Comparison of long-acting injectable antipsychotics with oral antipsychotics and hospital readmission rates in pediatric patients.

Introduction: Studies indicate that long-acting injectable antipsychotics (LAIAs) reduce the risk of relapse and hospitalization compared with oral antipsychotics (APs) in adults. Oral formulations of APs are well-studied in the pediatric population, but little is known regarding the off-label use of LAIAs in this population. Methods: This retrospective chart review evaluated readmission rates for pediatric patients admitted to a psychiatric ward in a large academic hospital between January 1, 2015, and December 1, 2022, requiring AP therapy. The experimental group included patients initiated on LAIA therapy, and the control group included patients initiated on a new oral AP. Patients were matched by several clinical factors. Results: Each group consisted of 38 patients. For the primary outcome, hospital readmission rates at 3 months, the LAIA group had a 13.2% readmission rate compared with 26.3% in the comparator group (p = .153). In months 4 through 6, there was a 5.3% versus 15.8% readmission rate, respectively (p = .139). In months 7 through 12, it was 7.9% versus 18.4% (p = .179). There were significantly fewer cumulative readmissions at the 1-year mark in the LAIA group (N = 9, 23.7%) compared with the oral AP group (N = 18, 47.4%) (p = .031). No statistically significant differences were seen in hospital length of stay although results numerically favored LAIA. Discussion: In a pediatric population, the administration of an LAIA when compared with the oral equivalent resulted in numerically fewer hospital readmissions, decreased length of stay, and fewer adverse effects, but these effects were not statistically significant except for cumulative readmissions at 1 year.

Management of cognitive and negative symptoms in schizophrenia.

Currently available antipsychotics provide only modest benefit in managing the cognitive and negative symptoms of schizophrenia even though these symptoms are often the most impairing in patients' daily lives. Certain antipsychotics may have slight benefits over others, and several nonpharmacologic and pharmacologic adjunctive treatments have been evaluated in recent clinical trials. Recently published meta-analyses and clinical studies of such treatments are reviewed. Potential strategies to manage cognitive and negative symptoms, including deprescribing of medications that may exacerbate these symptoms, are described using theoretical case examples.

Patient-reported perceptions of brexanolone in the treatment of postpartum depression: A qualitative analysis.

Introduction: Brexanolone demonstrates short-term efficacy for the treatment of postpartum depression (PPD). Postpartum depression is linked to infanticide and maternal suicide, and current treatment often fails to adequately control depressive symptoms. The purpose of this analysis is to further understand the experience(s) of women who have received brexanolone for the treatment of PPD. Methods: Semistructured interviews modeled after the theory of planned behavior (TPB) were conducted to assess women's perceptions of treatment for PPD with brexanolone. Women who received treatment with brexanolone at this inpatient facility were eligible to participate in this study. The TPB is often used to predict intention to perform health-related behaviors. Semistructured interviews were recorded and transcribed, and thematic analysis was conducted to identify common ideas across all interviews. Follow-up assessment of depressive and anxious symptoms was also conducted using the Patient Health Questionnaire-9 (PHQ-9) and Generalized Anxiety Disorder-7 (GAD-7), respectively. Results: Five of the 10 women who received treatment with brexanolone at this facility were interviewed, and common themes related to the TPB were analyzed. Attitudes toward brexanolone were favorable, and having a strong support system was a motivating factor in receiving treatment for PPD. Insurance approval, need for childcare, and poor understanding of symptoms of PPD were barriers to receiving treatment with brexanolone. Symptoms of depression and anxiety were rated as low at the time of the follow-up interview as measured by the PHQ-9 (mean 1.6, range 1 to 3) and GAD-7 (mean 2.8, range 2 to 4), respectively. Discussion: Brexanolone rapidly and sustainably reduced symptoms of PPD and was well-received by patients. Despite significant barriers to use, women who received treatment with brexanolone advocated for its availability as well as increased awareness of PPD.

Evaluation of the use of chlorpromazine for agitation in pediatric patients.

