Predictors of Daytime Consequences of Insomnia: The Roles of Quantitative Criteria and Nonrestorative Sleep.

BACKGROUND: The implications of removing nonrestorative sleep (NRS) and adding quantitative criteria in the most recent diagnostic criteria of insomnia disorder remain unresolved. The study was aimed to investigate how nighttime quantitative measures of sleep quality and NRS relate to daytime functioning in a general population sample. SAMPLING AND METHODS: Data of 905 subjects (mean age = 47.0 years; 64.5% females) in a population-based survey who had insomnia symptoms or NRS at least 1 night in a typical week were analyzed to evaluate their relationship with "functional impairment," "concerns/distress," and "interference with daily activities" over the past 30 days. Receiver-operating characteristic curve analysis was performed, while controlling for age and gender. RESULTS: Moderate to severe NRS was the first-level predictor of all 3 daytime variables. Insomnia frequency ≥3 times per week and sleep onset latency ≥10-20 min were second-level predictors. CONCLUSIONS: We found that NRS was more important than insomnia symptoms in determining daytime consequences of insomnia. On the basis of our findings we express concerns whether the removal of NRS from the most recent diagnostic criteria may lead to its underrecognition, but support the quantitative criteria on insomnia frequency of at least 3 nights per week.

Sleep in schizophrenia: A systematic review and meta-analysis of polysomnographic findings in case-control studies.

Polysomnographic studies have been performed to examine the sleep abnormalities in schizophrenia, but the results are inconsistent. An updated systematic review, meta-analysis, and moderator analysis was conducted. Major databases were searched without language restriction from 1968 to January 2014. Data were analyzed using the random-effects model and summarized using the Hedges's g. Thirty-one studies with 574 patients and 515 healthy controls were evaluated. Limited by the number of studies and a lack of patient-level data, moderator analysis was restricted to medication status, duration of medication withdrawal, and illness duration. We showed that patients with schizophrenia have significantly shorter total sleep time, longer sleep onset latency, more wake time after sleep onset, lower sleep efficiency, and decreased stage 4 sleep, slow wave sleep, and duration and latency of rapid eye movement sleep compared to healthy controls. The findings on delta waves and sleep spindles were inconsistent. Moderator analysis could not find any abnormalities in sleep architecture in medication-naïve patients. Patients with antipsychotic withdrawal for longer than eight weeks were shown to have less sleep architectural abnormalities, compared to shorter duration of withdrawal, but the abnormalities in sleep continuity were similar. Slow wave sleep deficit was found in patients with schizophrenia for more than three years, while sleep onset latency was increased in medication-naïve, medication-withdrawn, and medicated patients. Our study showed that polysomnographic abnormalities are present in schizophrenia. Illness duration, medication status, and duration of medication withdrawal are several of the clinical factors that contribute to the heterogeneity between studies.

Identification of Chinese medicine syndromes in persistent insomnia associated with major depressive disorder: a latent tree analysis.

BACKGROUND: Chinese medicine (CM) syndrome (zheng) differentiation is based on the co-occurrence of CM manifestation profiles, such as signs and symptoms, and pulse and tongue features. Insomnia is a symptom that frequently occurs in major depressive disorder despite adequate antidepressant treatment. This study aims to identify co-occurrence patterns in participants with persistent insomnia and major depressive disorder from clinical feature data using latent tree analysis, and to compare the latent variables with relevant CM syndromes. METHODS: One hundred and forty-two participants with persistent insomnia and a history of major depressive disorder completed a standardized checklist (the Chinese Medicine Insomnia Symptom Checklist) specially developed for CM syndrome classification of insomnia. The checklist covers symptoms and signs, including tongue and pulse features. The clinical features assessed by the checklist were analyzed using Lantern software. CM practitioners with relevant experience compared the clinical feature variables under each latent variable with reference to relevant CM syndromes, based on a previous review of CM syndromes. RESULTS: The symptom data were analyzed to build the latent tree model and the model with the highest Bayes information criterion score was regarded as the best model. This model contained 18 latent variables, each of which divided participants into two clusters. Six clusters represented more than 50 % of the sample. The clinical feature co-occurrence patterns of these six clusters were interpreted as the CM syndromes Liver qi stagnation transforming into fire, Liver fire flaming upward, Stomach disharmony, Hyperactivity of fire due to yin deficiency, Heart-kidney noninteraction, and Qi deficiency of the heart and gallbladder. The clinical feature variables that contributed significant cumulative information coverage (at least 95 %) were identified. CONCLUSION: Latent tree model analysis on a sample of depressed participants with insomnia revealed 13 clinical feature co-occurrence patterns, four mutual-exclusion patterns, and one pattern with a single clinical feature variable.

