Buspirone challenge test

The buspirone challenge test measures how much prolactin is released into the bloodstream when a single dose of the drug buspirone (a 5-HT1A serotonin receptor agonist) is orally administered. This test has been shown to distinguish ME/CFS patients from healthy controls, as well as being able to distinguish ME/CFS patients from patients with depression.

ME/CFS patients release substantially more prolactin into the blood when given buspirone compared to healthy controls and depressed patients. It is theorized this greater release of prolactin may be due to increased sensitivity or up-regulation of the serotonin receptors in the hypothalamus in ME/CFS, though this theory is questioned, and an alternative hypothesis is that the prolactin release is elicited by a dopamine receptor blockade.

It is also observed that the degree of shift in the sleep/wake cycle that an ME/CFS patient suffers from correlates with the degree of prolactin they release in the buspirone challenge.

Women display a large variation in their prolactin response to buspirone throughout the menstrual cycle (with maximum responses occurring premenstrually). By contrast, responses in men are consistent and reproducible. However Bakheit et al when testing women administered the buspirone challenge exclusively in the luteal phase of the menstrual cycle, and found significantly increased prolactin responses in women with ME/CFS compared to female healthy controls. Some preliminary work has also shown that the buspirone challenge is fairly reproducible in postmenopausal females.

Studies

 * A 1992 study by Bakheit, Behan et al on 15 ME/CFS patients, 13 patients with depression and 13 healthy controls found that buspirone-stimulated prolactin release in patients was significantly higher than in both depressed patients and healthy controls, indicating that the buspirone challenge test can distinguish ME/CFS patients from depressed patients, as well as distinguishing ME/CFS patients from healthy controls. The administration of a single does of buspirone was also found to cause excessive fatigue, lightheadedness and nausea in ME/CFS patients but not in controls. The authors stated that the prolactin release in response to buspirone administration seems to be mediated by 5-hydroxytryptamine (serotonin) receptors since the release can be blocked by specific 5-hydroxytryptamine antagonists such as mnethysergide and metergoline. The authors said their findings are consistent with an increased sensitivity of serotonin receptors in the hypothalamus.
 * In a 1995 study by Dr John Richardson, 25 ME/CFS patients who were positive for enterovirus infection (enteroviral VP1 protein detected in their blood) were administered a buspirone challenge test: the prolactin release in patients was found to be on average 3 times higher than the release in healthy controls, a highly significant difference. Richardson also found that the degree of shift in the sleep/wake cycle that the ME/CFS patients suffered from (which he termed "owl syndrome") correlated with the degree of prolactin release measured in the buspirone challenge.
 * A 1995 study by Cleare et al found the selective serotonin-releasing agent d-fenfluramine elicited a high degree of prolactin release in ME/CFS patients, an intermediate degree of release in healthy controls, and a low degree of release in depressed patients. The prolactin response to d-fenfluramine appears to be mediated by indirect activation of 5-HT2 receptors without 5-HT1A receptors playing a significant role.
 * A 1996 study by Sharpe et al found ME/CFS patients had significantly higher plasma prolactin concentrations and experienced more nausea and lightheadedness in response to buspirone than did controls. Prolactin response to buspirone, Sharpe et al 1996.pnger, no significant differences in the secretion of growth hormone in response to buspirone were observed between these groups. The authors questioned whether the exaggerated prolactin response reflects an increase in hypothalamic serotonin receptor sensitivity, since buspirone also binds to dopamine D2 receptors and thus this drug's ability to increase prolactin might be also be mediated by dopamine receptor blockade. They point out that prolactin and growth hormone release can be elicited by activation of 5-HT1A receptors in the hypothalamus, and thus one might expect both prolactin and growth hormone responses to buspirone to be greater in ME/CFS patients than controls. But this study found that ME/CFS patient growth hormone responses to buspirone were not significantly raised, which the authors suggest casts some doubt on the theory of increased hypothalamic serotonin receptor sensitivity in ME/CFS.
 * A 2001 case study observed that the exaggerated buspirone-stimulated prolactin release of an ME/CFS patient returned to normal once the patient had recovered from ME/CFS.