Abstract
Cognitive behavioral therapy for insomnia (CBT-I) is effective for not only primary insomnia (PI) but also comorbid insomnia (CI; insomnia associated with psychiatric/physical diseases or other types of sleep disorders). This study aimed to compare the outcomes of CBT-I implemented in the same manner between patients with PI and CI. In total, 41 adult patients who had completed CBT-I were enrolled in this retrospective analysis and divided into a PI group and a CI group. The authors then examined and compared the significance of changes after therapy between the two groups. The magnitude of improvement on the Japanese version of the Insomnia Severity Index (ISI-J) was analyzed as the primary endpoint. In the PI group (n = 24), both the ISI-J score and the dose of hypnotics decreased significantly following CBT-I. On the other hand, in the CI group (n = 17), only the dose of hypnotics decreased significantly; no statistically significant improvement was seen in the ISI-J score. Sleep onset latency and sleep quality rating in recorded sleep diaries were significantly correlated with improved ISI-J scores in the CI group only. CBT-I was shown to be effective for CI, but its efficacy for CI was inferior to that for PI in terms of impact on sleep and mental condition. These results suggest that in addition to the basic components of CBT-I, treatment for CI, especially when accompanied by severe insomnia symptoms, should include approaches targeting the comorbid disease.
Keywords: Insomnia, Comorbid insomnia, Primary insomnia, Cognitive behavioral therapy for insomnia, CBT-I
Introduction
Cognitive behavioral therapy for insomnia (CBT-I) is a non-pharmacological therapeutic approach with adequate evidence for the management of insomnia [1, 2]. CBT-I consists of multiple components, including sleep hygiene education, cognitive therapy, relaxation, stimulus control therapy, and sleep restriction therapy [2]. CBT-I is recommended by insomnia treatment guidelines as the first-line treatment for insomnia [3, 4].
In recent years, CBT-I has been shown to be effective for not only primary insomnia (PI) [5], but also insomnia associated with underlying psychiatric/physical disease and sleep disorders other than insomnia (i.e., comorbid insomnia [CI]) [6–9]. Previously reported meta-analyses have also indicated the effectiveness of CBT-I for CI [10, 11].
However, no clear consensus has been reached on whether the effect of CBT-I on CI is equivalent to that on PI. Randomized controlled trials analyzed in previously reported meta-analyses have included varying numbers of treatment sessions [6, 12, 13] and various interview methods in CBT-I [14], and some have also employed treatment approaches directed against comorbid diseases in addition to CBT-I [15–17]. The inconsistent design and form of CBT-I among studies have made a precise analysis of the differences in the efficacy of CBT-I between CI and PI impossible. Identifying this difference could help predict the extent of the effect of basic CBT-I on insomnia. For example, if the effect on CI were inferior to that on PI, then treating CI by using a comorbidity approach, as described in previous studies, would be clinically recommended.
Given this background, with the goal of verifying whether CBT-I exerts an equivalent degree of efficacy against CI and PI, the present study aimed to compare the efficacy of CBT-I implemented using the exact same contents and format between patients with PI and those with CI.
Materials and methods
Study design
The authors collected sleep parameters, psychological test results, and the status of oral hypnotic drug use before and after CBT-I from the medical records of patients with insomnia who had undergone CBT-I at our hospital. The patients were then divided into a CI group (insomnia with some comorbid diseases) and a PI group (insomnia without comorbid disease). The changes in the parameters/variables were analyzed as indicators of the treatment efficacy and then compared between patients with CI and PI.
The following baseline and posttreatment clinical data were collected 2 weeks prior to the start and within 2 weeks after the completion of CBT-I: results of self-reported questionnaires, sleep parameters recorded in a sleep diary, a dose of gamma-aminobutyric acid-A receptor agonists (GABAA-RA) as hypnotic drugs, and types of nightly intakes other than GABAA-RA. Furthermore, data were also collected on the dose of GABAA-RA at 6 months after posttreatment as an indicator of the long-term efficacy of CBT-I. For patients who ended treatment or were referred to other hospitals less than 6 months after posttreatment, data collected during the last visit to the authors’ hospital were used for the analyses.
