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Background: Aripiprazole once-monthly (AOM) has proven effective in the treatment of schizophrenia, although little is known about its impact on global functioning and quality of life beyond 1 year. Here, we investigate the continued impact of AOM on the participants of the ReLiAM study during the second year of follow-up. Methods: The participants who were evaluated at ≥ 1 time point during the second year of the ReLiAM study (months 15, 18, 21, and 24; year 1 completers) were assessed via the GAF scale. Secondary outcomes were reported on the SOFAS, CGI-S, and QLS. Results: 109 (86%) completed at least 1 post-12-month visit and 33 (30.3%) patients completed the final assessment at month 24. The improvements observed in the year 1 completers in GAF total score were maintained through to year 2 completers. The improvements in CGI-S and SOFAS that were observed at the end of year 1 were also maintained through the end of the second year. Similar trends of sustained improvement in GAF total score, CGI-S score, and SOFAS were observed in the post-hoc analyses of the year 2 completers. Seventy-four percent (74.3%) of year 1 completers experienced mild treatment-emergent adverse events during the second year, the most frequently reported being weight gain, akathisia, and insomnia. Seventeen percent (17.4%) experienced serious adverse events. Similar findings regarding effectiveness and tolerability were reported in the year 1 completers and in year 2 completers. Conclusions: These findings suggest that the favorable effectiveness, including tolerability observed during the first year following AOM initiation, are maintained and may even continue to improve during the second year of treatment. Trial registration: ClinicalTrials.gov NCT02131415, first posted on May 6, 2014. Overall trial status: Terminated. [ABSTRACT FROM AUTHOR]

In this study, we aimed to investigate the nationwide utilization of antipsychotic drugs (APDs) during radiotherapy and evaluate their association with survival in patients with breast cancer. This retrospective cohort study used the National Health Insurance Service database in Korea and included patients diagnosed with breast cancer from 2010 to 2020 who received radiotherapy. The APDs included in the analysis were aripiprazole, quetiapine, olanzapine, risperidone, haloperidol, and chlorpromazine, and the APD prescription details included prescription time, dosage, and duration. Among 170,226 patients with breast cancer treated with radiotherapy, 3361 (1.97%) received APD during radiotherapy. Use of APDs was significantly associated with higher mortality in all patients and in a subgroup of patients excluding those with metastasis or other cancers. Among patients taking APD during radiotherapy, those with accompanied psychiatric history and long-term APD use for ≥ 3 months were associated with lower mortality, whereas patients who started APD during radiotherapy had higher mortality than those who started APD before radiotherapy. The high mortality observed in breast cancer patients using APDs during radiotherapy could be influenced by the underlying conditions that necessitated APD use. Further studies are needed to determine the effects of APDs during radiotherapy in patients with breast cancer. [ABSTRACT FROM AUTHOR]

Background Case Presentation Conclusions Ischemic priapism is a rare pathological condition, and delayed intervention can result in irreversible sequelae. Most cases are attributed to the use of antipsychotics. The blockade of α1‐adrenergic receptors is thought to be associated with the disease onset, although data supporting this hypothesis are lacking. No consensus regarding the optimal choice of medication is available.A 59‐year‐old man with schizophrenia, who had been receiving long‐acting injections of risperidone, developed ischemic priapism after receiving paliperidone treatment. Following improvement in ischemic priapism, we administered a combination of aripiprazole and olanzapine, which improved his psychiatric symptoms. We did not observe any recurrence of ischemic priapism.Switching the antipsychotic drug causing ischemic priapism to patients having a relatively low affinity for α1‐adrenergic receptors may enable the treatment of schizophrenia without recurrence of ischemic priapism. In addition to the affinity for α1‐adrenergic receptor, differences in metabolic enzyme types and antipsychotic doses may be involved in the occurrence of ischemic priapism. Accumulating evidence is necessary to establish guidelines for selecting medication of patients with ischemic priapism. [ABSTRACT FROM AUTHOR]

Objective: The incidence of neuroleptic malignant syndrome (NMS), a rare, potentially fatal adverse effect of antipsychotics, among children and youth is unknown. This cohort study estimated NMS incidence in antipsychotic users age 5–24 years and described its variation according to patient and antipsychotic characteristics. Methods: We used national Medicaid data (2004–2013) to identify patients beginning antipsychotic treatment and calculated the incidence of NMS during antipsychotic current use. Adjusted hazard ratios (HRs) assessed the independent contribution of patient and antipsychotic characteristics to NMS risk. Results: The 1,032,084 patients had 131 NMS cases during 1,472,558 person-years of antipsychotic current use, or 8.9 per 100,000 person-years. The following five factors independently predicted increased incidence: age 18–24 years (HR [95% CI] = 2.45 [1.65–3.63]), schizophrenia spectrum and other psychotic disorders (HR = 5.86 [3.16–10.88]), neurodevelopmental disorders (HR = 7.11 [4.02–12.56]), antipsychotic dose >200mg chlorpromazine-equivalents (HR = 1.71 [1.15–2.54]), and first-generation antipsychotics (HR = 4.32 [2.74–6.82]). NMS incidence per 100,000 person-years increased from 1.8 (1.1–3.0) for those with none of these factors to 198.1 (132.8–295.6) for those with 4 or 5 factors. Findings were essentially unchanged in sensitivity analyses that restricted the study data to second-generation antipsychotics, children age 5–17 years, and the 5 most recent calendar years. Conclusion: In children and youth treated with antipsychotics, five factors independently identified patients with increased NMS incidence: age 18–24 years, schizophrenia spectrum and other psychotic disorders, neurodevelopmental disorders, first-generation drugs, and antipsychotic doses greater than 200 mg chlorpromazine-equivalents. Patients with 4 or 5 of these factors had more than 100 times the incidence of those with none. These findings could improve early identification of children and youth with elevated NMS risk, potentially leading to earlier detection and improved outcomes. [ABSTRACT FROM AUTHOR]

