Atypical Antipsychotics Research Articles

Evaluation of the Impact of the Addition of Atypical Antipsychotics to Continuous Infusion Propofol Therapy.

Purpose: The administration of sedatives to critically ill patients is a common practice in intensive care units (ICU) and has been associated with negative outcomes. To mitigate this, atypical antipsychotics are utilized as adjunctive therapy. This study aims to review and quantify overall effectiveness of the atypical antipsychotics quetiapine, risperidone, and olanzapine on reduction in the amount of continuous infusion propofol utilized in the ICU. Methods: This was an observational study that took place from February 27, 2021 to December 31, 2022. The primary outcome of this study was the percentage change in average propofol infusion rate (mcg/kg/min) from baseline to the greater than 24 to 48 hours period after atypical antipsychotic initiation. Secondary outcomes included ICU length of stay, duration of mechanical ventilation, QTc interval monitoring, and continuation of the antipsychotic without a valid indication. Descriptive statistics were utilized for the statistical analysis. Results: A total of 47 patients were included in the study. The average baseline propofol rate was 31 mcg/kg/min, which reduced 8.6% to 28.35 mcg/kg/min over the 0 to 24 hours period, was reduced by 19.4% compared to baseline to a rate of 25 mcg/kg/min during the greater than 24 to 48 hours period, and finally a percent reduction of 54.2% seen during the greater than 48 to 72 hours period to a rate of 14 mcg/kg/min. Conclusions: Patients who received an adjunctive antipsychotic saw resulting propofol rate reductions of 8.6% at 24 hours, 19.4% at 48 hours, and 54.2% at 72 hours. However, research on this topic should not end here, as further investigation with higher-level study design is needed to determine the true impact of these agents for this indication.

Antipsychotic Use and Psychiatric Hospitalization in First-Episode Non-affective Psychosis and Cannabis Use Disorder: A Swedish Nationwide Cohort Study.

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

Antipsychotic-associated neuroleptic malignant syndrome (NMS) in schizophrenia patients: a narrative review

Neuroleptic malignant syndrome (NMS) is a neurological disorder with an high mortality rate among schizophrenia patients who receive antipsychotics as the primary long-term therapy. Appropriate selection of antipsychotics in NMS should be carefully considered to obtain maximal effectiveness with minimal side effects. An evaluation of the safety profile of the antipsychotics is important due to their different treatment patterns and rapid onset of symptoms. This review article aimed to compare the safety profile of antipsychotics in relation to NMS in schizophrenia patients. It was a narrative review using multiple search engines included PubMed, Google Scholar, and Springer to collect publications from 2007 to 2023. Of the total 14 articles reviewed, 7 articles explained the role of antipsychotics in NMS, 5 articles about the onset of NMS, and 7 articles about mortality rate. The incidence of NMS was less then 0.11%, typical antipsychotics were the most common cause of NMS, especially high-potency antipsychotics compared with atypical antipsychotics. Meanwhile, the onset of NMS consistently occured within 30 d of antipsychotic initiation with a symptom duration of 1 to 30 d, and the mortality rate was also higher for typical antipsychotics. In conclusion, the choice of antipsychotics must be carefully considered and its use must be monitored due to the rapid onset and high mortality. The use of antipsychotics is not free from the risk of NMS. The heterogeneous symptoms of NMS require earlier detection to reduce disease progression.

Pediatric Extrapolation Approach for U.S. Food and Drug Administration Approval of Brexpiprazole in Patients Aged 13 to 17 Years with Schizophrenia.

