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Introduction: Nightmare disorder affects approximately 4% of adults, occurring in isolation or as part of other disorders such as posttraumatic stress disorder (PTSD), and can significantly impair quality of life. This paper provides the American Academy of Sleep Medicine (AASM) position regarding various treatments of nightmare disorder in adults., Methods: A literature search was performed based upon the keywords and MeSH terms from the Best Practice Guide for the Treatment of Nightmare Disorder in Adults that was published in 2010 by the AASM. The search used the date range March 2009 to August of 2017, and sought to find available evidence pertaining to the use of behavioral, psychological, and pharmacologic therapies for the treatment of nightmares. A task force developed position statements based on a thorough review of these studies and their clinical expertise. The AASM Board of Directors approved the final position statements., Determination of Position: Positions of "recommended" and "not recommended" indicate that a treatment option is determined to be clearly useful or ineffective/harmful for most patients, respectively, based on a qualitative assessment of the available evidence and clinical judgement of the task force. Positions of "may be used" indicate that the evidence or expert consensus is less clear, either in favor or against the use of a treatment option. The interventions listed below are in alphabetical order within the position statements rather than clinical preference: this is not meant to be instructive of the order in which interventions should be used., Position Statements: The following therapy is recommended for the treatment of PTSD-associated nightmares and nightmare disorder: image rehearsal therapy. The following therapies may be used for the treatment of PTSD-associated nightmares: cognitive behavioral therapy; cognitive behavioral therapy for insomnia; eye movement desensitization and reprocessing; exposure, relaxation, and rescripting therapy; the atypical antipsychotics olanzapine, risperidone and aripiprazole; clonidine; cyproheptadine; fluvoxamine; gabapentin; nabilone; phenelzine; prazosin; topiramate; trazodone; and tricyclic antidepressants. The following therapies may be used for the treatment of nightmare disorder: cognitive behavioral therapy; exposure, relaxation, and rescripting therapy; hypnosis; lucid dreaming therapy; progressive deep muscle relaxation; sleep dynamic therapy; self-exposure therapy; systematic desensitization; testimony method; nitrazepam; prazosin; and triazolam. The following are not recommended for the treatment of nightmare disorder: clonazepam and venlafaxine. The ultimate judgment regarding propriety of any specific care must be made by the clinician, in light of the individual circumstances presented by the patient, accessible treatment options, and resources., (© 2018 American Academy of Sleep Medicine.)

The study aims to identify prescribing and switching patterns of antipsychotics in clinical practice. A 16-month, prospective study was conducted at the Psychiatric Hospital Idrija, Slovenia. Inpatients (N = 311) with schizophrenia spectrum disorders were observed. The causes for switching antipsychotics and switching strategies were analyzed. Analyzing a total of 3954 prescriptions, the collected data confirmed that treatment strategies in this psychiatric hospital are very complex. It was found that 37 percent of inpatients had at least one switch. Moreover, switches that included three or more antipsychotics were detected. The most common causes for switching antipsychotics were adverse reactions and inefficacy or lack of efficacy. Among switching options, abrupt switch was recorded several times. As some patients are receiving several antipsychotics at the same time, it is possible that unusual switching occurs in clinical practice. It seems that the choice of switching strategy is also affected by the cause and urgency for switching an antipsychotic.

The main objective of the present study was to apply QbD methodology in the development of once-a-day sustained release quetiapine tablets. The quality target product profile (QTPP) was defined after the pharmaceutical properties and kinetic release of the innovator product, Seroquel XR 200 mg. For the D-optimal experimental design, the level and ratio of matrix forming agents and the type of extragranular diluent were chosen as independent inputs, which represented critical formulation factors. The critical quality attributes (CQAs) studied were the cumulative percentages of quetiapine released after certain time intervals. After the analysis of the experimental design, optimal formulas and the design space were defined. Optimal formulas demonstrated zero-order release kinetics and a dissolution profile similar to the innovator product, with f2 values of 74.53 and 83.74. It was concluded that the QbD approach allowed fast development of sustained release tablets with similar dissolution behavior as the innovator product.

Introduction: Patients with schizophrenia or bipolar disorder treated with antipsychotic medication can frequently experience lack of efficacy and persistent side-effects, so much so that switching from one antipsychotic to another with a different side-effect profile has become a recommended strategy for improving the tolerability and safety of long-term antipsychotic treatment. Aripiprazole is an atypical antipsychotic with proven efficacy in schizophrenia and bipolar I disorder, with a pharmacological profile distinct from other available antipsychotics and a side-effect profile that is different from other agents in the class; these characteristics make it a possible alternative in patients requiring a change in antipsychotic treatment due to lack of efficacy or persistent side-effects., Areas Covered: A panel of Italian experts in psychiatry met to discuss the appropriateness of current strategies for the switch to aripiprazole in patients with schizophrenia or bipolar disorder once a clinician has decided to adopt this choice and also to propose alternate strategies where required. The strategies for the switch to aripiprazole presented in this position paper consider various scenarios encountered in clinical practice, highlight the importance of tapering the prior antipsychotic based on its pharmacological characteristics and provide detailed guidance throughout the entire switching process. Literature searches were conducted using the PubMed database and the search strategy (aripiprazole and switching); additional references were added from the reference lists of the papers obtained and also from the authors' knowledge of the topic., Expert Opinion: Few studies have addressed the indications for antipsychotic switching and the best practical strategies to achieve the desired goal in the clinical practice setting. Studies on antipsychotic switching should clarify why, when and how a switch should be done. The results should standardize the reasons for switching an antipsychotic, assess the optimal time to switch and evaluate the best ways to switch. Both clinical and pharmacological factors should be considered when a patient needs to switch antipsychotics, and specific guidelines for antipsychotic switching that address all these factors are needed.