All treatment data were analyzed by physicians not involved in the treatment of the patients enrolled in the study. The authors set the change in the score on the Japanese version of the Insomnia Severity Index (ISI-J) as the primary outcome of this study and adopted the change in the dose of GABAA-RA as the secondary outcome [18].
Participants
The study participants were outpatients satisfying the following inclusion criteria: (1) completed all sessions of CBT-I between March 2012 and April 2020 at the Department of Psychiatry, Jikei University Katsushika Medical Center; and (2) diagnosed by a psychiatrist as having chronic insomnia disorder based the criteria of the International Classification of Sleep Disorders, Third Edition (ICSD-3) [19]. Patients who met any of the following criteria were excluded from the survey: (1) age less than 20 years; (2) judged to have difficulty in verbal communication due to severe physical or mental illness; and (3) judged to have physical difficulty in regular hospital visits.
All participants had begun taking hypnotics before baseline and expressed a desire to receive CBT-I for the treatment of insomnia. Of the comorbid diseases, the psychiatric disease was diagnosed on the basis of the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition [20], and sleep disorders on the basis of the ICSD-3.
To enable a comparison of the data before and after treatment, patients who discontinued CBT-I before completing all sessions were excluded from the analysis.
Treatment
CBT-I was implemented by two clinical psychologists who had received training for implementing CBT-I from the Japanese Society of Sleep Research (JSSR) and had experience in implementing CBT-I as therapists.
The therapists administered five sessions of CBT-I (bi-weekly session, 50 min/session, each in a face-to-face manner) to each patient. The CBT-I contents complied with the manual prepared by the JSSR [21], including interviews under the following topics: (1) knowledge about treatments for insomnia (sleep hygiene education); (2) relaxation (progressive muscle relaxation); (3, 4) sleep scheduling (sleep restriction therapy and stimulus control therapy); and (5) review and summary of past sessions. The content of each session was set as homework to check the degree of patient practice at the next session. Each patient was instructed to continue to maintain a sleep diary, beginning 2 weeks before the start of CBT-I. Sleep scheduling was continued from the third to the last session. The therapists gave no special guidance in relation to comorbid disease in the patients with CI (e.g., cognitive therapy for anxiety or depression, guidance about the use of continuous positive airway pressure [CPAP] for obstructive sleep apnea, daily life guidance/oral medication guidance for physical diseases). During the CBT-I implementation period, each patient was examined by a physician once every 4 weeks. The physician-in-charge provided the usual treatment and did not mention the contents of the CBT-I instructions. Guidance regarding dose reductions of the hypnotic drugs used was also given by the physician-in-charge in accordance with the relevant guidelines [22], as usually performed during clinical practice.
Measurements
The patients’ characteristics at baseline were as follows: type of insomnia (PI/CI), type of comorbid psychiatric disease/physical disease/sleep disorder, gender, age, education level, marital status, and presence/absence of a job.
The responses to the following questionnaires before and after treatment were also analyzed: the ISI-J [18, 23], the Japanese version of the Zung Self-rating Depression Scale (J-SDS) [24, 25], the 36-item Short-Form Health Survey of the Medical Outcomes Study (SF-36) [26, 27], and the 16-item Japanese version of the Dysfunctional Beliefs and Attitudes about Sleep scale (DBAS-J) [28, 29].
The 7-day mean of the following parameters in the sleep diaries measured during the weeks prior to the start and after the last session of CBT-I served as the baseline and posttreatment data, respectively: (1) total sleep time; (2) sleep efficiency; (3) sleep onset latency time; (4) wake time after sleep onset; and (5) sleep quality rating (rated from 0–10 on a Likert scale).
The GABAA-RA dose level was checked from the patients’ medical records at three-time points: baseline, posttreatment, and 6 months after posttreatment. The data were analyzed quantitatively after conversion to flunitrazepam equivalents (1 mg = 1) [30].