A pharmacokinetic (PK) bridging approach was successfully employed to support the dosing regimen and approval of brexpiprazole in pediatric patients aged 13-17 years with schizophrenia. Brexpiprazole was approved in 2015 for the treatment of schizophrenia and the adjunctive treatment of major depressive disorder in adults based on efficacy and safety data from clinical trials. On January 13, 2020, the US Food and Drug Administration issued a general advice letter to sponsors highlighting the acceptance of efficacy extrapolation of certain atypical antipsychotics from adult patients to pediatric patients considering the similarity in disease and exposure-response relationships. Brexpiprazole is the first atypical antipsychotic approved in pediatrics using this approach. The PK data available from pediatric patients aged 13-17 years have shown high variability due to the limited number of PK evaluable subjects, which limits a robust estimation of differences between adult and pediatric patients. The PK model-based approach was thus utilized to evaluate the appropriateness of the dosing regimen by comparing PK exposures in pediatric patients aged 13-17 years with exposures achieved in adults at the approved doses. In addition to exposure matching, safety data from a long-term open-label clinical study in pediatric patients informed the safety profile in pediatric patients. This report illustrates the potential of leveraging previously collected efficacy, safety, and PK data in adult patients to make a regulatory decision in pediatric patients for the indication of schizophrenia.

Effects of Prenatal Exposure to Second-Generation Antipsychotics on Development and Behavior Among Preschool-Aged Children: Preliminary Results From the National Pregnancy Registry for Psychiatric Medications.

Effects of Prenatal Exposure to Second-Generation Antipsychotics on Development and Behavior Among Preschool-Aged Children: Preliminary Results From the National Pregnancy Registry for Psychiatric Medications.

Drug-refractory irritability and related factors in autistic children

Objectives Autistic children frequently exhibit irritability, which can manifest as aggression, self-injurious behaviour, and severe tantrums, leading to significant impairments. Two atypical antipsychotics have been licensed by the Food and Drug Administration for the treatment of irritability in autistic children, although a significant percentage of these children do not respond to this treatment. This study aimed to determine the frequency of drug refractory irritability (DRI) and identify the risk factors in a large clinical sample of autistic children. Methods The medical records of 1279 children aged 2–18 years diagnosed with autism and undergoing clinical follow-up were retrospectively analysed. Socioeconomic and clinical characteristics, co-occurring psychiatric disorders and physical conditions were recorded. Results 55% of the sample used antipsychotics to treat irritability, and 8.2% met the DRI criteria. Older age, severe support requirement for autism, language impairment, anxiety disorders, sleep difficulties, gastrointestinal system, and dental problems were found to significantly increase the risk of DRI. Conclusion Our findings indicate that a significant proportion of the clinical sample of autistic children had DRI. The physical, psychiatric, and environmental risk factors identified in our study also highlight heterogeneity in the etiology of DRI. Further research on DRI is needed to develop treatment and prevention strategies.

Serum S100B protein and white matter changes in schizophrenia before and after medication

Schizophrenia patients have abnormalities in white matter (WM) integrity in brain regions. S100B has been shown to be a marker protein for glial cells. The atypical antipsychotics have neuroprotective effects on the brain. It is not clear whether antipsychotics can induce S100B changes and improve symptoms by protecting oligodendrocytes. To investigate WM and S100B changes and associations and determine the effect of quetiapine on WM and S100B in schizophrenia patients, we determined serum S100B levels with solid phase immunochromatography and fractional anisotropy（FA）values of 36 patients and 40 healthy controls. Patients exhibited significantly higher serum concentrations of S100B and decreased FA values in left postcentral，right superior frontal，right thalamus, and left inferior occipital gyrus, while higher in right temporal cortex WM compared with healthy controls. Following treatment with quetiapine, patients had decreased S100B and higher FA values in right cerebellum，right superior frontal，right thalamus, and left parietal cortex，and decreased FA values in right temporal cortex WM compared with pre-treatment values. Furthermore, S100B were negatively correlated with PANSS positive scores and positively correlated with FA values in the left postcentral cortex. In addition，the percentage change in FA values in the right temporal cortex was positively correlated with the percentage change in the S100B, percentage reduction in PANSS scores, and percentage reduction in PANSS-positive scores. Our findings demonstrated abnormalities in S100B and WM microstructure in patients with schizophrenia. These abnormalities may be partly reversed by quetiapine treatment.

