Informing the development of antipsychotic-induced weight gain management guidance: patient experiences and preferences - qualitative descriptive study.

BACKGROUND: Antipsychotic-induced weight gain (AIWG) is a substantial contributor to high obesity rates in psychiatry. Limited management guidance exists to inform clinical practice, and individuals with experience of managing AIWG have had no or minimal input into its development. A lack of empirical research outlining patient values and preferences for management also exists. Recommendations addressing weight management in psychiatry may be distinctly susceptible to ideology and sociocultural values regarding intervention appropriateness and expectations of self-management, reinforcing the need for co-produced management guidance. This study is the first to ask: how do individuals conceptualise preferred AIWG management and how can this be realised in practice? AIMS: 1. Explore the management experiences of individuals with unwanted AIWG. 2. Elicit their values and preferences regarding preferred management. METHOD: Qualitative descriptive methodology informed study design. A total of 17 participants took part in semi-structured interviews. Data analysis was undertaken using reflexive thematic analysis. RESULTS: Participants reported that clinicians largely overestimated AIWG manageability using dietary and lifestyle changes. They also reported difficulties accessing alternative management interventions, including a change in antipsychotic and/or pharmacological adjuncts. Participants reported current management guidance is oversimplified, lacks the specificity and scope required, and endorses a 'one-size-fits-all' management approach to an extensively heterogenous side-effect. Participants expressed a preference for collaborative AIWG management and guidance that prioritises early intervention using the range of evidence-based management interventions, tailored according to AIWG risk, participant ability and participant preference. CONCLUSION: Integration of this research into guideline development will help ensure recommendations are relevant and applicable, and that individual preferences are represented.

Psychiatric assessment and therapy in an adolescent with ALG6-CDG: a six-month follow-up case report.

ALG6-congenital disorder of glycosylation (ALG6-CDG) is a complex of rare inherited disorders caused by mutations in the ALG6 gene, which encodes the α-1,3-glucosyltransferase enzyme required for N-glycosylation. ALG6-CDG affects multiple systems and exhibits clinical heterogeneity. Besides developmental delays and neurological signs and symptoms, behavioral and psychological symptoms are also an important group of clinical features of ALG6-CDG. Here, we present the case of a 17-year-old Chinese girl with ALG6-CDG who first visited the psychiatric department with apathy, language reduction, and substupor symptoms. The psychiatric assessments and treatment processes performed are described and discussed in this report. During diagnostic process, we found a novel mutation, c.849delT, in ALG6 by whole-exome sequencing. The patient's symptoms improved with escitalopram and risperidone treatment. However, above a certain dosage, she was sensitive to extrapyramidal side effects. This study accumulates clinical experience for diagnosing and treating ALG6-CDG and improves our understanding of this rare genetic disorder.

Research Letter: Dispensing of psychotropic medications in Australia between 2013 and 2022.

OBJECTIVE: The objective of this study was to determine the proportion of Australians dispensed psychotropic medications between 2013 and 2022 according to their age. METHODS: Services Australia provided a de-identified 10% random Pharmaceutical Benefits Scheme sample that allowed us to determine, for each year, the proportion of Australians dispensed at least one script for antipsychotics, antidepressants, anxiolytics, or hypnotics. The classification of medications followed Anatomical Therapeutic Chemical coding. Participants were stratified into 10-year age groups from 0-9 to ⩾90 years, and sex was coded as male/female. We retrieved population numbers from the Australian Bureau of Statistics. RESULTS: The number of records per year ranged from 1,540,520 to 1,746,402, and 54.10% were for females. A greater proportion of older adults, particularly those aged ⩾70 years, were dispensed antipsychotics, antidepressants, anxiolytics and hypnotics than any other age group. The proportion of people who dispensed antipsychotics, anxiolytics and hypnotics declined between 2013 and 2022 but increased for antidepressants, most markedly for adolescents and young adults. Females were more frequently dispensed antidepressants, anxiolytics and hypnotics than males, but males were more frequently dispensed antipsychotics than females, albeit not in later life. CONCLUSION: Older age groups and females are the most frequent recipients of psychotropic medications dispensed in Australia.

Metabolic syndrome risk prediction in an Australian sample with first-episode psychosis using the psychosis metabolic risk calculator: A validation study.

