Effects Of Antipsychotic Medication Research Articles

Effects of antipsychotic medications in glucose and lipid metabolism at the fasted state in drug-naïve first episode patients with psychosis after six months and three years of treatment.

Diabetes and dyslipidemia are common in patients with psychosis and may be related to adverse effects of antipsychotic medications. Metabolic disturbances in first-episode patients with psychosis are common, even prior to any antipsychotic treatment, and antipsychotic medications are implicated in the development of metabolic syndrome, at least in the long run. We therefore aimed to follow a group of drug-naïve, first-episode patients with psychosis at different time points (baseline, six months, and 36 months after the initiation of antipsychotic treatment) in order to evaluate the progression of metabolic abnormalities after antipsychotic therapy and the time-course of their onset. We assessed glucose and lipid metabolism during the fasted state in 54 drug-naïve patients with first-episode psychosis (FEP) before the initiation of any antipsychotic treatment and compared them with matched controls. The same parameters were assessed in the patient group (n=54) after six months of antipsychotic treatment and in a subgroup of patients (n=39) after three years of continuous and stable treatment in comparison to baseline. Measurements were obtained for fasting serum concentrations of total cholesterol, triglycerides, high density lipoprotein (HDL), glucose, insulin, connecting peptide (C-peptide), homeostatic model assessment index (HOMA-IR), glycated hemoglobin (HbA1c) and body mass index (BMI). Insulin, C-peptide, triglyceride levels, and HOMA-IR index were significantly higher compared to controls. Total cholesterol, triglyceride levels and BMI, increased significantly in the patient group after six months of antipsychotic treatment. After three years of continuous antipsychotic treatment, we found statistically significant increases in fasting glucose, insulin, total cholesterol, triglyceride levels, HbA1c, HOMA-IR index, and BMI compared to baseline. In conclusion, FEP patients developed significant increases in BMI and serum lipid levels as soon as six months after antipsychotic treatment. These metabolic abnormalities persisted following 36 months of treatment and in addition, increases in fasting glucose, insulin, HbA1c and HOMA-IR were observed compared to baseline.

The effect of antipsychotic medications on QTc and delirium in paediatric cardiac patients with ICU delirium.

Children with prolonged hospital admissions for CHD often develop delirium. Antipsychotic medications (APMs) have been used to treat delirium but are known to prolong the QTc duration. There is concern for prolongation of the QTc interval in cardiac patients who may be more vulnerable to electrocardiogram (ECG) changes and may have postoperative QTc prolongation already. The goal of this study was to determine the effect of APM on QTc duration in postoperative paediatric cardiac patients and determine the effect of quetiapine and risperidone in treating delirium and QTc prolongation. Retrospective study, July 1, 2017-May 31, 2022. Tertiary children's hospital. Included were patients admitted to the paediatric cardiac ICU at Children's Healthcare of Atlanta. None. ECGs, delirium scores, and drug information were collected. Delirium was defined as Cornell Assessment of Pediatric Delirium (CAPD) score >9. Mixed effect models were performed to evaluate the effect of surgery on QTc change and the effect of antipsychotics on QTc and CAPD changes. There were 139 children, 55% male and 67% surgical admissions. Median age was 5.9 months. Mean QTc increased after cardiac surgery by 18 ms (p = 0.014, 95% CI 3.65-32.4). There was no significant change in QTc after antipsychotic administration (p = 0.064). The mean CAPD score decreased (12.5-7.2; p < 0.001). Quetiapine had the most improvement in delirium, and risperidone had the least improvement (77.8%, n = 14; 37.8%, n = 34, respectively; p = 0.002). The QTc interval did not have a statistically significant change after the administration of antipsychotics, while there was improvement in the CAPD score. APMs may be administered safely without significant prolongation of the QTc and are an effective treatment for delirium.