The Association Between Oral Bone Mineral Density–Reducing Medications and the Risk of 2-Year Implant-Related Complications Following Total Knee Arthroplasty

BackgroundCertain medications interfere with the bone remodeling process and may potentially increase the risk of complications after total knee arthroplasty (TKA). As patients undergoing TKA may be taking these bone mineral density (BMD)–reducing medications, it is unclear as to whether and which medications impact TKA outcomes. Therefore, the purpose of this study was to observe the impact of various BMD-reducing medications on 2-year implant-related complications following TKA. MethodsA retrospective analysis of patients undergoing primary TKA was conducted using a national administrative claims database. Patients were identified if they were taking any known BMD-reducing medication and were compared to control patients. To control for confounders associated with taking multiple agents, multivariable logistic regression analyses were conducted for each 2-year outcome (all-cause revision, loosening-indicated revision, and periprosthetic fracture–-indicated revision), with the output recorded as odds ratios (ORs). ResultsIn our study, 502,927 of 1,276,209 TKA patients (39.4%) were taking at least one BMD-reducing medication perioperatively. On multivariable analysis, medications associated with a higher likelihood of 2-year all-cause revision included first- and second-generation antipsychotics (SGAs) (OR: 1.42 and 1.26, respectively), selective serotonin reuptake inhibitors (SSRIs) (OR: 1.14), glucocorticoids (1.13), and proton pump inhibitors (PPIs) (OR: 1.23) (P < .05 for all). Medications associated with a higher likelihood of 2-year periprosthetic fracture included SGAs (OR: 1.51), SSRIs (OR: 1.27), aromatase inhibitors (OR: 1.29), and PPIs (OR: 1.42) (P < .05 for all). ConclusionsOf the drug classes observed, the utilization of perioperative PPIs, SSRIs, glucocorticoids, first-generation antipsychotics, and SGAs was associated with the highest odds of all-cause revision. Our findings suggest a relationship between these medications and BMD-related complications; however, further studies should seek to determine the causality of these relationships.

Oral Health Status and Factors Related to Oral Health in Patients with Schizophrenia: A Matched Case-Control Observational Study.

Background: Schizophrenia (SCZ) patients have disproportionately poor oral health outcomes owing to a multidimensional set of factors, such as pathophysiology of the disease, drug-related adverse effects and lower utilization rate of dental healthcare services. The aim of the present observational study was to compare the indicators of dental and periodontal health in patients with SCZ to those of nonaffected healthy controls; furthermore, the influence of various anamnestic factors and lifestyle habits on oral health status were also assessed. Methods: A total of 50 SCZ patients-in remission-receiving treatment at the Department of Psychiatry, University of Szeged, were compared with 50 age- and gender-matched healthy controls attending the Faculty of Dentistry, University of Szeged. Participants' dental (decayed, missing and filled surfaces [DMF-S] and decayed, missing and filled teeth [DMF-T]) and periodontal (plaque index [%], bleeding on probing [BOP%], pocket depth [PD] and attachment loss [AL]) status was measured according to the World Health Organization (WHO) criteria. Results: In total, 74.0%, 80.0% and 78.0% of SCZ patients received second-generation antipsychotics, benzodiazepines and mood stabilizers, respectively. Patients with SCZ had significantly higher DMFs (81.30 ± 40.16 vs. 61.64 ± 40.56; p = 0.010), D (8.18 ± 7.73 vs. 4.18 ± 4.22; p < 0.001) and DMF-T (18.20 ± 8.36 vs. 14.42 ± 8.21; p = 0.024) scores but significantly lower F (1.84 ± 0.29 vs. 4.62 ± 3.98; p < 0.001) scores compared to the controls; male subjects had significantly lower DMFs (74.52 ± 39.72 vs. 90.67 ± 39.1; p = 0.020) and DMF-T (16.52 ± 8.12 vs. 20.52 ± 8.32; p = 0.031) scores. Additionally, SCZ patients had significantly higher plaque indices (56.96 ± 23.19 vs. 27.44 ± 17.53; p < 0.001), BOP% (58.96 ± 22.89 vs. 23.56 ± 17.53; p < 0.001), PD (2.84 ± 0.67 vs. 2.19 ± 0.49; p = 0.024) and AL (3.39 ± 1.72 vs. 2.49 ± 0.76; p < 0.001) values compared to controls. Smoking > 10 cigarettes/day was associated with worse dental and periodontal indices, while consuming ≥ 4 units/week of alcohol was associated with worse periodontal indices, respectively (p < 0.05 in all cases). In contrast, coffee consumption rates and vitamin supplementation status had no significant effect on oral health status indicators. Conclusions: Our study highlights the overall poor oral health status of individuals affected by SCZ and the need for targeted preventive interventions.

