Treatment of Migraine Attacks with A Long-Acting Somatostatin Analogue (Octreotide, SMS 201-995)

Abstract

Long-acting somatostatin analogue (SMS 201-995) inhibits serotonin, bradykinin, prostaglandins, substance P, and vasoactive intestinal peptide, which may be involved in migraine. We therefore decided to test the efficacy of SMS 201-995 in relieving the pain of acute migraine attacks. Headache relief was defined as a reduction in severity from grade 3 or 2 (severe or moderate) to 1 or 0 (mild or none). Patients experiencing migraine attacks were evaluated clinically. A double-blind parallel group trial was performed in which patients randomly received either a subcutaneous injection of placebo (saline) or SMS 201-995 (100 micrograms). SMS 201-995 was significantly more effective than placebo in reducing headache grade at 2 h (1.5 +/- 0.6 vs 2.2 +/- 0.7; p < 0.01), 4 h (1.5 +/- 0.6 vs 2.1 +/- 0.8; p < 0.05) and 6 h (0.8 +/- 0.9 vs 2.1 +/- 0.8; p < 0.001) after the initiation of treatment. By 6 h, apparent headache relief (reduction in severity from grade 3 or 2 to 1 or 0) was experienced in 76.5% of SMS 201-995 treated patients and 25% of the placebo-treated group. Headache relief was significantly better in patients taking SMS 201-995 (p < 0.02). Furthermore, none of the patients became pain-free (headache grade 0) on placebo, while significantly more patients (47%) were pain-free on SMS 201-995 at 6 h (p < 0.01). Headache improvement started significantly earlier in those patients treated with SMS 201-995 than with placebo. SMS 201-995 significantly improves the pain of migraine attacks, 2 h after the beginning of treatment. Additionally, we observed no side effects of SMS 201-995. We therefore conclude that a single dose of 100 micrograms given subcutaneously is an effective and well-tolerated agent for the treatment of migraine attacks.

High prolactin levels as a worsening factor for migraine

“…Alteration of headache phenotypes after administration of dopamine agonists suggests that headache syndromes associated with prolactinomas may be the result of alterations in the dopamineprolactin axis rather than simply caused by the mass effects of the tumour, also because the headache begins months before hormonal symptoms for pituitary disorders appear [17,25]. The theory, stating that neuroendocrine mechanisms can be an important factor in triggering and aborting headache, is supported by the result of studies regarding the analgesic effect of somatostatin analogues [28][29][30][31]. Our seven cases seem to support the theory that high PRL levels alone are implicated in making the headache chronic.…”

The Association of Pituitary Tumors and Headache

“…These neuroanatomical areas are known to possess sst 2a receptors [47] and the use of somatostatin analogues in primary headache outside pituitary tumors has been investigated. Although there has been some evidence that octreotide may be beneficial in cluster headache [48] and migraine [49], it is not currently routinely used in clinical practice for the management of primary headache.…”

Cluster headache, hypothalamus, and orexin

“…Somatostatin or one of its analogs has demonstrated analgesic properties in the primary headaches migraine and CH [53,54]; however, a recent study of migraineurs using a cross-over randomized controlled trial design showed no signifi cant difference to placebo [55]. Experimental in vivo and in vitro evidence points to an inhibitory effect at the level of the spinal and trigeminal dorsal horns [56].…”