Curr Psychiatry Rep (2017) 19: 63

DOI 10.1007/s11920-017-0816-4

SLEEP DISORDERS (P GEHRMAN, SECTION EDITOR)

Effects of Antidepressants on Sleep

Adam Wichniak 1,2 & Aleksandra Wierzbicka 2 & Małgorzata Walęcka 1 &
Wojciech Jernajczyk 2

Published online: 9 August 2017

# The Author(s) 2017. This article is an open access publication

Abstract sleep. Each physician should also be aware that some

Purpose of Review The aim of this review article was to sum- antidepressants may worsen or induce primary sleep dis-
marize recent publications on effects of antidepressants on orders like restless legs syndrome, sleep bruxism, REM
sleep and to show that these effects not only depend on the sleep behavior disorder, nightmares, and sleep apnea,
kind of antidepressant drugs but are also related to the dose, which may result from an antidepressant-induced weight
the time of drug administration, and the duration of the gain.
treatment.
Recent Findings Complaints of disrupted sleep are very com- Keywords Depression . Sleep . Antidepressants . Insomnia
mon in patients suffering from depression, and they are listed
among diagnostic criteria for this disorder. Moreover,
midnocturnal insomnia is the most frequent residual symptom Introduction
of depression. Thus, all antidepressants should normalize
sleep. However, at least in short-term treatment, many antide- Depression is a severe and common mental disorder with
pressants with so-called activating effects (e.g. fluoxetine, 12-month prevalence as high as 3.2% in subjects without
venlafaxine) may disrupt sleep, while others with sedative comorbid physical disease and 9.3 to 23.0% in subjects
properties (e.g., doxepin, mirtazapine, trazodone) rapidly im- with chronic medical conditions [1]. Despite its frequent
prove sleep, but may cause problems in long-term treatment occurrence, high likelihood of a chronic course, negative
due to oversedation.For sleep-promoting action, the best ef- impact on quality of life and ability to work, and strong
fects can frequently be achieved with a very low dose, admin- association with an increased suicide risk, the available
istered early enough before bedtime and importantly, always treatment options for depression are still not satisfactory
as a part of more complex interventions based on the for many patients. The most neglected pharmacological
cognitive-behavioral protocol to treat insomnia (CBT-I). needs in the treatment of depression are the lack of
Summary For successful treatment of depression, it is nec- early-onset response to the treatment, the moderate re-
essary to understand the effects of antidepressants on sponse and low remission rate to the first antidepressant
trial, and side effects which frequently cause treatment
This article is part of the Topical Collection on Sleep Disorders non-compliance [2]. Among the most common side ef-
fects of antidepressants and residual symptoms leading
* Adam Wichniak to incomplete remission from depression are those related
[email protected] to sleep. The aim of this review article is to summarize
the literature published in recent years on how antidepres-
1
Third Department of Psychiatry, Institute of Psychiatry and
sants affect sleep, as an addition to our [3] and previous
Neurology, Sobieskiego 9, 02-957 Warsaw, Poland reviews on this topic [e.g. 4–8]. We also summarize recent
2
Center for Sleep Medicine, Department of Clinical Neurophysiology,
data which has shaped our personal view on the use of
Institute of Psychiatry and Neurology, Sobieskiego 9, antidepressants in treating insomnia in depressed and non-
02-957 Warsaw, Poland depressed subjects.
63 Page 2 of 7 Curr Psychiatry Rep (2017) 19: 63

