Sleep effects, antidepressant drugs

Staner, L., Luthringer, R. Macher, J. P. (1999). Effects of antidepressant drugs on sleep EEG in patients with major depression. Central Nerv. Syst. Drugs 11,... 

All antidepressant drugs have some effects on sleep architecture. Suppression of REM sleep associated with the treatment of depression was such a consistent finding in early studies that it was seen as essential for the antidepressant action. 

Many antidepressant drugs have pronounced effects on sleep. Several tricyclic compounds (amitriptyline and others) have sedative actions while others (imipramine and others) are less sedative or even stimulant. Monoamine oxidase inhibitors (MAOIs) have central stimulant effects and may cause insomnia. Specific serotonin reuptake inhibitors (SSRls) and combined serotonin, noradrenaline reuptake inhibitors (SNRIs) can also cause insomnia. 

Papadimitriou GN, Kerkhofs M, Kempenaers C, et al EEG sleep in patients with generalized anxiety disorder. Psychiatry Res 26 183-190, 1988 Papadimitriou GN, Christodoulou GN, Katsouyanni K, et al Therapy and prevention of affective illness by total sleep deprivation. J Affect Disord 27 107-116, 1993 Papp M, Muscat R, Willner P Additive effects of chronic treatment with antidepressant drugs and intermittent treatment with a dopamine agonist. Eur Neuropsy-chopharmacol 2 121-125, 1992... 

Other classes of drugs not included in Figure 22-3 that may exert sedative effects include most antipsychotic and many antidepressant drugs and certain antihistaminic agents (eg, hydroxyzine, promethazine). As discussed in other chapters, these agents differ from conventional sedative-hypnotics in both their effects and their major therapeutic uses. Since they commonly exert marked effects on the peripheral autonomic nervous system, they are sometimes referred to as "sedative-autonomic" drugs. Certain antihistaminics with sedative effects are available in over-the-counter sleep aids. Their autonomic properties and their long durations of action can result in adverse effects. 

The type of research described under this heading aims at correlating therapeutic outcome and pre-therapy sleep as well as therapy-induced sleep alterations. This section is voluntarily limited to the two therapies whose relationships to sleep are the most documented, i.e., antidepressant drugs and sleep deprivation therapy. The effects of these two therapies are examined in the light of the three theories. According to these theories, effective therapies have either to decrease the arousal level, to increase process S, or to restore the aminergic/cholinergic balance. 

Other classes of antidepressant drugs can sometimes cause somnambulism, and it seems likely that paroxetine provoked this rare adverse effect. Sleep-walking is thought to be initiated during slow-wave sleep, after which partial arousals activate motor behaviors in the absence of full consciousness. The disrupting effects of antidepressants on sleep architecture might lead to somnambulism in pre-disposed individuals. 

Regulation of mood, sleep, and aggression have all been shown to involve the serotoninergic system (17-19), and most antidepressant drugs currently being used inhibit 5-HT reuptake and/or act on 5-HT receptors (of which there are several subtypes). 5-HT is produced centrally from the amino acid tryptophan, and depressed mood can be induced experimentally by acute tryptophan depletion in healthy individuals. This effect is accentuated in those with a family history of depression (18-21). Similarly, depressive relapse can be initiated in individuals treated with MAO inhibitors or selective serotonin reuptake (SSRI) inhibitors by depleting tryptophan (22, 23). 

The most commonly used therapies for anxiety and depression are selective serotonin reuptake inhibitors (SSRIs) and the more recently developed serotonin noradrenaline reuptake inhibitors (SNRIs). SSRIs, which constitute 60% of the worldwide antidepressant and antianxiety market, are frequently associated with sexual dysfunction, appetite disturbances and sleep disorders. Because SSRIs and SNRIs increase 5-HT levels in the brain, they can indirectly stimulate all 14 serotonergic receptor subtypes [2,3], some of which are believed to lead to adverse side effects associated with these drugs. Common drugs for short-term relief of GAD are benzodiazepines. These sedating agents are controlled substances with addictive properties and can be lethal when used in combination with alcohol. The use of benzodiazepines is associated with addiction, dependency and cognitive impairment. 

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