High-dose Antipsychotics Research Articles

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

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

Personality Correlates of Certain Clinical Characteristics of Patients With Psychotic Disorders

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

Characterising the nature of psychiatric disorders and patterns of antipsychotic medications prescribed in a psychiatric ward in a public hospital in Tasmania.

We present an evaluation of antipsychotic prescribing in an inpatient psychiatry ward in Hobart, Tasmania, to establish pattern of use, alignment with other psychiatric wards orcentres and the recommendations in the Royal Australian and New Zealand College of Psychiatry Clinical Practice Guidelines, and to determine predictors of polypharmacy. A descriptive cross-sectional survey design was used. Data from 118 patients discharged from the Royal Hobart Hospital (RHH) Mental Health Inpatient Unit between 01/02/2021 to 01/08/2021 were evaluated. Antipsychotic polypharmacy (APP) was observed in 40% of patients. When low doses of adjunctive ('PRN') use of olanzapine and quetiapine were excluded, the APP proportion was 35%. APP was predicted by age and by a schizophrenia diagnosis. Long-acting injections (LAIs) were used in 46% of the patients. The most common LAI was risperidone (52%). Average daily dose of antipsychotic at the time of discharge was 529mg chlorpromazine (CPZ) equivalents. High dose antipsychotics (more than 1000mg CPZ equivalents per day) was observed in 13% of the patients. The observed prescribing practice is consistent with other clinical settings. Antipsychotic prescribing practice should, however, continue to be monitored to ensure adherence to best practice guidelines.

Prediction of Clinical Outcomes in Psychotic Disorders Using Artificial Intelligence Methods: A Scoping Review.

Psychotic disorders are major psychiatric disorders that can impact multiple domains including physical, social, and psychological functioning within individuals with these conditions. Being able to better predict the outcomes of psychotic disorders will allow clinicians to identify illness subgroups and optimize treatment strategies in a timely manner. In this scoping review, we aimed to examine the accuracy of the use of artificial intelligence (AI) methods in predicting the clinical outcomes of patients with psychotic disorders as well as determine the relevant predictors of these outcomes. This review was guided by the PRISMA Guidelines for Scoping Reviews. Seven electronic databases were searched for relevant published articles in English until 1 February 2024. Thirty articles were included in this review. These studies were mainly conducted in the West (63%) and Asia (37%) and published within the last 5 years (83.3%). The clinical outcomes included symptomatic improvements, illness course, and social functioning. The machine learning models utilized data from various sources including clinical, cognitive, and biological variables such as genetic, neuroimaging measures. In terms of main machine learning models used, the most common approaches were support vector machine, random forest, logistic regression, and linear regression models. No specific machine learning approach outperformed the other approaches consistently across the studies, and an overall range of predictive accuracy was observed with an AUC from 0.58 to 0.95. Specific predictors of clinical outcomes included demographic characteristics (gender, socioeconomic status, accommodation, education, and employment); social factors (activity level and interpersonal relationships); illness features (number of relapses, duration of relapses, hospitalization rates, cognitive impairments, and negative and disorganization symptoms); treatment (prescription of first-generation antipsychotics, high antipsychotic doses, clozapine, use of electroconvulsive therapy, and presence of metabolic syndrome); and structural and functional neuroimaging abnormalities, especially involving the temporal and frontal brain regions. The current review highlights the potential and need to further refine AI and machine learning models in parsing out the complex interplay of specific variables that contribute to the clinical outcome prediction of psychotic disorders.

The Relationship Between Antipsychotics, Cognitive Enhancers, and Major Adverse Cardiovascular/Cerebrovascular Events (MACCE) in Older Adults with Behavioral and Psychological Symptoms of Dementia.