Objectives: Dementia guidelines recommend antipsychotics are only used for behavioral and psychological symptoms when non-drug interventions fail, and to regularly review use. Population-level clinical quality indicators (CQIs) for dementia care in permanent residential aged care (PRAC) typically monitor prevalence of antipsychotic use but not prolonged use. This study aimed to develop a CQI for antipsychotic use >90 days and examine trends, associated factors, and variation in CQI incidence; and examine duration of the first episode of use among individuals with dementia accessing home care packages (HCPs) or PRAC., Methods: Retrospective cohort study, including older individuals with dementia who accessed HCPs (n = 50,257) or PRAC (n = 250,196). Trends in annual CQI incidence (2011-12 to 2015-16) and associated factors were determined using Poisson regression. Funnel plots examined geographical and facility variation. Time to antipsychotic discontinuation was estimated among new antipsychotic users accessing HCP (n = 2367) and PRAC (n = 15,597) using the cumulative incidence function., Results: Between 2011-12 and 2015-16, antipsychotic use for >90 days decreased in HCP recipients from 10.7% (95% CI 10.2-11.1) to 10.1% (95% CI 9.6-10.5, adjusted incidence rate ratio (aIRR) 0.97 (95% CI 0.95-0.98)), and in PRAC residents from 24.5% (95% CI 24.2-24.7) to 21.8% (95% CI 21.5-22.0, aIRR 0.97 (95% CI 0.96-0.98)). Prior antipsychotic use (both cohorts) and being male and greater socioeconomic disadvantage (PRAC cohort) were associated with higher CQI incidence. Little geographical/facility variation was observed. Median treatment duration in HCP and PRAC was 334 (interquartile range [IQR] 108-958) and 555 (IQR 197-1239) days, respectively., Conclusions: While small decreases in antipsychotic use >90 days were observed between 2011-12 and 2015-16, findings suggest antipsychotic use among aged care recipients with dementia can be further minimized., (© 2024 The Authors. International Journal of Geriatric Psychiatry published by John Wiley & Sons Ltd.)

We investigate estimation of causal effects of multiple competing (multi-valued) treatments in the absence of randomization. Our work is motivated by an intention-to-treat study of the relative cardiometabolic risk of assignment to one of six commonly prescribed antipsychotic drugs in a cohort of nearly 39 000 adults with serious mental illnesses. Doubly-robust estimators, such as targeted minimum loss-based estimation (TMLE), require correct specification of either the treatment model or outcome model to ensure consistent estimation; however, common TMLE implementations estimate treatment probabilities using multiple binomial regressions rather than multinomial regression. We implement a TMLE estimator that uses multinomial treatment assignment and ensemble machine learning to estimate average treatment effects. Our multinomial implementation improves coverage, but does not necessarily reduce bias, relative to the binomial implementation in simulation experiments with varying treatment propensity overlap and event rates. Evaluating the causal effects of the antipsychotics on 3-year diabetes risk or death, we find a safety benefit of moving from a second-generation drug considered among the safest of the second-generation drugs to an infrequently prescribed first-generation drug known for having low cardiometabolic risk., (© 2024 John Wiley & Sons, Ltd.)

Psychodermatology, the multidisciplinary field that explores the intricate interplay between the mind and the skin, has gained increasing recognition over the past decade. However, several knowledge gaps and unmet needs persist in the field. The objective of this narrative review was to investigate the unmet needs in the field of psychodermatology as they pertain to medical training, treatment, research, and care access. PubMed was searched from inception through December 2023 to identify articles related to psychodermatology. Findings revealed several unmet needs within the field of psychodermatology. First, there is a need for further investigation into the pathophysiology that links psychological stress to cutaneous disease including the development of novel therapies targeting key neuropeptides. Second, the existing literature focuses primarily on the pharmacologic treatment of body dysmorphic disorder and body-focused repetitive behaviors, as well as delusional parasitosis, for which the first-line agents are selective serotonin reuptake inhibitors and atypical antipsychotics, respectively. However, additional research into the efficacy and safety of the remaining psychotropic medications and the treatment of other common psychocutaneous diseases is required. Finally, there exists a significant gap in knowledge amongst clinicians tasked with treating psychocutaneous diseases. Dermatologists report low rates of training in psychodermatology and discomfort with prescribing psychotropic medications. In conclusion, increasing resources for dermatologist education on psychotropic agent use, development of new drugs targeting stress-induced skin conditions, and research on the psychocutaneous applications of current medications may greatly improve the quality and access of psychodermatology care., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

In elderly persons, antipsychotic drugs are clinically prescribed off-label for a number of disorders outside of their Food and Drug Administration (FDA)-approved indications (schizophrenia and bipolar disorder). The largest number of antipsychotic prescriptions in older adults is for behavioral disturbances associated with dementia. In April 2005, the FDA, based on a meta-analysis of 17 double-blind randomized placebo-controlled trials among elderly people with dementia, determined that atypical antipsychotics were associated with a significantly (1.6-1.7 times) greater mortality risk compared with placebo, and asked that drug manufacturers add a 'black box' warning to prescribing information for these drugs. Most deaths were due to either cardiac or infectious causes, the two most common immediate causes of death in dementia in general. Clinicians, patients, and caregivers are left with unclear choices of treatment for dementia patients with psychosis and/or severe agitation. Not only are psychosis and agitation common in persons with dementia but they also frequently cause considerable caregiver distress and hasten institutionalization of patients. At the same time, there is a paucity of evidence-based treatment alternatives to antipsychotics for this population. Thus, there is insufficient evidence to suggest that psychotropics other than antipsychotics represent an overall effective and safe, let alone better, treatment choice for psychosis or agitation in dementia; currently no such treatment has been approved by the FDA for these symptoms. Similarly, the data on the efficacy of specific psychosocial treatments in patients with dementia are limited and inconclusive. The goal of this White Paper is to review relevant issues and make clinical and research recommendations regarding the treatment of elderly dementia patients with psychosis and/or agitation. The role of shared decision making and caution in using pharmacotherapy for these patients is stressed.

