Comparative effectiveness research trial for antidepressant incomplete and non-responders with treatment resistant depression (ASCERTAIN-TRD) a randomized clinical trial.

Further research is needed to help improve both the standard of care and the outcome for patients with treatment-resistant depression. A particularly critical evidence gap exists with respect to whether pharmacological or non-pharmacological augmentation is superior to antidepressant switch, or vice-versa. The objective of this study was to compare the effectiveness of augmentation with aripiprazole or repetitive transcranial magnetic stimulation versus switching to the antidepressant venlafaxine XR (or duloxetine for those not eligible to receive venlafaxine) for treatment-resistant depression. In this multi-site, 8-week, randomized, open-label study, 278 subjects (196 females and 82 males, mean age 45.6 years (SD 15.3)) with treatment-resistant depression were assigned in a 1:1:1 fashion to treatment with either of these three interventions; 235 subjects completed the study. 260 randomized subjects with at least one post-baseline Montgomery-Asberg Depression Rating (MADRS) assessment were included in the analysis. Repetitive transcranial magnetic stimulation (score change (standard error (se)) = -17.39 (1.3) (p = 0.015) but not aripiprazole augmentation (score change (se) = -14.9 (1.1) (p = 0.069) was superior to switch (score change (se) = -13.22 (1.1)) on the MADRS. Aripiprazole (mean change (se) = -37.79 (2.9) (p = 0.003) but not repetitive transcranial magnetic stimulation augmentation (mean change (se) = -42.96 (3.6) (p = 0.031) was superior to switch (mean change (se) = -34.45 (3.0)) on the symptoms of depression questionnaire. Repetitive transcranial magnetic stimulation augmentation was shown to be more effective than switching antidepressants in treatment-resistant depression on the study primary measure. In light of these findings, clinicians should consider repetitive transcranial magnetic stimulation augmentation early-on for treatment-resistant depression.Trial registration: ClinicalTrials.gov, NCT02977299.

Relationship between Sleep Problems and Self-Injury: A Systematic Review.

Objective/Background: Previous studies suggested that sleep problems were related to non-suicidal self-injury. The current systematic review investigated more thoroughly this relationship.Methods: PubMED and Embase databases were searched. The keywords were "self-injury" OR "self-harm" OR "non-suicidal self-injury" OR "self-injurious behavior" OR "self-destructive behavior" OR "self-mutilation" AND "sleep problem" OR "sleep disturbance" OR insomnia OR nightmare OR "poor sleep quality" or "sleep disorders." A total of 16 studies were included in the present review.Results: The pattern of results indicated that sleep problems such as short sleep duration, sleep disturbances, and poor sleep quality were associated with non-suicidal self-injury. Additionally, emotional dysregulation, depression, and post-traumatic stress disorder appeared to mediate this relationship. Above all adolescents and young adults with sleep disruptions were at higher risk of non-suicidal self-injury.Conclusions:g Interventions to improve sleep quality and sleep duration might concomitantly decrease the risk of non-suicidal self-injury.

Bedtime doses of prazosin do not affect daytime salivary amylase markers in PTSD.

Overactivity of the noradrenergic (NE) system within the central nervous system (CNS) has been postulated as a key pathophysiology of posttraumatic stress disorder (PTSD). The activity of the enzyme salivary α-amylase (sAA) has been proposed as an indirect measure of CNS NE activity, and sAA is elevated in PTSD. As an antagonist of the α-1 NE receptor, prazosin would be expected to alter sAA values in PTSD patients. However, given its short half-life, it is not clear whether bedtime doses would have an effect on daytime sAA. In the present study, we assayed daytime sAA in 20 suicidal PTSD patients who were randomized to prazosin versus placebo at bedtime-only, and found no effect in daytime sAA. These findings are consistent with studies showing an advantage for twice daily dosing of prazosin in PTSD.

Screening for suicide risk in adult sleep patients.

