Psychiatrists effect on positive symptom severity and daily functioning during pharmacotherapy for first-episode psychosis patients.

Clinical outcomes after a first-episode of psychosis (FEP) are heterogeneous. Many patient-related factors such as gender and comorbidity have been studied to predict symptomatic outcomes. However, psychiatrist-related factors such as prescription behaviour and gender have received little attention. We assessed the relationship between patients' psychiatrists, psychosis severity and daily functioning in 201 patients remitted from an FEP for a duration of one year, treated by 18 different psychiatrists. We controlled for baseline severity, dose and type of antipsychotic medication, frequency of visits, and patients' education. Symptom severity, daily functioning, and antipsychotic drug use were assessed at baseline and at 3, 6, and, 12 months follow-up. We found that psychiatrists accounted for 9.1% of the explained variance in patients' symptom severity and 10.1% of the explained variance in daily functioning.These effects persisted even when controlling for factors such as baseline severity and the prescribed dose. The effect of prescribed dose on symptom severity and daily functioning differed between psychiatrists. Treatment centre, session frequency, and medication nonadherence were not related to symptom severity. Our results emphasize the importance of individual psychiatrist factors in symptomatic outcomes after an FEP. Further identification of psychiatrist-related factors such as the quality of therapeutic alliances and shared decision-making, may optimize psychiatrists' training with the goal of improving patient outcomes.

Evaluation of Antipsychotic-Induced Neuroleptic Malignant Syndrome Using a Self-Organizing Map.

Introduction In neuropsychiatric pharmacotherapy, neuroleptic malignant syndrome (NMS) is a potentially serious side effect of antipsychotics characterized primarily by fever, disorientation, extrapyramidal disorders, and autonomic nervous system imbalance, which can lead to death if left untreated. We visualized the NMS profile of antipsychotics using a self-organizing map (SOM). We combined it with decision tree analysis to discriminate between 31 antipsychotics in more detail than typical antipsychotic (TAP) and atypical antipsychotic (AAP) classifications. Method A total of 20 TAPs and 11 AAPs were analyzed. We analyzed NMS reports extracted from the Japanese Adverse Drug Event Report (JADER) database based on standardized Medical Dictionary for Regulatory Activities (MedDRA) queries (Standardized MedDRA Queries (SMQ) code: 20000044, including 68 preferred terms). The SOM was applied using the SOM package in R version 4.1.2 (R Foundation for Statistical Computing, Vienna, Austria). Results The Japanese Adverse Drug Event Report (JADER) database contained 887,704 reports published between April 2004 and March 2024. The numbers of cases of NMS (SMQ code: 20000044) reported for risperidone, aripiprazole, haloperidol, olanzapine, and quetiapine were 1691, 1294, 1132, 1056, and 986, respectively. After the antipsychotics were classified into six units using SOM, they were adapted for decision tree analysis. First, 31 antipsychotics branched off into groups with loss of consciousness, with one group (10 TAPs) consisting entirely of TAPs, and the other consisting of antipsychotics that were further separated into two groups with coma induced by TAPs and AAPs. Conclusion The results of this study provide a reference for healthcare providers when predicting the NMS characteristics induced by each drug in patients, thereby facilitating the effective treatment of schizophrenia.

Impact of Demographics and Insurance Coverage on Schizophrenia Treatment and Healthcare Resource Utilization Within an Integrated Healthcare System.

