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Table of Contents
ORIGINAL ARTICLE
Year : 2020  |  Volume : 34  |  Issue : 1  |  Page : 42-46

Poor sleep in medicated patients with remitted depressive disorder: A naturalistic study


1 Department of Psychiatry, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Dou-Liou Branch, Yunlin County, Yunlin
2 Department of Psychiatry, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University; Institute of Behavioral Medicine, College of Medicine, National Cheng Kung University; Department of Psychiatry, National Cheng Kung University Hospital, Dou-Liou Branch, Yunlin County, Yunlin
3 Department of Psychiatry, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University; Institute of Behavioral Medicine, College of Medicine, National Cheng Kung University, Yunlin County; Department of Psychiatry, Tainan Hospital, Ministry of Health and Welfare, Tainan City, Taiwan

Date of Submission12-Dec-2019
Date of Decision04-Feb-2020
Date of Acceptance05-Feb-2020
Date of Web Publication20-Mar-2020

Correspondence Address:
I Hui Lee
No. 138, Sheng Li Road, North District, Tainan 704
Yunlin
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/TPSY.TPSY_10_20

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  Abstract 


Objectives: Depression with partial remission and residual symptoms following treatments is common. Elucidating the problems remaining in the remitted patients would help optimize treatment. In this study, we intended to study remission rate and related factors as well as their unresolved problems in patients with treated depressive disorder. Methods: We included 65 medicated patients with depression for 6–12 months. We also chose 65 healthy persons as a control group. The study participants completed Beck Depression Inventory (BDI), checklists of side effects, Sheehan Disability Scale, World Health Organization Quality-of-Life-brief version, and Pittsburgh Sleep Quality Index (PSQI). Remission was defined as a BDI score of ≤ 15. Results: We found that the PSQI score was still higher in the remission group than the control group. Conclusion: Sleep problems, which may still be a commonly unresolved problem in medicated patients with depression, should be noticed by clinicians.

Keywords: depression, remission, residual symptoms, sleep


How to cite this article:
Lu TH, Chen PS, Chen KC, Lee I H, Yang YK. Poor sleep in medicated patients with remitted depressive disorder: A naturalistic study. Taiwan J Psychiatry 2020;34:42-6

How to cite this URL:
Lu TH, Chen PS, Chen KC, Lee I H, Yang YK. Poor sleep in medicated patients with remitted depressive disorder: A naturalistic study. Taiwan J Psychiatry [serial online] 2020 [cited 2020 May 25];34:42-6. Available from: http://www.e-tjp.org/text.asp?2020/34/1/42/281094




  Introduction Top


A systematic review of patients with antidepressant treatment duration of 8–12 weeks has shown a remission rate of < 50%[1]. Depressive patients with partial remission and residual symptoms following antidepressant treatment are common and have high rates of relapse[2],[3]. In major depressive disorder, standard treatment duration of > 6 months is recommended by most United States and European guidelines [4-6]. But most depressive patients using antidepressants are unable to maintain treatment for this duration due to side effects, unresolved symptoms, residual symptoms, and comorbidity, leading to poor treatment efficacy[7],[8].

Most studies showed that the residual symptoms after antidepressant treatment in remitted depressive patients are insomnia, anxiety, low mood, somatic discomfort, decreased concentration, and indecisiveness [2, 3, 9]. But the patients in those studies did not match the standard treatment duration, so it might be argued that the residual symptoms or poor treatment efficacy has been related to an insufficient treatment duration[10],[11]. Additionally, most of those studies were standard clinical drug trials that did not take place in real clinical settings, particularly in Asian countries.

In Taiwan, antidepressants were prescribed for several kinds of depressive disorders, including mixed anxiety–depressive disorder, dysthymic disorder, or depressive disorder not otherwise specified[12], however, only a few portion of depressive patients received full treatment duration of antidepressants[13]. Therefore, the sample could have selection bias, making it difficult to generalize the results. In the study, we intended (a) to probe the rate of remission and its related factors in individuals with depressive disorder, who had received more than six' months of antidepressant treatment in a naturalistic setting, and (b) to explore the unsolved problem among remitted patients.


  Methods Top


Study participants

In this study, we included 65 patients who were diagnosed with depressive disorders, including major depressive disorder, mixed anxiety–depression disorder, and depressive disorder not otherwise specified, but excluded patients with bipolar disorder. Patients were aged between 18 and 65 years and had received antidepressants in general medical or psychiatric outpatient clinics for 6–12 months, to achieve the sufficient treatment duration by the treatment guideline. Also, the dosage of their antidepressants had not been changed for at least two months, to exclude patients who had poor drug adherence. The depression diagnosis was assessed using the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, and the ICD-9 code recorded in the patients' medical records. Data on randomly selected healthy controls (n = 65), matching age and sex, were collected from previous studies that used the same assessment measures [14-17].

