The Effects of Ritanserin on Mood and Sleep in Abstinent Alcoholic Patients

Monti, Jaime M.; Alterwain, Paulo; Estévez, Francisco; Alvariño, F.; Giusti, M; Olivera, Silvia Leonor; Labraga, P.

doi:10.1093/sleep/16.7.647

Cited by 25 publications

(9 citation statements)

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“…They are given to improve sleep continuity and subjective well-being during the day. In line with this, Monti et al (22) reported improved sleep and mood in abstinent alcoholic patients. In a recent consensus report, Borbely et al (3) also concluded that the therapeutic profile of serotonergic drugs differ from that of the classical benzodiazepine hypnotics.…”

Section: Discussionmentioning

confidence: 61%

Effects of sertindole on sleep-wake states, electroencephalogram, behavioral patterns, and epileptic activity of rats

Coenen

Ateş

Skarsfeldt

et al. 1995

Pharmacology Biochemistry and Behavior

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COENEN, A. M. L., N. ATES, T. SRARSFELDT AND E. L. J. M. VAN LUIJTELAAR. Effects of sertittdole onsleep-wake states, electroencephalogram. behavioral potterns, and epileptic activity of rats. P HARMACOL BIOCHEM BEHAV 51(2/3) 353-357, 199X-In this study we addressed the effects of the S-HT, receptor antagonist sertindole in rats.The compound was administered in doses of 0.08. 0.32, and 1.28 mg/kg, whereas a control group received the solvent. The effects of sertindole on sleep-wake states, behavioral patterns, and background electroencephalogram were studied. Following injection of drug or solvent, we recorded the electroencephalogram and electromyogram for two periods of 4 h in the dark period of the light-dark cycle on 2 successive days. On the 1st day sertindole induced a significant increase in deep slow-wave sleep, but only with a dose of 0.32 mg/kg. Furthermore, a decrease in REM sleep in alI three drug groups was established. The suppression of REM sleep was still present on the 2nd day. Sertindole also induced a decrease in alternation between behavioral patterns on the 1st day. There were no significant changes in the spectral content of the background eleetroencephalogram. In a parallel experiment it appeared that sertindole had no main effects on epileptic spike-wave discharges. This was established with a dose of 1.28 mg/kg sertindole in rats with absence seizures. These Endings suggest that sertindole. similar to other compounds modulating 5-HT, receptors, influences sleep-wake states in rats by decreasing REM sleep and mildly increasing deep slow-wave sleep, whereas behavioral variation is slightly diminished, with no effects on the background EEG and almost no effects on spike-wave discharges. (15). It has been shown in rats that compounds which particularly modulate the 5-HT2 receptor influence sleep-wake states. For example, 5.HT, antagonists such as mianserin and ritanserin increase deep slow-wave sleep, which is accompanied by a decrease of REM sleep (1 l-13). A decrease of REM sleep was not found for RP 62203, a newer 5.HT, antagonist, which also enhanced deep slow-wave sleep (28). In accordance with this it was noted that the administration of selective 5-HT uptake inhibitors gives rise to increased waking (32).A new drug with promising biologic effects is sertindole, a powerful 5-HTz receptor antagonist (25). The question put forward in this experiment was whether sertindole also has effects on sleep-wake states and furthermore, on behavioral parameters, because it is preferable that putative hypnotics should only promote sleep without affecting behavioral patterns. Also, the effects of sertindole on the spectral content of the background electroencephalogram (EEG) were established. Classification of drugs according to their pharmacologic EEG fingerprint is increasingly important (8,20,36).Because it is known that drugs influencing sleep-wake states may also affect epileptic discharges, the putative epilepsy-modulating properties of sertindole were evaluated in a parallel experiment. This w...

