The aim of this review article was to summarize recent publications on effects of antidepressants on sleep and to show that these effects not only depend on the kind of antidepressant drugs but are also related to the dose, the time of drug administration, and the duration of the treatment. Complaints of disrupted sleep are
Antidepressant table activating sedating common in patients suffering from depression, and they are listed among diagnostic criteria for this disorder.
Moreover, midnocturnal insomnia is the most frequent residual symptom of depression. Thus, all antidepressants should normalize sleep. However, at least in short-term treatment, many antidepressants with so-called activating effects e. For sleep-promoting action, the best effects can frequently be achieved with a very "Antidepressant table activating sedating" dose, administered Antidepressant table activating sedating enough before bedtime and importantly, always as a part of more complex interventions based on the cognitive-behavioral protocol to treat insomnia CBT-I.
For successful treatment of depression, it is necessary to understand the effects of antidepressants on sleep. Each physician should also be aware that some antidepressants may worsen or induce primary sleep disorders like restless legs syndrome, sleep bruxism, REM sleep behavior disorder, nightmares, and sleep apnea, which may result from an antidepressant-induced weight gain.
Depression is a severe and common mental disorder with month prevalence as high as 3. Despite its frequent occurrence, high likelihood of a chronic course, negative impact on quality of life and ability to work, and strong association with an increased suicide risk, the available treatment options for depression are still not satisfactory for many patients.
The most neglected pharmacological needs in the treatment of depression are the lack of early-onset response to the treatment, the moderate response and low remission rate to the first antidepressant trial, and side effects which frequently cause treatment non-compliance [ 2 ].
Among the most common side effects of antidepressants and residual symptoms leading to incomplete remission from depression are those related to sleep. The aim of this review article is to summarize the literature published in recent years on how antidepressants affect sleep, as an addition to our [ 3 ] and previous reviews on this topic [e. We also summarize recent data which has shaped our personal view on the use of antidepressants in treating insomnia in depressed and non-depressed subjects.
The most detailed information on sleep in depression was provided by studies using polysomnography PSGthat is considered the gold standard for sleep assessment. Definitions of sleep parameters based on scoring of sleep stages in polysomnographic recording, and used to describe the sleep architecture. Graphically, the sleep architecture is displayed with a Antidepressant table activating sedating that is called hypnogram Fig.
Graph hypnogram representing changes of sleep stages in the "Antidepressant table activating sedating" of night in a depressed patient. Sleep in depression is characterized by disturbances of sleep continuity prolonged sleep latency, increased number and duration of awakenings from sleep, early morning awakeningreduction of deep slow wave sleepand disinhibition of REM sleep, with shortening of REM latency and prolongation of the first REM period.
Y-axis represents sleep stages: Patients with depression show abnormalities of sleep parameters across all three groups. Disrupted sleep continuity manifests as prolongation of sleep latency, increased number, and duration of awakenings from sleep expressed as increased wake after sleep onset WASO time, decreased sleep efficiency, and early morning awakenings. Early morning, awakening together with altered distribution of REM sleep is considered a biological marker of circadian rhythm disturbances in depression and is a characteristic biological marker of depression with melancholic features [ 9 ].
Sleep depth is substantially reduced in depressed patients. Furthermore, the distribution of deep sleep scored in PSG as sleep stage N3, also called delta or slow wave sleep SWSis altered in depressed patients.
In healthy subjects, the highest delta wave activity in EEG can be observed in the first sleep cycle, whereas in depressed patients there is a frequent shift of delta activity from the first to the second sleep cycle. It is expressed in sleep parameters as a reduced delta ratio ratio between delta wave activity in the first and second sleep cycle. Alterations of REM sleep are the most prominent feature of sleep architecture in depressed subjects. They include shortened REM sleep latency, increased REM sleep time especially in the first sleep cycle that is usually very short in healthy subjectsand increased REM sleep density.
The recent meta-analysis summarizing the current evidence from studies using PSG about sleep architecture in mental disorders has confirmed that disturbed sleep is a core symptom of depression. Although none of the sleep was specific to depression, the high prevalence and severity of sleep abnormalities in depressed patients are of a great importance.