In addition, whether the following drugs other than GABAA-RA were taken before sleep was investigated: (1) antidepressants; (2) antipsychotics; (3) melatonin receptor agonists; and (4) orexin receptor antagonists.
Statistical analysis
The data were analyzed using IBM SPSS Statistics 21.0 (IBM Corp., Armonk, NY, USA). The chi-squared test was used to check for any significant inter-group differences in the number of patients who had discontinued therapy prior to the completion of the planned number of sessions. The Mann–Whitney U test was used for inter-group comparisons of the background variables and the magnitude of improvement of various variables after treatment. The chi-square independence test was used for inter-group comparisons of binomial data. Wilcoxon’s signed-rank test was used to assess the significance of improvement of parameters within each group. Effect sizes (ES) were calculated by Hedges’ g estimation, as were their 95% confidence intervals (CIs). Hedges’ g is similar to Cohen’s d (with a pooled standard deviation [SD]) and positively biased estimators of an ES when sample sizes are small [31]. The effect of the treatment in reducing the dose of GABAA-RA was evaluated by a two-way repeated-measures analysis of variance using the data recorded at baseline, posttreatment, and 6 months after posttreatment in each group.
To explore the factors at baseline that could affect the differences in the efficacy of CBT-I, additional analyses were conducted to determine the correlation between the magnitude of improvement in ISI-J scores and other variables at baseline in each group. Spearman’s rank correlation coefficient with the magnitude of improvement in ISI-J scores was also calculated.
Results
Of the 50 patients enrolled in this study, 41 in whom the planned treatment was completed were included in the analysis; of these patients, 17 (41%) were classified into the CI group and 24 (59%) into the PI group (Fig. 1). Comorbid diseases in the CI group included psychiatric (major depressive disorder, social anxiety disorder, obsessive–compulsive disorder and somatic symptom disorder) and physical (chronic pain) diseases and sleep disorders other than insomnia (obstructive sleep apnea and restless legs syndrome). the percentage of patients who discontinued treatment prior to completion of the treatment sessions did not differ significantly between the CI group (3 patients, 15%) and PI group (6 patients, 20%) (p = 0.72). Treatment for comorbidities had begun before CBT-I and maintenance therapy (pharmacological therapy or CPAP therapy) was being provided. These treatments were continued without modification throughout the CBT-I implementation period.
Fig. 1.
Flowchart of patient selection for this study. CBT-I cognitive behavioral therapy for insomnia
Characteristics of the participants at baseline
No significant differences in any of the background variables were found between the CI and PI groups at baseline (Table 1). The severity of insomnia at baseline did not differ significantly between the two groups, with mean ISI-J scores (± SD) of 15.8 ± 4.8 in the CI group and 16.0 ± 3.6 in the PI group (p = 0.789).
Table 1.
Demographic and clinical characteristics of each group at baseline
| CI | PI | p | |||
|---|---|---|---|---|---|
| n = 17 | n = 24 | ||||
| Age, years (M; SD) | 65.4 | 11.5 | 61.5 | 17.5 | 0.771 |
| Female (n; %) | 7 | 41.2 | 12 | 50.0 | 0.577 |
| Education, years (M; SD) | 14 | 2.6 | 13.7 | 2.3 | 0.616 |
| Married (n; %) | 11 | 64.7 | 14 | 58.3 | 0.945 |
| Employed (n; %) | 10 | 58.8 | 9 | 37.5 | 0.267 |
| Nightly intake | |||||
| Dose of GABAA-RA, mg-flunitrazepam equivalent (M; SD) | 1.3 | 0.8 | 1.3 | 0.8 | 0.259 |
| Use of drugs other than GABAA-RA (n; %) | 6 | 35.3 | 7 | 29.2 | 0.678 |
| ISI-J score | 15.8 | 4.8 | 16.0 | 3.6 | 0.798 |
The types of drugs other than GABAA-RA taken in the CI group were antidepressants (trazodone, n = 3; paroxetine, n = 1), antipsychotics (risperidone, n = 1), and orexin receptor antagonists (suvorexant, n = 1); those in the PI group were antidepressants (trazodone, n = 3; mirtazapine n = 2), antipsychotics (quetiapine, n = 2), and orexin receptor antagonists (suvorexant n = 3)
CI comorbid insomnia; PI primary insomnia; M mean; SD standard deviation; GABAA-RA gamma aminobutyric acid-A receptor agonists; ISI-J Japanese version of the Insomnia Severity Index
Changes in clinical variables from baseline to posttreatment and comparison of the changes between the CI and PI groups
Only the PI group showed a significant improvement in ISI-J scores after CBT-I (Table 2). The PI group also showed improvements in many other clinical variables, whereas only sleep efficiency as recorded in the sleep diaries showed significant improvement in the CI group.