The Experience of Chronic Insomnia in Chinese Adults: A Study Using Focus Groups and Insomnia Experience Diaries.

The subjective experience in 43 Chinese adults with chronic primary insomnia was assessed using focus groups and insomnia experience diaries. Participants recruited from the community and a sleep clinic were diagnosed with DSM-IV-TR insomnia disorder and had sleep difficulties on 3 or more nights per week for at least 6 months. Six focus groups, of 6-8 participants each, were conducted; it was stopped as thematic saturation emerged in the last 2 groups. Using grounded theory approach, we identified 4 themes and 16 subthemes, covering beliefs about the nature and treatment of insomnia, behavioral responses to insomnia, cognitive-emotional and physiological arousal, and emotional experiences associated with insomnia. The findings are in general compatible with qualitative studies in the West, but some subthemes are influenced by Chinese cultural beliefs and values, in particular, use of the traditional Chinese medicine concept, being modest in sleep expectation, and a letting go attitude. Strategies for cultural adaptation of cognitive-behavioral therapy for insomnia in a Chinese society using patients' subjective experience are discussed.

Hypnotherapy for insomnia: a systematic review and meta-analysis of randomized controlled trials.

OBJECTIVE: To examine the efficacy and safety of hypnotherapy for insomnia as compared to placebo, pharmacological or non-pharmacological intervention, or no treatment. METHODS: A systematic search on major electronic databases was conducted up until March 2014. Inclusion criteria are: (1) randomized controlled trials (RCTs) or quasi-RCTs; (2) intervention targeted at improving sleep; (3) hypnosis as an intervention; and (4) English language articles. Sleep diary variable is the primary outcome measure. RESULTS: Six RCTs of hypnotherapy and seven on autogenic training or guided imagery, comprising 502 subjects, were included. Eleven of the 13 studies had low methodological quality, as indicated by a modified Jadad score below 3, and high risks of bias in blinding and design of the control interventions. No adverse events related to hypnosis were reported, though seldom investigated. Meta-analyses found hypnotherapy significantly shortened sleep latency compared to waitlist (standardized mean difference, SMD=-0.88, 95% confidence interval (CI): -1.56, -0.19, P=0.01, I(2)=15%), but no difference compared to sham intervention (SMD: -1.08, 95% CI: -3.15, 0.09, P=0.31, I(2)=90%). Similar results were found for autogenic training or guided imagery (SMD with waitlist=-1.16, 95% CI: -1.92, -0.40, P=0.003, I(2)=0%; SMD with sham intervention=-0.50, 95% CI: -1.19, 0.19, P=0.15, I(2)=0%). CONCLUSIONS: Generalizability of the positive results is doubtful due to the relatively small sample size and methodological limitations. Future studies with larger sample size and better study design and methodology are called for.

Acupuncture for residual insomnia associated with major depressive disorder: a placebo- and sham-controlled, subject- and assessor-blind, randomized trial.

