Treating sleep disorders following traumatic brain injury in adults: Time for renewed effort?

Traumatic brain injury (TBI) disrupts normal brain function and can lead to chronic symptoms of sleep disturbance, pain, irritability, and depression. Sleep disorders occur in 30-70% of individuals who have experienced TBI. Disturbed sleep impairs the recovery process and may exacerbate other issues that arise because of brain injury (e.g., headaches, depression). Noticeable benefits have been reported when sleep problems due to TBI are addressed and treated; for instance, treating post-TBI insomnia reduces the expression of inflammatory genes, potentially reducing ongoing neurological damage. In this review, we discuss twenty-four randomised clinical trials (RCT) published to date (August 2021), exploring interventions for sleep disturbances resulting from TBI. Treatment effects were observed for insomnia, circadian rhythm disorders, hypersomnia, and general sleep disturbance. However, the evidence remains limited and significant methodological issues are discussed with a recommendation for further research.

Adjunctive Ketamine With Relapse Prevention-Based Psychological Therapy in the Treatment of Alcohol Use Disorder.

OBJECTIVE: Early evidence suggests that ketamine may be an effective treatment to sustain abstinence from alcohol. The authors investigated the safety and efficacy of ketamine compared with placebo in increasing abstinence in patients with alcohol use disorder. An additional aim was to pilot ketamine combined with mindfulness-based relapse prevention therapy compared with ketamine and alcohol education as a therapy control. METHODS: In a double-blind placebo-controlled phase 2 clinical trial, 96 patients with severe alcohol use disorder were randomly assigned to one of four conditions: 1) three weekly ketamine infusions (0.8 mg/kg i.v. over 40 minutes) plus psychological therapy, 2) three saline infusions plus psychological therapy, 3) three ketamine infusions plus alcohol education, or 4) three saline infusions plus alcohol education. The primary outcomes were self-reported percentage of days abstinent and confirmed alcohol relapse at 6-month follow-up. RESULTS: Ninety-six participants (35 women; mean age, 44.07 years [SD=10.59]) were included in the intention-to-treat analysis. The treatment was well tolerated, and no serious adverse events were associated with the study drug. Although confidence intervals were wide, consistent with a proof-of-concept study, there were a significantly greater number of days abstinent from alcohol in the ketamine group compared with the placebo group at 6-month follow-up (mean difference=10.1%, 95% CI=1.1, 19.0), with the greatest reduction in the ketamine plus therapy group compared with the saline plus education group (15.9%, 95% CI=3.8, 28.1). There was no significant difference in relapse rate between the ketamine and placebo groups. CONCLUSIONS: This study demonstrated that treatment with three infusions of ketamine was well tolerated in patients with alcohol use disorder and was associated with more days of abstinence from alcohol at 6-month follow-up. The findings suggest a possible beneficial effect of adding psychological therapy alongside ketamine treatment.

The acute effects of alcohol on state rumination in the laboratory.

RATIONALE: Rumination is a repetitive, negative, self-focused thinking style associated with various forms of psychopathology. Recent studies suggest that rumination increases craving for alcohol and predicts harmful drinking and alcohol-related problems. However, the acute effects of alcohol on rumination have not been previously studied. It is proposed that alcohol may reduce ruminative thinking through decreasing negative mood. OBJECTIVES: In the present study, we aimed to test the previously unexplored effects of acute alcohol consumption on rumination in a hazardous drinking population. METHODS: We conducted a randomised placebo-controlled laboratory study to examine the effect of low (0.4 g kg-1) and high doses (0.8 g kg-1) of alcohol on state rumination compared to placebo. Participants completed a rumination induction task prior to receiving drinks. We then measured state rumination and mood at repeated time points; 30 min, 60 min and 90 min post-drinks consumption. RESULTS: We found a significant decrease in state rumination in the low-dose alcohol group compared to placebo at 30 min post-alcohol consumption, but no difference was observed between the high-dose alcohol and placebo groups. Mediation analysis provided evidence for an indirect effect of alcohol on state rumination through concurrent changes in negative mood. CONCLUSIONS: These findings suggest that acute alcohol consumption can regulate negative mood and concurrently rumination, providing preliminary evidence for the role of rumination in alcohol use disorders. Rumination may be a treatment target in alcohol use disorders.