Table 2.
Changes in scores after CBT-I compared with the values at baseline in each group and a comparison of the changes
| Baseline | Posttreatment | Changes between baseline and posttreatment within each group | Comparison of changes between CI and PI | |||||
|---|---|---|---|---|---|---|---|---|
| M | SD | M | SD | p | ES (95% CI) | p | ES (95% CI) | |
| ISI-J score | 0.006 | 0.935 (0.262, 1.608) | ||||||
| CI | 15.8 | 4.8 | 13.5 | 6.8 | 0.118 | − 0.390 (− 1.069, 0.288) | ||
| PI | 16.0 | 3.6 | 8.1 | 3.9 | < 0.001 | − 2.045 (− 2.791, − 1.298) | ||
| Sleep diary | ||||||||
| TST (min) | 0.511 | − 0.214 (− 0.859, 0.432) | ||||||
| CI | 339.7 | 75.9 | 359.9 | 60.1 | 0.156 | 0.288 (− 0.409, 0.984) | ||
| PI | 352.1 | 76.1 | 386.9 | 58.1 | 0.041 | 0.505 (− 0.095, 1.106) | ||
| SE (%) | 0.486 | − 0.227 (− 0.873, 0.419) | ||||||
| CI | 74.0 | 13.3 | 83.1 | 9.1 | 0.022 | 0.782 (0.063, 1.501) | ||
| PI | 75.4 | 9.8 | 87.4 | 7.3 | < 0.001 | 1.361 (0.706, 2.017) | ||
| SOL (min) | 0.383 | − 0.378 (− 1.028, 0.271) | ||||||
| CI | 40.1 | 33.3 | 23.3 | 13.7 | 0.069 | − 0.634 (− 1.334, 0.066) | ||
| PI | 29.7 | 20.0 | 26.1 | 23.3 | 0.728 | − 0.164 (− 0.749, 0.422) | ||
| WASO (min) | 0.329 | 0.012 (− 0.632, 0.656) | ||||||
| CI | 41.8 | 44.1 | 24.0 | 29.3 | 0.307 | − 0.461 (− 1.153, 0.230) | ||
| PI | 30.8 | 25.3 | 12.8 | 18.9 | 0.002 | − 0.790 (− 1.397, − 0.183) | ||
| Sleep quality rating | 0.039 | − 0.689 (− 1.351, − 0.027) | ||||||
| CI | 6.0 | 1.8 | 6.0 | 2.3 | 0.989 | − 0.005 (− 0.698, 0.688) | ||
| PI | 5.6 | 1.6 | 6.8 | 1.9 | 0.003 | 0.675 (0.068, 1.283) | ||
| SF-36 subscale score | ||||||||
| PF | 0.843 | − 0.068 (− 0.701, 0.565) | ||||||
| CI | 78.5 | 20.8 | 80.3 | 21.2 | 0.710 | 0.082 (− 0.591, 0.754) | ||
| PI | 87.5 | 12.4 | 90.0 | 9.8 | 0.154 | 0.220 (− 0.366, 0.807) | ||
| RP | 0.721 | − 0.114 (− 0.747, 0.519) | ||||||
| CI | 66.2 | 26.5 | 74.6 | 25.0 | 0.220 | 0.320 (− 0.357, 0.996) | ||
| PI | 76.7 | 20.8 | 85.6 | 19.6 | 0.043 | 0.432 (− 0.160, 1.023) | ||
| BP | 0.748 | − 0.102 (− 0.736, 0.531) | ||||||
| CI | 54.9 | 26.7 | 58.0 | 26.3 | 0.624 | 0.113 (− 0.560, 0.786) | ||
| PI | 71.8 | 24.3 | 76.8 | 22.4 | 0.338 | 0.211 (− 0.375, 0.797) | ||
| GH | 0.075 | − 0.589 (− 1.247, 0.068) | ||||||
| CI | 39.8 | 17.7 | 44.4 | 20.0 | 0.196 | 0.242 (− 0.453, 0.938) | ||
| PI | 49.0 | 16.7 | 62.9 | 16.4 | 0.001 | 0.826 (0.210, 1.442) | ||
| VT | 0.063 | − 0.703 (− 1.355, − 0.051) | ||||||
| CI | 50.1 | 25.4 | 47.1 | 24.2 | 0.496 | − 0.120 (− 0.793, 0.552) | ||
| PI | 47.9 | 17.5 | 57.7 | 17.5 | 0.017 | 0.547 (− 0.055, 1.148) | ||
| SF | 0.059 | − 0.705 (− 1.364, − 0.046) | ||||||