OBJECTIVE: To evaluate the efficacy and safety of acupuncture for residual insomnia and other residual symptoms associated with major depressive disorder (MDD). METHOD: 150 participants having significant insomnia for more than 3 months and a history of MDD (both based on DSM-IV-TR criteria) were recruited from 4 psychiatric outpatient clinics in Hong Kong from May 2011 to August 2013 to receive 9 sessions of treatment over 3 weeks. They were randomized to receive acupuncture, minimal acupuncture, or placebo acupuncture. Primary outcome was sleep diary-derived sleep efficiency. Secondary outcomes included other sleep diary parameters, actigraphy, anxiety and depressive symptoms, daytime functioning, and adverse events. RESULTS: The mean difference in sleep diary-derived sleep efficiency at 1-week posttreatment was -1.40 (95% CI, -7.08 to 4.28) between the acupuncture and minimal acupuncture groups and was 3.10 (95% CI, -3.64 to 9.84) between the acupuncture and placebo acupuncture groups. A χ(2) test showed that acupuncture produced a significantly higher proportion of participants achieving sleep-onset latency ≤ 30 minutes than did minimal acupuncture at 1-week posttreatment (P = .04). However, there was no significant between-group difference in most of the other outcomes. Treatment blinding was successful, as a majority of participants did not know which treatment they had received. CONCLUSIONS: Acupuncture was well tolerated, but the efficacy was only mild and similar to that of minimal acupuncture and placebo acupuncture. A high proportion of patients remained clinically significantly affected by insomnia after treatment. The finding raises certain doubts about the value of acupuncture and underscores the difficulties in the treatment of residual insomnia in MDD. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01707706.

Cross-cultural and comparative epidemiology of insomnia: the Diagnostic and statistical manual (DSM), International classification of diseases (ICD) and International classification of sleep disorders (ICSD).

OBJECTIVE: To compare the prevalence of insomnia according to symptoms, quantitative criteria, and Diagnostic and Statistical Manual of Mental Disorders, 4th and 5th Edition (DSM-IV and DSM-5), International Classification of Diseases, 10th Revision (ICD-10), and International Classification of Sleep Disorders, 2nd Edition (ICSD-2), and to compare the prevalence of insomnia disorder between Hong Kong and the United States by adopting a similar methodology used by the America Insomnia Survey (AIS). METHODS: Population-based epidemiological survey respondents (n = 2011) completed the Brief Insomnia Questionnaire (BIQ), a validated scale generating DSM-IV, DSM-5, ICD-10, and ICSD-2 insomnia disorder. RESULTS: The weighted prevalence of difficulty falling asleep, difficulty staying asleep, waking up too early, and non-restorative sleep that occurred ≥3 days per week was 14.0%, 28.3%, 32.1%, and 39.9%, respectively. When quantitative criteria were included, the prevalence dropped the most from 39.9% to 8.4% for non-restorative sleep, and the least from 14.0% to 12.9% for difficulty falling asleep. The weighted prevalence of DSM-IV, ICD-10, ICSD-2, and any of the three insomnia disorders was 22.1%, 4.7%, 15.1%, and 22.1%, respectively; for DSM-5 insomnia disorder, it was 10.8%. CONCLUSION: Compared with 22.1%, 3.9%, and 14.7% for DSM-IV, ICD-10, and ICSD-2 in the AIS, cross-cultural difference in the prevalence of insomnia disorder is less than what is expected. The prevalence is reduced by half from DSM-IV to DSM-5. ICD-10 insomnia disorder has the lowest prevalence, perhaps because excessive concern and preoccupation, one of its diagnostic criteria, is not always present in people with insomnia.

Comparison of scoring methods for the Brief Insomnia Questionnaire in a general population sample.