Effects of long-term antipsychotic medication on brain instability in first-episode schizophrenia patients: a resting-state fMRI study

Early initiation of antipsychotic treatment plays a crucial role in the management of first-episode schizophrenia (FES) patients, significantly improving their prognosis. However, limited attention has been given to the long-term effects of antipsychotic drug therapy on FES patients. In this research, we examined the changes in abnormal brain regions among FES patients undergoing long-term treatment using a dynamic perspective. A total of 98 participants were included in the data analysis, comprising 48 FES patients, 50 healthy controls, 22 patients completed a follow-up period of more than 6 months with qualified data. We processed resting-state fMRI data to calculate coefficient of variation of fractional amplitude of low-frequency fluctuations (CVfALFF), which reflects the brain regional activity stability. Data analysis was performed at baseline and after long-term treatment. We observed that compared with HCs, patients at baseline showed an elevated CVfALFF in the supramarginal gyrus (SMG), parahippocampal gyrus (PHG), caudate, orbital part of inferior frontal gyrus (IOG), insula, and inferior frontal gyrus (IFG). After long-term treatment, the instability in SMG, PHG, caudate, IOG, insula and inferior IFG have ameliorated. Additionally, there was a positive correlation between the decrease in dfALFF in the SMG and the reduction in the SANS total score following long-term treatment. In conclusion, FES patients exhibit unstable regional activity in widespread brain regions at baseline, which can be ameliorated with long-term treatment. Moreover, the extent of amelioration in SMG instability is associated with the amelioration of negative symptoms.

Identifying and managing treatment resistance early with the integration of a clozapine clinic within an early intervention for psychosis service.

Despite being the most effective antipsychotic medication for treatment-resistant psychosis, clozapine is often under-utilized with long delays to initiation. This study aimed to determine whether the integration of a clozapine clinic within an early intervention for psychosis service resulted in a change in the rate and time to initiation of clozapine, the number of trials of different antipsychotic medications prior to clozapine, community initiation and discontinuation rates. A clozapine clinic was established in the Early Psychosis Prevention and Intervention Centre in Melbourne. This was a pre- and post-evaluation study design. The 'clozapine clinic' cohort included those who commenced on clozapine from 01 January 2016 to 30 June 2018. Prior to the clozapine clinic, 24 young people commenced clozapine over the 30-month period compared to 36 in the clozapine clinic cohort (RR = 1.30, 95% CI: 0.75-2.28, p = .32). In the pre-clozapine clinic cohort, 4.6% of all those with a first episode of psychosis were commenced on clozapine compared to 6% in the clozapine clinic cohort. Prior to the clozapine clinic, the median time to the commencement of clozapine was 72 weeks (IQR: 38, 87), compared to 53.5 weeks (IQR: 38, 81.5) in the clozapine clinic (Z = -0.86, p = .393). The mean number of different antipsychotic medications prior to commencing clozapine remained stable at 3.2 (SD ± 1.1) in both cohorts (t = -0.20, p = .841). There was a lower rate of discontinuation in the clozapine clinic (43.5% vs. 14.7%, HR = 0.30, 95% CI: 0.09-0.98, p = .046). While this study was underpowered and there are limitations to the naturalistic study design, the findings lend support to the integration of a clozapine clinic within early intervention for psychosis services.

Cognitive functions following initiation of antipsychotic medication in adolescents and adults at clinical high risk for psychosis: a naturalistic sub group analysis using the MATRICS consensus cognitive battery

BackgroundThe effects of antipsychotic (AP) medications on cognitive functions in individuals at clinical high-risk (CHR) of psychosis are poorly understood. This study compared the effects of AP treatment on cognitive improvement in CHR adolescents and adults.MethodsA total of 327 CHR participants, with an age range of 13 to 45 years, who underwent baseline neuropsychological assessments and a 1-year clinical follow-up were included. Participants with CHR were categorized into four groups based on their age: adolescents (aged < 18) and adults (aged ≥ 18), as well as their antipsychotic medication status (AP+ or AP−). Therefore, the four groups were defined as Adolescent-AP−, Adolescent-AP+, Adult-AP−, and Adult-AP+.ResultsDuring the follow-up, 231 CHR patients received AP treatment, 94 converted to psychosis, and 161 completed the 1-year follow-up. The Adolescent-AP+ group had more positive symptoms, lower general functions, and cognitive impairments than the Adolescent-AP− group at baseline, but no significant differences were observed among adults. The Adolescent-AP+ group showed a significant increase in the risk of conversion to psychosis (p < 0.001) compared to the Adolescent-AP− group. The Adult-AP+ group showed a decreasing trend in the risk of conversion (p = 0.088) compared to the Adult-AP− group. The Adolescent-AP− group had greater improvement in general functions (p < 0.001), neuropsychological assessment battery mazes (p = 0.025), and brief visuospatial memory test-revised (p = 0.020), as well as a greater decrease in positive symptoms (p < 0.001) at follow-up compared to the Adolescent-AP+ group. No significant differences were observed among adults.ConclusionsEarly use of AP was not associated with a positive effect on cognitive function in CHR adolescents. Instead, the absence of AP treatment was associated with better cognitive recovery, suggesting that AP exposure might not be the preferred choice for cognitive recovery in CHR adolescents, but may be more reasonable for use in adults.