INTRODUCTION: Chlorpromazine is a first-generation antipsychotic used for behavioral problems in pediatric patients. However, other therapies may demonstrate both improved outcomes and fewer side effects. Within our institution, chlorpromazine has been the standard medication used for treatment of pediatric agitation. The study objective was to evaluate the appropriateness of chlorpromazine use (including efficacy, appropriate dosing, drug interactions, and tolerability) to optimize the treatment of pediatric agitation. METHODS: Data regarding drug interactions, patient behavior, dosing, and side effects was collected for each patient administered chlorpromazine from January 2019 through June 2019. Data were analyzed using descriptive statistics assessing the incidence of drug-drug interactions (DDIs), incidences of inefficacy, inappropriate dosing, and side effects. RESULTS: A total of 70 patients and 130 administrations of oral or intramuscular chlorpromazine were evaluated. Of these administrations, 49 (38%) resulted in a DDI. Eighteen (14%) administrations were ineffective for managing symptoms of agitation. Eleven (8%) administrations were dosed inappropriately, and 46 (35%) administrations resulted in side effects possibly caused by chlorpromazine. DISCUSSION: Results from this study demonstrate opportunities for improvement in patient care due to instances of drug interactions, inefficacy, inappropriate dosing, and side effects with the use of chlorpromazine.

Brexpiprazole in the treatment of schizophrenia and agitation in Alzheimer's disease.

Schizophrenia is a disabling psychiatric disorder marked by progressive loss of functionality in activities of daily living with each relapse. Antipsychotics, the mainstay of therapy for schizophrenia, treat hallucinations and delusions but may have intolerable side effects, including metabolic disturbances and extrapyramidal symptoms. Brexpiprazole, a second-generation antipsychotic with dopamine partial agonist properties, was approved by the US FDA in 2015 for the treatment of schizophrenia and adjunctive treatment of major depressive disorder and by the EU in 2018 for adults with schizophrenia. Additionally, brexpiprazole has recently been studied for the treatment of agitation in Alzheimer's dementia, an area of largely unmet need. Overall, well-tolerated brexpiprazole expands the armamentarium of treatment options available for these conditions.

An update on current treatment strategies and emerging agents for the management of schizophrenia.

Schizophrenia is a chronic neuropsychiatric disorder that has a significant impact on the functioning and quality of life of individuals affected by the disease. It affects 0.6% to 1.9% of individuals within the United States, and currently there is no cure. Guidelines recommend a combined treatment approach with both pharmacologic agents and psychological interventions for first-episode psychosis, acute exacerbations, and relapse prevention. Presently, multiple agents are available for the treatment of schizophrenia; however, the majority do not address negative symptoms and cognitive dysfunction, with many patients having debilitating residual symptoms, difficulties with adherence, and drug-related adverse effects. To address these concerns, new research evaluating investigational therapies has been undertaken to examine novel treatment strategies. This review summarizes the schizophrenia treatment guidelines, current treatment strategies, and emerging agents for the management of schizophrenia.

A Retrospective Multicenter Evaluation of Clozapine Use in Pediatric Patients Admitted for Acute Psychiatric Hospitalization.

OBJECTIVES: Clozapine is the drug of choice for treatment-resistant schizophrenia. While pediatric clozapine use is not contraindicated, the literature describing its clinical application is limited. The primary objective of this study was to assess the use of clozapine in a child and adolescent population by characterizing the documented safety and clinical benefits of the medication. METHODS: A multicenter retrospective study at sites in the United States and Australia included children and adolescents admitted to a psychiatric unit who were administered at least one dose of clozapine. Information related to demographics, patient history, past treatments, clozapine, and adverse events was collected. RESULTS: Eighty-two patients from eight sites were included in this study. Patients were predominantly clozapine naive (76.8%), and most had a discharge diagnosis of a primary psychotic disorder (61%) or bipolar disorder (25.6%). Four clozapine discontinuations occurred during hospitalization due to severe neutropenia, ileus, need for diagnostic clarification, and significant psychomotor retardation. The remainder (n = 78) were discharged on a mean clozapine dose of 218.1 ± 142.2 mg. Sedation (26.8%) and sialorrhea (17.1%) were the most common documented adverse events. The mean number of previously trialed antipsychotics before clozapine was 3.5 ± 1.4 (range 1-10). Improvement with clozapine was documented as significant (31.7%), moderate (32.9%), minimal (12.2%), no improvement (2.4%), and not described (20.7%). CONCLUSIONS: In this cohort, 95% of pediatric patients admitted with or started on clozapine during an acute psychiatric hospitalization were discharged on the medication. The high incidence of adverse events should reinforce to clinicians the need for vigilant monitoring. Pediatric guidelines recommend clozapine for refractory schizophrenia but stress the critical need to ensure an accurate diagnosis. Limited data exist for the use of clozapine in pediatric patients with other diagnoses.

Pharmacologic Treatment Options for Insomnia in Patients with Schizophrenia.

