Imran Khawaja

Psychological and Behavioral Interventions for Managing Insomnia Disorder: An Evidence Report for a Clinical Practice Guideline by the American College of Physicians

Sleep difficulties, including the inability to initiate or maintain sleep, are common in adults. Sleep difficulties are typically transient; however, when they become chronic and cause distress or daytime dysfunction, insomnia disorder may be present. The American Psychiatric Associations Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, defines insomnia disorder as a predominant symptom of difficulty with sleep initiation, difficulty maintaining sleep, or early-morning waking with inability to return to sleep causing clinically significant distress or impairment in activities, occurring at least 3 nights per week for 3 months or more (1). Furthermore, individuals must have adequate opportunity for sleep and the symptoms cannot be better explained by medical or mental conditions, including another sleep disorder (such as breathing-related sleep disorder), or medication or substance use. The term previously used for insomnia disorder is chronic insomnia (14), for which diagnostic criteria required sleep problems lasting from weeks to months. These criteria are empirically similar to current criteria for insomnia disorder. We use the term insomnia disorder even though much of the primary research has used other terminology (such as chronic insomnia and persistent insomnia). Between 6% and 10% of adults meet the diagnostic criteria for insomnia disorder (4). Duration ranges from 1 to 20 years across longitudinal studies (5). Insomnia disorder is more common in female patients and older adults (6, 7). Older adults typically report difficulty maintaining sleep as opposed to initiating sleep, which is common in younger adults (8). Many treatment types are available once insomnia disorder is accurately diagnosed by using established diagnostic criteria (4, 9). These include psychological and behavioral treatments, pharmacologic therapies, and complementary and alternative medicine. The American Academy of Sleep Medicine recommends psychological and behavioral interventions and supports short-term supplementary medication (9, 10). Psychological and behavioral interventions include cognitive behavioral therapy for insomnia (CBT-I), multicomponent behavioral therapy (brief behavioral therapy for insomnia), and single-component interventions (such as sleep hygiene and education, stimulus control, sleep restriction, and relaxation) (Table). Cognitive behavioral therapy for insomnia most commonly includes behavioral therapies (sleep restriction, stimulus control, relaxation training), cognitive therapy (cognitive restructuring) to change dysfunctional beliefs about sleep, as well as sleep hygiene education (3). Multicomponent behavioral therapies combine several behavioral therapies and do not include a cognitive component. Table. Psychological and Behavioral Interventions for Insomnia Disorder* Treatment goals include improving quality and quantity of sleep and associated impairments (10). Ideally, meaningful improvements in global outcomes measuring sleep and associated distress and dysfunction are realized. The Insomnia Severity Index (ISI) and the Pittsburgh Sleep Quality Index (PSQI) are commonly used for measuring global outcomes. Sleep outcomes include specific sleep variables (sleep-onset latency [SOL], wake time after sleep onset [WASO], total sleep time [TST], sleep efficiency (sleep time/time in bed), and sleep quality. Sleep variables can be measured objectively (with polysomnography or actigraphy) or subjectively (sleep diaries). Guidelines suggest monitoring symptoms with sleep diaries and polysomography is not indicated (10). We conducted a systematic review on the management of insomnia disorder for the Agency for Healthcare Research and Quality (11). This article reports evidence on psychological and behavioral interventions. Another article reports on the evidence on pharmacologic interventions and the comparison of pharmacologic interventions with psychological and behavioral interventions (12), and the full report provides evidence on complementary and alternative interventions. This evidence was used by the American College of Physicians to develop the guideline on the treatment of insomnia disorder in primary care. Evidence summarized here enhances previous reports (1315) by providing a comprehensive evaluation of psychological and behavioral interventions across all delivery modes with a primary emphasis on global outcomes. Methods Data Sources and Searches We searched bibliographic databases, including MEDLINE, Embase, and PsycINFO via Ovid, as well as the Cochrane Library, to identify randomized, controlled trials published from 2004 through September 2015 (Supplement). We identified studies published before 2004 by searching the citations in relevant systematic reviews. Supplement. Supplementary Material Study Selection Two investigators independently reviewed titles and abstracts of search results to identify potentially eligible references. Two investigators independently screened full texts of those references to determine whether inclusion criteria were met. We included randomized, controlled trials of psychological and behavioral interventions if they enrolled adults, provided at least 4 weeks of treatment, reported global or sleep outcomes, and were published in English. We excluded trials enrolling pure subgroups of patients with major medical conditions or conditions that may explain the sleep problems (such as menopause, pregnancy, and neurologic conditions). Data Extraction and Quality Assessment Risk of bias was independently assessed by two investigators using an instrument developed using Agency for Healthcare Research and Quality guidance (16) and was summarized as low, medium, or high on the basis of summary risk of bias and confidence that results were believable given limitations. Study, participant, and treatment characteristics; outcomes; and adverse events were extracted from eligible trials with low or moderate risk of bias. Data Synthesis and Analysis We used RevMan 5.2 (Nordic Cochrane Center) for pooling when adequate data were provided and populations, interventions, and outcomes were similar (17). DerSimonian and Laird random-effects estimates of risk ratios and absolute risk differences with 95% CIs were calculated for categorical outcomes, and weighted mean differences (WMDs) and/or standardized mean differences with 95% CIs were calculated for continuous outcomes. We assessed heterogeneity with the Cochran Q test and I 2 statistic (75% indicates substantial heterogeneity) (18). We analyzed the general adult population and older adults separately because sleep measures vary. We used established minimum important differences (MIDs) to capture clinical significance in global outcomes. The MID for the ISI is a 6-point change from baseline (19). Trials that conducted remitter or responder analysis on the basis of established MID offer simplistic interpretation. When trials provided mean scores, we interpreted WMDs in relation to MID by using the method of Johnson and colleagues (20). Weighted mean differences equal to or greater than the MID suggest that many patients gain important benefits, WMDs greater than half the MID but less than the MID suggest that an appreciable number of patients benefit, and WMDs less than half of the MID suggest that patients do not achieve important benefits (20). One investigator assessed strength of evidence for unique comparisons as high, moderate, low, or insufficient (21); assessments were confirmed through consensus. Role of Funding Source This topic was nominated to and funded by the Agency for Healthcare Research and Quality Effective Health Care Program. Key informants representing various perspectives offered suggestions as refined the review scope. Our draft protocol was shared with a technical expert panel that had the opportunity to review the draft report. The American College of Physicians provided support for this manuscript preparation. The authors are solely responsible for its contents. Results We identified 3572 citations; 559 required full-text review after title and abstract screening (Appendix Figure 1). Seventy-six articles (2297) reporting on 70 trials that compared psychological and behavioral interventions with inactive controls or other psychological and behavioral interventions were eligible. We extracted data and analyzed results for 60 trials with low to moderate risk of bias. We grouped trials by intervention type and comparison. Interventions for CBT-I had cognitive and behavioral components; multicomponent behavioral therapy interventions had several behavioral components and no cognitive component; and single-component interventions included sleep restriction, stimulus control, and relaxation. Appendix Figure 1. Summary of evidence search and selection. Intervention type totals do not equal total references because several trials were used in the analysis for 2 different types of interventions. RCT = randomized, controlled trial. Eligible trials (Tables 1 and 2 of the Supplement) enrolled individuals most commonly diagnosed with chronic insomnia according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, with mean durations of several years. Participants were predominantly female and white. Trials were conducted in the United States, Canada, the United Kingdom, Sweden, Australia, Norway, Scotland, the Netherlands, and China. Mean age was mid-40s in general adult populations and lower 70s in older adults. Baseline ISI scores were approximately 17, indicating moderate severity, and baseline SOL was more than 45 minutes. Comparisons varied across trials. Inactive controls included information (such as sleep hygiene education) or waitlist; trials infrequently used sham treatments. Adverse effects were rarely reported. Withdrawals were not always reported by group. Evidence on adverse effects and withdrawals was insufficient for all comparisons. We assessed strength of

