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Psychotropic medications have a broad range of mechanisms of action, which are presumed to be involved in their sleep-related adverse effects.
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Insomnia and daytime somnolence are common adverse effects of these medications.
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These effects can be beneficial or detrimental depending on the particular symptoms of the patient’s psychiatric disorder.
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Being aware of an agent’s most likely adverse effects on sleep can aid the prescriber in choosing an agent that is more likely to improve the sleep
Adverse Effects of Psychotropic Medications on Sleep
Section snippets
Key points
Antidepressants
People suffering from depressive disorders typically complain of difficulty falling asleep, frequent awakenings, early morning wakening, and non-refreshing sleep. Polysomnographic studies of depressed persons have confirmed these findings and show reduced rapid eye movement (REM) latency, increased REMs, increased total time in REM sleep, reduced slow wave sleep (SWS), and frequent awakenings throughout the night.1 Antidepressants are widely prescribed for mood and anxiety disorders. According
Subjective Effects
Subjective complaints of insomnia and daytime somnolence are common in people with depression being treated with selective serotonin reuptake inhibitors (SSRIs). Of the SSRIs currently indicated for the treatment of depression, fluoxetine’s effects on sleep have been the most thoroughly studied. These effects may represent a class effect. Fluoxetine has been found to cause both significant activation and sedation compared with placebo.6 Rates of activation tend to be stable at dosages between 5
Subjective Effects
Serotonin-norepinephrine reuptake inhibitors (SNRIs) are associated with frequent subjective complaints of insomnia and daytime somnolence as well as vivid dreams. Studies using polysomnography techniques have been limited. Most studies involve the use of the older SNRIs, venlafaxine and duloxetine (Fig. 2).
Polysomnographic Effects
Treatment with venlafaxine has been shown to cause an increase in wakefulness after sleep onset (WASO) after 1 month of treatment compared with placebo-treated groups.16 It significantly
Subjective Effects
Tertiary amine tricyclic antidepressants (TCAs; amitriptyline, trimipramine) tend to be more sedating, whereas secondary amine TCAs (desipramine, nortriptyline) tend to be more activating. Therefore, it may easier to choose a particular agent in this class that will have the desired effect on sleep profile compared with other classes of antidepressants. Sedating, tertiary amine TCAs tend to shorten SOL, improve sleep continuity and efficiency, and reduce WASO.28, 29, 30 Activating, secondary
Antipsychotics
Antipsychotics are indicated for the treatment of schizophrenia and other psychotic disorders. Many of the atypical antipsychotics also have indications for the treatment of bipolar disorder and adjunctive treatment of MDDs. Daytime somnolence and sedation seem to be a much more common problem with antipsychotics compared with insomnia. Antipsychotics are thought to exert much of their indicated effects through antagonism of dopamine receptors. Many typical and atypical antipsychotics also
Restless legs syndrome
Antipsychotic agents may cause or exacerbate RLS.50 A case series of 7 patients given low-dose quetiapine reported a dose-dependent provocation of RLS.56 The investigators noted that most of these patients suffered from affective disorders and were on concomitant antidepressants. The Prescribing Information for quetiapine notes the occurrence of restless legs syndrome (RLS) in 2% of persons on quetiapine versus none on placebo.57 Other case reports also seem to suggest that patients with
Nonbenzodiazepine hypnotics
Parasomnias like sleepwalking and sleep-related eating disorders (SRED) have been reported with nonbenzodiazepine hypnotics. In a review of parasomnias in psychiatric outpatients,62 sleepwalking was linked to zolpidem and zopiclone, whereas both sleepwalking and SRED were associated with zolpidem alone. Parasomnias with this class of medication were more likely in patients taking them regularly rather than on an as-needed basis.
Stimulants
Stimulants are commonly prescribed for the treatment of attention-deficit/hyperactivity disorder (ADHD). The relationship between sleep and medication in children with ADHD is complex. Insomnia or delayed SOL greater than 30 minutes is one of the most common adverse effects associated with stimulant medications.63 However, the effects of methylphenidate on sleep may depend on the length of time the child has been on the medication.64 In addition, there are reports of children having difficulty
Summary
Antidepressant and antipsychotic agents frequently result in sleep-related adverse effects, primarily insomnia and daytime somnolence. However, these effects have not been well evaluated. Data from placebo-controlled trials are available primarily in the form of spontaneous reports rather than systematic assessments. Where sleep-related effects have been specifically studied as end points, the data are limited to small sample sizes and with methodological inconsistencies. In addition,
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This article originally appeared in Psychiatric Clinics of North America, Volume 39, Issue 3, September 2016.
Dr K. Doghramji owns stock in Merck and is a consultant for Merck, Inspire, Jazz, Xenoport, Teva, Pfizer, and Pernix. Dr W. C. Jangro has nothing to disclose.