OBJECTIVE: The Brief Insomnia Questionnaire (BIQ) is a lay-administered, structured interview to derive insomnia disorders according to the Diagnostic and Statistical Manual, Fourth Edition, Text Revision (DSM-IV-TR), International Classification of Diseases, Tenth Edition (ICD-10) and research diagnostic criteria/International Classification of Sleep Disorders, Second Edition (RDC/ICSD-2). The concordance between diagnoses derived from the BIQ and clinical interviews was only moderate and the prevalence estimates based on the BIQ were significantly different from estimates based on clinical interviews. We hypothesized that a modification of the scoring algorithm closer to the diagnostic criteria would improve the performance of the BIQ. METHODS: Probability subsample of population-based epidemiological survey respondents (n=2011) completed clinical reappraisal (n=176) interviews. We compared the modified scoring with the original scoring in sensitivity, specificity, positive and negative predictive values, areas under the characteristic curve, and Cohen's kappa to detect DSM-IV-TR, ICD-10 and RDC/ICSD-2 insomnia diagnoses by the BIQ against clinical interviews. RESULT: The diagnostic accuracy was improved with the modified scoring. The areas under the receiver operating characteristic curve for the DSM-IV-TR, ICD-10, RDC/ICSD-2 and any of the insomnia diagnoses ranged from 0.76 to 0.87. Using the modified scoring, there was no significant difference between prevalence estimates based on the BIQ classification and clinical interviews. CONCLUSIONS: The BIQ with modified scoring enhanced case detection and produced more accurate prevalence estimates of DSM-IV-TR, ICD-10 and RDC/ICSD-2 insomnia disorders. With scoring algorithms now extended to DSM-5 and ICSD-3 diagnoses, the BIQ should be more widely used in clinical and research settings.

Self-help cognitive-behavioral therapy for insomnia: a meta-analysis of randomized controlled trials.

Self-help cognitive-behavioral therapy (CBT) is an increasingly popular treatment option for insomnia. The objective of this meta-analysis was to compile an up-to-date evaluation on the efficacy, adherence, acceptability and dropout rate of self-help CBT for insomnia. We systematically searched six key electronic databases up until May 2013. Two researchers independently selected relevant publications, extracted data, and evaluated methodological quality according to the Cochrane criteria. Twenty randomized controlled trials were included; 10 of which were published after the last review up until January 2007. Meta-analysis of self-help CBT vs. waiting-list, routine care or no treatment was performed. Results showed that self-help CBT improved sleep, sleep-related cognitions and anxiety and depressive symptoms. Effect sizes for sleep-diary-derived sleep efficiency, sleep onset latency, and wake after sleep onset at immediate posttreatment were 0.80, 0.66, and 0.55, respectively. The average dropout rate of self-help CBT at immediate posttreatment was 14.5%, which was not significantly different from the 16.7% in therapist-administered CBT. Subgroup analyses supported the added benefit of telephone consultation. In conclusion, self-help CBT is efficacious and acceptable as an entry level of a stepped care model for insomnia. In places where face-to-face treatments are unavailable or too costly, self-help CBT can be considered as a compromise.

Doxepin for insomnia: a systematic review of randomized placebo-controlled trials.

Doxepin, a sedating tricyclic drug, at 3 mg and 6 mg doses was recently approved by the U.S. food and drug administration (FDA) for the treatment of insomnia. The objective of this systematic review was to obtain a precise summary of the efficacy and safety of doxepin as a hypnotic. We searched key databases and trial registers up to March 2014 and contacted pharmaceutical companies and the FDA for unpublished data. A total of nine randomized placebo-controlled trials were analyzed. Six studies were on doxepin 1-6 mg/d, two on doxepin 25-300 mg/d, and one on ramelteon 8 mg and doxepin 3 mg combined. All low-dose studies were industry-sponsored. We found that low-dose doxepin had a small to medium effect size against placebo for sleep maintenance and sleep duration but not for sleep initiation at both immediate and short-term posttreatment. There was no significant next-day residual effect with low-dose doxepin. Headache and somnolence were the most common side effects. We concluded that low-dose doxepin for 1-2 nights appeared to be safe and effective in improving sleep. However, a clear conclusion on its short-term benefits and risks as well as withdrawal effects was not possible due to the small number of studies.

Sleep-wake disturbance in interepisode bipolar disorder and high-risk individuals: a systematic review and meta-analysis.