Polysomnographic Sleep Studies in Depression and pleasure in everyday activities. Because it is usually relat-
ed to the substantially increased physical daytime activity, it
The most detailed information on sleep in depression was increases homeostatic sleep need, which improves sleep depth
provided by studies using polysomnography (PSG), that is and duration. However in many patients, difficulties with
considered the gold standard for sleep assessment. Based on sleep persist. The Sequenced Treatment Alternatives to
registration of the three physiological parameters such as the Relieve Depression (STAR*D) study, which included a large
brain (EEG), muscle (EMG) and eye movements (EOG) bio- sample of outpatients with non-psychotic MDD who
electric activity, PSG allows human sleep to be scored into responded without remitting after up to 12 weeks treatment
sleep stages. Subsequently, it is possible to calculate several with citalopram, found that midnocturnal insomnia was the
sleep parameters (Table 1) that express sleep continuity, sleep most commonly observed residual symptom of depression,
depth, and distribution of sleep stages. as it was still present in 79% patients [13].
Graphically, the sleep architecture is displayed with a graph The observations on the high prevalence of subjective in-
that is called hypnogram (Fig. 1). somnia complaints and objective worsening of sleep architec-
Patients with depression show abnormalities of sleep pa- ture in PSG studies in depressed patients are important for the
rameters across all three groups. Disrupted sleep continuity choice of pharmacological treatment. Antidepressant drugs
manifests as prolongation of sleep latency, increased number, substantially differ in their acute effects on sleep. Some of
and duration of awakenings from sleep expressed as increased them alleviate sleep disturbances, but other may disrupt sleep,
wake after sleep onset (WASO) time, decreased sleep efficien- which is related to poor treatment compliance. Persistent in-
cy, and early morning awakenings. Early morning, awakening somnia symptoms may also result in unfavorable clinical out-
together with altered distribution of REM sleep is considered a come, e.g., increased suicide risk [14]. Therefore, it is impor-
biological marker of circadian rhythm disturbances in depres- tant to know what is the preferred pharmacological treatment
sion and is a characteristic biological marker of depression in a depressed patient with clinically relevant insomnia
with melancholic features [9]. Sleep depth is substantially re- symptoms.
duced in depressed patients. Furthermore, the distribution of
deep sleep scored in PSG as sleep stage N3, also called delta
or slow wave sleep (SWS), is altered in depressed patients. In Effects on Antidepressants on Sleep
healthy subjects, the highest delta wave activity in EEG can be
observed in the first sleep cycle, whereas in depressed patients It is well known that some classes of antidepressant drugs may
there is a frequent shift of delta activity from the first to the deteriorate sleep quality mainly due to activation of serotoner-
second sleep cycle. It is expressed in sleep parameters as a gic 5-HT2 receptors and increased noradrenergic and dopami-
reduced delta ratio (ratio between delta wave activity in the nergic neurotransmission (Table 2). Among them, most prom-
first and second sleep cycle). Alterations of REM sleep are the inent are serotonin and norepinephrine reuptake inhibitors
most prominent feature of sleep architecture in depressed sub- (SNRI), norepinephrine reuptake inhibitors (NRI), mono-
jects. They include shortened REM sleep latency, increased amine oxidase inhibitors (MAOI), selective serotonin reup-
REM sleep time (especially in the first sleep cycle that is take inhibitors (SSRI), and activating tricyclic antidepressants
usually very short in healthy subjects), and increased REM (TCA).
sleep density. The recent meta-analysis summarizing the cur- On the contrary, antidepressants with antihistaminergic ac-
rent evidence from studies using PSG about sleep architecture tion, like sedating TCA, mirtazapine, mianserine, or strong
in mental disorders has confirmed that disturbed sleep is a core antagonistic action at serotonergic 5-HT2 receptors, like traz-
symptom of depression. It was found that affective disorders odone and nefazodone quickly improve sleep. Some patients
and major depression were associated with alterations in most show improvement of sleep quality already after the first drug
variables compared to healthy controls [10••]. Although none dose [15], which was specially discussed for mirtazapine as
of the sleep parameters was specific to depression, the high related to the faster onset of antidepressant action [16].
prevalence and severity of sleep abnormalities in depressed In a recent review article on the prevalence of treatment
patients are of a great clinical importance. The complaints of emergent insomnia and somnolence in depressed patients, it
insomnia are present in 60–90% of patients with major depres- was shown that subjective complaints of insomnia or daytime
sion, depending on the episode’s severity. When it comes to somnolence were frequent in patients suffering from depres-
bipolar disorder, insomnia is present during a depressive epi- sion or anxiety disorders treated with SSRI and SNRI [16].
sode in 60% of patients, while 20–30% suffer from prolonged Based on data from the US Food and Drug Administration
sleep (hypersomnia) and increased daytime sleepiness [11, (FDA) study register [16], the average prevalence of
12]. Fortunately, in most patients, sleep disturbances diminish treatment-emergent insomnia in clinical trials with SSRI was
with the improvement of depressive symptoms, especially if 17% as compared to 9% out of patients randomized to the
the clinical improvement is related to the recurrence of interest placebo arm. The average rate of treatment emergent
Curr Psychiatry Rep (2017) 19: 63 Page 3 of 7 63