A Possible Role of Akkermansia muciniphila in the Treatment of Olanzapine-Induced Weight Gain.

Second-generation antipsychotics are mainly used in both acute and long-term treatment of major psychiatric disorders. Although better tolerated than first-generation antipsychotic drugs, they can frequently induce weight gain and metabolic disorders, of these, olanzapine is one of the drugs more likely to induce these side effects. There is consistent evidence of the role of gut microbiota in modulating the gut-brain axis with complex crosstalk with the host involving satiety signaling pathways, food intake behavior, and weight and metabolic regulation. Second-generation antipsychotics induce important gut microbiota modification thus contributing together with the central and peripheral receptors blockade mechanism to weight gain induction and metabolic impairment. These drugs can alter the composition of gut microbiota and induce dysbiosis, often reducing the concentration of Akkermansia muciniphila, a bacterium that is also decreased in patients with diabetes, obesity, metabolic syndrome, or chronic inflammatory diseases. Probiotic administration can be a safe and well-tolerated approach to modulate microbiotaandoffer an integrative strategy in psychiatric patients suffering antipsychotic side effects. Multiple strain probiotics and Akkermansia muciniphila alone have been administered both in mice models and in clinical populations demonstrating efficacy on antipsychotic-induced metabolic impairment and showing a contribution in reducing induced weight gain.Akkermansia muciniphila can improve several parameters altered by olanzapine administration, such as weight gain, insulin resistance, hyperglycemia, liver function, systemic inflammation, and gut barrier function. Although we do not have jet trials in the psychiatric population, this probiotic may be a complementary approach to treating olanzapine-induced weight gain and metabolic side effects.

Safety of Atypical Antipsychotics in a Child and Adolescent Inpatient Setting: A Naturalistic Study.

This study's objective was to investigate the adverse effects of atypical antipsychotics (AAPs) on the metabolic, hematological, and endocrinological systems in the inpatient environment for children and adolescents with diverse psychiatric disorders. A retrospective assessment of 208 children's and adolescents' medical records was conducted. All patients were on AAP monotherapy. At baseline and after treatment, measurements of body weight, height, body mass index (BMI), BMI z-score, fasting blood glucose (FBG), total cholesterol, low-density lipoprotein cholesterol, triglycerides, high-density lipoprotein cholesterol, complete blood count, liver functions, thyroid functions, and prolactin levels were made. Scores from the Children's Global Assessment Scale (CGAS) and the Health of the Nation Outcome Scales for Children and Adolescents (HoNOSCA) were preserved. The overall patient population had a mean age of 14.50 ± 2.32 years, 139 girls, and 69 boys. Of the patients, 63 (30.29%) were on risperidone (RIS), 69(33.17%) were on aripiprazole (ARI), 32 (15.39%) were on quetiapine (QUE), 42 (20.19%) were on olanzapine (OLA), and 2 (0.96%) were on clozapine (CLO). In the OLA group, the BMI and BMI z-score increased more than in the RIS, QUE, and ARI groups (P = .030, P = .014, and P = .001, respectively) (P = .001). The mean difference in CGAS and HoNOSCA between the start of antipsychotic medication and hospital discharge was statistically different for all four groups (P = .001 for all). The mean FBG levels in the OLA group increased statistically significantly (P = .013, P = .021) in contrast to the RIS group. In addition, a statistically significant difference in triglycerides across the groups was found (P = .003). According to the findings of our study, children and adolescents appear to be at a significant risk for psychotropic-induced PRL increase, weight gain, metabolic, and hematological consequences. To prevent serious health problems, a meticulous risk-benefit assessment for AAPs treatment should be done between clinicians and patients and their families.