Background: Symptoms of sleep disorders, such as disturbances in sleep initiation and continuity, are commonly reported in patients with schizophrenia, especially in the acute phase of illness. Studies have shown that up to 80% of patients diagnosed with schizophrenia report symptoms of insomnia. Sleep disturbances have been shown to increase the risk of cognitive dysfunction and relapse in patients with schizophrenia. Currently, there are no medications approved specifically for the treatment of insomnia in patients with schizophrenia. Methods: A literature search was performed through OVID and PubMed to compile publications of pharmacotherapy options studied to treat insomnia in patients with schizophrenia. Articles were reviewed from 1 January 2000 through 1 March 2018 with some additional earlier articles selected if deemed by the authors to be particularly relevant. Results: Pharmacotherapies collected from the search results that were reviewed and evaluated included melatonin, eszopiclone, sodium oxybate, and antipsychotics. Conclusions: Overall, this review confirmed that there are a few evidence-based options to treat insomnia in patients with schizophrenia, including selecting a more sedating second-generation antipsychotic such as paliperidone, or adding melatonin or eszopiclone. Further randomized controlled trials are needed.

Brexpiprazole.

OBJECTIVE: To review the pharmacology and clinical data for brexpiprazole in schizophrenia and major depressive disorder (MDD). DATA SOURCES: An English-language literature search using PubMed and MEDLINE was performed using the term brexpiprazole. All articles containing human clinical trial data published up to September 2016 were evaluated for inclusion as well as information from the manufacturer's product labeling. STUDY SELECTION/DATA EXTRACTION: Phase 3 trials for brexpiprazole were evaluated. Key in vitro and animal data were incorporated into the pharmacology and pharmacokinetic sections where appropriate. DATA SYNTHESIS: Four phase 3 trials have evaluated the use of brexpiprazole as a primary therapy for schizophrenia or as an antidepressant adjunct for MDD. For its schizophrenia indication, brexpiprazole was studied in 2 placebo-controlled trials of approximately 1300 patients, with 4 mg of brexpiprazole consistently showing superiority over placebo. For MDD, brexpiprazole was compared with placebo as an adjunct to antidepressants in approximately 1000 patients who had failed trials of 1 to 3 prior antidepressants. The 2-mg and 3-mg dosages of brexpiprazole showed consistent superiority over placebo in the MDD trials. Common treatment emergent adverse effects included akathisia and weight gain. CONCLUSIONS: Brexpiprazole showed efficacy for the treatment of schizophrenia in the range of 2 to 4 mg/d and as an adjunct to antidepressant therapy in MDD when dosed at 2 to 3 mg/d. Advantages of this drug include once-daily dosing, good tolerability, and lack of effect on sexual function. Disadvantages include the lack of long-term safety data and potentially high cost.

Topiramate in the treatment of Prader-Willi syndrome: A case report.

BACKGROUND: Prader-Willi syndrome (PWS), a neurologic disorder caused by a mutation of chromosome 15, is characterized by such symptoms as hypotonia, hypogonadism, hyperphagia, cognitive impairment, and difficult behaviors. One of the most concerning symptoms is hyperphagia, which can lead to uncontrolled obesity. Obesity is a major cause of increased morbidity and mortality in patients with PWS; however, diagnosing PWS early in life improves the prognosis. CASE SUMMARY: An 11-year-old African American boy with a past medical history significant for PWS, attention deficit/hyperactivity disorder, oppositional defiant disorder, obesity, and asthma was admitted after he became violent and destructive at his foster home while trying to get food. The patient had a 28-day stay on the children's crisis intervention unit where quetiapine was discontinued and he was maintained on clonidine 0.1 mg 3 times daily, hydroxyzine 25 mg in the morning and 50 mg at bedtime, montelukast 5 mg daily and titrated on methylphenidate 10 mg in the morning and 5 mg in the afternoon, topiramate 100 mg twice daily, and aripiprazole 10 mg twice daily. The patient displayed improved behavior control and less food-related aggression; he denied any side effects of medications. DISCUSSION: This case demonstrates the positive effects of topiramate for reducing aggression and demand for food in a child with PWS most likely due to an increase in satiety. It is hard to definitively attribute the positive response directly to topiramate. Further research should be conducted to determine if topiramate is an effective treatment option in these individuals.

Evaluation of the use of electrocardiogram monitoring in patients on psychotropic medications that have a risk of QT prolongation.