Background Currently, guidance on the most effective treatment for patients with clozapine-resistant schizophrenia-spectrum disorders (SSD) is lacking. While augmentation strategies to clozapine with aripiprazole and electroconvulsive therapy (ECT) have been demonstrated to be effective in patients with clozapine-resistant schizophrenia spectrum disorders (CRS), head-to-head comparisons between these addition strategies are unavailable. We therefore aim to examine the feasibility of a larger randomized, single-blind trial comparing the effectiveness, cost-effectiveness, and safety of aripiprazole addition vs. ECT addition in CRS. Methods In this multi-center, randomized, single-blind feasibility study, the feasibility of recruiting 20 participants with CRS who will be randomized to either aripiprazole or bilateral ECT addition will be assessed. The main endpoint is the number of patients willing to be randomized. The number of screened individuals and reasons to decline participation will be recorded. Effects will be estimated for the benefit of the foreseen larger trial. To that end, differences between both arms in symptom severity will be assessed using blinded video assessments. In addition, tolerability (e. g., cognitive functioning), safety, quality of life, recovery, and all-cause discontinuation will be compared. The follow-up period is 16 weeks, after which non-responders will be given the option to switch to the other treatment. Discussion Strengths of this feasibility trial include maintaining blinding with video assessment, a possibility to switch groups in case of non-response, and a broad set of outcome measures. Identification of factors contributing to non-participation and drop-out will generate valuable information on trial feasibility and may enhance recruitment strategies in a follow-up RCT. Trial registration The study has been approved by the Medical Research Ethics Committee of the Amsterdam University Medical Center, location AMC, and was registered on 1 May 2022 in the EU Clinical Trials Register (EudraCT) under the trial name 'EMECLO' (2021–006333–19). [ABSTRACT FROM AUTHOR]

Introduction While antipsychotics are often prescribed for behavioral and psychological symptoms of dementia (BPSD), typically on an off-label basis, these medications have serious adverse effects. This study investigated the long-term use of antipsychotics among inpatients with dementia displaying severe BPSD, focusing on how prescriptions change over time. Methods Medical charts at Kusakabe Memorial Hospital were retrospectively reviewed from October 2012 to September 2021. The study included patients diagnosed with dementia, admitted for BPSD, and were continuing antipsychotics at 3 months of their admission. Antipsychotic dosages were categorized as high (≥300 mg/d), medium (100–300 mg/d), and low (<100 mg/d) based on chlorpromazine equivalents and tracked until 15 months during hospitalization. Binary logistic regression was used to identify factors associated with dosage reductions between months 3 and 6. Results This study involved 188 patients, with an average age of 81.2 years, 67% of whom were diagnosed with Alzheimer's dementia. At 3 months, 15.4% were taking high, 44.1% on medium, and 40.4% on low dosages of antipsychotics. The highest average dosage was observed at 3 months, with a subsequent decrease over time. By the 12th month, 20–30% of patients in all dosage categories had stopped their antipsychotic medication. Significant factors for dosage reduction included higher initial doses (OR 1.003, 95%Cl: 1.001–1.006, P=0.01) and male gender (OR 2.481, 95%Cl: 1.251–4.918, P=0.009). Discussion A trajectory of antipsychotic dosage in inpatients with severe BPSD has rarely been reported. This research emphasizes the need for personalized strategies in managing long-term pharmacotherapy for this vulnerable group of patients. [ABSTRACT FROM AUTHOR]

Tardive dyskinesia and dystonia are intractable extrapyramidal symptoms caused by the blockade of dopamine receptors by antipsychotic drugs. In addition to the reduction or discontinuation of the causative drug, valbenazine for tardive dyskinesia and botulinum toxin for tardive dystonia have been reported to be effective. However, their efficacy has not been fully demonstrated. In this study, we report the case of a female patient with bipolar disorder, valbenazine-resistant tardive dystonia, and tardive dyskinesia who achieved improvement in extrapyramidal symptoms with electroconvulsive therapy. Additionally, we conducted a narrative literature review on the safety and efficacy of electroconvulsive therapy for tardive dyskinesia and dystonia. [ABSTRACT FROM AUTHOR]

Psychiatric disorders are common in patients on hemodialysis. To the best of our knowledge there are no reported cases of psychosis developing in hemodialysis patients in the context of nephrectomy, and there is limited data on the use of long-acting antipsychotics in hemodialysis, which are generally not recommended in chronic kidney disease. We present the case of a 40-year-old lady with bilateral nephrectomy receiving hemodialysis who developed psychosis that resulted in her refusing to continue hemodialysis and was irregularly compliant with oral antipsychotics, necessitating the use of a long-acting injection. We report on the approach to clinical reasoning in the choice of aripiprazole and the need for a long-acting injection. Based on its pharmacological and pharmacokinetic properties oral aripiprazole 20 mg was commenced and after establishing tolerability and response, the patient was switched to long-acting aripiprazole 400 mg monthly achieving full remission of psychotic symptoms after 6 months with maintained improvement after 12 months. Based on its properties, aripiprazole may be a reasonable option in the treatment of psychosis in patients on hemodialysis with nephrectomy and can be considered even as a long-acting injection in these patients. [ABSTRACT FROM AUTHOR]