Table 1 Definitions of sleep

parameters based on scoring of Parameters of sleep continuity
sleep stages in polysomnographic
recording, and used to describe Sleep latency Time from start of the recording (“lights out”) to the
the sleep architecture onset of sleep. Normal values are typically below 30
min in young and below 45 min in elderly patients.
Total sleep time (TST) The total time spent asleep during the sleep episode. This is
equal to the time in bed less the awake time. In insomnia
research as shortened sleep time are considered usually
values below 6.5 h in young and below 6 h in elderly patients
(these values are not applicable to short sleepers)
Sleep efficiency (SE) The ratio of total sleep time to time in bed expressed as a
percentage of time spent asleep during the recording period.
Normal values are typically above 90% in young and above
85% in elderly patients.
Wake after sleep onset (WASO) The total time scored as awake occurring after the sleep onset.
Typically WASO should not exceed 30 min.
Parameters of sleep depth
Total and relative amounts of stage N3 Total duration in minutes and as percentage relative to total sleep
time of sleep stage N3. The amount of stage N3 decreases with
older age, normal values are around 10% for elderly and
20–25% for young subjects.
Delta sleep ratio The ratio of slow wave sleep in the first and second sleep cycle.
Normally, values exceed 1.1
Parameters of REM sleep
REM latency The number of minutes from the onset of sleep to the onset of the
first REM sleep period. Reduced values are typically below 65
min in young and 50 min. in elderly patients.
Total and relative amounts of stage REM Total duration in minutes and as percentage relative to total sleep
time of sleep stage REM. Normal values are 20–25%.
REM density The ratio of the intensity of rapid eye movements phasic activity
(number and duration of rapid eye movements) to duration of
REM sleep, e.g., can be expressed as number of rapid eye
movements per minute of REM sleep.

somnolence in patients being treated with SSRI amounted to 2%) was reported in the study with citalopram. The highest
16% as compared to 8% out of patients receiving placebo. The rate of treatment-emergent insomnia and somnolence was
lowest rate of treatment emergent insomnia complaints (below found in patients suffering from obsessive-compulsive

Fig. 1 Graph (hypnogram) representing changes of sleep stages in the REM sleep, with shortening of REM latency and prolongation of the first
course of night in a depressed patient. Sleep in depression is characterized REM period. Y-axis represents sleep stages: W- wake, R- REM sleep, N1
by disturbances of sleep continuity (prolonged sleep latency, increased – stage 1 NREM sleep, N2 – stage 2 NREM sleep, N3 -stage 3 NREM
number and duration of awakenings from sleep, early morning sleep (slow wave sleep, deep sleep), and X-axis represents time and pages
awakening), reduction of deep (slow wave sleep), and disinhibition of of sleep recording
63 Page 4 of 7 Curr Psychiatry Rep (2017) 19: 63

Table 2 Effects of antidepressants on sleep

Drug class Sleep continuity SWS REM latency REM sleep Mechanism of action
related to effect on sleep

Sedative TCA ↑ ↑ ↑ ↓ antihistaminergic effect, inhibition of

(e.g., amitriptyline, doxepin, trimipramine) serotonin, and norepinephrine reuptake
Activating TCA ↓ ↓ ↑ ↓ inhibition of serotonin and
(e.g., imipramine, desipramine) norepinephrine reuptake
MAOI ↓/0 ? ↑ ↓ inhibition of monoamine
(e.g., tranylcypromine, moclobemide) oxidase enzyme
SSRI ↓/0 0/↑ ↑ ↓ selective inhibition of
(e.g., fluoxetine, escitalopram, serotonin reuptake
paroxetine, sertraline)
SNRI and NRI ↓ 0//↑ ↑ ↓ inhibition of serotonin and
(e.g., venlafaxine, duloxetine, reboxetine) norepinephrine reuptake
Agomelatine ↑ ↑ 0 0 agonism at melatonin M1 and M2 receptors,
antagonism at serotonergic 5-HT2C receptors
Bupropion 0/↓ 0/↑ 0/↓ 0/↑ inhibition of norepinephrine and
dopamine reuptake
Sedative antidepressants ↑ ↑ 0 0 antihistaminergic effect, antagonism at
(e.g., mirtazapine, trazodone) serotonergic 5-HT2A receptors
Vortioxetine 0/↓ ? ↑ ↓ inhibition of serotonin reuptake and modulation
of serotonergic receptors activity

TCA tricyclic antidepressants, MAOI monoamine oxidase inhibitors, SSRI selective serotonin reuptake inhibitors, SNRI serotonin norepinephrine
reuptake inhibitors, NRI norepinephrine reuptake inhibitors, ↑ increase, ↓ decrease, 0 no or minimal effect, ? unknown

