Subcutaneous Sumatriptan Research Articles

Efficacy of subcutaneous sumatriptan in postcraniotomy pain and opioid consumption.

Traditional pain management pathways following craniotomy are predicated on opioids. However, narcotics can confound critical neurological examination, contribute to respiratory depression, lower the seizure threshold, and lead to medication habituation, dependence, and/or abuse. Alternative medications to better address postoperative pain while mitigating opioid-related adverse effects remain insufficiently studied. Preliminary studies suggest sumatriptan, a 5-HT (1B/1D) receptor agonist known to regulate dural vasoactivity and inflammation, may moderate pain following trigeminal microvascular decompression and chronic postcraniotomy headache. In this study, the authors evaluated the efficacy of sumatriptan to modulate pain and opioid requirements following craniotomy surgery. This was a single academic center, retrospective cohort study of 300 consecutive adult patients who underwent elective craniotomy surgery between 2015 and 2022. Patients were equally divided between a control and a sumatriptan cohort contingent upon administration of 6 mg of subcutaneous sumatriptan within 1 hour of surgery completion and prior to opioid administration. Postoperative opioid consumption at 6, 12, and 24 hours, as well as admission total, inpatient length of stay, and 30-day global reevaluation, were assessed. Three hundred patients were included for analysis. Significant differences were seen in baseline hypertension (p < 0.01), hyperlipemia (p < 0.01), anxiety (p = 0.04), and operative time (p = 0.02). A significant reduction of mean postoperative pain scores at 12 (p = 0.03) and 24 (p < 0.01) hours and total opioid consumption (p = 0.04) was observed in the sumatriptan cohort. Subgroup analysis revealed significantly lower postoperative pain scores at 6 (p = 0.05), 12 (p < 0.01), and 24 (p < 0.01) hours in patients who underwent burr hole placement in the sumatriptan cohort as compared with controls; however, no significant difference in opioid consumption was noted. No adverse events related to sumatriptan administration were noted throughout the study. Postoperative single-dose subcutaneous sumatriptan following elective craniotomy may reduce pain scores and opioid requirements. Additional studies are needed to better understand nuanced differences in opioid modulation and optimal patient selection.

Migraine treatment – updated recommendations 2024 –development of the Expert Group of the Headache Section ofthe Polish Neurological Society and the Polish Society for theStudy of Pain

Migraine is one of the most frequent disabling neurological conditions with a major impact on the patients qualityof life. Migraine treatment recommendations are provided based on a review of the literature from randomizedclinical trials and the consensus of a national expert panel. All available medical reference systems were screened for the range of past and present clinical studies on migraine with and without aura and on migraine-like syndromes.The results of these studies were presented in accordance with the recommendations of the Migraine Section ofthe Polish Neurological Society and the Polish Society for the Study of Pain. For the acute treatment of migraineattacks, oral non-steroidal antiinflammatory drug (NSAID), triptans and new class of drugs gepants and ditans arerecommended. The administration should follow the concept of stratified treatment. Before intake of NSAID andtriptans, oral metoclopramide is recommended. In very severe attacks, subcutaneous sumatriptan are drugs of firstchoice. Status migrainosus can be treated by cortoicosteroids, although this is not universally held to be helpful. Forthe prophylaxis of migraine, old and new drugs – betablockers flunarizine, valproic acid, and topiramate as well asmonoclonal anti CGRP antibodies, gepants and botulin toxin are drugs of first choice.

Management of cluster headache: Treatments and their mechanisms.

