Antipsychotic Research Articles

Hepatotoxicity of antipsychotics: an exploratory pharmacoepidemiologic and pharmacodynamic study integrating FAERS data and in vitro receptor-binding affinities.

Antipsychotic psychopharmacotherapy is associated with the risk of drug-induced liver injury (DILI). However, understanding specific risk factors remains challenging due to limited data. This study investigates the relationship between receptor binding affinities and occupancies of antipsychotics and their associated hepatotoxic risks. A disproportionality analysis with calculation of the Reporting Odds Ratio (ROR) and the Information Component (IC) was conducted using data fromthe FDA Adverse Event Reporting System (FAERS) to identify signals related to the Standardised MedDRA Query "drug-related hepatic disorders", which served as a proxy for drug-induced hepatotoxicity. This was followed by a pharmacoepidemiologic-pharmacodynamic approach to investigate the relationship between the ROR and substance-related receptor binding affinities and occupancy, which was estimated based on in vitro receptor-binding profiles. Significant signals were identified for several antipsychotics, including chlorpromazine, loxapine, olanzapine, and quetiapine, with chlorpromazine and loxapine showing the highest RORs for DILI. Gender-specific analysis revealed a higher frequency of signals in female patients. Statistically significant negative correlations were identified between the ROR for drug-related hepatic disorders and the affinity for serotonin receptor 5-HT1A (r (17) = -0.68, p = 0.0012), while a positive correlation was observed for cholinergic receptors (r (17) = 0.46, p = 0.048). No significant correlations were found related to other receptors or drug properties. Our findings suggest that the serotonin and probably the cholinergic system may play a role in the development of DILI related to antipsychotic medications. The identification of antipsychotics with a higher association with DILI, such as chlorpromazine, underscores the need for careful monitoring in clinical practice. However, our findings need further longitudinal studies to confirm causality. A better understanding of the associations may inform clinical decision-making, particularly in patients with an increased susceptibility to liver damage.

Changes in Antipsychotic Medication Adherence Among Medicaid Beneficiaries with Schizophrenia During COVID-19.

To identify patterns of medication adherence during the pandemic and factors associated with these patterns among Medicaid-enrolled individuals with schizophrenia who had highly adherent medication use prior to the COVID-19 pandemic. We used Medicaid claims from Philadelphia to identify individuals with schizophrenia ≥ 18years of age, their demographic characteristics, and health service use. We used group trajectory models to identify adherence trends, and ANOVA to examine associations between adherence groups and demographic characteristics and service use. The sample included 1,622 individuals. A 4-group trajectory model best fit our data. Seventy percent of individuals averaged about 92% adherence throughout the study period; 10% experienced a pronounced decline when the pandemic started (pandemic non-adherers); 11% experienced a sharp decline mid-pandemic (late non-adherers); and 9% experienced a sharp decline at the beginning of the pandemic and returned to higher adherence after a year (disrupted adherers). Adherers were least likely to be diagnosed with a substance use disorder, and had more telehealth visits, mental health outpatient visits, and fewer emergency department visits on average. Late non-adherers were more likely than adherers to have substance use disorders and physical health conditions. Pandemic non-adherers had more co-occurring psychiatric disorders than adherers and had the lowest use of case management. Three in ten previously adherent individuals with schizophrenia became less adherent to antipsychotic medications, either at the onset or later in the pandemic. Our findings point to telehealth and case management as critical strategies for treatment engagement, especially during public health crises, and well as the need to address co-occurring conditions.

Treatment of Parkinson's Disease Psychosis-A Systematic Review and Multi-Methods Approach.

Parkinson's disease psychosis (PDP) is a prevalent non-motor symptom associated with Parkinson's disease. The treatment options for PDP are limited, and its pharmacological management remains ambiguous. This study aimed to evaluate the existing evidence in relation to clinical practice. This multi-methods study consisted of a systematic review of reviews, adhering to the PRISMA guidelines. The review was registered with PROSPERO. Following data extraction and assessment using the AMSTAR 2 tool, a narrative synthesis was performed. In the second phase of the study, a questionnaire was developed, validated, piloted, and distributed to the heads of specialized PD clinics in Germany and Austria. The search resulted in the inclusion of eleven reviews. The quality of eight of these reviews was rated as high (n = 7) or moderate (n = 1). The reviews indicated that clozapine and pimavanserin demonstrated the highest efficacy and tolerability. Other antipsychotic medications either failed to alleviate PDP symptoms or resulted in distinct motor complications. The survey findings also favored clozapine for its efficacy in managing PDP and improving quality of life, although quetiapine was regarded as effective and pimavanserin was not available. Clinicians reported initiating antipsychotic treatment at various stages of PDP, with a tendency to reduce the dosage or discontinue D2 agonists or anticholinergics. The reviewed literature and the survey results consistently favored clozapine for its efficacy and tolerability in treating PDP. It may be considered the first-line treatment, with pimavanserin as an alternative option.

