Reduction In Headache Severity Research Articles

Does Early Migraine Treatment Shorten Time to Headache Peak and Reduce Its Severity?

To explore whether early treatment would shorten the duration of headache from headache onset to its peak and reduce headache severity at peak. Prior clinical studies almost exclusively focused on headache relief after dosing. No data are available on whether early intervention affects the duration from headache onset to peak and headache severity at peak. Adult migraineurs were enrolled in this observational study from multi-site headache clinics. Patients recorded their migraine experiences via an electronic diary over 1 month. Patients reported the time and pain severity at onset, dosing, and peak. We used a linear mixed model to evaluate the impact of the timing of treatment and to adjust for covariates and correlation of observations within subjects. A total of 182 patients reported 970 migraine episodes, 620 of which were treated before headaches progressed to peak. Mean time from headache onset to peak varied from 1.9 hours to 8.9 hours for patients treated within 15 minutes of onset and those who waited for 4 or more hours, respectively. However, early intervention was not associated with reduced headache severity at peak. In multivariate analysis, early treatment, use of triptans, and mild migraine headache in the past 3 months were significantly associated with shorter time from onset to headache peak. A separate model indicated that the timing of medication was not associated with the duration between dosing and headache peak, but use of triptans shortened the time from dosing to headache peak. Early treatment and use of triptans may lead to shorter duration from migraine headache onset to its peak but did not alleviate headache severity at peak. This could result in decreased migraine burden by reducing total migraine headache duration.

Epidural blood patch in post dural puncture headache: a randomised, observer-blind, controlled clinical trial

Objectives:To determine the efficacy of epidural blood patch (EDBP) for the treatment of post dural puncture headache (PDPH).Methods:We randomised 42 patients who presented with PDPH, lasting 24 h to 1...

The broad treatment expectations of migraine patients

The objective was to define the overall treatment expectations of migraineurs. Many studies have defined the expectations of patients regarding their acute migraine treatment but little information is available regarding overall expectations. During routine first visits to the author’s headache clinic patients were asked about their expectations of treatment as well as demographics and headache characteristics. Demographics were recorded and expectations were compared between different forms of migraine and between females and males. One thousand seven hundreds and fifty patients were diagnosed with ICHD-II 1.1, 1.2, 1.5.1 and 1.6, 1207 with migraine and 543 with probable migraine. A percentage of 27.8 expected a cure from their treatment, 79.7% to be symptomfree, 95.2% a reduction in frequency of headaches, 95.6% a reduction in severity of headaches and 95.5% an improved quality of life. Males had greater expectations for reduction in severity of migraines than females. Patients with migraine were more likely to expect a cure and a reduction in headache severity than patients with probable migraine. Patients with aura with every headache were more likely to expect reduced frequency of headache than patients with no aura. Some patients did expect a cure for their headaches and knowing patients’ expectations may facilitate headache management and education, and achieve more realistic outcomes.

Intra-oral orthosis vs amitriptyline in chronic tension-type headache: a clinical and laser evoked potentials study.

BackgroundIn the present study, we examined clinical and laser-evoked potentials (LEP) features in two groups of chronic tension-type headache (CTTH) patients treated with two different approaches: intra-oral appliance of prosthesis, aiming to reduce muscular tenderness, and 10 mg daily amitriptyline.MethodsEighteen patients with diagnosed CTTH participated in this open label, controlled study. A baseline evaluation was performed for clinical features, Total Tenderness Score (TTS) and a topographic analysis of LEPs obtained manually and the pericranial points stimulation in all patients vs. healthy subjects. Thereafter, patients were randomly assigned to a two-month treatment by either amitriptyline or intra-oral appliance.Results and discussionBoth the intra-oral appliance and amitriptyline significantly reduced headache frequency. The TTS was significantly reduced in the group treated with the appliance. The amplitude of P2 response elicited by stimulation of pericranial zones showed a reduction after amitriptyline treatment.Both therapies were effective in reducing headache severity, the appliance with a prevalent action on the pericranial muscular tenderness, amitriptyline reducing the activity of the central cortical structures subtending pain elaborationConclusionThe results of this study may suggest that in CTTH both the interventions at the peripheral and central levels improve the outcome of headache.

