Preservation of Muscle during Treatment for Obesity in Adults with Intellectual Disabilities.

OBJECTIVES: Adults with intellectual disabilities will frequently experience sedentary behavior and excessive weight, which may cause or exacerbate a multitude of medical and behavioral problems. This study examined a program to encourage increased activity and weight loss in an outpatient service for adults with intellectual disabilities. METHODS: Behavioral methods were used to treat obesity in 33 male and 21 female adults with intellectual disabilities for a mean of 9 months. They were retrospectively analyzed to determine the effects of treatment on muscle and adiposity using body composition analysis. RESULTS: The 54 participants of the original 122 (44.3%) who did not drop out were divided into three groups: weight loss ≥3 kg/3% (n = 20, 37%), weight loss <3 kg/3% (n = 17, 31.5%), and no weight loss or weight gain (n = 17, 31.5%). Only men and women who lost ≥3 kg/3%, demonstrated significant gain of relative muscle mass. Those who gained weight lost muscle mass. CONCLUSIONS: If motivation remains high and follow-up is reasonably long, then a multicomponent obesity treatment program can lead to significant weight loss with preservation of muscle in adults with intellectual disabilities.

Concept article: Antidepressant-induced destabilization in bipolar illness mediated by serotonin 3 receptor (5HT3).

OBJECTIVES: Antidepressants used by patients with bipolar disorder have been associated with destabilization with an increase in mania, depression, and cycling. The most commonly proposed mechanism, that antidepressants 'overshoot' their antidepressant effect to create a manic or mixed state, is unlikely since antidepressants have actually been found to be ineffective in treating bipolar depression. Beginning with known bipolar-specific pathophysiologic abnormalities provides the greatest likelihood of insight. METHODS: PubMed was queried with 'bipolar', 'sodium', 'intracellular sodium', 'serotonin 3', '5HT3', '5-hydroxytryptamine type 3 receptors', and 'antidepressant' either individually or in combination. RESULTS: Pathologic mood states (both mania and depression) are associated with increased intracellular sodium (Na) concentrations that depolarize the resting membrane potential to increase cellular excitability (mania) or cause depolarization block (depression). Stimulation of the serotonin (5HT) receptors depolarizes the post-synaptic neuron. Stimulation of 5HT3 may be of particular importance since it is coupled to a cation channel that directly depolarizes the membrane. These effects directly impact the physiology of patients with bipolar disorder to alter neuronal excitability in a fashion that worsens both mania and depression. PROPOSED CONCEPT: The most consistently observed biological abnormality in individuals going through mania or bipolar depression involves a decline in Na pump activity, with consequent elevation of intracellular Na levels. Antidepressant treatment potentiates this, particularly by activation of 5HT3. This hypothesis can be tested by coadministering a 5HT3 antagonist (e.g., vortioxetine or ondansetron) to achieve blockade of that receptor while treating bipolar depression with a serotoninergic antidepressant.

An overview of the efficacy and safety of brexpiprazole for the treatment of schizophrenia in adolescents.

INTRODUCTION: The onset of psychotic symptoms occurs prior to age 19 in 39% of the patients with schizophrenia. There are limited approved treatment options for adolescents with schizophrenia. Brexpiprazole was approved by the United States Food and Drug Administration (FDA) for treatment of schizophrenia in adolescents in 2022. AREAS COVERED: Extrapolation of adult data to youth and use of pharmacologic modeling coupled with open long-term safety data were used by the FDA to approve brexpiprazole for adolescent schizophrenia. They were all reviewed herein. EXPERT OPINION: D2 receptor partial agonist antipsychotic agents are preferred in the early phase of treatment of psychotic disorders. Approval of brexpiprazole in adolescent schizophrenia provides an additional option. Brexpiprazole was approved by the FDA on the basis of extrapolation of adult data without controlled trials in adolescents. This reduces placebo exposure in young people. Two previous agents (asenapine and ziprasidone) approved for adult schizophrenia failed to separate from placebo in adolescent schizophrenia studies; this partially undermines the process of extrapolation. For brexpiprazole, the paucity of data in adolescents relegates it to a second-line agent. More research on brexpiprazole is needed to delineate its relative role in the management of adolescent schizophrenia.

