Comparison of intravenous valproate versus intramuscular dihydroergotamine and metoclopramide for acute treatment of migraine headache

OBJECTIVE: To determine the effectiveness and tolerability of intravenous valproate for the acute treatment of migraine headache with or without aura (International Headache Society diagnostic criteria 1.1 and 1.2) compared with intramuscular metoclopramide 10 mg followed 10 minutes later by intramuscular dihydroergotamine 1 mg. BACKGROUND: Divalproex sodium is approved for prophylaxis of migraine headache. We studied the possible effectiveness of intravenous sodium valproate for the treatment of acute migraine headache. Valproate offers a treatment option for patients with migraine who recently have used a triptan or dihydroergotamine, theoretically avoiding the risk of drug interactions or cardiovascular complications. DESIGN/METHODS: In an open-label randomization, patients with an established diagnosis of migraine with or without aura were administered either intravenous valproate or intramuscular dihydroergotamine with metoclopramide to treat moderate-to-severe migraine headache of 24 to 96 hours' duration. Forty patients alternately received either 500 mg intravenous valproate or 10 mg metoclopramide intramuscularly followed by 1 mg dihydro- ergotamine. Patients rated severity of headache and the presence or absence of nausea, photophobia, or phonophobia at baseline, and at 1, 2, 4, and 24 hours. RESULTS: With intravenous valproate, 50% of patients reported headache improvement from moderate or severe to none or mild at 1 hour following treatment, 60% reported such improvement at 2 hours, 60% at 4 hours, and 60% at 24 hours. Corresponding improvement rates for dihydroergotamine were 45% at 1 hour, 50% at 2 hours, 60% at 4 hours, and 90% at 24 hours. Intravenous valproate and intramuscular dihydroergotamine provided similar relief from associated migrainous symptoms (nausea, photophobia, and phonophobia) during the first 4 hours following treatment. While none of the patients who received intravenous valproate experienced drug-related side effects during treatment, 15% of patients who took dihydroergotamine experienced one or more episodes of nausea and diarrhea during the first 4 hours of treatment. CONCLUSIONS: Intravenous valproate is similar in effectiveness to dihydroergotamine/metoclopramide as abortive therapy for prolonged moderate-to-severe acute migraine headache. Although the results were not statistically significant (P =.3635), intravenous valproate appears to offer a safe, effective, and well-tolerated treatment for patients with acute migraine. Relative to dihydroergotamine/metoclopramide, however, headache relief was not as likely to be sustained at 24 hours as with intravenous valproate.     

舒马普坦与散利痛治疗偏头痛急性发作疗效比较

目的比较舒马普坦与散利痛治疗偏头痛急性发作的疗效。方法57例偏头痛患者随机单盲分为舒马普坦与散利痛组,头痛开始发作时分别服用舒马普坦50 mg及散利痛1片,分别观察患者服药后起效的时间,服药后4小时的治疗有效率,各组服药后0.5、1、2、4小时头痛消失的比例及VAS评分,服药后24小时内完全止痛维持的时间,药物不良反应。结果起效时间散利痛组(1.02±0.67)小时,舒马普坦组(0.79±0.49)小时;服药后4小时治疗有效率分别为89.29%、93.10%;不良反应发生率分别为14.29%、10.34%;舒马普坦组服药后1小时头痛消失率(62.09%)高于散利痛组(32.14%),P=0.024。结论舒马普坦与散利痛均能有效治疗偏头痛急性发作,舒马普坦1小时头痛消失率高于散利痛。     

Intranasal sumatriptan for migraine in children

Question I am seeing more and more children and adolescents with headaches that can be defined as migraine headache. I have read about intranasal sumatriptan as an abortive therapy. Is this an effective treatment?Answer Acute migraine headache among children and adolescents is common and treatment is challenging. Intranasal sumatriptan is a safe and mostly effective option for children and adolescents. Currently the recommended dose is 20 mg for children who weigh more than 40 kg and 10 mg for children who weigh between 20 and 39 kg. Larger trials should be conducted to overcome the limitations of small sample sizes, potential low plasma concentration, and placebo effects witnessed in studies to date.Migraine headache is common in children, with a mean age of onset of 7 years for boys and 11 years for girls, and a prevalence of 8% to 23% by 15 years of age.^1–3 Migraine can cause substantial morbidity associated with missed school, reduced participation in sports, and even depression.^4,5The pathogenesis of migraine is multifactorial⁶ and diagnosis is made based on symptoms. (For more information, see the International Headache Society’s headache classifications.⁷)     