Objective: Medication documentation is a critical aspect of quality patient care. The current study examined whether electronic medical records provide medication documentation that is more complete and faster to retrieve than traditional paper records., Method: This study involves a comparison of archived paper medical records to recent electronic medical records through chart review. A convenient sample of three large community mental health centers in Indiana was used. Medical charts for 180 patients with schizophrenia were rated on a checklist composed of 16 items that was adapted from a national project. Documentation that existed before implementation of the electronic medical record system was compared with that after implementation at each of the three centers. The main outcome measures were completeness and retrieval time of medication documentation., Results: Electronic medical records provided medication documentation that was more complete and faster to retrieve than paper records across all centers and within each center. On average, electronic medical records were 40% more complete and 20% faster to retrieve., Conclusion: Electronic records have potential to improve medication management for patients in mental health centers over traditional records. However, medication documentation for patients diagnosed with schizophrenia was found to be deficient in many areas, regardless of documentation format.

The effective treatment in the early stages of schizophrenia is of critical importance to improve the prognosis. Schizophrenia affects patients' relatives too. The effects of early or late initiation of long-acting injectable antipsychotics (LAI-APs) on the patient have been shown, yet their effects on the caregiver are still unknown. We aimed to determine how the time of initiation of LAI-APs affects the caregiver burden by comparing the patients who were started on LAI-APs in the first 5 years of diagnosis and those who were started at a later period. Patients were classified as 'early-LAI' and 'late-LAI' according to the time of initiation of a LAI-AP. Their caregivers were also classified as the same way, as 'caregiver-early' and 'caregiver-late' and were compared in terms of caregiver burden. The quality of life, depression, anxiety, and caregiver burden scores of the caregiver-late group were significantly worse. The time of initiation of LAI-APs and the functioning levels of the patients were found to be determinant factors for the caregiver burden. This is the first study to investigate the effects of LAI-AP's initiation time on the caregivers to our knowledge. The use of LAI-APs in the early stages is associated with better outcomes for the caregiver., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Clozapine-induced myocarditis (CIM) is among the most important adverse events limiting the use of clozapine as the most effective treatment for schizophrenia. CIM necessitates the immediate termination of clozapine, often resulting in its permanent discontinuation with considerable detrimental effects on patients' psychopathology and long-term outcome. Consequently, a clozapine re-challenge after CIM is increasingly regarded as a viable alternative, with published reports indicating a success rate of approximately 60%. However, published cases of re-challenges after CIM remain limited. Here, we provide a narrative review of the current state of research regarding the epidemiology, pathophysiology, risk factors, diagnosis and clinical management of CIM as well as a synthesis of current recommendations for re-challenging patients after CIM. This includes a step-by-step guide for this crucial procedure based on the current evidence regarding the pathophysiology and risk factors for CIM. Slow dose titration regimes and addressing risk factors including concomitant valproate and olanzapine are crucial both to prevent CIM and to ensure a safe and successful re-challenge. Furthermore, we discuss the utility of C-reactive protein, troponin, N-terminal-pro hormone and brain natriuretic peptide, therapeutic drug-monitoring and cardiac magnetic resonance imaging for CIM screening and diagnosis as well as for post-CIM re-challenges., (© 2024. The Author(s).)

Background: Schizophrenia is a severe and chronic neuropsychiatric disorder that involves profound impairment of psychopathology in cognition, emotion, perception, and other aspects of behavior. Factors, such as the nature of the disease, length of hospital stay, duration of illness, and side effects of psychotropic drugs, may contribute to poor oral health and the risk of developing bruxism in patients with schizophrenia., Aim: To evaluate the prevalence of bruxism and associated factors in patients with schizophrenia., Methods: This cross-sectional study was conducted in a single center with 211 patients with schizophrenia. Study participants were graded according to "probable" bruxism based on positive clinical inspection, with or without a positive self-report. The type of antipsychotic treatment used in participants was evaluated in three categories: typical antipsychotic monotherapy, atypical antipsychotic monotherapy, and a combination of both. Binary logistic regression models were used to evaluate associations between probable bruxism and different factors., Results: The mean age of the study participants was 51.02 ± 9.29 years, and 112 (52.5%) were males. Probable bruxism was identified in 87 (41.2%) of the study participants. Younger age (AOR = 0.88, 95% CI = 0.838-0.928, P < 0.001), higher duration of illness (AOR = 1.50, 95% CI = 1.278-7.545, P < 0.001), and combination antipsychotic therapy (AOR = 3.042, 95% CI = 1.278-7.545, P = 0.015) were significant factors associated with probable bruxism among patients with schizophrenia on treatment., Conclusion: The relatively high prevalence of probable bruxism in patients with schizophrenia and its relation to antipsychotics was observed. There is a need for more research on the causes and treatment of bruxism in schizophrenia., (Copyright © 2024 Copyright: © 2024 Nigerian Journal of Clinical Practice.)