KIOS: A smartphone app for self-monitoring for patients with bipolar disorder.

OBJECTIVES: This study examined the use of a self-monitoring/self-management smartphone application (app) for patients with bipolar disorder. The app was specifically designed with patient-centered computational software system based on concepts from nonlinear systems (chaos) theory. METHODS: This was a randomized, active comparator study of use of the KIOS app compared to an existing free app that has high utilization rates known as eMoods, over 52 weeks, and performed in three academic centers. Patients were evaluated monthly utilizing the Bipolar Inventory of Symptoms Schedule (BISS). The primary outcome measure was the persistence of using the app over the year of the study. RESULTS: Patients assigned to KIOS persisted in the study longer than those assigned to eMoods; 57 patients (87.70%) in the KIOS group versus 42 (73.69%) in the eMoods group completed the study (p = 0.03). By 52 weeks, significantly more of KIOS group (84.4%) versus eMoods group (54%) entered data into their programs (χ2 = 14.2, df = 1, p = 0.0002). Patient satisfaction for KIOS was greater (F = 5.21, df = 1, 108, p = 0.025) with a standardized effect size (Cohen's d) of 0.41. There was no difference in clinical outcome at the end of the study between the two groups. CONCLUSIONS: This is the first randomized comparison study comparing two apps for the self-monitoring/self-management of bipolar disorder. The study revealed greater patient satisfaction and greater adherence to a patient-centered software program (KIOS) than a monitoring program that does not provide feedback (eMoods).

Protest behaviors among patients placed in seclusion in a psychiatric emergency service.

BACKGROUND: Patients placed in seclusion for behavioral dyscontrol often perceive that the health care team is treating them inappropriately. These patients may express their indignation in many ways. To better characterize these behaviors, we conducted a study of protest behaviors in a psychiatric emergency service. METHODS: Video surveillance of seclusion room occupants is routinely reviewed as part of our safety protocol. For 1 month in 2022, we noted the frequency and timing of potential protest behaviors such as disrobing and evacuation. Descriptive statistics were applied. RESULTS: A total of 41 seclusion events (8.1%) occurred over the surveillance period, which included 504 initial emergency psychiatric evaluations. Six patients (14.6%) engaged in protest behaviors (all within 5 minutes of being placed in seclusion), including 3 (7.3%) who urinated and 3 (7.3%) who disrobed. One patient urinated almost immediately (2.4%), and another urinated 25 minutes after entering seclusion; the latter was not interpreted as a protest behavior. CONCLUSIONS: Immediate behaviors in seclusion that are different from behaviors that led to seclusion can be interpreted as protest behaviors. The 2 most often observed protest behaviors were urination and disrobing.

Biological rhythms are correlated with Na+, K+-ATPase and oxidative stress biomarkers: A translational study on bipolar disorder.

BACKGROUND: Bipolar disorder (BD) is a chronic, severe, and multifactorial psychiatric disorder. Although biological rhythms alterations, sodium potassium pump (Na+, K+-ATPase) changes, and oxidative stress appear to play a critical role in the etiology and pathophysiology of BD, the inter-connection between them has not been described. Therefore this study evaluated the association between biological rhythms, Na+, K+-ATPase, and oxidative stress parameters in BD patients and the preclinical paradoxical sleep deprivation model (PSD). METHODS: A translational study was conducted, including a case-control protocol with 36 BD and 46 healthy controls (HC). Subjects completed the Biological Rhythm Interview of Assessment in Neuropsychiatry (BRIAN). In addition, Erythrocyte Na+, K+-ATPase activity, and oxidative and nitrosative stress markers were assessed (4-hydroxynonenal [4-HNE], 8-isoprostane [8-ISO], thiobarbituric acid reactive substances [TBARS], carbonyl, 3-nitrotyrosine [3-nitro]). In the preclinical protocol, the same biomarkers were evaluated in the frontal cortex, hippocampus, and striatum from mice submitted to the PSD. RESULTS: BD patients had a significantly higher total score of BRIAN versus HCs. Additionally, individuals with BD showed decreased Na+, K+-ATPase activity and increased oxidative stress parameters compared to HC without psychiatric disorders. This difference was driven by actively depressed BD subjects. The mice submitted to the PSD also demonstrated decreased Na+, K+-ATPase activity and increased oxidative stress parameters. LIMITATIONS: BRIAN biological underpinning is less well characterized; We did not control for medication status; Sample size is limited; PSD it is not a true model of BD. CONCLUSIONS: The present study found a significant correlation between Na+, K+-ATPase and oxidative stress with changes in biological rhythms, reinforcing the importance of these parameters to BD.