Effects of antidepressant and antipsychotic medication on peripheral brain-derived neurotrophic factor concentration: Systematic review and meta-analysis

Brain-derived neurotrophic factor (BDNF) is an important regulatory protein in the pathophysiology of psychiatric disorders. Several studies have reported the relationship between peripheral BDNF concentrations and the use of psychoactive drugs. However, the results remain controversial. This study aimed to evaluate the effects of psychoactive drugs on BDNF concentrations and to explore the association between changes in BDNF concentrations and improvements in clinical scores. A systematic review and meta-analysis were conducted. Six electronic databases, including PubMed, Scopus, Medline, Web of Science, Google Scholar and Science Direct, were searched. Changes in BDNF concentrations were compared before and after psychoactive treatment, using the standardized mean difference (SMD) and 95 % confidence interval (95 % CI). Twenty-three studies were included. A significant increase in serum BDNF concentrations was observed after treatment with antipsychotics (SMD=0.43; 95 %CI: 0.26, 0.60) and antidepressants (SMD=0.49; 95 %CI: 0.23, 0.74). However, the plasma BDNF concentration was not affected by antidepressant and antipsychotic medication. Although an improvement in clinical scores was observed after treatment, no significant association was observed between changes in BDNF concentrations and the changes in the Positive and Negative Syndrome Scale (PANSS) and the Hamilton Depression Rating Scale (HAM-D) scores. In conclusion, antidepressants and antipsychotics increase serum BDNF concentrations.

Differential effects of cannabis constituents on schizophrenia-related psychosis: a rationale for incorporating cannabidiol into a schizophrenia therapeutic regimen.

Schizophrenia is a serious mental health disorder that confers one of the highest mortality rates of all psychiatric illnesses. Although the disorder's psychotic symptoms are treatable with conventional antipsychotics, they remain incurable. Moreover, medication adherence is poor, and individuals with schizophrenia choose to self-medicate with illicit substances, including cannabis. It is well-established that the delta-9-tetrahydrocannabinol (delta-9-THC) component of cannabis elicits psychotomimetic effects at high doses; worsens schizophrenia-related psychosis; commonly develops into cannabis use disorder in individuals with schizophrenia; and increases the risk of earlier-onset schizophrenia symptoms in those harboring genetic susceptibility. However, individuals with schizophrenia commonly use cannabis and cannabis derivatives such as cannabidiol (CBD). These products seem to alleviate psychotic symptoms and relieve adverse side effects of antipsychotic medications. Therefore, one notion that has gained traction is the potential utility of cannabis-derived cannabidiol (CBD) as adjunct treatment to reduce schizophrenia-associated psychosis and other symptoms. Currently, preclinical and clinical data remain inconclusive. The present review distinguishes the mechanisms underlying schizophrenia-associated vs. cannabis-induced psychosis; reviews the evidence for delta-9-THC-mediated exacerbation vs. CBD-mediated amelioration of schizophrenia-associated psychosis; and describes potential approaches for incorporating CBD into schizophrenia therapeutic regimen in a safe and efficacious manner.

Synergistic action of vitamin D3 and A on motor activity regulation in mice model of extrapyramidal syndrome: Correlational insights into astrocyte regulation, cytokine modulation, and dopaminergic activity