Background: Patients with schizophrenia often face challenges related to cognitive function, affecting their daily functioning and overall quality of life. The choice of antipsychotic treatment may play a crucial role in determining cognitive outcomes., Study Question: Our study aimed to investigate whether there was a difference in cognitive ability between the patients with schizophrenia receiving oral antipsychotics (OAP) versus long-acting injectable antipsychotics (LAI-APs)., Study Design: We conducted a cross-sectional study using analytical methods between January 1, 2020, and January 1, 2022. Participants were divided into 2 groups: patients undergoing treatment with OAP and patients undergoing treatment with LAI-AP. All participants underwent version A of Brief Assessment of Cognition in Schizophrenia (BACS)., Measures and Outcomes: The primary objective was to compare cognitive function in patients with schizophrenia treated with LAI antipsychotics versus OAP using BACS. Primary outcome measures include overall BACS score, with secondary measures focusing on specific cognitive domains. This study contributes to the understanding of the cognitive effects of different antipsychotic formulations in schizophrenia treatment., Results: Although there was a slightly higher intelligence quotient in the LAI-AP group (102.2 vs. 101.32, P = 0.5401), it was not statistically significant. Olanzapine was the most commonly prescribed antipsychotic, with 48% of patients in the LAI-AP group and 40% in the OAP group. The LAI-AP group outperformed in all BACS evaluations. The most notable difference was in the token motor task (57.78 ± 17.03 vs. 50.04 ± 18.82, P = 0.0335), while the Tower of London test showed the smallest difference (17.26 ± 2.61 vs. 15.48 ± 3.47, P = 0.0046). Regression analysis revealed no significant variance in intelligence quotient scores; however, a significant discrepancy in BACS scores was evident, favoring the LAI treatment for better cognitive outcomes., Conclusions: The use of long-acting antipsychotic treatment in individuals with schizophrenia offers promising advantages in preserving cognitive function., Competing Interests: The authors have no conflicts of interest to declare., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Therapeutic drug monitoring (TDM) of antipsychotics for dose titration or detection of noncompliance is not uncommon in daily practice. Normally, TDM implies measuring a drug concentration in venous blood samples. This technique is invasive and requires trained assistants and patients normally need to go to an outpatient clinic. Over the past decades, sensitivity of analytical equipment has improved leading to a growing interest in microsampling techniques. These techniques are minimally invasive, require a small volume (<100 μL), usually result in stable samples, and can be collected by the patient or a caregiver at home. Before a microsampling technique can be used in daily routine, proper method development and a clinical validation study should be performed., Method: For this review, the databases of PubMed and Embase were systematically searched. Currently available microsampling techniques for antipsychotics in blood, serum, or plasma are summarized. Subsequently, it has also been assessed whether these techniques are sufficiently validated for TDM monitoring in daily practice., Results: Several microsampling techniques are available today, for example, dried blood spot sampling, dried plasma extraction cards, and volumetric absorptive microsampling. Eighteen studies were identified in which a microsampling technique for 1 or a few antipsychotics was chemically analytically and clinically validated. However, the majority of these studies have relevant shortcomings that mean its usefulness for different antipsychotics is not yet well established., Conclusions: Microsampling for TDM can be recommended for patients using clozapine. For TDM of other antipsychotics, it is a very promising development., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Introduction: Adverse event (AE) data in randomized controlled trials (RCTs) allow quantification of a drug's safety risk relative to placebo and comparison across medications. The standard US label for Food and Drug Administration-approved drugs typically lists AEs by MedDRA Preferred Term that occur at ≥ 2% in drug and with greater incidence than in placebo. We suggest that the drug label can be more informative for both patients and physicians if it includes, in addition to AE incidence (percent of subjects who reported the AE out of the total subjects in treatment), the absolute prevalence (percent of subject-days spent with an AE out of the total subject-days spent in treatment) and expected duration (days required for AE incidence to be reduced by half). We also propose a new method to analyze AEs in RCTs using drug-placebo difference in AE prevalence to improve safety signal detection., Methods: AE data from six RCTs in schizophrenia were analyzed (five RCTs of the dopamine D 2 receptor-based antipsychotic lurasidone and one RCT of the novel trace amine-associated receptor 1 [TAAR1] agonist ulotaront). We determined incidence, absolute prevalence, and expected duration of AEs for lurasidone and ulotaront vs respective placebo. We also calculated areas under the curve of drug-placebo difference in AE prevalence and mean percent contribution of each AE to this difference., Results: A number of AEs with the same incidence had different absolute prevalence and expected duration. When accounting for these two parameters, AEs that did not appear in the 2% incidence tables of the drug label turned out to contribute substantially to drug tolerability. The percent contribution of a drug-related AE to the overall side effect burden increased the drug-placebo difference in AE prevalence, whereas the percent contribution of a placebo-related AE decreased such difference, revealing a continuum of risk between drug and placebo. AE prevalence curves for drug were generally greater than those for placebo. Ulotaront exhibited a small drug-placebo difference in AE prevalence curves due to a relatively low incidence and short duration of AEs in the ulotaront treatment arm as well as the emergence of disease-related AEs in the placebo arm., Conclusion: Reporting AE absolute prevalence and expected duration for each RCT and incorporating them in the drug label is possible, is clinically relevant, and allows standardized comparison of medications. Our new metric, the drug-placebo difference in AE prevalence, facilitates signal detection in RCTs. We piloted this metric in RCTs of several neuropsychiatric indications and drugs, offering a new way to compare AE burden and tolerability among treatments using existing clinical trial information., (© 2023. The Author(s).)