Peer-led recovery groups for people with psychosis in South Africa (PRIZE): Results of a randomized controlled feasibility trial.

The aims of this feasibility trial were to assess the acceptability and feasibility of peer-led recovery groups for people with psychosis in a low-resource South African setting, to assess the feasibility of trial methods, and to determine key parameters in preparation for a definitive trial. The design was an individually randomised feasibility trial comparing recovery groups in addition to treatment as usual (TAU) with TAU alone. Ninety-two isiXhosa-speaking people with psychosis and forty-seven linked caregivers were recruited from primary care clinics and randomly allocated to trial arms in a 1:1 allocation ratio. TAU comprised anti-psychotic medication delivered in primary care. The intervention arm comprised six recovery groups including service users and caregivers. Two-hour recovery group sessions were delivered weekly in a 2-month auxiliary social worker (ASW)-led phase, then a 3-month peer-led phase. To explore acceptability and feasibility, a mixed methods process evaluation included 25 in-depth interviews and 2 focus group discussions at 5months with service users, caregivers and implementers, and quantitative data collection including attendance and facilitator competence. To explore potential effectiveness, quantitative outcome data (functioning, relapse, unmet needs, personal recovery, stigma, health service use, medication adherence and caregiver burden) were collected at baseline, 2months and 5months post randomisation. Trial registration: PACTR202202482587686. Qualitative interviews revealed that recovery groups were broadly acceptable with most participants finding groups to be an enjoyable opportunity for social interaction, and joint problem-solving. Peer facilitation was a positive experience; however a minority of participants did not value expertise by lived experience to the same degree as expertise of professional facilitators. Attendance was moderate in the ASW-led phase (participants attended 59% sessions on average) and decreased in the peer-led phase (41% on average). Participants desired a greater focus on productive activities and financial security. Recovery groups appeared to positively impact on relapse. Relapse occurred in 1 (2.2%) of 46 participants in the recovery group arm compared to 8 (17.4%) of 46 participants in the control arm (risk difference -0.15 [95% CI: -0.26; -0.05]). Recovery groups also impacted on the number of days in the last month totally unable to work (mean 1.4days recovery groups vs 7.7days control; adjusted mean difference -6.3 [95%CI: -12.2; -0.3]). There were no effects on other outcomes. Peer-led recovery groups for people with psychosis in South Africa are potentially acceptable, feasible and effective. A larger trial, incorporating amendments such as increased support for peer facilitators, is needed to demonstrate intervention effectiveness definitively.

Intermittent theta burst stimulation in adolescents and young adults with depressive disorders: protocol of a randomized, sham-controlled study with a sequential Bayesian design for adaptive trials.

Intermittent theta burst stimulation (iTBS), a variant of repetitive transcranial magnetic stimulation (rTMS), is an established treatment for adults with major depressive disorder (MDD). Due to its favorable safety profile, iTBS is also a promising early intervention in the transition phase from adolescence to early adulthood, but thishas not been systematically investigated to date. Thus, the EARLY-BURST trial investigates the efficacy and safety of iTBS over the left dorsolateral prefrontal cortex (lDLPFC) in treatment-seeking young patients (age 16-26years) with depressive disorders (i.e. major depressive disorder, persistent depressive disorder, bipolar depression), allowing for relevant co-morbidities. Participants have not received antidepressant or antipsychotic medication during the last 12months except for short-term (< 2weeks) on-demand medication. The trial will employ a novel sequential Bayesian, randomized, double-blind, parallel-group, sham-controlled design. Up to 90 patients at two clinical sites (Munich, Augsburg) will be randomized 1:1 to the treatment groups, with sequential analyses starting after 26 patients in each group completed the treatment. The primary outcome will be the difference in depression severity at week 6 (post-treatment visit) between active iTBS and sham iTBS, assessed with the Montgomery-Åsberg Depression Rating Scale (MADRS). The trial is planned to be expanded towards a three-arm leapfrog design, contingent on securing additional funding. Thus, in addition to potentially providing evidence of iTBS's efficacy in adolescents and young adults with depressive disorders, the EARLY-BURST trial aims at setting the stage for subsequent platform trials in this dynamic research field, where novel adaptive study designs are required to meet the need for rapidly testing promising new vs established rTMS protocols.Trial registration: DRKS00033313.