disorder (OCD) being treated with high-dose fluvoxamine, 31 and usually have little or no effect on REM sleep [3, 6, 7, 17••].
and 27%, respectively [17••]. In clinical trials with SNRI, Although both the sleep-disrupting and sleep-promoting effects
treatment-emergent insomnia was reported on average in of the antidepressants are the strongest only in the first few
13% out of SNRI-treated patients as compared to 7% out of weeks of treatment, in some patients they may persist, aggra-
the placebo arm and treatment-emergent somnolence in 10% vating insomnia complaints or causing daytime somnolence
of SNRI-treated patients in comparison to 5% out of patients [18]. Therefore, for the depressed patients with clinically sig-
receiving placebo. Both treatment-emergent insomnia and nificant insomnia, a treatment with a sedative antidepressant is
somnolence were the most frequent (both equal to 24%) in usually more recommended [19]. It was recently shown that
patients with generalized anxiety disorders treated with such treatment significantly reduces the need to use benzodiaz-
venlafaxine. The lowest rate of treatment emergent insomnia epines in patients with MDD [20•]. Such an approach, combi-
and somnolence (both below 2%) was reported for nation treatment with benzodiazepines and SSRI/SNRI is often
levomilnacipran. On the contrary to the treatment with SSRI necessary to reduce anxiety and insomnia as early as in the first
and SNRI, in clinical studies with sedating antidepressants, week of treatment. However, there is a related risk that the
e.g., mirtazapine and trazodone, the reported prevalence of patient suffering from depression and insomnia will not be able
treatment-emergent insomnia complaints in patients with ma- to stop such treatment after 14–28 days of therapy and will
jor depressive disorder (MDD) was very low (below 2%). develop a dependence [21, 22]. On the other hand, because
However, the rate of treatment-emergent somnolence was the sleep complaints usually improve after a few weeks of ef-
very high, 54% in patients being treated with mirtazapine as fective treatment of depression with SSRI/SNRI, it is important
compared to 18% out of patients in the placebo arm and 46% to consider whether the use of hypnotics is not a better short-
in patients being treated with trazodone as compared to 19% term treatment option for a patient than risking oversedation
out of patients receiving placebo. It is important to note that during treatment with a sedative antidepressant. The sedating
acute effects of antidepressants on sleep are reflected not only effect of those antidepressants is usually an increasing problem
in the patients’ subjective complaints but they can also be dem- in long-term maintenance treatment, frequently resulting in a
onstrated in studies with PSG (Table 2). While SSRI, SNRI, need to reduce the drug dose. It may substantially diminish the
and activating TCA increase REM latency, suppress REM efficacy of the maintenance treatment. The sedative antidepres-
sleep, and may impair sleep continuity, sedating antidepressants sants may also induce a weight gain, what is particularly shown
decrease sleep latency, improve sleep efficiency, increase SWS, for mirtazapine but not for trazodone [23].
Curr Psychiatry Rep (2017) 19: 63 Page 5 of 7 63