OBJECTIVE: To examine the accuracy and likely clinical usefulness of the Psychosis Metabolic Risk Calculator (PsyMetRiC) in predicting up-to six-year risk of incident metabolic syndrome in an Australian sample of young people with first-episode psychosis. METHOD: We conducted a retrospective study at a secondary care early psychosis treatment service among people aged 16-35 years, extracting relevant data at the time of antipsychotic commencement and between one-to-six-years later. We assessed algorithm accuracy primarily via discrimination (C-statistic), calibration (calibration plots) and clinical usefulness (decision curve analysis). Model updating and recalibration generated a site-specific (Australian) PsyMetRiC version. RESULTS: We included 116 people with baseline and follow-up data: 73% male, mean age 20.1 years, mean follow-up 2.6 years, metabolic syndrome prevalence 13%. C-statistics for both partial- (C = 0.71, 95% CI 0.64-0.75) and full-models (C = 0.72, 95% CI 0.65-0.77) were acceptable; however, calibration plots demonstrated consistent under-prediction of risk. Recalibration and updating led to slightly improved C-statistics, greatly improved agreement between observed and predicted risk, and a narrow window of likely clinical usefulness improved significantly. CONCLUSION: An updated and recalibrated PsyMetRiC model, PsyMetRiC-Australia, shows promise. Validation in a large sample is required to confirm its accuracy and clinical usefulness for the Australian population.

Effects of antipsychotic treatment on cardio-cerebrovascular related mortality in schizophrenia: A subanalysis of a systematic review and meta-analysis with meta-regression of moderators.

To further explore the role of different antipsychotic treatments for cardio-cerebrovascular mortality, we performed several subgroup, sensitivity and meta-regression analyses based on a large previous meta-analysis focusing on cohort studies assessing mortality relative risk (RR) for cardio-cerebrovascular disorders in people with schizophrenia, comparing antipsychotic treatment versus no antipsychotic. Quality assessment through the Newcastle-Ottawa Scale (NOS) and publication bias was measured. We meta-analyzed 53 different studies (schizophrenia patients: n = 2,513,359; controls: n = 360,504,484) to highlight the differential effects of antipsychotic treatment regimens on cardio-cerebrovascular-related mortality in incident and prevalent samples of patients with schizophrenia. We found first generation antipsychotics (FGA) to be associated with higher mortality in incident samples of schizophrenia (oral FGA [RR=2.20, 95 %CI=1.29-3.77, k = 1] and any FGA [RR=1.70, 95 %CI=1.20-2.41, k = 1]). Conversely, second generation antipsychotics (SGAs) and clozapine were associated with reduced cardio-cerebrovascular-related mortality, in prevalent samples of schizophrenia. Subgroup analyses with NOS score ≥7 (higher quality) demonstrated a significantly increased cardio-cerebrovascular disorder-related mortality, among those exposed to FGAs vs SGAs. Meta-regression analyses demonstrated a larger association between antipsychotics and decreased risk of mortality with longer follow-up, recent study year, and higher number of adjustment variables. Overall, this subanalysis of a systematic review contributes to the evolving understanding of the complex role of antipsychotic treatment for cardio-cerebrovascular mortality in schizophrenia, paving the way for more targeted interventions and improved patient outcomes.

Early-life risperidone alters locomotor responses to apomorphine and quinpirole in adulthood.

An escalating trend of antipsychotic drug use in children with ADHD, disruptive behavior disorder, or mood disorders has raised concerns about the impact of these drugs on brain development. Since antipsychotics chiefly target dopamine receptors, it is important to assay the function of these receptors after early-life antipsychotic administration. Using rats as a model, we examined the effects of early-life risperidone, the most prescribed antipsychotic drug in children, on locomotor responses to the dopamine D1/D2 receptor agonist, apomorphine, and the D2/D3 receptor agonist, quinpirole. Female and male Long-Evans rats received daily subcutaneous injections of risperidone (1.0 and 3.0 mg/kg) or vehicle from postnatal day 14-42. Locomotor responses to one of three doses (0.03, 0.1, and 0.3 mg/kg) of apomorphine or quinpirole were tested once a week for four weeks beginning on postnatal day 76 and 147 for each respective drug. The locomotor activity elicited by the two lower doses of apomorphine was significantly greater in adult rats, especially females, administered risperidone early in life. Adult rats administered risperidone early in life also showed more locomotor activity after the low dose of quinpirole. Overall, female rats were more sensitive to the locomotor effects of each agonist. In a separate group of rats administered risperidone early in life, autoradiography of forebrain D2 receptors at postnatal day 62 revealed a modest increase in D2 receptor density in the medial caudate. These results provide evidence that early-life risperidone administration can produce long-lasting changes in dopamine receptor function and density.