BackgroundExtrapyramidal syndromes (EPS) represent neurological side effects of antipsychotic medications, characterized by motor disturbances. While previous studies have indicated the neuroprotective effects of vitamin D and A against EPS, the underlying mechanisms of this protection remain unclear. MethodsTwenty-four adult mice were categorized into four groups: positive and negative control groups, one receiving a dopamine antagonist, and the other receiving both a dopamine antagonist and vitamins D and A. Sections of the corticobasal loop, specifically the motor cortex (M1) and basal nuclei (CPu), were prepared for Immunohistochemistry (IHC) and stained with Glial Fibrillary Acidic Protein (GFAP) to visualize reactive astrocytes. ELISA assays for TNF-α, IL-6, IL-4, IL-13, and dopamine levels were performed on homogenized brain sections. ResultsThe EPS group exhibited a significant increase in TNF-α and IL-6 levels in M1 and CPu. Treatment with dopamine agonists and vitamin D&A resulted in significant reductions in IL-6 levels. Only the Vitamin D&A group showed a significant decline in TNF-α. The EPS group recorded significant decreases in IL-4 and IL-13, with IL-13 significantly elevated in the dopamine agonist and Vitamin D&A groups. IL-4 was notably increased in the Vitamin D&A groups. Dopamine concentration significantly declined in the EPS group, with improvements observed in the groups treated with dopamine agonists, and vitamin D&A. Reactive astrocytes were significantly expressed in the M1 and CPu of the EPS group but poorly expressed in other groups. ConclusionsEPS is linked to astrocyte activation, an upsurge in pro-inflammatory cytokines, a decline in anti-inflammatory cytokines, and dopamine in the corticobasal loop. Administration of vitamin D3 and A was found to suppres pro-inflammatory cytokines and repress anti-inflammatory cytokines associated with astrocyte activation.

Assessing regional intracortical myelination in schizophrenia spectrum and bipolar disorders using the optimized T1w/T2w-ratio.

Dysmyelination could be part of the pathophysiology of schizophrenia spectrum (SCZ) and bipolar disorders (BPD), yet few studies have examined myelination of the cerebral cortex. The ratio of T1- and T2-weighted magnetic resonance images (MRI) correlates with intracortical myelin. We investigated the T1w/T2w-ratio and its age trajectories in patients and healthy controls (CTR) and explored associations with antipsychotic medication use and psychotic symptoms. Patients with SCZ (n = 64; mean age = 30.4 years, s.d. = 9.8), BPD (n = 91; mean age 31.0 years, s.d. = 10.2), and CTR (n = 155; mean age = 31.9 years, s.d. = 9.1) who participated in the TOP study (NORMENT, University of Oslo, Norway) were clinically assessed and scanned using a General Electric 3 T MRI system. T1w/T2w-ratio images were computed using an optimized pipeline with intensity normalization and field inhomogeneity correction. Vertex-wise regression models were used to compare groups and examine group × age interactions. In regions showing significant differences, we explored associations with antipsychotic medication use and psychotic symptoms. No main effect of diagnosis was found. However, age slopes of the T1w/T2w-ratio differed significantly between SCZ and CTR, predominantly in frontal and temporal lobe regions: Lower T1w/T2w-ratio values with higher age were found in CTR, but not in SCZ. Follow-up analyses revealed a more positive age slope in patients who were using antipsychotics and patients using higher chlorpromazine-equivalent doses. While we found no evidence of reduced intracortical myelin in SCZ or BPD relative to CTR, different regional age trajectories in SCZ may suggest a promyelinating effect of antipsychotic medication.

The cognitive effects of stopping and starting antipsychotics on changes in cognitive functioning

Objectives The current study uses longitudinal data from the National Alzheimer’s Coordinating Center (NACC) to assess the effects of antipsychotic medication use on changes in cognitive functioning among adults in the United States. Methods Linear mixed models were conducted that included study visits, days between visits, sex, age, education, and medical history (i.e. diabetes, seizures, traumatic brain injury, stroke, and Parkinson’s disease). The Neuropsychiatric Inventory Questionnaire (NPI-Q) was used to create variables assessing changes in psychotic symptoms, manic symptoms, and agitation/disinhibition. Results The results indicated that starting an antipsychotic medication was associated with a greater decline in semantic fluency (Fruit and Vegetable Naming), processing speed (Digit Symbol and Trail Making Test, Part A), and cognitive flexibility (Trail Making Test, Part B). Conversely, stopping an antipsychotic medication was protective against declines in the same cognitive skills. The effect of antipsychotic medications on cognitive functioning did not appear to differ by reported changes in psychiatric symptoms after adjusting for false discovery. Conclusion The results suggest that prescribers should consider discontinuance of an antipsychotic if the patient is reporting cognitive problems and their symptoms are manageable off the medications. The findings hope to spark future research into the effects of antipsychotic use on biomarkers of progressive dementias (e.g. Alzheimer’s disease).