Response to Letter by Magrini et al

Response: Magrini and associates argue that particular working conditions entailing frequent Valsalva maneuvers may represent a risk factor for the development of migraine in subjects with right-to-left shunt. This is a clever and intriguing observation that, besides being biologically plausible, raises the hypothesis, never considered so far, that the beneficial effect of atrial septal repair on migraine in stroke patients might result not so much from the correction of the shunt but mainly from changes in lifestyle that reduce the number or the strength of Valsalva strains. This variable will have to be taken into account in future studies. However, …

Almotriptan in the acute treatment of migraine in patients 11–17 years old: an open–label pilot study of efficacy and safety

The objective was to investigate the safety and efficacy of almotriptan in patients aged 11–17 years old with acute migraine. Fifteen patients aged 11–17 with a history of migraine with or without aura were treated with almotriptan. Reduction in headache severity, disability and adverse effects were studied. Almotriptan in doses ranging from 6.25 to 12.5 mg was well tolerated. There were virtually no adverse effects except for one case of transient mild stiffness. Of the 15 patients, only 2 demonstrated no efficacy without adverse effects. In the other 13 patients, not only was almotriptan effective, but again, no significant adverse effects were reported. Almotriptan is probably safe and effective in patients aged 11–17. This small open–label pilot study should support the feasibility of a large randomised controlled study to demonstrate tolerability and efficacy of almotriptan in children and adolescents with episodic migraine.

Efficacy and tolerability of frovatriptan in acute migraine treatment: systematic review of randomized controlled trials

To evaluate the efficacy and tolerability of frovatriptan in acute migraine treatment. Systematic review and meta-analysis of randomized controlled trials. Clinical trials of frovatriptan were systematically identified through electronic searches and historical searches up until February 2005. Studies were included if they were (i) double-blind, randomized, placebo controlled trials that evaluated frovatriptan 2.5 mg in acute migraine treatment and (ii) reporting the efficacy data in terms of pain-free, headache response, headache recurrence, or relief of migraine-associated symptoms. Two authors extracted data independently. Disagreements were resolved through discussion. The efficacy was estimated using risk ratio (RR), risk difference, and number needed to treat together with 95% confidence intervals. Five trials involving a total of 2,866 patients were included. Frovatriptan 2.5 mg was more effective than placebo in rendering patient pain-free (RR 3.70, 95% CI 2.59-5.29, P < 0.0001 at 2 h and 2.67, 95% CI 2.21-3.22, P < 0.0001 at 4 h post-dose). It was also superior to placebo in reducing headache severity. The pooled RR was 1.66 (95% CI 1.48-1.88, P < 0.0001) and 1.83 (95% CI 1.66-2.00, P < 0.0001), respectively, at 2 and 4 h after treatment. In those whose headache was relieved at 4 h, the risk of headache recurrence within 24 h was reduced by 26% with frovatriptan (RR 0.74, 95% CI 0.59-0.93, P = 0.009). Frovatriptan was also superior to placebo in improving symptoms associated with migraine. At 2 h after dosing, frovatriptan reduced the risk of nausea by 14% (95% CI 6-20%, P = 0.0005), photophobia 17% (95% CI 12-22%, P < 0.0001), and phonophobia 14% (95% CI 17-20%, P < 0.0001). The corresponding numbers at 4 h after dosing were 37% (95% CI 30-43%, P < 0.0001), 34% (95% CI 29-39%, P < 0.0001) and 30% (95% CI 23-36%, P < 0.0001), respectively. Frovatriptan caused more adverse events than did placebo (RR 1.31, 95% CI 1.07-1.62, P = 0.01). The available evidence suggests that frovatriptan is more effective but may cause more adverse events than placebo in the treatment of acute moderate to severe migraine. It is effective in providing pain relief and reducing the risk of recurrence. However, its effectiveness relative to other more established agents needs to be better defined by appropriate head to head trials.

