Use Of Antipsychotic Medications Research Articles

Atypical Antipsychotics Use and Neuroleptic Malignant Syndrome: A Review With a Clinical Perspective

Neuroleptic malignant syndrome (NMS) is a potentially life-threatening idiosyncratic reaction associated with the use of antipsychotic medications, characterized by hyperthermia, muscle rigidity, and alterations in consciousness. Despite a reduction in its incidence due to the predominance of atypical antipsychotics in contemporary treatment regimens, NMS remains a critical neuropsychiatric emergency that warrants vigilant attention. There is a hypothesis proposing that catatonia and NMS may exist along a continuum of the same disorder, and evidence suggests that lorazepam may offer therapeutic benefits for both conditions. It is potential for the concurrent occurrence of NMS and serotonin syndrome when antipsychotics and antidepressants are administered concomitantly. This paper presents a case of NMS following the reinitiation of antipsychotic treatment over an extended duration, a scenario inadequately addressed in existing reports, and discusses strategies for its management in clinical practice.

Neuronal alterations in AKT isotype expression in schizophrenia.

Schizophrenia is characterized by substantial alterations in brain function, and previous studies suggest insulin signaling pathways, particularly involving AKT, are implicated in the pathophysiology of the disorder. This study demonstrates elevated mRNA expression of AKT1-3 in neurons from schizophrenia subjects, contrary to unchanged or diminished total AKT protein expression reported in previous postmortem studies, suggesting a potential decoupling of transcript and protein levels. Sex-specific differential AKT activity was observed, indicating divergent roles in males and females with schizophrenia. Alongside AKT, upregulation of PDPK1, a critical component of the insulin signaling pathway, and several protein phosphatases known to regulate AKT were detected. Moreover, enhanced expression of the transcription factor FOXO1, a regulator of glucose metabolism, hints at possible compensatory mechanisms related to insulin signaling dysregulation. Findings were largely independent of antipsychotic medication use, suggesting inherent alterations in schizophrenia. These results highlight the significance of AKT and related signaling pathways in schizophrenia, proposing that these changes might represent a compensatory response to a primary defect of canonical insulin signaling pathways. This research underscores the need for a detailed understanding of these signaling pathways for the development of effective therapeutic strategies.

Schizophrenia, Off-Label Antipsychotics, and Dementia Risk in People with HIV.

Comorbidities such as schizophrenia and medication such as antipsychotics may influence the risk of dementia among people living with HIV (PLWH). The objective of this paper is to assess the associations among HIV patients with schizophrenia, off-label antipsychotics, and dementia risk. US Department of Veterans Affairs healthcare facilities from 2000 to September 2023. Retrospective cohort study of PLWH treated by the U.S. Department of Veterans Affairs with prior history of schizophrenia, off-label antipsychotic use and neither schizophrenia nor antipsychotic use. Propensity score matched non-HIV controls were included for the respective HIV groups. The hazard of dementia is estimated using Cox proportional hazards models. PLWH and schizophrenia, were found to have a 2.49 higher hazard of dementia compared to HIV patients with no history of schizophrenia or antipsychotic medication use (HR=2.49, 95%CI=(1.85-3.35)). PLWH and off-label antipsychotic use were found to have a 1.77-fold higher hazard of dementia compared to HIV patients with no history of schizophrenia or antipsychotic medication use (HR=1.77, 95% CI=(1.37-2.28)). Propensity score matched analysis reveals that, among schizophrenia patientis, those with HIV had a 1.65-fold higher hazard of dementia (HR=1.65, 95%CI=(1.12-2.44)). Among patients with no schizophrenia or antipsychotic medication, those with HIV had a 1.47 fold higher hazard of dementia (HR=1.47, 95%CI=(1.33-1.63)). This study demonstrates that among PLWH, history of schizophrenia or off-label antipsychotic medication use are associated with substantial increases in dementia incidence. Furthermore, propensity-matched control analysis reveals that HIV infection itself is independently and significantly associated with elevated dementia risk.