Purpose: Little is known about the impact of health disparities on antipsychotic treatment and healthcare resource utilization (HRU) among patients with schizophrenia. The objective of this analysis is to examine treatment patterns and HRU by age, race/ethnicity, and insurance coverage among patients with schizophrenia in an integrated delivery network (IDN). Patients and Methods: This cross-sectional study used electronic health record data from MedStar Health, an IDN in the Baltimore-Washington, DC, area. Patients were aged ≥18 years and had ≥2 outpatient encounters or ≥1 hospitalization with a diagnosis of schizophrenia between January 1, 2017 and March 31, 2021. Outcomes assessed included oral antipsychotic prescriptions, long-acting injectable antipsychotic (LAI) utilization, hospitalizations, emergency department (ED) visits, and outpatient visits. Analyses compared subgroups based on age, race/ethnicity (non-Hispanic Black, non-Hispanic White, and other), and type of insurance coverage at index (Medicare, Medicaid, and other) during 12 months of follow-up. Results: A total of 78.1% of patients had ≥1 prescription for an antipsychotic and 69.1% received ≥1 second-generation antipsychotic. Second-generation long-acting injectables (SGA LAI) were utilized by 9.0% of patients, with the elderly and Medicaid beneficiaries having the lowest SGA LAI utilization. Overall, 61.7% of patients had ≥1 hospitalization, 56.4% had ≥1 outpatient visit, and 50.5% had ≥1 ED visit. Hospitalizations and ED visits were most common in those 18 to 24 years of age and in Medicaid beneficiaries, whereas outpatient visits were more common for the elderly and Medicare beneficiaries. Conclusion: At the population level, the results indicate widespread underprescription/underutilization of antipsychotics that have been shown to improve clinical and economic outcomes in patients with schizophrenia, particularly SGA LAI. Within specific subpopulations, disparities in treatment selection and HRU were observed, suggesting the need for increased attention to at-risk groups to ensure consistent quality of care regardless of age, race/ethnicity, or insurance coverage.

Dosing levels of antipsychotics and mood stabilizers in bipolar disorder: A Nationwide cohort study on relapse risk and treatment safety.

BACKGROUND: Finding effective treatment regimens for bipolar disorder is challenging, as many patients suffer from significant symptoms despite treatment. This study investigated the risk of relapse (psychiatric hospitalization) and treatment safety (non-psychiatric hospitalization) associated with different doses of antipsychotics and mood stabilizers in persons with bipolar disorder. METHODS: Individuals aged 15-65 with bipolar disorder were identified from Finnish national health registers in 1996-2018. Studied antipsychotics included olanzapine, risperidone, quetiapine, aripiprazole; mood stabilizers lithium, valproic acid, lamotrigine, and carbamazepine. Medication use was divided into three time-varying dose categories: low, standard, and high. The studied outcomes were risk of psychiatric hospitalization (relapse) and the risk of non-psychiatric hospitalization (treatment safety). Stratified Cox regression in within-individual design was used. RESULTS: The cohort included 60,045 individuals (mean age 41.7 years, SD 15.8; 56.4% female). Mean follow-up was 8.3 years (SD 5.8). Of antipsychotics, olanzapine and aripiprazole were associated with a decreased risk of relapse in low and standard doses, and risperidone in low dose. The lowest adjusted hazard ratio (aHR) was observed for standard dose aripiprazole (aHR 0.68, 95% CI 0.57-0.82). Quetiapine was not associated with a decreased risk of relapse at any dose. Mood stabilizers were associated with a decreased risk of relapse in low and standard doses; lowest aHR was observed for standard dose lithium (aHR 0.61, 95% CI 0.56-0.65). Apart from lithium, high doses of antipsychotics and mood stabilizers were associated with an increased risk of non-psychiatric hospitalization. Lithium was associated with a decreased risk of non-psychiatric hospitalization in low (aHR 0.88, 95% CI 0.84-0.93) and standard doses (aHR 0.81, 95% CI 0.74-0.88). CONCLUSIONS: Standard doses of lithium and aripiprazole were associated with the lowest risk of relapse, and standard dose of lithium with the lowest risk of non-psychiatric hospitalization. Quetiapine was not associated with decreased risk of relapse at any dose.

Antipsychotic Drugs: A Concise Review of History, Classification, Indications, Mechanism, Efficacy, Side Effects, Dosing, and Clinical Application.