In the postmortem environment, some drugs and metabolites may degrade due to microbial activity, even forming degradation products that are not produced in humans. Consequently, underestimation or overestimation of perimortem drug concentrations or even false negatives are possible when analyzing postmortem specimens. Therefore, understanding whether medications may be susceptible to microbial degradation is critical in order to ensure that reliable detection and quantitation of drugs and their degradation products is achieved in toxicology screening methods. In this study, a "simulated postmortem blood" model constructed of antemortem human whole blood inoculated with a broad population of human fecal microorganisms was used to investigate the stability of 17 antidepressant and antipsychotic drugs. Microbial communities present in the experiments were determined to be relevant to postmortem blood microorganisms by 16S rRNA sequencing analyses. After 7 days of exposure to the community at 37°C, drug stability was evaluated using liquid chromatography coupled with diode array detection (LC-DAD) and with quadrupole time-of-flight mass spectrometry (LC-QTOF-MS). Most of the investigated drugs were found to be stable in inoculated samples and noninoculated controls. However, the 1,2-benzisothiazole antipsychotics, ziprasidone and lurasidone, were found to degrade at a rate comparable with the known labile control, risperidone. In longer experiments (7 to 12 months), where specimens were stored at -20°C, 4°C, and ambient temperature, N-dealkylation degradation products were detected for many of the drugs, with greater formation in specimens stored at -20°C than at 4°C., (© 2022 John Wiley & Sons, Ltd.)

Background: The most common causes of death in schizophrenia are cardiovascular disorders, which are closely related to metabolic syndrome/obesity. To better understand the development of metabolic alterations early in the course of illness, we quantified daily medication exposure in the first days of the first hospitalization for psychosis and related it to changes in weight and metabolic markers., Study Design: We recruited participants with first episode psychosis (FEP, N = 173) during their first psychiatric hospitalization and compared them to controls (N = 204). We prospectively collected weight, body mass index, metabolic markers, and exact daily medication exposure at admission and during hospitalization., Study Results: Individuals with FEP gained on average 0.97 ± 2.26 BMI points or 3.46 ± 7.81 kg of weight after an average of 44.6 days of their first inpatient treatment. Greater antipsychotic exposure was associated with greater BMI increase, but only in people with normal/low baseline BMI. Additional predictors of weight gain included type of medication and duration of treatment. Medication exposure was not directly related to metabolic markers, but higher BMI was associated with higher TGC, TSH, and lower HDL. Following inpatient treatment, participants with FEP had significantly higher BMI, TGC, prolactin, and lower fT4, HDL than controls., Conclusion: During their first admission, people with FEP, especially those with normal/low baseline BMI, showed a rapid and clinically significant weight increase, which was associated with exposure to antipsychotics, and with metabolic changes consistent with metabolic syndrome. These findings emphasize weight monitoring in FEP and suggest a greater need for caution when prescribing metabolically problematic antipsychotics to people with lower BMI., (© 2023 The Authors. Acta Psychiatrica Scandinavica published by John Wiley & Sons Ltd.)

Impaired consciousness is a frequent phenomenon after general anesthesia. In addition to the classical causes (e.g., overhang of sedatives), an impairment of consciousness can also be an adverse side effect of drugs. Many drugs used in anesthesia can trigger these symptoms. Alkaloids, such as atropine can trigger a central anticholinergic syndrome, opioids can promote the occurrence of serotonin syndrome and the administration of a neuroleptic can lead to neuroleptic malignant syndrome. These three syndromes are difficult to diagnose due to the individually very heterogeneous symptoms. Mutual symptoms, such as impaired consciousness, tachycardia, hypertension and fever further complicate the differentiation between the syndromes; however, more individual symptoms, such as sweating, muscle tension or bowl sounds can be helpful in distinguishing these syndromes. The time from the trigger event can also help to differentiate the syndromes. The central anticholinergic syndrome is the fastest to appear, usually taking just a few of hours from trigger to clinical signs, serotonin syndrome takes several hours up to 1 day to show and neuroleptic malignant syndrome usually takes days. The clinical symptoms can range from mild to life-threatening. Generally, mild cases are treated with discontinuation of the trigger and extended observation. More severe cases can require specific antidotes. The specific treatment recommended for central anticholinergic syndrome is physostigmine with an initial dose of 2 mg (0.04 mg/kg body weight, BW) administered over 5 min. For serotonin syndrome an initial dose of 12 mg cyproheptadine followed by 2 mg every 2 h is recommended (maximum 32 mg/day or 0.5 mg/kgBW day -1 ) but this medication is only available in Germany as an oral formulation. For neuroleptic malignant syndrome 25-120 mg dantrolene (1-2.5 mg/kgBW maximum 10 mg/kgBW day -1 ) is the recommended treatment., (© 2023. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Rationale: Posttraumatic stress disorder (PTSD) is highly prevalent among veterans. Many veterans with PTSD respond well to serotonin reuptake inhibitors (SRIs). Nonresponders may be prescribed augmenting medications, which are not as well-studied in PTSD., Aims and Objectives: We used Veterans Health Administration electronic records to compare mental health outcomes (PTSD symptoms and rates of mental health hospitalizations and psychiatric emergency room visits) in patients with PTSD who were prescribed four different groups of augmenting medications (atypical antipsychotics, mirtazapine, prazosin or tricyclic antidepressants) in addition to SRIs-from the year before to the year after the start of the augmenting medication., Method: We included data from 169,982 patients with a diagnosis of PTSD (excluding patients with comorbid bipolar or psychotic disorders) seen in Veterans Affairs care from 2007 to 2015 who were taking an SRI and filled a new prescription for one of the four augmenting medications for at least 60 days., Results: Patients evidenced minimal (<2%) reduction in PTSD symptoms and a larger reduction in psychiatric hospitalizations and psychiatric emergency room visits after receiving augmenting medications; this effect was largely similar across the four medication groups. Initiating augmenting medications was preceded by increases in PTSD symptoms, psychiatric hospitalizations and psychiatric emergency room visits. After initiating an augmenting medication, PTSD symptoms/hospitalizations/emergency room visits returned to baseline levels (before the start of the augmenting medication), but generally did not improve beyond baseline., Conclusion: Importantly, these effects could be explained by regression to the mean, additional interventions or confounding. These findings should be further explored with placebo controlled randomized clinical trials., (© 2022 John Wiley & Sons Ltd.)