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: < 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

Caudate nucleus volume in medicated and unmedicated patients with early- and adult-onset schizophrenia

The caudate nucleus is a part of the striatum, and striatal hyperdopaminergia is considered central to the pathophysiology of schizophrenia. How caudate volume is affected in schizophrenia and what role antipsychotics play remains unclear. In early-onset schizophrenia (EOS), where psychosis emerges during a neurodevelopmentally critical phase, the caudate may exhibit a heightened vulnerability to the effects of antipsychotic medications. We hypothesized effects of both antipsychotic medication use and age of onset on caudate in schizophrenia. We included adult patients with EOS (n = 83) and adult-onset schizophrenia (AOS) (n = 246), adult healthy controls (HC, n = 774), adolescent patients with non-affective psychosis (n = 56) and adolescent HC (n = 97). We obtained T1-weighted MRI scans using a 1.5T Siemens scanner and General Electric 3T scanners. In our main analysis, we tested for main and interaction effects of diagnosis and current antipsychotic medication use on caudate volume. Adult patients with EOS (p < 0.001) and AOS (p = 0.002) had both larger caudate than HC. Age of onset (EOS/AOS) interacted with antipsychotic use (p = 0.004) which was associated with larger caudate in EOS (p < 0.001) but not in AOS (p = 0.654). Conversely, among medicated patients only, EOS had larger caudate than AOS (p < 0.001). No other subcortical structures showed differences between medicated EOS and AOS. Medicated adolescent patients with non-affective psychosis and medicated adult patients with EOS showed similar caudate volumes. The results may indicate a schizophrenia-related and a medication-induced caudate increase, the latter restricted to patients with EOS and possibly occurring already in adolescence shortly after disease onset.

Long-Acting Injectable Antipsychotic Medication Use in Youth: A Systematic Review of the Literature Along with MedWatch Safety Data and Prescriber Attitudes.

Objectives: Long-acting injectable (LAI) antipsychotic medications are being prescribed to children and adolescents along a broad age range from 2 to 17 years old. However, there is no U.S. Food and Drug Administration (FDA) approved indication for the use of any LAI in a pediatric population. The goal of this article is to perform a systematic literature review regarding the use of LAIs in a pediatric population, to obtain pediatric LAI safety data, and to survey prescriber attitudes regarding LAI use in youth. Methods: A search for relevant articles between June 1986 and June 2021 was conducted. Safety data were obtained from FDA MedWatch postmarketing adverse event reports regarding LAI use in children and adolescents. A survey of practicing Child and Adolescent Psychiatrists in Wisconsin was done regarding the use of LAIs in youth. Results: The predominant reasons for LAI use in youth were illness severity and treatment noncompliance. Twenty-six of 30 identified studies and reports favored LAI use in youth, but were of low to very low quality. Overall, 587 FDA MedWatch reports between June 1986 and June 2021 were identified. Most adverse events occurred in modest numbers. Extrapyramidal symptoms accounted for 18% of all MedWatch reports, neuroleptic malignant syndrome accounted for 3% of all reports, and deaths accounted for 2% of all reports. The concern for safety was reflected in prescriber survey results along with a recognition that LAIs can be helpful to target severe psychiatric symptoms and address treatment noncompliance. Conclusions: No randomized controlled studies were found. Identified published studies and reports were of low to very low quality. However, it appeared reasonable that the use of LAIs in a select group of pediatric patients can be helpful to target severe psychiatric symptoms and to enhance treatment compliance.

Trajectories of daily antipsychotic use and weight gain in people hospitalized for the first episode of psychosis.