Evaluating lumateperone for its use in treating depressive episodes associated with bipolar I or II disorder in adults.

INTRODUCTION: Lumateperone is a novel antipsychotic medication that has recently received approval by the United States Food and Drug Administration for treatment of major depressive episodes of type I and II bipolar disorder. It is approved for use as monotherapy or as an adjunctive treatment to lithium or valproic acid. AREAS COVERED: Clinical trials performed with lumateperone for bipolar disorder were reviewed. Additionally, pharmacodynamic actions of lumateperone are reviewed. Lumateperone is superior to placebo whether used alone or in combination with a mood stabilizer in patients with type I or type II bipolar disorder. It achieves this effect with minimal dopamine blockade-related side effects due to less than 50% dopamine D2 receptor occupancy. While the pharmacodynamic profile of lumateperone is unique, the mechanism of action in bipolar depression remains obscure. EXPERT OPINION: Lumateperone is an antipsychotic with full antagonist effects at the post-synaptic D2, and partial agonist effects at the presynaptic D2. This unique profile allows for both antipsychotic and antidepressant effects at the same dose, which does not produce dopamine-related side effects. Consequently, lumateperone is exceptionally well tolerated compared to other antidepressant-acting antipsychotic agents. It is now the only agent approved as an adjunct to the mood stabilizer for bipolar II depression.

Xanomeline-Trospium and Muscarinic Involvement in Schizophrenia.

Schizophrenia is a severe mental illness that has its onset in late adolescence or early adulthood and is associated with significant dysfunction across multiple domains. The pathogenesis of schizophrenia remains unknown, but physiologic understanding of the illness has been driven by the dopamine hypothesis. However, acetylcholine (ACh) clearly plays a role with mixed results regarding effect on psychosis. Selective muscarinic M1 and M4 agonists, such as xanomeline, originally developed to aid in cognitive loss with Alzheimer's, showed promise in proof-of-concept study in 20 patients with schizophrenia. Unfortunately, tolerability problems made muscarinic agonists impractical in either condition. However, coadministration of trospium, a lipophobic, non-selective muscarinic antagonist previously used for the treatment of overactive bladder, with xanomeline resulted in a significant reduction of cholinergic adverse effects. A recent randomized, placebo-controlled study of the antipsychotic effects of this combination in 182 patients with acute psychosis revealed improved tolerability with 80% of subjects staying to the end of the 5 weeks study. At the end of the trial, the treatment group saw a -17.4 change in the positive and negative symptom scale (PANSS) score from baseline compared to a -5.9 change in the placebo arm (P < 0.001). Furthermore, the negative symptom subscore, was also superior in the active arm (P < 0.001). These early studies are exciting because they suggest that the cholinergic system may be recruited to treat a severe and disabling disorder with suboptimal treatment options. Xanomeline-trospium combination is currently in phase III studies.

Narrative review of the advances in the pharmacotherapeutic management of juvenile-onset schizophrenia.