Antipsychotics and cognitive enhancers are often used to treat psychosis and behavioral disturbances in individuals with dementia; however, these drugs have been linked with various adverse events including both metabolic and cerebro/cardiovascular events. Thus, this study sought to estimate the risk of major adverse cardiovascular/cerebrovascular events (MACCE) across four behavioral and psychological symptoms of dementia (BPSD) treatment models by exploring potential associations between antipsychotics (APs), cognitive-enhancing medications, dosage, and earlier MACCE onset. Patients were obtained from the Loma Linda University Medical Center database who were age ≥50 or older and who were diagnosed with dementia and BPSD symptoms. Treatment group and drug dosing were analyzed using Cox regression analyses to predict time until MACCE onset. Patient age at dementia diagnosis, sex, smoking status, race/ethnicity, and previous MACCE diagnoses were included as covariate variables. The final study population consisted of 1162 individuals. Results indicated a significant effect of medication type on duration until MACCE, (p< 0.001), with the odds of experiencing a MACCE being 96.3% higher for individuals treated with both APs and cognitive enhancers (p<0.001). There was also a significant effect of AP dosage on duration until MACCE (p<0.001) and a significant effect of cognitive enhancer dosage on duration until a MACCE, (p< 0.001). The odds of experiencing a MACCE sooner were 238% higher for those on high doses of APs (p<0.001) and 76% higher for individuals on high doses of cognitive enhancers (p<0.010). The use of APs at high doses was associated with the greatest risk of an adverse medical outcome in older adults with dementia with concurrent behavioral symptoms. Use of AP medications in this population should include close monitoring for cardiovascular/cerebrovascular events.

Haloperidol, Olanzapine, and Risperidone Induce Morphological Changes in an In Vitro Model of Human Hippocampal Neurogenesis.

Induced pluripotent stem cell (iPSC) based neuronal differentiation is valuable for studying neuropsychiatric disorders and pharmacological mechanisms at the cellular level. We aimed to examine the effects of typical and atypical antipsychotics on human iPSC-derived neural progenitor cells (NPCs). Proliferation and neurite outgrowth were measured by live cell imaging, and gene expression levels related to neuronal identity were analyzed by RT-QPCR and immunocytochemistry during differentiation into hippocampal dentate gyrus granule cells following treatment of low- and high-dose antipsychotics (haloperidol, olanzapine, and risperidone). Antipsychotics did not modify the growth properties of NPCs after 3 days of treatment. However, the characteristics of neurite outgrowth changed significantly in response to haloperidol and olanzapine. After three weeks of differentiation, mRNA expression levels of the selected neuronal markers increased (except for MAP2), while antipsychotics caused only subtle changes. Additionally, we found no changes in MAP2 or GFAP protein expression levels as a result of antipsychotic treatment. Altogether, antipsychotic medications promoted neurogenesis in vitro by influencing neurite outgrowth rather than changing cell survival or gene expression. This study provides insights into the effects of antipsychotics on neuronal differentiation and highlights the importance of considering neurite outgrowth as a potential target of action.

Association of somatic comorbidity and treatment adherence in patients with psychotic disorder

BackgroundIncreased risk for somatic comorbidity in individuals with schizophrenia has been well established. In addition, psychiatric patients with somatic illnesses are more likely to have more psychiatric readmissions. Increased burden of treatment related to chronic somatic comorbidities may be associated with lower adherence to psychiatric medication. MethodsCross-sectional study of 275 patients with schizophrenia spectrum disorder. A general practitioner performed a complete physical health checkup for all participants, including a complete medical examination and laboratory tests. Patients’ adherence, attitudes, insight, and side-effects were evaluated using the Attitudes toward Neuroleptic Treatment Scale. Overall symptomatology was measured using the Brief Psychiatric Rating Scale. Regression analysis was used to investigate interactions and associations among health beliefs, disease burden, and treatment adherence. Separate regression models were utilized to account for the complexity of health behavior and treatment adherence pathways. ResultsPatients’ somatic comorbidity and health behavior were not associated with adherence or attitudes toward antipsychotic treatment. High dose of antipsychotics and obesity were related to the need for medical interventions, while a healthy diet reduced the risk. Higher BPRS score and older age were associated with having somatic symptoms. Somatic comorbidities had no negative effects on treatment adherence or attitudes. ConclusionThis study focuses on exploring possible associations between health beliefs and treatment adherence pathways in patients with psychotic disorders. Contrary to our hypotheses, we found no evidence to support our health belief and diseases burden models and their associations.

