Excessive Daytime Sleepiness and Insomnia Symptoms in Adolescents With Major Depressive Disorder: Prevalence, Clinical Correlates, and the Relationship With Psychiatric Medications Use

Yudong Shi; Wei Li; Changhao Chen; Xiaoping Yuan; Yingying Yang; Song Wang; Zhiwei Liu; Feng Geng; Jiawei Wang; Xiangfen Luo; Xiangwang Wen; Lei Xia; Huanzhong Liu

doi:10.30773/pi.2023.0013

Psychiatry Investig > Volume 20(11); 2023 > Article

Shi, Li, Chen, Yuan, Yang, Wang, Liu, Geng, Wang, Luo, Wen, Xia, and Liu: Excessive Daytime Sleepiness and Insomnia Symptoms in Adolescents With Major Depressive Disorder: Prevalence, Clinical Correlates, and the Relationship With Psychiatric Medications Use

Original Article

Psychiatry Investigation 2023;20(11):1018-1026.

Published online: November 21, 2023

DOI: https://doi.org/10.30773/pi.2023.0013

Excessive Daytime Sleepiness and Insomnia Symptoms in Adolescents With Major Depressive Disorder: Prevalence, Clinical Correlates, and the Relationship With Psychiatric Medications Use

Yudong Shi^1,^2,^3,^*

, Wei Li^1,^*

, Changhao Chen^4,^*

, Xiaoping Yuan¹

, Yingying Yang^1,^2,³

, Song Wang^1,^2,³

, Zhiwei Liu⁵

, Feng Geng⁶

, Jiawei Wang⁷

, Xiangfen Luo⁸

, Xiangwang Wen⁹

, Lei Xia^1,^2,³

, Huanzhong Liu^1,^2,³

¹Department of Psychiatry, Chaohu Hospital of Anhui Medical University, Hefei, Anhui, China

²Department of Psychiatry, School of Mental Health and Psychological Sciences, Anhui Medical University, Hefei, Anhui, China

³Anhui Psychiatric Center, Anhui Medical University, Hefei, Anhui, China

⁴Department of Psychiatry, Suzhou Second People’s Hospital, Suzhou, Anhui, China

⁵Department of Psychiatry, Fuyang Third People’s Hospital, Fuyang, Anhui, China

⁶Department of Psychiatry, Hefei Fourth People’s Hospital, Hefei, Anhui, China

⁷Department of Psychiatry, Bozhou People’s Hospital, Bozhou, Anhui, China

⁸Department of Psychiatry, The Second Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui, China

⁹Department of Psychiatry, Ma’anshan Fourth People’s Hospital, Ma’anshan, Anhui, China

Correspondence: Lei Xia, MD Department of Psychiatry, Chaohu Hospital of Anhui Medical University, 64 Chaohu North Road, Hefei, Anhui 238000, China Tel: +86-18256012080, Fax: +86-0551-82324252, E-mail: xialei@ahmu.edu.cn

Correspondence: Huanzhong Liu, MD, PhD Department of Psychiatry, Chaohu Hospital of Anhui Medical University, 64 Chaohu North Road, Hefei, Anhui 238000, China Tel: +86-0551-82324616, Fax: +86-0551-82324252, E-mail: huanzhongliu@ahmu.edu.cn

^* These authors contributed equally to this work.

Received January 16, 2023 Revised May 21, 2023 Accepted July 28, 2023

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Objective

Excessive daytime sleepiness (EDS) and insomnia symptoms are common in patients with major depressive disorder (MDD), which might lead to a poor prognosis and an increased risk of depression relapse. The current study aimed to investigate the prevalence, and sociodemographic and clinical correlates of EDS and insomnia symptoms among adolescents with MDD.

Methods

The sample of this cross-sectional study included 297 adolescents (mean age=15.26 years; range=12-18 years; 218 females) with MDD recruited from three general and four psychiatric hospitals in five cities (Hefei, Bengbu, Fuyang, Suzhou, and Ma’anshan) in Anhui Province, China between January and August, 2021. EDS and insomnia symptoms, and clinical severity of depressive symptoms were assessed using Epworth sleepiness scale, Insomnia Severity Index, and Clinical Global Impression-Severity.