| CI | 78.7 | 22.4 | 72.8 | 29.7 | 0.439 | − 0.218 (− 0.893, 0.456) | ||
| PI | 69.3 | 17.1 | 80.5 | 20.6 | 0.029 | 0.576 (− 0.021, 1.172) | ||
| RE | 0.077 | − 0.576 (− 1.222, 0.069) | ||||||
| CI | 71.6 | 27.5 | 70.1 | 28.3 | 0.850 | − 0.051 (− 0.724, 0.621) | ||
| PI | 73.9 | 24.3 | 85.9 | 20.0 | 0.013 | 0.531 (− 0.063, 1.126) | ||
| MH | 0.038 | − 0.750 (− 1.404, − 0.096) | ||||||
| CI | 57.9 | 15.3 | 51.5 | 22.8 | 0.223 | − 0.325 (− 1.002, 0.352) | ||
| PI | 57.5 | 13.2 | 64.1 | 15.9 | 0.049 | 0.445 − 0.147, 1.036) | ||
| J-SDS score | 0.005 | 1.029 (0.295, 1.762) | ||||||
| CI | 42.6 | 8.2 | 45.5 | 9.0 | 0.109 | 0.329 (− 0.416, 1.075) | ||
| PI | 43.3 | 8.0 | 39.2 | 8.0 | 0.016 | − 0.609 (− 1.259, 0.042) | ||
| DBAS-J score | 0.008 | 0.889 (0.067, 1.711) | ||||||
| CI | 81.9 | 29.3 | 81.0 | 30.7 | 0.905 | − 0.030 (− 0.798, 0.739) | ||
| PI | 92.2 | 22.3 | 64.3 | 26.9 | 0.010 | − 1.092 (− 1.950, − 0.235) | ||
| Dose of drugs other than GABAA-RA | ||||||||
| Antidepressants, mg-imipramine equivalent | 0.174 | 0.431 (− 0.189, 1.045) | ||||||
| CI | 5.1 | 13.3 | 5.9 | 13.3 | 0.332 | − 0.237 (− 0.722, 0.244) | ||
| PI | 6.0 | 16.8 | 3.9 | 10.7 | 0.213 | 0.257 (− 0.146, 0.655) | ||
| Antipsychotics, mg-chlorpromazine equivalent | 1.000 | 0.000 (− 0.609, 0.609) | ||||||
| CI | 5.9 | 24.3 | 5.9 | 24.3 | 1.000 | 0.000 (− 0.464, 0.464) | ||
| PI | 3.2 | 10.7 | 3.2 | 10.7 | N/A | N/A | ||
| Orexin receptor antagonist (suvorexant, mg) | 0.407 | 0.261 (− 0.353, 0.871) | ||||||
| CI | 0.9 | 3.6 | 0.9 | 3.6 | N/A | N/A | ||
| PI | 2.5 | 6.8 | 1.7 | 5.6 | 0.328 | 0.201 (− 0.199, 0.596) | ||
CBT-I cognitive behavioral therapy for insomnia; CI comorbid insomnia; PI primary insomnia; M mean; SD standard deviation; ES effect size (Hedges’ g); 95% CI 95% confidence interval; ISI-J Japanese version of the Insomnia Severity Index; TST total sleep time; SE sleep efficiency; SOL sleep onset latency; WASO wake after sleep onset; SF-36 36-item Short Form Health Survey of the Medical Outcomes Study; PF physical functioning; RP role-physical; BP bodily pain; GH general health perception; VT vitality; SF social functioning; RE role-emotional; MH mental health; J-SDS Japanese version of the Zung Self-rating Depression Scale; DBAS-J 16-item Japanese version of Dysfunctional Beliefs and Attitudes about Sleep scale; N/A not applicable