Enlarged pituitary gland volume: a possible state rather than trait marker of psychotic disorders.

Enlarged pituitary gland volume could be a marker of psychotic disorders. However, previous studies report conflicting results. To better understand the role of the pituitary gland in psychosis, we examined a large transdiagnostic sample of individuals with psychotic disorders. The study included 751 participants (174 with schizophrenia, 114 with schizoaffective disorder, 167 with psychotic bipolar disorder, and 296 healthy controls) across six sites in the Bipolar-Schizophrenia Network on Intermediate Phenotypes consortium. Structural magnetic resonance images were obtained, and pituitary gland volumes were measured using the MAGeT brain algorithm. Linear mixed models examined between-group differences with controls and among patient subgroups based on diagnosis, as well as how pituitary volumes were associated with symptom severity, cognitive function, antipsychotic dose, and illness duration. Mean pituitary gland volume did not significantly differ between patients and controls. No significant effect of diagnosis was observed. Larger pituitary gland volume was associated with greater symptom severity (F = 13.61, p = 0.0002), lower cognitive function (F = 4.76, p = 0.03), and higher antipsychotic dose (F = 5.20, p = 0.02). Illness duration was not significantly associated with pituitary gland volume. When all variables were considered, only symptom severity significantly predicted pituitary gland volume (F = 7.54, p = 0.006). Although pituitary volumes were not increased in psychotic disorders, larger size may be a marker associated with more severe symptoms in the progression of psychosis. This finding helps clarify previous inconsistent reports and highlights the need for further research into pituitary gland-related factors in individuals with psychosis.

Schizophrenia patients discharged on antipsychotic polypharmacy from a public psychiatric hospital in Taiwan, 2006–2021

The aim of this study was to identify the factors associated with antipsychotic polypharmacy (APP), investigate whether APP could affect the risk of rehospitalization, and explore temporal trends in APP use. Schizophrenia patients discharged from the study hospital between 2006 and 2021 (n = 16,722) were included in the analysis. The logistic regression model was employed to determine the predictors significantly associated with APP use. Survival analysis was used to compare time to rehospitalization between APP and antipsychotic monotherapy (AMT). The temporal trend of APP use was analyzed using the Cochran-Armitage Trend test. In comparison with the patients (n = 10,909) who were discharged on AMT, those (n = 5,813) on APP were significantly more likely to be male gender, to receive LAIs, to take clozapine, to take anticholinergic agents, to have a greater number of previous hospitalizations, and to have a higher CPZ equivalent dose of antipsychotic prescription. The prescription rate of APP significantly increased from 18.4 % in 2006 to 44.9 % in 2021. Compared with AMT, APP was associated with more clozapine use, more LAI use, higher doses of antipsychotics, and an increased risk of rehospitalization. In addition, the prescription of APP continued to increase during the study period.

Decrease in cognitive performance and increase of the neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios with higher doses of antipsychotics in women with schizophrenia: a cross-sectional study