Efficacy of 1,000 mg Effervescent Acetylsalicylic Acid and Sumatriptan in Treating Associated Migraine Symptoms

Recently a new effervescent acetylsalicylic acid (ASA) tablet with high buffering capacity has been developed. In this double-blind, 3-arm, multicenter, parallel-group study, 433 patients were treated either with 1,000 mg effervescent ASA or 50 mg encapsulated sumatriptan or placebo. The primary endpoint was the percentage of patients with complete remission of the 3 accompanying symptoms nausea, photophobia and phonophobia within 2 h after intake of the study drug. 43.8% of patients treated with ASA, 43.7% of patients treated with sumatriptan and 30.9% of patients treated with placebo showed complete remission of all 3 accompanying symptoms (p < 0.05 for ASA and sumatriptan vs. placebo). Both active treatments were superior to placebo regarding the individual symptoms photophobia and phonophobia, but not for nausea. The percentage of patients with reduction in headache severity from moderate or severe to mild or no pain (secondary objective) was 49.3% for ASA, 48.8% for sumatriptan and 32.9% for placebo. All active treatments were superior to placebo (p < 0.05). 25.3, 24.4 and 14.5% of patients treated with ASA, sumatriptan or placebo were pain free at 2 h. Drug-related adverse events were reported in 3.9, 4.7 and 6.7% of patients treated with placebo, ASA or sumatriptan. The study showed that administration of effervescent ASA leads to remission of the migraine symptoms nausea, photophobia and phonophobia, reduces migraine headache and is comparable to sumatriptan.

Efficacy of oral ketoprofen in acute migraine: a double‐blind randomized clinical trial.

Neurology. 2002 Jun 11;58(11):1660‐1665Background: Certain nonsteroidal anti‐inflammatory drugs are effective in the acute treatment of migraine attacks. The authors report a double‐blind, placebo‐controlled, randomized cross‐over trial of a dual‐release formulation of oral ketoprofen in the acute treatment of migraine attacks.Methods: The authors compared the efficacy of two doses of ketoprofen (75 or 150 mg) with that of placebo (primary analysis) and zolmitriptan 2.5 mg (secondary analysis) on one to four consecutive attacks in 235 intent‐to‐treat patients (out of 257 randomized patients) with migraine with or without aura. The principal efficacy outcome was headache relief (reduction in headache severity from severe or moderate to mild or absent at 2 hours).Results: Results are based on 838 attacks with a severe or moderate headache that were evaluable at 2 hours. Relief was reported for 62.6% of headaches treated with ketoprofen 75 mg, 61.6% with ketoprofen 150 mg, and 66.8% with zolmitriptan. The difference between the three active treatments and placebo (27.8% relief) was highly significant, both tests of ketoprofen vs placebo being globally controlled at a 5% level for the type I error (primary analysis). Headaches at 2 hours disappeared more frequently for the active treatments than for placebo. The authors also demonstrated efficacy on most other secondary outcomes. The tolerance of ketoprofen was good (similar to that of placebo).Conclusions: Oral ketoprofen (75 mg or 150 mg) in a dual‐release formulation is an effective and well‐tolerated drug in the acute treatment of migraine attacks.Comment: Almost none of the studies comparing triptans to nonsteroidal anti‐inflammatory drugs (NSAIDs) or non‐triptans show a superiority for triptans for the primary endpoint of headache response at 2 hours. Most of the studies show a superiority for triptans over NSAIDs for the secondary endpoint of pain‐free at 2 hours. Pain‐free response appears linked to sustained pain‐free response, that is to the migraine not recurring. Dr. Julio Pascual's prospective study (Pascual J, Fite B, Lopez‐Gil A. Comparison of triptan tablet consumption per attack: a prospective study of migraineurs in Spain. Headache. 2002;42:93‐98) on tablet consumption per attack in Spain found that non‐triptan tablet use per attack was always higher than triptan use. Dr. Jean Schoenen has raised the issue that this may be due to inadequate doses for the NSAIDs. However, in the aspirin‐metoclopramide vs sumatriptan studies (eg, Tfelt‐Hansen P, Henry P, Mulder LJ, Scheldewaert RG, Schoenen E, Chazot G. The effectiveness of combined oral lysine acetylsalicylate and metoclopramide compared with oral sumatriptan for migraine. Lancet. 1995;346:923‐926) the 1000‐mg dose of aspirin seems adequate, and yet pain‐free numbers favored sumatriptan. It is possible that the key difference in NSAIDs versus triptans is not in the ability to give relief, but in the ability to yield a sustained pain‐free result. The probable superiority of triptans in this regard might reduce the likely need for re‐dosing in an attack, and decrease the risk for medication overuse headache. Further studies comparing triptans and non‐triptans should use pain‐free, sustained pain‐free, and number of doses per attack as primary endpoints rather than headache response. SJT