Metabolic Side Effects from Antipsychotic Treatment with Clozapine Linked to Aryl Hydrocarbon Receptor (AhR) Activation.

Metabolic syndrome (MetS) is the most common adverse drug reaction from psychiatric pharmacotherapy. Neuroreceptor blockade by the antipsychotic drug clozapine induces MetS in about 30% of patients. Similar to insulin resistance, clozapine impedes Akt kinase activation, leading to intracellular glucose and glutathione depletion. Additional cystine shortage triggers tryptophan degradation to kynurenine, which is a well-known AhR ligand. Ligand-bound AhR downregulates the intracellular iron pool, thereby increasing the risk of mitochondrial dysfunction. Scavenging iron stabilizes the transcription factor HIF-1, which shifts the metabolism toward transient glycolysis. Furthermore, the AhR inhibits AMPK activation, leading to obesity and liver steatosis. Increasing glucose uptake by AMPK activation prevents dyslipidemia and liver damage and, therefore, reduces the risk of MetS. In line with the in vitro results, feeding experiments with rats revealed a disturbed glucose-/lipid-/iron-metabolism from clozapine treatment with hyperglycemia and hepatic iron deposits in female rats and steatosis and anemia in male animals. Decreased energy expenditure from clozapine treatment seems to be the cause of the fast weight gain in the first weeks of treatment. In patients, this weight gain due to neuroleptic treatment correlates with an improvement in psychotic syndromes and can even be used to anticipate the therapeutic effect of the treatment.

Comparative Effectiveness of Antipsychotics in Patients With Schizophrenia Spectrum Disorder

Antipsychotics are the cornerstone of maintenance treatment in schizophrenia spectrum disorders, but it is unclear which agents should be prioritized by prescribers. To investigate the clinical effectiveness of antipsychotics, including recent market entries, in comparison with oral olanzapine in relapse and treatment failure prevention among individuals with schizophrenia spectrum disorder. This comparative effectiveness research study with a within-individual analysis included data from Swedish health care registers of inpatient and specialized outpatient care, sickness absence, and disability pensions among all individuals aged 16 to 65 years who were diagnosed with schizophrenia spectrum disorder from January 1, 2006, to December 31, 2021, including an incident cohort and a prevalent cohort. Specific antipsychotics. The risks for psychosis relapse hospitalization and treatment failure (psychiatric hospitalization, death, or change in an antipsychotic medication) were adjusted for the temporal order of treatments, time since cohort entry, and concomitant drugs. Comparisons of all antipsychotics with oral olanzapine, the most commonly used antipsychotic, were investigated. Among the full cohort of 131 476 individuals, the mean (SD) age of the study cohort was 45.7 (16.2) years (70 054 men [53.3%]). During a median follow-up of 12.0 years [IQR, 5.2-16.0 years], 48.5% of patients (N = 63 730) experienced relapse and 71.1% (N = 93 464) underwent treatment failure at least once. Compared with oral olanzapine, paliperidone 3-month long-acting injectable (LAI) was associated with the lowest adjusted hazard ratio (AHR) in the prevention of relapses (AHR, 0.66; 95% CI, 0.51-0.86), followed by aripiprazole LAI (AHR, 0.77 [95% CI, 0.70-0.84]), olanzapine LAI (AHR, 0.79 [95% CI, 0.73-0.86]), and clozapine (AHR, 0.82 [95% CI, 0.79-0.86]). Quetiapine was associated with the highest risk of relapse (AHR, 1.44 [95% CI, 1.38-1.51]). For prevention of treatment failure, paliperidone 3-month LAI was associated with the lowest AHR (AHR, 0.36 [95% CI, 0.31-0.42]), followed by aripiprazole LAI (AHR, 0.60 [95% CI, 0.57-0.63]), olanzapine LAI (AHR, 0.67 [95% CI, 0.63-0.72]), and paliperidone 1-month LAI (AHR, 0.71 [95% CI, 0.68-0.74]). This comparative effectiveness research study demonstrated large differences in the risk of relapse and treatment failure among specific antipsychotic treatments. The findings contradict the widely held conception that all antipsychotics are equally effective in relapse prevention.