Results

The prevalence of EDS and insomnia symptoms in adolescents with MDD was 39.7% and 38.0%, respectively. Binary logistic regression analyses showed that EDS symptoms were significantly associated with higher body mass index (odds ratio [OR]=1.097, 95% confidence interval [CI]=1.027-1.172), more severe depressive symptoms (OR=1.313, 95% CI=1.028-1.679), and selective serotonin reuptake inhibitors use (OR=2.078, 95% CI=1.199-3.601). And insomnia symptoms were positively associated with female sex (OR=1.955, 95% CI=1.052-3.633), suicide attempts (OR=1.765, 95% CI=1.037-3.005), more severe depressive symptoms (OR=2.031, 95% CI=1.523-2.709), and negatively associated with antipsychotics use (OR=0.433, 95% CI=0.196-0.952).

Conclusion

EDS and insomnia symptoms are common among adolescents with MDD. Considering their negative effects on the clinical prognosis, regular screening and clinical managements should be developed for this patient population.

Keywords: Major depressive disorder, Excessive daytime sleepiness, Insomnia, Adolescents

INTRODUCTION

Major depressive disorder (MDD) is often comorbid with sleep disturbances [1]. Over 80% of patients with MDD report experiencing insomnia-related symptoms, and about half report hypersomnia symptoms [2,3]. Besides being common concomitant symptoms in patients with MDD, sleep disturbances are also recognized to be an important predictor of a poor prognosis [4].

Excessive daytime sleepiness (EDS) is defined as falling asleep that is difficult to control during the daytime [5]. The prevalence rate of EDS symptoms in general population was 18.0%-29.2% across studies using different measurement instruments [6-8]. The rate in adult patients with MDD was 33.6%-57.2% [9-11]. EDS symptoms are associated with lower cognitive function and quality of life [12-15]. And individuals with EDS symptoms were more likely to develop disability and mortality than those without these symptoms [16]. In adolescents, EDS symptoms may negatively impact academic performance and individual developments, leading to a higher unemployment rate and a lower income level in the future [17,18]. Several prospective and cross-sectional studies have demonstrated that EDS is positively associated with a high level of depression in women [19], adolescents [20,21], and adults with MDD [9]. Moreover, current depressive episodes in adolescents may contribute to the occurrence of EDS [22,23]. In addition, EDS symptoms were also found to be associated with higher body mass index (BMI) and selective serotonin reuptake inhibitors (SSRIs) use in adults with MDD [9]. To date, fewer studies have examined the prevalence and clinical factors of EDS among adolescents with MDD.

Insomnia is a common sleep complaint characterized by difficulty falling asleep, difficulty maintaining sleep and waking up too early [24]. The prevalence of insomnia symptoms in patients with MDD was 45.0%-86.5% [25-27], and severe insomnia was a characteristic feature associated with the risk of adolescent depressive episodes [28]. Insomnia symptoms negatively impact on cognitive functions of patients with MDD, such as attentional-executive functions and information processing speed [29,30]. They are also associated with increased risk of suicidality and depression relapse [30,31]. A prospective 6-year follow-up study involving 1,713 patients with MDD found that individuals with insomnia symptoms were approximately 1.42 times more likely to attempt suicide than those without insomnia symptoms [32]. A recent study found that MDD patients with insomnia had a significantly shorter relapse time than those without insomnia, with 1-year relapse rates of 43.4% and 7.4%, respectively [33]. Furthermore, patients with comorbid depression and insomnia were more inclined to have treatment-resistant depression in the future [34]. Given this high prevalence and the negative impacts, it is important to reveal the characteristics of insomnia symptoms in MDD patients, especially in the key population subgroup of adolescents.

Specifically, since some patients with MDD have sleep symptoms and psychiatric symptoms, sedative-hypnotics and antipsychotics are often used in addition to antidepressants. These medications may be associated with EDS or insomnia symptoms due to various effect on the sleep architecture [35]. For example, previous studies have found that the use of some antidepressants is associated with insomnia symptoms (e.g., venlafaxine and duloxetine) [36,37]; use of some other medications that may improve insomnia symptoms (e.g., mirtazapine and trazodone) [38,39]. In addition, most antipsychotic drugs can promote sleep quality of patients at night, such as olanzapine and quetiapine [40,41]. However, they may also be associated with EDS symptoms due to their effect on the histaminergic system [42,43]. Similarly, benzodiazepines may improve patients’ insomnia symptoms while causing EDS symptoms [9,44]. This study categorized psychiatric medications to explore their possible effects on sleep in adolescents with MDD.