Supplementation with omega-3 polyunsaturated fatty acids in the management of recurrent migraines in adolescents

To examine whether dietary supplementation with fish oil rich in very long-chain n-3 polyunsaturated fatty acids might reduce frequency and severity of migraines in adolescents. Twenty-seven adolescents suffering from frequent migraines for at least 1 year (mean 4 +/- 1 years since migraine onset) participated in a randomized, double-blind, cross-over study consisting of 2 months of fish oil, 1-month washout period, and 2 months of placebo (olive oil). Participants self-assessed severity and duration of headache episodes (7-point faces and 10-point visual analog pain scales, 5-point frequency and severity rating scale) throughout the study. At the end of every 2-month treatment period, participants rated the effectiveness of treatment on a 7-point Likert scale (1,"not effective, not worthwhile"; 4,"moderately effective, moderately worthwhile"; 7, "totally effective, totally worthwhile"). A score of > or = 4 on the Likert scale was considered as improvement. Twenty-three adolescents (16 girls, 7 boys, 18 Whites, 3 Hispanics, 1 African-American, 1 Cape Verdean, mean age 15 +/- 1 years) completed the study. Compared with frequency of headaches before the study (31 +/- 4 episodes/2 months), there was a significant (p <.0001) reduction in headache frequency during fish oil treatment (4 +/- 1 episodes/2 months) and during placebo (olive oil) treatment (4 +/- 1 episodes/2 months) but no significant (NS) difference between treatments. Likewise, self-assessment on a 7-point faces pain scale revealed a significant reduction in headache severity during fish oil treatment (2.9 +/- 0.5, p =.01) and during placebo (olive oil) treatment (3.5 +/- 0.4, <p =.03), compared with headache severity before study (5.0 +/- 0.3) and no significant difference between treatments. Patients' ratings of treatments revealed that 87% experienced reduction in headache frequency, 74% experienced reduction in headache duration, and 83% experienced reduction in headache severity during treatment with fish oil, compared with 78% who experienced reduction in headache frequency, 70% who experienced reduction in headache duration, and 65% who experienced reduction in headache severity during treatment with placebo (olive oil, NS). About 91% stated that they would recommend fish oil to friends or relatives with headaches vs. 91% who would recommend placebo (olive oil, NS). Patients experienced a similar reduction in frequency, duration, and severity of headaches during treatment with fish oil and during treatment with olive oil. Although there was no significant difference between treatments, the marked improvement from baseline experienced by the patients suggests that the effect should not be dismissed as simply a placebo effect. In fact, results of this preliminary study suggest that both fish oil and olive oil may be beneficial in the treatment of recurrent migraines in adolescents. Further studies are warranted to compare each of these treatments with other interventions.

Zolmitriptan reverses blink reflex changes induced during the migraine attack in humans

The question about the 5-hydroxytryptamine (5-HT) 1B–1D receptors agonists, if the clinical efficacy in migraine attacks is linked with the action at the central level or at the peripheral one, is still unresolved. We evaluated the effects of zolmitriptan and sumatriptan on blink reflex in thirty migraine without aura patients during the attacks in order to assess the central action on the trigeminal system. Both drugs were effective in reducing headache severity compared to placebo. In the migraine attack an increased area of the R3 component on the pain side was observed; it was suppressed by zolmitriptan, which confirmed its action on the central trigeminal circuits, though the clinical relevance of this effect could be questioned.

Intravenous propofol: unique effectiveness in treating intractable migraine.