Chronic treatment with the antipsychotic lurasidone modulates the neuroinflammatory changes associated with the vulnerability to chronic mild stress exposure in female rats

Stress exposure is a key risk factor for the developmentof depressive-like conditions. However, despite the higher incidence of Major Depressive Disorder in the female population, classical stress-based experimental paradigms have primarily focused on males. In the present study, we used the well-established chronic mild stress (CMS) paradigm to investigate the development of anhedonia, a cardinal symptom of affective disorders, in the female animals and we also studied the potential effect of the antipsychotic drug lurasidone in normalizing the alterations brought about by stress exposure. We found that three weeks of CMS exposure produced a significant reduction of sucrose intake in 50% of the animals (vulnerable, CMS-V), whereas the others were resilient (CMS-R). The development of an anhedonic phenotype in CMS-V was associated with a significant elevation of different immune markers, such as Complement C3 and C4, and inflammatory cytokines, including INFß and Il1ß in dorsal and ventral hippocampus. Interestingly, sub-chronic treatment with the antipsychotic drug lurasidone was able to revert the anhedonic phenotype while normalizing most of the molecular alterations found in rats vulnerable to CMS exposure. This study extends the ability of lurasidone to normalize the anhedonic phenotype in CMS rats also to females. Moreover, we provide novel evidence on lurasidone’s potential effectiveness in treating mental disorders characterized by immune-inflammatory dysfunction.

Effects of synbiotic supplementation on the components of metabolic syndrome in patients with schizophrenia: a randomized, double-blind, placebo-controlled trial

BackgroundAntipsychotic drugs may have adverse effects on the components of metabolic syndrome. Previous studies have shown that changes in the intestinal microbiome are associated with metabolic disturbances in patients with schizophrenia. The objective of this study was to determine the effects of synbiotics on the components of metabolic syndrome as primary outcomes in patients with schizophrenia. Secondary outcomes were HbA1c, insulin resistance, LDL-c, and anthropometric measurements.MethodsIn this double-blind, placebo-controlled trial, seventy patients with schizophrenia receiving antipsychotic drugs who had at least two criteria of metabolic syndrome were randomly divided into two groups to receive either two capsules of a synbiotic supplement or a placebo daily for 8 weeks. Anthropometric indices and biochemical parameters were measured at baseline and after the intervention.ResultsFifty-five patients completed the study. The synbiotic supplement significantly decreased waist circumference and HbA1C compared to placebo (-2.66 ± 4.20 vs. 3.03 ± 4.50 and − 0.26 ± 0.54 vs. 0.20 ± 0.75, respectively). Although BMI did not change significantly in the synbiotic + antipsychotic group, it increased in the placebo + antipsychotic group (-0.37 ± 1.00 vs. 0.61 ± 1.09 P < 0.5). LDL-c and triglyceride (TG) levels decreased significantly in the synbiotic + antipsychotic group, but the change was not significantly different from that of the placebo + antipsychotic group. FBS, HDL-c, systolic and diastolic blood pressure, insulin resistance, and total cholesterol were not significantly different between the two groups after intervention.ConclusionSynbiotic supplement may decrease waist circumference, HbA1c, LDL and TG and prevent BMI increase in patients receiving antipsychotic drugs.Trial registrationIranian Registry of Clinical Trials (IRCT Number: IRCT20090901002394N45), Date: 26-12-2019.

A Literature-Based Study of Tardive Dyskinesia- From Pathogenesis to Treatment

: Tardive dyskinesia (TD) is induced by antipsychotic drugs that have dopamineantagonising properties. It frequently causes physical and mental anguish in individuals, lowering their quality of life. Recent research on the aetiology and pathogenesis of TD indicates that genetic predisposition, treatment options, age, sex, and lifestyle factors are among the key risk factors contributing to the development of TD. Various genetic polymorphisms along with severe oxidative stress and other diseased conditions help to precipitate TD while on antipsychotic medications or other dopamine receptor blockers. Individuals diagnosed with schizophrenia are at a higher likelihood of developing TD. The current piece of literature aims to review the probable underlying mechanisms of TD, explore its pathophysiology, address the diagnostic challenges, and present the available treatment options. This comprehensive analysis draws from a range of published peerreviewed publications, presenting the information in a clear and accessible manner.