Many studies have already explored sleep disturbances, such as EDS and insomnia symptoms in adults with MDD, which remain not yet clear among adolescent patients. Therefore, the current study aimed to investigate the prevalence of EDS and insomnia symptoms, and the sociodemographic and clinical correlates, such as severity of depressive symptoms, BMI, psychiatric medications use (antidepressants and antipsychotics), etc. in adolescents with MDD.

METHODS

Study design and participants

This was a cross-sectional study conducted in three general and four psychiatric hospitals in five cities (Hefei, Bengbu, Fuyang, Suzhou, and Ma’anshan) in Anhui Province, China from January to August, 2021. Adolescents were invited to participate in this study if they met the following criteria: 1) diagnosed as MDD according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition using a structured clinical interview; 2) aged 12-18 years, Han Chinese; and 3) able to understand the content of questionnaires. Patients with other psychiatric or neurological disorders and/or intellectual disability were excluded.

All participants and their guardians have signed an informed consent form after understanding the purpose and process of the study. This study was approved by the Medical Ethics Committee of Chaohu Hospital of Anhui Medical University (202009-kyxm-04).

Data collection measurements

Sociodemographic and clinical data were collected by a predesigned questionnaire, including sex (males or females), age (years), education (secondary school or senior secondary school), physical diseases (yes or no), BMI, age of onset (years), first-episode (yes or no), number of hospitalizations, duration of illness (months), and the use of psychiatric medications (antidepressants, benzodiazepines, hypnotics, and antipsychotics). Doses of antipsychotics, antidepressants, benzodiazepines, and hypnotics were converted using chlorpromazine [45], fluoxetine [46], and diazepam equivalents [47], respectively. We also asked each patient a standard question: “Have you ever attempted suicide during the last 12 months (coded as yes/no)?” [48]. The investigators then confirmed the information about the patient’s suicide attempts by reviewing patient’s medical records and an interview with the patient’s parents.

EDS symptoms was assessed using the Chinese version of the 8-item Epworth sleepiness scale (ESS) (Cronbach’s α=0.814) [49,50], and the Cronbach’s α value for this sample in this study was 0.745. The eight items are evaluated on a 4-point scale, ranging from “0=would never drowse” to “3=high chance of drowsing,” with higher total score indicating more severe EDS symptoms. Participants with a total ESS score of ≥11 points were considered as “having EDS symptoms.” [20] In addition, insomnia symptoms were assessed using the 7-item Insomnia Severity Index (ISI) (Cronbach’s α=0.804) [51,52], and the Cronbach’s α value of this study was 0.844. Each items is evaluated on a 5-point scale, ranging from “0= none” to “4=very severe.” A higher total score of ISI indicated more severe insomnia symptoms (normal: 0-7; subthreshold insomnia: 8-14; moderate clinical insomnia: 15-21; and severe clinical insomnia: 22-28). In this study, participants with a total ISI score of ≥15 were considered as “having insomnia symptoms.” Finally, clinical severity of depressive symptoms in adolescents with MDD was assessed using Clinical Global Impression-Severity (CGI-S) [53,54].

Statistical analysis

Mean±standard deviation and frequency distributions (%) were calculated for the descriptions of continuous and categorical variables, respectively. Sociodemographic and clinical characteristics were compared between the insomnia symptoms and non-insomnia symptoms groups, and the EDS symptoms and non-EDS symptoms groups using independent samples t-test, Mann-Whitney U test, and chi-square test as appropriate. Binary logistic regression models were used to examine the risk factors associated with EDS and insomnia, with EDS or insomnia as the dependent variables, and the variables which were significant in univariate analysis (p<0.05) as independent variables. All statistical analyses were performed using IBM SPSS version 23.0 (IBM Corp., Armonk, NY, USA). A p-values of less than 0.05 (two-tailed) were considered significant.