Revealing receptor-ligand interactions of atypical antipsychotic drugs and screening anti-schizophrenia ingredients in Magnolia officinalis based on 5-HTR2A-SNAP-Tag/CMC and DRD2-SNAP-Tag/CMC models

Schizophrenia is a serious mental illness with unknown etiology, and shows increasing incidence and high lifetime prevalence rate. The main receptors related to the disease are DRD2 and 5-HTR2A. Thus, a comprehensive understanding of the interaction mode between antipsychotic drugs with relevant receptors is very important for developing more effective drugs. 5-HTR2A-SNAP-Tag/CMC and DRD2-SNAP-Tag/CMC models constructed in this work provided a new method for studying the interaction between atypical antipsychotics and the two receptors. The results of comparative experiments showed that the new models not only met the high selectivity and specificity of the screening requirements but were also more stable and long-lasting than the traditional CMC model. Binding assays showed that the effects of three atypical antipsychotics (including clozapine, olanzapine, and quetiapine) on 5-HTR2A were stronger than their effects on DRD2. Additionally, two potentially active components, magnolol and honokiol, were screened in Magnolia officinalis methanol extract using the 5-HTR2A-SNAP-Tag/CMCHPLC-MS system. Nonlinear chromatographic analysis and molecular docking were conducted to study the interactions between screened compounds and the two receptors. The binding constants (KA) of magnolol and honokiol with 5-HTR2A were 17,854 ± 1,117 M–1 and 38,858 ± 4,964 M–1, respectively, and KA values with DRD2 were 4,872 ± 1,618 M–1 and 20,692 ± 10,267 M–1, respectively. We concluded that the established models are reliable for studying receptor-ligand interactions and screening antagonists of schizophrenia.

Neuroleptic malignant syndrome: a neuro-psychiatric emergency

Characterised by fever, altered mental status, muscle rigidity and autonomic dysfunction, neuroleptic malignant syndrome is a life-threatening idiosyncratic reaction to antipsychotic medication; around one in 10 cases end in cardiac arrest. The primary cause of neuroleptic malignant syndrome is dopamine receptor blockade, and the standard causative agent is an antipsychotic drug. While first-generation (typical) neuroleptics such as haloperidol, fluphenazine, trifluoperazine and prochlorperazine pose the greatest risk, neuroleptic malignant syndrome has been reported with second-generation (atypical) neuroleptics such as risperidone, clozapine, olanzapine and ziprasidone. Paramedic awareness of neuroleptic malignant syndrome as a neuropsychiatric emergency is paramount to reducing serious morbidity and even death in patients presenting with symptoms and a history of antipsychotic use. Treatment is individualised and based on clinical presentation, with supportive medical therapy being a key intervention.

Analysis of Medicare Patients Treated with Pimavanserin versus Other Atypical Antipsychotics: A Cost-Offset Model Evaluating Skilled Nursing Facility Stays and Long-Term Care Admissions in Parkinson's Disease Psychosis.