We need to better understand the risk factors and predictors of medication-related weight gain to improve metabolic health of individuals with schizophrenia. This study explores how trajectories of antipsychotic medication (AP) use impact body weight early in the course of schizophrenia. We recruited 92 participants with first-episode psychosis (FEP, n=92) during their first psychiatric hospitalization. We prospectively collected weight, body mass index (BMI), metabolic markers, and exact daily medication exposure during 6-week hospitalization. We quantified the trajectory of AP medication changes and AP polypharmacy using a novel approach based on meta-analytical ranking of medications and tested it as a predictor of weight gain together with traditional risk factors. Most people started treatment with risperidone (n=57), followed by olanzapine (n=29). Then, 48% of individuals remained on their first prescribed medication, while 33% of people remained on monotherapy. Almost half of the individuals (39/92) experienced escalation of medications, mostly switch to AP polypharmacy (90%). Only baseline BMI was a predictor of BMI change. Individuals in the top tercile of weight gain, compared to those in the bottom tercile, showed lower follow-up symptoms, a trend for longer prehospitalization antipsychotic treatment, and greater exposure to metabolically problematic medications. Early in the course of illness, during inpatient treatment, baseline BMI is the strongest and earliest predictor of weight gain on APs and is a better predictor than type of medication, polypharmacy, or medication switches. Baseline BMI predicted weight change over a period of weeks, when other traditional predictors demonstrated a much smaller effect.

Antipsychotics and chronic dystonia at a Botulinum Toxin clinic.

Chronic dystonia, characterised by sustained muscle contractions and abnormal postures, poses clinical challenges, especially when associated with antipsychotic medication use. To delineate the demographic and clinical profiles of adults with dystonia and examine the association with antipsychotic medication. Botulinum Toxin Clinic at Tygerberg Hospital, Cape Town, South Africa. We conducted a retrospective cohort study of adult patients seen at the Botulinum Toxin Clinic between January 2018 and June 2022. Of the 119 patients studied, those assessed with antipsychotic-induced dystonia (32.69%) presented at a younger age (p < 0.001), were more likely female (p = 0.04), received higher average dose of Botulinum toxin (p < 0.001), and incurred a higher estimated Botulinum toxin treatment cost (p = 0.01) compared to those with primary dystonia. Logistic regression identified age and Botulinum toxin dose as factors associated with psychotropic-related dystonia (p = 0.005 and p = 0.012, respectively). Clinical and demographic factors are associated with dystonia in adults taking antipsychotic medication. These patients generally manifested symptoms at an earlier age, had a higher male prevalence, and required prolonged treatment with Botulinum toxin, leading to increased costs. In those assessed with antipsychotic-induced dystonia, a comorbid diagnosis of a mood disorder was more common than that of a psychotic disorder. By identifying the demographic and clinical profile of individuals with dystonia because of antipsychotic medication, this study provides a basis for preventative strategies and enhanced patient care.

Antipsychotic prescription patterns among schizophrenia patients in Guangdong Province, China’s 686 program: A retrospective study

Schizophrenia is a severe mental disorder. However, there is limited data on the prescribing patterns of patients under China’s Central Government Support for the Local Management and Treatment of Severe Mental Illnesses Program, known as the “686 program.” This study aimed to investigate the use of antipsychotic medications and associated factors among discharged schizophrenia patients in Guangdong Province, within the 686 Program. This study encompassed schizophrenia patients who were discharged from the Affiliated Brain Hospital, Guangzhou Medical University and enrolled in the 686 Program between January 2019 and December 2019. A total of 1645 hospitalized schizophrenia patients were included in the analysis. Clinical and sociodemographic data were acquired from medical records upon discharge. A total of 15 unique antipsychotic medications were utilized, comprising 4 first-generation (FGAs) and 11 second-generation (SGAs) options. FGAs were prescribed at a rate of 8.3%, while SGAs dominated at 98.8%. Risperidone (40.8%), olanzapine (30.2%), clozapine (24.6%), and amisulpride (15.4%) emerged as the top 4 prescribed medications. Additionally, mood stabilizers were used by 20.4%, antidepressants by 14.8%, sedative-hypnotics by 33.6%, anticholinergics by 26.9%, and other internal medicine drugs by 46.4%. Notably, 60.5% received antipsychotic monotherapy (AMT), while 39.5% underwent antipsychotic polypharmacy (APP). Predictors of polypharmacy included multiple hospital admissions, longer hospital stays, and undergoing modified Electroconvulsive Therapy (mECT) during hospitalization. In Guangdong Province, China’s 686 Program, hospitalized patients commonly receive multiple antipsychotic medications simultaneously. Due to the varying outcomes in current studies on the benefits and risks of polypharmacy, it’s vital to educate psychiatrists about the importance of AMT to reduce APP. Additionally, randomized, controlled trials are essential to identify the safest and most effective antipsychotic combinations, as well as to understand which patient profiles may benefit from these combinations.