Outpatient visits for sleep-related difficulties and the rate of suicide in the United States have both increased by more than 20% since 1999. Research suggests that anywhere from 75% to 91% of suicide decedents had contact with a physician within the year prior to fatally attempting suicide. Although the prevalence of such contacts among sleep clinicians is unknown, it is important to note that sleep disturbances in general are both a risk factor and potential warning sign for suicide. Screening for suicide risk among sleep patients is recommended, especially among those with a history of psychiatric and chronic medical conditions. Using evidence-based screening tools, such as the Columbia suicide severity rating scale, when screening patients for suicide risk is recommended despite the need for more research on the efficacy of suicide screening. For sleep clinic professionals who do not have the time to comprehensively assess and manage suicide risk, they are encouraged to implement suicide prevention policies within their departments and clinics and to follow the best available evidence to inform these policies. A protocol for screening for suicide risk in sleep clinics is outlined along with triage and documentation recommendations.

A Pilot, Randomized Clinical Trial of Bedtime Doses of Prazosin Versus Placebo in Suicidal Posttraumatic Stress Disorder Patients With Nightmares.

PURPOSE/BACKGROUND: Observational studies show an association between nightmares and suicide. Prazosin is proposed as a nightmare treatment. This pilot, randomized clinical trial tested whether treatment of nightmares with prazosin would reduce suicidal ideas in suicidal posttraumatic stress disorder (PTSD) patients. METHODS/PROCEDURES: Twenty adult, suicidal PTSD patients with nightmares were blindly and randomly assigned 1:1 to escalating doses of prazosin versus placebo at bedtime only for 8 weeks. All participants had comorbid mood disorders and received stable doses of mood disorder medication. Outcomes of interest were measured weekly and included severity of suicidal ideation, nightmares, PTSD, insomnia, and depression. Longitudinal mixed-effects models assessed change in outcomes over time. FINDINGS/RESULTS: All psychometric measures improved over 8 weeks. However, nighttime measures of nightmares and insomnia showed significantly less improvement in the prazosin group, whereas there was no significant change in daytime measures of suicidal ideation and daytime-only PTSD symptoms. Two patients required emergency psychiatric hospitalization, but there were no suicide attempts and no deaths. IMPLICATIONS/CONCLUSIONS: This study confirmed an effect of nighttime-only prazosin on nighttime symptoms of insomnia and nightmares in suicidal PTSD patients who are experiencing nightmares. Surprisingly, the effect was in the direction opposite of what we expected. Furthermore, prazosin showed no signal on daytime measures including suicidal ideation. The results do not support a larger study of nighttime-only prazosin in suicidal PTSD patients but leave open the possibility of benefit from daytime administration of prazosin.

Paradoxical insomnia and subjective-objective sleep discrepancy: A review.

Paradoxical insomnia is characterized by discrepancy between subjective and objective assessments of sleep and is challenging to diagnosis and treat. Typically, polysomnographic (PSG) findings show significantly longer total sleep time than patients' report of sleep, and the difference between subjective and PSG sleep is greater than that seen in other insomnia subtypes. Subjective-objective sleep discrepancy may also present in different clinical pictures, as marked discrepancies between patients' perception of sleep and objective findings are common in a variety of medical, sleep and psychiatric disorders. However, there is a paucity of literature about the etiology and treatment of sleep discrepancy and paradoxical insomnia. Therefore, the underlying neurophysiological mechanisms of sleep discrepancy and paradoxical insomnia should be further investigated. Additionally, well-controlled clinical trials are needed to establish an evidence based intervention for treatment.

Neurogenetics of acute and chronic opiate/opioid abstinence: treating symptoms and the cause.