Patients with Parkinson's disease psychosis (PDP) treated with pimavanserin (PIM) versus other atypical antipsychotics (AAPs) including quetiapine (QUE) may have health-care cost savings due to fewer skilled nursing facility-stays (SNF-stays) and long-term care admissions (LTCA). A decision analytic model was developed using the 2019 Medicare Patient Driven Payment Model (PDPM) to estimate SNF-stays and LTCA associated per-patient- per-year (PPPY) facility and rehabilitation costs among patients that initiated PIM vs QUE or vs other-AAPs (i.e, quetiapine, risperidone, olanzapine, aripiprazole). Model inputs were derived for: (i) annual SNF-stay and LTCA rates from an analysis of Medicare beneficiaries with PDP, and (ii) annual mean rehabilitation and resident care-stay costs from PDPM case-mix adjusted value-based payment rates for 5 rehabilitation components (ie, physical-therapy, occupational-therapy, nursing, speech-language pathology, non-therapy ancillary), and an additional variable-per-diem for room/board services. PPPY costs were estimated from (i) SNF-stay and (ii) LTCA rates multiplied by annual mean costs of stay in 2022 USD. Probabilistic sensitivity analysis (PSA) was performed using 1000 Monte Carlo simulations. Overall SNF-stay rates of 20.2%, 31.4%, and 31.7%, and LTCA rates of 23.2%, 33.8%, 34.6% were observed for PIM, QUE, and other-AAPs, respectively. Based on annual mean costs, PPPY SNF-stay rehabilitation and resident related costs for PIM ($41,808) vs QUE ($65,172) or vs other-AAPs ($65,664), resulted in $23,364 and $23,856 PPPY cost savings, respectively. Similarly, PPPY LTCA rehabilitation and resident related costs for PIM ($47,957) vs QUE ($70,091) or vs other-AAPs ($71,566) resulted in $22,134 and $23,609 PPPY cost-savings for PIM, respectively. PSA suggested PIM would provide cost-savings vs QUE or other-AAPs in >99% of iterations. In this analysis, PIM demonstrated nearly 36% and 32% lower PPPY SNF-stays and LTCA costs, respectively, vs QUE or other-AAPs. Research examining additional cost-offsets (i.e., fewer falls/fractures) associated with SNF-stay or LTCA may be needed.

Cognitive and Motor Function Effects of Antipsychotics in Traumatic Brain Injury: A Systematic Review of Pre-Clinical Studies.

Traumatic brain injury (TBI) survivors often suffer from agitated behaviors and will most likely receive pharmacological treatments. Choosing an optimal and safe treatment that will not interfere with neurological recovery remains controversial. By interfering with dopaminergic circuits, antipsychotics may impede processes important to cognitive recovery. Despite their frequent use, there have been no large randomized controlled studies of antipsychotics for the management of agitated behaviors during the acute TBI recovery period. We conducted a systematic review and meta-analysis of pre-clinical studies evaluating the effects of antipsychotics post-TBI on both cognitive and motor recovery. MEDLINE and Embase databases were searched up to August 2, 2023. Pre-clinical studies evaluating the effects of antipsychotics on cognitive and motor functions post-TBI were considered. Risk of bias was evaluated with the Systematic Review Centre for Laboratory Animal Experimentation (SYRCLE) tool. We identified 15 studies including a total of 1188 rodents, mostly conducted in male Sprague-Dawley rats using cortical impact injury. The analysis revealed no consistent effect of haloperidol on motor functions, but risperidone was associated with a significant impairment in motor function on day 5 post-injury (7.05 sec; 95% confidence interval [CI]: 1.47, 12.62; I2 = 92%). Other atypical antipsychotics did not result in impaired motor function. When evaluating cognitive function, haloperidol- (23.00 sec; 95% CI: 17.42-28.59; I2 = 7%) and risperidone-treated rats (24.27 sec; 95% CI: 16.18-32.36; I2 = 0%) were consistently impaired when compared to controls. In studies evaluating atypical antipsychotics, no impairments were observed. Clinicians should avoid the regular use of haloperidol and risperidone, and future human studies should be conducted with atypical antipsychotics.

