Antipsychotic Dose Research Articles

Prescribing of antipsychotics for people diagnosed with severe mental illness in UK primary care 2000-2019: 20-year investigation of who receives treatment, with which agents and at what doses.

Contemporary data relating to antipsychotic prescribing in UK primary care for patients diagnosed with severe mental illness (SMI) are lacking. To describe contemporary patterns of antipsychotic prescribing in UK primary care for patients diagnosed with SMI. Cohort study of patients with an SMI diagnosis (i.e. schizophrenia, bipolar disorder, other non-organic psychoses) first recorded in primary care between 2000 and 2017 derived from Clinical Practice Research Datalink. Patients were considered exposed to antipsychotics if prescribed at least one antipsychotic in primary care between 2000 and 2019. We compared characteristics of patients prescribed and not prescribed antipsychotics; calculated annual prevalence rates for antipsychotic prescribing; and computed average daily antipsychotic doses stratified by patient characteristics. Of 309 378 patients first diagnosed with an SMI in primary care between 2000 and 2017, 212,618 (68.7%) were prescribed an antipsychotic between 2000 and 2019. Antipsychotic prescribing prevalence was 426 (95% CI, 420-433) per 1000 patients in the year 2000, reaching a peak of 550 (547-553) in 2016, decreasing to 470 (468-473) in 2019. The proportion prescribed antipsychotics was higher among patients diagnosed with schizophrenia (81.0%) than with bipolar disorder (64.6%) and other non-organic psychoses (65.7%). Olanzapine, quetiapine, risperidone and aripiprazole accounted for 78.8% of all antipsychotic prescriptions. Higher mean olanzapine equivalent total daily doses were prescribed to patients with the following characteristics: schizophrenia diagnosis, ethnic minority status, male gender, younger age and greater relative deprivation. Antipsychotic prescribing is dominated by olanzapine, quetiapine, risperidone and aripiprazole. We identified potential disparities in both the receipt and prescribed doses of antipsychotics across subgroups. To inform efforts to optimise prescribing and ensure equity of care, further research is needed to understand why certain groups are prescribed higher doses and are more likely to be treated with long-acting injectable antipsychotics compared with others.

EFEITOS TERAPÊUTICOS DA DIETA CETOGÊNICA NO TRATAMENTO DA ESQUIZOFRENIA: UMA REVISÃO DE LITERATURA

Nutritional interventions, such as the ketogenic diet (KD), have been used for centuries in the management of neurological conditions, including epilepsy. This study is a literature review that investigates the benefits of KD as an adjunct in the treatment of schizophrenia, focusing on its ability to enhance the effectiveness of medication and enable the reduction of antipsychotic dosages without compromising symptom control. The research was conducted using the PUBMED and MEDLINE databases, with DeCS and MeSH descriptors combined with Boolean operators, resulting in 35 studies published over the last 10 years. After applying inclusion criteria, articles addressing schizophrenia and ketogenic diet in their titles and abstracts were selected. The results indicate that KD can improve the response to medication in schizophrenic patients, reducing behavioral deficits and symptoms, with efficacy equivalent to or greater than that of antipsychotics, while also minimizing metabolic side effects. However, the variability in responses and the lack of extensive clinical trials limit definitive conclusions. Despite this, KD emerges as a promising strategy to optimize the pharmacological management of schizophrenia, requiring future studies to validate its safety, efficacy, and applicability in clinical practice.

Thinning of central foveal thickness in the retina of patients with schizophrenia.

The neural retina shares a common embryonic origin with the brain and yields pathological changes like that in the brain in various neuropsychiatric disorders, including schizophrenia. Non-invasive examination by optical coherence tomography (OCT) revealed retinal structure abnormalities in patients with schizophrenia. This study investigated retina structures in 29 patients with schizophrenia and 25 healthy controls in a Chinese Han ethnic population with spectral domain OCT. Measurements of central foveal thickness (CFT) as well as other retinal structures in macular and peripapillary subregions were performed. Associations between OCT parameters and clinical features, including severity of positive and negative symptoms, disease duration and antipsychotic dosage were analyzed. With controlling for age and sex, patients showed significantly thinner CFT, thinner central macular thickness, and thinner total retinal thickness in subregions of the central, inner superior, inner temporal, and inner nasal macula of both eyes, thinner ganglion cell complex in a subregion of the left eye, as well as larger cup volume in the peripapillary region of the right eye. In addition, CFT also negatively correlated with severity of negative symptoms. These findings suggest that CFT has the potential to be a disease biomarker of schizophrenia.