To report the unique effectiveness of propofol, an intravenous anesthetic agent, in treating refractory migraines and other headaches in the setting of an outpatient headache center. We initially observed the dramatic abolition of ongoing migraine in patients (n=6) being treated with propofol in preparation for epidural and other nerve blocks in the headache and pain clinic. The reduction of headache severity was virtually 100%. We decided to treat an additional cohort of patients with intravenous propofol in the headache clinic; these patients had intractable migraines that were refractory to the usual abortive treatments. Subanesthetic doses of propofol were employed in this study. This is the first known report of the utility of this agent specifically for the treatment of intractable headache. Seventy-seven patients were treated for intractable headache in the clinic with intravenous propofol, for both migraine and nonmigrainous headache refractory to the usual methods of abortive treatment. The average reduction in headache intensity was 95.4% after an average of 20 to 30 minutes of intravenous propofol treatment, using a patient-rated visual analog scale of 0 to 10. Sixty-three of 77 patients reported complete abolition of their headache. The average dose of propofol was 110 mg, which is well within the usual range of preanesthetic doses and is clearly subanesthetic. Moreover, only three of the treated patients reported a return of the headache on the day following treatment. The neuropharmacology of propofol and the putative multiple mechanisms of action upon various neurotransmitter systems in the brain, particularly gamma aminobutyric acid A receptor subtypes, are discussed to explain the results in our patients. The use of intravenous propofol may represent a new, rapid, and highly effective form of abortive headache treatment in the headache clinic or emergency room setting and may offer an alternative to other treatment modalities for acute migraine and other severe intractable headaches. The effectiveness of propofol raises many new questions about the pathophysiology of migraine and other headaches.

Early clinical experience with subcutaneous naratriptan in the acute treatment of migraine: a dose-ranging study.

Naratriptan is a novel, potent agonist at the 5HT1B/1D receptor. A total of 335 migraine patients were treated in this randomized, double-blind, placebo-controlled, dose-ranging, in-clinic study, to evaluate the efficacy, safety and tolerability of five doses of subcutaneous (sc) naratriptan (0.5, 1, 2.5, 5 or 10 mg) in comparison with sc sumatriptan (6 mg) and placebo in the acute treatment of a moderate/severe migraine attack. Headache relief [reduction of headache severity from moderate or severe (grade 2/3) to mild or none (grade 1/0)] at 1 and 2 h after each dose, was reported by a statistically significantly higher proportion of patients for all doses of sc naratriptan and sc sumatriptan (6 mg) than for placebo. The percentages of patients with headache relief at 2 h post-dose were: naratriptan (0.5 mg) 65%, (1 mg) 75%, (2.5 mg) 83%, (5 mg) 94% and (10 mg) 91%; sumatriptan (6 mg) 89%; placebo 41%, (P < 0.005). The earliest report of a statistically significant difference compared with placebo for the times assessed was with sc naratriptan (10 mg) at 10 min post-dose (P = 0.023). The percentages of patients reporting adverse events were dose-related; sc naratriptan (0.5 mg) 33%, (1 mg) 29%, (2.5 mg) 43%, (5 mg) 59% and (10 mg) 71%; sc sumatriptan 53%; placebo 22%. There were no clinically significant changes in electrocardiogram (ECG), vital signs or laboratory parameters. Systemic exposure increased proportionally to the dose, the absorption of sc naratriptan was rapid (tmax = 10 min) and the half-life was 5 h. In conclusion, sc naratriptan was an effective and well-tolerated acute treatment for migraine. Copyright 1998 Lippincott Williams & Wilkins

The efficacy of subcutaneous sumatriptan in the treatment of recurrence of migraine headache.

OBJECTIVES: To investigate the efficacy of a second subcutaneous dose of 6 mg sumatriptan in the treatment of recurrence of headache after successful treatment of a migraine attack with an...

Sumatriptan. A pharmacoeconomic review of its use in migraine.