BackgroundWe explored the relationship between symptoms, cognitive performance, neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), and platelet-to-lymphocyte ratio (PLR) (three markers of inflammation), and antipsychotic dose (in chlorpromazine units) in male and female patients with schizophrenia.MethodsWe conducted a cross-sectional analysis in patients with schizophrenia of the complete blood count and the results of neuropsychological testing, using the Welch t-test to compare groups and the Pearson test for correlations.ResultsWe found that the NLR and the PLR are higher among women with schizophrenia when compared with men. In women, the NLR and the PLR correlate positively with antipsychotic drug dose and inversely with a working memory test (Direct Digit Span). Higher doses of antipsychotics are associated with worse working and semantic memory and mental flexibility in the women in our sample.ConclusionHigher doses of antipsychotics were associated with worse working and semantic memory and mental flexibility in women with schizophrenia. No such correlations were present in men, suggesting that, in female patients, cognitive performance deteriorates as the antipsychotic dose is increased, a finding that could be mediated by inflammatory mechanisms, given the demonstrated relationship to biomarkers of inflammation – e.g., the NLR and the PLR.Trial registrationNCT03788759 (ClinicalTrials.gov).

Development and acceptability testing of a decision aid for considering whether to reduce antipsychotics in individuals with stable schizophrenia.

Continued antipsychotic treatment is the key to preventing relapse. Maintenance antipsychotic monotherapy and optimal dose use are recommended for individuals with stable schizophrenia because of their undesirable effects. Decision aids (DAs) are clinical conversation tools that facilitate shared decision-making (SDM) between patients and health-care providers. This study aimed to describe the development process and results of acceptability testing of a DA for individuals with stable schizophrenia, considering (i) whether to continue high-dose antipsychotics or reduce to the standard dose and (ii) whether to continue two antipsychotics or shift to monotherapy. A DA was developed according to the guidelines for the appropriate use of psychotropic medications and International Patient Decision Aid Standards (IPDAS). First, a DA prototype was developed based on a previous systematic review and meta-analysis conducted for identifying the effects of continuing or reducing antipsychotic treatment. Second, mixed-method survey was performed among individuals with schizophrenia and health-care providers to modify and finalize the DA. The DA consisted of an explanation of schizophrenia, options to continue high-dose antipsychotics or reduce to the standard dose, options to continue two antipsychotics or shift to monotherapy, pros and cons of each option, and a value-clarification worksheet for each option. The patients (n = 20) reported acceptable language use (75%), adequate information (75%), and well-balanced presentation (79%). Health-care providers (n = 20) also provided favorable overall feedback. The final DA covered six IPDAS qualifying criteria. A DA was successfully developed for schizophrenia, considering whether to reduce antipsychotics, which can be used in the SDM process.

Prescription of High Dose of Antipsychotics in Two Rehabilitation Wards of Chronically Unwell Patients

AimsThe Royal College of Psychiatry (RCPsych) Consensus and the NICE guidelines have set out quality standards for the prescription of antipsychotics. There are concerns, however, regarding the over prescription across different psychiatric units: doses above BNF limits, multiple antipsychotics prescribed, lack of adequate monitoring of physical health and lack of availability of a clear rationale when high dose antipsychotic therapy (HDAT) is used. In the current audit, we sought to review the frequency HDAT is used in a female rehabilitation ward of patients with psychosis and a male rehabilitation ward of patients with dual diagnosis psychosis and/or autism. We also examined whether appropriate considerations are taken prior to prescribing HDAT and if the mandatory monitoring is in place when someone is on HDAT.MethodsA set of standards was set out and an audit tool was formulated that took the format of a table for data collection. Data were collected and anonymised, by looking at the medication charts and patients’ records, to identify if essential steps prior to/during HDAT prescribing are followed. All service users, 10 in each ward, that were in admission during the period between 7th and 13th November 2022, where included in the study.Data were compared directly with standards set out based on NICE guidelines and the RCPsych consensus. The data were input into Excel spreadsheet, then analysed and presented in tabular and graphs’ format.ResultsA total of 20 medication charts were reviewed over the five-day period. Only one out of ten individuals with ASD in Springs Centre was treated on HDAT and a clear rationale was documented to justify its use. All patients in both wards had the HDAT form and side effects scale form completed and filed. All patients had documentation of HDAT use on T2/T3 forms.40% of patients at Kenton Lodge were on HDAT. These patients required use of at least one depot due to lack of compliance. There was four patients overall treated on combination of antipsychotics. One patient did not have physical health monitoring at baseline due to refusing consent.ConclusionIn a small proportion of cases, HDAT may be justified, as long as the safety implications are considered and monitoring requirements observed.We recommend that audits of high dose antipsychotic prescribing can be performed periodically as a matter of routine practice. Also, to introduce a formal psychosis assessment scale to identify whether improvement has been accomplished since HDAT initiation.