Associations between actigraphy estimates of sleep and circadian rhythmicity and psychotropic medications in bipolar disorders: An exploratory study

IntroductionDisturbances in sleep and circadian rhythmicity (CR) are frequent in individuals with bipolar disorders (BD). Very few studies explored the associations between psychotropic medications and these disturbances in euthymic BD. Therefore, we aimed at exploring the associations between several classes of medications (lithium, sedative/non-sedative Atypical Antipsychotics (AAP), anticonvulsants, antidepressants, benzodiazepines) and sleep disturbances and CR dimensions in a sample of euthymic individuals with BD. MethodsWe included euthymic adults with BD type 1 or 2 assessed with 21 days of actimetry. We used a Principal Component Analysis (PCA) of sleep and CR estimates to generate dimensions to be studied in association with the current use of psychotropic medications, with adjustments for potential confounding factors. ResultsWe included individuals with BD-1 (n = 116) or BD-2 (n = 37). The PCA led to four dimensions of sleep and CR estimates. Benzodiazepines were associated with better sleep quality (pcorrected = 0.032). Aripiprazole was associated with less robust CR (pcorrected = 0.016), but with earlier peak of activity patterns (pcorrected = 0.020). Sedative AAPs were associated with better sleep quality, which was no longer significant after correction. We found no association between lithium or anticonvulsants and CR. LimitationsThe cross-sectional design and the possible non-representativeness of the sample were limitations of our study. ConclusionsIn euthymic individuals with BD, benzodiazepines may have a positive effect on sleep quality, while aripiprazole may have mixed effects on CR (less robust but with earlier peak of activity patterns). No association with lithium or anticonvulsants observed. Further studies are warranted to replicate and extend these results.

Treat bipolar depression with atypical antipsychotics and mood stabilisers; new therapies require further study

Treat bipolar depression with atypical antipsychotics and mood stabilisers; new therapies require further study

Association between CNS-active drugs and risk of Alzheimer's and age-related neurodegenerative diseases.

As neuropsychiatric conditions can increase the risk of age-related neurodegenerative diseases (NDDs), the impact of CNS-active drugs on the risk of developing Alzheimer's Disease (AD), non-AD dementia, Multiple Sclerosis (MS), Parkinson's Disease (PD) and Amyotrophic Lateral Sclerosis (ALS) was investigated. A retrospective cohort analysis of a medical claims dataset over a 10 year span was conducted in patients aged 60 years or older. Participants were propensity score matched for comorbidity severity and demographic parameters. Relative risk (RR) ratios and 95% confidence intervals (CI) were determined for age-related NDDs. Cumulative hazard ratios and treatment duration were determined to assess the association between CNS-active drugs and NDDs at different ages and treatment duration intervals. In 309,128 patients who met inclusion criteria, exposure to CNS-active drugs was associated with a decreased risk of AD (0.86% vs 1.73%, RR: 0.50; 95% CI: 0.47-0.53; p <.0001) and all NDDs (3.13% vs 5.76%, RR: 0.54; 95% CI: 0.53-0.56; p <.0001). Analysis of impact of drug class on risk of AD indicated that antidepressant, sedative, anticonvulsant, and stimulant medications were associated with significantly reduced risk of AD whereas atypical antipsychotics were associated with increased AD risk. The greatest risk reduction for AD and NDDs occurred in patients aged 70 years or older with a protective effect only in patients with long-term therapy (>3 years). Furthermore, responders to these therapeutics were characterized by diagnosed obesity and higher prescriptions of anti-inflammatory drugs and menopausal hormonal therapy, compared to patients with a diagnosis of AD (non-responders). Addition of a second CNS-active drug was associated with greater reduction in AD risk compared to monotherapy, with the combination of a Z-drug and an SNRI associated with greatest AD risk reduction. Collectively, these findings indicate that CNS-active drugs were associated with reduced risk of developing AD and other age-related NDDs. The exception was atypical antipsychotics, which increased risk. Potential use of combination therapy with atypical antipsychotics could mitigate the risk conferred by these drugs. Evidence from these analyses advance precision prevention strategies to reduce the risk of age-related NDDs in persons with neuropsychiatric disorders.