Assessment of Monitoring and Management Practices of Antipsychotic-Induced Hyperprolactinemia at a Medical City in Riyadh, Saudi Arabia: A Retrospective Cohort Study.

Hyperprolactinemia is a commonly underestimated adverse effect of antipsychotic medications. There are still no consensus guidelines for the optimal monitoring and treatment strategies. The aim of the study was to assess the monitoring and treatment practices of antipsychotic- induced hyperprolactinemia, in addition to the prevalence and risk factors associated with it. A retrospective cohort observational study was conducted among patients attending the psychiatric clinics at an academic tertiary hospital in Riyadh, Saudi Arabia, from May 2020 until May 2021, by reviewing each patient's medical record for up to five years. Among the 662 patients, 35 patients (5.3%) and 242 patients (36.6%) had their serum prolactin levels monitored (at baseline and at follow-up, respectively). The prevalence of hyperprolactinemia was observed in 212 patients (32%). Only 76 patients (36%) were symptomatic. Female gender, younger age, and bipolar disorder had a significantly higher risk of developing hyperprolactinemia. 60% of the confirmed cases received treatment, of which 76 (60%) were adherent to treatment guidelines. The most common treatment strategies implemented were dose reduction (42.5%) and aripiprazole augmentation (29.1%). It is imperative to conduct a baseline check of prolactin levels before commencing any antipsychotic therapy. Similarly, routine prolactin level monitoring is recommended regardless of symptoms in patients treated with antipsychotics with a possible prolactin-raising effect. Adherence to evidence-based treatment guidelines can improve patient quality of life and therapeutic compliance.

Reviewing the Awareness of Mental Health Staff of the Possible Visual Side Effects of Antipsychotic Medications

Objective: A staff awareness project was undertaken in order to assess the awareness of clinical staff working in a UK community psychiatry practice of the visual side effects of antipsychotic medications. Study Design: A staff questionnaire was provided to assess baseline knowledge of the visual side effects of antipsychotic medication (the First Questionnaire). Subsequently, a short information sheet was provided regarding the visual side effects of antipsychotic medications. A Second Questionnaire for clinical staff was provided to assess reflections on knowledge gained. Results: 100% of respondents to the Second Questionnaire found the information sheet informative in refreshing or providing knowledge. 100% of the respondents to the Second Questionnaire also found the information sheet had improved their knowledge of the impact of antipsychotic on vision, and how it can be managed. 100% of respondents stated the information provided would influence their care of patients on antipsychotics and how they might approach care. Conclusion: Antipsychotic medications can cause ocular complications and visual side effects. Staff and patient education regarding these potential side effects can help promote patient safety.

Group-Based Trajectory Modeling to Identify Patterns of Antipsychotic-Associated Weight Gain Among Children and Adolescents.

Antipsychotic-associated weight gain (AAWG) is a common adverse effect of second-generation antipsychotic (SGA) medications among children and adolescents. This study applied group-based trajectory modeling to identify latent trajectories of AAWG among children and adolescents and associated risk factors. This was a retrospective analysis of the IQVIA Ambulatory EMR-US database from 2016 to 2021. The cohort consisted of patients aged 6 to 19 years who were SGA naive and received at least 90 days of continuous SGA prescriptions. Group-based trajectory modeling was used to identify latent trajectories of AAWG development during a 24-month period since SGA initiation, and multinomial logistic regression analysis was conducted to examine the risk factors associated with the identified AAWG trajectories. A total of 16,262 patients were included. Group-based trajectory modeling identified the following 4 distinctive AAWG trajectories: persistent severe weight gain (4.2%), persistent moderate weight gain (20.1%), minor weight change (69.6%), and gradual weight loss (6.1%). Compared with the minor weight change group, younger age (12-17 vs 5-11: odds ratio [OR], 0.634; 95% confidence interval [CI], 0.521-0.771), lower baseline body mass index z -score (OR, 0.216; 95% CI, 0.198-0.236), and receiving olanzapine as the initial SGA (olanzapine vs aripiprazole: OR, 1.686; 95% CI, 1.673-1.699) were more likely to follow severe weight gain trajectories. The area under the receiver operating characteristic curves for comparing severe weight gain versus minor weight change groups and moderate weight vs minor weight change groups in the multinomial regression model were 0.91 and 0.8, respectively. A quarter of pediatric SGA recipients experienced persistent weight gain during the SGA treatment. The risk of having persistent AAWG can be predicted using patient characteristics collected before SGA initiation and the initial SGA agent.