The risk of diabetes and HbA1c deterioration during antipsychotic drug treatment: A Danish two-cohort study among patients with first-episode schizophrenia.

Antipsychotics increase the risk of developing diabetes, but clinical trials are not generalizable with short follow-up, while observational studies often lack important information, particularly hemoglobin A1c (HbA1c). We followed two Danish cohorts with schizophrenia. First, using Danish nationwide registers, we identified all individuals diagnosed with first-episode schizophrenia (FES) between 1999 and 2019 (n = 31,856). Exposure was a redeemed prescription for an antipsychotic, and the outcome was diabetes, defined via hospital-based diagnosis and redeemed prescriptions for glucose-lowering drugs. Adjusted Cox regression calculated hazard rate ratios (HRR). Second, using data from the Central Denmark Region, we identified all individuals diagnosed with FES from October 2016 to September 2022 (n = 2671). Using a within-subject design, we analyzed the change in HbA1c during the 2 years after initiation of specific antipsychotics compared to the 2 years before. In the nationwide cohort, 2543 (8.0%) individuals developed diabetes (incidence rate = 9.39 [95% CI = 9.03-9.76] per 1000 person-years). Antipsychotics, compared to periods without, were associated with an increased risk of developing diabetes (HRR = 2.04, 95% CI = 1.75-2.38). We found a dose-response association, particularly for second-generation antipsychotics, and different risk rates for specific antipsychotics. In the Central Denmark Region cohort, a total of 9.2% developed diabetes but mean HbA1c levels remained stable at 37 mmol/mol during the 2 years after initiation of antipsychotic medication. This comprehensive real-world two-cohort study emphasizes that diabetes affects almost 10% of patients with FES. Antipsychotics increase this risk, while HbA1c deterioration requires longer treatment. These findings are important for clinicians and young patients with FES.

Clinical characteristics and toxicological spectrum analysis of 493 cases of acute poisoning in children

ObjectiveThis retrospective study aimed to analyze the clinical characteristics and toxicological spectrum of acute poisoning in children treated at our pediatric intensive care unit. The findings provide a basis for the treatment and prevention of acute poisoning in children.MethodsClinical data of hospitalized children aged 0 to14 years with acute poisoning, treated between January 2015 and December 2023, were collected and analyzed. The analysis included the types of poisoning, sex and age distribution of children, routes and causes of poisoning, time from poisoning to medical consultation, length of hospital stays, and treatment outcomes.ResultsAmong the 493 cases of acute poisoning in children, pesticide poisoning (n = 252, 51.1%) was the most common type, followed by medication poisoning (n = 182, 36.9%). Chemical poisoning accounted for 7.7% (n = 38), while food poisoning and inhalation of harmful gases accounted for 3.0% (n = 15) and 1.2% (n = 6), respectively. The main route of poisoning was oral ingestion (n = 477, 96.8%), while accidental ingestion accounted for a large proportion (n = 379, 79.4%), and adolescents aged 11 to 14 years accounted for 20.6% (n = 98).Apart from the predominance of girls attempting suicide by self-administering antipsychotic medications (n = 88, 75.9%) due to depression, there was no significant difference in sex distribution among other types of poisoning children. The highest incidence of poisoning except children who self-administer antipsychotic drugs occurred in children aged 1–3 years (n = 267, 54.2%) and 8–14 years (n = 135, 27.4%), with the highest proportion in the preschool age group. The average time from poisoning to medical consultation was 33.4 ± 54.9 h, and majority of children received treatment within 48 h after poisoning (n = 423, 85.8%). The overall effective treatment rate was 96.8%.ConclusionAcute poisoning in children has complex and diverse causes, with accidental ingestion being the main route. Prevention should be emphasized, including strengthening child safety education and improving parental supervision. Moreover, psychological health education is crucial for adolescents during their puberty. In the event of acute poisoning, prompt medical consultation and appropriate treatment are necessary to mitigate adverse outcomes.