Fortunately, in most patients, sleep disturbances diminish with the improvement of depressive symptoms, especially if the clinical improvement is related to the recurrence of interest and pleasure in everyday activities. Because it is usually related to the substantially increased physical daytime activity, it increases homeostatic sleep need, which improves sleep depth and duration. However in many patients, difficulties with sleep persist. The observations on the high prevalence of subjective insomnia complaints and objective worsening of sleep architecture in PSG studies in depressed patients are important for the choice Antidepressant table activating sedating pharmacological treatment.
Antidepressant drugs substantially differ in their acute effects on sleep. Some of them alleviate sleep disturbances, but other may disrupt sleep, which is related to poor treatment compliance. Persistent insomnia symptoms may also result in unfavorable clinical outcome, e. Therefore, it Antidepressant table activating sedating important to know what is the preferred pharmacological treatment in a depressed patient with clinically relevant insomnia symptoms.
On the contrary, antidepressants with antihistaminergic action, like sedating TCA, mirtazapine, mianserine, or strong antagonistic action at serotonergic 5-HT2 receptors, like trazodone and nefazodone quickly improve sleep. Some patients show improvement of sleep quality already after the first drug dose [ 15 ], which was specially discussed for mirtazapine as related to the faster onset of antidepressant action [ 16 ].
In a recent review article on the prevalence of treatment emergent insomnia and somnolence in depressed patients, it was shown that subjective complaints of insomnia or daytime somnolence were frequent in patients suffering from depression or anxiety disorders treated with SSRI and SNRI [ 16 ].
Although both the sleep-disrupting and sleep-promoting effects of the antidepressants are the strongest only in the first few weeks of treatment, in some patients they may persist, aggravating insomnia complaints or causing daytime somnolence [ 18 ]. Therefore, for the depressed patients with clinically significant insomnia, a treatment with a sedative antidepressant is usually more recommended [ 19 ].
The sedating effect of those antidepressants is usually an increasing problem in Antidepressant table activating sedating maintenance treatment, frequently resulting in a need to reduce the drug dose. It may substantially diminish the efficacy of the maintenance treatment.
The sedative antidepressants may also induce a weight gain, what is particularly shown for mirtazapine but not for trazodone [ 23 ]. Agomelatine should be considered as an alternative approach to the treatment of depressed patients with marked insomnia symptoms. Agomelatine is a non-sedative antidepressant drug exerting agonistic action at melatonergic M1 and M2 Antidepressant table activating sedating, and antagonistic action at serotonergic 5-HT2c receptors [ 24 ]. Such pharmacodynamic profile is related to sleep-promoting action without the risk of sedation and weight gain.
Moreover, both drugs differ significantly in their effect on sleep continuity. In the second week, agomelatine slightly improves sleep continuity increased total sleep time and sleep efficiency and escitalopram worsens it [ 25 ]. Moreover, treatment with agomelatine is not related to the suppression of REM sleep: Effects on sleep has recently been also reported for a vortioxetine, with clinical action mediated mainly by selective blockade of serotonin reuptake and direct modulation of serotonergic receptors activity such as 5-HT3, 5-HT7, 5-HT1D, and 5-HT1B "Antidepressant table activating sedating" 27 ].
Both drugs also decrease total sleep time and increase duration of sleep stage N1. The use of antidepressants, also those with sedative properties, may impair sleep due to the induction of sleep disorders or worsening already existing ones. Moreover, although antidepressants are recommended for the treatment of post-traumatic sleep disorder, they can induce nightmares.
We observe this side effect most frequently during the treatment with mirtazapine, just as it was recently reported [ 31 ].
Finally, antidepressants inducing weight gain are contraindicated in patients with sleep apnea, that is an overlooked but frequent sleep disorder in people suffering from mental illness [ 32 Antidepressant table activating sedating. Insomnia belongs to the most frequent disorders of the brain [ 33 ].
Although insomnia is not regarded as a severe mental disorder, it shares many features with depression. In order to offer a patient an effective treatment of insomnia, there is a need for a Antidepressant table activating sedating perspective, one that reaches far beyond the prescription of hypnotics.
However, in daily clinical practice, the use of pharmacotherapy for insomnia is very common. However, due to the lack of methodologically sound randomized clinical trials in insomnia, only one of them, doxepin, is approved by FDA for the treatment of sleep maintenance insomnia.