The management of cluster headache is similar to that of other primary headache disorders and can be broadly divided into acute and preventive treatments. Acute treatments for cluster headache are primarily delivered via rapid, non-oral routes (such as inhalation, nasal, or subcutaneous) while preventives include a variety of unrelated treatments such as corticosteroids, verapamil, and galcanezumab. Neuromodulation is becoming an increasingly popular option, both non-invasively such as vagus nerve stimulation when medical treatment is contraindicated or side effects are intolerable, and invasively such as occipital nerve stimulation when medical treatment is ineffective. Clinically, this collection of treatment types provides a range of options for the informed clinician. Scientifically, this collection provides important insights into disease mechanisms. Two authors performed independent narrative reviews of the literature on guideline recommendations, clinical trials, real-world data, and mechanistic studies. Cluster headache is treated with acute treatments, bridge treatments, and preventive treatments. Common first-line treatments include subcutaneous sumatriptan and high-flow oxygen as acute treatments, corticosteroids (oral or suboccipital injections) as bridge treatments, and verapamil as a preventive treatment. Some newer acute (non-invasive vagus nerve stimulation) and preventive (galcanezumab) treatments have excellent clinical trial data for episodic cluster headache, while other newer treatments (occipital nerve stimulation) have been specifically tested in treatment-refractory chronic cluster headache. Most treatments are suspected to act on the trigeminovascular system, the autonomic system, or the hypothalamus. The first-line treatments have not changed in recent years, but new treatments have provided additional options for patients.

447 Modulation of Patient Reported Outcomes and Opioid Consumption Following Open Craniotomy: The Efficacy and Safety of Subcutaneous Sumatriptan

INTRODUCTION: Traditional pain management regimens following open craniotomy commonly employ opioid medications. As a medication class, opioids present a considerable adverse effect profile and the potential for medication abuse. Alternative medication regimens to better address post-craniotomy pain while mitigating opioid-related adverse effects are insufficiently studied. However, as a dural-based 5-HT1D receptor agonist that regulates vasoconstriction and inflammatory peptide signaling, sumatriptan shows promise to improve pain scores and reduce opioid requirements. METHODS: This is a single academic center, retrospective cohort study of 130 consecutive adult patients undergoing open craniotomy between 7/2015 and 8/2021. Patients were divided between a Control and Sumatriptan cohort contingent upon administration of a single 6mg subcutaneous injection of sumatriptan within 1-hour of surgery completion and prior to opioid administration. Opioid consumption at 6, 12 and 24-hours postoperative and admission total, inpatient length of stay (LOS) and 30-day global representation/readmission were evaluated. RESULTS: 130 patients were equally divided between the Sumatriptan and Control cohorts for analysis. No difference in baseline demographics was noted. A significant reduction of mean pain score at 6, 12 and 24-hours following surgery substantially favored the Sumatriptan cohort (p &lt; 0.05). Further, a nonsignificant reduction in opioid requirements was observed at all timepoints favoring the sumatriptan cohort (p &gt; 0.05). 30-day global ED evaluation and readmission rates between cohorts were similar (p &gt; 0.05). Overall LOS in the Sumatriptan and Control cohorts were 5.3 ± 3.6 vs 6.5 ± 5.6 days (p &gt; 0.05). No difference in the rate of incisional or intracerebral hemorrhage was noted between cohorts (p &gt; 0.05). CONCLUSIONS: In the present study, patients in the Sumatriptan cohort demonstrated enhanced pain control and reduced opioid requirements suggesting sumatriptan represents a safe and efficacious agent for the modulation of pain following open craniotomy.

PATHOPHYSIOLOGY IN CLUSTER HEADACHE: AN UPDATE

Cluster headache (CH) is a rare and very painful primary headache syndrome, with an estimated population prevalence of 0.12%. This condition can be episodic (ECH), lasting from 7 days to a year. A consensus statement from the European Headache Federation defines refractory CCH as a CCH with at least three severe attacks per week, even though at least three consecutive trials of adequate preventive care have been tested and managed with both acute and preventive treatment. Inhaled oxygen and subcutaneous sumatriptan are the two most effective acute treatment options for people with CH. Several preventive medications are also available, and the most effective is verapamil. However, most of these agents are not supported by strong clinical evidence. In some patients, this option may be ineffective, particularly in those with chronic CH. Surgical procedures for chronic refractory forms of disorder should then be considered.

Clinical Profile of Chronic Cluster Headaches in a Regional Headache Center in Japan.