The introduction of the first antipsychotic drug, chlorpromazine, was a milestone for psychiatry. The authors review the history, classification, indications, mechanism, efficacy, side effects, dosing, drug initiation, switching, and other practical issues and questions related to antipsychotics. Classifications such as first-generation/typical versus second-generation/atypical antipsychotics are neither valid nor useful; these agents should be described according to the Neuroscience-based Nomenclature (NbN). Antipsychotic drugs are not specific for treating schizophrenia. They reduce psychosis regardless of the underlying diagnosis, and they go beyond nonspecific sedation. All currently available antipsychotic drugs are dopamine blockers or dopamine partial agonists. In schizophrenia, effect sizes for relapse prevention are larger than for acute treatment. A major unresolved problem is the implausible increase in placebo response in antipsychotic drug trials over the decades. Differences in side effects, which can be objectively measured, such as weight gain, are less equivocal than differences in rating-scale-measured (subjective) efficacy. The criteria for choosing among antipsychotics are mainly pragmatic and include factors such as available formulations, metabolism, half-life, efficacy, and side effects in previous illness episodes. Plasma levels help to detect nonadherence, and once-daily dosing at night (which is possible with many antipsychotics) and long-acting injectable formulations are useful when adherence is a problem. Dose-response curves for both acute treatment and relapse prevention follow a hyperbolic pattern, with maximally efficacious average dosages for schizophrenia of around 5 mg/day risperidone equivalents. Computer apps facilitating the choice between drugs are available. Future drug development should include pharmacogenetics and focus on drugs for specific aspects of psychosis.

Cognitive profiles across the psychosis continuum.

Cognitive impairments are core features in individuals across the psychosis continuum and predict functional outcomes. Nevertheless, substantial variability in cognitive functioning within diagnostic groups, along with considerable overlap with healthy controls, hampers the translation of research findings into personalized treatment planning. Aligned with precision medicine, we employed a data driven machine learning method, self-organizing maps, to conduct transdiagnostic clustering based on cognitive functions in a sample comprising 228 healthy controls, 200 individuals at ultra-high risk for psychosis, and 98 antipsychotic-naïve patients with first-episode psychosis. The self-organizing maps revealed six clinically distinct cognitive profiles that significantly predicted baseline functional level and changes in functional level after one year. Cognitive flexibility in particular, as well as specific executive functions emerged as cardinal in differentiating the profiles. The application of self-organizing maps appears to be a promising approach to inform clinical decision-making based on individualized cognitive profiles, including patient allocation to different interventions. Moreover, this method has the potential to enable cross-diagnostic stratification in research trials, utilizing data-driven subgrouping informed by categories from underlying dimensions of cognition rather than from clinical diagnoses. Finally, the method enables cross-diagnostic profiling across other data modalities, such as brain networks or metabolic subtypes.

Characterising the nature of psychiatric disorders and patterns of antipsychotic medications prescribed in a psychiatric ward in a public hospital in Tasmania.

OBJECTIVE: We present an evaluation of antipsychotic prescribing in an inpatient psychiatry ward in Hobart, Tasmania, to establish pattern of use, alignment with other psychiatric wards or centres and the recommendations in the Royal Australian and New Zealand College of Psychiatry Clinical Practice Guidelines, and to determine predictors of polypharmacy. METHODS: A descriptive cross-sectional survey design was used. Data from 118 patients discharged from the Royal Hobart Hospital (RHH) Mental Health Inpatient Unit between 01/02/2021 to 01/08/2021 were evaluated. RESULTS: Antipsychotic polypharmacy (APP) was observed in 40% of patients. When low doses of adjunctive ('PRN') use of olanzapine and quetiapine were excluded, the APP proportion was 35%. APP was predicted by age and by a schizophrenia diagnosis. Long-acting injections (LAIs) were used in 46% of the patients. The most common LAI was risperidone (52%). Average daily dose of antipsychotic at the time of discharge was 529 mg chlorpromazine (CPZ) equivalents. High dose antipsychotics (more than 1000 mg CPZ equivalents per day) was observed in 13% of the patients. CONCLUSIONS: The observed prescribing practice is consistent with other clinical settings. Antipsychotic prescribing practice should, however, continue to be monitored to ensure adherence to best practice guidelines.

Childhood trauma types in relation to antipsychotic effectiveness in schizophrenia spectrum disorders: A prospective, pragmatic, randomized controlled study.