RESULTS

Participant characteristics

A total of 310 adolescents with MDD were invited to participate in this study, and 297 (response rate=95.8%) completed the assessments and were included in the statistical analyses. The mean age of the sample was 15.26±1.71 years, more than two-thirds (73.4%) were female, and comorbid physical diseases were present in 14 patients (including hip dislocation, congenital heart disease, gastritis, meniscal injury, gastritis, etc.). The proportion of adolescents taking antidepressants, benzodiazepines, hypnotics, and antipsychotics was 67.3%, 6.1%, 4.4%, and 15.2%, respectively. More than half (51.5%) of adolescents reported suicide attempts during the past 12 months (Table 1).

EDS and insomnia symptoms

The prevalence of EDS and insomnia symptoms in the adolescents with MDD was 39.7% (95% confidence interval [CI]=34.1%-45.3%) and 38.0% (95% CI=32.5%-43.6%), respectively. The adolescents with EDS symptoms had higher BMI and antidepressant doses, more severe depressive symptoms and lower rate of first-episode, and reported more frequent use of SSRIs than those without EDS symptoms (all p<0.05) (Table 1). In addition, the adolescents with insomnia symptoms had a higher proportion of females, a higher risk of suicide attempts, a lower doses of antipsychotics, and more severe depressive symptoms, and reported less frequent use of antipsychotics than those without insomnia symptoms (all p<0.05) (Table 1).

Factors associated with EDS and insomnia symptoms

Binary logistic regression analyses revealed that EDS symptoms were significantly associated with higher BMI (odds ratio [OR]=1.097, 95% CI=1.027-1.172, p=0.008), severity of depressive symptoms (OR=1.313, 95% CI=1.028-1.679, p=0.029), and SSRIs use (OR=2.078, 95% CI=1.199-3.601, p=0.009) (Table 2). The analyses also showed that insomnia symptoms were positively associated with female sex (OR=1.955, 95% CI=1.052-3.633, p=0.034), suicide attempts (OR=1.765, 95% CI=1.037-3.005, p=0.036), severity of depressive symptoms (OR=2.031, 95% CI=1.523-2.709, p<0.001), and negatively associated with antipsychotics use (OR=0.433, 95% CI=0.196-0.952, p=0.037) (Table 3). However, neither EDS nor insomnia has been found to be associated with psychiatric medications dose.

DISCUSSION

To the best of our knowledge, this is the first study to investigate the prevalence and clinical correlates of both EDS and insomnia symptoms in Chinese adolescents with MDD. We found that the prevalence of EDS and insomnia symptoms among adolescents with MDD was 39.7% and 38.0%, respectively, which were higher than in Chinese adolescents in the general population. Two recent large-scale surveys found a 29.2% prevalence of EDS symptoms among adolescents in Beijing and a 9.5% prevalence of insomnia symptoms among children and adolescents in Hong Kong. Consistent with the results of our study, two studies conducted in Canada [55] and Finland [56] found much higher rates of EDS (39.0%) and insomnia symptoms (51%) among adolescents with MDD. The underlying pathophysiological mechanisms between sleep disturbances and MDD are complex. Many factors, including genetic overlap, dysregulation of monoamine neurotransmitters, overactive hypothalamic-pituitary-adrenocortical system, inflammatory responses (e.g., elevated IL-6 and TNF levels), and circadian rhythm disturbances, may underlie the pathology of the bidirectional effects between sleep disturbances and depression [4,57].

Moreover, we found that the greater severity of depression, the greater the probability of EDS and insomnia symptoms the adolescents were likely to suffer. This positive correlation between depression severity and EDS/insomnia symptoms have been also found in adults with MDD [31]. Meanwhile, patients with MDD co-occurring insomnia and/or hypersomnia symptom have more lifetime episodes of the depression, longer duration of current episode, and suffer from more depressive symptoms [58]. Therefore, sleep disturbances should be monitored and managed in adolescents with MDD, especially in those individuals with more severe depressive symptoms.

