An interlaboratory study to evaluate the utility of gas chromatography-mass spectrometry and gas chromatography-infrared spectroscopy spectral libraries in the forensic analysis of fentanyl-related substances.

Synthetic opioids such as fentanyl account for over 71,000 of the approximately 107,000 overdose deaths reported in the United States in 2021. Fentanyl remains the fourth most identified drug by state and local forensic laboratories, and the second most identified drug by federal laboratories. The unambiguous identification of fentanyl-related substances (FRS) is challenging due to the absence or low abundance of a molecular ion in a typical gas chromatography-mass spectrometry (GC-MS) analysis and due to a low number of fragment ions that are similar among the many potential isomers of FRS.

Longitudinal Course of Adverse Events With Esketamine Nasal Spray: A Post Hoc Analysis of Pooled Data From Phase 3 Trials in Patients With Treatment-Resistant Depression.

To describe the tolerability of esketamine nasal spray based on the adverse event profile observed during treatment sessions occurring early and later over the course of treatment. In 2 long-term, phase 3 studies (NCT02493868, October 1, 2015-February 16, 2018; NCT02497287, September 30, 2015-October 28, 2017), patients with treatment-resistant major depressive disorder (per ) and nonresponse to ≥ 2 oral antidepressants received esketamine nasal spray (56 or 84 mg) twice weekly during a 4-week induction phase, weekly for weeks 5-8, and weekly or every 2 weeks thereafter as maintenance treatment, in conjunction with a new oral antidepressant. A post hoc analysis using descriptive statistics evaluated occurrence (incidence, frequency, severity) and recurrence (incidence and severity) of events of specific interest.

Subanalysis of the CYP-GUIDES Trial: CYP2D6 Functional Stratification and Operational Timeline Selection.

CYP-GUIDES (Cytochrome Psychotropic Genotyping Under Investigation for Decision Support) was a Randomized Controlled Trial comparing 2 outcomes in hospitalized patients with major depressive disorder treated according to the patient's CYP2D6 genotype and functional status versus standard psychotropic therapy. The primary outcome was hospital Length of Stay (LOS) and the secondary was Re-Admission Rate (RAR) 30 days after discharge. Methodology, total results and database of the trial have been published.

Efficacy of Esketamine Nasal Spray Plus Oral Antidepressant Treatment for Relapse Prevention in Patients With Treatment-Resistant Depression: A Randomized Clinical Trial.

Importance: Controlled studies have shown short-term efficacy of esketamine for treatment-resistant depression (TRD), but long-term effects remain to be established.

Objective: To assess the efficacy of esketamine nasal spray plus an oral antidepressant compared with an oral antidepressant plus placebo nasal spray in delaying relapse of depressive symptoms in patients with TRD in stable remission after an induction and optimization course of esketamine nasal spray plus an oral antidepressant.

Design, Setting, And Participants: In this phase 3, multicenter, double-blind, randomized withdrawal study conducted from October 6, 2015, to February 15, 2018, at outpatient referral centers, 705 adults with prospectively confirmed TRD were enrolled; 455 entered the optimization phase and were treated with esketamine nasal spray (56 or 84 mg) plus an oral antidepressant.

The Opioid Epidemic: Moving Toward an Integrated, Holistic Analytical Response.

In many jurisdictions, public safety and public health entities are working together to enhance the timeliness and accuracy of the analytical characterization and toxicology testing of novel synthetic opioids. The improved sharing and early detection of these analytical data are intended to inform surveillance, interdiction efforts, patient intervention and treatment, all of which are critical to curbing the opioid epidemic. Forensic practitioners working to identify novel synthetic opioids struggle to provide timely results when encountering new or unknown substances, such as the fentanyl analogs.

Efficacy and Safety of Intranasal Esketamine Adjunctive to Oral Antidepressant Therapy in Treatment-Resistant Depression: A Randomized Clinical Trial.

Importance: Approximately one-third of patients with major depressive disorder (MDD) do not respond to available antidepressants.

Objective: To assess the efficacy, safety, and dose-response of intranasal esketamine hydrochloride in patients with treatment-resistant depression (TRD).

Design, Setting, And Participants: This phase 2, double-blind, doubly randomized, delayed-start, placebo-controlled study was conducted in multiple outpatient referral centers from January 28, 2014, to September 25, 2015.

Sleep Patterns and Neuropsychiatric Symptoms in Hospitalized Patients With Dementia.

