Elsevier

Sleep Medicine Reviews

Volume 13, Issue 5, October 2009, Pages 363-377
Sleep Medicine Reviews

Clinical Review
Effects of nicotine on sleep during consumption, withdrawal and replacement therapy

https://doi.org/10.1016/j.smrv.2008.12.003Get rights and content

Summary

Smoking constitutes the most important behavioural health risk in the Western world. By acting on various neurotransmitter systems, nicotine consumption also influences sleep and mood. Studies on the relationship between smoking, sleep disturbances, sleep-related disorders and depression led to dissimilar results. The aim of the present work is to provide a descriptive overview of the existing data regarding the relationship of nicotine consumption, withdrawal, replacement therapy and sleep disturbances in both animals and humans. Primarily symptoms of insomnia, such as increased sleep latency, sleep fragmentation and decreased slow wave sleep with reduced sleep efficiency and increased daytime sleepiness, were observed during nicotine consumption. Furthermore, most studies indicated a nicotine induced rapid eye movement (REM) sleep suppression. The effects on sleep due to therapeutic nicotine substitution after smoking cessation were often masked by withdrawal symptoms. Depressive non-smokers experienced a mood improvement under nicotine administration comparable to the effect of anti-depressants. In turn, depressive symptoms and sleep impairment during nicotine withdrawal had a negative impact on abstinence rates. Smoking was also associated with an increased prevalence of sleep-related respiratory disorders, which further worsened sleep quality and daytime sleepiness. The partly inconsistent findings of the analysed 52 studies result mostly from different methodology, necessitating a more unified approach with regard to subjects' assessment of smoking status, control for co-morbidity and use of medication as well as outcome criteria.

Introduction

Cigarette smoking is a major public health problem. One half of all long-term smokers die prematurely as a consequence of tobacco consumption.1 In industrialised countries smoking is recognised as the most significant avoidable single cause for a multiplicity of chronic diseases.2 Although the health consequences of smoking are well documented, the influence of nicotine consumption, nicotine withdrawal and substituted nicotine on sleep have not been extensively studied.

Nicotine stimulates cholinergic neurotransmission via the wide-spread α7 and α4β2 nicotinergic acetylcholine (ACh) receptors and indirectly alters the glutaminergic, dopaminergic and serotonergic systems in the brain.3 Chronic nicotine consumption is usually coupled with physical and psychological dependence. Withdrawal symptoms include sleep disturbances, the craving for tobacco, dysphoria, fear, anhedonia, irritability or restlessness and increased appetite. Insomnia complaints during nicotine withdrawal are reported in up to 39% of cases.4, 5

Additionally, depressive symptoms are common in prolonged nicotine withdrawal,6 and there is a complex relationship between nicotine dependence and depression. Not only do depressive patients smoke more frequently, but during nicotine withdrawal there is also an increase in depressive episodes.7 Furthermore, sleep disturbances and changes in REM sleep are common in depressive patients; and the presence of depressive symptoms is associated with lower nicotine abstinence rates.8

It is speculated that the negative health effects of smoking could at least partly be related to the effects of nicotine on sleep.9 Disturbed sleep due to nicotine use in turn might worsen the withdrawal process, and may therefore be a relevant risk factor for relapse. This implies the necessity to adapt smoking cessation therapies to the specific requirements of groups at risk, e.g., smokers with depression (most of whom also have insomniac symptoms) or sleep problems.

The present descriptive review aims to provide an overview of investigations on smoking and its effect on sleep as well as smoking cessation with and without nicotine substitution. Also included in the review were studies, which investigated patients with depression, looked at nocturnal respiration in smokers and examined the therapeutic use of nicotine.

Section snippets

Methods

The electronic data bases Medline+ (Ovid), PreMedline (Ovid), Cumulative Index to Nursing & Allied Health Literature – CINAHL (Ovid), PsycINFO (Elton B. Stephens Company – EBSCO), and Embase were searched in October 2007 for relevant publications regarding the effects of nicotine on sleep. The keywords included “sleep”, “sleep disturbance”, “insomnia”, “smoking”, “smoking cessation”, “nicotine”, “nicotine withdrawal”, “tobacco” and “tobacco withdrawal”. Both German and English original articles

Studies investigating the effects of nicotine on sleep in animals

Out of the eight studies in animals, six investigated in vivo nicotine effects on the sleep EEG, one specified the nicotine receptors relevant to sleep in knock-out mice, and one reported on neural sleep regulation on the basis of rat midbrain slices (see Table 1). Lena et al.17 showed that the effects of nicotine on sleep in β2-AchR-knock-out mice were transmitted mainly by the β2 subunit of the ACh receptors. Several of the studies described a dose-dependent effect of nicotine on sleep, with

Outlook

Both in population-representative samples and under controlled conditions, smoking and acute nicotine application led to complaints of insomnia, increased sleep fragmentation and sleep onset latency, decreased sleep efficiency, reduced SWS time and increased daytime sleepiness. These symptoms appear to be reversible after cessation.40, 33

Similar sleep changes were also observed during acute nicotine withdrawal. The extent of the sleep impairment correlated with individual plasma nicotine

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