Costs and outcomes of early versus delayed migraine treatment with sumatriptan

OBJECTIVE: To evaluate the impact on costs and outcomes of early migraine treatment with sumatriptan while pain is mild versus sumatriptan treatment of moderate to severe pain. BACKGROUND: Migraines result in substantial pain, impairment, and costs. Recent clinical studies have shown that early treatment with sumatriptan when migraine pain is mild is more effective than sumatriptan treatment when pain is moderate to severe. DESIGN/METHODS: We developed a decision analytical model to assess the costs and outcomes per treated migraine attack, comparing early treatment while pain is mild versus delayed treatment when pain may become moderate/severe using 50 and 100 mg of sumatriptan. Parameters for the model were derived from published literature and analysis of migraine patient diary data. For each patient group the model determined the duration of mild and moderate/severe migraine pain, the proportion of patients pain free at 4 hours after initial therapy with no recurrence, medical care costs, and work loss costs (from migraine-related absenteeism and decreased productivity) during a 24-hour period. Total costs were calculated as the sum of medical care costs plus work loss costs. RESULTS: Early treatment with sumatriptan when migraine pain is mild resulted in substantially decreased total costs per treated attack as compared with treatment when pain is moderate/severe. Early treatment also resulted in decreased time with headache pain, an increased proportion of patients pain free at 4 hours without recurrence, and decreased physician and emergency department visits. Treatment with 100 mg sumatriptan resulted in better outcomes than did treatment with 50 mg sumatriptan, but outcomes with either dose for early treatment of mild pain were superior to those for either dose in delayed treatment when pain may be moderate/severe. CONCLUSIONS: Model-based results indicate that on a treated attack basis, early treatment of migraine with sumatriptan while pain is mild leads to decreased costs and improved outcomes compared to delayed sumatriptan treatment.     

Oral sumatriptan in the acute treatment of migraine and migraine recurrence in general practice

We investigated the efficacy, safety and tolerability compared with placebo of a second dose of oral sumatriptan 100 mg in 1349 general practice patients who had already treated a moderate or severe migraine headache with 100 mg sumatriptan 4 h earlier. Headache was relieved by the first sumatriptan dose in about 70% of patients, but the second dose did not produce significantly more relief than placebo, either in nonresponders or in the group as a whole, nor did it reduce other symptoms (photophobia, nausea, vomiting, etc,) at 8 h, or influence the incidence of headache recurrence. The drug was well-tolerated, and a further single dose was effective in treating recurrence after initial relief. A single 100 mg dose of sumatriptan is an effective acute treatment for migraine. A second dose should be reserved for treating headache recurrence.      

Oral rizatriptan versus oral sumatriptan: a direct comparative study in the acute treatment of migraine. Rizatriptan 030 Study Group

Rizatriptan is a potent, oral, 5-HT1B/1D agonist with more rapid absorption and higher bioavailability than oral sumatriptan. It was postulated that this would result in more rapid onset of effect. This randomized, double-blind, triple-dummy, parallel-groups study compared rizatriptan 5 mg, rizatriptan 10 mg, sumatriptan 100 mg, and placebo in 1268 outpatients treating a single migraine attack. Headache relief rates after rizatriptan 10 mg were consistently higher than sumatriptan at all time points up to 2 hours, with significance at 1 hour (37% versus 28%, P = 0.010). All active agents were significantly superior to placebo with regard to headache relief and pain freedom at 2 hours (P < or = 0.001). The primary efficacy endpoint of time to pain relief through 2 hours demonstrated that, after adjustment for age imbalance, rizatriptan 10 mg had earlier onset than sumatriptan 100 mg (P = 0.032; hazard ratio 1.21). Rizatriptan 10 mg was also superior to sumatriptan on pain-free response (P = 0.032), reduction in functional disability (P = 0.015), and relief of nausea at 2 hours (P = 0.010). Significantly fewer drug-related clinical adverse events were reported after rizatriptan 10 mg (33%, P = 0.014) compared with sumatriptan 100 mg (41%). We conclude that rizatriptan 10 mg has a rapid onset of action and relieves headache and associated symptoms more effectively than sumatriptan 100 mg.     