An analysis of multiple comparisons is conducted to account for correlations among various investigated variables across four categories of antipsychotics

Background: First-generation antipsychotics are dopamine receptor antagonists, while second-generation atypical antipsychotics are serotonin-dopamine antagonists. Aim: The study aims to compare the effectiveness of current anti-psychotic drugs in treating schizophrenia, focusing on their correlation with responsiveness rates in positive, negative, and psychopathological symptoms. Methods: The study focuses on schizophrenia-spectrum disorders in adults and elderly psychiatric patients at the Princess Aisha Bint Al Hussein Medical Centre. The study will assess the initial severity of patients and evaluate the therapeutic effectiveness of four categorical-based oral and LA-APDs: older oral drugs, older oral and depot drugs, newer oral drugs, and newer oral and depot drugs. The reduction percentages in each component will be monitored, and a Chi Square test will be performed to analyze other variables. Pearson or spearman correlations will be used to explore correlation values. Results: Upon aggregating the various symptom categories into a unified score using the Positive and Negative Scoring Scale (PANSS), this study revealed that 63.7% of patients exhibited a positive response, whereas 36.7% of patients did not respond favourably. This equated to 110 out of 303 patients responding, compared to 193 patients who did not respond. The Pearson and Spearman correlations exhibited a statistically significant positive relationship, with values of +0.581±0.038 and +0.574±0.040, respectively (χ 2=131.885, p-value=0.000). Conclusion: Our study concluded that Psychopathological symptom therapy and patient adherence improved significantly. The efficiency of pleasant symptoms decreased significantly, whereas negative symptoms increased slightly.

Trajectories and Predictors for the Development of Clinically Significant Weight Gain in Children and Adolescents Prescribed Second-Generation Antipsychotics.

Background: As many as 60% of pediatric patients taking second-generation antipsychotics (SGA) experience weight gain (antipsychotic-induced weight gain). However, the subgroup that experienced substantial weight increase was poorly understood. This study aimed to identify the development and predictors of clinically significant weight gain (CSWG) among pediatric SGA recipients. Methods: A retrospective analysis of the 2016 to 2021 IQVIA Ambulatory EMR-US database was conducted. The study cohort comprised SGA-naive patients ages 5 to 19, continuously prescribed SGA for ≥90 days. CSWG was defined as a weight gain in BMI z-score >0.5. The development of CSWG was described using the group-based trajectory model approach, and multinomial logistic regression analysis was conducted to examine the risk factors associated with the CSWG trajectories. Results: Of the 16,262 SGA recipients who met the inclusion criteria, 4 distinctive CSWG trajectories were identified: (1) Rapid (14.6%), (2) Gradual (12.6%), (3) Transit (7%), and (4) no CSWG (65.8%). Factors associated with a higher likelihood of having rapid or gradual CSWG versus nonsignificant weight gain were being younger (OR [95% CI] = 12-17 vs. 5-11, Rapid, 0.727 [0.655-0.806]; Gradual, 0.776 [0.668-0.903]), male (Rapid, 1.131 [1.021-1.253]), non-Hispanic White (Black vs. White: Rapid, 0.833 [0.709-0.98]), with lower baseline BMI z-score (Rapid, 0.376 [0.361-0.392]; Gradual, 0.449 [0.424-0.476]), and receiving olanzapine as the initial SGA (Rapid, 1.38 [1.093-1.74]). The Area under the Receiver operating characteristic (ROC) Curve for the comparison of rapid and gradual CSWG with no CSWG trajectory were 0.83 and 0.80, respectively. Conclusions: SGA recipients experienced four distinctive CSWG trajectories (Rapid, Gradual, Transient, and No CSWG). The risk of CSWG could be predicted using patient characteristics at the SGA initiation. This insight highlights the importance of personalized monitoring and timely intervention strategies for at-risk individuals who experienced persistent CSWG in real practice.