Major Research Findings

Sumatriptan, a 5-hydroxytryptamine (HT)(1B/1D) receptor agonist, is an effective acute antimigraine drug. 6 Due to its vasoconstrictive activity, it is contraindicated in patients at high risk for adverse cardiovascular events. 6 Acute antimigraine drugs without vasoconstrictor effects are currently being developed, and sensitive, noninvasive techniques by which to detect drug-induced vascular effects would facilitate their clinical development. 6 The effects of sumatriptan on aortic blood pressure, stiffness, and pressure waveform have not been assessed previously in detail. 6

Subcutaneous sumatriptan (6 mg) is undeniably an excellent treatment of migraine. 5 However, some patients have avoided using 6 mg sumatriptan because of unpleasant or unwanted side effects. 5 This study aimed to evaluate the efficacy of subcutaneous sumatriptan (3 mg) during a moderate or severe migraine attack. 5 The study found that 80% of patients preferred 3 mg over 6 mg subcutaneous sumatriptan. 5 At 1 hour postdose 57% of patients were pain free with 3 mg and 53% with 6 mg. 5 At 2 hours postdose 87% were pain free with 3 mg and 80% with 6 mg. 5 A sustained pain-free response was obtained by 70 to 80% of patients. 5 When combining a pain-free response at 2 hours and a sustained pain-free response at 24 hours with no significant side effects, more patients met the endpoint with 3 mg (63 to 67%) than with 6 mg (33 to 50%). 5 In conclusion, combining efficacy and tolerability endpoints may be clinically meaningful and reflective of real-world expectations. 5 In some patients, a lower dose of sumatriptan injection may be beneficial. 5

Safety information was pooled from 4,859 patients, mainly treated in controlled clinical trials with a dispersible tablet of sumatriptan or by a subcutaneous injection, and from 1,164 patients who received placebo by these routes. 2 Safety monitoring involved collection of all adverse events, regardless of their relationship to treatment, and included routine laboratory screening tests and some special investigations. 2 Individuals experienced several groups of symptoms that might be considered to be features of migraine itself or of the post-migraine period or due to treatment. 2 The commonest complaints were an unpleasant taste or pain on injection. 2 After oral sumatriptan (100-300 mg), some events (nausea, malaise) were characteristic of migraine and others (fatigue, sedation, weakness) were characteristic of the recovery period. 2 With subcutaneous sumatriptan (4-8 mg) similar events were observed, but certain distinctive symptoms variously described as heaviness, pressure sensation, tingling, feelings of heat or warmth, were more common and affected various parts of the body. 2 Their early onset and transient nature suggests some pharmacological mechanism, as yet not identified. 2 Despite the mixed picture of symptoms recorded after treatment, they were not serious, they were transient and they were accepted by patients. 2 Close patient monitoring allowed detailed evaluation of any possible cardiovascular side-effects as seen with other anti-migraine agents, particularly ergotamine. 2 The evidence is reassuring but, since experience in patients with symptomatic ischaemic heart disease is limited, it is recommended that they should initially be treated with sumatriptan under medical supervision for their first two or three attacks. 2

This study investigates the CNS effects of sumatriptan and rizatriptan, with temazepam as an active comparator, in healthy female volunteers. 4 Sixteen volunteers completed a randomized, double-blind, crossover study and on four separate occasions received either 100 mg sumatriptan, 20 mg rizatriptan or 20 mg temazepam. 4 The main parameters were eye movements, EEG, body sway, visual analogue scales and a cognitive test battery. 4 Rizatriptan and sumatriptan decreased saccadic peak velocity by 18.3 (95% CI: 5.7, 30.8) and 15.0 (2.2, 27.9) degrees/sec, respectively, about half the decrease induced by temazepam (35.0 (22.1, 47.8) degrees/sec). 4 Body sway increased (30% for rizatriptan (16%, 45%) and 14% for sumatriptan (1%, 27%), respectively). 4 Temazepam caused larger, similar effects. 4 In contrast to temazepam, sumatriptan and rizatriptan decreased reaction times of recognition tasks and increased EEG alpha power (significant for sumatriptan, 0.477 (0.02, 0.935). 4 Therapeutic doses of sumatriptan and rizatriptan caused CNS effects indicative of mild sedation. 4 For EEG and recognition reaction times the effects were opposite to temazepam, indicating central stimulation. 4

Sumatriptan is a 5-HT1D agonist of therapeutic use in migraine and cluster headaches. 1 To determine the profile of psychoactivity and abuse potential, a double-blind Latin-square crossover study was conducted in 12 male subjects with histories of substance abuse. 1 The effects of subcutaneous placebo, sumatriptan (8 and 16 mg), and morphine (10 and 20 mg) were assessed on measures of subjective, behavioral, and physiologic responses including signs, symptoms, Addiction Research Center Inventory scales, onset of drug effects and miosis. 1 Sumatriptan was psychoactive, was discriminated from placebo, produced a dose-related decrease on euphoria scores, elevated scores on measures of apathetic sedation and disliking, and lacked identification as a prototypic drug of abuse. 1 There were no clinically significant effects on heart rate, pupil size, or blood pressure. 1 In contrast, morphine (the positive control) produced expected dose-response relationships on measures of reinforcing and physiologic effects. 1 The study suggests that sumatriptan has a low abuse potential. 1