A Longitudinal Treatment Effect Analysis of Antipsychotics on Behavior of Residents in Long-Term Care

ObjectiveThe proportion of long-term care (LTC) residents being treated with antipsychotic medication is high, and these medications may exacerbate behavioral symptoms. We used propensity scores to investigate the effect of antipsychotic use on the worsening of behavioral symptoms among residents in LTC facilities. DesignA retrospective study. Setting and participantsResidents in LTC in 8 provinces and 1 territory in Canada, without severe aggressive behavior at baseline and reassessed at follow-up, between March 2000 and March 2022. MethodsWe used propensity score matching and weighting to balance baseline covariates and logistic regression to estimate the effect of antipsychotics on the worsening of behavioral symptoms in the original, matched, and weighted cohorts. The treatment variable was use of antipsychotic medication at baseline and the outcome was worsening of behavior at follow-up. ResultsA total of 494,215 participants were included [318,234 women and 175,981 men; mean age 82.8 years (SD 10.1; range 18–112)].130 558 (26.4%) used antipsychotics at baseline and 88,632 (17.9%) had worsening behavior in follow-up. In the matched cohort, there were 249,698 participants, and 124,849 were matched (1:1) in each treatment group. There was a significant association between antipsychotic use at baseline and worsening in behavior at follow-up in the adjusted regression models [OR 1.27 (95% CI 1.25–1.29), <0.0001] as well as in matched [OR 1.20 (95% CI 1.17–1.21), <0.0001] and weighted [OR 1.26 (95% CI 1.24–1.28), <0.0001] cohorts. Conclusions and implicationsThis study further evidence to support the cautious use of antipsychotics in LTC facilities. Future research in LTC facilities could include a more granular analyses of behavior change, including bidirectional analyses between different symptom severity classifications.

Acute treatment residual depression symptoms and functional impairment among depressive patients of different age groups and education levels in China: A prospective, multicenter, randomized study.

A prospective, multicenter, randomized study evaluated the efficacy of major depressive disorder (MDD) patients after 2-3 months of acute treatment based on the dual factors of education and age. This study classified the included patients into four groups using two classification parameters: age (≤45 years, vs.>45 years) and education years (≤12vs.>12). We analyzed age, gender, marital status, personal income, depression onset history, medication use, and follow-up across various groups. We evaluated residual somatic symptoms and social functioning in depression patients was conducted using the 16-item Quick Inventory of Depressive Symptomatology Self-report (QIDS-SR16), the Patient Health Questionnaire-15 (PHQ15), and the Sheehan Disability Scale (SDS). In China, 16 hospitals, 553 depression patients, and 428 fulfilled the inclusion criteria. Baseline patient data revealed significant differences among the different age groups in gender, marital status, income, first onset age, physical illness, combination of antipsychotics, and benzodiazepines use (all p<.05). Statistically significant differences were observed in overall comparisons among the four groups, encompassing the QIDS-SR16 score, PHQ15 score, and various SDS parameters (all p<.05). However, no statistically significant differences (all p>.05) were found in residual somatic symptoms and social functioning parameters between different education levels (≤12 years vs.>12 years) at baseline, 3 months, and 6 months, based on total scores on the scale. Repeated measures mixed model indicates that the QIDS-SR16 assessment indicates statistical differences among various marital statuses, income levels, medical histories, and antipsychotic medication use (p<.05). Furthermore, PHQ-15 and SDS assessments reveal statistical differences between single and married/cohabiting statuses, physical comorbidities, 3 and 6 months follow-ups compared to baseline (p<.05). This study indicates that compared to depressive patients>45 years old, those ≤45 years old often exhibit more residual depression, somatic symptoms, and severe social functional impairment; patients' education levels less influence this trend.

