Pharmacology of Psychiatric Drugs and Their Effects on Sleep
This chapter provides an overview of psychotropic drugs encountered in psychiatry and includes the effects on sleep of those frequently prescribed for depression, anxiety, psychosis, dementia and ADHD, with a small section about recreational drugs. Drugs
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Pharmacology of Psychiatric Drugs and Their Effects on Sleep Sue Wilson
5.1
Introduction
This chapter provides an overview of psychotropic drugs encountered in psychiatry and includes the effects on sleep of those frequently prescribed for depression, anxiety, psychosis, dementia and ADHD, with a small section about recreational drugs. Drugs which treat, exacerbate or provoke sleep disorders are covered in the last section. Most drugs which affect the brain do so by affecting neurotransmitter function in the brain, which they can do by: • Simulating the action of a brain neurotransmitter on the receptor (agonists, partial agonists) • Blocking its action on postsynaptic receptors (antagonists) • Changing the receptor’s sensitivity (allosteric modulators) • Increasing the amount of neurotransmitter present in the synapse, either by increasing the release of it into the synaptic cleft, blocking its transportation out of the cleft or preventing the action of enzymes which break it down The brain’s arousal is maintained by parallel neurotransmitter systems whose cell bodies are located in brainstem or midbrain centres, with projections to the thalamus and forebrain. These activating neurotransmitters are noradrenaline, serotonin, acetylcholine, dopamine, histamine as well as the orexin system with cell bodies in the hypothalamus which promotes wakefulness through regulating arousal pathways (and inhibiting sedating ones). For all these arousing neurotransmitters, waking can be promoted by increasing their function, and sleep or sedation by decreasing their function in the brain. S. Wilson Division of Brain Sciences, Centre for Psychiatry, Imperial College London, London, UK e-mail: [email protected] © Springer-Verlag GmbH Germany, part of Springer Nature 2018 H. Selsick (ed.), Sleep Disorders in Psychiatric Patients, https://doi.org/10.1007/978-3-642-54836-9_5
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The promotion of sleep is regulated by a number of other neurotransmitters; primary amongst these is gamma-aminobutyric acid (GABA), the main inhibitory neurotransmitter in the brain. The majority of brain cells are inhibited by GABA, so increasing its function reduces arousal and produces sleep and eventually anaesthesia. There are many subsets of GABA neurons distributed throughout the brain, but a particular cluster in the hypothalamus (ventrolateral preoptic nucleus) can be considered to be the sleep ‘switch’ (Saper et al. 2005). These neurons switch off brain arousal systems at the level of the cell bodies and therefore promote sleep. GABA receptors in the cortex can also promote sedation and sleep by inhibiting the target neurons of the arousal system. Most drugs used in insomnia, and benzodiazepines used in anxiety, act by increasing the effects of GABA at the GABA-A receptor (allosteric modulation).
5.2
Drugs for Depression
Many of these drugs are used not only to treat depression but also anxiety disorders, and most have profound effects on sleep architecture, particularly on rapid eye movement (REM) sleep; some also
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