Agomelatine should be considered as an alternative ap- Treatment of Insomnia Disorder with Low-Dose
proach to the treatment of depressed patients with marked Antidepressants
insomnia symptoms. Agomelatine is a non-sedative antide-
pressant drug exerting agonistic action at melatonergic M1 Insomnia belongs to the most frequent disorders of the brain
and M2 receptors, and antagonistic action at serotonergic 5- [33]. In industrialized countries, approximately 6% of the
HT2c receptors [24]. Such pharmacodynamic profile is related adults suffer from insomnia as a disorder [34] and as many
to sleep-promoting action without the risk of sedation and as 50% may suffer from transient insomnia symptoms [35•].
weight gain. In comparison to escitalopram, agomelatine is Although insomnia is not regarded as a severe mental disor-
known to improve sleep latency after both short (after 2 weeks) der, it shares many features with depression. In order to offer a
and long (after 24 weeks) treatment. Moreover, both drugs patient an effective treatment of insomnia, there is a need for a
differ significantly in their effect on sleep continuity. In the broader perspective, one that reaches far beyond the prescrip-
second week, agomelatine slightly improves sleep continuity tion of hypnotics. Current treatment guidelines [36••] strongly
(increased total sleep time and sleep efficiency) and recommend the use of cognitive-behavioral therapy (CBT-I)
escitalopram worsens it [25]. Moreover, treatment with as the initial treatment for chronic insomnia disorder and only
agomelatine is not related to the suppression of REM sleep: short-term use of the sleep-promoting drugs in patients with
it restores cyclical sleep profile, may increase the amount of insufficient response to CBI-I. However, in daily clinical prac-
SWS, and most importantly leads to the improvement of day- tice, the use of pharmacotherapy for insomnia is very com-
time alertness [26]. mon. The most frequently used drugs to treat insomnia aside
Effects on sleep has recently been also reported for a from benzodiazepines and non-benzodiazepine (eszopiclone/
vortioxetine, with clinical action mediated mainly by selective zopiclone, zaleplon, zolpidem) hypnotics are sedative antide-
blockade of serotonin reuptake and direct modulation of sero- pressants. However, due to the lack of methodologically
tonergic receptors activity (such as 5-HT3, 5-HT7, 5-HT1D, sound randomized clinical trials in insomnia, only one of
and 5-HT1B) [27]. In a study which has compared the effects them, doxepin, is approved by FDA for the treatment of sleep
of vortioxetine and paroxetine to the placebo in a group of 24 maintenance insomnia. Furthermore, recent recommendations
healthy male volunteers, it has been shown that the discourage the use of other drugs from this class than doxepin
vortioxetine dose of 20 and 40 mg similarly to the paroxetine for the insomnia treatment [37••]. In our opinion, sedative
dose of 20 mg suppresses REM sleep by increasing REM antidepressants are a valuable treatment option of insomnia
sleep latency and diminishing duration of REM sleep. Both in a situation in which despite being in CBT-I therapy, the
drugs also decrease total sleep time and increase duration of patient still requires sleep-promoting drugs more than 3–4
sleep stage N1. These negative effects of vortioxetine on sleep times per week. The use of sedative antidepressants should
continuity are significant only for the higher dose [28•]. be also considered when there is a comorbid mood or anxiety
According to the FDA clinical trial register, the rate of disorder because such patients are at increased risk of devel-
treatment-emergent insomnia complaints or somnolence dur- oping hypnotic dependency. Moreover, in many insomnia pa-
ing the therapy with vortioxetine is lower when compared to tients, physiological parameters, e.g., hormone secretion,
SSRI and SNRI drugs [17••]. whole body, and brain metabolic rate, are altered in a similar
The use of antidepressants, also those with sedative fashion to the depressed ones what is called a hyperarousal
properties, may impair sleep due to the induction of sleep [38, 39], supporting the use of sedative antidepressants to treat
disorders or worsening already existing ones. Mianserin such patients. The pros and cons of using sedative antidepres-
and mirtazapine may induce restless legs syndrome in as sants in insomnia patients were discussed extensively in the
many as 28% of patients [29]. Treatment-emergent RLS earlier papers. This is especially true for trazodone that is very
has also been described for SSRI and venlafaxine [30]. often used as a sleep-promoting drug [3, 39–42]. Frequently
SSRI, SNRI, and TCA are known to induce or exacerbate expressed concern with the usage of sedative antidepressants
sleep bruxism and disturb regulation of muscle tone dur- in insomnia is that their side effect profile and interactions
ing REM sleep, causing REM sleep without atonia, which with other drugs may be underrated [40]. Indeed, although
may induce or worsen REM Sleep Behavior Disorder [3, there is evidence for efficacy of sedative antidepressants to
6]. Moreover, although antidepressants are recommended promote sleep, for example for TCA in a form of a recent
for the treatment of post-traumatic sleep disorder, they can meta-analytic study [43•], it is important to remember that
induce nightmares. We observe this side effect most fre- these drugs should be used in insomnia patients only in a very
quently during the treatment with mirtazapine, just as it low dose, e.g., for doxepin as low as 3 to 6 mg or 25–50 mg
was recently reported [31]. Finally, antidepressants induc- for trazodone. Many psychiatrists are astonished that a seda-
ing weight gain are contraindicated in patients with sleep tive antidepressant can promote sleep in such a low dose.
apnea, that is an overlooked but frequent sleep disorder in Firstly, it should be noted that such low doses are appropriate
people suffering from mental illness [32]. only for patients with primary insomnia. In the presence of a
63 Page 6 of 7 Curr Psychiatry Rep (2017) 19: 63