A prospective double-blind study of nasal sumatriptan versus IV ketorolac in migraine

We conducted a study to compare the efficacy in migraine headache of nasal sumatriptan and intravenous ketorolac. The study was a prospective, double-blind study done with a convenience sample of 29 patients presenting to the emergency department (ED) with acute migraine. Patients received either 20 mg of nasal sumatriptan or 30 mg of intravenous ketorolac. Patients scored the severity of their headache on a 100-mm visual analog scale (VAS) of pain prior to medication, and again 1 hour after medication. Differences between initial and 1-hour scores were analyzed. Before treatment, no difference existed between the groups in the intensity of headache. One hour after medication, the sumatriptan group had a decrease in pain score of 22.937 mm and the ketorolac group a decrease of 71.462 mm on the VAS. The decrease in pain score with ketorolac was significantly greater than that with sumatriptan (P < 0.001). The study therefore showed that both sumatriptan and ketorolac effectively reduced the pain associated with acute migraine headache, but that intravenous ketorolac produced a greater reduction in pain than did nasal sumatriptan.     

A comparative trial of zolmitriptan and sumatriptan for the acute oral treatment of migraine

OBJECTIVE: This randomized, double-blind, parallel group multicenter study compared response rates and tolerability of zolmitriptan with sumatriptan in the acute treatment of migraine. METHODS: A sample consisting of 1445 outpatients with an established diagnosis of migraine was randomized to zolmitriptan, 2.5 mg or 5 mg, or sumatriptan, 25 mg or 50 mg. Patients took 1 tablet for moderate/severe migraine and a second identical tablet, if necessary, for recurrent headache of moderate/severe intensity 4 to 24 hours after the initial dose. Up to six attacks were treated during a 6-month period. The primary outcome measure was headache response 2 hours after the initial dose. Secondary end points included 1-hour and 4-hour headache response and pain relief over 24 hours. RESULTS: A headache response at 2 hours was noted in 67.1% of patients taking zolmitriptan, 2.5 mg, and 64.8% of those taking zolmitriptan, 5 mg, versus 59.6% of patients taking sumatriptan, 25 mg, and 63.8% of those taking sumatriptan, 50 mg. At 2 and 4 hours, the differences between zolmitriptan, 2.5 mg, and sumatriptan, 25 mg, were statistically significant (odds ratio=1.49 and 1.67, respectively; both P<.001). Statistically significant differences between zolmitriptan, 2.5 mg, and sumatriptan, 50 mg, were seen at 2 and 4 hours post dose (odds ratio=1.21 and 1.23, respectively; both P<.05). At 1 hour post dose, the headache response rate for zolmitriptan, 2. 5 mg, was numerically higher than response rates for sumatriptan, 25 mg and 50mg (odds ratio=1.16, odds ratio=1.06, though they failed to reach statistical significance; P=.061, P=.461 respectively). Differences between zolmitriptan, 5 mg, and sumatriptan, 25 mg, were statistically significant at 1, 2, and 4 hours (odds ratio=1.43, 1. 46, and 1.78, respectively; all P<.001) and at 1 and 4 hours versus sumatriptan, 50 mg (odds ratio=1.28, P=.002; odds ratio=1.29, P=.012, respectively). Although not statistically significant at 2 hours, more patients responded to zolmitriptan, 5 mg, than to sumatriptan, 50 mg (odds ratio=1.16, P=.064). Patients receiving zolmitriptan, 2. 5 mg or 5 mg, achieved more pain relief over 24 hours than patients receiving sumatriptan, 25 mg (odds ratio=1.47, and 1.54 respectively, both P<.001) or sumatriptan, 50 mg (odds ratio=1.17, P=.021; odds ratio=1.22, P=.005, respectively). All treatments were well tolerated. CONCLUSIONS: Zolmitriptan, 2.5 mg and 5 mg, was at least as effective as sumatriptan, 25 mg or 50 mg, for all parameters studied. Zolmitriptan, 2.5 mg, was significantly more effective than sumatriptan, 50 mg, in terms of headache response at 2 and 4 hours. Patients taking zolmitriptan were significantly more likely to have pain relief over 24 hours than those taking sumatriptan.     