Treatment with antipsychotics (APs) for schizophrenia spectrum disorders (SSDs) is generally effective, however, a significant proportion does not respond favorably. Childhood trauma (CT) subtypes (physical, sexual, and emotional abuse, physical and emotional neglect) could influence treatment effectiveness; however, research is scarce. Heterogeneity in AP response could be explained by differentiating by CT subtype. The present study was based on the Bergen-Stavanger-Trondheim-Innsbruck (BeSt InTro) study. CTQ-SF assessed CT subtypes in SSDs (n = 98). CT subtypes were examined in relation to psychosis symptoms measured by PANSS during one year of treatment with APs, by means of linear mixed effects (LME) models. Results were significant for CT subtypes, where increased levels of sexual abuse and physical neglect were associated with increased mean levels of psychosis symptoms throughout the course of treatment from baseline to 52 weeks. AP effectiveness may thus be influenced by CT subtype in SSDs. The results support clinical guidelines recommending a focus on assessment and treatment of trauma in SSDs.

Olanzapine-Induced Weight Gain and Glycolipid Metabolism Aberrations in First-Episode and Antipsychotic-Naïve Schizophrenia Patients: A Longitudinal Study.

OBJECTIVE: Limited research has delved into the comprehensive impact of monotherapy on weight and glycolipid metabolism in schizophrenia (SCZ) patients. Our study aims to longitudinally investigate the multidimensional effects of olanzapine (OLA) monotherapy on weight and glycolipid metabolism in first-episode and antipsychotic-naïve (FEAN) SCZ patients. METHODS: A total of 74 FEAN-SCZ patients were recruited, as well as 58 sex- and age-matched healthy controls. Eligible patients underwent a 4-week OLA treatment regimen, with weight assessments conducted at baseline and week 4. Moreover, lipid profiles and fasting plasma glucose (FPG) were measured at baseline and week 4. Insulin, leptin (LEP), and adiponectin (APN) levels were determined using enzyme-linked immunosorbent assay (ELISA) kits. RESULTS: At baseline, FEAN-SCZ patients showed elevated levels of insulin, low-density lipoprotein (LDL), impaired insulin sensitivity, and reduced levels of APN compared to the healthy controls. Following 4-week OLA treatment, patients showed an increase in body mass index (BMI) of 0.96 kg/m2. Additionally, FPG, quantitative insulin sensitivity check index (QUICKI), HOMA-insulin sensitivity index (HOMA-ISI), and fasting plasma glucose to insulin ratio (G/I) displayed significant decreases, while insulin, HOMA-IR, and LEP levels showed significant increases. Stepwise regression analysis revealed that baseline FPG independently predicted the change in BMI after 4 weeks of OLA treatment. CONCLUSION: FEAN-SCZ patients exhibited pre-existing alterations in glucose homeostasis. After 4 weeks of OLA treatment, SCZ patients experienced significant weight gain, deteriorating insulin resistance, and increased LEP levels. In addition, baseline FPG emerged as a predictor of BMI changes after 4 weeks of OLA treatment.

Normocytic Anemia as a Side Effect of Clozapine: A Case Report.

This brief case report aims to shed light on an uncommon blood-related side effect potentially associated with clozapine use, an atypical antipsychotic primarily prescribed for treatment-resistant schizophrenia. A 70-year-old white male with a significant past medical history of schizophrenia controlled with clozapine was evaluated over approximately two months. Regular blood work was conducted to monitor his absolute neutrophil count, which is known to drop while on clozapine. During his stay, it was noticed that his hemoglobin levels were declining without a clear reason. Through the method of exclusion, the most common causes of anemia were ruled out, and it was determined that the patient's anemia was secondary to clozapine, a side effect that is not commonly reported. The precise mechanism by which clozapine affects hemoglobin levels remains unclear. However, some studies suggest potential direct bone marrow toxicity. This is supported by the rapid improvement in hemoglobin observed after clozapine discontinuation in this case. This case highlights a potential association between clozapine use and normocytic anemia. It emphasizes the significance of regular blood work monitoring not only for the absolute neutrophil count but also for hemoglobin. This rare case underscores the importance of considering red blood cell parameters in patients on clozapine, offering insights that go beyond the commonly reported agranulocytosis side effect and potentially expanding awareness of adverse hematological effects associated with this antipsychotic medication. Further research is crucial to unravel the underlying mechanisms and establish definitive causality.