Over the past decade, researchers have shifted focus from the manic and depressive episodes to the interepisode period in the study of sleep-wake disturbance in bipolar disorder. The objective of this systematic review was to compile and synthesize studies that employed sleep diary, actigraphy, polysomnography, and questionnaires to compare sleep-wake patterns in people with interepisode bipolar disorder or high-risk individuals vs. normal controls and/or people with primary insomnia. We searched key databases until June 2013. Our search identified 21 eligible studies, yielding 24 sleep-wake variables. A total of 531 people with interepisode bipolar disorder, 157 high-risk individuals, 678 normal controls and 67 adults with primary insomnia were evaluated. Using a random-effects model, our analyses suggest that adults with interepisode bipolar disorder appear worse than normal controls in most variables and comparable to adults with primary insomnia in certain aspects. Sleep onset latency, wake after sleep onset, and variability of sleep-wake variables were most consistently impaired in interepisode bipolar disorder. In comparison with controls, high-risk individuals were found to have higher variability in sleep efficiency and lower relative amplitude. The findings provide a foundation for the search for candidate endophenotypes and the development of novel interventions for bipolar disorder.

The use of conventional and complementary therapies for insomnia among Hong Kong Chinese: a telephone survey.

OBJECTIVE: To examine the prevalence and utilization pattern of complementary and alternative medicine (CAM) for insomnia in Hong Kong. METHODS: Respondents were selected from the general population and interviewed by telephone Their sleep was assessed by a Chinese version of the Brief Insomnia Questionnaire (BIQ) and CAM use by a checklist. Prevalence findings were weighted by the BIQ insomnia diagnosis, age, and sex. RESULTS: 402 respondents completed the survey. The population-weighted prevalence of any treatment in the past 12 months was 21.3%, any CAM use at 12.3%, any conventional treatment at 6.5%, and alcohol use at 1.6%; however, 46.6% of the BIQ insomnia cases did not seek treatment. The most commonly used CAM modalities was Chinese herbal medicine (7.9%), followed by acupuncture (1.7%) and Western herbal products (1.7%). Most CAM therapies were used infrequently and without consultation of healthcare professionals. Only BIQ insomnia diagnosis and being female were found predictive of CAM use. CONCLUSIONS: Apart from Chinese herbal medicine and acupuncture, the use of conventional treatments, CAM, and alcohol for trouble sleeping was all less common in Hong Kong. Public education on the consequences of insomnia and various treatment modalities is needed.

Assessment of fatigue using the Multidimensional Fatigue Inventory in patients with major depressive disorder.

OBJECTIVES: There are problems with the fatigue measures currently used in depressed patients. The Multidimensional Fatigue Inventory (MFI-20) covering general fatigue, physical fatigue, mental fatigue, reduced activity and reduced motivation has been widely used in patients with cancer and chronic fatigue syndrome. To address the multidimensional nature of fatigue, we examined the validity and reliability of a Chinese version of the MFI-20 in major depressive disorder (MDD). METHODS: Data were derived from a randomized controlled trial of acupuncture in 137 patients with partially remitted MDD. The test-retest reliability, internal consistency, construct and concurrent validity and sensitivity to change of the MFI-20 were analyzed. RESULTS: The MFI-20 was found to have good internal consistency (Cronbach's alpha=0.89) and 1-week test-retest reliability (Pearson correlation of the total score=0.73). Factor analysis showed 5 factors, but the factor structure was different from that in medical conditions. The 2 most prominent factors, explaining 46% of the total variance, were both associated with physical and mental energy but different in directions. There were adequate concurrent validity and sensitivity to change as evidenced by the significant correlations between the MFI-20 scores and depressive and anxiety symptoms, general health and quality of life. CONCLUSION: The Chinese MFI-20 is a valid and reliable instrument for the assessment of fatigue in MDD patients with residual symptoms. The construct of fatigue in MDD seems to be different from that in medical conditions. Further studies are needed to examine the MFI-20 in MDD patients from other cultures.