Comparison of Team-Based and Problem-Based Approaches to Dementia Care in Nursing Homes and Their Effects on Resident Outcomes During the COVID-19 Pandemic: A Mixed-Methods Study

ObjectivesCompare the effectiveness of 2 nonpharmacologic approaches to dementia care in nursing homes on 12- and 18-month resident outcomes, which was after the emergence of COVID-19. Design and InterventionA cluster randomized pragmatic trial, which included an embedded convergent mixed-methods design. Nursing homes were randomized to a team-based (TB) or problem-based (PB) intervention arm. Setting and ParticipantsResidents (n = 2658 at baseline) and staff (n = 327) from 52 nursing homes in the United States. MethodsThe exploratory quantitative analysis used a difference-in-differences model to compare the change in TB arm resident outcomes between baseline, 12 months, and 18 months relative to the PB arm using the Minimum Data Set 3.0. Outcomes included antipsychotic medication use, behavioral symptoms, wandering, and rejection of care. Staff interview data were analyzed in a 3-phase team-based rapid qualitative analysis approach, after which data were integrated. ResultsRejection of care decreased by 5.9 percentage points in the TB arm relative to the PB arm at 12 months (95% CI –11.7 to −0.2). Emergent results indicated that COVID-19 visitation restrictions prevented PB staff from working with families to manage rejection of care as was done before the pandemic, whereas TB staff described using collaboration strategies not hindered by the pandemic. There was no statistically significant difference between arms in antipsychotic medication use, behavioral symptoms, and wandering at either follow-up period. When integrated, qualitative data provided contradictory information on antipsychotic medication use and confirmatory information on behavioral symptoms and wandering. Conclusions and ImplicationsThe exploratory nature and mixed results of the quantitative data analysis limited the ability to determine a clear benefit of one approach over the other. Findings suggest that dementia care delivery faced complex challenges during COVID-19 and required engagement from a broad range of nursing home staff underscoring the importance of equipping all staff with foundational dementia care knowledge.

A Cluster Randomized Trial: Mixed Methods Comparison of 2 Approaches to Promote Nonpharmacologic, Resident-Centered Dementia Care in Nursing Homes

ObjectivesNursing home dementia care initiatives have prioritized nonpharmacologic approaches to manage behavioral symptoms. This study compares the effectiveness of 2 nonpharmacologic approaches on resident outcomes. Design and InterventionCluster randomized controlled trial using a convergent mixed methods design to compare the team-based and problem-based approaches to dementia care. The team-based arm received facility-wide training, providing a shared language and knowledge across staff. The problem-based arm received discipline-specific web-based training for certain staff. Setting and ParticipantsResidents living with dementia (n = 2728) in 53 nursing homes; 327 staff. MethodsOutcomes were antipsychotic medication use, behavioral symptoms, rejection of care, and wandering captured with the Minimum Data Set. Exploratory quantitative analysis compared change in outcomes between baseline and 6-month follow-up, across arms using a difference-in-difference model. Qualitative data were collected via staff interviews. Integration of quantitative and qualitative data determined whether these sources provided confirmatory, emergent, or contradictory information on outcomes. ResultsResident wandering increased 3.51 percentage points (95% CI 0.6, 6.4) in the team-based arm compared to the problem-based arm, without increase in adverse events. Data integration confirmed this finding. Staff in the team-based arm described wandering as a positive coping strategy for the resident. We found mixed results for the other 3 outcomes. There was no statistically significant difference in antipsychotic medication use across arms, but staff interviews did reveal differences. There were trends of increased behavioral symptoms in the team-based arm and increased rejection of care in the problem-based arm (neither statistically significant), which were confirmed by qualitative findings. Conclusions and ImplicationsIntegration results suggest a benefit for resident wandering in the team-based approach, compared with the problem-based approach. Although findings are exploratory, training for all nursing home staff that accounts for diverse education and training needs may influence care delivery and have benefits for residents living with dementia.

Usability and Feasibility of the Antipsychotic Medication Decision Aid in a Community Program for First-Episode Psychosis.