Interictal psychosis of epilepsy: What is the role of the neurologist?

Psychotic disorders are more frequent in people with epilepsy than the general population. They constitute one of the most serious psychiatric comorbidities which require an immediate psychopharmacologic intervention. Yet, access to psychiatrists is often limited or not available and the neurologists taking care of these patients are called-upon to start treatment with antipsychotic medication. The purpose of this manuscript is to provide clinicians with pragmatic psychopharmacologic strategies to treat interictal psychotic disorders in patients with epilepsy. We review the case of a 45 years-old man with a 35-year history of treatment-resistant focal epilepsy of bitemporal origin who developed a de-novo psychotic episode that began with insomnia, mood lability and agitation and evolved into paranoid delusions, auditory hallucinations and a thought disorder. The patient was diagnosed with an interictal psychotic episode and was treated with aripiprazole which resulted in significant improvement after reaching a 20 mg /day dose and allowed for the patient to be discharged home. In summary, interictal psychotic episodes of epilepsy are relatively frequent in patients with epilepsy and require of an early psychopharmacologic treatment to facilitate their remission or stabilization until mental health professionals can take over their long-term care. Compared to primary psychotic disorders, interictal psychotic episodes respond better and at lower doses of antipsychotic drugs.

Prescribing Trends and Associated Outcomes of Antiepileptic Drugs and Other Psychotropic Medications in US Nursing Homes: Proposal for a Mixed Methods Investigation.

BACKGROUND: Pilot data suggest that off-label, unmonitored antiepileptic drug prescribing for behavioral and psychological symptoms of dementia is increasing, replacing other psychotropic medications targeted by purposeful reduction efforts. This trend accelerated during the COVID-19 pandemic. Although adverse outcomes related to this trend remain unknown, preliminary results hint that harms may be increasing and concentrated in vulnerable populations. OBJECTIVE: Using a mixed methods approach including both a retrospective secondary data analysis and a national clinician survey, this study aims to describe appropriate and potentially inappropriate antiepileptic and other psychoactive drug prescribing in US nursing homes (NHs), characteristics and patient-oriented outcomes associated with this prescribing, and how these phenomena may be changing under the combined stressors of the COVID-19 pandemic and the pressure of reduction initiatives. METHODS: To accomplish the objective, resident-level, mixed-effects regression models and interrupted time-series analyses will draw on cohort elements linked at an individual level from the Centers for Medicare and Medicaid Services' (CMS) Minimum Data Set, Medicare Part D, Medicare Provider Analysis and Review, and Outpatient and Public Use Files. Quarterly cohorts of NH residents (2009-2021) will incorporate individual-level data, including demographics; health status; disease variables; psychotropic medication claims; comprehensive NH health outcomes; hospital and emergency department adverse events; and NH details, including staffing resources and COVID-19 statistics. To help explain and validate findings, we will conduct a national qualitative survey of NH prescribers regarding their knowledge and beliefs surrounding changing approaches to dementia care and associated outcomes. RESULTS: Funding was obtained in September 2022. Institutional review board exemption approval was obtained in January 2023. The CMS Data Use Agreement was submitted in May 2023 and signed in March 2024. Data access was obtained in June 2024. Cohort creation is anticipated by January 2025, with crosswalks finalized by July 2025. The first survey was fielded in October 2023 and published in July 2024. The second survey was fielded in March 2024. The results are in review as of July 2024. Iterative survey cycles will continue biannually until December 2026. Multidisciplinary dissemination of survey analysis results began in July 2023, and dissemination of secondary data findings is anticipated to begin January 2025. These processes are ongoing, with investigation to wrap up by June 2027. CONCLUSIONS: This study will detail appropriate and inappropriate antiepileptic drug use and related outcomes in NHs and describe disparities in long-stay subpopulations treated or not treated with psychotropics. It will delineate the impact of the pandemic in combination with national policies on dementia management and outcomes. We believe this mixed methods approach, including processes that link multiple CMS data sets at an individual level and survey-relevant stakeholders, can be replicated and applied to evaluate a variety of patient-oriented questions in diverse clinical populations. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/64446.