Real-World Treatment of Schizophrenia in Adults With a 22q11.2 Microdeletion: Traitement dans le monde réel de la schizophrénie chez des adultes atteints du syndrome de microdélétion 22q11.2.

One in every 4 individuals born with a 22q11.2 microdeletion will develop schizophrenia. Thirty years of clinical genetic testing capability have enabled detection of this major molecular susceptibility for psychotic illness. However, there is limited literature on the treatment of schizophrenia in individuals with a 22q11.2 microdeletion, particularly regarding the issue of treatment resistance. From a large, well-characterized adult cohort with a typical 22q11.2 microdeletion followed for up to 25 years at a specialty clinic, we studied all 107 adults (49 females, 45.8%) meeting the criteria for schizophrenia or schizoaffective disorder. We performed a comprehensive review of lifetime (1,801 patient-years) psychiatric records to determine treatments used and the prevalence of treatment-resistant schizophrenia (TRS). We used Clinical Global Impression-Improvement (CGI-I) scores to compare within-individual responses to clozapine and nonclozapine antipsychotics. For a subgroup with contemporary data (n = 88, 82.2%), we examined antipsychotics and dosage at the last follow-up. Lifetime treatments involved on average 4 different antipsychotic medications per individual. Sixty-three (58.9%) individuals met the study criteria for TRS, a significantly greater proportion than for a community-based comparison (42.9%; χ2 = 10.38, df = 1, p < 0.01). The non-TRS group was enriched for individuals with genetic diagnosis before schizophrenia diagnosis. Within-person treatment response in TRS was significantly better for clozapine than for nonclozapine antipsychotics (p < 0.0001). At the last follow-up, clozapine was the most common antipsychotic prescribed, followed by olanzapine, risperidone, and paliperidone. Total antipsychotic chlorpromazine equivalent dosages were in typical clinical ranges (median: 450 mg; interquartile range: 300, 750 mg). The results for this large sample indicate that patients with 22q11.2 microdeletion have an increased propensity to treatment resistance. The findings provide evidence about how genetic diagnosis can inform clinical psychiatric management and could help reduce treatment delays. Further research is needed to shed light on the pathophysiology of antipsychotic response and on strategies to optimize outcomes.

Antipsychotic discontinuation in nonaffective first-episode psychosis after clinical remission: Insights from the PEPsNa naturalistic study

The predictors of clinical evolution after nonaffective first-episode psychosis (NAFEP) have yet to be fully elucidated. It is important to weigh the long-term benefits of maintained antipsychotic (AP) treatment against the risks of relapse upon discontinuation. Between January 2017 and December 2022, we recruited 211 NAFEP patients from the Programa de Primeros Episodios Psicóticos de Navarra (PEPsNa) who achieved clinical remission within two years and continued follow-up. Clinicians recommended discontinuation of antipsychotics for 47 participants, resulting in significantly fewer relapses (10.6%, p≤ 0.05) and a longer relapse-free survival time (95% confidence interval= 16.9 to 18.2 months). For every four individuals out of 72 who voluntarily discontinued APs (in contrast to those who were advised to discontinue APs), there was one more relapse (number needed to harm= 4; p≤ 0.01). Moreover, one additional relapse was prevented for every seven individuals who continued APs instead of voluntarily discontinuing APs (number needed to treat= 7; p≤ 0.05). Lower premorbid risk factors and better clinical profiles, such as shorter DUP, shorter time to remission, good real-world performance, better neurocognitive functioning, lack of a schizophrenia spectrum diagnosis, and a lower average dose of APs led clinicians to recommend AP discontinuation after achieving remission from NAFEP. This guided discontinuation of APs did not lead to a higher risk of relapse, but participants who voluntarily withdrew from treatment had a higher risk of relapse.

