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Biological clocks such as circadian, ultradian, and infradian rhythms have their own organizations, independently from environmental conditions. Although there is biological sustainability, psychiatric disorders and also psychotropic medications have important effects on the synchronization of biological clocks. Various biological mediators such as glutamate, ? aminobutyric acid, histamine, dopamine, acetylcholine, serotonin and their receptor systems take on the mediation of inner clocks via psychotropic drugs.
Histaminergic activity is highly increased during wakefulness. H1 antagonists, generally increase Slow-Wave Sleep and stage 2 sleep and reduce rapid eye movement sleep. Diphenhydramine can cause subjective sedation and decreased sleep latency with no effect on memory or learning processes. The long elimination half-lives of these drugs can result in next-day sedation and impairment of psychomotor and cognitive function the next morning.
Benzodiazepines shorten sleep-onset latency, increase total sleep time and stage 2 sleep, and suppress rapid eye movement sleep and slow-wave sleep. The risk of rebound insomnia is greatest with rapid elimination of benzodiazepines.
About 65% of major depressive disorder patients report sleep complaints. Based on polysomnography studies, sleep architecture is estimated to be disturbed in up to 90% of depressed patients. Except desipramine, all TCAs block H1 and ?1 receptors to varying degrees. As a general rule, the noradrenergic TCAs (e.g. desipramine, protriptyline) are considered 'activating'. These agents have a tendency to increase sleep-onset latency as well as to decrease total sleep time, associated with an increase in wake time after sleep onset. Paroxetine and şuoxetine clearly suppress REM sleep, both among healthy volunteers and depressed patients. Compared to other SSRIs, citalopram may be less activating and therefore less likely to disrupt sleep continuity.
Lithium and valproate have many acute, subacute, and chronic effects on systems, at the cellular and molecular levels. Lithium treatment modifies circadian rhythms in humans and in most animals, primarily by lengthening the period of the cycle.
Most of the sleep-promoting effects of antipsychotic drugs have been related to their potency to antagonize ? adrenergic, histaminergic, or cholinergic neurotransmission. Among classical antipsychotics, drugs having these properties, such as phenothiazines and thioxanthenes, are clearly sedative and promote sleep. Among atypical antipsychotics, drugs having this pharmacodynamics profile are olanzapine, clozapine, and quetiapine. Clozapine and olanzapine increase total sleep time and sleep efficiency and have no clear-cut effect on REM sleep.