Objective Little is known about the prevalence and characteristics of chronic cluster headache (CCH) in Japan. We therefore characterized the clinical profile of CCH in Japan by surveying patients with CCH who were registered at a Japanese regional headache center. We also reviewed the existing literature for the prevalence and clinical characteristics of CCH reported in various populations. Methods In this single-center retrospective study, we assessed consecutive patients with cluster headache (CH) who visited a regional tertiary headache center between February 2011 and July 2020. They were treated following the Clinical Practice Guideline for Chronic Headache 2013. We compared their demographic characteristics and clinical features according to the CCH onset pattern (primary vs. secondary). Results Of 420 patients with CH, 19 (4.2%) had CCH (9 primary and 10 secondary). The incidence of CCH in Japan is relatively low compared to that in Western countries but is comparable to that in other Asian countries. CCH showed a higher predominance of men than women. Compared to primary CCH, secondary CCH included a higher proportion of current smokers and older patients during clinic visits. Subcutaneous sumatriptan and oxygen inhalation were the most common abortive treatments, and oral prednisolone and verapamil were the most common preventive treatments. Home oxygen therapy was effective in six of seven patients. Only two patients with coexisting migraine received calcitonin gene-related peptide (CGRP)-targeted therapies. Conclusions CCH remains refractory to treatment. Improving treatment outcomes will require maximizing the use of currently available drugs and expanding the use of neuromodulation, nerve block, and CGRP-targeted therapies.

Efficacy and Safety of Subcutaneous Sumatriptan for Acute Migraine Attacks Compared with other treatments: A Systematic Review and Network Meta-analysis. (P12-2.005)

Efficacy and Safety of Subcutaneous Sumatriptan for Acute Migraine Attacks Compared with other treatments: A Systematic Review and Network Meta-analysis. (P12-2.005)

Cluster headache in adults.

SUMMARYCluster headache is characterised by attacks of very severe, unilateral headache lasting 15–180 minutes, up to eight times per day. The attacks are associated with cranial autonomic symptoms on the same side and a sense of agitation or restlessnessFirst-line acute abortive treatments include intranasal or subcutaneous sumatriptan or high-flow oxygen. Neuromodulation may benefit some patientsFirst-line preventive therapy is high-dose verapamil. Close monitoring is required for the adverse effect of arrhythmiaThere are several emerging therapies that have either proven efficacy, or possible benefit for cluster headache. They include drugs aimed at the calcitonin gene-related peptide

Sumatriptan 3 mg subcutaneous : Clinical relevance of acute treatment of migraine despite dose reduction

Triptans are ahighly effective substance class in the acute treatment of migraine attacks. They contribute to a substantial improvement in the quality of life and help to reduce the socioeconomic burden of the disease. Sumatriptan is the only triptan that is available for subcutaneous administration. It is primarily indicated in patients with the need for rapid relief or insufficient enteral resorption due to nausea and vomiting. In the treatment of migraine attacks with 6 mg subcutaneous sumatriptan the number needed to treat (NNT) is 2.3 for freedom from pain within 2 h and the NNT is 2.1 for pain relief within 2 h; however, the fast resorption of sumatriptan after subcutaneous administration induces more side effects than the oral route, for example dizziness, paresthesia or chest pressure sensation. Clinical studies showed that reducing the subcutaneous dose to 3 mg in migraine treatment has significantly better tolerability with high response rates and freedom from pain within 2 h with 66.7% (3 mg) or 50% (6 mg).

Naratriptan is as effective as sumatriptan for the treatment of migraine attacks when used properly. A mini-review.