When the magnitude of change in each variable after treatment was compared between the two groups, a significantly greater change in the direction of improvement in ISI-J scores was noted in the PI group compared with the CI group (p = 0.006, ES: 0.935, 95% CI [0.262, 1.608]). The changes in sleep quality rating in the sleep diaries (p = 0.039, ES: − 0.689, 95% CI [− 1.351, − 0.027]), SF-36 Mental Health (MH) subscale score (p = 0.038, ES: − 0.750, 95% CI [− 1.404, − 0.096]), J-SDS score (p = 0.005, ES: 1.029, 95% CI [0.295, 1.762]), and DBAS-J score (p = 0.008, ES: 0.889, 95% CI [0.067, 1.711]) were also significantly greater in the PI than in the CI group.
No significant changes in any of the doses of drugs other than GABAA-RA were found after CBT-I in both groups. In addition, no significant differences in the amount of changes in any of the doses of drugs other than GABAA-RA from baseline to posttreatment were found between the PI and CI groups.
Change in the dose of GABAA-RA after treatment and over the long term
When the dose of GABAA-RA at baseline was compared with posttreatment, a significant dose reduction was noted in both the PI and CI groups (Table 3). A comparison of the drug dose between baseline and 6 months after posttreatment also revealed continued dose reduction in both groups. The group × time interaction was not significant (F = 1.18, p = 0.305), but the main effect of time was (F = 30.24, p < 0.001).
Table 3.
Changes in the dose of GABAA-RA after treatment as compared with that at baseline in each group
| Baseline | Posttreatment | 6-month follow-up | Group | Time | Group × Time | |||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| M | SD | M | SD | M | SD | F | p | F | p | F | p | |
| 3.65 | 0.064 | 30.24 | < 0.001* | 1.18 | 0.305 | |||||||
| CI | 1.30 | 0.75 | 1.04* | 0.76 | 0.932* | 0.80 | ||||||
| PI | 1.25 | 0.84 | 0.879* | 0.76 | 0.759* | 0.78 | ||||||
The interaction of time × group was tested by two-way analysis of variance (split-plot design). On the basis of its results, the significance of changes in the dose of GABAA-RA in each group was evaluated with Bonferroni-adjusted alphas, p < 0.016 (0.05/3)
GABAA-RA gamma aminobutyric acid-A receptor agonists; M mean; SD standard deviation; CI comorbid insomnia; PI primary insomnia
*Significant difference from baseline within the group (p < 0.016)
Correlation between the magnitude of improvement in ISI-J scores and the baseline values of the clinical variables
In the CI group, sleep onset latency and sleep quality in the sleep diaries were significantly correlated with the magnitude of change in ISI-J scores (Table 4). The magnitude of change in ISI-J scores showed a positive correlation with sleep onset latency (Spearman’s rho = 0.495, p = 0.043). Subjective sleep quality showed a negative correlation with ISI-J scores (Spearman’s rho = − 0.489, p = 0.046).