A dose-defining study of sumatriptan suppositories in the acute treatment of migraine

In this dose-ranging, randomised, multinational, multicentre, double-blind, placebo-controlled, parallel group study, 431 patients treated a single migraine attack with study medication: sumatriptan suppository 6 mg, 12.5 mg, 25 mg, 50 mg, 100 mg, or placebo. Patients were treated in the clinic with a single dose in suppository form. All doses of sumatriptan, except 6 mg, were significantly better than placebo (p < 0.004) and achieved similar rates of headache relief within two hours of dosing. The highest response rate was in the 25 mg group (72%) compared with placebo (37%) (p < 0.001). Fewer patients required rescue medication in the active groups (1% 100 mg to 13% 6 mg) compared with placebo (17%), and more patients were able to work and function normally two hours after dosing (41%, 100 mg; 20%, placebo). The overall incidence of adverse events was similar in the placebo, 6 mg and 12.5 mg groups (14-17%) but higher in the 25 mg, 50 mg and 100 mg groups (25%, 32% and 29% respectively). Analysis of plasma sumatriptan levels indicated rapid rectal absorption for all doses (median tmax = 1.0 hr). It is concluded that sumatriptan, in doses above 6 mg, is an effective and well tolerated treatment for acute migraine. From this study doses of 12.5 mg and 25 mg sumatriptan were identified as having the best efficacy/safety profile and were evaluated further.     

A clinical trial of trimethobenzamide/diphenhydramine versus sumatriptan for acute migraines

BACKGROUND: Although various classes of medication are used to treat acute migraine in the emergency department (ED), no treatment offers complete pain relief without side effects or recurrence of headache. Consequently, even though several antiemetic medications as well as SQ sumatriptan have demonstrated efficacy and tolerability for the ED treatment of migraine, there remains a need for more effective parenteral therapies. Open-label studies suggest that the combination of trimethobenzamide and diphenhydramine (TMB/DPH) may provide effective relief in a high proportion of migraineurs. OBJECTIVE: To test the hypothesis that ED patients with acute migraine, given intramuscular TMB/DPH, would have a larger reduction in their pain scores than patients given SQ sumatriptan. METHODS: This was an ED-based, randomized, double-blind, "double-dummy" clinical trial comparing 2 parenteral treatments for acute migraine headaches. Subjects received a combination of TMB 200 mg and DPH 25 mg as a single intramuscular injection or 6 mg of SQ sumatriptan. Pain scores, disability scores, associated symptoms, and adverse effects were assessed for 2 hours in the ED and by telephone 24 hours after medication administration. The primary outcome was the between-group difference in reduction of pain intensity as measured by a validated numerical rating scale 2 hours after medication administration. This study was designed to detect superiority of TMB/DPH; therefore, a 1-tailed t-test was used. An interim analysis was planned to terminate the trial if predetermined endpoints in the primary outcome variable were reached. RESULTS: The trial was stopped by the data monitoring committee after 40 subjects were enrolled because a substantial benefit in the primary outcome was found favoring sumatriptan. Baseline pain scores were comparable between the 2 groups. By 2 hours, sumatriptan subjects had improved by a mean of 6.1 and the TMB/DPH subjects had improved by a mean of 4.4 (95% CI for difference of 1.7: -0.1 to 3.4). By 24 hours after medication administration, sumatriptan subjects had a mean improvement from baseline of 4.9 as compared to 5.3 for TMB (95% CI for difference of -0.4: -2.4 to 1.6). The need for rescue medication was comparable between the groups. No serious or frequent adverse effects were noted in either group. CONCLUSIONS: SQ sumatriptan is probably superior to TMB/DPH for treating the pain of acute migraine at 2 hours. However, TMB/DPH was well-tolerated, efficacious, and relieved pain comparably to sumatriptan at 24 hours. TMB/DPH might have a role in select populations in which sumatriptan is contraindicated or likely to be ineffective.     

Prospective large-scale study of the tolerability of subcutaneous sumatriptan injection for acute treatment of migraine

To investigate prospectively serious adverse events associated with sumatriptan injection, we studied 12,339 typical migraineurs for up to 12 months each. This study imitated the ordinary clinical use of sumatriptan injection except that: (a) a short, written informed consent was required, (b) there was a centralized, automated dispensing service that audited each patient's product use, (c) patients were sometimes reviewed by telephone, and (d) drug supply and medical consultation were without charge. All adverse events were recorded regardless of etiology. There were 25 fatalities during the study, none being attributable to sumatriptan injection. Of six strokes in the study, two occurred soon after treatment of a migraine attack with sumatriptan injection; whether these were migraine-related or drug-related is discussed. None of the three myocardial infarctions was due to sumatriptan injection use. We conclude that sumatriptan injection is well tolerated when used in accordance with labeling.     