INTRODUCTION: Schizophrenia usually begins with prodromal symptoms in adolescence. In 39% of patients, onset of psychotic symptoms occurs prior to age 19. Advances in the treatment of psychosis with medications over the last decade are reviewed in this paper. AREAS COVERED: Understanding how to prescribe antipsychotics early in schizophrenia requires an understanding of the pathophysiology of the disease. The current structure of the dopamine hypothesis is reviewed. Risperidone, paliperidone, olanzapine, quetiapine, and aripiprazole have become established treatments prior to 2012. Since 2012, lurasidone (2017) and brexpiprazole (2022) have also been approved. Lurasidone was approved based on placebo-controlled studies, but brexpiprazole has been approved on the bases of open safety trials. In comparative trials, aripiprazole was better tolerated and less likely to cause hyperprolactinemia and metabolic abnormalities. EXPERT OPINION: Antipsychotics can induce adaptive changes in the brain that predispose patients to future problems such as tardive dyskinesia and supersensitivity psychosis. When pathophysiology of schizophrenia, and a clear understanding of the pharmacology of existing antipsychotics are included in the evidence-based analysis, use of partial agonists, which are less likely to induce adaptive changes in the brain and less likely to induce metabolic and prolactin side effects, become the preferred agents.

Catatonia Secondary to Depolarization Block.

Catatonia is a severe psychomotor disorder that is associated with a 60-fold increased risk of premature death. Its occurrence has been associated with multiple psychiatric diagnoses, the most common being type I bipolar disorder. Catatonia can be understood as a disorder of ion dysregulation with reduced clearance of intracellular sodium ions. As the intraneuronal sodium concentration increases, the transmembrane potential is increased, and the resting potential may ultimately depolarize above the cellular threshold potential creating a condition known as depolarization block. Neurons in depolarization block do not respond to stimulation but are constantly releasing neurotransmitter; they mirror the clinical state of catatonia - active but non-responsive. Hyperpolarizing neurons, e.g., with benzodiazepines, is the most effective treatment.

Frequency of Modification of Pharmacological Treatment Is Equivalent for Virtual and In-Person Psychiatric Visits.

Background: During the coronavirus pandemic there was a rapid adoption of telehealth services in psychiatry, which now accounts for 40% of all visits. There is a dearth of information about the relative efficacy of virtual and in-person psychiatric evaluations. Methods: We examined the rate of medication changes during virtual and in-person visits as a proxy for the equivalence of clinical decision-making. Results: A total of 280 visits among 173 patients were evaluated. The majority of these visits were telehealth (224, 80%). There were 96 medication changes among the telehealth visits (42.8%) and 21 among the in-person visits (37.5%) (z = -1.4, p = 0.16). Conclusion: Clinicians were equally as likely to order a medication change if they saw their patient virtually or in person. This suggests that remote assessments yielded similar conclusions to in-person assessments.

Telehealth for Assessing and Managing Tardive Dyskinesia: Expert Insights from a Cross-Disciplinary Virtual Treatment Panel.

Introduction: Publications on the integration of telehealth in the care of patients with movement disorders are increasing, but little has been presented regarding its use in tardive dyskinesia (TD), a drug-induced movement disorder associated with prolonged exposure to dopamine receptor blocking agents. This study was conducted to address that knowledge gap, based on insights from a panel of TD experts. Methods: In 2020, six neurologists, three psychiatrists, and three psychiatric nurse practitioners participated in individual semistructured interviews about in-person and virtual TD assessment and management in their practices. Two virtual roundtables were then conducted to consolidate findings from these interviews. Results: The panel agreed that despite the challenges of virtual TD assessment (e.g., technology issues, difficulty observing entire body, inability to conduct thorough neurological examinations), telehealth can offer benefits (e.g., fewer missed appointments, reduced time/cost, easier access to family/caregiver feedback). The panel also agreed that telehealth should be combined with periodic in-person visits, and they recommended an in-person TD assessment within 6 months before the first virtual visit and at least one in-person assessment every 6 months thereafter. Additional best practices for TD telehealth included implementing video, involving family/caregivers, and providing preappointment instructions to help patients prepare their technology and environment. Conclusions: Telehealth is not a substitute for in-person visits but can be a helpful complement to in-person clinical care. Clinicians can optimize virtual visits in patients at risk of TD by using targeted questions to identify TD and evaluate its impact and by providing education about approved TD treatments.

Asenapine, Aggression, and Affinity.

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