Correlates of daytime sleepiness in patients with posttraumatic stress disorder and sleep disturbance.

OBJECTIVE To assess the correlates of daytime sleepiness in patients with a lifetime diagnosis of posttraumatic stress disorder (PTSD) and ongoing sleep disturbance not due to sleep apnea or other diagnosed sleep disorders. METHOD The sample consisted of 26 veterans receiving mental health care at the Minneapolis VA Medical Center, Minneapolis, Minnesota. The Epworth Sleepiness Scale was the primary outcome measure. Other sleep-related instruments consisted of the Pittsburgh Sleep Quality Scale, a daily sleep log, and daily sleep actigraphy. In addition, data included 3 symptom ratings (Posttraumatic Stress Disorder Checklist, Clinician Administered PTSD Scale [CAPS], and Beck Depression Inventory). Data were collected from 2003 to 2005. Current and lifetime PTSD diagnoses were based on DSM-IV criteria and were obtained by experienced psychiatrists using the CAPS interview. RESULTS Univariate analyses showed that daytime sleepiness on the Epworth Sleepiness Scale was associated with daytime dysfunction on the Pittsburgh Sleep Quality Index (P < .001), less use of sleeping medication (P = .02), and more self-rated posttraumatic symptoms (P = .05). Within posttraumatic symptom categories, hypervigilance symptoms were more correlated with daytime sleepiness (P = .03) than were reexperiencing and avoidance symptoms (P = .09 for both). CONCLUSION In this selected sample, daytime sleepiness was most strongly and independently associated with daytime dysfunction.