comorbid mood disorder, the antidepressants have to be used Compliance with Ethical Standards
in a recommended therapeutic dose [42]. Secondly, such treat-
Conflict of Interest Aleksandra Wierzbicka, Małgorzata Walęcka, and
ment should be used only when combined with behavioral
Wojciech Jernajczyk declare that they have no conflict of interest.
interventions from CBT-I protocol. When a patient restricts Adam Wichniak received speaker honoraria and congress travel
time in bed and uses stimulus control technique, even low- grants from Angelini, Janssen-Cilag, Lundbeck, Sanofi, and Servier.
dosage pharmacological treatment starts to work. Thirdly, to
be effective in treating sleep-onset insomnia, sedative antide- Human and Animal Rights and Informed Consent This article does
not contain any studies with human or animal subjects performed by any
pressants have to be taken much earlier than hypnotics in
of the authors.
regard to their pharmacokinetics, especially the time they take
to reach the maximum serum concentration (Cmax). It usually Open Access This article is distributed under the terms of the Creative
means at least 2 hours before sleep (in the case of more rapid Commons Attribution 4.0 International License (http://
creativecommons.org/licenses/by/4.0/), which permits unrestricted use,
drug action the patient should be encouraged to shorten this distribution, and reproduction in any medium, provided you give appro-
time). In our opinion, sedative antidepressants are a safe priate credit to the original author(s) and the source, provide a link to the
class of drugs when given in low doses. We use them in Creative Commons license, and indicate if changes were made.
many patient groups where hypnotics are contraindicated,
e.g., in the elderly patients, in patients with sleep apnea
and in patients with a history of alcohol and substance References
abuse. Despite the fact that the use of atypical antipsy-
chotics, mostly quetiapine [44], is increasing for treatment Papers of Particular Interest, Published Recently, Have Been
of insomnia accompanying bipolar disorder and schizo- Highlighted as:
phrenia, we hold the conviction that sedative antidepres- • Of importance
sants are a valuable treatment option for such patients as •• Of major importance
well. Based on our clinical experience and review of pub-
lished case reports, we believe that the use of sedative 1. Moussavi S, Chatterji S, Verdes E, Tandon A, Patel V, Ustun B.
antidepressants in a low dose is not related to the in- Depression, chronic diseases, and decrements in health: results
from the world health surveys. Lancet. 2007;370:851–8.
creased risk of phase shift in bipolar disorder [45].
2. Greden JF. Unmet need: what justifies the search for a new antide-
Moreover, we have observed that for the treatment of pressant? J Clin Psychiatry. 2002;63(Suppl 2):3–7.
insomnia low doses (5–10 mg) of citalopram administered 3. Wichniak A, Wierzbicka A, Jernajczyk W. Sleep and antidepressant
in the morning can be an alternative to sedative antide- treatment. Curr Pharm Des. 2012;18:5802–17.
4. Le Bon O. Contribution of sleep research to the development of
pressants with good treatment effects [46].
new antidepressants. Dialogues Clin Neurosci. 2005;7:305–13.
5. Mendlewicz J. Sleep disturbances: core symptoms of major depres-
sive disorder rather than associated or comorbid disorders. World J
Conclusions Biol Psychiatry. 2009;10:269–75.
6. Wilson S, Argyropoulos S. Antidepressants and sleep: a qualitative
review of the literature. Drugs. 2005;65:927–47.
Disturbed sleep is a core symptom of depression and its 7. Gursky JT, Krahn LE. The effects of antidepressants on sleep: a
normalization is necessary to achieve remission from the review. Harv Rev Psychiatry. 2000;8:298–306.
illness. In the long term, all antidepressants which show 8. Thase ME. Depression, sleep, and antidepressants. J Clin
clinical efficacy improve sleep secondary to improvement Psychiatry. 1998;59(Suppl 4):55–65.
9. Wichniak A, Wierzbicka A, Jernajczyk W. Sleep as a biomarker for
of mood and daytime activity. However, in the short term, depression. Int Rev Psychiatry. 2013;25:632–45.
while some of them may impair sleep due to the activat- 10.•• Baglioni C, Nanovska S, Regen W, Spiegelhalder K, Feige B, Nissen
ing effects, other may improve sleep due to the sedative C, et al. Sleep and mental disorders: a meta-analysis of polysomno-
properties. Although sleep-promoting action is desired in graphic research. Psychol Bull. 2016;142:969–90. This large meta-
analysis presents polysomnographic (PSG) characteristics of
depressed patients with coexisting anxiety or insomnia, it sleep in affective, anxiety, eating, pervasive developmental, bor-
may be problematic during the maintenance treatment af- derline and antisocial personality, attention-deficit-hyperactivity
ter recovery from depression due to oversedation. Thus, it disorders and schizophrenia. It has been found that no sleep
is necessary to understand the effects of these drugs on parameter was exclusively altered in one condition; however,
no two conditions shared the same PSG profile.
the sleep and daytime alertness. It is particularly notewor- 11. Abad VC, Guilleminault C. Sleep and psychiatry. Dialogues Clin
thy that for sleep-promoting effect, it is sufficient to use a Neurosci. 2005;7:291–303.
sedative antidepressant in a low dose. In such dose, these 12. Kaplan KA, Harvey AG. Hypersomnia across mood disorders: a
drugs can be also combined with other antidepressants as review and synthesis. Sleep Med Rev. 2009;13:275–85.
13. McClintock SM, Husain MM, Wisniewski SR, Nierenberg AA,
an alternative to hypnotic drugs, especially if there is a Stewart JW, Trivedi MH, et al. Residual symptoms in depressed
clinical necessity to promote sleep for longer than 2– outpatients who respond by 50% but do not remit to antidepressant
4 weeks with a frequency higher than 3–4 times per week. medication. J Clin Psychopharmacol. 2011;31:180–6.
Curr Psychiatry Rep (2017) 19: 63 Page 7 of 7 63