Long‐term sample stability of five atypical antipsychoticdrugs risperidone, paliperidone, clozapine, quetiapine and olanzapine and the antidepressant drug mirtazapine in serum was studied by use of a newly developed and validated analytical method based on solid‐phase extraction and liquid chromatography–tandem mass spectrometry. Ascorbic acid was used as an antioxidative agent to stabilize olanzapine during storage and sample preparation. We assessed analyte stability on long‐term storage in serum samples at 25°C, 5°C, −20°C and −80°C, and during five freeze–thaw cycles. Analytes were stable for 23 days at room temperature except for olanzapine and mirtazapine (17 days). All analytes were stable for at least 30 days at 5°C. All analytes were stable for 270 days at −20°C, except for paliperidone and mirtazapine with 60 days and 180 days, respectively. All analytes were stable for 270 days at −80°C. Furthermore, all analytes were stable for five freeze–thaw cycles. We recommend storage at −80°C when samples drawn for analysis of antipsychotic drugs are stored for more than 60 days, whereas a temperature of −20°C is sufficient for storage less than 60 days. [ABSTRACT FROM AUTHOR]

Background and Hypothesis There is a paucity of research on treatment outcomes of patients with psychosis and cannabis use disorder (CUD). We aimed to compare the effectiveness of antipsychotics in reducing the risk of hospitalization in patients with first-episode psychosis (FEP) and co-occurring CUD. Study Design We utilized a nationwide Swedish cohort of patients with longitudinal register data from the year 2006 to 2021. Participants were patients with FEP and co-occurring CUD (n  = 1820, 84.73% men, mean age 26.80 years, SD 8.25 years). The main outcome was hospitalization due to psychotic relapse. Hospitalization due to any psychiatric disorder or substance use disorder (SUD) were examined as secondary outcomes. Within-individual Cox regression models were used to study these associations. Study Results Use of any antipsychotic was associated with a 33% risk reduction of psychotic relapse (aHR = 0.67; 95% CI 0.60–0.75). Clozapine (0.43; 0.29–0.64), long-acting injectable (LAI) formulations of risperidone (0.40; 0.22–0.71), aripiprazole (0.42; 0.27–0.65), and paliperidone (0.46; 0.30–0.69) were associated with the lowest risk of relapse. The association between the LAI formulation of olanzapine and hospitalization due to psychosis was statistically non-significant (0.61; 0.35–1.05). Clozapine was associated with an 86% risk reduction of hospitalization due to SUD (0.14; 0.05–0.44). Of oral non-clozapine antipsychotics, aripiprazole was associated with the lowest risk of hospitalization due to psychotic relapse (0.61; 0.45–0.83). Conclusions These findings support the use of clozapine, LAI formulations of second-generation antipsychotics other than olanzapine, or oral aripiprazole to prevent hospitalization in FEP and co-occurring CUD. [ABSTRACT FROM AUTHOR]

Background: Increased awareness of the factors contributing to the diagnostic disparities seen in bipolar disorder between individuals of different heritage is needed to achieve equity in diagnosis and treatment. One such inequity is the provision of earlier treatment. Earlier treatment of patients diagnosed with bipolar disorder may prolong time to recurrence of mood episodes and reduce functional impairment and other poor outcomes associated with disease progression. The aim of this post hoc analysis was to study the efficacy and safety of long-acting injectable aripiprazole once-monthly 400 mg (AOM 400) in patients with earlier-stage bipolar I disorder (BP-I). Data from a 52-week multicenter, double-blind, placebo-controlled, randomized withdrawal trial of AOM 400 versus placebo in patients with BP‑I (NCT01567527) were analyzed. Those patients in the lowest quartiles for age (18–≤32 years; n = 70) or disease duration (0.13–≤4.6 years; n = 67) at baseline were categorized with earlier-stage BP-I. The primary endpoint was time from randomization to recurrence of any mood episode. Other endpoints included proportion of patients with recurrence of any mood episode, and change from baseline in Young Mania Rating Scale (YMRS) and Montgomery–Åsberg Depression Rating Scale (MADRS) total scores. Results: Maintenance treatment with AOM 400 significantly delayed time to recurrence of any mood episode versus placebo in patients aged 18–≤32 years (hazard ratio [HR]: 2.46 [95% confidence interval (CI) 1.09, 5.55]; p = 0.0251) or with disease duration 0.13–≤4.6 years (HR: 3.21 [95% CI 1.35, 7.65]; p = 0.005). This was largely driven by a lower proportion of patients in the AOM 400 group with YMRS total score ≥15 or clinical worsening. Changes from baseline in MADRS total score in both earlier-stage groups indicated AOM 400 did not worsen depression versus placebo. The safety profile of AOM 400 was consistent with the original study. Note that the original study included patients who had previously been stabilized on AOM 400 monotherapy, which may have enriched the population with patients who respond to and tolerate AOM 400. Conclusions: In this post hoc analysis, AOM 400 prolonged time to recurrence of any mood episode versus placebo in earlier-stage BP-I. These findings support early initiation of maintenance treatment with AOM 400. [ABSTRACT FROM AUTHOR]

Quetiapine is a second-generation atypical antipsychotic drug that has been commonly prescribed for the treatment of schizophrenia, major depressive disorder (depression), and other psychological disorders. Targeted inhibition of hyperpolarization-activated cyclic-nucleotide gated (HCN) channels, which generate Ih, may provide effective resistance against schizophrenia and depression. We investigated if HCN channels could contribute to the therapeutic effect of quetiapine, and its major active metabolite norquetiapine. Two-electrode voltage clamp recordings were used to assess the effects of quetiapine and its active metabolites 7-hydroxyquetiapine and norquetiapine on currents from HCN1 channels expressed in Xenopus laevis oocytes. Norquetiapine, but not quetiapine nor 7-hydroxyquetiapine, has an inhibitory effect on HCN1 channels. Norquetiapine selectively inhibited HCN1 currents by shifting the voltage-dependence of activation to more hyperpolarized potentials in a concentration-dependent manner with an IC50 of 13.9 ± 0.8 µM for HCN1 and slowing channel opening, without changing the kinetics of closing. Inhibition by norquetiapine primarily occurs from in the closed state. Norquetiapine inhibition is not sensitive to the external potassium concentration, and therefore, likely does not block the pore. Norquetiapine inhibition also does not dependent on the cyclic-nucleotide binding domain. Norquetiapine also inhibited HCN4 channels with reduced efficacy than HCN1 and had no effect on HCN2 channels. Therefore, HCN channels are key targets of norquetiapine, the primary active metabolite of quetiapine. These data help to explain the therapeutic mechanisms by which quetiapine aids in the treatment of anxiety, major depressive disorder, bipolar disorder, and schizophrenia, and may represent a novel structure for future drug design of HCN inhibitors. [ABSTRACT FROM AUTHOR]