The authors examined 28 dementia inpatients receiving treatment as usual. Beginning-to-end differences in neuropsychiatric symptoms and actigraphic sleep patterns were measured. Using a mixed-model, the authors regressed neuropsychiatric symptoms on average sleep minutes (between-subjects effect) and each night's deviation from average (within-subject effect).

The neurologist's role in supporting transition to adult health care: A consensus statement.

The child neurologist has a critical role in planning and coordinating the successful transition from the pediatric to adult health care system for youth with neurologic conditions. Leadership in appropriately planning a youth's transition and in care coordination among health care, educational, vocational, and community services providers may assist in preventing gaps in care, delayed entry into the adult care system, and/or health crises for their adolescent patients. Youth whose neurologic conditions result in cognitive or physical disability and their families may need additional support during this transition, given the legal and financial considerations that may be required.

A Double-Blind, Randomized, Placebo-Controlled, Dose-Frequency Study of Intravenous Ketamine in Patients With Treatment-Resistant Depression.

Objective: Ketamine, an N-methyl-d-aspartate glutamate receptor antagonist, has demonstrated a rapid-onset antidepressant effect in patients with treatment-resistant depression. This study evaluated the efficacy of twice- and thrice-weekly intravenous administration of ketamine in sustaining initial antidepressant effects in patients with treatment-resistant depression.

Method: In a multicenter, double-blind study, adults (ages 18-64 years) with treatment-resistant depression were randomized to receive either intravenous ketamine (0.

Sleep Disturbances in Schizophrenia.

Sleep disturbances are prevalent in patients with schizophrenia and play a critical role in the morbidity and mortality associated with the illness. Subjective and objective assessments of sleep in patients with schizophrenia have identified certain consistent findings. Findings related to the sleep structure abnormalities have shown correlations with important clinical aspects of the illness.

The Relationship Between Sleep Disturbances and Psychiatric Disorders: Introduction and Overview.

Changes in the psychiatric diagnostic guidelines with the transition from Diagnostic and Statistical Manual of Mental Disorders (DSM)-IV to DSM-V include acknowledgment that primary sleep disorders such as insomnia can occur in conjunction with medical and psychiatric disorders. This change in viewpoint regarding the definition of primary sleep disorders opens the way to the recognition that patients with psychiatric disorders demonstrate a high prevalence of sleep disturbances, with complaints of insomnia and excessive daytime sleepiness being especially commonly reported. Recent investigations have pointed to a bidirectional relationship between sleep disturbances and psychiatric disorders.

A 12-week, randomized, double-blind, placebo-controlled, sequential parallel comparison trial of ziprasidone as monotherapy for major depressive disorder.

Objective: To study ziprasidone monotherapy for major depressive disorder, defined according to the DSM-IV.

Method: One hundred twenty outpatients were enrolled between June 2008 and September 2010 in a 12-week study that was divided into two 6-week periods according to the sequential parallel comparison design. Patients were randomized in a 2:3:3 fashion to receive ziprasidone for 12 weeks, placebo for 6 weeks followed by ziprasidone for 6 weeks, or placebo for 12 weeks.

Thyrotropin-releasing hormone as a treatment for cancer-related fatigue: a randomized controlled study.

Background: Fatigue is a common and often disabling symptom for cancer patients. To date, no pharmacological interventions have shown reliable efficacy in treatment of cancer-related fatigue (CF). Thyrotropin-releasing hormone (TRH), a key regulator of homeostasis, exerts arousing and analeptic actions in instances of behavioral depression.

Thyrotropin-releasing hormone can relieve cancer-related fatigue: hypothesis and preliminary observations.

Fatigue in cancer patients is highly prevalent, predominantly idiopathic, difficult to manage, and has a significant negative impact on quality of life. Thyrotropin-releasing hormone (TRH) exerts normotrophic, state-dependent therapeutic effects in a variety of experimental and clinical situations. To evaluate TRH as a treatment for cancer-related fatigue, an ongoing randomized, placebo-controlled, crossover pilot study of breast cancer patients has been initiated and this report presents preliminary observations conducted with three of these patients over 4 consecutive weeks, thereby involving a total of six TRH treatments and six saline controls.

New approaches for the treatment of sleep disorders.

Epidemiological studies have established that sleep disorders are common and often untreated. Besides having a negative impact on overall health, these conditions can significantly disrupt normal daily functions. While a number of drugs are employed in the treatment of sleep disorders, safety, tolerability, and variable efficacy limit their utility.

The thyrotropin-releasing hormone (TRH)-immune system homeostatic hypothesis.

Decades of research have established that the biological functions of thyrotropin-releasing hormone (TRH) extend far beyond its role as a regulator of the hypothalamic-pituitary-thyroid axis. Gary et al. [Gary, K.