This review begins with a comprehensive history of opioid dependence and treatment in the United States. The focus is an evidence-based treatment model for opioid/opiate dependent individuals. The role of reward genetic polymorphisms and the epigenetic modifications that lead to vulnerability to use and misuse of opiates/opioid to treat pain are reviewed. The neurochemical mechanisms of acute opiate withdrawal and opiate/opioid reward mechanisms are explored with a goal of identifying specific treatment targets. Alterations in functional brain connectivity based on neurobiological mechanisms in heroin dependence and abstinence are also reviewed. A new clinical model an alternative to merely blocking acute withdrawal symptoms as identified in the DSM -5 is proposed. Genetic diagnosis at the onset of detoxification, to determine risk stratification, and identify polymorphic gene targets for pharmaceutical and nutraceutical interventions, followed by the simultaneous initiation of Medication Assisted Therapy (MAT), to enable psychological extinction, and steady pro-dopaminergic therapy with the goal of developing "dopamine homeostasis" is recommended. The objective of these interventions is to prevent future relapse by treating all "Reward Deficiency Syndrome" (RDS) behaviors and eventually make an addiction-free life possible.

Representations of ECT in English-Language Film and Television in the New Millennium.

OBJECTIVE: The aim of the study was to survey the media landscape to determine whether visual depictions of electroconvulsive therapy (ECT) are becoming more or less medically accurate in the new millennium. METHOD: English-language film and television shows depicting ECT were analyzed for patient demographics, administrator roles, indication, consent, anesthesia, paralytics, bite block, lead placement, electroencephalogram, and outcome. RESULTS: Thirty-nine ECT scenes were viewed, and just 3 included all 5 essential tools of modern ECT: anesthesia, paralytic, electrodes, electroencephalogram, and a bite block. CONCLUSIONS: Media depictions of ECT do not reflect current practice. Too often, ECT is portrayed as a torture technique rather than an evidenced-based therapy, and even in a therapeutic setting, it is too often shown with outdated techniques.

A multi-site randomized clinical trial to reduce suicidal ideation in suicidal adult outpatients with Major Depressive Disorder: Development of a methodology to enhance safety.

BACKGROUND/AIMS: Suicide is a major public health concern, yet there are very few randomized clinical trials that have been conducted to reduce suicidal ideation in patients at risk of suicide. We describe the rationale and refinements of such a trial that is designed to assess the effect of a hypnotic medication on suicidal ideation in adult outpatients currently experiencing suicidal ideation. METHODS: "Reducing Suicidal Ideation Through Insomnia Treatment" is a multi-site randomized clinical trial that includes three recruiting sites and one data management site. This 4-year study is in its second year of recruitment. The purpose of the study is to compare hypnotic medication versus placebo as an add-on treatment to a selective serotonin reuptake inhibitor as a means of reducing suicidal ideation in depressed adult outpatients with insomnia and suicidal ideation. The safety features of the study follow the 2001 National Institutes of Health guidelines for studies that include patients at risk of suicide. RESULTS: In total, 584 potential participants have undergone telephone screening; 67% of these failed the phone screen, most often due to an absence of expressed suicidal ideation (26% of the telephone screen fails). A total of 115 people appeared for a face-to-face baseline assessment, and 40 of these had completed a taper off of their ineffective psychotropic medications before the baseline assessments. In all, 64% of those who completed baseline assessments failed to proceed to randomization, most commonly because of no clinically significant suicidal ideation (51% of those excluded at baseline). One participant was offered and accepted voluntary psychiatric hospitalization in lieu of study participation. Thus far, 40 participants have been randomized into the study and 88.7% of scheduled visits have been attended, with 93.8% adherence to the selective serotonin reuptake inhibitor and 91.6% adherence to the randomized hypnotic versus placebo. None of the randomized participants have required hospitalization or had a suicide attempt. CONCLUSION: By carefully considering the inclusion and exclusion criteria and other safety features, the safe conduct of randomized clinical trials in suicidal adult patients is possible, including the inclusion of participants who have undergone a prescribed tapering off of psychotropic medications prior to baseline assessment.