Naratriptan, marketed in a low oral dose of 2.5 mg, is generally regarded as a less-effective triptan with a slower onset of action than most other triptans in the treatment of migraine attacks. In this review, naratriptan will be compared with sumatriptan, the standard triptan. Papers on pharmacodynamics and pharmacokinetics and results from comparative clinical trials with oral and subcutaneous naratriptan versus other triptans were retrieved from PubMed. Naratriptan and sumatriptan have similar effects in relevant animal models. In a randomized controlled trial, oral naratriptan 2.5 mg is less effective than oral sumatriptan 100 mg after both 2 h and 4 h. In contrast, oral naratriptan 10 mg has a similar time-effect curve as oral sumatriptan 100 mg, in both its steepness and the efficacy at 2 h and 4 h. Subcutaneous naratriptan 10 mg (88% pain free at 2 h) was in one trial superior to subcutaneous sumatriptan 6 mg (55% pain free at 2 h). Naratriptan was marketed for the treatment of migraine attacks as the "gentle triptan" in a low oral dose of 2.5 mg, a dose with no more adverse events than placebo. This low dose results in the slow onset of action and low efficacy of oral naratriptan, but in high doses oral naratriptan is similar to oral sumatriptan. Based on one randomized controlled trial, subcutaneous naratriptan has probably the greatest effect of any triptan.

Effect of dural inflammatory soup application on activation and sensitization markers in the caudal trigeminal nucleus of the rat and the modulatory effects of sumatriptan and kynurenic acid

BackgroundThe topical inflammatory soup can model the inflammation of the dura mater causing hypersensitivity and activation of the trigeminal system, a phenomenon present in migraineurs. Calcitonin gene-related peptide, transient receptor potential vanilloid-1 receptor, and neuronal nitric oxide synthase are important in the sensitization process there.5-HT1B/1D receptor agonists, triptans are used as a treatment of migraine. Kynurenic acid an NMDA antagonist can act on structures involved in trigeminal activation.AimWe investigated the effect of inflammatory soup induced dural inflammation on the calcitonin gene-related peptide, transient receptor potential vanilloid-1 receptor, and neuronal nitric oxide synthase levels in the caudal trigeminal nucleus. We also tested whether pretreatment with a well-known antimigraine drug, such as sumatriptan and kynurenic acid, a compound with a different mechanism of action, can affect these changes and if their modulatory effects are comparable.Material and methodsAfter subcutaneous sumatriptan or intraperitoneal kynurenic acid the dura mater of adult male Sprague-Dawley rats (n = 72) was treated with inflammatory soup or its vehicle (synthetic interstitial fluid). Two and a half or four hours later perfusion was performed and the caudal trigeminal nucleus was removed for immunohistochemistry.Results and conclusionInflammatory soup increased calcitonin gene-related peptide, transient receptor potential vanilloid-1 receptor, and neuronal nitric oxide synthase in the caudal trigeminal nucleus compared to placebo, which was attenuated by sumatriptan and kynurenic acid. This suggests the involvement of 5-HT1B/1D and NMDA receptors in neurogenic inflammation development of the dura and thus in migraine attacks.

Efficacy of medications in adult patients with trigeminal neuralgia compared to placebo intervention: a systematic review with meta-analyses.

BackgroundTrigeminal neuralgia (TN) is characterized by brief, unilateral, sharp, stabbing, and shooting pain of the fifth cranial nerve. The objective of this systematic review with meta-analysis was to determine the effect of medications compared to placebo in adult patients with TN.MethodsReview authors identified randomized placebo-controlled trials (RCTs) from PubMed, Web of Science, Cochrane, and EMBASE up to February 2021. We assessed the inclusion and exclusion criteria as well as the risk of bias of the studies based on the Cochrane Handbook. A total of 324 unduplicated references were scanned independently and reduced to eight relevant RCTs, with 89 patients included. Medications investigated included oral carbamazepine, subcutaneous sumatriptan, lidocaine (intranasal, 8% spray on the oral mucosa or intravenous), buprenorphine (ganglionic local opioid analgesia), and oral Nav1.7, a selective sodium channel blocker.ResultsMeta-analyses showed that overall patients receiving lidocaine reported a significantly lower post-treatment intensity of pain −3.8 points on a 0–10 scale (95% Cl = −4.653 to −2.873; P < 0.001). Patients who received lidocaine were 8.62 times more likely to have pain improvement than patients on placebo (P < 0.001). In one RCT, patients receiving oral carbamazepine showed a significant improvement in pain intensity of −32% compared to the placebo (P < 0.001). In one trial, patients receiving 3 mg subcutaneous sumatriptan had a significantly lower intensity of pain on average −6.1 points on a scale of 0–10 compared to placebo (P < 0.001) and a significant improvement in pain intensity of −75% compared to the improvement in the placebo group (P < 0.001). Patients who received subcutaneous sumatriptan were 10 times more likely to have pain improvement than those who received placebo (P = 0.001) in one study. Due to the unclear/high risk of bias and small sample size, the quality of the evidence for lidocaine in the treatment of TN was low.ConclusionFurther studies are needed for carbamazepine, sumatriptan, buprenorphine, and oral Nav1.7 sodium channel blockers, as only one study reported outcomes.