Dopamine D2 receptor occupancy (D2RO) significantly influences the clinical effectiveness and safety of many antipsychotic drugs. Maintaining a D2RO range of 65%–80% provides the best antipsychotic effects while minimizing adverse reactions. Data from a Phase III trial were used to establish an exposure–response relationship for monthly intramuscular Risperidone ISM (75 and 100 mg) or placebo administered to adults with schizophrenia. Pharmacodynamic analysis was based on an Emax model for Positive and Negative Syndrome Scale (PANSS) developed in NONMEM. Plasma concentrations of the active moiety were derived using a previously developed population pharmacokinetic model, which was used for D2RO simulations in conjunction with a published Emax model. The optimal D2RO range (65%–80%) was reached for the median within hours following the first injection of both Risperidone ISM doses. At steady state, median D2RO for both doses remained above 65% throughout the 28‐day dosing period and demonstrated lower variability than oral risperidone. PANSS response did not differ significantly between dose groups, most likely because active moiety concentrations had already reached the plateau of the concentration–response relationship. The pharmacokinetic/pharmacodynamic analysis showed a profound placebo effect (−11.7%), and an additional maximal drug effect (−6.6%) resulting in a total PANSS improvement over time of −18.3%. Pharmacokinetic/pharmacodynamic modeling quantified a PANSS improvement over time after Risperidone ISM administration. The response was not significantly different in either dose group, likely because D2RO was already above the proposed efficacy threshold (65%) within 1 h after the first Risperidone ISM injection and remained above this level following repeated administrations. [ABSTRACT FROM AUTHOR]

Bipolar disorder is the fourth most debilitating psychiatric illness in the world regarding Disability Adjusted Life Years and manic episodes frequently lead to lengthy hospitalizations which restricts the freedom of patients. Therefore, decreasing the length of hospitalization with safer agents is of utmost importance in the treatment of manic episodes. Aripiprazole is a medication known for its efficacy in managing mania associated with bipolar disorder. Aripiprazole long‐acting injection is approved for the treatment of mania associated with bipolar disorder in adults and found efficacious as a maintenance treatment. In the treatment of schizophrenia, European Medicines Agency has approved a simplified starting strategy of aripiprazole once a month, with two 400 mg injections and a single oral 20 mg dose of aripiprazole. To the best of our knowledge, no previous study has reported the safety, tolerability, and efficacy of this regimen in adult bipolar disorder patients. We present a case series of eight patients who were admitted to the hospital in a manic episode with psychotic features. We observed that the double injection start regimen was effective in treating manic symptoms with no specific severe adverse events. We conclude from a small sample of manic patients that a double injection start regimen has good efficacy and tolerability. [ABSTRACT FROM AUTHOR]

Introduction: Bipolar disorder is a recurrent mental health disorder with a prevalence rate of 1.4%. On average, there can be a delay of 9.5 years from the initial presentation of symptoms to a confirmed diagnosis. Individuals living with bipolar disorder have a reduced life expectancy. There is limited evidence regarding the effectiveness of antidepressants in treating bipolar disorder. The ASCEnD clinical trial will test the clinical and cost‐effectiveness of the aripiprazole/sertraline combination in comparison with quetiapine for the treatment of bipolar depression (individuals who suffer from depressive episodes in bipolar disorder) and will include a nested qualitative study. Methods: The qualitative study will use semi‐structured interviews to explore pilot trial participants' and clinicians' perspectives on recruitment procedures, the acceptability of the intervention, the management of bipolar disorder and attitudes to medication combinations. Conclusion: Findings will inform recruitment strategies and optimise training for the participating sites in the ASCEnD full trial. They will also help to illuminate the lived experience of people with bipolar disorder and the clinicians who work with people with bipolar disorder. The discussion will explore perspectives on the delay in diagnosis, having a diagnosis, the impact of living with bipolar disorder and attitudes to treatment, including drug combinations. Patient or Public Contribution: A Lived Experience Advisory Panel (LEAP) has been convened with the support of the McPin Foundation, which will contribute to the ASCEnD trial and its nested qualitative study to provide input on the design and delivery of the trial and qualitative study, analysis of qualitative data and dissemination of findings. [ABSTRACT FROM AUTHOR]