Sleep Disturbances in Posttraumatic Stress Disorder: Updated Review and Implications for Treatment

Sleep disturbances are common in adults with PTSD and range from insomnia and nightmares to periodic leg movements and disruptive nocturnal behaviors. Together these findings suggest profound disturbances in rapid eye movement (REM) and non-REM (NREM) sleep, although there is a lack of consensus regarding a distinct profile of objective sleep disturbances associated with PTSD. Prospective, longitudinal studies have established that sleep disturbances represent a risk factor for the development and course of PTSD, suggesting that sleep is an important neurobiological mechanism in the etiology and maintenance of this disorder. This research highlights the importance of early identification and treatment of sleep disturbances in at-risk and trauma exposed populations. A number of psychological and pharmacological treatments are effective at treating sleep disturbances in PTSD. Additional research is needed to further develop clinical guidelines informing when and how to integrate sleep-specific treatment with PTSD focused clinical care.

Obstructive Sleep Apnea and Depression: A Review

Obstructive sleep apnea is a common sleep disorder associated with several medical conditions, increased risk of motor vehicle accidents, and overall healthcare expenditure. There is higher prevalence of depression in people with obstructive sleep apnea in both clinical and community samples. Many symptoms of depression and obstructive sleep apnea overlap causing under-diagnosis of obstructive sleep apnea in depressed patients. Sleep problems, including obstructive sleep apnea, are rarely assessed on a regular basis in patients with depressive disorders, but they may be responsible for antidepressant treatment failure. The mechanism of the relationship between obstructive sleep apnea and depression is complex and remains unclear. Though some studies suggest a mutual relationship, the relationship remains unclear. Several possible pathophysiological mechanisms could explain how obstructive sleep apnea can cause or worsen depression. Increased knowledge of the relationship between obstructive sleep apnea and depression might significantly improve diagnostic accuracy as well as treatment outcomes for both obstructive sleep apnea and depression.

Violent Parasomnia With Recurrent Biting and Surgical Interventions: Case Report and Differential Diagnosis

ABSTRACT A case is reported of recurrent, injurious self-biting during sleep, requiring surgical interventions, in a 55-year-old obese man with a 20-year history of violent complex parasomnia, with greatly increased frequency and severity of episodes induced by work stress during the preceding 3 years. After clinical evaluation and overnight, hospital-based video-polysomnography, the cause of the chronic injurious parasomnia was deemed to be a non-rapid eye movement (NREM) sleep parasomnia comorbid with severe obstructive sleep apnea. Therapy with bedtime clonazepam and bilevel positive airway pressure was effective, with injurious parasomnia relapse occurring with cessation of either or both of these therapies. The differential diagnosis of sleep-related biting should now include NREM sleep parasomnia (with or without comorbid obstructive sleep apnea), besides previously reported cases of REM sleep behavior disorder (RBD), sleep-related dissociative disorder, sleep-related rhythmic movement disorder and anticipated cases of parasomnia overlap disorder (RBD + NREM sleep parasomnia), sleep-related biting seizures, and sleep-related eating disorder.

Urdu translation of the Hamilton Rating Scale for Depression: Results of a validation study.

Objective: To develop a standardized validated version of the Hamilton Rating Scale for Depression (HAM-D) in Urdu. Methods: After translation of the HAM-D into the Urdu language following standard guidelines, the final Urdu version (HAM-D-U) was administered to 160 depressed outpatients. Inter-item correlation was assessed by calculating Cronbach alpha. Correlation between HAM-D-U scores at baseline and after a 2-week interval was evaluated for test-retest reliability. Moreover, scores of two clinicians on HAM-D-U were compared for inter-rater reliability. For establishing concurrent validity, scores of HAM-D-U and BDI-U were compared by using Spearman correlation coefficient. The study was conducted at Mayo Hospital, Lahore, from May to December 2014. Results: The Cronbach alpha for HAM-D-U was 0.71. Composite scores for HAM-D-U at baseline and after a 2-week interval were also highly correlated with each other (Spearman correlation coefficient 0.83, p-value < 0.01) indicating good test-retest reliability. Composite scores for HAM-D-U and BDI-U were positively correlated with each other (Spearman correlation coefficient 0.85, p < 0.01) indicating good concurrent validity. Scores of two clinicians for HAM-D-U were also positively correlated (Spearman correlation coefficient 0.82, p-value < 0.01) indicated good inter-rater reliability. Conclusion: The HAM-D-U is a valid and reliable instrument for the assessment of Depression. It shows good inter-rater and test-retest reliability. The HAM-D-U can be a tool either for clinical management or research.