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Section: Discussionmentioning

confidence: 61%

Effects of sertindole on sleep-wake states, electroencephalogram, behavioral patterns, and epileptic activity of rats

Coenen

Ateş

Skarsfeldt

et al. 1995

Pharmacology Biochemistry and Behavior

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“…However, data suggest that 5-HT 2A receptor antagonism can improve subjective sleep 54. Moreover, 5-HT 2A receptor antagonists may improve clinical symptoms of depression, anxiety, and/or psychosis in specific patient populations 55,56. These data suggest a potentially unique clinical opportunity for this neurochemical mechanism, as discussed in more detail below.…”

Section: Clinical Efficacy Of 5-ht2a Receptor Antagonistsmentioning

confidence: 99%

“…For example, in abstinent alcoholics with dysthymia and exhibiting less than six hours sleep/night at baseline, ritanserin treatment for 2–4 weeks significantly increased total sleep time (placebo at second week showed no change in total sleep time, compared with an average 47 minute increase from baseline with ritanserin [ P < 0.05]; placebo at the fourth week showed an average five-minute increase from baseline in total sleep time, compared with an average 48-minute increase with ritanserin [ P < 0.05]) 55. WASO was also reduced ( P < 0.05) after only four weeks of treatment with ritanserin, and sleep efficiency improved ( P < 0.05) after two or four weeks in these patients 55. Importantly, symptoms of depression and anxiety were also significantly reduced by ritanserin; Hamilton Depression Scale scores were reduced by greater than 50% ( P = 0.01) and Hamilton Anxiety Scale scores were similarly reduced ( P = 0.01) 55…”

Section: Clinical Efficacy Of 5-ht2a Receptor Antagonistsmentioning

confidence: 99%

Role of 5-HT2A receptor antagonists in the treatment of insomnia

Vanover¹,

Davis²

2010

NSS

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Insomnia encompasses a difficulty in falling asleep (sleep-onset insomnia) and/or a difficulty in staying asleep (SMI). Several selective serotonin-2A (5-HT 2A ) receptor antagonists have been in development as potential treatments for SMI. However, none have shown a sufficiently robust benefit-to-risk ratio, and none have reached market approval. We review the role of the 5-HT 2A mechanism in sleep, the preclinical and clinical data supporting a role for 5-HT 2A receptor antagonism in improving sleep maintenance, and the status of 5-HT 2A receptor antagonists in clinical development. Overall, the polysomnography data strongly support an increase in slow-wave sleep and a decrease in waking after sleep onset following treatment with 5-HT 2A receptor antagonists, although it has been more difficult to show subjective improvements in sleep with these agents. The incidence and prevalence of SMI, whether primary or secondary to psychiatric, neurologic, or other medical conditions, will increase as our population ages. There will be an increased need for safe and efficacious treatments of insomnia characterized by difficulty maintaining sleep, and there remains much promise for 5-HT 2A receptor antagonism to play a role in these future treatments.

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“…Der Nutzen von serotonerg wirksamen Substanzen wie die des 5-HT2-RezeptorAntagonisten Ritanserin bei der Behandlung von Schlafstörungen abstinenter Alkoholabhängiger ist umstritten [81,82,63].…”

Section: Neurobiologie Des Schlafs Und Der Alkoholabhängigkeit -Theraunclassified

Die Bedeutung des Schlafs für gesunde Alkoholkonsumenten und alkoholabhängige Patienten

et al. 2004

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This article deals with the effects of alcohol on sleep and sleep EEG of healthy individuals and alcohol-dependent patients during different phases of alcohol dependency. Healthy individuals initially experience an improvement in sleep, although a greater quantity of alcohol can lead to problems of sleep maintenance during the second half of the night. Pre-existing sleep deprivation or sleep restriction potentiates the effects of alcohol. Alcohol-dependent patients are found to be more prone to sleep problems than healthy individuals, which can facilitate the development of alcoholism. These patients experience difficulty falling asleep and suffer from a reduced total sleep time during all phases of the disorder, often accompanied by other sleep disorders such as sleep apnea syndrome or periodic leg movements during sleep. Certain predictors for the risk of relapse in abstinent alcoholics have been identified. Neurobiological findings in sleep and alcohol dependency are discussed. The cholinergic-aminergic reciprocal interaction model of REM and non-REM sleep regulation is significant in this context. Therapeutic implications are discussed.

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The Effects of Ritanserin on Mood and Sleep in Abstinent Alcoholic Patients

Cited by 25 publications

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Effects of sertindole on sleep-wake states, electroencephalogram, behavioral patterns, and epileptic activity of rats

Effects of sertindole on sleep-wake states, electroencephalogram, behavioral patterns, and epileptic activity of rats

Role of 5-HT2A receptor antagonists in the treatment of insomnia

Die Bedeutung des Schlafs für gesunde Alkoholkonsumenten und alkoholabhängige Patienten

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