A Longitudinal Treatment Effect Analysis of Antipsychotics on Behavior of Residents in Long-Term Care.

OBJECTIVE: The proportion of long-term care (LTC) residents being treated with antipsychotic medication is high, and these medications may exacerbate behavioral symptoms. We used propensity scores to investigate the effect of antipsychotic use on the worsening of behavioral symptoms among residents in LTC facilities. DESIGN: A retrospective study. SETTING AND PARTICIPANTS: Residents in LTC in 8 provinces and 1 territory in Canada, without severe aggressive behavior at baseline and reassessed at follow-up, between March 2000 and March 2022. METHODS: We used propensity score matching and weighting to balance baseline covariates and logistic regression to estimate the effect of antipsychotics on the worsening of behavioral symptoms in the original, matched, and weighted cohorts. The treatment variable was use of antipsychotic medication at baseline and the outcome was worsening of behavior at follow-up. RESULTS: A total of 494,215 participants were included (318,234 women and 175,981 men; mean age 82.8 years [SD 10.1; range 18-112]).130 558 (26.4%) used antipsychotics at baseline and 88,632 (17.9%) had worsening behavior in follow-up. In the matched cohort, there were 249,698 participants, and 124,849 were matched (1:1) in each treatment group. There was a significant association between antipsychotic use at baseline and worsening in behavior at follow-up in the adjusted regression models (OR 1.27 [95% CI 1.25-1.29], <0.0001) as well as in matched (OR 1.20 [95% CI 1.17-1.21], <0.0001) and weighted (OR 1.26 [95% CI 1.24-1.28], <0.0001) cohorts. CONCLUSIONS AND IMPLICATIONS: This study further evidence to support the cautious use of antipsychotics in LTC facilities. Future research in LTC facilities could include a more granular analyses of behavior change, including bidirectional analyses between different symptom severity classifications.

Individualized multi-modal MRI biomarkers predict 1-year clinical outcome in first-episode drug-naïve schizophrenia patients.

Background: Antipsychotic medications offer limited long-term benefit to about 30% of patients with schizophrenia. We aimed to explore the individual-specific imaging markers to predict 1-year treatment response of schizophrenia. Methods: Structural morphology and functional topological features related to treatment response were identified using an individualized parcellation analysis in conjunction with machine learning (ML). We performed dimensionality reductions using the Pearson correlation coefficient and three feature selection analyses and classifications using 10 ML classifiers. The results were assessed through a 5-fold cross-validation (training and validation cohorts, n = 51) and validated using the external test cohort (n = 17). Results: ML algorithms based on individual-specific brain network proved more effective than those based on group-level brain network in predicting outcomes. The most predictive features based on individual-specific parcellation involved the GMV of the default network and the degree of the control, limbic, and default networks. The AUCs for the training, validation, and test cohorts were 0.947, 0.939, and 0.883, respectively. Additionally, the prediction performance of the models constructed by the different feature selection methods and classifiers showed no significant differences. Conclusion: Our study highlighted the potential of individual-specific network parcellation in treatment resistant schizophrenia prediction and underscored the crucial role of feature attributes in predictive model accuracy.

Effectiveness of Vitamin E in Treatment of Antipsychotic-Induced Tardive Dyskinesia and Extrapyramidal Symptoms: A Case Report.