In this study, adolescent patients with higher BMI were more likely to have EDS symptoms. Hein et al. [9] also found a positive association between EDS symptoms and BMI among adults with MDD. The mechanism of the effect of high BMI on EDS could be tentatively explained by the following causes. First, obesity is strongly associated with obesity hypoventilation syndrome and obstructive sleep apnea (OSA), both of which predispose people to shorter deep sleep duration at night, increased waking, hypoventilation, decreased overall sleep quality, and daytime sleepiness [59,60]. Second, inflammatory cytokines may be a bridge between BMI and EDS. Specifically, higher BMI is often associated with elevated levels of inflammatory factors (e.g., TNF-α and IL-6) that contribute to the development of EDS [61]. Another study revealed that the use of the TNF-α antagonist etanercept resulted in a significant reduction in EDS symptoms in obese patients with OSA, suggesting a contribution of inflammatory cytokines to the pathogenesis of EDS symptoms [62]. Considering the coexistence of obesity and EDS leads to emotional instability and inadequate response to antidepressants [63], for those obese adolescents with MDD, increasing physical activity is advocated to lower their BMI levels and thus reduce the symptoms of EDS [64].

In addition, our study found that female adolescents were twice as likely as males to have insomnia symptoms, repeating previous findings in children (females vs. males, 1.47-fold risk) and adults (females vs. males, 1.39-fold risk) with MDD [65,66]. The link between insomnia and sex may involve sex differences in brain structure and the increased sensitivity of women to sex steroid hormone fluctuations and locus coeruleus-norepinephrine arousal circuit [67]. However, we did not find such sex differences in the prevalence of EDS. These findings suggest that we should pay more attention to insomnia-related problems in female adolescents with MDD than males.

Furthermore, we found that adolescents with a history of suicide attempts were more likely to have insomnia symptoms than those without suicide attempts. Similarly, in a previous study with a clinical sample of patients with bipolar disorder, individuals with a history of suicide attempts reported a higher prevalence of insomnia symptoms and poorer sleep quality, leading to a greater risk of future suicide attempts [68]. On the other hand, many studies have revealed that frequent insomnia is a predictor of suicidality [32,69]. These evidences suggest that the correlation between insomnia and suicide attempts may not be a one-way effect, but rather a complex interaction.

More importantly, we found that SSRIs use was associated with a higher risk of EDS in adolescents with MDD. This could be explained by the effect of SSRIs on sleep architecture. For example, SSRIs can inhibit rapid eye movement (REM) sleep, increase REM latency, duration of light sleep, and wake-up time, and worsen sleep quality in patients [70,71]. Thus, SSRIs may cause fatigue and easy sleepiness during the day, which may lead to an increased risk of EDS. On the contrary, as a nonSSRI, mirtazapine has been shown to be a sedative antidepressant that does not inhibit REM and can reduce EDS by increasing sleep efficiency and improving daytime fatigue [72,73]. In addition, we found that antipsychotics use was associated with a lower risk of insomnia symptoms. The off-label use of antipsychotic medications in patients with MDD is common in China [74]. For example, quetiapine and olanzapine, in addition to treating psychotic symptoms associated with depression, can simultaneously improve insomnia symptoms in patients with depression [75,76]. A randomized controlled trial found that olanzapine can reduce sleep latency and increase total sleep duration and sleep efficiency in patients with depression [77]. Similarly, a recent study found that quetiapine had a protective effect on nighttime sleep [38]. However, this current study did not find an association between the use of benzodiazepines, hypnotics and the dosage of psychotropic medications with the risk of insomnia or EDS, which may be related to insufficient sample size, age of subjects, and different population.

Account for the results should be with caution due to the following limitations. First, this was a cross-sectional survey, hence the direction of causality between EDS or insomnia symptoms and clinical variables could not be examined. Second, all participants were recruited from seven hospitals in one province, and the results may not be generalizable to all Chinese adolescents with MDD. Third, regarding the assessment of depression status, the CGI-S scale was used in this study, which may not be as accurate as the Hamilton Depression Scale. Fourth, EDS and insomnia are assessed by self-reported scales (ESS and ISI) and are missing other information about sleep, such as time to fall asleep, sleep efficiency, sleep duration (e.g., Pittsburgh Sleep Quality Index), and objective measures (e.g., polysomnography or actigraphy recordings). Finally, the absence of investigation of other comorbid sleep disorders potentially affecting EDS (e.g., narcolepsy, circadian rhythm sleep-wake disorder, etc.).