THE CHOICE OF ANTIPSYCHOTICS: CONTEMPORARY KNOWLEDGE

Antipsychotics are a group of psychoactive drugs that eliminate delusions and hallucinations, improve the ability to test reality and lead to the reintegration of psychological functions and enable a return to reality. In addition to antipsychotic, they also have sedative, anxiolytic, antidepressant, antimanic stabilizing, anti-suicidal and antiemetic effects, therefore the drugs are used in the treatment of various other non-psychotic disorders. The objective of this paper is to point out the contemporary findings in the best choice of antipsychotics.We live in the period of psychopharmacology’s rapid progress and our possibilities in the treatment of psychotic disorders are increasing. In recent decades, treatment with antipsychotics has been significantly improved due to the development of new antipsychotics with better therapeutic effect and safer profile of side effects. The basic mechanism of action of antipsychotics is dopamine receptors, with an effect on the noradrenaline, serotonin, histamine, adrenergic, and cholinergic systems, and indirectly on the gamma-aminobutyric acid and glutamine system. All this makes the mechanism of action of antipsychotics extremely complex. There are several different subdivisions of antipsychotics, and in clinical practice the most common division is the so-called typical and atypical. Typical antipsychotics that achieve their mechanism of action by blocking the D2 receptor show effectiveness in the treatment of positive symptoms of schizophrenia, but have a much lower effect in the treatment of negative, affective and cognitive symptoms. They often have significant side effects. Atypical antipsychotics work on both positive and negative symptoms of psychosis. In severe forms of psychosis, they are often insufficient in the treatment of positive symptoms, so we are forced to use a combination of antipsychotics. Although antipsychotic monotherapy is the ideal therapy, in practice we are often forced to combine two or more antipsychotics, as well as combine antipsychotics with other groups of psychopharmaceuticals. It is not easy to answer whether combinations of antipsychotics are useful or not. The key to success is an individual approach, careful selection of the type and dose of antipsychotics, and the inclusion of psycho and socio-therapeutic methods that are indicated in each case individually. Keywords: antipsychotics, choice, contemporary knowledge.

EANM perspective on clinical PET and SPECT imaging in schizophrenia-spectrum disorders: a systematic review of longitudinal studies.

There is a need for biomarkers in psychiatry to improve diagnosis, prognosis and management, and with confirmed value in follow-up care. Radionuclide imaging, given its molecular imaging characteristics, is well-positioned for translation to the clinic. This systematic review lays the groundwork for integrating PET and SPECT imaging in the clinical management of schizophrenia-spectrum disorders. Systematic search of PubMed, Embase, Web of Science and Cochrane library databases was conducted from the earliest date available until February 2024. The focus was on longitudinal studies evaluating PET or SPECT imaging in individuals with a schizophrenia-spectrum or another psychotic disorders. Quality assessment was done using the Newcastle-Ottawa Scale (NOS), NIH scale for before-after studies and Cochrane Risk of Bias tool version 2 (Cochrane RoB2). Studies were further categorised into three groups: preclinical and diagnosis, predicting disease course or personalising treatment. Fifty-six studies were included in the systematic review investigating in total 1329 patients over a median of 3 months. Over two-thirds used PET tracers, whereas the remaining studies employed SPECT tracers. The most frequently investigated system was dopaminergic transmission, followed by cerebral metabolism and blood flow. [18F]FDOPA demonstrated large effect size in predicting conversion of subjects at risk and treatment response. Additionally, treatment dosage could be optimised to reduce side effects using [123I]IBZM or [11C]raclopride. Molecular imaging holds significant promise for real-life application in schizophrenia, with two particularly encouraging avenues being the prediction of conversion/response to antipsychotic medication and the improved management of antipsychotic dosage. Further longitudinal studies and clinical trials will be essential for validating both the clinical effectiveness and economic sustainability, as well as for exploring new applications.