Cognitive impairment in adults under compulsory psychiatric care: association with psychotic symptoms and high-dose antipsychotics

Background There is limited evidence on the association between cognitive function, psychotic symptoms and doses of antipsychotics in adults under compulsory psychiatric care. Aims We assessed (a) the degree of cognitive impairment in adults involuntarily hospitalised for compulsory psychiatric care and (b) correlation of Montreal Cognitive Assessment (MoCA) score with psychotic symptoms, polypharmacy and prescription of high-dose antipsychotics. Method This was a nationwide, cross-sectional study, conducted at the only referral state hospital for compulsory psychiatric care in Cyprus (December 2016–February 2018). Τhe MoCA was applied for the assessment of cognitive functioning. The Positive and Negative Syndrome Scale (PANSS) was applied for the assessment of psychotic symptoms. Results The sample comprised 187 men and 116 women. The mean MoCA score was 22.09 (reported scale range (RSR): 3–30); the mean PANSS general symptoms subscale score was 49.60 (RSR = 41–162). The participants who reported positive psychiatric history (mean 21.71, s.d. 5.37), non-adherence to pharmacotherapy (mean 21.32, s.d. 5.56) and prescription of high-dose antipsychotics (with medication prescribed as needed: mean 21.31, s.d. 5.70; without medication prescribed as needed: mean 20.71, s.d. 5.78) had lower mean MoCA scores compared with those who reported negative psychiatric history (mean 23.42, s.d. 4.51; P = 0.017), adherence to pharmacotherapy (mean 23.10, s.d. 6.61; P = 0.003) and no prescription of high-dose antipsychotics (with medication prescribed as needed: mean 22.56, s.d. 4.90; without medication prescribed as needed: mean 22.60 s.d. 4.94; P = 0.045–0.005), respectively. Mean MoCA score was mildly and inversely associated with total PANSS score (r = −0.15, P = 0.03), PANSS general (r = −0.18, P = 0.002) and PANSS negative (r = −0.16, P = 0.005) symptoms subscales, respectively. Conclusions Our findings support the evaluation of cognitive functioning in adults under compulsory psychiatric care via the MoCA tool, with focus on those prescribed high-dose antipsychotics, with positive mental health history and non-adherence to pharmacotherapy.

Risks of complicated acute appendicitis in patients with psychiatric disorders

BackgroundAcute appendicitis often presents with vague abdominal pain, which fosters diagnostic challenges to clinicians regarding early detection and proper intervention. This is even more problematic with individuals with severe psychiatric disorders who have reduced sensitivity to pain due to long-term or excessive medication use or disturbed bodily sensation perceptions. This study aimed to determine whether psychiatric disorder, psychotropic prescription, and treatment compliance increase the risks of complicated acute appendicitis.MethodsThe diagnosis records of acute appendicitis from four university hospitals in Korea were investigated from 2002 to 2020. A total of 47,500 acute appendicitis-affected participants were divided into groups with complicated and uncomplicated appendicitis to determine whether any of the groups had more cases of psychiatric disorder diagnoses. Further, the ratio of complicated compared to uncomplicated appendicitis in the mentally ill group was calculated regarding psychotropic dose, prescription duration, and treatment compliance.ResultsAfter adjusting for age and sex, presence of psychotic disorder (odds ratio [OR]: 1.951; 95% confidence interval [CI]: 1.218–3.125), and bipolar disorder (OR: 2.323; 95% CI: 1.194–4.520) was associated with a higher risk of having complicated appendicitis compared with absence of psychiatric disorders. Patients who are taking high-daily-dose antipsychotics, regardless of prescription duration, show high complicated appendicitis risks; High-dose antipsychotics for < 1 year (OR: 1.896, 95% CI: 1.077–3.338), high-dose antipsychotics for 1–5 years (OR: 1.930, 95% CI: 1.144–3.256). Poor psychiatric outpatient compliance was associated with a high risk of complicated appendicitis (OR: 1.664, 95% CI: 1.014–2.732).ConclusionsThis study revealed a close relationship in the possibility of complicated appendicitis in patients with severe psychiatric disorders, including psychotic and bipolar disorders. The effect on complicated appendicitis was more remarkable by the psychiatric disease entity itself than by psychotropic prescription patterns. Good treatment compliance and regular visit may reduce the morbidity of complicated appendicitis in patients with psychiatric disorders.