Manejo do delirium para o clínico geral

This paper is part of a larger project in medical education regarding central themes in psychiatry and aims to improve the clinical knowledge of medical students and practitioners both. Given the high prevalence of delirium in hospital settings and the poor prognosis associated with it, it is of the utmost importance that not only its adequate management is known, but also measures to prevent it are implemented widely. Delirium is a clinical syndrome in which the main components are altered attention, fluctuating level of consciousness, and disorganized thought; generally, symptoms fluctuate in intensity during the day. Delirium has hyperactive, hypoactive, and mixed presentations. Prevalence is higher in critically ill patients and its presentation denotes a worse prognosis; therefore, its early detection and prevention are paramount. Treatment consists of treating base causes, precipitating factors, and administering antipsychotic medications, commonly haloperidol for hyperactive forms.

Inhibition of HCN1 currents by norquetiapine, an active metabolite of the atypical anti-psychotic drug quetiapine.

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

Assessment of Adverse Effects Associated with Antipsychotics in Patients with Schizophrenia

Schizophrenia causes major disruptions in a person's life, making it challenging to go to work or school, maintain a routine, interact with others, finish daily duties, or take care of oneself. This study aimed to assess adverse effects of antipsychotics in patients with schizophrenia. This study is relevant in identifying the side effects and improving the treatment options which HELPs reducing side effects and improved quality of life of patients. Antipsychotic drugs can lessen or alleviate psychotic symptoms like delusions and hallucinations. Antipsychotic medications can have side effects that range from being mildly unpleasant to extremely unpleasant. A total of 42 patients complying the inclusion criteria were included in the study among which The majority were in the age group of 35-44 and with male gender dominanc. The study observed no significant relationship between the occurrence of the side effects and age but found to have a significant relation between weight gain and male gender. The drug which was most prescribed was Risperidone, followed by Olanzapine. From this study it was evident that, side effects such as akathisia, tremors, insomnia, weight gain, dizziness, weight gain etc was due to second generation antipsychotics from usage over a longer period of time. This study observed that male age groups were more prone to get weight gain as side effect while taking second generation side effects. While no significant comparison with age was found. The study concluded that adverse effect can be attenuated by alternating the drugs instead of long term usage.

12492 Clinical Resolution Of Parkinsonism And Dementia Following Radio Frequency Ablation Of A Parathyroid Adenoma

Abstract Disclosure: P. Finny: None. T. George: None. A.K. Francis: None. Background: Parkinsonism is a rare neurological manifestation of primary hyperparathyroidism. Radiofrequency ablation (RFA) of parathyroid adenomas is a novel treatment modality. Clinical Case: A 78 year old lady presented to our Emergency department with hypercalcemic encephalopathy. She had long standing Diabetes mellitus, Bronchial asthma and Parkinsonism with dementia for the past 14 years. She was bed bound with dependence on carers for activities of daily living (ADL). She had been diagnosed elsewhere in 2018 to have primary hyperparathyroidism due to a right inferior parathyroid adenoma and had a right hemithyroidectomy with a failed parathyroidectomy. She was being managed with Cinacalcet 60 mg daily for the past 4 years. Prior to this admission she had discontinued Cinacalcet for a few days. Her initial serum calcium was 15.3 mg/dl (8.7-10.7), phosphorus 1.80 mg/dl (2.5-4.5) and PTH 451 pg/ml (15- 88). She was aggressively treated with intravenous normal saline hydration followed by Furosemide injection. Then she was given Calcitonin injections subcutaneously and IV Zoledronic acid infusion. Her calcium dropped to 11.8 mg/dl within 48 hours of admission, and her sensorium improved. Imaging studies showed no visible parathyroid adenoma on ultrasound, but the 4D CT scan of the neck revealed a left inferior parathyroid adenoma of size 1.1 x 1.2 cm. This was concordant on the Technetium 99m Sestamibi scan. Her MRI Brain showed bilateral globus pallidus calcification. In view of her multiple comorbidities making her a poor candidate for general anaesthesia, non-surgical options were considered. A percutaneous ultrasound guided RFA of the left parathyroid adenoma was successfully performed. Post procedure the PTH dropped from 321 pg/ml to 54.9 pg/ml within 24 hours. The calcium, phosphorus and PTH remained normal. Her Parkinsonism and dementia significantly improved and we could wean her off the anti- parkinsonian and anti-psychotic medication. She became ambulant and regained her cognitive functions. This clinical and biochemical remission was maintained over the next 22 months of follow up. Conclusion: RFA is a novel therapeutic option in treating parathyroid adenomas among surgically unfit patients. Reversal of advanced Parkinsonism following correction of chronic hypercalcemia led to this patient regaining a good quality of life. 4D CT scan of the neck is useful in localizing the parathyroid adenoma when there is discordance between the ultrasound and Sestamibi scan.