14. Kay DB, Dombrovski AY, Buysse DJ, Reynolds CF, Begley A, Szanto legs syndrome—case report and literature review. Psychiatr Pol.
K. Insomnia is associated with suicide attempt in middle-aged and older 2015;49:921–30.
adults with depression. Int Psychogeriatr. 2016;28:613–9. 31. Buschkamp JA, Frohn C, Juckel G. Mirtazapine induces night-
15. Schmid DA, Wichniak A, Uhr M, Ising M, Brunner H, Held K, et al. mares in depressed patients. Pharmacopsychiatry. 2017.
Changes of sleep architecture, spectral composition of sleep EEG, the 32. Szaulińska K, Pływaczewski R, Sikorska O, Holka-Pokorska J,
nocturnal secretion of cortisol, ACTH, GH, prolactin, melatonin, ghrel- Wierzbicka A, Wichniak A, et al. Obstructive sleep apnea in severe
in, and leptin, and the DEX-CRH test in depressed patients during mental disorders. Psychiatr Pol. 2015;49:883–95.
treatment with mirtazapine. Neuropsychopharmacology. 2006;31: 33. Wittchen HU, Jacobi F, Rehm J, Gustavsson A, Svensson M,
832–44. Jonsson B, et al. The size and burden of mental disorders and other
16. Thompson C. Onset of action of antidepressants: results of different disorders of the brain in Europe 2010. Eur Neuropsychopharmacol.
analyses. Hum Psychopharmacol. 2002;17(Suppl 1):S27–32. 2011;21:655–79.
17.•• Doghramji K, Jangro WC. Adverse effects of psychotropic medi- 34. Ohayon MM. Epidemiology of insomnia: what we know and what
cations on sleep. Psychiatr Clin North Am. 2016;39:487–502. This we still need to learn. Sleep Med Rev. 2002;6:97–111.
study presents effects of psychotropic medications such as anti- 35.• Nowicki Z, Grabowski K, Cubala WJ, Nowicka-Sauer K,
depressants, antipsychotics, stimulants, and benzodiazepines Zdrojewski T, Rutkowski M, et al. Prevalence of self-reported in-
on sleep based on analysis of data from US Food and Drug somnia in general population of Poland. Psychiatr Pol. 2016;50:
Administration (FDA) study register. It shows that that medi- 165–73. This study shows the high prevalence of insomnia
cation has significant impact on sleep, resulting in both benefi- symptoms in a representative sample of Polish general
cial and adverse effects on sleep. population.
18. Fava M. Daytime sleepiness and insomnia as correlates of depres- 36.•• Qaseem A, Kansagara D, Forciea MA, Cooke M, Denberg TD.
sion. J Clin Psychiatry. 2004;65(Suppl 16):27–32. Management of chronic insomnia disorder in adults: a clinical prac-
19. Jindal RD, Thase ME. Treatment of insomnia associated with clin- tice guideline from the American College of Physicians. Ann Intern
ical depression. Sleep Med Rev. 2004;8:19–30. Med. 2016;165:125–33. This publication presents guidelines for
20.• Hashimoto T, Shiina A, Hasegawa T, Kimura H, Oda Y, Niitsu T, chronic insomnia treatment indicating that cognitive-
et al. Effect of mirtazapine versus selective serotonin reuptake in- behavioral therapy should be used as a first line treatment.
hibitors on benzodiazepine use in patients with major depressive 37.•• Sateia MJ, Buysse DJ, Krystal AD, Neubauer DN, Heald JL.
disorder: a pragmatic, multicenter, open-label, randomized, active- Clinical practice guideline for the pharmacologic treatment of
controlled, 24-week trial. Ann General Psychiatry. 2016;15:27. chronic insomnia in adults: an American Academy of sleep medi-
This study demonstrates that mirtazapine as the first-choice cine clinical practice guideline. J Clin Sleep Med. 2017;13:307–49.
antidepressant for current depressive episodes reduces benzo- This publication contains recent recommendations for clini-
diazepine use in patients with MDD. cians in choosing a specific pharmacological agent for treat-
21. Jindal RD, Friedman ES, Berman SR, Fasiczka AL, Howland RH, ment of chronic insomnia in adults.