The research protocol was approved by the institutional review board at National Cheng Kung University Hospital (protocol number = BR-100-014, date of approval = April 11, 2011). All patients were informed about the study, and all provided signed informed consent.

Medications

The 65 participants had all used antidepressants for > 6 months but < 1 year. The pharmacological types of antidepressants were selective serotonin reuptake inhibitor (SSRI), serotonin-norepinephrine reuptake inhibitor (SNRI), noradrenergic and specific serotonergic antidepressant (NaSSA), norepinephrine and dopamine reuptake inhibitor, as well as serotonin antagonist and reuptake inhibitor. Data on concomitant psychiatric medication, such as mood stabilizers, hypnotics, and antipsychotics, were also collected.

Assessments

Patients who were willing to give informed consent were screened to determine whether they were eligible to enter the study.

  • We collected study participants' demographic data, history of systemic illness and mental illness, history of antidepressant treatment, concomitant drugs, and clinical diagnosis, including past psychiatric history, comorbid psychiatric history, and family history
  • The clinical presentations were divided into four domains using different kinds of questionnaire: (a) Beck Depression Inventory (BDI). BDI data were not taken for the control group because the items of this questionnaire are generally used to rate the levels of depression, not for screening[18]; (b) Checklists of side effects; (c) Sheehan Disability Scale (SDS)[19]; (d) World Health Organization Quality-of-Life-brief version (WHOQOL-BREF)[20]; and (e) Pittsburgh Sleep Quality Index (PSQI)[21].


Definition of residual symptoms and remission

The BDI assessment was carried out through self-reported questionnaire. In general, depression remission is defined as a Hamilton Depression Rating Scale (HAMD) score of ≤ 7[22]. We defined remission as BDI ≤ 15, which was equal to HAMD ≤ 7 (according to the result of linear regression of this cohort when HAMD is the independent variable and BDI is the dependent variable: constant = 3.05, beta = 0.26, p = 0.01. Only 41 (63.1%) patients had completed HAMD). We divided the participants into remission and nonremission groups.

Statistical analysis

We calculated frequencies, means, and standard deviations to provide a descriptive analysis of the demographic and clinical characteristics of patients. The Chi-square test and analysis of variance were adapted to compare differences between remission, nonremission, and control groups. Least significant difference was carried as post hoc tests.

The data were analyzed using Statistical Package for Social Science software version 17.0 (SPSS Inc., Chicago, Illinois, USA). The differences between groups were considered significant if p < 0.05.


  Results Top


We included 65 medicated patients with depression in the study. Of them, 50 (76.9%) were defined as remission patients (BDI ≤ 15). We also enrolled 65 healthy controls. No significant differences existed in age, gender, educational years, episodes, first episode onset age, physical comorbidity, psychiatric comorbidity, psychiatric history, or family psychiatric history between the groups [Table 1]. Most of the medicated patients with depression (55.4%) had no severe physical illness, and the majority had a history of psychiatric conditions (73.8%), including depressive disorder (60.0%). A family history of psychiatric conditions was reported by about 49.2% of the patients, including depressive disorder (30.8%) [Table 1].
Table 1: Demographic and clinical characteristics of participants

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No significant differences in antidepressants use and number of drug side effects were found between remitted patients and nonremitted patients [Table 2]. Most patients were treated with SSRIs (64.6%), with a smaller number treated with SNRIs (27.7%). But remitted patients used less mood stabilizer and more benzodiazepines (BZDs) than nonremitted patients. As shown in [Table 2], 72.3% of the patients which included day-time anxiolytics use were also prescribed with BZDs.
Table 2: Medications and side effects in patients with depression

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[Table 3] lists the comparisons of BDI, SDS, WHOQOL-BREF, and PSQI of nonremitted antidepressants users, remitted antidepressants users, and healthy controls. The remission group showed no significant difference with control group in the subscale of social life in SDS and WHOQOL-BREF. The nonremission group showed lower scores than the remission group in all questionnaires except PSQI. Both the nonremission and remission groups had worse scores than the healthy control group in the PSQI. Sleep problems were the prominent unresolved residual symptom in the remitted depression group (as shown in post hoc for PSQI: nonremission group = remission group > control group).
Table 3: Differences in symptoms, functionality, quality of life, and sleep quality between groups

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  Discussion Top


In our study [Table 1] and [Table 2], the remission rate was 77%, which is higher than that in other studies on antidepressant use[1],[23]. The result of our study might be related to our definition of remission in the dimension of mood, BDI ≤ 15. This cutoff point was higher than that in other studies[22], although some participants used HAMD ≤ 7[22], as calculated using regression analysis. The self-reported BDI questionnaires and clinician-administered HAMD can be correlated, which has been supported by others[22]. High remission rate in patients who received medication for > 6 months also supports longer treatment duration needed for depressive disorders, although selection bias existed in this naturalistic study design.