Psychotropic medication use in people living with severe and persistent mental illness in the Australian community: a cross-sectional study

BackgroundPsychotropic polypharmacy and high-dose prescribing may play a role in therapy, however, with associated risks. The aim of this study was to describe current prescribing practices and use of four psychotropic medication groups (antipsychotics, antidepressants, mood stabilisers and benzodiazepines), focusing on polypharmacy (across and within groups) and high-dose prescribing in adults experiencing severe and persistent mental illness (SPMI) in the Australian community.Methods318 people taking psychotropic medication for SPMI had a medication review undertaken by a community pharmacist. Participants were recruited as part of an RCT from three Australian states/territories between September 2020-July 2021. All psychotropic medication and daily doses were recorded and reviewed for alignment with current clinical guidelines. Univariate and multiple logistic regression models investigated factors associated with antipsychotic, antidepressant, and mood stabiliser polypharmacy, and antipsychotic and antidepressant high-dose therapy. Variables included age, gender, geographic location, self- reported mental illness(es), hospital admission(s) in previous 6-months and prescriber type.Results806 psychotropic medications were prescribed for the 318 participants. Mood stabiliser polypharmacy was recorded in 19.0% of participants prescribed mood stabilisers; antipsychotic polypharmacy in 18.4% of participants prescribed antipsychotics; antidepressant polypharmacy in 11.3% of those prescribed antidepressants; and three participants (5.1%) were prescribed two benzodiazepines concurrently. Almost 18.6% of the cohort was receiving high-dose treatment; 18 participants were prescribed high-dose antipsychotics and 39 high-dose antidepressants, with two participants prescribed both. Adjusted logistic regression for polypharmacy found male gender, psychiatrist as sole prescriber, or multiple prescribers, were associated with antipsychotic polypharmacy. The adjusted model for high-dose therapy found psychiatrist as sole prescriber was significantly associated with antipsychotic and antidepressant high-dose prescribing.ConclusionPsychotropic polypharmacy was common in this community cohort experiencing SPMI. Whilst polypharmacy is not always inappropriate, it is a complex construct with potential benefits alongside potential risks. Benefits and harms need to be balanced however this practice is not supported by clear guidance to assist health practitioners. This study highlights the important need for regular medication reviews and strengthened communication between consumers and all healthcare professionals involved in community mental health care, to support safe and effective use of psychotropic medications.

Antipsychotic Use and Risk of Low-Energy Fractures in People With Schizophrenia: A Nationwide Nested Case-Control Study in Finland.