Migraine is a common illness characterised by severe, often throbbing and/or unilateral headache, which may be accompanied by sensitivity to light or noise. A minority of migraine attacks are preceded by transient visual or sensory disturbances. Migraine is associated with reductions in health-related quality of life both during and between attacks. Despite methodological limitations in cost-of-illness studies, it is clear that the cost of migraine to society is substantial. Indirect costs (primarily workplace productivity losses) make up 75 to 90% of total costs. Direct costs, such as the cost of drug treatment, physician consultation, hospitalisation and emergency room treatment, make up most of the remainder. Sumatriptan is an effective and well tolerated agent in the treatment of migraine. Its main advantage over other agents used in the acute management of migraine appears to be its rapid onset of action. Sumatriptan reduces headache severity within 2 hours of oral administration in 50 to 67% of patients and within 1 hour of subcutaneous administration in 70 to 80% of patients. Headache recurs in approximately 40% of patients who initially respond to oral or subcutaneous sumatriptan; however, a second dose of the drug is effective against the symptoms of recurrence in a majority of patients. Some patients experience relief of non-headache migraine symptoms, including nausea, vomiting, photophobia and phonophobia. Adverse events reported after sumatriptan are generally mild and transient. Data from studies of patients who used their usual therapies and sumatriptan in nonblinded, sequential phases indicate that both workplace and nonworkplace productivity losses were reduced during sumatriptan therapy. A cost-benefit analysis applied to some of these workplace productivity data indicated that, including direct costs and productivity savings, sumatriptan was associated with a net reduction in total cost of migraine. In retrospective cost analyses, sumatriptan was associated with increased prescription costs: the effect of the drug on other direct treatment costs was less clear. A retrospective pharmacoeconomic model suggested that the cost-effectiveness of subcutaneous sumatriptan versus subcutaneous dihydroergotamine depended on which outcome measure was of greatest interest. For measures of rapid relief of migraine, sumatriptan was superior, but the cost of achieving rapid relief was substantial. Sumatriptan improved global quality-of-life scores compared with patients' usual therapy in a randomised crossover trial and appeared to do the same when the drugs were administered in nonblinded, sequential phases in trials which used general and migraine-specific quality-of-life instruments. Thus, sumatriptan is associated with a fast onset of action and improvements in health-related quality of life in patients with migraine. However, the cost of achieving rapid relief of migraine symptoms may be substantial. Compared with patients' usual treatments, sumatriptan appeared to reduce workplace and non-workplace productivity losses. However, few economic data from well controlled prospective comparisons of sumatriptan with other available agents are available to quantify the effect of sumatriptan on the overall cost of migraine.

Combined Oral Lysine Acetylsalicylate and Metoclopramide in the Acute Treatment of Migraine: A Multicentre Double-Blind Placebo-Controlled Study

This multicentre, double-blind, randomized, placebo-controlled, parallel study was designed to evaluate the efficacy of combined oral lysine acetylsalicylate and metoclopramide (LAS-MCP) in the acute treatment of migraine attacks. A total of 266 patients, 18-65 years old, with two to six attacks of migraine with or without aura (IHS criteria) per month were included. The patients had to treat two migraine attacks with LAS-MCP (1620 mg lysine acetylsalicylate--the equivalent of 900 mg aspirin--combined with 10 mg metoclopramide) or placebo. The main outcome measure was headache relief (reduction in headache severity from grade 3 or 2--severe or moderate--to grade 1 or 0--mild or none) 2 h after treatment. LAS-MCP was superior to placebo for headache relief (56% vs 28%) and for the following secondary outcome measures: complete headache relief (18% vs 7%; p < 0.001), nausea (28% vs 44%; p < 0.001), vomiting (3% vs 11%; p = 0.001), use of rescue medication (47% vs 68%; p < 0.001), global efficacy judged as good or excellent (32% vs 14%; p < 0.001). The tolerability was considered as good in 94% of treated attacks in both groups. Combined oral lysine acetylsalicylate and metoclopramide is an effective and well-tolerated acute treatment of migraine attacks.

Efficacy of subcutaneous sumatriptan in the acute treatment of early‐morning migraine: a placebo‐controlled trial