Cost-Utility Analysis of Antipsychotic Reduction and Discontinuation in Patients with Long-term Schizophrenia and Psychosis in English Mental Health Trusts: The RADAR Study.

OBJECTIVES: The current recommended treatment for patients with recurrent episodes of schizophrenia and related conditions is antipsychotic medication. However, many antipsychotic users remain functionally impaired and experience serious physical and mental side effects. This study aims to assess the cost-effectiveness of a gradual antipsychotic reduction and discontinuation strategy compared to maintenance treatment over 24 months from a mental health services, health and social care, and societal perspectives. METHODS: Nineteen mental health trusts recruited patients to the RADAR randomised controlled trial. Quality adjusted life years (QALYs) were calculated from patient-reported EQ-5D-5L, with years of full capability (YFCs) calculated from the patient-reported ICECAP-A. Mental health services use and medication was collected from medical records. Other resource use and productivity loss was collected using self-completed questionnaires. Costs were calculated from published sources. RESULTS: 253 participants were randomised: 126 assigned to antipsychotic dose reduction and 127 to maintenance. There were no significant differences between arms in total costs for any perspectives. There were no significant difference in QALYs (-0.035; 95% CI: -0.123 to 0.052), whereas YFCs were significantly lower in the reduction arm compared to the maintenance arm (baseline-adjusted difference: -0.103; 95% CI: -0.192 to -0.014). The reduction strategy was dominated by maintenance for all analyses and was not likely to be cost-effective. CONCLUSIONS: It is unlikely that gradual antipsychotic reduction and discontinuation strategy is cost-effective compared with maintenance over two-years for patients with schizophrenia and other recurrent psychotic disorders who are on long-term antipsychotics.

Tricyclic Antidepressant and Antipsychotic Toxicity: Clomipramine and Ziprasidone Overdose.

This case report details an intentional overdose attempt utilizing tricyclic antidepressants (TCAs) and atypical antipsychotics with significant neurologic, pulmonary, and cardiac toxicity. In conjunction with the local poison control center, progression of the clinical toxidrome was anticipated, aggressively managed, and successfully treated. This case highlights the dangers of significant TCA toxicity, peak onset of toxicity within six hours, and the amplification of clinical toxidromes with co-ingestions.

Comparison of intramuscular haloperidol and other short-acting injectable antipsychotics for management of acute agitation in an adult inpatient psychiatry unit.

Introduction: There is no consensus on the optimal antipsychotic for acute agitation. Whereas haloperidol is frequently used and has proven efficacy, second generation antipsychotics show similar efficacy and improved safety and tolerability. This study aimed to determine the effectiveness of short-acting intramuscular (IM) haloperidol versus other IM antipsychotics for acute agitation in adults admitted to an inpatient psychiatry unit. Methods: This was a retrospective medical record review of patients who received 1 or more doses of a short-acting IM antipsychotic, including chlorpromazine, haloperidol, olanzapine, or ziprasidone. The primary endpoint was the need for subsequent IM antipsychotic(s) or physical restraint within 2 hours of the initial IM antipsychotic. Secondary endpoints assessed outcomes at 24 hours and adverse events. Results: One hundred six patients were included. Four patients in the haloperidol group and 0 patients in the other antipsychotic group received an additional IM antipsychotic or required physical restraints within 2 hours (5.3% versus 0%, p = .319). More patients in the other antipsychotic group required an additional dose of IM antipsychotic within 24 hours compared with the haloperidol group (p = .0096). More adverse events were seen in patients who received haloperidol. Discussion: Haloperidol was used more frequently than other short-acting IM antipsychotics. Whereas the effectiveness at 2 hours was not significantly different between groups, patients who received haloperidol were more likely to experience adverse events and were more often subjected to polypharmacy with benzodiazepines and/or diphenhydramine. This study further supports the use of olanzapine and ziprasidone for acute agitation in patients hospitalized in inpatient psychiatry.

The Atypical Face of Neuroleptic Malignant Syndrome: A Case Report of Ileus and Absent Rigidity.