Background: Tiapride is an atypical antipsychotic used to treat alcohol withdrawal, aggressiveness and agitation, headache, dyskinesias, tic and Tourette's disorder. More recently, it has been proposed for the treatment of delirium and agitation in hospitalised patients with COVID-19. Although its safety profile makes it suitable for use in vulnerable populations, the use of tiapride for psychiatric disorders is limited. This work aims to systematically review the available evidence on the efficacy and tolerability of tiapride in individuals with a psychiatric disorder., Methods: We searched PubMed, Embase, PsycINFO, GreyLit, OpenGrey, and ProQuest up to March 2020 for randomised controlled trials focussing on the use of tiapride in the treatment of individuals with a psychiatric disorder (e.g., mood disorder, schizophrenia spectrum, substance use disorder). The Risk of Bias 2 was performed for the quality assessment of the included studies., Results: We identified 579 records. Of them, six studies (published between 1982 and 2010) were included in the review. Four studies referred to alcohol withdrawal, and two to the management of agitation in elderly patients with dementia. None of the studies reported significant differences between tiapride and other active comparators in terms of efficacy and tolerability. The overall risk of bias was moderate to high., Conclusion: Tiapride may be considered as a relatively safe treatment option for selected patients with alcohol withdrawal or agitation in dementia. However, solid evidence of its efficacy in the scientific literature is lacking. High-quality trials remain necessary to fully sustain its use in clinical practice., (© 2022 John Wiley & Sons Ltd.)

Abstract: Long-term institutionalization of the forensic psychiatry patient population places a psychological burden on patients and family members as well as a financial burden on the health care system at large. Although electroconvulsive therapy is a well-established tool for patients with treatment-resistant schizophrenia, it is infrequently used in the forensic setting. This review serves to demonstrate an example of electroconvulsive therapy in combination with clozapine as a means of reducing length of hospitalization in a forensic psychiatric patient. Furthermore, this review will discuss factors limiting the prescribing of electroconvulsive therapy to this patient population including ethical considerations and availability., Competing Interests: The authors have no conflicts of interest or financial disclosures to report., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Cognitive impairments associated with schizophrenia (CIAS) represent a central element of the symptomatology of this severe mental disorder. CIAS substantially determine the disease prognosis and hardly, if at all, respond to treatment with currently available antipsychotics. Remarkably, all drugs presently approved for the treatment of schizophrenia are, to varying degrees, dopamine D 2 /D 3 receptor blockers. In turn, rapidly growing evidence suggests the immense significance of systems other than the dopaminergic system in the genesis of CIAS. Accordingly, current efforts addressing the unmet needs of patients with schizophrenia are primarily based on interventions in other non-dopaminergic systems. In this review article, we provide a brief overview of the available evidence on the importance of specific systems in the development of CIAS. In addition, we describe the promising targets for the development of new drugs that have been used so far. In doing so, we present the most important candidates that have been investigated in the field of the specific systems in recent years and present a summary of the results available at the time of drafting this review (May 2022), as well as the currently ongoing studies., (© 2022. The Author(s).)

Long-acting injectable (LAI) antipsychotic medications may be an important modality of reducing costs, improving symptoms, and fostering quality of life outcomes for those with schizophrenia. Our objective was to systematically review and conduct a meta-analysis of the effectiveness of LAIs compared with oral antipsychotics on medication adherence, symptom remission/relapse, rehospitalization, outpatient visits, emergency department visits, healthcare costs, and social functioning. We performed a systematic search of PsycInfo, CINAHL, PubMed, and Scopus databases to examine studies meeting inclusion criteria prior to August 30th, 2020. Randomized controlled trials, retrospective studies, prospective studies among people with schizophrenia with at least 6-month follow-up data were obtained. Overall effect sizes and associated 95% confidence intervals (CI) were estimated with random-effects modeling. We found 75 articles meeting our inclusion criteria, including 341 730 individuals with schizophrenia. Systematic review results indicated that LAIs compared with orals improved medication adherence (25/29 studies), symptom remission/relapse (10/18 studies), rehospitalizations (26/49 studies), emergency department visits (9/17 studies), medical costs (11/15 studies), and social functioning (5/9 studies); however, LAIs also increased outpatient visits (7/16 studies) and pharmacy costs (10/10 studies). Meta-analytic results of studies with similar outcome measures did not find differences between LAIs and orals in respect to outcomes, except lowering emergency department visits and increasing pharmacy costs. The differences between the results of the narrative synthesis and the meta-analyses were possibly because of the low availability of studies with similar outcomes in the pooled analyses. Our overall results suggest that LAIs are at least comparable to orals in supporting important healthcare outcomes for those with schizophrenia. These findings support clinical practice in encouraging providers to prescribe LAIs when indicated., (© 2021 John Wiley & Sons Australia, Ltd.)