New Onset of Compulsive Gambling Associated With Modafinil: A Case Report.

To the Editor: We describe a case of compulsive gambling associated with the use of modafinil in a patient with idiopathic hypersomnia. Modafinil is a wakefulness-promoting agent that is approved by the US Food and Drug Administration for hypersomnolence associated with narcolepsy, obstructive sleep apnea, shift work sleep disorder, and fatigue associated with multiple sclerosis.1 Modafinil prescribing information reports psychiatric adverse experiences including mania, delusions, hallucinations, suicidal ideation, and depression.1 Tarrant and colleagues2 have described a case of a patient with minor gambling, who reported a 10-fold increase in his slot-machine use after taking modafinil. However, new-onset impairment of impulse control has been more commonly described in patients receiving dopamine agonist therapy for restless legs syndrome and Parkinson’s disease.3 Case report. A 46-year-old white woman with history of idiopathic hypersomnia diagnosed in 2005 at another sleep center presented to our sleep clinic as a transfer of care in 2010. She had history of excessive daytime sleepiness dating back to early school years. She had also experienced hypnogogic hallucinations and occasional sleep paralysis. There was no clear history of cataplexy. In 2005, her primary complaint included excessive sleepiness and snoring. She underwent diagnostic polysomnography (PSG) and a multiple sleep latency test (MSLT with 4 naps). Review of these records indicated an unremarkable PSG. Results from a MSLT performed after 8 hours of PSG-documented sleep showed a sleep latency of 4 minutes 45 seconds with no sleep-onset rapid-eye-movement periods. She was diagnosed with narcolepsy without cataplexy (based on International Classification of Sleep Disorders, second edition4), and modafinil was started at a dose of 200 mg in the morning and a 100-mg additional dose if needed for residual daytime sleepiness. She had a good response to the medication and no longer required daily naps. The patient’s hypersomnolence symptom remained stable on a dose of 200 mg of modafinil for a year when she developed impulsive gambling. She was not taking any other medications at that time. She tried to curtail her gambling, but could not, and would go to casinos and lose significant amounts of money until she was seen in our sleep center in 2010. She described losing up to

Poor Sleep Quality at Discharge as a Predictor of Readmission to a Psychiatry Partial Hospitalization Program.

1,000 each time and reported losing

Obstructive Sleep Apnea in Posttraumatic Stress Disorder Comorbid With Mood Disorder: Significantly Higher Incidence Than in Either Diagnosis Alone

20,000 in the past 5 years prior to the visit to our clinic. She has tried behavior modifications such as talking to her husband when there was an urge to gamble, but had little success. In the year 2010, she was switched from modafinil to methylphenidate, which helped resolve gambling severity within a month. She was never restarted on modafinil after this as she did not want to risk having another episode of gambling again. On a follow-up visit the next year, she reported improvement in the compulsive gambling. She still had urges, but was able to exercise control over the impulses. In regard to her hypersomnolence symptoms, however, she had better results with modafinil. A more divided dose of methylphenidate was recommended during the visit. The patient has continued to take methylphenidate since 2010 and has had no reported side effects. She was taking a sustained dose of methylphenidate with good response. Impulse-control disorders (ICD) are characterized by excessive rumination and/or unwanted behaviors that lead to dysfunction or interference with work or social functioning.5 In a group of patients treated with dopaminergic agents, up to 17% of patients developed ICDs, of which 5% was pathological gambling. Mean time to onset of symptoms was 9.5 months.6 Modafinil is a non-amphetamine stimulant medication, and the exact mechanism of action is unknown.7 The wakefulness-promoting action useful in narcolepsy treatment could be due to activation of orexin neurons in the hypothalamus.6 In addition, modafinil has been shown to inhibit dopamine transporter and increase cortical and caudate dopamine concentrations.8 The effects of modafinil on impulse control are poorly studied. Zack and Poulos9 found that modafinil can have bidirectional effects on pathological gambling patients, ie, it can increase desire to gamble, disinhibition, and risky decision-making in low-impulsivity subjects, while decreasing these indexes in high-impulsivity subjects. In our patient, a previous history of gambling was not associated with disruption in her life. Moreover, there was no previous psychiatric comorbidity. She did not describe episodic hypersomnia, suggestive of Kleine-Levin syndrome, which commonly is associated with behavioral disturbances. However, the patient developed a new-onset pathological gambling and an inability to stop despite financial and social repercussions. Symptoms began after the use of modafinil, with significant improvement in gambling preoccupation and urges once the medication was stopped. While the majority of patients who develop ICDs while using dopaminergic agents for Parkinson’s disorder will have remission of symptoms, ICDs, particularly pathological gambling, can persist.10