In summary, EDS and insomnia symptoms are common in adolescents with MDD, especially in those with more severe depressive symptoms. EDS symptoms were associated higher BMI, and insomnia symptoms were associated with female sex and the history of suicide attempts. The effects of psychiatric medications on sleep architecture need to be treated with caution; antipsychotics may improve insomnia, while SSRIs may contribute to the development of EDS. Considering the negative effects of EDS and insomnia symptoms on the clinical prognosis, regular screening and clinical managements should be developed for this key patient population.

Notes

Availability of Data and Material

The data used for this study are available from the corresponding author on reasonable request.

Conflicts of Interest

The authors have no potential conflicts of interest to disclose.

Author Contributions

Conceptualization: all authors. Data curation: Yudong Shi, Lei Xia. Formal analysis: Yudong Shi, Wei Li, Changhao Chen. Investigation: Yudong Shi, Wei Li, Changhao Chen, Xiaoping Yuan, Yingying Yang, Song Wang, Zhiwei Liu, Feng Geng, Jiawei Wang, Xiangfen Luo, Xiangwang Wen. Methodology: Yudong Shi, Lei Xia, Huanzhong Liu. Project administration: Lei Xia, Huanzhong Liu. Supervision: Lei Xia, Huanzhong Liu. Validation: Lei Xia, Huanzhong Liu. Visualization: Yudong Shi, Lei Xia, Huanzhong Liu. Writing—original draft: Yudong Shi, Lei Xia. Writing—review & editing: Yudong Shi, Lei Xia, Huanzhong Liu.

Funding Statement

This study was supported by the National Clinical Key Specialty Project Foundation (CN); and the Scientific Research Project of Anhui Higher Education Institutions (Grant No. 2022AH050671); and Anhui Medical University Clinical Science Foundation; and Research Fund of Anhui Institute of translational medicine (2022zhyx-B01).

Table 1.

Socialdemographic and clinical characteristics of adolescents participate in this study

Variable		Total (N=297)	EDS (N=118)	Non-EDS (N=179)	χ²/T/Z	p	IS (N=113)	Non-IS (N=184)	χ²/T/Z	p
Female		218 (73.4)	91 (77.1)	127 (70.9)	0.410	0.522	93 (82.3)	125 (67.9)	7.400	0.007^*
Senior secondary school		156 (52.5)	68 (57.6)	88 (49.2)	2.044	0.153	64 (56.6)	92 (50.0)	1.237	0.266
First-episode		170 (57.2)	59 (50.0)	111 (62.0)	4.192	0.041^*	65 (57.5)	105 (57.1)	0.006	0.938
Physical diseases		14 (4.7)	7 (5.9)	7 (3.9)	0.647	0.421	5 (4.4)	9 (4.9)	0.034	0.854
Antidepressants					10.788	0.005^*			0.407	0.816
	None	97 (32.7)	30 (25.4)	67 (37.4)			39 (34.5)	58 (31.5)
	SSRIs	162 (54.5)	78 (66.1)	84 (46.9)			59 (52.2)	103 (56.0)
	Others	38 (12.8)	10 (8.5)	28 (15.6)			15 (13.3)	23 (12.5)
Benzodiazepines		18 (6.1)	8 (6.8)	10 (5.6)	0.178	0.673	9 (8.0)	9 (4.9)	1.161	0.281
Hypnotics		13 (4.4)	6 (5.1)	7 (3.9)	0.234	0.628	4 (3.5)	9 (4.9)	0.068	0.794
Antipsychotics		45 (15.2)	18 (15.3)	27 (15.1)	0.002	0.968	10 (8.8)	35 (19.0)	5.635	0.018^*
Suicide attempts		153 (51.5)	60 (50.8)	93 (52.0)	0.035	0.852	74 (65.5)	79 (42.9)	14.255	<0.001^*
Age (yr)		15.26±1.71	15.44±1.62	15.14±1.77	-1.630	0.104	15.30±1.82	15.24±1.64	-0.259	0.796
BMI (kg/m²)		20.85±3.68	21.60±4.47	20.36±2.96	-2.006^†	0.045^*	21.29±4.29	20.58±3.22	-0.815^†	0.415
Age of onset (yr)		13.68±1.99	13.78±2.04	13.60±1.96	-0.794^†	0.427	13.70±1.97	13.60±1.99	-0.127^†	0.889
Number of hospitalizations		0.42±0.69	0.48±0.74	0.38±0.65	-1.020^†	0.308	0.38±0.60	0.45±0.74	-0.462^†	0.644
Duration of illness (mo)		20.48±18.28	20.27±18.56	20.62±18.15	-0.297^†	0.767	21.02±18.54	20.33±18.26	-0.545^†	0.586
CGI-S		4.33±1.02	4.54±0.99	4.19±1.02	-2.937^†	0.003^*	4.78±0.86	4.06±1.03	-5.882^†	<0.001^*
Antidepressant dose (mg)^‡		22.11±20.38	25.82±21.90	19.67±18.98	-2.324	0.020^*	22.20±20.63	22.03±20.29	-0.202	0.840
Antipsychotic dose (mg)^§		33.96±112.53	37.37±129.11	31.72±100.43	-0.126	0.900	17.50±65.51	44.08±132.61	-2.358	0.018^*
Benzodiazepine dose (mg)^ǁ		0.82±5.38	0.52±2.40	1.03±6.66	-0.384	0.701	1.24±7.49	0.57±3.52	-1.065	0.287
Hypnotic dose (mg)^ǁ		0.23±1.12	0.30±1.35	0.19±0.94	-0.506	0.613	0.18±0.93	0.26±1.23	-0.552	0.581