Alterations in the hub structure of whole-brain functional networks in patients with drug-naïve schizophrenia: Insights from electroencephalography-based research.

This study aimed to identify atypical hubs in the whole-brain networks of patients with schizophrenia (SZ) and examine the effects of antipsychotic medications, using electroencephalography (EEG) data. We estimated the functional connectivity across all electrodes by applying the phase lag index to the EEG signals of 21 drug-naïve patients with SZ and 31 age-matched healthy controls. Betweenness centrality (BC), a measure of hub status, was calculated for each electrode and frequency band. Data from 14 patients were re-evaluated after initiating treatment with antipsychotic medications. BC values decreased significantly at the Fz site in the beta band, decreased significantly at Pz in the gamma band, and increased significantly at O1 in the gamma band among patients with SZ. These changes persisted after antipsychotic treatment and were unrelated to clinical symptoms. The abnormal hub topology we observed, especially in the high-frequency band, may reflect the pathophysiology of SZ, and this study highlights the utility of BC analysis of EEG data for detecting alterations in the whole-brain networks of patients with SZ.

Effects of Clozapine on Cortical Inhibition

Abstract Background Preclinical and clinical investigations have revealed deficits in cortical inhibition in individuals with schizophrenia. Transcranial magnetic stimulation, a commonly used noninvasive measurement technique, is used for assessing these deficits. Limited research has been conducted on the effects of antipsychotic medications on cortical inhibition. This study aimed to evaluate the effects of clozapine on cortical inhibition with transcranial magnetic stimulation longitudinally and compare it with unaffected controls. Methods Ten patients who started clozapine were assessed at baseline, with 8 reassessed after 4 months. Eight age- and sex-matched unaffected controls were included. Psychopathology, neurocognitive performance, formal thought disorder, and disability were assessed, and the cortical excitability parameters (resting motor threshold, cortical silent period, short-interval intracortical inhibition, intracortical facilitation, and short-latency afferent inhibition [SAI]) were measured at baseline and four months after clozapine treatment. Results Resting motor threshold, ICF, and SAI were significantly different between patients and controls at baseline, whereas resting motor threshold, SAI, and ICF became similar to controls after clozapine with only ICF having a trend for significance. Clozapine prolonged cortical silent period significantly in the patients. Conclusions This is the first study to investigate the effect of clozapine on SAI, a potential cholinergic biomarker, and the first follow-up study to investigate the relationship between the effects of clozapine on cortical inhibition and cognition. Clozapine seems to cause an increase in cortical inhibition through GABAergic and possibly cholinergic mechanisms. However, additional follow-up studies with larger sample sizes are required to reach more robust conclusions.

Atypical antipsychotic use does not impact weight gain for individuals with extreme anorexia nervosa: a retrospective case–control study

BackgroundThere are no U.S. Food and Drug Administration (FDA)-approved medications for the treatment of anorexia nervosa (AN). Various medication classes have been evaluated for benefits in this population, including antipsychotics. Studies focused on use of antipsychotics for assistance with weight restoration in AN produced conflicting results. While current evidence does not suggest that antipsychotic medications can be generally recommended for persons with AN, some individuals might benefit from an antipsychotic medication for anxiety, mood, and the cognitive distortions that accompany the illness. It is well-established that atypical antipsychotics can cause weight gain when taken by other psychiatric populations. This published data can understandably limit the willingness of persons with AN to trial these medications. Given the conflicting results of studies examining antipsychotic-related weight gain in AN, it is currently hypothesized that individuals with extreme anorexia nervosa, restricting type, do not experience the weight gain seen in other psychiatric populations utilizing atypical antipsychotics.MethodsTwo hundred seventy-six individuals with extreme AN were enrolled in this retrospective, case–control study between April 1, 2016 and June 30, 2022 utilizing study-specific inclusion and exclusion criteria. Clinical and demographic data, including use of atypical antipsychotics and weights, were retrospectively obtained from chart review. Variables were assessed for normality using univariate statistics. Continuous variables were described using means (M) and standard deviations (SD) or medians and interquartile ranges (IQR) based on normality. Differences in weight gain between cohorts was ascertained via independent samples t-test. P values of < 0.05 were considered statistically significant, and all analyses were completed using SAS Enterprise Guide software version 7.1 (SAS Institute, Cary, NC) and R version 4.3.1 (R Core Team, 2023).ResultsUse of antipsychotics in this population of individuals with extreme AN did not impact the rate of weight gain (M: 1.7 kg/week, SD: 0.9 and 0.8, for cases and controls respectively).ConclusionsWeight gain is often cited by individuals with AN as a feared side effect of antipsychotic medications. In this study, there was no difference in weight trends for individuals taking atypical antipsychotic medications during the refeeding process compared with individuals who were not.