Although antipsychotic medications are considered first-line treatment for psychosis, rates of discontinuation and nonadherence are high, and debate persists about their use. This pilot study aimed to explore the usability, feasibility, and potential impact of a shared decision making (SDM) intervention, the Antipsychotic Medication Decision Aid (APM-DA), for decisions about use of antipsychotic medications. A pilot randomized controlled trial was conducted with 17 participants in a first-episode psychosis program. Nine participants received the APM-DA, and eight received usual care. After their appointments, intervention group participants had less decisional conflict and greater satisfaction with decisions than control group participants had. Use of the APM-DA did not increase appointment length. Comparison of the intervention outcomes with the control outcomes was limited because of the small sample. The results support the feasibility and usability of an SDM process via the use of the APM-DA in routine community psychosis care.

Schizophrenia and Heart Health: Are Antipsychotics a Friend or Foe?

Schizophrenia is one of the most disabling of the psychiatric diseases. The Brief Psychiatric Rating Scale Extended (BRSE) is used to evaluate the severity of psychiatric symptoms. Long-acting injectable (LAI) antipsychotics are commonly used and are preferred over oral antipsychotic medications. A two-center-based cross-sectional study was performed on 130 patients diagnosed with schizophrenia or schizoaffective disorder based on the International Classification of Diseases 10 criteria. We studied the relation between the development of cardiovascular risk factors and the antipsychotic medication that was administered in these patients. Our study demonstrates strong links between several cardiovascular risk factors and the duration of psychosis; the duration of the LAI antipsychotic treatment; the duration between the onset of the disease and the start of LAI antipsychotic treatment; and the use of specific LAI antipsychotic medications.

Prion diseases motor and neuropsychiatric symptom cluster pharmacotherapy: structured scoping review

BackgroundPrion diseases are a group of rare, neurodegenerative conditions that are invariably fatal and cause a variety of symptoms, which can prove challenging to control. Through this paper, we aim...

Quetiapine, Clozapine, and Pimavanserin Treatment Response in Monogenic Parkinson's Disease Psychosis: A Systematic Review.

Psychotic symptoms frequently occur in idiopathic Parkinson's disease (PD) and often require treatment with antipsychotic therapy. Most antipsychotics have the potential to worsen the motor symptoms of PD; quetiapine, clozapine, and pimavanserin are commonly used for the treatment of idiopathic PD because these medications tend to be comparatively well tolerated. Although psychotic symptoms may also occur in monogenic forms of PD, no reviews have focused on the use of antipsychotic medications in this context. The objective of the present systematic review was to characterize the effectiveness and tolerability of quetiapine, clozapine, and pimavanserin in monogenic PD-associated psychosis. A literature search was performed with PubMed, Scopus, and Embase. The search yielded 24 eligible articles describing 30 individuals, although treatment response with respect to psychotic symptoms was described in only 11 cases; of these, six individuals experienced symptomatic improvement or remission (four with clozapine and two with quetiapine), two exhibited a poor therapeutic response (one to clozapine and one to quetiapine), and the other three responded initially to antipsychotic therapy before experiencing a recurrence of symptoms. The use of quetiapine and clozapine in GBA variant-associated PD is briefly reviewed separately. Notably, no reports of pimavanserin therapy were identified. In keeping with the idiopathic PD literature, relatively low doses of medication were used in most cases. Lastly, side effects were rarely reported. Although quetiapine and particularly clozapine may be effective and well tolerated in the treatment of monogenic PD psychosis, this review highlights the paucity of available evidence to guide clinical decision making in this context.

Reproducible gut microbial signatures in bipolar and schizophrenia spectrum disorders: A metagenome-wide study