Olanzapine (OLZ) and lithium carbonate (Li2CO3) are the main drugs for treating mental disorders related to dopamine (DA). A highly conductive carbon paper sensing electrode is used to investigate the effects of OLZ and Li2CO3 on DA oxidation due to its amplification of oxidation peak currents. Different chemical properties of drugs have different effects on DA oxidation. The presence of OLZ fouling on the electrode surface due to the irreversible adsorption weakens the sensing activity and thus reduces the DA oxidation peak current. However, the fixed DA oxidation peak potential at 0.22 V indicates no interaction between them. The hydrolysis effect of Li2CO3 increases the solution pH from 7.47 to 9.73, which promotes the deprotonation of DA, leading to a 156 mV negative shift of the DA oxidation peak potential. Additionally, a 94% decrease of the DA peak current may be related to the generation of polydopamine in alkaline media. [ABSTRACT FROM AUTHOR]

Background: We investigated the mortality risk associated with the initiation of antipsychotic treatment among patients with dementia and whether comorbidities related to the cardiovascular system and diabetes interact with antipsychotic treatment to increase the mortality risk beyond the risk of death independently associated with antipsychotics and comorbidity alone., Methods: We designed a matched cohort study using nationwide registry data. All Danish residents aged 65-95 years diagnosed with dementia between 2009 and 2014 were included. Dementia was assessed as a first-time registered dementia diagnosis in the Danish National Patient Register or the Danish Psychiatric Central Research Register and/or a first-time prescription for antidementia medication. Patients exposed to antipsychotics were matched with up to three unexposed patients. Cox proportional hazards models were used to compare rates of death within 180 days after the initiation of antipsychotic treatment. The models were adjusted for potential confounders. Analyses were stratified for diabetes, heart disease, and cerebrovascular disease, and we calculated the relative excess risk due to interaction (RERI)., Results: The study cohort included 8244 exposed patients and 24,730 unexposed patients. A total of 5938 patients died during the first 180 days of follow-up. Patients exposed to antipsychotics had a significantly higher adjusted risk of death (hazard ratio: 1.35, 95% confidence interval: 1.27-1.43) than unexposed patients. Crude mortality rates were higher among patients with heart disease and diabetes when antipsychotic treatment was initiated compared with patients without comorbidities. Relative risk estimates did not differ between patients with and without heart disease, cerebrovascular disease, and diabetes, and RERI suggested no positive additive interaction. Risk analysis suggested higher mortality in patients without cerebrovascular disease who initiated antipsychotics., Conclusion: This nationwide study adds to the evidence that antipsychotic treatment is associated with increased mortality and suggests that attention should be paid to all initiators of antipsychotics irrespective of cardiovascular disease and diabetes., (© 2022 The American Geriatrics Society.)

Patients with dementia can experience hallucinations and delusions because of their underlying neurodegenerative condition, a syndrome known as dementia-related psychosis. Dementia-related psychosis contributes to morbidity and mortality among patients with dementia and increases the burden on caregivers and the health care system. With no pharmacological treatment currently approved in the United States for this condition, patients are often treated off-label with antipsychotics. Though typical and atypical antipsychotics have demonstrated variable to modest efficacy in dementia-related psychosis, serious safety concerns arise with their use. Accordingly, clinical and Centers for Medicare & Medicaid Services guidelines recommend trying antipsychotics only when other therapies have failed and encourage treatment discontinuation of antipsychotics after 4 months to assess whether ongoing therapy is needed. Discontinuation of effective antipsychotic treatment, however, may increase the risk for relapse of symptoms and the associated morbidities that accompany relapse. A randomized medication withdrawal clinical trial design allows assessment of relapse risk after discontinuation and can provide initial information on longer-term safety of therapy for dementia-related psychosis. Given the substantial unmet need in this condition, new, well-tolerated therapies that offer acute and sustained reduction of symptoms while also preventing recurrence of symptoms of psychosis are critically needed., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc.)