Who can benefit more from its twelve-week treatment: A prospective cohort study of blonanserin for patients with schizophrenia

BACKGROUND Blonanserin (BNS) is a well-tolerated and effective drug for treating schizophrenia. AIM To investigate which types of patients would obtain the most benefit from BNS treatment. METHODS A total of 3306 participants were evaluated in a 12-week, prospective, multicenter, open-label post-marketing surveillance study of BNS. Brief psychiatric rating scale (BPRS) scores were calculated to evaluate the effectiveness of BNS, and its safety was assessed with the incidence of adverse drug reactions. Linear regression was used to screen the influencing factors for the reduction of BPRS total score, and logistic regression was used to identify patients with a better response to BNS. RESULTS The baseline BPRS total score (48.8 ± 15.03) decreased to 27.7 ± 10.08 at 12 weeks (P &lt; 0.001). Extrapyramidal symptoms (14.6%) were found to be the most frequent adverse drug reactions. The acute phase, baseline BPRS total score, current episode duration, number of previous episodes, dose of concomitant antipsychotics, and number of types of sedative-hypnotic agents were found to be independent factors affecting the reduction of BPRS total score after treatment initiation. Specifically, patients in the acute phase with baseline BPRS total score ≥ 45, current episode duration &lt; 3 months, and ≤ 3 previous episodes derived greater benefit from 12-week treatment with BNS. CONCLUSION Patients in the acute phase with more severe symptoms, shorter current episode duration, fewer previous episodes, and a lower psychotropic drug load derived the greatest benefit from treatment with BNS.

Music to Their Ears: Reducing Antipsychotic Use With a Personalized Music Intervention for Rural Veterans.

Background This project investigates a music intervention to deprescribe antipsychoticsin rural Veterans with dementia. Methods The Veterans Health Administration Home-Based Primary Care Program is care provided in the home by an interdisciplinary team with the goals of decreasing hospitalizations and falls, providing education to patients and caregivers, and improving quality of life. Eighteen Home Based Primary Care Veterans with dementia and active antipsychotic prescriptions were identified with the goal to deprescribe antipsychotics in 50% of them using a music intervention. Individualized playlists and assessments for Veteran quality of life and caregiver burden were evaluated. Phone visits tracked music utilization and captured the voice of the customer. Results Antipsychotic dose reduction occurred in five of eight Veterans, totaling eight dose reductionsand one discontinuation. Veteran quality of life improved; however, caregiver burden increased initially. The caregiver burden did improvewhen an outlier was removed. The voice of the customer favored music intervention. Conclusions A personalized music intervention is a feasible approach for reducing antipsychotic use in rural Veterans, improving quality of life, and potentially reducing caregiver burden.

Exploring the longitudinal course of motor dexterity in first-episode psychosis: a 10-year follow-up.

This study aimed to examine longitudinal changes in motor dexterity (MD) performance in first episode of psychosis (FEP), focusing on diagnosis-specific trajectories. Participants were recruited from the project PAFIP in Spain (134 FEP, 84 HC). MD was assessed using the Grooved Pegboard Test at baseline and at 10-year follow-up. Clinical and premorbid data were collected for the patients. FEP participants were classified as having schizophrenia (SCZ) or other psychosis (OP) and compared with a group of healthy controls (HC). MD correlated significantly with age and intelligence in all participants. MD in SCZ patients was additionally correlated with premorbid adjustment and negative symptoms, whereas in the OP group the association was with antipsychotic dose. SCZ patients showed a slight decline in MD at follow-up, whereas the OP and HC groups remained stable. There may be different long-term trajectories of MD across diagnoses in FEP patients. Early developmental factors such as premorbid adaptation and cognitive function, together with age-related changes, may influence a mild decline in MD specifically in schizophrenia.