BackgroundNumerous studies report gut microbiome variations in bipolar disorder (BD) and schizophrenia spectrum disorders (SSD) compared to healthy individuals, though, there is limited consensus on which specific bacteria are associated with these disorders. MethodsIn this study, we performed a comprehensive metagenomic shotgun sequencing analysis in 103 Dutch patients with BD/SSD and 128 healthy controls matched for age, sex, body mass index and income, while accounting for diet quality, transit time and technical confounders. To assess the replicability of the findings, we used two validation cohorts (total n = 203), including participants from a distinct population with a different metagenomic isolation protocol. ResultsThe gut microbiome of the patients had a significantly different β-diversity, but not α-diversity nor neuroactive potential compared to healthy controls. Initially, twenty-six bacterial taxa were identified as differentially abundant in patients. Among these, the previously reported genera Lachnoclostridium and Eggerthella were replicated in the validation cohorts. Employing the CoDaCoRe learning algorithm, we identified two bacterial balances specific to BD/SSD, which demonstrated an area under the receiver operating characteristic curve (AUC) of 0.77 in the test dataset. These balances were replicated in the validation cohorts and showed a positive association with the severity of psychiatric symptoms and antipsychotic use. Last, we showed a positive association between the relative abundance of Klebsiella and Klebsiella pneumoniae with antipsychotic use and between the Anaeromassilibacillus and lithium use. ConclusionsOur findings suggest that microbial balances could be a reproducible method for identifying BD/SSD-specific microbial signatures, with potential diagnostic and prognostic applications. Notably, Lachnoclostridium and Eggerthella emerge as frequently occurring bacteria in BD/SSD. Last, our study reaffirms the previously established link between Klebsiella and antipsychotic medication use and identifies a novel association between Anaeromassilibacillus and lithium use.

Physical restraint and associated agitation.

Physical restraint of patients in intensive care units (ICUs) has an estimated prevalence of 50%. Many medical centres do not have specific protocols for physical restraint, and the decision of whether to physically restrain a patient is up to the nursing staff. Disadvantages of physical restraint include injuries, exacerbation of agitation and an increased risk of developing post-traumatic stress disorder (PTSD). To report prevalence and outcomes in terms of morbidity and mortality of physical restraint in general ICU patients in an 800-bed secondary medical centre. This retrospective study included 647 patients admitted to a general ICU in an 800-bed secondary medical centre in Kfar Saba, Israel, between January and December 2020. Data included demographics, medical history, length of stay, need for mechanical ventilation, number of ventilation days, 28-day mortality, reason for admission, agitation rate assessed by Richmond Agitation and Sedation Scale (RASS) score, need for physical restraint and need for anti-psychotics. Among the patients, 40% (256 of 647) required physical restraint. Older adult patients had a greater likelihood of being physically restrained along with those admitted because of sepsis or acute respiratory failure. Among the study sample, 11% (71 of 647) required anti-psychotics. Patients who were restrained had longer duration of ventilation (5.9 ± 8.2 vs. 0.36 ± 1.4 days; p < .001) and higher 28-day mortality (0.26 ± 0.45 vs. 0.07 ± 0.25, Z = 6.86, p < .001). There was no difference in medical history, except for chronic drug abuse, which was more frequent in the restraint group (18 [6.9%] vs. 11 [2.8%], respectively; p = .019), as well as the use of anti-psychotic medications (24 [9.3%] vs. 19 [4.8%], respectively; p = .034) and anti-depressants (55 [21.2%] vs. 59 [14.8%], respectively; p = .042). The restraint group had higher disease severity scores, as reflected in requirements for vasopressor support (174 [67.2%] vs. 69 [17.3%], respectively; p < .001) and need for dialysis (39 [15.1%] vs. 19 [4.8%], respectively; p < .001); higher frequency of in-hospital anti-psychotic treatment (60 [23.2%] vs. 11 [2.8%], respectively; p < .001); a greater tendency for agitation events and more severe agitation scores (episodes of RASS above zero [1.7 ± 4.0 vs. 0.04 ± 0.27, respectively; p < .001] and maximum RASS score [0.19 ± 1.6 vs. 0.01 ± 0.54, respectively; p < .001]). Overall, advanced age, number of ventilation days and need for dialysis were associated with increased 28-day mortality. In the restraint group, advanced age, chronic use of diuretics and the use of dialysis during ICU admission were associated with increased mortality risk. Restrained patients tended to have higher morbidity and mortality during ICU and hospital stays, as well as a greater tendency for agitation events and more severe agitation scores, with an increased need for in-hospital anti-psychotic treatment. These findings regarding patient characteristics might be used to formulate treatment plans to reduce the rate of physical restraint in the ICU. Because restrained ICU patients tend to have higher morbidity and mortality, treatment plans should be formulated to reduce the rate of physical restraint in the ICU. NCT04771793.

Megacolon associated with the chronic use of antipsychotic medication

Megacolon associated with the chronic use of antipsychotic medication