Values are presented as mean±standard deviation or number (%).

^* p<0.05;

^† Mann-Whitney U-test;

^‡ chlorpromazine equivalents;

^§ fluoxetine equivalents;

^ǁ diazepam equivalents.

EDS, excessive daytime sleepiness; IS, insomnia; SSRIs, selective serotonin reuptake inhibitors; BMI, body mass index; CGI-S, Clinical Global Impression-Severity

Table 2.

Independent correlates of EDS in adolescents with major depressive disorder

Variable	Unadjusted OR (95% CI)	p	Adjusted OR (95% CI)^†	p
BMI	1.097 (1.027, 1.172)	0.006^*	1.097 (1.027, 1.172)	0.008^*
CGI-S	1.422 (1.119, 1.805)	0.004^*	1.313 (1.028, 1.679)	0.029^*
Antidepressants
None	Ref	-	-	-
SSRIs	2.074 (1.221, 3.521)	0.007^*	2.078 (1.199, 3.601)	0.009^*
Others	0.798 (0.344, 1.849)	0.598	0.886 (0.374, 2.099)	0.784

^* p<0.05;

^† adjusted for first-episode, antipsychotic dose, BMI, CGI-S, and antidepressants.

EDS, excessive daytime sleepiness; OR, odds ratio; CI, confidence interval; BMI, body mass index; CGI-S, Clinical Global Impression-Severity; SSRIs, selective serotonin reuptake inhibitors; Ref, reference group

Table 3.

Independent correlates of insomnia in adolescents with major depressive disorder

Variables	Unadjusted OR (95% CI)	p	Adjusted OR (95% CI)^†	p
Female (ref. male)	2.195 (1.237, 3.896)	0.007^*	1.955 (1.052, 3.633)	0.034^*
Suicide attempts (ref. no)	2.522 (1.552, 4.098)	<0.001^*	1.765 (1.037, 3.005)	0.036^*
CGI-S	2.176 (1.654, 2.863)	<0.001^*	2.031 (1.523, 2.709)	<0.001^*
Antipsychotics (ref. no)	0.413 (0.196, 0.872)	0.020^*	0.433 (0.196, 0.952)	0.037^*

^* p<0.05;

^† adjusted for antipsychotic dose, female, suicide attempts, CGI-S, and antipsychotics.

OR, odds ratio; CI, confidence interval; CGI-S, Clinical Global Impression-Severity; ref, reference group

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