Thyrotropin-releasing hormone (TRH) in the neuroaxis: therapeutic effects reflect physiological functions and molecular actions.

Nearly four decades of research have yielded thousands of publications on the physiology, pharmacology and therapeutic effects of TRH and TRH mimetic analogs. This work addresses both the neuroendocrine and the extrahypothalamic actions and functions of the tripeptide. The many reports of clinical effects of TRH in diverse medical conditions, unrelated to pituitary or thyroid function, can appear bewildering, as can its widespread involvement in a plethora of neuronal and physiological processes.

Effects of psychiatric medications on sleep and sleep disorders.

Insomnia is a significant public health concern that has prompted substantial efforts to develop treatment and management strategies. A significant proportion of complaints of insomnia are related to psychiatric conditions such as anxiety disorders and depression, and treatments for these disorders are known to exert both direct and indirect benefits on sleep as well as some negative effects on sleep and sleep physiology. Insomnia is also a prominent symptom of a number of other psychiatric disorders, including schizophrenia and bipolar disorder.

Self-criticism and depressive symptomatology interact to predict middle school academic achievement.

Although previous research has implicated adolescent depression in academic difficulties, few studies have explored the role of cognitive/personality factors in this area. To address this gap, the present study examines the role of self-criticism in academic functioning among early adolescent students over a 1-year interval. We hypothesized and found that adolescent self-criticism and depressive symptomatology interacted to predict decreased grade point average (GPA) over time, an interaction that was found predominantly in boys.

Rapid antidepressant response after nocturnal TRH administration in patients with bipolar type I and bipolar type II major depression.

Background: Thyrotropin-releasing hormone (TRH) is a tripeptide that produces endocrine and behavioral effects in animals and humans. Some studies have shown transient antidepressant activity after morning administration of TRH. We hypothesized that nocturnal administration of TRH, when the circadian sensitivity of the TRH receptor is at its peak, may result in a more robust antidepressant effect.

Amantadine for weight gain associated with olanzapine treatment.

Patients with schizophrenia (Sch), schizoaffective, schizophreniform, or bipolar (BP) I disorders [Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV)]; not manic or acutely psychotic [Brief Psychiatric Rating Scale (BPRS) total score < or =45]; treated with olanzapine for 1-24 months; and who had gained > or =5% of their initial body weight were examined to determine whether amantadine could attenuate weight gain or promote weight loss. Olanzapine (Olz; 5-20 mg/day) was co-administered with double-blind treatment of 100-300 mg/day amantadine (Olz+Amt, n=60) or placebo (Olz+Plc, n=65). Visit-wise analysis of weight showed that weight change from baseline [last-observation-carried-forward (LOCF)] in the Olz+Amt group was significantly different from the Olz+Plc group at weeks 8 (P=0.

Demonstration of the efficacy and safety of a novel substance P (NK1) receptor antagonist in major depression.

The efficacy and safety of a selective NK(1) antagonist, L-759274, was investigated in outpatients with diagnosis of major depressive disorder with melancholic features, following evidence obtained with the novel compound aprepitant that Substance P (NK(1)) antagonists may provide a unique mechanism of antidepressant activity. A randomized, double-blind placebo-controlled study was carried out. Patients, male or female, aged 18-60, scoring >/=25 points on total of first 17 items of 21-item Hamilton Depression Scale (HAMD), and scoring >/=4 (moderately ill) on Clinical Global Impressions-Severity Scale were randomized to oral L-759274 40 mg daily (n=66) or placebo (n=62) for 6 weeks.

Comparative effects of mirtazapine and fluoxetine on sleep physiology measures in patients with major depression and insomnia.

Background: Sleep complaints are common in patients with major depressive disorder (MDD). Both MDD and antidepressant drugs characteristically alter objective sleep measures. This study compares the effects of mirtazapine and fluoxetine on sleep continuity measures in DSM-IV MDD patients with insomnia.

The thyrotropin-releasing hormone (TRH) hypothesis of homeostatic regulation: implications for TRH-based therapeutics.

The functions of thyrotropin-releasing hormone (TRH) in the central nervous system (CNS) can be conceptualized as performed by four anatomically distinct components that together comprise a general TRH homeostatic system. These components are 1) the hypothalamic-hypophysiotropic neuroendocrine system, 2) the brainstem/midbrain/spinal cord system, 3) the limbic/cortical system, and 4) the chronobiological system. We propose that the main neurobiological function of TRH is to promote homeostasis, accomplished through neuronal mechanisms resident in these four integrated systems.