7087 An Unusual Movement Disorder, Case of Diabetic Striatopathy!

Abstract Disclosure: S. Azmat: None. O. Lodhi: None. R. Safi: None. H. harb: None. H. Ashok: None. M.F. Siddiqui: None. J.L. Gilden: None. Background: Non-ketotic Hyperglycemia Hemichorea-Hemiballismus Syndrome (NKH-CB) is rare complication of poorly controlled diabetes mellitus (DM) characterized by continuous, irregular jerky movements localized to one side of the body. It is commonly seen in type 2 DM and is often presented in females of East Asian descent. NKH-CB is often misdiagnosed due to its rarity and radiographic features easily mistaken for intracerebral hemorrhage.Case: A 70-year-old Latino male with type 2 diabetes mellitus, hypertension, bipolar disorder and past history of two cerebrovascular accidents presented to ED with non-radiating, midsternal chest pain. ACS was ruled out with negative serial troponins and normal EKG. Vital signs were significant for elevated blood pressure 151/64 mmHg. Labs showed blood glucose=447 mg/dL. Physical examination revealed large amplitude involuntary movements in left upper and lower extremities and facial region. He also veered to the left when ambulating. The patient reported that these abnormal movements were occurring for last three weeks although sensation was preserved bilaterally. Code stroke was called; non-contrast CT showed unilateral hyper density of the right caudate and putamen with no evidence of acute intracranial hemorrhage or large arterial territory infarction. CT Angiogram did not show any signs of stenosis or occlusion. He received intravenous fluids and 8 units lispro insulin in ED. Was admitted for further evaluation and received basal/bolus insulin therapy with target blood glucose of 140-160 mg%. He also received risperidone for his mental condition. Subsequent testing revealed hemoglobin A1C of 16.9% (reference range: &amp;lt; 5.7%). MRI Brian showed unilateral T1 hyperintensity involving right caudate and putamen corresponding to the hypodensity seen on CT. Neurology service was consulted. Based on clinical signs/symptoms coupled with neuroimaging, he was diagnosed with non-ketotic Hyperglycemia Hemichorea-Hemiballismus Syndrome. On day 2 with resolution of hyperglycemia, amplitude and frequency of involuntary arm movements were minimal. The patient was discharged with Lantus 7 and metformin 1000 mg for DM and risperidone for symptoms management. Conclusion: Diabetic neuropathy is commonly known to result in small and/or large fiber sensorimotor polyneuropathy, proximal motor, and acute mononeuropathies as well as entrapments, radiculopathies, autonomic neuropathies, and even cognitive disorders. This case describes rare case of simultaneous NKH-CB with history of CVA and antipsychotic medication use in a patient with poorly controlled DM which resolved with treatment of hyperglycemia. Thus offers valuable insights into the diagnostic challenges associated with this condition as well as potential links to other neurological complications. One should also remain vigilant of potential onset of seizures commonly seen with NKH. Presentation: 6/3/2024

8288 Navigating Diagnostic Challenges of Amiodarone Induced Thyrotoxicosis in a Psychiatrically Complex Patient within a Community Hospital Setting