Neuroleptic malignant syndrome (NMS) is a rare life-threatening condition associated with the use of antipsychotic medications. This case report describes a male patient in his early 30s who presented with fever, breathlessness, and lower limb weakness, ultimately diagnosed with NMS despite the absence of muscular rigidity. On examination, he was febrile, tachycardic, and tachypneic with an oxygen saturation of 88% and elevated blood pressure. On auscultation diffuse crepitations in both lungs were revealed. Neurological assessment indicated motor strength of 3/5 in both lower limbs, without rigidity, sensory loss, or cerebellar signs. It was noted that he was on irregular atypical antipsychotic medication for the past one year. Laboratory investigations revealed leukocytosis, elevated transaminases, dyselectrolytemia, elevated creatine phosphokinase (CPK), and serum creatinine. NMS was not initially considered due to the lack of muscular rigidity. However, the patient later developed autonomic dysregulation manifestations, such as paralytic ileus. Once organic causes were excluded, NMS was diagnosed. Supportive therapy included 23 cycles of hemodialysis and colonic decompression for pseudo-obstruction. He was treated with intravenous fluids and dopamine receptor agonist medications. NMS usually presents with fever, muscular rigidity, altered mental status, and autonomic instability; yet, the absence of muscular rigidity in this patient is a distinctive and unusual feature.

Living systematic review and meta-analysis of plasma-concentrations of antipsychotic drugs in carriers and non-carriers of variant CYP450 genotypes: Living systematic review protocol.

Introduction: Carriers of variant alleles of genes that encode liver CYP450 and UGT enzymes may experience abnormal plasma levels of antipsychotics and, consequently, worse efficacy or tolerability. Although pharmacogenomics is a rapidly developing field, current guidelines often rely on limited, underpowered evidence. We have previously demonstrated that meta-analysis is a viable strategy for overcoming this problem. Here, we propose a project that will expand our previous work and create a living systematic review and meta-analysis of drug plasma level differences between carriers and non-carriers of variant genotype-predicted phenotypes for every pharmacokinetic drug-gene interaction relevant to commonly used antipsychotic drugs. Protocol: First, a baseline systematic review and meta-analysis will be conducted by searching for observational pharmacogenomics-pharmacokinetic studies. Data on dose-adjusted drug plasma levels will be extracted, and participants will be grouped based on their genotype for each drug-gene pair separately. Differences in plasma drug levels between different phenotypes will be compared using a random-effect ratio-of-means meta-analysis. The risk of bias will be assessed using ROBINS-I, and the certainty of evidence will be assessed using GRADE. Following the establishment of baseline results, the literature search will be re-run at least once every six months, and the baseline data will be updated and re-evaluated as new evidence is published. A freely available website will be designated to present up-to-date results and conclusions. Discussion: This systematic review will provide evidence-based results that are continuously updated with evidence as it emerges in the rapidly developing field of pharmacogenomics. These results may help psychiatrists in their decision-making, as clinicians are becoming increasingly aware of the patients' genetic data as testing becomes more widespread and cheaper. In addition, the results may serve as a scientific basis for the development of evidence-based pharmacogenomics algorithms for personalized dosing of antipsychotics to mitigate potentially harmful drug-gene interactions.

Efficacy and tolerability of antipsychotic polypharmacy for schizophrenia spectrum disorders. A systematic review and meta-analysis of individual patient data.

BACKGROUND: Antipsychotic polypharmacy (APP) is frequently prescribed for schizophrenia-spectrum disorders. Despite the inconsistent findings on efficacy, APP may be beneficial for subgroups of psychotic patients. This meta-analysis of individual patient data investigated moderators of efficacy and tolerability of APP in adult patients with schizophrenia-spectrum disorders. DESIGN: We searched PubMed, EMBASE, and the Cochrane Central Register of Randomized Trials until September 1, 2022, for randomized controlled trials comparing APP with antipsychotic monotherapy. We estimated the effects with a one-stage approach for patient-level moderators and a two-stage approach for study-level moderators, using (generalized) linear mixed-effects models. Primary outcome was treatment response, defined as a reduction of 25 % or more in the Positive and Negative Syndrome Scale (PANSS) score. Secondary outcomes were study discontinuation, and changes from baseline on the PANSS total score, its positive and negative symptom subscale scores, the Clinical Global Impressions Scale (CGI), and adverse effects. RESULTS: We obtained individual patient data from 10 studies (602 patients; 31 % of all possible patients) and included 599 patients in our analysis. A higher baseline PANSS total score increased the chance of a response to APP (OR = 1.41, 95 % CI 1.02; 1.94, p = 0.037 per 10-point increase in baseline PANSS total), mainly driven by baseline positive symptoms. The same applied to changes on the PANSS positive symptom subscale and the CGI severity scale. Extrapyramidal side effects increased significantly where first and second-generation antipsychotics were co-prescribed. Study discontinuation was comparable between both treatment arms. CONCLUSIONS: APP was effective in severely psychotic patients with high baseline PANSS total scores and predominantly positive symptoms. This effect must be weighed against potential adverse effects.