In order to accelerate drug development and avoid unnecessary drug trials in vulnerable pediatric populations, the US Food and Drug Administration (FDA) released a general advice letter to sponsors permitting the effectiveness of atypical antipsychotics for the treatment of schizophrenia in adults to be extrapolated to adolescents. Extrapolation is based on the evidence‐based assumptions that (1) disease characteristics and (2) response to therapy, are similar in adults and adolescents. Whereas the FDA validated the extrapolation approach using data from multiple drug development programs, aripiprazole data are the most relevant to confirm the validity of the extrapolation approach for brexpiprazole, since aripiprazole and brexpiprazole both modulate dopaminergic and serotonergic signaling in the brain. The aims of this analysis were (1) to quantitatively assess the aripiprazole exposure (average steady‐state concentration)–response (Positive and Negative Syndrome Scale total score change from baseline) similarity between adults and adolescents with schizophrenia, (2) to extend the aripiprazole exposure–response modeling to brexpiprazole using adult data, and (3) to use the brexpiprazole model to predict schizophrenia symptom response in adolescents. Disease–drug–dropout models were developed using patient‐level data from clinical studies of aripiprazole (1007 adults, 294 adolescents) and brexpiprazole (1235 adults) in schizophrenia. The aripiprazole model demonstrated similar exposure–response between adults and adolescents with schizophrenia, validating the extrapolation approach. Extrapolation of the brexpiprazole adult exposure–response model to adolescents predicted the efficacy of brexpiprazole in adolescents aged 13‐17 years with schizophrenia. [ABSTRACT FROM AUTHOR]

Purpose: Many patients with Alzheimer's disease (AD) also have psychosis, and it has been reported that these patients have more severely impaired cognitive functions than patients without psychosis. The glutamatergic system in the brain is known to play an important role in memory and learning in the neural circuits. However, there has been limited research on how antipsychotic drugs affect the glutamatergic system of AD. Therefore, we aimed to investigate the effects of aripiprazole on the glutamatergic system in an animal model of AD using functional molecular imaging. Procedures: In this study, 5xFAD mice were used as the animal model. At the age of 5 months, the mice were divided into wild-type, vehicle control, and aripiprazole-treated groups (n = 6 per group). The aripiprazole-treated group was administered aripiprazole for 2 months at a dose of 1 mg·kg−1·day−1. At 7 months of age, the animals underwent behavioral tests and glutamate positron emission tomography (PET) scans. Results: The aripiprazole-treated group exhibited alleviated memory impairment in a novel object recognition test. Moreover, this group displayed 7–8% higher binding in the glutamate PET scan than the vehicle-treated 5xFAD group. Postmortem examination confirmed the recovery of glutamatergic damage. Conclusions: The administration of aripiprazole alleviated memory impairment and restored the damaged glutamatergic system in 5xFAD mice. Although the use of aripiprazole in AD patients may be a constraint in terms of safety, we confirmed the possibility that the administration of antipsychotic drugs can be effective in AD. [ABSTRACT FROM AUTHOR]

Introduction: Tourette syndrome (TS) is a childhood-onset neurobehavioral disorder characterized by tics. Pharmacotherapy is advised for patients whose symptoms affect their quality of life. Areas covered: The authors review the tic phenomenology and TS diagnostic criteria. The bulk of this article focuses on pharmacotherapeutic options for treating tics. They also highlight pharmacotherapies in the research pipeline. Expert opinion: Tic treatment must be tailored to individual needs. Behavioral therapy is the first line of treatment. Most with bothersome tics need pharmacotherapy and rarely, for medication-refractory cases, surgical therapy is indicated. Alpha-2 agonists are considered in patients with mild tics, especially in those with attention deficit with or without hyperactivity. Second-generation antipsychotics like aripiprazole and tiapride may be considered for severe tics. However, prescribers should be mindful of potential side effects, especially drug-induced movement disorders. Botulinum toxin injections may be considered for focal motor tics. Topiramate can be considered when other treatments are ineffective, and its benefits outweigh the risks. The same holds true for vesicular monoamine transporter-2 inhibitors, as they are deemed to be safe and effective in real-world use and open-label trials despite not meeting primary endpoints in placebo-controlled trials. Cannabinoids may be considered in adults if the approaches above do not control tics. [ABSTRACT FROM AUTHOR]

Background: Antipsychotic medications are the primary treatment for schizophrenia, with olanzapine being an effective medication for schizophrenia. The economic cost for each individual with schizophrenia is high, with antipsychotic medication being a major expense. This study aims to develop an economic decision model that compares different treatment options for schizophrenia patients, including olanzapine Orally Dispersible Tablets (ODT), olanzapine [ODT + Standard Oral Tablet (SOT)], risperidone (ODT + SOT), and aripiprazole (ODT + SOT), to determine their cost-effectiveness with an objective to optimize healthcare resource allocation in Morocco. Methods: The study used published medical literature and a clinical expert panel to develop a decision analytic model. This model was designed to capture parameters such as adherence levels, treatment discontinuation, relapse with and without hospitalization, quality-adjusted life years (QALYs), treatment-related adverse events, healthcare resource utilization, and associated costs. The main outcomes of interest included the total annual direct cost per treatment, QALYs, and incremental cost-effectiveness ratio (ICER) per 1 QALY gained. One-way and probabilistic sensitivity analyses were employed to account for parameter uncertainty. Results: According to the simulation model, the ODT and ODT + SOT as a group form of olanzapine was the most effective treatment option in terms of the lowest percentages of inpatient relapse, and patients who remained stable (11% and 79% respectively) than risperidone (19% and 62% respectively) and aripiprazole ODT (26% and 50% respectively) and ODT + SOT formulation groups. Olanzapine (ODT + SOT) therapy group was cost-effective when compared to the combined group of ODT + SOT forms of risperidone [ICER: Moroccan Dirham (MAD) 103,907], and aripiprazole (ICER: MAD 65,047). Additionally, olanzapine ODT was found to be cost-effective compared to olanzapine SOT with an ICER of MAD 3921, risperidone ODT with an ICER of MAD 1,02,298, risperidone SOT with an ICER of MAD 31,088, and aripiprazole ODT or SOT formulations. All the above ICERs fall under the willingness-to-pay threshold in Morocco of MAD 250,832.40. Sensitivity analyses confirmed the reliability of the findings. Conclusions: The model concluded that olanzapine ODT is the most cost-effective first-line treatment option for schizophrenia in Morocco when compared to other atypical antipsychotic medications in ODT and SOT formulations. [ABSTRACT FROM AUTHOR]

