Subcutaneous Sumatriptans for Acute Migraine Attacks in Adults

Derry CJ, Derry S, Moore RA. Sumatriptan (all routes of administration) for acute migraine attacks in adults - overview of Cochrane reviews. Cochrane Database Syst Rev. 2014;2014(5):CD009108.

Study Population: 9365 adults with active migraine

Pain-free or headache relief at one and two hours

Fatigue, malaise, dizziness, vertigo, nausea, vomiting, taste disturbance, chest pain, sweating, numbness, paresthesias, drowsiness, flushing, back pain

Migraines are common and most often described as painful pulsatile headaches with nausea and sensory sensitivities. Sumatriptan is one of many medications available for treatment of acute migraine attacks.

The Cochrane systematic review discussed here1 evaluated sumatriptan for acute migraines administered subcutaneously (the most studied and commonly utilized route of administration). Studies included adults with migraine, used single-dose sumatriptan, and were randomized, double-blinded, and placebo-controlled. The overall pain and headache pain were assessed using standard pain scales. The total number of participants in 35 included studies was 9365.

Outcomes included ‘pain-free’, ‘headache relief’, and adverse events within 24-hours. Pain-free indicated participants initially with moderate or severe pain experiencing complete resolution. Headache relief indicated moderate or severe pain with subsequent reduction to mild or no pain.

More patients were pain-free at one hour with 4mg subcutaneous sumatriptan than placebo (relative risk [RR] 4.7; 95%CI, 2.8-7.7; absolute risk difference [ARD] 27%; Numberneeded-to-treat [NNT] 4. For 6mg sumatriptan dosing RR was 5.6; 95%CI, 4.6-6.8; ARD 34%; NNT 3). Similar results were found at two hours. Sumatriptan was also superior to placebo for headache relief at one hour with 4mg (RR 2.6; 95%CI, 2.0-3.2; ARD 41%; NNT 3) and 6mg dosing (RR 2.7; 95%CI, 2.5-2.9; ARD 45%; NNT 3). Again, two hour results were similar.

Subcutaneous sumatriptan administration increased adverse events (RR 1.8, 95%CI, 1.6 to 2.2; ARD 30%; number-needed-to-harm [NNH] 3 for a single subcutaneous 4mg dose, and NNH 4 for 6mg dose). Treatments were however described as well-tolerated with most adverse events mild or moderate in severity and self-limiting. Events included fatigue, malaise, dizziness, vertigo, nausea, vomiting, taste disturbance, chest pain, sweating, numbness, paresthesias, drowsiness, flushing, and back pain.

Authors of the Cochrane reviews deemed the quality of the evidence largely high and the results reliable. Moreover, additional reviews suggest similar benefits using other routes of administration including oral and intranasal, helping to confirm the consistency of these findings.1 However, other routes also were associated with increased adverse events (except for oral 25mg dose) with NNH of 13 for 50 mg oral, 5 for 100 mg oral, and 4 for 20 mg intranasal.

One important source of potential bias is publication bias, in that unpublished data could theoretically alter the outcomes and conclusions of this review, a concern unfortunately confirmed in the setting of other pharmaceuticals developed prior to the advent and common use of trial registries.2 In regards to adverse events, the review found high variability and often poor quality in assessing and reporting.

Of note, in the current milieu it is unusual to see placebo controls in studies of active migraine. For instance, rigorous comparison finds metoclopramide, a common, safe, inexpensive antiemetic, equivalent or superior to subcutaneous sumatriptan for acute migraine.3 In addition, while apparently safe in the setting of carefully screened trial populations, in higher risk patients triptan medications may cause rare serious, potentially fatal adverse events such as coronary vasospasm, myocardial infarction, and ischemic colitis, though much of the evidence is derived from animal models and case reports.4^, 5^, 6 For this reason, sumatriptans are generally contraindicated in patients with known ischemic heart disease, angina pectoris, or poorly controlled hypertension or renal disease.7 The widespread availability of safer, less costly, equally effective agents may help explain why sumatriptan is rarely used in acute care settings where acute migraine patients are typically treated.8 For instance, rigorous comparison finds metoclopramide, a common, safe, inexpensive antiemetic, to be equivalent or superior to subcutaneous sumatriptan for acute migraine.3 Sumatriptan may still hold benefit in ease of administration (subcutaneous vs intravenous).

In summary, existing evidence supports subcutaneous sumatriptan over placebo for treatment of migraine headache. Adverse events occur at a similar rate to benefits, but appear mild and well-tolerated. Therefore, we have assigned a color recommendation of Green (Benefits > Harms) for subcutaneous sumatriptan compared to placebo. However, given the availability of other abortive medications for migraines with even safer side effect profiles, sumatriptan does not necessarily serve as first-line treatment for some clinicians.

The original manuscript was published in Academic Emergency Medicine as part of the partnership between TheNNT.com and AEM.

February 3, 2021