Long-term evaluation of sumatriptan and naproxen sodium for the acute treatment of migraine in adolescents

Objectives.— To evaluate the long‐term safety, tolerability, effectiveness, impact on quality of life, and medication satisfaction of sumatriptan/naproxen sodium in the acute treatment of migraine headache in adolescents. Methods.— This 12‐month, multicenter, open‐label, safety study was conducted in adolescents (aged 12‐17 years) with an average of 2‐8 migraines/month typically lasting >2 hours untreated for >6 months prior to initiation. Subjects were instructed to treat migraines as early as possible and were allowed to rescue 2 hours post dose with a single dose of a naproxen‐containing product, over‐the‐counter pain reliever, or anti‐emetics. Subjects were advised not to take a second tablet of sumatriptan/naproxen sodium without at least a 24‐hour headache‐free period. Safety evaluations included adverse events, laboratory tests, and vital signs and electrocardiogram evaluation. Other evaluations included freedom from pain, quality of life, and medication satisfaction. Results.— Of the 656 subjects enrolled, 622 (95%) treated at least 1 migraine with sumatriptan/naproxen sodium, of which 435 (70%) and 363 (58%) completed 6 and 12 months of the study, respectively. Overall, there were 12,927 exposures to sumatriptan/naproxen sodium: on average 2.5 tablets were taken per month per subject. The most common treatment‐related adverse events were nausea (7%), dizziness (3%), muscle tightness (3%), and chest discomfort (3%). There were no deaths; 4 subjects had 5 serious adverse events (suicide attempt, hemolytic anemia and syncope, suicidal ideation, spontaneous abortion) unrelated to sumatriptan/naproxen sodium and resolved without sequelae. Seven percent of subjects discontinued participation in the study because of an adverse event; 5% of subjects discontinued due to lack of efficacy. Overall, 42% of the migraine attacks were pain‐free within 2 hours of treatment with sumatriptan/naproxen sodium, subjects reported improvements from baseline in 2 of 3 quality of life domains over time, and were generally satisfied with the efficacy and overall treatment at the end of the study. Conclusion.— In adolescent migraineurs, after up to 12 months and over 12,000 exposures to sumatriptan/naproxen sodium, there were no new or clinically significant findings in the safety parameters, including the frequency and nature of adverse events, as compared to the individual components or to the adverse event profile in adults. In addition, sumatriptan/naproxen sodium provided freedom from pain over time, improvements in quality of life and medication satisfaction.     

Oral sumatriptan for the acute treatment of probable migraine: first randomized, controlled study

OBJECTIVE: To evaluate the efficacy and tolerability of sumatriptan tablets in adults who meet International Headache Society (IHS) criteria for probable migraine but who do not meet IHS criteria for migraine with or without aura. BACKGROUND: Headaches with some but not all of the features of migraine meet criteria for probable migraine, a form of migraine recognized by the IHS. Probable migraine attacks are also prevalent and frequently underdiagnosed. METHODS: This was a randomized, multicenter, double-blind, placebo-controlled, parallel-group study. Adults (18 to 65 years) with a 1-year history of headaches that met 2004 IHS criteria for probable migraine without aura (same operational definition as 1988 IHS migrainous disorder) were eligible for enrollment. All patients were triptan- and ergot-na?ve and had never been diagnosed with migraine. Patients were randomized in a 1:1:1:1 fashion to receive sumatriptan 25, 50, or 100 mg conventional tablets or matching placebo and were instructed to treat a single moderate or severe probable migraine attack. A post hoc analysis was conducted to evaluate the population of patients who achieved headache relief sustained throughout the immediate posttreatment period. Patients who reported relief within 2 hours and subsequently lost headache relief within 4 hours were considered nonresponders. RESULTS: At 2 hours, more patients treated with sumatriptan achieved headache relief, the primary efficacy measure, compared with placebo, but differences only approached statistical significance for 100 mg (P= .053). The 2-hour headache relief rate in the sumatriptan 25 or 50 mg groups was not significantly different than placebo. The time to use of rescue was significantly shorter in the placebo group compared with the sumatriptan 100 mg group (P= .002). The time to use of rescue in the sumatriptan 25 or 50 mg groups was not significantly different than placebo. More patients treated with placebo (22%) lost headache relief within 4 hours compared with patients treated with sumatriptan 25 mg (17%), 50 mg (14%), or 100 mg (7%). A post hoc analysis demonstrated that at 2 hours, headache relief sustained through 4 hours (S 0-4 hours) was achieved in 44%, 49%, and 57% of patients treated with sumatriptan 25, 50, and 100 mg, respectively, compared with 34% of patients treated with placebo (P < .05 for sumatriptan 50 and 100 mg vs. placebo). All doses of sumatriptan were well tolerated and no serious adverse events were reported. CONCLUSION: These results suggest that oral sumatriptan may be effective and is well tolerated for the acute treatment of probable migraine without aura, however, the difference between sumatriptan and placebo was not statistically significant for the a priori defined primary endpoint.     