Medication Exposure and Mortality in Patients With Schizophrenia

The use of antipsychotics, antidepressants, and benzodiazepines may influence the risk of mortality in people with schizophrenia. However, many observational studies have not accounted for immortal time bias (ITB), which occurs when there is a period during which patients in the exposed group are necessarily alive and misclassified as exposed (the period between start of follow-up and initiation of drug). Ignoring ITB may lead to misinterpretation of the association between these drugs and mortality. To examine whether the cumulative dose of antipsychotics, antidepressants, and benzodiazepines is associated with mortality risk in patients with schizophrenia and discuss the potential impacts of ignoring ITB. This cohort study used administrative data from Québec, Canada, including patients aged 17 to 64 years diagnosed with schizophrenia between January 1, 2002, and December 31, 2012. Data analysis was performed from June 22, 2022, to September 30, 2024. The primary outcome was all-cause mortality, with follow-up from January 1, 2013, to December 31, 2017, or until death. Mortality risk was assessed for low, moderate, and high exposure to antipsychotics, antidepressants, and benzodiazepines. Cox proportional hazards regression models with time-fixed exposure (not controlling for ITB) and time-dependent exposure (controlling for ITB) were performed. The cohort included 32 240 patients (mean [SD] age, 46.1 [11.6] years; 19 776 [61.3%] men), of whom 1941 (6.0%) died during follow-up. No dose-response association was found for antipsychotics with mortality using the time-fixed method. However, high-dose antipsychotic use was associated with increased mortality after correcting for ITB (adjusted hazard ratio [AHR], 1.28; 95% CI, 1.07-1.55; P = .008). Antidepressants showed a reduced mortality risk using the time-fixed method, but only at high doses when correcting for ITB (AHR, 0.86; 95% CI, 0.74-1.00; P = .047). Benzodiazepines were associated with increased mortality risk regardless of the method. The findings of this study do not dispute the known efficacy of antipsychotics in schizophrenia, but they call into question the magnitude of long-term mortality benefits.

The Effects of Cognitive Remediation on Negative Symptoms in Schizophrenia-Spectrum Illness: A Meta-analytic Investigation of Efficacy.

The number of clinical efficacy trials of Cognitive Remediation (CR), a behavioral intervention consisting of cognitive task practice and/or strategy training to improve cognitive skills in schizophrenia, has increased substantially over the past 25 years. While recent reviews have highlighted the effects of CR on cognition and function, CR effects on negative symptoms remain understudied. Given the overlap between negative symptoms and cognition, CR effects might be expected. Electronic databases were evaluated up to September 2023 using a broad range of search terms. Sixty-nine unique, controlled trials that used negative symptoms as an outcome were meta-analyzed. Data were independently extracted with excellent (>98%) reliability. Random effects models assessed the effects of CR on summary and expressive vs. experiential negative symptoms. Moderator analyses evaluated a broad array of treatment and participant factors. The meta-analysis (5319 participants) revealed that CR produced a small effect size improvement on summary negative symptoms (Hedge's g = 0.179). Sample differences in age, duration of illness, symptoms, and antipsychotic dosage did not serve as a barrier to treatment benefit. CR also produced small-to-moderate improvements in alogia (Hedge's g = 0.312) but not experiential negative symptoms. Programs of CR that utilized bridging activities that relate training of cognitive skills to activities of daily living produced greater improvement in negative symptoms (g = 0.281 vs 0.055). Longer CR programs also produce larger effects on negative symptoms. CR produces small, consistent reductions in negative symptoms in people with schizophrenia. Variations in CR effects may be linked to different treatment ingredients.

Incidence of Neuroleptic Malignant Syndrome During Antipsychotic Treatment in Children and Youth: A National Cohort Study.

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.

Deconstructing Cognitive Impairment in Psychosis With a Machine Learning Approach