Utility of measuring CSF hypocretin-1 level in patients with suspected narcolepsy.

OBJECTIVES: The patho-aetiology of narcolepsy Type I (NT1) is the loss of hypocretin-1 secreting neurons in the hypothalamus. Diagnostic criteria for NT1 include excessive daytime sleepiness (EDS) for at least three months not explained by any other condition, cataplexy and cerebrospinal fluid (CSF) hypocretin-1 concentrations lower than 110 pg/ml. In this study we evaluated the utility of measuring CSF hypocretin-1 levels in patients with suspected narcolepsy (N). METHODS: The study included 29 consecutively recruited patients at a tertiary sleep centre presenting with EDS for exclusion of N. All patients were examined using an extensive clinical interview followed by two weeks of actigraphy and sleep diary recordings, polysomnography (PSG) and multiple sleep latency testing (MSLT). Additionally, HLA-typing, urinary screening for substances of abuse and a lumbar puncture to measure CSF hypocretin-1 expression using radioimmunoassay were carried out. RESULTS: In sum, 19 patients (66%) had a CSF hypocretin-1 level <110 pg/ml, of whom two had current severe depression without any features of narcolepsy except EDS. The predictive potential of hypocretin-1 measurement in diagnosing narcolepsy revealed a positive predictive value (PPV) of 89%, a specificity of 83%, with both negative predictive value (NPV) and sensitivity equal to 100%. CONCLUSIONS: Despite a high sensitivity and specificity, the MSLT is not always a reliable diagnostic test for narcolepsy and where this uncertainty exits, CSF hypocretin-1 concentrations <110 pg/ml can be useful. However, due to a lower PPV and specificity at this cut-off, it may also not be entirely reliable as a stand-alone diagnostic test, particularly in the context of severe depression.

Evidence for the efficacy of melatonin in the treatment of primary adult sleep disorders.

Melatonin is a physiological hormone involved in sleep timing and is currently used exogenously in the treatment of primary and secondary sleep disorders with empirical evidence of efficacy, but very little evidence from randomised, controlled studies. The aim of this meta-analysis was to assess the evidence base for the therapeutic effects of exogenous melatonin in treating primary sleep disorders. An electronic literature review search of MEDLINE (1950-present) Embase (1980- present), PsycINFO (1987- present), and Scopus (1990- present), along with a hand-searching of key journals was performed in July 2013 and then again in May 2015. This identified all studies that compared the effect of exogenous melatonin and placebo in patients with primary insomnia, delayed sleep phase syndrome, non 24-h sleep wake syndrome in people who are blind, and rapid eye movement-behaviour disorder. Meta-analyses were performed to determine the magnitude of effect in studies of melatonin in improving sleep. A total of 5030 studies were identified; of these citations, 12 were included for review based on the inclusion criteria of being: double or single-blind, randomised and controlled. Results from the meta-analyses showed the most convincing evidence for exogenous melatonin use was in reducing sleep onset latency in primary insomnia (p = 0.002), delayed sleep phase syndrome (p < 0.0001), and regulating the sleep-wake patterns in blind patients compared with placebo. These findings highlight the potential importance of melatonin in treating certain first degree sleep disorders. The development of large-scale, randomised, controlled trials is recommended to provide further evidence for therapeutic use of melatonin in a variety of sleep difficulties.

Does personality play a role in continuous positive airway pressure compliance?