Droperidol for acute migraine headache.

The use of intramuscular droperidol to treat acute migraine headache has not been previously reported in the emergency medicine literature. It is a promising therapy for migraine. The authors performed a pilot review of all patients receiving droperidol for migraine in our emergency department (ED) to evaluate its efficacy. We used a retrospective case series, in a suburban ED with an annual patient census of 48,000. All patients with a discharge diagnosis of migraine headache who were treated with i.m. droperidol during a consecutive 5-month period in our ED were identified. All patients received droperidol 2.5 mg intramuscular. As per ED protocol, their clinical progress was closely followed and documented at 30 minutes after drug administration (t30). Demographic and clinical variables were recorded on a standardized, closed-question, data collection instrument. The primary outcome measurement was relief of symptoms at t30 to the point that the patient felt well enough to go home without further ED intervention (symptomatic relief). Thirty-seven patients were treated (84% female), with an ED diagnosis of acute migraine with droperidol during the study period. The mean age was 36 +/- 12 years. Analgesics had been used within 24 hours before ED presentation by 62% of patients. At t30, 30 (81%) patients had symptomatic relief, 2 (5%) felt partial relief but required rescue medication, and 5 (14%) had no relief of symptoms. Drowsiness (14%) and mild akathisia (8%) were the only adverse reactions observed following drug administration. Droperidol 2.5 mg intramuscular may be a safe and effective therapy for the ED management of acute migraine headache. Randomized, controlled trials are warranted to further validate the findings of this preliminary study.     

Intravenous versus oral corticosteroids for treatment of acute asthma exacerbations

OBJECTIVE: To compare the duration of hospitalization of patients treated with either oral or intravenous corticosteroids for an acute asthma exacerbation. METHODS: A retrospective chart review was performed on a random sample of inpatients. Patients were included with the following: a discharge diagnosis of an acute asthma exacerbation, a past medical history significant for asthma, age between 16 and 60 years, and treatment with either oral or intravenous corticosteroids at the time of admission. Exclusion criteria included: patients receiving chronic prednisone therapy, a past medical history significant for chronic obstructive pulmonary disease, an admission to the intensive care unit, or a consistent smoking habit of at least 1 pack daily. Length of hospitalization was the primary outcome measured. Secondary outcomes included 24-hour peak expiratory flow rate, 24-hour pulse oximetry (pO(2)), and amount of beta-agonist and ipratropium used. RESULTS: Fifty-three patients were included in the final data analysis. Patients were grouped by route of corticosteroid administration (intravenous or oral). No significant differences were noted between the 2 groups for race, gender, age, height, weight, admission peak expiratory flow rate, admission pO(2), or types of asthma medications used prior to admission. No significant differences were demonstrated in any of the outcome measures. CONCLUSIONS: Both the intravenous and oral corticosteroid groups demonstrated similar clinical outcomes and lengths of hospitalization in the treatment of acute asthma exacerbations. These results support the initial use of oral corticosteroids for the treatment of acute asthma exacerbations in adult patients admitted to a general medical service.     

Intravenous versus intramuscular midazolam in treatment of chemically induced generalized seizures in swine

Midazolam is a water-soluble benzodiazepine proven to be efficacious in sedation, hypnosis, and induction and maintenance of anesthesia. Because of its water solubility, it is a desirable drug for the control of status epilepticus when intravenous (IV) access is not obtainable. This study compares intramuscular (IM) versus IV routes of administration of midazolam in the control of tonic-clonic activity produced by chemically induced generalized seizures in a swine model. When midazolam was administered by IV route, tonic-clonic activity lasted a mean of 34 ± 5.4 seconds, and when administered by IM route, the tonic-clonic activity lasted a mean of 116 ± 41 seconds. Both were considerably abbreviated when compared with the expected duration of pentylenetetrazol-induced seizures in the swine model. Serum levels of midazolam achieved by the IV route were considerably higher than those achieved by the IM route. It is concluded that midazolam is effective in the control of tonic-clonic manifestations of generalized seizures when administered by the IV or the IM route and that no correlation exists between serum levels achieved and the time to control the seizure.