Objectives: To investigate the effect of aripiprazole on prolactin levels in patients with schizophrenia and analyze whether varying baseline prolactin levels affect the effectiveness and safety of aripiprazole, in a real-life diagnostic and therapeutic setting in a post-hoc analysis. Methods: In this post-hoc analysis, patients with schizophrenia in the acute phase were divided into an elevated-prolactin group and a normal-prolactin group. After 8 weeks of aripiprazole treatment, changes in the proportion of patients with an abnormal prolactin level were analyzed in both groups, and the efficacy and safety of aripiprazole were compared between the two groups. Results: The elevated-prolactin group had more women, a longer duration of disease, and lower Positive and Negative Syndrome Scale (PANSS) total and subscale scores at baseline compared with the normal-prolactin group (all P < 0.05), and there was no significant difference in the proportion of patients with prior use of antipsychotic medication between the two groups. Regardless of previous antipsychotic use, patients in both groups developed hyperprolactinemia (23/168 [13.7%] in those who had taken antipsychotics vs. 43/375 [11.4%] in those who had not). After 8 weeks of aripiprazole treatment, the proportion of patients with abnormal prolactin in the elevated-prolactin group significantly decreased with prolonged treatment (P < 0.001), and aripiprazole had no significant effect on the normal-prolactin group (P = 0.250). Normalprolactin group showed better efficacy than the elevated-prolactin group, and the differences in efficacy between the two groups was observed from week 4 to the endpoint (all p<0.05). In total, 87.2% (68/78) patients experienced mild to moderate adverse events in the elevated-prolactin group, which was significantly more frequent compared with the normal-prolactin group 71.0% (365/514). Conclusions: In this real-world study, for patients with acute schizophrenia, aripiprazole was effective in lowering the proportion of patients with abnormal prolactin levels, while it had no significant effect on patients with normal baseline prolactin. After adjusting for factors such as sex, age, prior antipsychotic drugs use history and disease severity, effectiveness and safety of aripiprazole in patients with normal baseline prolactin was significantly better than that in patients with elevated baseline prolactin. [ABSTRACT FROM AUTHOR]

Background: In this cross‐sectional study, we compared fasting serum asprosin levels and metabolic parameters between patients receiving one of three atypical antipsychotics (olanzapine, risperidone, or aripiprazole) and healthy subjects. Methods: The study population included 62 adult outpatients with schizophrenia and 22 healthy controls, matched for age and gender. Patients were in remission and had been on stable monotherapy with one of these atypical antipsychotics for over 6 months. Body Mass Index (BMI) and fasting serum levels of asprosin, glucose, HA1c, insulin, and lipid profile were compared across the investigated groups. Additionally, the number of participants meeting the insulin resistance criterion, defined as homeostasis model assessment for insulin resistance (HOMA‐IR) >2.5, as well as the number of participants with elevated BMI levels (men >27 kg/m2, women >25 kg/m2) were compared among the groups. Results: We observed statistically significant differences in BMI and fasting serum levels of glucose, HA1c, insulin, triglyceride (TG), high‐density lipoprotein cholesterol, and asprosin among patients receiving olanzapine or risperidone, as compared to those receiving aripiprazole and healthy subjects. Patients on aripiprazole exhibited values comparable to healthy subjects, whereas those on risperidone or olanzapine showed significantly higher values, with the highest observed in the olanzapine group. Additionally, the prevalence of participants meeting the insulin resistance criterion and those with elevated BMI was also greater in individuals receiving olanzapine or risperidone compared to those on aripiprazole and healthy subjects. Serum asprosin levels showed a significant positive correlation with BMI and several metabolic parameters, including HbA1c, fasting insulin, HOMA‐IR, and TG. No significant differences were observed among the investigated groups in terms of serum levels of total cholesterol and low‐density lipoprotein cholesterol. Conclusions: Our cross‐sectional study highlights the association between elevated asprosin levels, weight gain, and metabolic disorders in patients treated with olanzapine and risperidone. Given the bidirectional nature of the relationship between serum asprosin levels and these metabolic disturbances, further research is warranted to elucidate potential causative pathways. [ABSTRACT FROM AUTHOR]

Background: Patients undergoing antipsychotic treatment for psychiatric disorders may experience challenges in functioning, either stemming from the severity of the illness or from the tolerability issues of prescribed medications. Objectives: The aims of this cross-sectional study are to investigate the impact of adverse effects of antipsychotic drugs on patients' daily life functioning, comparing oral and long-acting injectable (LAI) antipsychotics, and further dividing antipsychotics by receptor-binding profiles based on recently defined data-driven taxonomy. Methods: This study involved patients with schizophrenia and bipolar spectrum disorders taking oral or LAI antipsychotics. Disability and functioning levels were assessed using the World Health Organization Disability Assessment Schedule 2.0 (WHODAS), and the adverse effects of medications were evaluated using the Udvalg for Kliniske Undersogelser (UKU) Side Effect Rating Scale and its subscales. Results: The total sample consisted of 126 participants with a diagnosis of schizophrenia-spectrum or bipolar disorder, and included 54 males and 72 females ranging from 18 to 78 years of age (mean 45.1, standard deviation 14); 78 patients were taking oral antipsychotics and 48 were taking LAI antipsychotics, with subcategories of muscarinic (31), adrenergic/low dopamine (25), serotonergic/dopaminergic (23), dopaminergic (1), LAI muscarinic (15), LAI adrenergic (6), and LAI serotonergic/dopaminergic (25). The UKU total score for adverse effects showed significant correlations with WHODAS total score (ρ = 0.475; p < 0.001). Compared with oral antipsychotics, LAIs showed significantly lower scores in psychological (p = 0.014), autonomic (p = 0.008), other (p = 0.004), and sexual adverse effects (p = 0.008), as well as the UKU total score (p = 0.002). The Kruskal–Wallis test showed a significant difference in adverse effects between LAI and oral muscarinic subgroups, with LAIs having lower scores compared with antipsychotics binding to muscarinic receptors (p = 0.043). Conclusion: These findings indicate clinically relevant differences in adverse effects among formulations, warranting further investigation for future observational studies. [ABSTRACT FROM AUTHOR]