Sleep Disturbances in Elderly Patients

To the Editor: Sleep disturbances commonly co-occur with mental disorders and often are sufficiently severe to warrant targeted treatment.1 Left untreated, sleep disturbances may exacerbate comorbid conditions and complicate recovery.2 Moreover, sleep disturbances are considered modifiable risk factors for onset and relapse of mental disorders.3 Numerous prospective longitudinal studies have demonstrated that the specific sleep disturbance of insomnia is a risk factor for psychiatric disorders and suicidal ideation or behavior.4–6 Very little work has been done to examine sleep disturbance as a risk factor for relapse within the context of acute psychiatric treatment within a partial hospital setting. The purpose of this retrospective chart review study was to examine the long-term follow-up over 18 months after discharge from a partial hospitalization program to determine if poor sleep quality at discharge predicts early readmission into the program. In our previous work,7 it was demonstrated that sleep improved for patients who completed this program. In this follow-up study, we examined whether patients with higher scores on the Pittsburgh Sleep Quality Index (PSQI)8 at discharge (indicating worse sleep quality) were at increased risk for rehospitalization, controlling for covariates related to mental health status. Method. The PSQI was completed by 183 patients at the time of entry into a psychiatry partial hospitalization program (typically lasting 1 month) and again at discharge. The PSQI is a self-report scale for measuring sleep quality and has shown evidence of good reliability and validity.8 A retrospective chart review was conducted to examine predictors of readmission over an 18-month follow-up period. The institutional review board of the Minneapolis VA Health Care System (Minneapolis, Minnesota) approved this study. Data were collected between November 2007 and March 2009. Results. The mean age of the patients was 48.2 years. Most participants were male (91.2%, n = 165), 152 (84.0%) were white, 56 (30.9%) were married, and 34 (18.8%) were currently employed. The mean number of mental health diagnoses (DSM-IV criteria) was 2.15. Poor sleep quality defined by a PSQI score ≥ 6 was significantly associated with readmission (P = .02), with 13.2% of patients with poor sleep quality readmitted compared to 0% with good sleep quality. As shown in Table 1, PSQI scores significantly predicted readmission over 18 months after controlling for covariates associated with mental health status, including total number of mental health diagnoses, employment status, marital status, age, and ethnicity (odds ratio = 2.10; 95% CI, 1.16–3.69). For every increase in 1 standard deviation on the PSQI, patients were twice as likely to be readmitted. Neither change in continuous PSQI scores nor change in categories based on clinical cutoffs over the course of treatment predicted readmission. Table 1. Step-Wise Multiple Logistic Regression Predicting Readmission to Psychiatry Partial Hospitalization Program 18 Months After Discharge Overall, we found that poor sleep quality at discharge is predictive of readmission to a partial hospitalization program, suggesting the need for a higher level of sleep-focused care during and following psychiatric admission. Our earlier work7 suggests that sleep disturbances did improve over the course of treatment, but change in sleep was not predictive of readmission. This study highlights the need to identify and treat patients who have poor sleep quality following intensive mental health treatment to support remission and recovery. There are several limitations to this study. First, covariates were determined from records and therefore are most likely less accurate than information obtained from diagnostic interviews. The data were also limited to dichotomous diagnoses; although this is not expected to introduce systematic bias regarding the direction and significance of the findings, it did prevent a more fine-grained analysis of continuous mental health symptom covariates for which sleep quality may be a proxy. Despite these limitations, this study is one of the first to evaluate the outcome following partial hospital treatment in those with poor sleep quality at discharge. This study highlights the importance of assessing poor sleep quality prior to discharge and incorporating behavioral or pharmacologic treatments for sleep disturbances into treatment planning.