Thase ME. Effects of sertraline on sleep architecture in patients with 38. Bonnet MH, Arand DL. Hyperarousal and insomnia: state of the
depression. J Clin Psychopharmacol. 2003;23:540–8. science. Sleep Med Rev. 2010;14:9–15.
22. Furukawa TA, Streiner DL, Young LT. Antidepressant and benzo- 39. Riemann D, Spiegelhalder K, Feige B, Voderholzer U, Berger M,
diazepine for major depression. Cochrane Database Syst Rev. 2002; Perlis M, et al. The hyperarousal model of insomnia: a review of the
CD001026. concept and its evidence. Sleep Med Rev. 2010;14:19–31.
23. Serretti A, Mandelli L. Antidepressants and body weight: a com- 40. Mendelson WB, Roth T, Cassella J, Roehrs T, Walsh JK, Woods
prehensive review and meta-analysis. J Clin Psychiatry. 2010;71: JH, et al. The treatment of chronic insomnia: drug indications,
1259–72. chronic use and abuse liability. Summary of a 2001 new clinical
24. Hickie IB, Rogers NL. Novel melatonin-based therapies: potential drug evaluation unit meeting symposium. Sleep Med Rev. 2004;8:
advances in the treatment of major depression. Lancet. 2011;378: 7–17.
621–31. 41. Wiegand MH. Antidepressants for the treatment of insomnia : a
25. Quera-Salva MA, Hajak G, Philip P, Montplaisir J, Keufer-Le GS, suitable approach? Drugs. 2008;68:2411–7.
Laredo J, et al. Comparison of agomelatine and escitalopram on 42. Wilson SJ, Nutt DJ, Alford C, Argyropoulos SV, Baldwin DS,
nighttime sleep and daytime condition and efficacy in major depres- Bateson A, et al. British Association for Psychopharmacology con-
sive disorder patients. Int Clin Psychopharmacol. 2011;26:252–62. sensus statement on evidence-based treatment of insomnia,
26. Quera-Salva MA, Lemoine P, Guilleminault C. Impact of the novel parasomnias and circadian rhythm disorders. J Psychopharmacol.
antidepressant agomelatine on disturbed sleep-wake cycles in de- 2010;24:1577–601.
pressed patients. Hum Psychopharmacol. 2010;25:222–9. 43.• Liu Y, Xu X, Dong M, Jia S, Wei Y. Treatment of insomnia with
27. Sowa-Kucma M, Panczyszyn-Trzewik P, Misztak P, Jaeschke RR, tricyclic antidepressants: a meta-analysis of polysomnographic ran-
Sendek K, Styczen K, et al. Vortioxetine: a review of the pharma- domized controlled trials. Sleep Med. 2017;34:126–33. This meta-
cology and clinical profile of the novel antidepressant. Pharmacol analysis summarizes the evidence on effects of tricyclic antide-
Rep. 2017;69:595–601. pressants on sleep in insomnia patients. TCAs has been found
28.• Wilson S, Hojer AM, Buchberg J, Areberg J, Nutt DJ. as an effective pharmacological treatment for insomnia, but
Differentiated effects of the multimodal antidepressant may cause dangerous side effects.
vortioxetine on sleep architecture: part 1, a pharmacokinetic/ 44. Thompson W, Quay TA, Rojas-Fernandez C, Farrell B, Bjerre LM.
pharmacodynamic comparison with paroxetine in healthy men. J Atypical antipsychotics for insomnia: a systematic review. Sleep
Psychopharmacol. 2015;29:1085–91. This is the first polysom- Med. 2016;22:13–7.
nographic study presenting effects of vortioxetine on sleep ar- 45. Wichniak A, Jarkiewicz M, Okruszek L, Wierzbicka A, Holka-
chitecture in comparison to placebo and paroxetine. Pokorska J, Rybakowski JK. Low risk for switch to mania during
29. Rottach KG, Schaner BM, Kirch MH, Zivotofsky AZ, Teufel LM, treatment with sleep promoting antidepressants.
Gallwitz T, et al. Restless legs syndrome as side effect of second Pharmacopsychiatry. 2015;48:83–8.
generation antidepressants. J Psychiatr Res. 2008;43:70–5. 46. Jernajczyk W, Sobańska A, Wierzbicka A, Wichniak A,
30. Narowska D, Bozek M, Krysiak K, Antczak J, Holka-Pokorska J, Szatkowska E. The therapy of primary insomnia with citalopram.
Jernajczyk W, et al. Frequent difficulties in the treatment of restless J Sleep Res. 2006;15(Suppl. 1):154.