KEY POINTS: Continuous positive airway pressure (CPAP) adherence is low among individuals with obstructive sleep apnoea.Type D personality and high scores on the depression and hypochondriasis scales on the Minnesota Multiphasic Personality Inventory (MMPI) have been identified as factors contributing to non-compliance with CPAP.Further research into personality type may assist in understanding why some people adhere to CPAP, while others fail.Obstructive sleep apnoea (OSA) is a condition characterised by repetitive, intermittent partial or complete collapse/obstruction of the upper airway during sleep. Continuous positive airway pressure (CPAP) is highly efficacious in treating OSA but its effectiveness is limited due to suboptimal acceptance and adherence rates, with as many as 50% of OSA patients discontinuing CPAP treatment within the first year. Until recently, research has focused on examining mechanistic and demographic factors that could explain nonadherence (e.g. age, sex, race and education level) with limited applicability in a prospective or clinical manner. More recent research has focused on personality factors or types of patients with OSA who comply and do not comply with CPAP adherence in an attempt to enhance the accuracy of predicting treatment compliance. Type D personality has been found to be prevalent in one third of patients with OSA. The presence of Type D personality increases noncompliance and poor treatment outcomes due to negative affectivity, social inhibition, unhealthy lifestyle, and a reluctance to consult and/or follow medical advice. Conversely, individuals who are more likely to adhere to CPAP treatment tend to have a high internal locus of control and high self-efficacy, self-refer for treatment, and have active coping skills. By assessing personality and coping skills, the clinician may gain insight into the likelihood of a patient's adherence to treatment. If the patient displays potential risk factors for CPAP noncompliance, the clinician can offer the patient education, refer them to a support group, engage in behavioural/motivational therapy and undertake regular follow-up visits or phone calls incorporating troubleshooting to increase CPAP adherence, especially in individuals with Type D personality.

Misdiagnosis of narcolepsy.

BACKGROUND: Narcolepsy is a chronic primary sleep disorder, characterized by excessive daytime sleepiness and sleep dysfunction with or without cataplexy. Narcolepsy is uncommon, with a low prevalence rate which makes it difficult to diagnose definitively without a complex series of tests and a detailed history. The aim of this study was to review patients referred to a tertiary sleep centre who had been labelled with a diagnosis of narcolepsy prior to referral in order to assess if the diagnosis was accurate, and if not, to determine the cause of diagnostic misattribution. METHODS: All patients seen at a sleep centre from 2007-2013 (n = 551) who underwent detailed objective testing including an MSLT PSG, as well as wearing an actigraphy watch and completing a sleep diary for 2 weeks, were assessed for a pre-referral and final diagnosis of narcolepsy. RESULTS: Of the 41 directly referred patients with a diagnostic label of narcolepsy, 19 (46 %) were subsequently confirmed to have narcolepsy on objective testing and assessment by a sleep physician using ICSD-2 criteria. CONCLUSIONS: The diagnosis of narcolepsy was incorrectly attributed to almost 50 % of patients labelled with a diagnosis of narcolepsy who were referred for further opinion by a variety of specialists and generalists. Accurate diagnosis of narcolepsy is critical for many reasons, such as the impact it has on quality of life, driving, employment, insurance and pregnancy in women as well as medication management.

Career progress in online and blended learning environments.

OBJECTIVE: The authors examined the career achievement of early- and mid-career researchers in social, behavioral, and mental health who participated in a career-development conference. METHOD: Trainees participated in a career-development conference either through attending a live conference supplemented with an online version of the conference (Combined: N=46) or through the online version of the conference alone (Web-Only: N=60). An objective measure tracked the trainees' publications, involvement in research projects, honors and grant awards, collaborations, and scientific presentations before and 9 months after participation in the career-development conference. RESULTS: Statistical analysis showed that trainees improved for each category measured, with no significant differences across the Combined and Web-Only groups. The strongest variable affecting improvement was Time, and the most significant time effect was seen in the production of presentations and publications. A significant Gender difference was present, with women showing greater total career progress than men. CONCLUSION: Career-development conferences can support career growth for trainees. Online training provides a cost-effective and time-efficient alternative to in-person methods, while still enhancing key markers of career progress.