Stevens-Johnson syndrome-toxic epidermal necrolysis overlap in a patient taking quetiapine and famotidine: a case report.

BACKGROUND: Stevens-Johnson syndrome-toxic epidermal necrolysis (SJS-TNE) overlap is a rare skin disorder characterized by erythema, blisters, extensive exfoliation, epidermal detachment, the involvement of multiple mucosae, and positive Nikolsky's sign. SJS-TEN has a high mortality rate. Our case involves a rare occurrence of drug-induced Stevens-Johnson syndrome-toxic epidermal necrolysis overlap with a delayed onset in the setting of quetiapine and famotidine therapy. CASE PRESENTATION: An 82-year-old Taiwanese female was admitted to our hospital for decreased urine output, generalized edema, and multiple skin blisters and bedsores. With further spread of the lesions, multiple ruptured bullae with shallow erosions on the face, trunk, and limbs and mucosal involvement affected 20% of the total body surface area. Nikolsky's sign was positive. A diagnosis of Steven-Johnson syndrome was highly suspected. One month prior, she had started famotidine and quetiapine. Intravenous methylprednisolone treatment was initiated, which ameliorated the skin lesions after 3 days. However, new lesions developed after only 1 day of methylprednisolone tapering. The patient died 12 days after admission. CONCLUSION: Stevens-Johnson syndrome-toxic epidermal necrolysis is a rare skin disorder. Although it is mainly acute and has a high mortality rate, delayed onset can still occur. Quetiapine and famotidine are generally safe and effective for treating geriatric and gastrointestinal problems, but rare drug hypersensitivity reactions can lead to debilitating consequences. Therefore, increased clinical awareness and the initiation of supportive care are imperative. Optimal management guidelines are still lacking, and confirmation of developed guidelines through randomized controlled trials is needed. Collaboration for better management strategies is warranted.

Effect of Lurasidone on Life Engagement in Schizophrenia: Post-Hoc Analysis of the JEWEL Study.

Purpose: To evaluate the effect of lurasidone on a new, patient Life Engagement scale in schizophrenia. Patients and Methods: This post-hoc analysis included participants (ages 18 to 74) diagnosed with schizophrenia who were randomized to lurasidone (40 mg/day) or placebo in a 6-week double-blind efficacy study and those who continued in a subsequent 12-week open-label extension study during which patients received either 40 or 80/mg day lurasidone (flexibly dosed). Change in life engagement was measured using the Positive and Negative Syndrome Scale (PANSS) 11-item Life Engagement subscale score, and individual subscale items, at week 6 during the double-blind phase and extension phase week 12 during the open-label extension phase. Results: Analysis focused on 478 subjects randomized to lurasidone or placebo during the 6-week trial, and 146 who received lurasidone during the extension phase. During the 6-week trial, there was a significantly greater change on the PANSS11 Life Engagement subscale score from baseline to week 6 in the lurasidone group compared to the placebo group (mean changes of -6.4 and -4.8, respectively, p = 0.006; effect size = 0.27). Further improvement was evident during the extension phase for patients who received lurasidone in both phases, with a mean change from double-blind baseline to week 12 of the open-label treatment phase of -10.1 on in PANSS11 Life Engagement subscale. Conclusion: This post-hoc analysis suggests that lurasidone may improve life engagement in patients with schizophrenia, a meaningful outcome from patients' perspective. Further studies are needed to confirm this effect. Eudract Number: Trial registration: EudraCT Numbers: 2016-000060-42; 2016-000061-23.

A hybrid model for predicting response to risperidone after first episode of psychosis.