Cognitive functioning is associated with various factors, such as age, sex, education, and childhood adversity, and is impaired in people with psychosis. In addition to specific effects of the disorder, cognitive impairments may reflect a greater exposure to general risk factors for poor cognition. To determine the extent that impairments in cognition in psychosis reflect risk factor exposures. This cross-sectional study examined the relationship between exposures and cognitive function using data from the Bipolar-Schizophrenia Network on Intermediate Phenotypes studies 1 and 2 across 6 sites. Participants included healthy controls; patients with schizophrenia, schizoaffective disorder, or bipolar I disorder with psychosis; and relatives of patients. Predictive modeling was performed using extreme gradient boosting regression to train a composite cognitive score prediction model with nested cross-validation. Shapley additive explanations values were used to examine the relationship between exposures and cognitive function. Exposures were chosen based on associations with cognition previously identified: age, sex, race and ethnicity, childhood adversity, education, parental education, parental socioeconomic status, parental age at birth, substance use, antipsychotic dose, and diagnosis. Cognition was assessed using the Brief Assessment of Cognition in Schizophrenia. A total of 3370 participants were included: 840 healthy controls, 709 patients with schizophrenia, 541 with schizoaffective disorder, 457 with bipolar I disorder with psychosis, and 823 relatives of patients. The mean (SD) age was 37.9 (13.3) years; 1887 were female (56%) and 1483 male (44%). The model predicted cognitive scores with high accuracy: out-of-sample Pearson correlation between predicted and observed cognitive composite score was r = 0.72 (SD = 0.03). Individuals with schizophrenia (z = -1.4), schizoaffective disorder (z = -1.2), and bipolar I disorder with psychosis (z = -0.5) all had significantly worse cognitive composite scores than controls. Factors other than diagnosis and medication accounted for much of this impairment (schizophrenia z = -0.73, schizoaffective disorder z = -0.64, bipolar I disorder with psychosis z = -0.13). Diagnosis accounted for a lesser proportion of this deficit (schizophrenia z = -0.29, schizoaffective disorder z = -0.15, bipolar I disorder with psychosis z = -0.13), and antipsychotic use accounted for a similar deficit across diagnostic groups (schizophrenia z = -0.37, schizoaffective disorder z = -0.33, bipolar I disorder with psychosis z = -0.26). This study found that transdiagnostic factors accounted for a meaningful share of the variance in cognitive functioning in psychosis. A significant proportion of the cognitive impairment in psychosis may reflect factors relevant to cognitive functioning in the general population. When considering interventions, a diagnosis-agnostic, symptom-targeted approach may therefore be appropriate.

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

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

Association between treatment resistance and cognitive function in schizophrenia.

Treatment-resistant schizophrenia (TRS) affects around 30% of individuals with schizophrenia. About half of the patients with TRS who are treated with clozapine do not show a meaningful clinical response, that is, clozapine resistance. To date, the relationship between cognitive function and treatment response categories is not entirely clear. This study evaluated the cognitive performance across subgroups stratified by treatment response, and we hypothesised that cognitive impairment increases with increased treatment resistance. This study was conducted at the Institute of Mental Health, Singapore, and included healthy controls and people with schizophrenia categorised into these groups: antipsychotic-responsive schizophrenia (ARS), clozapine-responsive TRS (TRS-CR) and clozapine-resistant TRS (ultra-treatment-resistant schizophrenia [UTRS]). Cognitive function was assessed using the Brief Assessment of Cognition-Short Form. Symptoms were measured with the Positive and Negative Syndrome Scale (PANSS). The planned statistical analyses included adjustments for covariates such as age, sex, PANSS scores and antipsychotic dose, which might affect cognitive function. There were significant differences in overall cognitive performance between the groups: ARS had the least impairment, followed by TRS-CR and UTRS. Antipsychotic dose, and PANSS negative and disorganisation/cognitive factors were significant predictors of overall cognitive function in all patient groups. Our study found differences in cognitive function that aligned with levels of treatment resistance: the greater the degree of treatment resistance, the poorer the cognitive function. Interventions to improve negative and disorganisation symptoms might be effective to enhance the cognitive function and treatment outcomes in schizophrenia.

Deprescribing antipsychotics in patients with schizophrenia: findings from a specialized clinic.

While antipsychotic medication reduces the risk of relapse for patients with schizophrenia, high prevalence of adverse effects results in low adherence. Lower doses of antipsychotics have been associated with increased level of function but also with increased risk of relapse. This study presents findings from a specialized deprescribing clinic. In addition, we aim to identify clinical predictors for relapse. Patients diagnosed with schizophrenia were referred to the clinic, which offers a six-month guided tapering program. Antipsychotic dose was reduced by 10% every four weeks. Patients were monitored closely for symptom progression or decrease in level of function, with defined cut-offs prompting a pause in or cessation of dose reduction. After 12 months, the antipsychotic dose was reduced from 404 (±320 mg) to 255 (±236 mg) chlorpromazine equivalent. Of the 88 patients included, 22 (27%) experienced relapse during the six-month tapering period, while 29 (37%) experienced relapse at the 12-month follow-up visit and nine patients were antipsychotic free. Patients who remained stable experienced a slightly increased level of functioning and markedly fewer side effects (p < 0.001). Following relapse, patients were clinically stabilized and showed an improved attitude toward antipsychotic medication. The predictive models were weak. We show that most patients undergoing guided antipsychotic tapering remained stable after one year and improved in level of function, while most patients who relapsed were quickly stabilized. Our inability to create strong predictive models could be due to limitations in the study design, warranting future studies exploring tapering of antipsychotics in patients with schizophrenia.