Low-energy fractures (LEF) are more frequent in people with schizophrenia than the general population, and the role of prolactin-increasing antipsychotics is unknown. We conducted a nested case-control study using Finnish nationwide registers (inpatient, specialized outpatient care, prescription drug purchases). We matched each person with schizophrenia aged 16-85 years and incident LEF (cases) with 5 age/sex/illness duration-matched controls with schizophrenia, but no LEF. We investigated the association between cumulative exposure (duration, and Defined Daily Doses, DDDs) to prolactin-increasing/sparing antipsychotics and LEF. Adjusted conditional logistic regression analyses were performed. Sensitivity analyses were conducted. Out of 61 889 persons with schizophrenia between 1972 and 2014, we included 4960 cases. Compared with 24 451 controls, 4 years or more of exposure to prolactin-increasing antipsychotics was associated with increased risk of LEF (adjusted odds ratio (aOR) from aOR = 1.22, 95%CI = 1.09-1.37 to aOR = 1.38, 95%CI = 1.22-1.57, for 4-< 7 />13 years of exposure, respectively), without a significant association for prolactin-sparing antipsychotics. All cumulative doses higher than 1000 DDDs of prolactin-increasing antipsychotics were associated with LEF (from aOR = 1.21, 95%CI = 1.11-1.33, 1000-<3000 DDDs, to aOR = 1.64, 95%CI = 1.44-1.88, >9000 DDDs). Only higher doses of prolactin-sparing antipsychotics reached statistical significance (aOR = 1.24, 95%CI = 1.01-1.52, 6000-<9000 DDDs, aOR = 1.45, 95%CI = 1.13-1.85, >9000 DDDs). Sensitivity analyses confirmed the main analyses for prolactin-increasing antipsychotics. For prolactin-sparing antipsychotics, significant associations were limited to extreme exposure, major LEF, older age group, and males. Long-term exposure to prolactin-increasing antipsychotics at any dose, and high cumulative doses of prolactin-sparing antipsychotics is associated with significantly increased odds of LEF. Monitoring and addressing hyperprolactinemia is paramount in people with schizophrenia receiving prolactin-increasing antipsychotics.

Managing treatment resistance in schizophrenia: A joint study in Hong Kong and Singapore

This study surveyed clinicians in psychiatry in Hong Kong and Singapore to understand their familiarity and prescribing practices in treatment-resistant schizophrenia (TRS) and clozapine-resistant schizophrenia (CRS). All clinicians in psychiatry in both regions were invited through email to participate in an anonymous online survey. The survey collected information on the participants' characteristics, their familiarity and experience with clozapine use, and their treatment practices in TRS and CRS. Data collection took place between September 2019 and February 2020 in Hong Kong and December 2018 and March 2019 in Singapore. 261 clinicians responded to the survey, with response rates of 19% (105 out of 556 participants) in Hong Kong and 50% (156 out of 309 participants) in Singapore. The majority of respondents (99.0% in Hong Kong; 87.9% in Singapore) were familiar with treatment guidelines for TRS. However, approximately half (54.2% in Hong Kong; 41.7% in Singapore) delayed the prescription of clozapine when indicated. In terms of alternatives to clozapine, approximately half or more of the clinicians in both regions would use high dose antipsychotics, long-acting injectable antipsychotics, antipsychotic polypharmacy, while the adjuvant use of mood stabilizers and electroconvulsive therapy differed between the two regions. In those with CRS, between 10 and 20% of the respondents added adjuvant mood stabilizers or antipsychotics, and 3-10% would use an antidepressant. Clozapine delays occur in spite of clinicians' familiarity with treatment guidelines. More research is needed to guide the use of augmentation strategies and the search for effective treatments beyond clozapine.