A phase 1 randomized study of hemodynamic effects and pharmacokinetic interactions during concomitant use of rimegepant and sumatriptan in healthy adults

Objective: This randomized, partially-blinded, placebo-controlled study evaluated hemodynamic effects, pharmacokinetic interactions, and safety of concomitant administration of oral rimegepant and subcutaneous sumatriptan. Methods: Healthy non-smokers aged ≥18 and ≤40 years (men) or ≥18 and ≤50 years (women) were enrolled. On Day 1, subjects received 12 mg of sumatriptan as 2 subcutaneous 6 mg injections separated by 1 hour. From Days 2 to 4, subjects received rimegepant or placebo once daily (randomized 6 to 1, rimegepant to placebo). On Day 5, subjects received rimegepant or placebo, followed 2 hours later by 2 subcutaneous 6 mg injections of sumatriptan, separated by 1 hour. Sumatriptan was administered at the same times as on Day 1. Results: All 42 dosed subjects were analyzed. There were no significant differences in the time-weighted average of mean arterial pressure, diastolic blood pressure, or systolic blood pressure between treatment with rimegepant + sumatriptan and sumatriptan alone. Co-administration of rimegepant and sumatriptan had no effect on the pharmacokinetics of either drug. Overall, 93% (39/42) of subjects experienced ≥1 adverse event; injection site reaction was most common (60% [29/42]). Conclusions: Concomitant administration of oral rimegepant and subcutaneous sumatriptan to healthy adults was without hemodynamic or pharmacokinetic interaction and was safe and well tolerated.

Migraine Treatment in Emergency Departments of Brazil: A Retrospective Study of 2 Regions.

This study describes the approaches, medications used, and time of care for migraineurs, who have been in emergency departments (ED) from 2 different regions of Brazil. Retrospective, cross-sectional, observational, non-randomized study of migraine patients seen at 2 headache centers in Brazil. Eighty-four migraine patients (15 men and 69 women) were divided into 2 groups: chronic (19%, n=16) and episodic migraineurs (81%, n=68). In the ED, medications were used in the following order of frequency: dipyrone or metamizole (89.3%, 75/84), nonsteroidal anti-inflammatory drugs (57.1%; 48/84) opioids (51.1%; 43/84), metoclopramide (29.8%; 25/84), dexamethasone (28.6%; 24/84), chlorpromazine (13.1%; 11/84), and subcutaneous sumatriptan (7.1%; 6/84). The average time in the care center was 8.2hours, but only 23 patients (27.4%) left the hospital with greater than 50% relief in headache severity. Dipyrone and nonsteroidal anti-inflammatories were the most used drugs, but nearly half received opioids. More efficient drugs were poorly used. Considering the number of patients leaving the hospital with headache relief, a changing treatment paradigm should be carried out in Brazil.

Onset of action in placebo-controlled migraine attacks trials: A literature review and recommendation.