Negative Impacts of Psychiatric Medications on Oral Health: A Literature Review.

Evidence reveals that people with mental illnesses have a greater risk of experiencing oral diseases such as dry mouth and dental caries and have greater oral treatment needs. This is related to multifactorial causes such as factors related to the condition itself, symptoms, side effects of polypharmacy, anda lack of accessibility to dental services. This article aims to provide a summary of the reported prevalence of the most common mental illnesses in Saudi Arabia (SA), such as schizophrenia, obsessive-compulsive disorder (OCD), bipolar disorders, and dementia. The article further aims to review the negative impacts of anti-psychotic medications on oral health and the role of dentists toward people with mental illnesses. PubMed, Scopus, and Google Scholar were searched using the following keywords: special care dentistry, schizophrenia, OCD, bipolar disorder, and dementia. The main inclusion criteria were any studies describing "dental management of patients with mental illnesses" and "dental management of patients treated with anti-psychotic medications."Thematic analysis was used to summarize the findings of the included studies into main headings. Forty-eight articles/studies discussed dentistry, people with mental illnesses, and/or the negative impacts of psychotic medication on oral health. All studies were published between 1991 and 2021. In SA, the number of people with mental illnesses is increasing. Therefore, it is crucial for the dental team to understand the negative impacts of anti-psychotic medications on oral health, such as dry mouthand the increased risk of dental caries. This necessitates the need for regular dental visits and patient education on how they can mitigate the side effects of anti-psychotic medications on oral and general health.

Antipsychotic Medications and Mortality in Children and Young Adults

Dose-related effects of antipsychotic medications may increase mortality in children and young adults. To compare mortality for patients aged 5 to 24 years beginning treatment with antipsychotic vs control psychiatric medications. This was a US national retrospective cohort study of Medicaid patients with no severe somatic illness or schizophrenia or related psychoses who initiated study medication treatment. Study data were analyzed from November 2022 to September 2023. Current use of second-generation antipsychotic agents in daily doses of less than or equal to 100-mg chlorpromazine equivalents or greater than 100-mg chlorpromazine equivalents vs that for control medications (α agonists, atomoxetine, antidepressants, and mood stabilizers). Total mortality, classified by underlying cause of death. Rate differences (RDs) and hazard ratios (HRs) adjusted for potential confounders with propensity score-based overlap weights. The 2 067 507 patients (mean [SD] age, 13.1 [5.3] years; 1 060 194 male [51.3%]) beginning study medication treatment filled 21 749 825 prescriptions during follow-up with 5 415 054 for antipsychotic doses of 100 mg or less, 2 813 796 for doses greater than 100 mg, and 13 520 975 for control medications. Mortality was not associated with antipsychotic doses of 100 mg or less (RD, 3.3; 95% CI, -5.1 to 11.7 per 100 000 person-years; HR, 1.08; 95% CI, 0.89-1.32) but was associated with doses greater than 100 mg (RD, 22.4; 95% CI, 6.6-38.2; HR, 1.37; 95% CI, 1.11-1.70). For higher doses, antipsychotic treatment was significantly associated with overdose deaths (RD, 8.3; 95% CI, 0-16.6; HR, 1.57; 95% CI, 1.02-2.42) and other unintentional injury deaths (RD, 12.3; 95% CI, 2.4-22.2; HR, 1.57; 95% CI, 1.12-2.22) but was not associated with nonoverdose suicide deaths or cardiovascular/metabolic deaths. Mortality for children aged 5 to 17 years was not significantly associated with either antipsychotic dose, whereas young adults aged 18 to 24 years had increased risk for doses greater than 100 mg (RD, 127.5; 95% CI, 44.8-210.2; HR, 1.68; 95% CI, 1.23-2.29). In this cohort study of more than 2 million children and young adults without severe somatic disease or diagnosed psychosis, antipsychotic treatment in doses of 100 mg or less of chlorpromazine equivalents or in children aged 5 to 17 years was not associated with increased risk of death. For doses greater than 100 mg, young adults aged 18 to 24 years had significantly increased risk of death, with 127.5 additional deaths per 100 000 person-years.