Antidepressants are prescribed for several kinds of depressive disorders, not only for major depressive disorder in clinical practice[12], where structured diagnostic interviews are difficult to be applied. Unlike standardized clinical trials, our study sample with heterogeneity could offer clinical implications.

Most importantly, sleep problems [Table 3] were reconfirmed to be prominent residual symptoms in the remission group[24]. That sleep problems had not been completely resolved with antidepressant use is likely, even after the full duration of the prescription, with 1-year prevalence of insomnia about 19.3% [3, 25, 26]. In other studies, insomnia and short sleep duration have been reported to be strongly associated with residual symptoms in nonremitted and remitted depression[27],[28]. Sleep problems have been proposed to be a precursor to the onset of depression, a residual symptom of depression, or a side effect of antidepressants[29]. Moreover, it was even speculated that complete remission of depressive disorder depends on the relief of sleep disturbances[24]. Even the prescription rate of NaSSA, a kind of sedative antidepressants, was higher in remission group; the sleep problems showed no significant difference between remission and nonremission groups. This result reminded us that sedative antidepressants might have limited effect on sleep problems in depressive patients. Also, to relieve sleep problems, high prescription rate (80%) of BZDs in the remission group is reasonable in this study. In the realistic condition, it is difficult to stop BZDs even in patients with much improved depressive symptoms. It might be related to residual sleep disturbance in the remission group, as shown in this study. The anticipatory anxiety or even dependence on BZDs might also be the reason. Further evaluation about the continuation of BZD use and integration of pharmacological and nonpharmacological intervention for sleep problems in depressive patient is a major challenge for the clinicians[30].

As sleep is an endogenous presentation in depression, sleep problems in remitted depression are a critical issue. In addition, sleep problems were found to be major residual symptoms no matter in remitted or non-remitted depression, even after a six-month antidepressant treatment. The pathology of sleep problems in depression may not be related to the monoamine deficiency hypothesis only. Circadian rhythm disturbance, the hyperactivity of hypothalamic–pituitary–adrenal axis, and epigenome will also be the possible mechanisms[31]. Therefore, alternative medical treatment[32]. or nonpharmacological intervention should be considered[33].

Study limitations

  • No structural interview was done for diagnosis by psychiatrists to reconfirm the diagnosis in this study. The study sample had heterogeneous diagnoses of depressive disorders, therefore, to represent any single diagnosis is difficult. But this condition could be a clinical characteristic of clinical reality in Taiwan.
  • The sample sizes of patients in remission (n = 50) and those in nonremission (n = 15) were not comparable in this study. Pair-wise comparison between those cases and normal controls suffered from lack of power and skewness. Furthermore, heterogeneous and poorer responders could have terminated their antidepressant treatment more early, resulting in increasing the rate of remission in this study.
  • We did not collect important personal and clinical variables such as personality traits, detailed social supports, stress factors, sexual dysfunction, and nonpharmacological interventions in normal controls in this study. Further integration of the above factors could provide a more detailed understanding of the residual symptoms in patients with remitted depression.
  • Those study participants received different kinds of antidepressants during the treatment duration for at least six months. The medication effects to the residual symptoms were not controlled in this study.


Summary

  • Sleep problem was the predominant unresolved residual problem, even in remitted depressive patients after a six-month use with antidepressant
  • Clinicians should be reminded of residual poor sleep, which could remarkably improve the quality and functioning of life in depressive patients.



  Acknowledgments Top


The authors thank Tsai Hua Chang, Chien Ting Lin, and Shih-Hsien Lin for their advice and all the study participants.

The funding institutions of this study had no further rôle in the study design; the collection, analysis, and interpretation of data; the writing of this paper; or the decision to submit it for publication.


  Financial Support and Sponsorship Top


This work was supported by the National Science Council of Taiwan (NSC 93-2314-B-006-107, NSC 97-2314-B-006-006-MY3, NSC 100-2314-B-006-041-MY3, and NSC 101-2314-B-006-065) as well as the National Cheng Kung University Hospital (NCKUH-9903019 and NCKUH-10305006).


  Conflicts of Interest Top


All authors declare no competing interests in writing this report.



 
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