To evaluate the efficacy of self-administered subcutaneous sumatriptan in the acute treatment of early-morning migraine attacks. A double-blind, randomized, placebo-controlled, cross-over study. Thirteen neurology centres in France. Patients of either sex, 18-65 years old, with two to six attacks of migraine (according to the International Headache Society (IHS) criteria, with or without aura) per month, of which at least two had to be early-morning migraine attacks. One-hundred-and-one patients were included, 96 being evaluable for the first attack and 81 for the cross-over design. Two migraine attacks (grade 2/3) were treated with sumatriptan (6 mg) or placebo, with an optional second injection 1-24 h later. Main outcome measures. The primary end-point was headache relief: reduction in headache severity from grade 2/3 (moderate/severe) to grade 1/0 (mild/none) 2 h after treatment. Sumatriptan was superior to placebo for headache relief (32 [78%] vs. 11 [28%] at the first attack; 29 [73%] vs. 8 [20%] at the second; P < 0.001). Because of a significant carry-over effect for some of the secondary end-points, a parallel-group analysis of the first attack was performed, which confirmed a significantly higher efficacy of sumatriptan for all end-points: pain-free rate (22 [46%] vs. 7 [15%]; P = 0.001) and use of a second injection (26 [53%] vs. 38 [81%]; P = 0.004). Sumatriptan was preferred by 74% of patients vs. 17% for placebo, and 9% expressed no preference (P < 0.0001). After complete relief, headache reappeared in 8/23 (35%) patients with sumatriptan and 3/7 (43%) with placebo. Adverse events were significantly more frequent with sumatriptan but they were minor and transient. Subcutaneous sumatriptan auto-injection is an effective and well-tolerated acute treatment of early-morning migraine attacks allowing earlier return to normal activity.

Sumatriptan: a selective 5-hydroxytryptamine receptor agonist for the acute treatment of migraine.

The clinical pharmacology, pharmacokinetics, clinical efficacy, adverse effects, and associated drug interactions of the novel antimigraine drug sumatriptan are reviewed. English-language publications pertaining to sumatriptan were identified via a search of the MEDLINE computerized database. Open and controlled clinical studies were reviewed in assessing clinical efficacy, although only the results of controlled, randomized trials from the basis for the conclusions pertaining to the effectiveness of sumatriptan. The primary measure of drug effectiveness in all clinical studies was significant improvement in headache severity scores. Secondary measures included functional ability, time to relief, rescue medication use, associated symptoms of nausea/vomiting and photo/phonophobia, and, in some studies, headache recurrence rate. These data were obtained from each published clinical trial and used in the overall analysis of sumatriptan efficacy. Sumatriptan is a serotonin agonist that has been studied for the acute treatment of migraine and cluster headache. The drug appears to work via specific serotonin receptors to mediate selective vasoconstriction within the cranial vasculature and to prevent the release of inflammatory mediators from trigeminal nerve terminals. The recommended dose of sumatriptan is 6 mg given subcutaneously at the onset of headache; an oral formulation is under investigation. In the published clinical trials of the oral and subcutaneous dosage forms to date, sumatriptan was effective in reducing headache severity from moderate/severe to mild/absent in approximately 70-80 percent of patients treated with active drug, compared with only 20-30 percent in the placebo groups, and 48 percent in the oral ergotamine tartrate/caffeine (Cafergot)-treated group. Secondary measures of effectiveness also favored sumatriptan. There may be a higher rate of headache recurrence with sumatriptan compared with placebo or Cafergot, although further study is necessary to confirm this observation. Adverse effects associated with sumatriptan administration generally were mild and transient and included tingling, warm/hot sensations, and pressure and tightness in the chest and neck. No significant drug interactions have yet been identified. Sumatriptan appears to represent a safe and effective alternative to the ergot alkaloids for the abortive treatment of acute migraine. However, further clinical trials, especially those yielding comparative data with current antimigraine agents, are needed to determine the full therapeutic contribution of sumatriptan.

Double‐Blind Study of Belladonna‐Ergotamine‐Phenobarbital for Interval Treatment of Recurrent Throbbing Headache

SYNOPSISIn a double‐blind study comparing crossover and parallel group designs, 55 patients with recurrent throbbing headache were given either belladonna‐ergotamine‐phenobarbital (BEP) or placebo for headache prophylaxis. Analysis of the crossover design showed BEP to be significantly more effective than placebo in reduction of headache severity and overall effectiveness. During BEP treatment, patients had less days during which medications for relief of headache symptoms were required. Although there were period effects favoring BEP, no significant differences between treatments were observed in the parallel design. The greater variability in the parallel portion of the study precluded demonstration of statistical significance with this number of patients. The crossover design indicates that BEP offers benefits in the prophylaxis of recurrent throbbing headache, without serious or frequent side effects.