Table 4.
Correlations between the clinical variables at baseline and changes in ISI-J scores between baseline and posttreatment within each group
| Change in ISI-J scores in the CI group | Change in ISI-J scores in the PI group | |
|---|---|---|
| Sleep diary | ||
| TST (min) | 0.168 | 0.178 |
| SE (%) | − 0.005 | − 0.095 |
| SOL (min) | 0.495* | 0.043 |
| WASO (min) | − 0.114 | 0.283 |
| Sleep quality rating | − 0.489* | − 0.138 |
| SF-36 subscale score | ||
| PF | − 0.093 | 0.158 |
| RP | 0.207 | − 0.220 |
| BP | − 0.073 | 0.091 |
| GH | 0.115 | − 0.500* |
| VT | − 0.264 | 0.368 |
| SF | 0.243 | 0.423 |
| RE | 0.021 | − 0.096 |
| MH | − 0.313 | − 0.110 |
| J-SDS score | 0.125 | 0.195 |
| DBAS-J score | − 0.113 | 0.271 |
CI comorbid Insomnia; PI primary insomnia; ISI-J Japanese version of the Insomnia Severity Index; TST total sleep time; SE sleep efficiency; SOL sleep onset latency; WASO wake after sleep onset; SF-36 36-item Short Form Health Survey of the Medical Outcomes Study; PF physical functioning; RP role-physical; BP bodily pain; GH general health perception; VT vitality; SF social functioning; RE role-emotional; MH mental health; J-SDS Japanese version of the Zung Self-rating Depression Scale; DBAS-J 16-item Japanese version of Dysfunctional Beliefs and Attitudes about Sleep scale
*p < 0.05
**p < 0.01
Discussion
Whereas previous studies have used CBT-I that included therapeutic approaches to comorbidities, the present study used CBT-I with only standard components, which allowed us to identify differences in the effects of CBT-I on CI and PI. The results showed that the effect of CBT-I on CI was different from that of PI. CBT-I improved ISI-J scores in both the PI and CI groups, but the magnitude of the score improvement was significantly lower in the CI than in the PI group. On the other hand, an effect of CBT-I on the tapering of the GABAA-RA dose was noted in both groups. These results indicate that the therapeutic effect of CBT-I on CI was partly equivalent to that on PI and sustained.
In the present study, the variables correlated with the magnitude of improvement in ISI-J scores also differed between the CI and PI groups, indicating differences in the effects of CBT-I on the two groups. In the CI group, improvement in ISI-J scores was correlated with high subjective sleep quality and short sleep onset latency at baseline. These results suggest that CBT-I without consideration of comorbidities will not produce satisfactory treatment effects for CI with severe insomnia symptoms. Therefore, in such cases, it may be necessary to add comorbidity-specific treatments to CBT-I.
In addition, the effects of CBT-I on sleep-related parameters other than ISI-J scores were significantly greater in the PI than in the CI group. However, improved sleep efficiency according to the sleep diaries was found in both groups.
The improved sleep efficiency may have been obtained by behavioral therapy approaches such as sleep restriction therapy and stimulus control therapy. Since significant improvement in sleep efficiency was observed in both groups, it can be said that the participants in this study complied with the instructions in CBT-I.