Patient response to antipsychotic drugs varies and may be related to clinical and genetic heterogeneity. This study aimed to determine the performance of clinical, genetic, and hybrid models to predict the response of first episode of psychosis (FEP). patients to the antipsychotic risperidone. We evaluated 141 antipsychotic-naïve FEP patients before and after 10 weeks of risperidone treatment. Patients who had a response rate equal to or higher than 50% on the Positive and Negative Syndrome Scale were considered responders (n = 72; 51%). Analyses were performed using a support vector machine (SVM), k-nearest neighbors (kNN), and random forests (RF). Clinical and genetic (with single-nucleotide variants [SNVs]) models were created separately. Hybrid models (clinical+genetic factors) with and without feature selection were created. Clinical models presented greater balanced accuracy 63.3% (confidence interval [CI] 0.46-0.69) with the SVM algorithm than the genetic models (balanced accuracy: 58.5% [CI 0.41-0.76] - kNN algorithm). The hybrid model, which included duration of untreated psychosis, Clinical Global Impression-Severity scale scores, age, cannabis use, and 406 SNVs, showed the best performance (balanced accuracy: 72.9% [CI 0.62-0.84] - RF algorithm). A hybrid model, including clinical and genetic predictors, can provide enhanced predictions of response to antipsychotic treatment.

Increased antipsychotic drug concentration in hospitalized patients with mental disorders following COVID-19 infection: a call for attention.

Purpose: Examine the alterations in antipsychotic concentrations following coronavirus disease-2019 (COVID-19) infection among hospitalized patients with mental disorders and conduct an analysis of the factors influencing these changes. Methods: Data were collected from inpatients at Beijing Huilongguan Hospital between December 12, 2022, and January 11, 2023, pre- and post-COVID-19. Based on the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, 329 inpatients with mental disorders were included (3 with incomplete data excluded). Primary outcomes assessed changes in antipsychotic concentrations pre- and post-COVID-19, while secondary outcomes examined factors linked to concentration increases and antipsychotic dose adjustments. Results: Clozapine (P < 0.001), aripiprazole (P < 0.001), quetiapine (P = 0.005), olanzapine (P < 0.001), risperidone (P < 0.001), and paliperidone (P < 0.001) concentrations increased post-COVID-19 in patients with mental disorders. Notably, clozapine concentration surpassing pre-infection levels was highest. Clozapine users were more likely to adjust their dose (50.4%) compared to olanzapine (17.5%) and other antipsychotics. Moreover, traditional Chinese patent medicines and antibiotics during COVID-19 infection were associated with antipsychotic reduction or withdrawal (OR = 2.06, P = 0.0247; OR = 7.53, P = 0.0024, respectively). Conclusion: Antipsychotic concentrations in hospitalized patients with mental disorders increased after COVID-19 infection, that may be related not only to COVID-19, but also to the use of Chinese patent medicines during infection. The pre-infection concentration and types of antipsychotics, patient's gender, and combination of traditional Chinese medicine or antibiotics, were factors found to correlate with increased drug concentrations and necessitate dose adjustments.

Brain-wide Anatomical Connectivity and Prediction of Longitudinal Outcomes in Antipsychotic-Naïve First Episode Psychosis.

BACKGROUND: Disruptions of axonal connectivity are thought to be a core pathophysiological feature of psychotic illness, but whether they are present early in the illness, prior to antipsychotic exposure, and whether they can predict clinical outcome remains unknown. METHODS: We acquired diffusion-weighted MRI to map structural connectivity between each pair of 319 parcellated brain regions in 61 antipsychotic-naive individuals with First Episode Psychosis (FEP; 15-25 years, 46% female) and a demographically matched sample of 27 control participants, along with clinical follow-up data in patients three months and 12 months after the scan. We used connectome-wide analyses to map disruptions of inter-regional pairwise connectivity and connectome-based predictive modelling to predict longitudinal change in symptoms and functioning. RESULTS: Individuals with FEP showed disrupted connectivity in a brain-wide network linking all brain regions when compared with controls (pFWE=.03). Baseline structural connectivity significantly predicted change in functioning over 12 months (r=.44;pFWE=.041), such that lower connectivity within fronto-striato-thalamic systems predicted worse functional outcomes. CONCLUSIONS: Brain-wide reductions of structural connectivity exist during the early stages of psychotic illness and cannot be attributed to antipsychotic medication. Moreover, baseline measures of structural connectivity can predict change in patient functional outcomes up to one year after engagement with treatment services.

Assessing the Clinical Efficacy of Therapeutic Drug Monitoring for Risperidone and Paliperidone in Patients with Schizophrenia: Insights from a Clinical Data Warehouse.