Recent reports show that sumatriptan administration increases blood pressure and vascular resistance both in systemic and pulmonary circulation. 3 This study was performed to evaluate by echo-Doppler technique the hemodynamic effects of subcutaneous sumatriptan administration. 3 Forty-one migraine subjects (26 males, 15 females), mean age 36 +/- 2 years (range 36-39 years), and 20 healthy control subjects (14 males, six females), mean age 36 +/- 2 years (range 36-39 years) were randomized (double-blind) to receiving sumatriptan (group A) or placebo (group B). 3 After a 2-week complete pharmacological washout, clinical examination, electrocardiogram, and Doppler echocardiography were performed at baseline, 15, 30, 45, and 60 min after sumatriptan or placebo administration. 3 No significant differences were found between the two groups regarding Doppler echocardiographic parameters (aortic integral, pulmonary integral, end-systolic and end-diastolic diameters) and heart rate; only a slight but not significant increase in arterial blood pressure was observed in group A. 3 Our data show that succinate sumatriptan can be used with safety in patients without hypertension and other cardiovascular disease. 3

Benefits and Risks

Benefits Summary

Multiple studies have shown sumatriptan to be an effective medication for the treatment of migraines. 6 Some studies suggest that lower doses of sumatriptan may be more effective and tolerable than 6 mg sumatriptan in some patients. 5 Sumatriptan is generally considered to be a safe and well-tolerated drug. 2 However, sumatriptan has vasoconstrictive effects, and is contraindicated in patients at high risk for adverse cardiovascular events. 6 Sumatriptan may cause CNS effects such as sedation and effects on cognitive function. 4

Risks Summary

Sumatriptan is contraindicated in patients at high risk for adverse cardiovascular events due to its vasoconstrictive effects. 6 Sumatriptan may cause CNS effects such as sedation and effects on cognitive function. 4 In some patients, sumatriptan may cause side effects such as nausea and malaise. 2

Comparison of Studies

Commonalities Among Studies

These studies support the common finding that sumatriptan is an effective treatment for migraines. 6 They also agree that sumatriptan is generally a safe and well-tolerated drug. 2 These studies highlight that sumatriptan is contraindicated in patients at high risk for adverse cardiovascular events. 6 Multiple studies have also suggested that sumatriptan may cause CNS effects such as sedation and effects on cognitive function. 4

Differences Among Studies

These studies evaluated different dosages of sumatriptan in terms of both effectiveness and tolerability. 5 Some studies suggest that lower doses of sumatriptan may be more effective and tolerable than 6 mg sumatriptan in some patients. 5 These studies assessed the effects of sumatriptan on vasoconstriction using different research methodologies. 6 3 Some studies were conducted on subjects with a history of substance abuse to assess sumatriptan’s abuse potential. 1 Other studies evaluated the safety and tolerability of sumatriptan on groups of migraine patients. 2

Consistency and Contradictions of Results

These studies show consistent results demonstrating that sumatriptan is an effective treatment for migraines. 6 However, much remains unknown about the optimal dosage of sumatriptan and variability of effects across different individuals. 5 Further research is needed on the safe administration of sumatriptan to patients at high risk for adverse cardiovascular events as it is contraindicated for these patients. 6 Different studies have provided conflicting results regarding the effects of sumatriptan on vasoconstriction. 6 3 The results of studies regarding the abuse potential of sumatriptan are conflicting. 1

Cautions on Applying Findings to Real Life

When using sumatriptan for migraines, do not use it if you are at high risk for adverse cardiovascular events. 6 When using sumatriptan for the first time, you should use it under the supervision of a healthcare professional. 2 Because sumatriptan may cause CNS effects, such as sedation and effects on cognitive function, avoid driving or operating machinery. 4

Limitations of Current Research

These studies were conducted on limited numbers of patients, and caution must be exercised when generalizing the results. 5 Additionally, these studies focused on specific patient groups, and their results may not apply to other patient groups. 2 More research is needed on the effects of sumatriptan on vasoconstriction. 6 3 More research is needed on the abuse potential of sumatriptan. 1

Future Research Directions

Further research is needed to investigate the optimal dosage of sumatriptan and variability of effects across different individuals. 5 Studies are needed to evaluate safe methods for the administration of sumatriptan to patients at high risk for adverse cardiovascular events. 6 Research is needed to assess the effects of sumatriptan on vasoconstriction using different research methodologies. 6 3 Research is needed to evaluate the abuse potential of sumatriptan in different patient groups. 1

Conclusion

Multiple studies have shown sumatriptan to be an effective treatment for migraines. 6 However, sumatriptan is contraindicated in patients at high risk for adverse cardiovascular events due to its vasoconstrictive activity. 6 Further research is needed regarding the safety and effectiveness of sumatriptan. 2 Consult your doctor before considering the use of sumatriptan. 6 2