Antipsychotic medications, while crucial in managing severe psychiatric disorders such as schizophrenia and bipolar disorder, are frequently associated with extrapyramidal symptoms (EPS) and tardive dyskinesia (TD). TD, characterized by repetitive, involuntary movements, especially of the face and limbs, poses a substantial clinical challenge due to its often irreversible nature. Conventional management strategies, including dose reduction and switching to atypical antipsychotics, frequently offer limited success, prompting exploration of alternative therapies. This case report highlights the effectiveness of vitamin E, a potent antioxidant, in treating a 28-year-old male with severe antipsychotic-induced EPS and TD, unresponsive to traditional therapies. The patient, who had been receiving paliperidone injections as part of his psychotic disorder treatment regimen, developed marked EPS, including muscle rigidity, a parkinsonian gait, significant motor disturbances as well as tardive dyskinesia. Despite discontinuation of paliperidone and initiation of procyclidine, propranolol, clonazepam, and omega-3 supplements, his symptoms persisted. Introduction of oral vitamin E at 400 IU daily led to a dramatic improvement, with an 80% reduction in EPS and TD symptoms within weeks. The patient's Abnormal Involuntary Movement Scale (AIMS) score decreased from 24 to 4, and his overall quality of life improved significantly. Gradual increase of vitamin E dosage to 1200 IU daily, coupled with tapering of other medications, eventually led to complete resolution of symptoms, as evidenced by an AIMS score of 0. The patient maintained symptom-free status during follow-up, with no recurrence of psychotic symptoms. This case underscores the potential role of vitamin E as a viable adjunctive treatment for TD, particularly in patients who do not respond adequately to conventional therapies. While the literature presents mixed evidence regarding vitamin E's effectiveness, this case adds to the growing body of research suggesting its benefits, especially when introduced early in the disease course. Further large-scale studies are warranted to establish the most effective treatment protocols and identify patient populations most likely to benefit from vitamin E therapy.

Are circadian rhythms more favorable with lithium than with other mood stabilizers? An exploratory actigraphy study in euthymic bipolar disorder type 1.

BACKGROUND: Bipolar Disorder (BD) is associated with alterations of circadian rhythms of activity (CRA). Experimental research suggests that lithium (Li) modifies CRA, but this has been rarely explored in BD using actigraphy. METHODS: The sample comprised 88 euthymic BD-I cases with 3 weeks of actigraphy. We used a Principal Component Analysis (PCA) to generate CRA dimensions. We then used linear regression analyses to compare these dimensions between groups of individuals defined according to prescribed mood stabilizers: Li monotherapy ("Li" group, n = 28), anticonvulsant or atypical antipsychotic monotherapy ("AC or AAP" group, n = 27) or combined treatments ("Li+AC or Li+AAP" group, n = 33). Analyses were adjusted for potential confounders (gender, age, body mass index, depressive symptoms, co-prescribed benzodiazepines and antidepressants, smoking status and past alcohol use disorder). RESULTS: The PCA identified two dimensions: "robust CRA" (high amplitude and interdaily stability, with low intradaily variability) and "late chronotype". Univariate analyses showed higher scores for "robust CRA" in the "Li" versus the "AC or AAP" (p = 0.021) or "Li+AC or Li+AAP" groups (p = 0.047). These findings remained significant after adjustments (respectively p = 0.010 and p = 0.019). Post-hoc analyses suggested lower variability, higher stability and higher amplitude of CRA in the "Li" group. Medication groups were similar for the "late chronotype" dimension (p = 0.92). CONCLUSIONS: This actigraphy study is the first to show more favorable CRA in BD-I individuals receiving a Li monotherapy when compared with those receiving other classes or combinations of mood stabilizers. Replications in larger samples are required. Prospective studies are also warranted to elucidate whether the introduction of Li or other mood stabilizers might influence CRA in BD-I.

Drugs with glutamate-based mechanisms of action in psychiatry.

