual arousal may be included.

Sex, migraine and serotonin interrelationships.

Sexual deficiency or frank impotence in man could be due to an imbalance of monoamines, particularly 5-HT, at the mating center level. An absolute or relative excess of 5-HT seems to antagonize testosterone at the level of the mating center receptors in the brain. Plasma testosterone levels in so-called psychological impotence are normal. When the 5-HT concentration in sexually deficient men is sufficiently decreased with parachlorophenylalanine (PCPA) treatment and testosterone levels increased following its administration, a vivid sexual stimulation appears in about half of the untractable cases. Similar results are observed by substituting testosterone with monoamine oxydase inhibitor (MAOI) in PCPA-treated volunteers. Furthermore, MAOI-PCPA are administered to emphasize the brain shift between serotonin and catecholamines. Yet the PCPA-MAOI treatment avoids the prostate carcinogenic risk of testosterone administration in aging males, and seems to have euphorizing effects stronger than those expected only from MAOI therapy. Because of the several side effects of PCPA-MAOI testosterone, the present experiments should be interpreted very cautiously.

[Aphrodisiac action of MAO inhibitors and of parachlorophenylalanine (PCPA) in sexual asthenias]. / Azione afrodisiaca degli inibitori delle MAO e della paraclorofenilalanina (PCPA) nelle astente sessuali

The sexual function in man can be modified decreasing brain serotonin by PCPA and increasing brain cathecolamines by monoamineoxidase inhibitors. In 5 volunteers, sexual deficient men, the combination of PCPA with phenelzine (IMAO) stressed an increase in sexual stimulation, measured by number of erections. In two subjects this effect lasted for 2 months. A clear improvement in mood has also been shown. This pharmacological combination opens new and interesting possibilities in sexual deficiency treatment.