Pharmacological management of psychopathology in people with intellectual disabilities and/or autism spectrum disorder

SUMMARYOn average, 49–63% of people with intellectual disabilities and/or autism spectrum disorder (ASD) are prescribed psychotropic medications to treat psychopathology, including psychiatric illness, behaviours that challenge and the core symptoms and associated behaviours of these developmental disorders. In many cases, psychotropics, particularly antipsychotics, are used off-label without a proper indication, particularly to manage behaviours that challenge. The RCTs show moderate evidence supporting the efficacy of low-dose risperidone and some preliminary evidence for aripiprazole in treating behaviours that challenge among children with ASD and/or intellectual disabilities. The RCT-based evidence for the other psychotropics is equivocal, so no definitive conclusions can be made on their efficacy. Polypharmacy and the use of high doses of antipsychotics are prevalent in this population, leading to the risk of adverse events and drug–drug interactions. Despite various national and international guidelines, and government initiatives encouraging reduced psychotropic use, there is little evidence of this happening; on the contrary, the use of antidepressants, mood stabilisers and benzodiazepines may be increasing. A concerted multi-agency effort is urgently needed to address this significant public health concern of the overmedication of people with intellectual disabilities and/or ASD.

Analyze the Influencing Factors and Predictability of Metabolic Syndrome in Schizophrenic Patients Treated with Olanzapine through Decision Tree Model

Abstract: Olanzapine is a typical antipsychotic that has demonstrated efficacy for the treatment of schizophrenia, but the patients treated with olanzapine usually appear it’s specific adverse events such as metabolism. It shows some factors that may affect metabolism such as age, BMI, high-dose antipsychotics, etc. Up to now the main predictors for metabolism in a patient with schizophrenia have not been comprehensively evaluated. Subjects and research methods: In this prospective cohort study, a total of 202 inpatients with schizophrenia at Vietnamese National Psychiatric Hospital No1 were included. The univariate regression and decision tree model were applied to find out the statistically significant factors. Results: The factors influencing metabolism were: baseline waist, baseline triglyceride, baseline HDL, age, baseline BMI, baseline metabolism, cholesterol ≥6.2 history, and schizophrenia duration. The final decision tree model included 3 important nodes: baseline waist &lt; 89 cm, baseline triglyceride &lt;3.1 mmol/l, age &lt;36. The predictive accuracy and other parameters were good to be able to apply for predictive purposes: accuracy 0.88, precision 0.90, recall 0.69, f1-score 0.78. Conclusion: The final model was good to predict no metabolism (0 code). In contrast, it is necessary to verify the metabolism status and have appropriate routine monitoring.&#x0D; Keywords: Metabolism, schizophrenia, olanzapine, predictive model, decision tree model.

Machine-Learning for Prescription Patterns: Random Forest in the Prediction of Dose and Number of Antipsychotics Prescribed to People with Schizophrenia.

ObjectiveWe aimed to predict antipsychotic prescription patterns for people with schizophrenia using machine learning (ML) algorithms.MethodsIn a cross-sectional design, a sample of community mental health service users (SUs; n = 368) with a primary diagnosis of schizophrenia was randomly selected. Socio-demographic and clinical features, including the number, total dose, and route of administration of the antipsychotic treatment were recorded. Information about the number and the length of psychiatric hospitalization was retrieved. Ordinary Least Square (OLS) regression and ML algorithms (i.e., random forest [RF], supported vector machine, K-nearest neighborhood, and Naïve Bayes) were used to estimate the predictors of total antipsychotic dosage and prescription of antipsychotic polytherapy (APP).ResultsThe strongest predictor of the total dose was APP. The number of Community Mental Health Centers (CMHC) contacts was the most important predictor of APP and, with APP omitted, of dosage. Treatment with anticholinergics predicted APP, emphasizing the strong correlation between APP and higher antipsychotic dose. RF performed better than OLS regression and the other ML algorithms in predicting both antipsychotic dose (root square mean error = 0.70, R2 = 0.31) and APP (area under the receiving operator curve = 0.66, true positive rate = 0.41, and true negative rate = 0.78).ConclusionAPP is associated with the prescription of higher total doses of antipsychotics. Frequent attenders at CMHCs, and SUs recently hospitalized are often treated with APP and higher doses of antipsychotics. Future prospective studies incorporating standardized clinical assessments for both psychopathological severity and treatment efficacy are needed to confirm these findings.