Psychopharmacotherapy of major psychiatric disorders is mostly based on drugs that modulate serotonergic, dopaminergic, or noradrenergic neurotransmission, either by inhibiting their reuptake or by acting as agonists or antagonists on specific monoamine receptors. The effectiveness of this approach is limited by a significant delay in the therapeutic mechanism and self-perpetuating growth of treatment resistance with a consecutive number of ineffective trials. A growing number of studies suggest that drugs targeting glutamate receptors offer an opportunity for rapid therapeutic effect that may overcome the limitations of monoaminergic drugs. In this article, we present a review of glutamate-modulating drugs, their mechanism of action, as well as preclinical and clinical studies of their efficacy in treating mental disorders. Observations of the rapid, robust, and long-lasting effects of ketamine and ketamine encourages further research on drugs targeting glutamatergic transmission. A growing number of studies support the use of memantine and minocycline in major depressive disorder and schizophrenia. Amantadine, zinc, and Crocus sativus extracts yield the potential to ameliorate depressive symptoms in patients with affective disorders. Drugs with mechanisms of action based on glutamate constitute a promising pharmacological group in the treatment of mental disorders that do not respond to standard methods of therapy. However, further research is needed on their efficacy, safety, dosage, interactions, and side effects, to determine their optimal clinical use.

Effects of Antipsychotics on the Hypothalamus-Pituitary-Adrenal Axis in a Phencyclidine Animal Model of Schizophrenia.

Schizophrenia (SCH) is a mental disorder that requires long-term antipsychotic treatment. SCH patients are thought to have an increased sensitivity to stress. The dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis, observed in SCH, could include altered levels of glucocorticoids, glucocorticoid receptors (GRs), and associated proteins. The perinatal administration of phencyclidine (PCP) to rodents represents an animal model of SCH. This study investigated the effects of perinatal PCP exposure and subsequent haloperidol/clozapine treatment on corticosterone levels measured by ELISA and the expression of GR-related proteins (GR, pGR, HSP70, HSP90, FKBP51, and 11ß-Hydroxysteroid dehydrogenase-11ß-HSD) determined by Western blot, in different brain regions of adult rats. Six groups of male rats were treated on the 2nd, 6th, 9th, and 12th postnatal days (PN), with either PCP or saline. Subsequently, one saline and one PCP group received haloperidol/clozapine from PN day 35 to PN day 100. The results showed altered GR sensitivity in the rat brain after PCP exposure, which decreased after haloperidol/clozapine treatment. These findings highlight disturbances in the HPA axis in a PCP-induced model of SCH and the potential protective effects of antipsychotics. To the best of our knowledge, this is the first study to investigate the effects of antipsychotic drugs on the HPA axis in a PCP animal model of SCH.

Long-Acting Injectable Antipsychotic Medication Use in Youth: A Systematic Review of the Literature Along with MedWatch Safety Data and Prescriber Attitudes.

Objectives: Long-acting injectable (LAI) antipsychotic medications are being prescribed to children and adolescents along a broad age range from 2 to 17 years old. However, there is no U.S. Food and Drug Administration (FDA) approved indication for the use of any LAI in a pediatric population. The goal of this article is to perform a systematic literature review regarding the use of LAIs in a pediatric population, to obtain pediatric LAI safety data, and to survey prescriber attitudes regarding LAI use in youth. Methods: A search for relevant articles between June 1986 and June 2021 was conducted. Safety data were obtained from FDA MedWatch postmarketing adverse event reports regarding LAI use in children and adolescents. A survey of practicing Child and Adolescent Psychiatrists in Wisconsin was done regarding the use of LAIs in youth. Results: The predominant reasons for LAI use in youth were illness severity and treatment noncompliance. Twenty-six of 30 identified studies and reports favored LAI use in youth, but were of low to very low quality. Overall, 587 FDA MedWatch reports between June 1986 and June 2021 were identified. Most adverse events occurred in modest numbers. Extrapyramidal symptoms accounted for 18% of all MedWatch reports, neuroleptic malignant syndrome accounted for 3% of all reports, and deaths accounted for 2% of all reports. The concern for safety was reflected in prescriber survey results along with a recognition that LAIs can be helpful to target severe psychiatric symptoms and address treatment noncompliance. Conclusions: No randomized controlled studies were found. Identified published studies and reports were of low to very low quality. However, it appeared reasonable that the use of LAIs in a select group of pediatric patients can be helpful to target severe psychiatric symptoms and to enhance treatment compliance.