Background: Heautoscopic hallucinations are rare visual experiences consisting of the perception of the image of one's own body or face within space. Method: The point of view can be internal, like in front of a mirror, or external. Results: Heautoscopic phenomena are classified among the disorders of somatoagnosia, or disorders related to the alteration of the body schema. It is not clear which sensory system is primarily involved in the generation of this alteration. Discussion: This case report discusses a 21-year-old male student with first episode psychosis who presented heautoscopic hallucinations. His neurological and medical examinations were unremarkable. By explaining the theoretical background on the heterogeneity of autoscopic phenomena in psychiatric and neurological disease, our clinical observation contributes for the first time to enrich the literature on autoscopic hallucinations in patients with non-affective psychosis. [ABSTRACT FROM AUTHOR]

Introduction Little is known about the interplay between genetics and epigenetics on antidepressant treatment (1) response and remission, (2) side effects, and (3) serum levels. This study explored the relationship among single nucleotide polymorphisms (SNPs), DNA methylation (DNAm), and mRNA levels of four pharmacokinetic genes, CYP2C19 , CYP2D6 , CYP3A4 , and ABCB1 , and its effect on these outcomes. Methods The Canadian Biomarker Integration Network for Depression-1 dataset consisted of 177 individuals with major depressive disorder treated for 8 weeks with escitalopram (ESC) followed by 8 weeks with ESC monotherapy or augmentation with aripiprazole. DNAm quantitative trait loci (mQTL), identified by SNP-CpG associations between 20 SNPs and 60 CpG sites in whole blood, were tested for associations with our outcomes, followed by causal inference tests (CITs) to identify methylation-mediated genetic effects. Results Eleven cis- SNP-CpG pairs (q<0.05) constituting four unique SNPs were identified. Although no significant associations were observed between mQTLs and response/remission, CYP2C19 rs4244285 was associated with treatment-related weight gain (q =0.027) and serum concentrations of ESCadj (q <0.001). Between weeks 2-4, 6.7% and 14.9% of those with *1/*1 (normal metabolizers) and *1/*2 (intermediate metabolizers) genotypes, respectively, reported ≥2 lbs of weight gain. In contrast, the *2/*2 genotype (poor metabolizers) did not report weight gain during this period and demonstrated the highest ESCadj concentrations. CITs did not indicate that these effects were epigenetically mediated. Discussion These results elucidate functional mechanisms underlying the established associations between CYP2C19 rs4244285 and ESC pharmacokinetics. This mQTL SNP as a marker for antidepressant-related weight gain needs to be further explored. [ABSTRACT FROM AUTHOR]

Binge eating disorder (BED) is the most common specific eating disorder (ED). It is frequently associated with attention deficit hyperactivity disorder (ADHD), depression, bipolar disorder (BD), anxiety disorders, alcohol and nicotine use disorder, and obesity. The aim of this narrative review was to summarize the evidence for the pharmacological treatment of BED and its comorbid disorders. We recommend the ADHD medication lisdexamfetamine (LDX) and the antiepileptic and antimigraine drug topiramate for the pharmacological treatment of BED. However, only LDX is approved for the treatment of BED in some countries. Medications to treat diseases frequently comorbid with BED include atomoxetine and LDX for ADHD; citalopram, fluoxetine, sertraline, duloxetine, and venlafaxine for anxiety disorders and depression; aripiprazole for manic episodes of BD; lamotrigine, lirasidone and lumateperone for depressive episodes of BD; naltrexone for alcohol use disorder; bupropion for nicotine use disorder; and liraglutide, semaglutide, and the combination of bupropion and naltrexone for obesity. As obesity is a frequent health consequence of BED, weight gain-inducing medications, such as the atypical antipsychotics olanzapine or clozapine, the novel antidepressant mirtazapine and tricyclic antidepressants, and the mood stabilizer valproate should be avoided where possible. It is currently unclear whether the novel and promising glucagon, glucose-dependent insulinotropic polypeptide (GIP), and glucagon-like peptide 1 (GLP-1) receptor agonists like tirzepatide and retatrutide help with BED and its comorbidities. However, these compounds have been reported to reduce binge eating in individuals with obesity or overweight. [ABSTRACT FROM AUTHOR]

Identifying stable and consistent resting-state functional connectivity patterns across illness trajectories has the potential to be considered fundamental to the pathophysiology of schizophrenia. We aimed to identify consistent resting-state functional connectivity patterns across heterogeneous schizophrenia groups defined based on treatment response. In phase 1, we used a cross-sectional case-control design to characterize and compare stable independent component networks from resting-state functional magnetic resonance imaging scans of antipsychotic-naïve participants with first-episode schizophrenia (n = 54) and healthy participants (n = 43); we also examined associations with symptoms, cognition, and disability. In phase 2, we examined the stability (and replicability) of our phase 1 results in 4 groups (N = 105) representing a cross-sequential gradation of schizophrenia based on treatment response: risperidone responders, clozapine responders, clozapine nonresponders, and clozapine nonresponders following electroconvulsive therapy. Hypothesis-free whole-brain within- and between-network connectivity were examined. Phase 1 identified posterior and anterior cerebellar hypoconnectivity and limbic hyperconnectivity in schizophrenia at a familywise error rate–corrected cluster significance threshold of p <.01. These network aberrations had unique associations with positive symptoms, cognition, and disability. During phase 2, we replicated the phase 1 results while comparing each of the 4 schizophrenia groups to the healthy participants. The participants in 2 longitudinal subdatasets did not demonstrate a significant change in these network aberrations following risperidone or electroconvulsive therapy. Posterior cerebellar hypoconnectivity (with thalamus and cingulate) emerged as the most consistent finding; it was replicated across different stages of treatment response (Cohen's d range −0.95 to −1.44), reproduced using different preprocessing techniques, and not confounded by educational attainment. Posterior cerebellar-thalamo-cingulate hypoconnectivity is a consistent and stable state-independent neural marker of schizophrenia. [ABSTRACT FROM AUTHOR]

