The Somatostatin Analogue Octreotide Impairs Sleep and Decreases EEG Sigma Power in Young Male Subjects

Abstract

The long-acting somatostatin (SRIF) analogue octreotide decreased nonrapid eye movement sleep (NREMS) in the rat. This effect is opposite to the promotion of sleep after growth hormone (GH)-releasing hormone (GHRH) in various species including humans. Therefore, it appears likely that GHRH and SRIF, besides their opposite action on pituitary GH release, interact reciprocally in sleep regulation. In previous studies, SRIF impaired sleep in elderly subjects, although sleep in young men remained unchanged. We hypothesized that octreotide is a useful tool to study the role of SRIF in human sleep regulation. We examined the effect of subcutaneous administration of 0.1 mg octreotide at 2245 on the sleep EEG of seven young male controls (age, mean 7 SD, 22.3 7 3.0 years). In comparison to placebo, octreotide administration prompted decreases of sleep stage 4 during the total night and of rapid eye movement sleep (REMS) density during the first half of the night. Intermittent wakefulness increased during the second half of the night. The spectral analysis of total night NREMS revealed a significant decrease of sigma power. Similar to the effect of the short-acting SRIF in the elderly, the long-acting SRIF analogue octreotide impaired sleep in young healthy subjects. Obviously, the influence of octreotide on sleep is superior to that of short-acting SRIF, which did not affect sleep in young men. We suggest a reciprocal interaction of GHRH and SRIF in sleep regulation.

Anxiolytic and antidepressant actions of somatostatin: the role of sst2 and sst3 receptors

“…There is evidence that central somatostatin is involved in several processes, such as sleep architecture (Beranek et al 1997;Danguir 1986;Frieboes et al 1997;Hajdu et al 2003;Obal et al 2003;Steiger et al 1992;Toppila et al 2000;Ziegenbein et al 2004), epileptiform activity (Binaschi et al 2003;Buckmaster et al 2002;Mazarati and Telegdy 1992;Moneta et al 2002;Tallent and Qiu 2008;Tallent and Siggins 1999;Vezzani and Hoyer 1999), memory formation and retention (Dournaud et al 1996;Dutar et al 2002;Dyer and Cain 2007;Gastambide et al 2009;Justino et al 1997;Kluge et al 2008;Lamirault et al 2001;Low et al 1998;Matsuoka et al 1994Matsuoka et al , 1995Nilsson et al 1993;Tashev and Belcheva 2008;Tokita et al 2005;Zeyda et al 2001), locomotor activity (Hathway et al 2004;Izquierdo-Claros et al 2001;Marazioti et al 2005Marazioti et al , 2006Marazioti et al , 2008Raynor et al 1993;Santis et al 2009;Tashev et al 2001Tashev et al , 2004, and nociception (Betoin et al 1994;Carlton et al 2001;…”

Somatostatin analog treatment is associated with an increased sleep latency in patients with long-term biochemical remission of acromegaly

“…In rats, the long-acting somatostatin analog octreotide suppressed NREMS after repeated injections [13]. Moreover, octreotide reduced stage 4 NREMS and REMS during the first half of the night and increased intermittent wakefulness during the second half of the night in young healthy adults [15]. We could not identify polysomnographic studies of the effects of the depot preparations of octreotide or lanreotide on sleep parameters, which are interesting in the light of our results.…”

“…In rats, repeated injections of octreotide caused decreases in non-rapid eye movement sleep (NREMS) time and NREMS intensity [13]. In healthy young male subjects octreotide decreased stage 4 NREMS and REMS during the first half of the night [15]. Based on these observations, it is possible that somatostatin treatment in patients with acromegaly may also adversely affect sleep.…”

Sleep Characteristics in Children with Growth Hormone Deficiency

“…Animal and clinical studies have shown that all the components of the somatotropic system are involved in the physiology of sleep regulation: growth hormone-releasing hormone (GHRH) [1,2], somatostatin [3], growth hormone (GH) [4,5,6,7], insulin-like growth factor-I (IGF-I) [8], and the natural GH secretagogue ghrelin [9]. …”