INTRODUCTION: Many psychotropic medications carry a risk of prolonging the QT interval and increasing the risk of developing Torsade de pointes (TdP). The goal of this study was to evaluate whether patients taking psychotropic agents with a known risk of TdP are being monitored at a community hospital through the use of electrocardiograms (EKGs). METHODS: This was a retrospective chart review of 100 adult patients-50 from general medicine floors and 50 from psychiatric units-who were taking at least one psychotropic agent with a known risk of TdP during hospitalization. RESULTS: The mean number of medications with QT-prolongation risk administered to the psychiatric and general medicine patients was 4.2 ± 1.7 and 3.9 ± 2.0, respectively (P = .7484). Thirty-two of the psychiatric patients (64%) and 48 of the general medicine patients (96%) received EKGs during their hospitalization (P < 0.0001). Of those newly starting the target medications, 58% (18 of 31) of the psychiatric patients and 71% (5 of 7) of the general medicine patients received a baseline EKG. The difference was not statistically significant (P = .6807). Overall, 8 patients (8%) had corrected QT (QTc) intervals >500 ms. Four had repeat EKGs performed, and none had medication changes made to decrease TdP risk. DISCUSSION: Many inpatients on psychiatric medications received multiple medications with a risk of TdP, but not all received monitoring through baseline or repeat EKGs when warranted. Patients with QTc intervals >500 ms were not appropriately managed to lower their risk of TdP. Pharmacists thus can help improve the monitoring and management of QT prolongation.

Implications for multiple sclerosis in the era of the Affordable Care Act: a clinical overview.

Multiple sclerosis (MS) is a chronic, often debilitating disease of the central nervous system (CNS) that affects between 400,000 and 570,000 persons in the United States, with an incidence among females 2 to 3 times that of males. The cause of MS is currently unknown, but immediate family history, low blood levels of vitamin D, and cigarette smoking, among other factors, appear to increase the risk of developing MS. MS is considered an immune-mediated disease, whereby immune cells target and attack the CNS, predominantly the axonal membrane known as the myelin sheath. Depending on which areas of the brain or spinal cord are affected, this can result in a variety of waxing and waning neurologic symptoms. Most patients will eventually suffer from progressive disability that can greatly impact their quality of life. Symptoms such as fatigue, difficulty with ambulation, and depression are common among patients with MS and can affect their ability to work and care for themselves. Costs due to treatment and lost productivity place a significant economic burden on patients, caregivers, families, and society. Current and future treatments may help limit the personal and societal costs of MS by delaying disability and disease progression.

Teriflunomide for the treatment of relapsing multiple sclerosis: a review of clinical data.

OBJECTIVE: To review the pharmacology and clinical data for teriflunomide in relapsing multiple sclerosis (MS). DATA SOURCES: A literature search from 1966 to May 2013 using PubMed/MEDLINE, Web of Science, International Pharmaceutical Abstracts, Academic Search Premiere, Science Citation Index, and the national clinical trials registry was performed using the terms teriflunomide, HMR1726, and A771726. All articles containing human clinical trial data and relevant pharmacologic information were reviewed. STUDY SELECTION/DATA EXTRACTION: Phase 2 and phase 3 clinical trials for teriflunomide were evaluated. All peer-reviewed articles with clinically relevant information were reviewed. Priority for inclusion was placed on randomized controlled trials. DATA SYNTHESIS: Three phase 2 and three phase 3 clinical trials have evaluated teriflunomide as monotherapy or as adjunctive therapy in approximately 3000 patients with relapsing forms of MS. The phase 3 studies used annualized relapse rate, magnetic resonance imaging changes, and Expanded Disability Status Scale scores as outcome measures. One additional Phase 3 clinical study is ongoing. The annualized relapse rates and magnetic resonance imaging findings were improved compared to those with placebo and similar to or improved compared with those with subcutaneously administered interferon-ß-1a 44 µg thrice weekly. Durability of response is supported by open-label extension studies. Common adverse events include increased liver function enzymes, alopecia, diarrhea, influenza, nausea, and paresthesias. Treatment discontinuation was not common and occurred in approximately 10% of patients in phase 3 studies. CONCLUSIONS: Teriflunomide is an effective and safe oral treatment option for relapsing MS. It can be used as monotherapy or added to an interferon or glatiramer acetate. It reduces the rate of relapse and may slow disease progression. The advantages of this drug are the convenience of oral administration and good tolerability. The disadvantage is the lack of long-term safety data and data about the benefit of combination therapy.