Migraine patients want acute treatment to provide complete relief of the migraine attack within 30 minutes. Traditionally, "speed of onset of effect" is evaluated by estimating the time-point for first statistical separation of drug and placebo. The estimated onset of effect can be a few percent difference of patients being pain free in very large randomised, controlled trials. This difference, however, can be clinically irrelevant. Placebo-controlled randomised, controlled trials with pain freedom results from 30 min to 2-4 hours were retrieved from the literature. For each time-point, the therapeutic gain (drug minus placebo) (TG) was calculated. Therapeutic gain for being pain free of 5% was chosen for the definition of "onset of action", since this is approximately 1/3 of the 16% TG and 1/4 of 21% of TG for sumatriptan 50 mg and 100 mg, respectively. A total of 22 time-effect curves based on randomised, controlled trials were analysed. Based on the "onset of action" of 5% pain freedom, the evaluated drugs and administration forms can be classified as follows: i) Early time to onset, ≤30 min (three randomised, controlled trials); ii) medium time to onset, 60 min (nine randomised, controlled trials); iii) delayed time to onset, 90-120 min (10 randomised, controlled trials). Only three non-oral administration forms with a triptan (subcutaneous sumatriptan and nasal zolmitriptan) resulted in an "onset of action" at ≥30 min; in the future, early onset of action should be a priority in the development of new drugs or new administration-forms for the treatment of acute migraine attacks.

Cluster headache not responsive to sumatriptan: A retrospective study.

Subcutaneous sumatriptan, a 5HT1B/1D agonist, is the most effective drug in cluster headache acute treatment. About 25% of the patients do not respond to subcutaneous sumatriptan; the reasons for this are unknown. In this study, we compare clinical characteristics of cluster headache patients responding and non-responding to subcutaneous sumatriptan. We retrospectively investigated the clinical records of 277 cluster headache patients. Patients reporting repeated satisfactory response to subcutaneous sumatriptan within 15 minutes were considered responders. Of 206 cluster headache patients who had used subcutaneous sumatriptan (mean age 45.6, 16% females, 48% chronic), 91% were responders, and 9% non-responders. Compared to responders, non-responders had longer and more frequent attacks: 60 (median; IQR 38-90) vs. 100 (60-120) minutes (p = 0.028), 4 (2.5-5) vs. 3 (2-4) attacks/day (p = 0.024). No other difference was found. In cluster headache attacks with long duration and high frequency, pain mechanisms not involving 5HT1B/1D receptors may play a more relevant role.

Subcutaneous sumatriptan reduces cilostazol induced headache in migraine patients.

The authors have previously tried to develop a model for the testing of novel drug candidates for migraine, using the headache and migraine provoking agent cilostazol. Previous studies have used sumatriptan tablets as the validating drug, but they were not sufficiently effective. In this study we test the effect of subcutaneous sumatriptan on cilostazol induced headache in patients with migraine without aura. Thirty patients with migraine without aura received 200 mg cilostazol on two different study days. The induced headache was treated with subcutaneous sumatriptan in a randomized, double-blind cross-over design. The patients filled out a self-reported headache questionnaire until 12 h after cilostazol. All 30 patients experienced headache (range 3-10) on both study days and the headache fulfilled the criteria for a migraine-like attack in 73% on the sumatriptan day and in 77% on the placebo day. Sumatriptan injection reduced the headache score 2 h after treatment (p = 0.003). The difference between headache intensity on the sumatriptan day and the placebo day was significant at both 2 h (p = 0.01) and 4 h (p = 0.0007) after treatment. Subcutaneous sumatriptan reduces cilostazol induced headache in migraine patients. The cilostazol model may be useful as a tool to test the potential of new anti-migraine drugs.Trial registration: The study is registered on clinicaltrials.gov (NCT03422796).

Pharmacotherapy for Cluster Headache.