Abstract Disclosure: M.S. Shah: None. K.P. Sanu: None. S. Humayon: None. R. Chawla: None. N.K. Bains: None. This case delves into the intricate diagnostic and therapeutic journey of a 64-year-old male who presented to a community hospital with psychosis. Medical history was pertinent for ventricular arrhythmias treated with amiodarone 400 mg once daily, bipolar disorder with medication non-compliance and heart failure with reduced ejection fraction status post automatic implantable cardioverter-defibrillator placement. Collaboration with the patient's family revealed a history of repeated hospitalizations for similar presentations as well as recent weight loss. The challenge lay in distinguishing between manic episodes and other potential underlying medical causes. The patient's recent weight loss and amiodarone use prompted a thyroid panel, revealing a TSH of 0.01 mlU/L (n = 0.27 to 4.20 mIU/L), free T4 of &amp;gt;7.77ng/dL (n = 0.93 to 1.70 ng/dL), and free T3 of &amp;gt;7.51ng/dL (n = 2.00 to 4.40 pg/mL). Inadequate facilities for a radioactive iodine uptake (RAIU) scan and thyroid doppler ultrasound heightened the diagnostic challenge, making the history and physical exam pivotal in steering the course of this patient's care. The Burch-Wartofsky score was found to be elevated at 30 due to delirium and abdominal pain reported in the emergency department. Amiodarone use for over two years with no prior history of thyroid dysfunction, along with the absence of a goiter or thyroid antibodies suggestive of Graves disease heightened the suspicion for amiodarone-induced thyrotoxicosis type 2 (AIT type 2). Due to the lack of RAIU scan and thyroid ultrasound to better differentiate between AIT type 1 and type 2, the patient was treated with methimazole and prednisone along with an antipsychotic medication regimen. The discontinuation of antipsychotic medications became necessary due to QTc prolongation and subsequent defibrillator discharge. The patient's further improvement without psychiatric medications highlighted the success of the tailored treatment strategy, emphasizing the importance of accurate diagnosis in patients with psychiatric comorbidities. The patient’s relatively rapid clinical response also aids in differentiating AIT type 1 from type 2. This case brings awareness to the importance of a comprehensive history and physical exam, particularly in the setting of a community hospital with limited diagnostic resources. Despite the inability to obtain history directly from the patient and having diagnostic constraints, the judicious use of available resources and clinical acumen led to the diagnosis of Amiodarone-induced thyrotoxicosis type 2. Clinicians should keep a broad differential to avoid confirmation bias in treating psychiatric patients with a complex medical history. This case serves as a testament to the importance of a holistic approach to patient care and the need for ongoing advancements in diagnostic capabilities within community healthcare settings. Presentation: 6/2/2024

In-depth analysis of antipsychotic-induced akathisia: An integrative literature review

Background: Antipsychotic-induced akathisia poses a significant challenge in clinical practice due to its frequent oversight in diagnosis and associated severe consequences such as suicidal behavior and compromised treatment adherence. Understanding the underlying mechanisms and implementing effective management strategies are imperative in addressing this clinical concern. Objective: provide an updated understanding of the correlation between antipsychotics and akathisia, discussing its pathophysiology, diagnosis, assessment, and current as well as prospective treatment options. Methods: An integrative literature review was conducted utilizing Pubmed and Virtual Health Library databases, supplemented by additional resources to broaden the study's scope. Results and Discussion: Among the 204 studies analyzed, 17 met the criteria for inclusion in the review, complemented by 7 articles focusing on assessment scales. The study explores the impact of neuroleptic medications on akathisia's pathophysiology, diagnostic approaches, symptomatology, assessment tools, and management strategies. Conclusion: Robust research endeavors are crucial to consolidate evidence, identify gaps, and offer a holistic perspective on akathisia. The profound comprehension of the condition reveals paths to enhance patients' quality of life.

Understanding the medication regimens associated with anticholinergic burden in older people's mental health services in the UK.

Medications with anticholinergic properties are associated with a range of adverse effects that tend to be worse in older people. To investigate medication regimens with high anticholinergic burden, prescribed for older adults under the care of mental health services. Clinical audit of prescribing practice, using a standardised data collection tool. Fifty-seven trusts/healthcare organisations submitted data on medicines prescribed for 7915 patients: two-thirds (66%) were prescribed medication with anticholinergic properties, while just under a quarter (23%) had a medication regimen with high anticholinergic burden (total score ≥3 on the anticholinergic effect on cognition (AEC) scale). Some 16% of patients with a diagnosis of dementia or mild cognitive impairment were prescribed medication regimens with a high anticholinergic burden, compared with 35% of those without such diagnoses. A high anticholinergic burden was mostly because of combinations of commonly prescribed psychotropic medications, principally antidepressant and antipsychotic medications with individual AEC scores of 1 or 2. Adults under the care of older people's mental health services are commonly prescribed multiple medications for psychiatric and physical disorders; these medication regimens can have a high anticholinergic burden, often an inadvertent consequence of the co-prescription of medications with modest anticholinergic activity. Prescribers for older adults should assess the anticholinergic burden of medication regimens, assiduously check for adverse anticholinergic effects and consider alternative medications with less anticholinergic effect where indicated. The use of a scale, such as the AEC, which identifies the level of central anticholinergic activity of relevant medications, can be a helpful clinical guide.