Validity and reliability of the Brief Insomnia Questionnaire in the general population in Hong Kong.

OBJECTIVES: The Brief Insomnia Questionnaire (BIQ) was first validated in the U.S. for insomnia disorders according to the Diagnostic and Statistical Manual, Fourth Edition, Text Revision (DSM-IV-TR), International Classification of Diseases, Tenth Edition (ICD-10) and research diagnostic criteria/International Classification of Sleep Disorders, Second Edition (RDC/ICSD-2). We aimed to determine the validity and reliability of a Hong Kong Chinese version of the BIQ to derive the DSM-5 in addition to other insomnia diagnoses in a general population sample. METHODS: Probability subsamples of population-based epidemiological survey respondents (n=2011) completed test-retest (n=120) and clinical reappraisal (n=176) interviews. RESULTS: Short-term test-retest reliability was moderate for most BIQ items (Pearson r>0.40), except for the number of nights with problems staying asleep, amount of time awake, duration of sleep problems and sleep onset latency. The areas under the receiver operating characteristic curve for the DSM-IV-TR, DSM-5, ICD-10 and RDC/ICSD-2 insomnia disorder ranged from 0.76 to 0.86, indicating high individual-level concordance between BIQ and clinical-interview diagnoses. The use of super-normal control and BIQ symptom-level data further improves the diagnostic concordance. Prevalence estimates based on the BIQ dichotomous classification were comparable with estimates based on clinical interviews for the DSM-5, RDC/ICSD-2 and any of the DSM-IV-TR, ICD-10 and RDC/ICSD-2 insomnia disorders. CONCLUSION: The Hong Kong Chinese version of the BIQ generates accurate prevalence estimates for insomnia disorders in the general population. Modification of the BIQ scoring algorithms and use of trained interviewers may further improve its diagnostic performance.

Randomized non-invasive sham-controlled pilot trial of electroacupuncture for postpartum depression.

BACKGROUND: Postpartum depression affects 10-15% of mothers. Although acupuncture was efficacious for major depressive disorder in pregnancy and in women outside the perinatal period, there has been no randomized controlled study on the feasibility, tolerability, and efficacy of acupuncture for postpartum depression. METHODS: This was a randomized, subject- and assessor-blind, parallel-group, sham-controlled trial. Twenty women within six months postpartum with DSM-IV-diagnosed major depressive disorder of mild severity, defined as a 17-item Hamilton Depression Rating Scale (HDRS(17)) score of 12 to 19, were randomly assigned to either electroacupuncture or non-invasive sham acupuncture two sessions weekly for four weeks. RESULTS: There was significant reduction in HDRS(17) score from baseline to 4-week posttreatment in both groups, with an effect size 1.4 and 1.8 for electroacupuncture and sham acupuncture, respectively. Improvement was observed as early as two weeks after commencing acupuncture. The response and remission rate in the electroacupuncture group at 4-week posttreatment was 33% and 44%, respectively; for the sham acupuncture group, it was 60% and 50%, respectively. There was no significant between-group difference in all outcome measures, including the HDRS(17), Edinburgh Postnatal Depression Scale, Hospital Anxiety and Depression Scale, Clinical Global Impression, and Sheehan Disability Scale. Treatment credibility, success of blinding, and adverse events were similar between groups. LIMITATION: Small sample size and high attrition rate. No waiting list observation group. CONCLUSION: Both electroacupuncture and non-invasive sham acupuncture were effective for postpartum depression. Further studies utilizing larger sample size, better recruitment strategies, and home-based acupuncture treatment are warranted. CLINICAL TRIAL INFORMATION: Pilot Study on the Use of Acupuncture for Postpartum Depression; ClinicalTrials.gov Registration #NCT01178008; URL - http://clinicaltrials.gov/ct2/show/NCT01178008?term=postpartum+acupuncture&rank=1.