Mathew et al found that 73% of their patients had substantial headache relief (mild or no pain) 30 minutes after receiving valproate 300 mg IV.51 There was no control group. Two out of 66 patients reported mild, transient light headedness. Edwards et al Fostamatinib manufacturer compared valproate 500 mg IV

to DHE 1 mg IV plus metoclopramide 10 mg IV; headache relief at 4 hours was the same in both groups (60%).40 Tanen et al compared valproate 500 mg IV to prochlorperazine 10 mg IV; pain reduction (VAS) at 1 hour was greater for prochlorperazine (−64.5 vs −9.0; P < .01) with no difference in sedation between the treatments.9Table 4 summarizes the studies involving valproate. Octreotide, a somatostatin analogue, can inhibit neuropeptides that may be involved in headache pathogenesis (prostaglandins, substance P). Miller et al compared octreotide 100 µg IV to prochlorperazine 10 mg IV; pain reduction (VAS) was greater for prochlorperazine (−50.5 vs −33.3; P < .01).10 Intravenous lidocaine has been used to treat neuropathic pain; its mechanism of action

involves the blockade of sodium channels. Bell et al compared lidocaine 50 mg IV (repeated up to 150 mg) to chlorpromazine 12.5 mg IV (repeated up to Rapamycin 37.5 mg) and to DHE 1 mg IV (repeated once); pain reduction (11-PPS) was greater with chlorpromazine than lidocaine or DHE (−79.5% vs −50% vs −36.7%; P < .05).18 Nitrous oxide is a well-known anesthetic, analgesic, and anxiolytic often used in dentistry and surgery. Triner et al compared nitrous oxide (50%) plus oxygen (50%) to oxygen (100%) alone.52 A scented mask spray was used to blind the scent of nitrous oxide, which is mildly sweet smelling. Pain reduction (VAS) at 20 minutes was greater for nitrous oxide/oxygen (−48 vs −6.5; P < .05). Post-discharge follow up was not done. No side effects were reported. Propofol is a hypnotic/sedative that acts as a GABAA receptor agonist and a sodium channel blocker. Krusz et al used open-label propofol to treat 77 patients with intractable headaches.53 Propofol was administered as needed, averaging 110 mg (10 mg/mL), a sub-anesthetic dose. Eighty-two

percent of patients were pain free at 30 minutes. Side effects included transient drowsiness or slurred speech, and 8 patients briefly exhibited involuntary finger movements. PFKL Bupivacaine is a long-acting local anesthetic that blocks sodium and potassium channels on pain-signaling neurons. Mellick et al reported on the efficacy of injecting 0.5% bupivacaine 1.5 mL IM bilaterally (3 mL total) 2-3 cm lateral to the spinous process in the lower cervical region (at the 6th or 7th cervical vertebrae).54 Complete, rapid pain relief was achieved in 271/417 patients (65.1%), and partial relief was reported by an additional 85 (20.4%). The most common side effect was muscle soreness at the injection site. Table 4 summarizes the studies involving octreotide, lidocaine, nitrous oxide, propofol, and bupivacaine.