Purpose: To develop and validate a population pharmacokinetic (PPK) model of valproic acid (VPA) in adult Chinese patients with bipolar disorder, and provide guidance for individualized therapy in this population., Methods: A total of 1104 serum concentrations from 272 patients were collected in this study. The data analysis was performed using a nonlinear mixed-effects modeling approach. Covariates included demographic parameters, biological characteristics, and concomitant medications. Bootstrap validation (1000 runs), normalized prediction distribution error (NPDE), and external validation of 50 patients were employed to evaluate the final model., Results: A one-compartment model with first-order absorption and elimination was developed for VPA extended-release tablets. VPA clearance was significantly influenced by three variables: sex (12% higher in male patients), daily dose (increasing with the 0.13 exponent), and body weight (increasing with the 0.56 exponent). Typical values for the absorption rate constant (K a ), apparent clearance (CL/F), and apparent distribution volume (V/F) for a female patient weighing 70 kg administered VPA 1000 mg/day were 0.18 h -1 , 0.46 L/h, and 12.84 L, respectively. The results of model evaluation indicated a good stable and precise performance of the final model., Conclusions: A qualified PPK model of VPA was developed in Chinese patients with bipolar disorder. This model could be used as a suitable tool for the personalization of VPA dosing for bipolar patients., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Ondansetron is a selective serotonin (5HT3) receptor antagonist that is under evaluation as an adjunctive treatment for schizophrenia, and a novel treatment for hallucinations in Parkinson's disease. Ondansetron reverses sensory gating deficits and improves visuoperceptual processing in animal models of psychosis, but it is unclear to what extent preclinical findings have been replicated in humans. We systematically reviewed human studies that evaluated the effects of ondansetron and other 5HT3 receptor antagonists on sensory gating deficits or sensory processing. Of 11 eligible studies, eight included patients with schizophrenia who were chronically stable on antipsychotic medication; five measured sensory gating using the P50 suppression response to a repeated auditory stimulus; others included tests of visuoperceptual function. Three studies in healthy participants included tests of visuoperceptual and sensorimotor function. A consistent and robust finding (five studies) was that ondansetron and tropisetron (5HT3 antagonist and α7-nicotinic receptor partial agonist) improved sensory gating in patients with schizophrenia. Tropisetron also improved sustained visual attention in non-smoking patients. There was inconsistent evidence of the effects of 5HT3 antagonists on other measures of sensory processing, but interpretation was limited by the small number of studies, methodological heterogeneity and the potential confounding effects of concomitant medication in patients. Despite these limitations, we found strong evidence that selective 5HT3 antagonists (with or without direct α7-nicotinic partial agonist effects) improved sensory gating. Future studies should investigate how this relates to potential improvement in neurocognitive symptoms in antipsychotic naive patients with prodromal or milder symptoms, in order to understand the clinical implications., (© 2022. The Author(s).)

Background: Atypical antipsychotic medications have often been used in the treatment of behavioral and psychological symptoms of dementia (BPSD). Recently, the US Food and Drug Administration (FDA) issued new safety information concerning atypical antipsychotic drugs, indicating that their use may increase the risk of cardiovascular adverse events among elderly adults with BPSD. Based on this information, the Japanese Ministry of Health, Labor and Welfare issued a similar warning against the use of atypical antipsychotic drugs licensed in Japan. We then sought to determine whether or not the use of typical antipsychotics should be recommended to replace atypical antipsychotics. In this paper, we discuss the influence of these warnings on the withholding of use of risperidone exemplified in seven case histories. Methods: Seven inpatients who exhibited BPSD received risperidone monotherapy in our hospital. In response to the FDA notice, the atypical antipsychotics used to treat these patients were replaced with typical antipsychotic agents. Results: During the period of risperidone administration, all patients exhibited clinical improvement compared with their baseline results and showed no adverse events. Two of our seven patients developed psychotic exacerbation and exhibited extrapyramidal symptoms coinciding with the replacement of risperidone with conventional antipsychotics. Conclusion: To the best of our knowledge, this is the first clinical report on the influence of the FDA alert on the use of atypical antipsychotics for psychotic symptoms in older patients with dementia in Japan. In two of our seven BPSD cases, there was no benefit from taking conventional antipsychotics. Our results lead to the conclusion that the use of typical antipsychotics should not be recommended to replace atypical antipsychotics. Although close attention should be paid to the FDA alert, clinicians must take into consideration the balance of benefits and risks when evaluating the appropriate use of antipsychotics in older patients with dementia. [ABSTRACT FROM AUTHOR]

Risperidone and aripiprazole, commonly used antipsychotics in children with autism spectrum disorder (ASD), have previously been associated with elevated fracture risk in other populations. The aim of this study was to evaluate and compare the risk of fracture among children with ASD using risperidone or aripiprazole. This was a retrospective, propensity-score matched cohort study, set between January 2013 and December 2018. We used the MarketScan Medicaid insurance data, which covers multiple states of the United States. We included ASD children aged 2-18 years, who were new users of aripiprazole or risperidone and with no prior history of antipsychotic use or fractures. The main exposure was the continued use of aripiprazole or risperidone. The incidence rates of any fracture during follow-up were evaluated, and the risk between aripiprazole and risperidone was compared via Cox-proportional hazard models. Results were stratified by age, sex, duration of exposure and fracture site. In total, 3312 patients (78% male; mean [SD] age 11.0 [3.7] years) were identified for each cohort. Over the full duration of follow-up, fracture incidence rates per 1000 patient-years were 23.2 for risperidone and 38.4 for aripiprazole (hazard ratio and 95% confidence interval: 0.60 [0.44-0.83]). Risks were similar between cohorts throughout the first 180 days on treatment, but significantly higher in the aripiprazole group thereafter. Extremity fractures drove most of the increased risk, with the biggest differences in lower leg and ankle fractures. Differences widened for children aged 10 years or younger (HR [95% CI]: 0.47 [0.30-0.74]). In conclusion, compared to aripiprazole, risperidone was associated with 40% lower risk of fracture. Further analysis on the mechanism and long-term bone health of antipsychotic-treated children with ASD is warranted. LAY SUMMARY: We compared the risk of bone fractures among 6624 children with autism spectrum disorder (ASD), half of whom used risperidone and half of whom used aripiprazole. Taking other factors into account, risks were similar between the two groups throughout the first 180 days on treatment, but significantly higher in the aripiprazole group thereafter. The biggest differences were in lower leg and ankle fractures. Overall, compared with aripiprazole, risperidone was associated with 40% lower risk of fracture., (© 2021 The Authors Autism Research © 2021 International Society for Autism Research and Wiley Periodicals LLC.)