Brain metabolite levels in remitted psychotic depression with consideration of effects of antipsychotic medication

BackgroundThe neurobiology of psychotic depression is not well understood and can be confounded by antipsychotics. Magnetic resonance spectroscopy (MRS) is an ideal tool to measure brain metabolites non-invasively. We cross-sectionally assessed brain metabolites in patients with remitted psychotic depression and controls. We also longitudinally assessed the effects of olanzapine versus placebo on brain metabolites.MethodsFollowing remission, patients with psychotic depression were randomized to continue sertraline + olanzapine (n = 15) or switched to sertraline + placebo (n = 18), at which point they completed an MRS scan. Patients completed a second scan either 36 weeks later, relapse, or discontinuation. Where water-scaled metabolite levels were obtained and a Point-RESolved Spectroscopy sequence was utilized, choline, myo-inositol, glutamate + glutamine (Glx), N-acetylaspartate, and creatine were measured in the left dorsolateral prefrontal cortex (L-DLPFC) and dorsal anterior cingulate cortex (dACC). An ANCOVA was used to compare metabolites between patients (n = 40) and controls (n = 46). A linear mixed-model was used to compare olanzapine versus placebo groups.ResultsCross-sectionally, patients (compared to controls) had higher myo-inositol (standardized mean difference [SMD] = 0.84; 95%CI = 0.25–1.44; p = 0.005) in the dACC but not different Glx, choline, N-acetylaspartate, and creatine. Longitudinally, patients randomized to placebo (compared to olanzapine) showed a significantly greater change with a reduction of creatine (SMD = 1.51; 95%CI = 0.71–2.31; p = 0.0002) in the dACC but not glutamate + glutamine, choline, myo-inositol, and N-acetylaspartate.ConclusionsPatients with remitted psychotic depression have higher myo-inositol than controls. Olanzapine may maintain creatine levels. Future studies are needed to further disentangle the mechanisms of action of olanzapine.

A systematic review of clozapine-associated inflammation and related monitoring.

Clozapine is an effective antipsychotic medication used for treatment-resistant schizophrenia. However, it is underutilized due to rigorous hematologic monitoring requirements and many adverse drug reactions. Publications have highlighted the occurrence of inflammatory reactions, some life-threatening, particularly during the early stages of clozapine treatment. Although guidelines have suggested monitoring for inflammatory processes during clozapine initiation, screening in clinical practice is not universal. This systematic review aimed to investigate the relationship between clozapine and inflammation and assess the importance of monitoring for inflammatory reactions. A comprehensive literature search yielded 6,915 unique publication records after removal of duplicates. After a rigorous screening process, 75 publications were included in the review, which focused on three main aspects: i) the impact of clozapine on inflammatory markers, ii) monitoring cardiac and other organ function during clozapine-associated inflammatory processes, and iii) monitoring non-specific signs and symptoms of inflammation. Elevated levels of C-reactive protein (CRP) and several proinflammatory cytokines have been observed in association with clozapine treatment. However, the practicality of measuring specific markers in clinical practice remains uncertain. Current evidence supports monitoring CRP levels during the first 4 to 8 weeks of treatment, especially to facilitate myocarditis screening. Further research is needed to establish clinically-relevant CRP thresholds for intervention. The implementation of monitoring protocols during the early phase of clozapine treatment may mitigate adverse reactions and allow for continued use of clozapine. Future studies should also explore the association between clozapine-associated inflammation and pneumonia, as well as investigate the impact of inflammation on clozapine metabolism to predict the need for dose adjustment. These endeavors may facilitate the development and implementation of evidence-based guidelines for the monitoring of clozapine-associated inflammation.