An analysis of the effects on variables other than sleep parameters showed improvement in a larger number of variables in the PI than in the CI group. It has been reported that treatment of insomnia by CBT-I leads to improvement/alleviation of not only nocturnal sleep-related symptoms and activities of daily living [32] but also depressive symptoms in patients with insomnia accompanied by depression [33]. CBT-I can eliminate negative beliefs in/attitudes about sleep aggravated by insomnia [8, 34]. In the present study, however, the magnitudes of improvement in J-SDS, SF-36, and DBAS-J scores were lower in the CI than in the PI group. The inter-group difference in therapeutic efficacy against depression was particularly marked in the MH score among the subscales of the SF-36 and the J-SDS score. According to a previous report, CBT-I in cases of insomnia associated with sleep apnea resulted in the temporary aggravation of drowsiness immediately after sleep restriction therapy [35]. In the present study, it also appears likely that sleep restriction therapy imposed a greater mental burden on patients with insomnia associated with other types of sleep disorders or painful diseases than on patients with PI. It has also been reported that combining CBT-I with psychotherapy for the underlying disease reinforces the efficacy of CBT-I for insomnia associated with psychiatric diseases such as depression [36]. Taken together, our findings suggest that CBT-I shows limited therapeutic efficacy against insomnia in patients with CI, as it does not include a therapeutic intervention for comorbid disease.
This study had some limitations. First, the sample size was small relative to the number of comorbid diseases, so a sufficient analysis of factors affecting the therapeutic efficacy was not possible. The less consistent efficacy of CBT-I in patients with CI may be explained by the fact that the comorbid diseases in cases of CI are diverse. Differences in efficacy have been observed between previous meta-analyses, suggesting that CBT-I may be less effective for insomnia comorbid with other sleep disorders [10, 11]. In our study, the inclusion of insomnia comorbid with other sleep disorders may have reduced the overall effect of CI. Second, we excluded data from patients who had discontinued treatment prior to completion. Therefore, we cannot comment on the possible differences in the characteristics between patients who had discontinued and completed treatment. Third, polysomnography was not performed prior to the therapeutic intervention. Therefore, we cannot rule out the possibility that patients with unknown types of sleep disorders were included in the PI group. Fourth, other than an overall evaluation utilizing a depression rating scale and a quality-of-life scale, we did not perform a thorough evaluation of the symptoms of the comorbid diseases in the CI group. We confirmed that treatments for comorbidities had been continued without modification throughout the CBT-I implementation period, but we did not quantitatively confirm whether comorbidity symptoms remained stable. In addition, previous studies have suggested that CBT-I may be effective in improving comorbidity symptoms [8, 11, 33, 37], but we did not verify this effect in the present study. Therefore, this study may have underestimated the efficacy of CBT-I on comorbidities in CI. Lastly, only the change in the required dose level of oral hypnotic drugs was used to evaluate long-term therapeutic efficacy, so other parameters potentially showing improvement in long-term efficacy may have been overlooked.
Conclusion
In the present study, the efficacy of CBT-I, implemented in exactly the same manner, was compared between patients with CI and those with PI. The results revealed that CBT-I led to a significant and continuous reduction in the dose level of hypnotic drugs (GABAA-RA) in the CI group, similar to the effects in the PI group. However, the effects in terms of the other variables were inferior in the CI group compared with the PI group.
For CBT-I to exert an equivalent degree of efficacy in cases of CI, especially those with severe insomnia symptoms as recorded in a sleep diary, as in cases of PI, it may be useful to add an approach tailored to the type of comorbid disease to the basic components of CBT-I.
Author contributions
Conceptualization: MI, WY; methodology: MI; formal analysis and investigation: MI, AH, MA, TU; Writing—original draft preparation: MI; writing—review and editing: WY; supervision: HI, MS.
Funding
There is no funding source for this study.
Declarations
Conflict of interest
Masayuki Iwashita, Wataru Yamadera, Ayana Hotchi, Tomohiro Utsumi, Misato Amagai, Junpei Ishii, Takako Suzuki, Hiroshi Itoh and Masahiro Shigeta declare that they have no conflict of interest.
Ethical approval
This study was approved by the Jikei University Ethics Committee (No. 9520).
Research involving human participants and/or animals
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
Informed consent
For this type of study formal consent is not required.
Footnotes
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
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