This study investigated the usage patterns and impact of therapeutic drug monitoring (TDM) for risperidone and paliperidone in patients diagnosed with schizophrenia, utilizing retrospective real-world data sourced from a single center's Clinical Data Warehouse. Our study cohort comprised patients diagnosed with schizophrenia undergoing treatment with either risperidone or paliperidone. Data on demographic characteristics, comorbidities, medication utilization, and clinical outcomes were collected. Patients were categorized into two groups: those undergoing TDM and those not undergoing TDM. Additionally, within the TDM group, patients were further stratified based on their risperidone and paliperidone concentrations relative to the reference range. The findings revealed that patients in the TDM group received higher risperidone and paliperidone doses (320 mg/day and 252 mg/day, p = 0.0045) compared to their non-TDM counterparts. Nevertheless, no significant disparities were observed in hospitalization rates, duration of hospital stays, or compliance between the two groups (p = 0.9082, 0.5861, 0.7516, respectively). Subgroup analysis within the TDM cohort exhibited no notable distinctions in clinical outcomes between patients with concentrations within or surpassing the reference range. Despite the possibility of a selection bias in assigning patients to the groups, this study provides a comprehensive analysis of TDM utilization and its ramifications on schizophrenia treatment outcomes.

Understanding profiles of patients with treatment-resistant depression by stringency of health plan prior authorization criteria for approval of esketamine nasal spray.

OBJECTIVES: In the United States (US), prescription drug coverage is subject to prior authorization (PA) criteria, which may vary between health plans and may exceed drug label requirements. This study aimed to characterize profiles and treatment history of patients with treatment-resistant depression (TRD) who initiated esketamine nasal spray, by stringency of their health plans' PA criteria relative to the esketamine label. METHODS: Adults with evidence of TRD (≥2 antidepressant courses of adequate dose and duration) prior to initiating esketamine were identified using US insurance claims data (03/2016-02/2022). Based on health plan PA criteria for esketamine obtained from Managed Markets Insight & Technology data (05/2020-02/2022), patients were grouped into stringent (PA criteria exceeds label) and non-stringent (PA criteria less stringent or equal to label) cohorts. Patient treatment history before esketamine initiation was compared using Wilcoxon rank sum and Fisher's exact tests. RESULTS: The stringent cohort included 168 patients (mean age: 45 years, 63% female) and the non-stringent cohort included 400 patients (mean age: 45 years, 70% female). During the ongoing major depressive episode before esketamine initiation, the stringent versus non-stringent cohort completed 3.9 versus 3.8 antidepressant treatment courses, on average (p = 0.217); 94.6% versus 96.8% used augmentation therapy (p = 0.240), including 59.3% versus 58.1% with an antipsychotic (p = 0.844), respectively. CONCLUSIONS: Regardless of health plan stringency, on average, patients exceeded US label-mandated number of antidepressant trials before esketamine initiation, which questions the need for health insurance plans PA criteria above label.

Orlistat for the treatment of antipsychotic-induced weight gain: an eight-week multicenter, randomized, placebo-controlled, double-blind trial.

BACKGROUND: Weight gain and metabolic disorders are commonly induced by antipsychotics. Orlistat is a lipase inhibitor used for weight control. The effect of orlistat on weight gain and metabolic disturbances in people (especially women) treated with antipsychotics has not been sufficiently studied. This study aimed to investigate the efficacy of orlistat in mitigating antipsychotic-induced weight gain and abnormal glycolipid metabolism. METHODS: Patients with schizophrenia or bipolar disorder with a weight gain ≥ 7% after taking antipsychotics were recruited. Participants were randomly allocated to two groups: one received eight weeks of orlistat (360 mg/day) and the other received a placebo. Anthropometric and fasting serum biochemical parameters were measured at baseline, week 4 and week 8. RESULTS: Sixty individuals (orlistat:placebo = 32:28) participated in the study. After controlling for the study center, the eight-week changes in body mass index (BMI), cholesterol (CHOL), high-density lipoprotein cholesterol (HDL-CH) and low-density lipoprotein cholesterol (LDL-CH) were significantly different between the groups. According to the mixed linear models, CHOL and LDL-CH were significantly lower in the orlistat group than in the control group at week 8. The week 0-to-8 slopes of BMI, CHOL and LDL-CH were also significantly lower in the orlistat group. CONCLUSIONS: These findings suggested that orlistat is an effective intervention for attenuating weight gain and serum lipid disturbances in antipsychotic-treated patients. TRIAL REGISTRATION: ClinicalTrials.gov NCT03451734.