Background: Researches done over different parts of the world show that hyperprolactinemia in psychotic patients is dependent on many factors such as age, gender, any thyroidal abnormality, drugs such as antipsychotics or antidepressants, psychological stress, and genre of psychosis. In patients taking antipsychotic treatments, prolactin blood levels may rise up to 10 times the normal values. It is very important to differentiate between prolactin-secreting tumor in pituitary and antipsychotic-induced hyperprolactinemia. There has been fewer researches on this topic in Eastern India, so it aims to properly estimate the amount of prolactin rise; a patient has to face after taking anti-psychotic medications and might also help the psychiatrists to adjust the dosage of anti-psychotics or to add some other drugs to lower the prolactin level along with the anti-psychotics in Eastern India. Aim and Objectives: The aims and objectives of the study are to estimate serum prolactin in diagnosed psychiatric patients taking antipsychotic drugs for at least 3 months and to study the difference in serum prolactin between recently diagnosed psychiatric patients taking antipsychotic drugs for at least 3 months and age and gender-matched mentally healthy patients without any psychiatric complication and without any history of in taking antipsychotic drugs. Materials and Methods: The study was conducted over a period of 4 months at Central Laboratory, Dept of Biochemistry, MCK. Before the conduct of the study, informed consent was taken. Patients diagnosed with psychiatric illness and consuming at least one antipsychotic drug for at least 3 months were enrolled after going through inclusion--exclusion criteria. Serum prolactin was measured with help of CLIA (ADVIA CENTAUR). Results: As per our study done in Eastern Indian population, in the female group of psychiatric patients (aged between 18 and 45 years) taking antipsychotics, the prolactin level was 23.6 ± 4.5 ng/ml, and in age-matched control female group, prolactin level was 9.2 ± 3.1 ng/mL, the difference is statistically significant (P < 0.001). Moreover, in male psychiatric patients (aged between 18 and 45 years) taking antipsychotics, the prolactin level was 14.3 ± 1.7 ng/mL, and in age-matched control male group, prolactin level was 8.5 ± 1.5 ng/mL, the difference is statistically significant (P < 0.001). Conclusion: As per our study, psychiatric patients of both gender taking antipsychotic drugs had higher serum prolactin level than age and gender-matched mentally healthy persons not taking antipsychotic drugs. While the limitation of this study was its small sample size, another issue that must be taken into consideration is the fact that prolactin levels can also depend on menstrual cycles in women. In our study, there were 40 (57%) females who were still menstruating. [ABSTRACT FROM AUTHOR]

Background: Reducing falls and fractures remains an important clinical goal in managing older residents with Parkinson's disease psychosis (PDP) in long-term care/nursing home (LTC/NH) settings. Objectives: This analysis examined risk of all-cause falls or fractures among PDP residents on continuous monotherapy with pimavanserin (PIM) versus (i) other atypical antipsychotics (AAPs) [quetiapine (QUE), risperidone (RIS), olanzapine (OLA), aripiprazole (ARI)] and (ii) QUE. Methods: A retrospective analysis of parts A, B, and D claims from a 100% Medicare sample (2013–2019) in LTC/NH settings was conducted. LTC/NH residents in the USA initiating continuous monotherapy (PIM versus other AAPs; PIM versus QUE) for ≥ 6 months between 01 January 2014 and 31 December 2018 were 1:1 propensity score matched (PSM) on 31 variables (age, sex, race, region, and 27 Elixhauser comorbidities). Outcomes included three measures: risks of falls only, fractures only, and falls/fractures during 6-months follow-up. Demographic characteristics were described using chi-square and t-tests. Generalized linear models were used to assess difference in risks of falls/fractures. Results: Of 7187 residents, 47.59% (n = 3420) were female and mean age was 78.8 (± 7.75) years. In total, 14% (n = 1005) were on PIM and 86% (n = 6182) were on other AAPs. After PSM, falls only among PIM residents (n = 1005) was 4.58% (n = 46) versus 7.66% (n = 77) for other AAPs (n = 1005) [relative risk (RR) = 0.63 (0.46, 0.86), p < 0.05] and 8.26% (n = 83) for QUE (n = 1005) residents (p < 0.05). Fractures only among PIM residents was 1.39% (n = 14) compared with 2.09% (n = 21) for other AAPs (p = 0.31) and 1.89% (n = 19) for QUE (p = 0.49), respectively. Taken together, falls/fractures among PIM residents were 5.67% (n = 57) versus 9.05% (n = 91) for other AAPs [RR = 0.63 (0.46, 0.86), p < 0.05] and 9.55% (n = 96) for QUE (p < 0.05), respectively. Conclusions: In this analysis of LTC/NH residents with PDP, PIM had a 37% and 41% lower risk of all-cause falls/fractures versus other AAPs and versus QUE, respectively. [ABSTRACT FROM AUTHOR]