Cluster headache is characterised by attacks of excruciating unilateral headache or facial pain lasting 15 min to 3 h and is seen as one of the most intense forms of pain. Cluster headache attacks are accompanied by ipsilateral autonomic symptoms such as ptosis, miosis, redness or flushing of the face, nasal congestion, rhinorrhoea, peri-orbital swelling and/or restlessness or agitation. Cluster headache treatment entails fast-acting abortive treatment, transitional treatment and preventive treatment. The primary goal of prophylactic and transitional treatment is to achieve attack freedom, although this is not always possible. Subcutaneous sumatriptan and high-flow oxygen are the most proven abortive treatments for cluster headache attacks, but other treatment options such as intranasal triptans may be effective. Verapamil and lithium are the preventive drugs of first choice and the most widely used in first-line preventive treatment. Given its possible cardiac side effects, electrocardiogram (ECG) is recommended before treating with verapamil. Liver and kidney functioning should be evaluated before and during treatment with lithium. If verapamil and lithium are ineffective, contraindicated or discontinued because of side effects, the second choice is topiramate. If all these drugs fail, other options with lower levels of evidence are available (e.g. melatonin, clomiphene, dihydroergotamine, pizotifen). However, since the evidence level is low, we also recommend considering one of several neuromodulatory options in patients with refractory chronic cluster headache. A new addition to the preventive treatment options in episodic cluster headache is galcanezumab, although the long-term effects remain unknown. Since effective preventive treatment can take several weeks to titrate, transitional treatment can be of great importance in the treatment of cluster headache. At present, greater occipital nerve injection is the most proven transitional treatment. Other options are high-dose prednisone or frovatriptan.

Subcutaneous sumatriptan: association with decreases in postoperative pain and opioid use after elective cranial surgery.

Sumatriptan, a serotonin receptor agonist, has been used in the management of primary headache disorders and has been shown to affect trigeminal dural afferents. There is limited literature on the safety and efficacy of sumatriptan for postcraniotomy pain management. This study aimed to identify whether subcutaneous sumatriptan is a safe and efficacious pain management strategy after elective craniotomy. The authors retrospectively reviewed patients who underwent supratentorial or suboccipital craniotomy between 2016 and 2019 that was performed by a single provider at a single institution to identify patients given subcutaneous sumatriptan in the postoperative period. Pain scores and intravenous and oral opioid use were compared in patients with (n = 15) and without (n = 45) sumatriptan administration. Patients with and without sumatriptan administration had no significant differences in baseline characteristics or surgery type. There were no sumatriptan-related complications. The average pain score decreased from 3.9 to 1.3 within 1 hour after sumatriptan administration (p = 0.014). In both adult and pediatric patients there was decreased postoperative pain (adults: pain score of 1.1 vs 7.1, p < 0.001; pediatric: 1.1 vs 3.9, p = 0.007) within the first 48 hours. There were decreases in intravenous opioid use, length of intravenous opioid use, maximum dose of intravenous opioid used, oral opioid use, length of oral opioid use, and maximum dose of oral opioid used in both adult and pediatric patients. The authors identified subcutaneous sumatriptan as a safe and efficacious tool for postoperative pain management after craniotomy. Large multicenter randomized controlled studies are needed to further evaluate the specific role of sumatriptan in postoperative pain management after craniotomy.

Ultra-rapid brain uptake of subcutaneous sumatriptan in the rat: Implication for cluster headache treatment.

In spite of the substantial therapeutic efficacy of triptans, their site of action is still debated. Subcutaneous sumatriptan is the most efficacious symptomatic treatment for cluster headache (CH) patients, showing therapeutic onset within a few minutes after injection even in migraine patients. However, whether subcutaneous sumatriptan is able to reach the CNS within this short time frame is currently unknown. Here, by means of liquid chromatography/mass spectrometry, we investigated peripheral and brain distribution of subcutaneous sumatriptan soon after injection in rats at a dose equivalent to that used in patients. Tissue sumatriptan contents were compared to those of oxazepam, a prototypical lipophilic, neuroactive drug. We report that sumatriptan accumulated within brain regions of relevance to migraine and CH pathogenesis such as the hypothalamus and the brainstem as soon as 1 and 5 minutes after injection. Notably, sumatriptan brain distribution was faster than that of oxazepam, reaching concentrations exceeding its reported binding affinity for 5HT1B/D receptors, and in the range of those able to inhibit neurotransmitter release invivo. Our findings indicate that sumatriptan distributes within the CNS soon after injection, and are in line with prompt pain relief by parenteral sumatriptan in CH patients.