Personality Correlates of Certain Clinical Characteristics of Patients With Psychotic Disorders

Abstract: Our study aimed to link personality traits (Big Five plus proneness to psychotic-like experiences and behaviors, conceptualized as Disintegration) with clinical characteristics (gender, age, density of episodes, average antipsychotic doses, functionality, and symptom scores). We analyzed 137 patients with psychotic disorders (ICD-10: F20–F29) who had at least one psychotic episode, with illness duration ≤10 years, in remission. Canonical correlation analysis revealed that (1) Psychotic fragility (defined by high density of illness episodes, older age, and more severe symptoms) is associated with high Disintegration and Neuroticism; (2) Disorder severity (high antipsychotic doses, dysfunctionality, severe symptoms, younger age) is linked to low Agreeableness and Openness; and (3) Well-functioning patients (better functionality, milder symptoms) are predicted by a resilient personality profile. These findings deepen our understanding of personality–psychopathology relationships.

Renal Impairment and Dose Adjustment of Long-Acting Injectable Antipsychotics: Are We Getting It Right? A Case Report.

Renal impairment is defined as an estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m2 with or without kidney damage. Creatinine, which is found in serum and urine, is a common biomarker to estimate renal function and is used in most eGFR equations. Renal impairment can decrease or increase drug effects, necessitating therapeutic adjustments. Increased effect is related to drug accumulation that leads to increased elimination time and potential toxicity. eGFR plays a crucial role in drug dosing, particularly for renally excreted medications. However, the lack of recognition of pre-existing renal impairment and the incorrect interpretation of eGFR equations remain challenges. This case report explores the significance of eGFR in patients with psychiatric conditions, especially in the context of long-acting antipsychotic drug dosing.

Verification of successful maintenance by serum drug level during a guided antipsychotic reduction to reach minimum effective dose (GARMED) trial.

Inconsistent results regarding the risk of relapse and better subjective outcomes of previous antipsychotic dose reduction trials in patients with remitted psychosis have not been verified using therapeutic drug monitoring (TDM). This study examined plasma drug concentrations of a dose-tapering trial which exhibited the potential of successful maintenance under lower antipsychotic dosages. A 2-year open-label randomized prospective trial recruited remitted patients to undergo guided antipsychotic tapering. Blood samples were collected at baseline, annually, and after each dose reduction. Plasma aripiprazole/dehydroaripiprazole concentrations were determined using LC-MS/MS. The relationship between the dose and serum drug levels was examined using Spearman's correlation. Divided at 120 ng/mL, relapse rate, global function, quality of life, and psychopathology were compared between high- and low- drug level groups. A total of 126 blood samples were collected, after excluding13 samples due of non-adherence. The correlation coefficients between dosage and drug level were 0.853 (aripiprazole) and 0.864 (dehydroaripiprazole), and the dose and concentration plots were parallel along the tapering trajectories, except patients with non-adherence. The concentration-to-dose ratio of aripiprazole in this cohort, 17.79 ± 7.23 ng/mL/mg, was higher than that in Caucasian populations. No significant differences were observed in the clinical outcomes between the high- and low-level groups. Remarkably, 12 of 15 patients maintained remission at plasma aripiprazole concentrations of <120 ng/mL. The lower-than-expected doses reached in our antipsychotic tapering trial were substantiated to provide adequate prophylactic effects by TDM results in a subset of patients treated with aripiprazole, even considering the differences in pharmacogenomics between ethnicities.