In our opinion, sedative antidepressants are a valuable treatment option of insomnia in a situation in which despite being in CBT-I therapy, the patient still requires sleep-promoting drugs more than 3—4 times per week.
The use of sedative antidepressants should be also considered when there is a comorbid mood or anxiety disorder because such patients are at increased risk of developing hypnotic dependency. Moreover, in many insomnia patients, physiological parameters, e. The pros and cons of using sedative antidepressants in insomnia patients were discussed extensively in the earlier papers. This is especially true for trazodone that is very often used as a sleep-promoting drug [ 339 — 42 ]. Frequently expressed concern with the usage of sedative antidepressants in insomnia is that their side effect profile and interactions with other drugs may be underrated [ 40 ].
Many psychiatrists are astonished that a sedative antidepressant can promote sleep in such a low dose. Firstly, it should be noted that such low doses are appropriate only for patients with primary insomnia. In the presence of a comorbid mood disorder, the antidepressants have to be used in a recommended therapeutic dose [ 42 ].
Secondly, such treatment Antidepressant table activating sedating be used only when combined Antidepressant table activating sedating behavioral interventions from CBT-I protocol.
When a patient restricts time in bed and uses stimulus control technique, even low-dosage pharmacological treatment starts to work.
Thirdly, to be effective in treating sleep-onset insomnia, sedative antidepressants have to be taken much earlier than hypnotics in regard to their pharmacokinetics, especially the time they take to reach the maximum serum concentration Cmax. In our opinion, sedative antidepressants are a safe class of drugs when given in low doses.
We use them in many patient groups where hypnotics are contraindicated, e. the fact that the use of atypical antipsychotics, mostly quetiapine [ 44 ], is increasing for treatment of insomnia accompanying bipolar disorder and schizophrenia, we hold the conviction that sedative antidepressants are a valuable treatment option for such patients as well. Based on our clinical experience and review of published case reports, we believe that the use of sedative antidepressants in a low dose is not related to the increased Antidepressant table activating sedating of phase shift in bipolar disorder [ 45 ].
Disturbed sleep is a core symptom of depression and its normalization is necessary to achieve remission from the illness. In the long term, all antidepressants which show clinical efficacy improve sleep secondary to improvement of mood and daytime activity.
However, in the short term, while some of them may impair sleep due to the activating effects, other may improve sleep due to the sedative properties. Although sleep-promoting action is desired in depressed patients with coexisting anxiety or insomnia, it may be problematic during the maintenance "Antidepressant table activating sedating" after recovery from depression due to oversedation. Thus, it is necessary to understand the effects of these drugs on the sleep and daytime alertness.
It is particularly noteworthy that for sleep-promoting effect, it is sufficient use a sedative antidepressant in a low dose.
This article does not contain any studies with human or animal subjects performed by any of the authors. This article is part of the Topical Collection on Sleep Disorders.
Center for Biotechnology InformationU. Published online Aug 9. Author information Copyright and License information Disclaimer. This article has been cited by other articles in PMC.
Abstract Purpose of Review The aim of this review article was to summarize recent publications on effects of antidepressants on sleep and to show that these effects not only depend on the kind of antidepressant drugs but are also related to the dose, the time of drug administration, and the duration of the treatment.
Recent Findings Complaints of disrupted sleep are very common in patients suffering from depression, and they are listed among diagnostic criteria for this disorder. Summary For successful treatment of depression, it is necessary to understand the effects of antidepressants on sleep. Depression, Sleep, Antidepressants, Insomnia.
Introduction Depression is a severe and common mental disorder with month prevalence as high as 3. Polysomnographic Sleep Studies in Depression The most detailed information on sleep in depression was provided by studies using polysomnography PSGthat is considered the gold standard for sleep assessment.
Table 1 Definitions of sleep parameters based on scoring of sleep Antidepressant table activating sedating in polysomnographic recording, and used to describe the sleep architecture. Table 1. Definitions of sleep "Antidepressant table activating sedating" based on scoring of sleep stages in.
While SSRI, SNRI, and activating TCA increase REM latency, suppress The sedative antidepressants may also induce a weight gain, what is. Activating/sedating side-effects in randomized clinical trials evaluating fluoxetine versus other antidepressants.