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BMC Medicine Jun 2024Among patients diagnosed with schizophrenia, the presence of substance use poses an aggravating comorbidity, exerting a negative impact on the course of the disease,...
BACKGROUND
Among patients diagnosed with schizophrenia, the presence of substance use poses an aggravating comorbidity, exerting a negative impact on the course of the disease, adherence to therapeutic regimens, treatment outcomes, duration of hospital stays, and the frequency of hospitalizations. The primary objective of the present study is to investigate the relationship between comorbid substance use disorders, antipsychotic treatment, and the length of stay in individuals hospitalized for treatment of schizophrenia.
METHODS
We conducted a retrospective analysis of electronic health records spanning a 12-month period, specifically focusing on adult patients diagnosed with schizophrenia who were discharged from the University Hospital of Psychiatry Zurich between January and December 2019. We documented the number and types of diagnosed substance use disorder, the antipsychotic treatment, the length of stay, and the number of previous hospitalizations for each patient.
RESULTS
Over a third (n = 328; 37.1%) of patients with schizophrenia had comorbid substance use with cannabis being the most frequent consumed substance. Patients with substance use (either single or multiple) were more frequently hospitalized; those with multiple substance use more frequently than those with a single substance use (F(2, 882) = 69.06; p < 0.001). There were no differences regarding the rate of compulsory admission. Patients with no substance use had a lower HoNOS score at discharge (F(2, 882) = 4.06). Patients with multiple substance use had a shorter length of stay (F(2, 882) = 9.22; p < 0.001), even after adjusting for duration of illness, previous hospitalizations, diagnosis, and antipsychotic treatment.
CONCLUSIONS
In patients with schizophrenia, comorbid single or multiple substance use has a relevant negative impact on treatment and thus on the course of disease. Substance use in patients with schizophrenia should therefore receive special attention in order to reduce re-hospitalization rates and improve the clinical outcome.
Topics: Humans; Retrospective Studies; Schizophrenia; Male; Length of Stay; Female; Adult; Substance-Related Disorders; Middle Aged; Antipsychotic Agents; Comorbidity; Hospitalization; Switzerland; Young Adult
PubMed: 38853281
DOI: 10.1186/s12916-024-03447-3 -
Actas Dermo-sifiliograficas Jun 2024
PubMed: 38852843
DOI: 10.1016/j.ad.2023.07.032 -
Current Opinion in Psychiatry Jun 2024People with schizophrenia experience three to five times higher prevalence of diabetes and obesity than the general population, contributing to a 20-year reduced...
PURPOSE OF REVIEW
People with schizophrenia experience three to five times higher prevalence of diabetes and obesity than the general population, contributing to a 20-year reduced lifespan. The impacts of weight gain extend beyond physical health, affecting people's self-esteem, quality of life, and triggering treatment nonadherence, leading to relapse and deteriorations in health. Clinical guidelines recommend patients with antipsychotic-induced weight gain are treated with cognitive behaviour therapy and lifestyle changes; however, effective treatments for obesity in schizophrenia are critically lacking. Glucagon-like peptide-1 receptor agonists (GLP-RAs) have shown large effects in weight loss in the general population; however, effects are less clear in people with schizophrenia. This review aims to assess the clinical trials that have been completed, are in progress, and directions for future trials.
RECENT FINDINGS
To date, six clinical trials have been completed, four of which have published their findings. Three further trials are currently in progress.
SUMMARY
Results from completed trials suggest that GLP-1RAs decrease weight in people with schizophrenia, however effect sizes are mostly smaller than studies based on the general population. Future trials could focus on dual or triple agonist agents, and/or explore the effects of GLP-1 s at antipsychotic medication commencement, to potentially prevent antipsychotic weight gain.
PubMed: 38847529
DOI: 10.1097/YCO.0000000000000952 -
Juntendo Iji Zasshi = Juntendo Medical... 2023Alongside non-pharmacological intervention, pharmacotherapy particularly with atypical antipsychotics is assumed to be effective for behavioral and psychological...
Pharmacotherapy in Patients with Alzheimer-type Dementia Presenting with Behavioral and Psychological Symptoms of Dementia: A Retrospective Chart Review of 102 Patients Available for 12-month Follow-up after Initiation of Treatment.
OBJECTIVES
Alongside non-pharmacological intervention, pharmacotherapy particularly with atypical antipsychotics is assumed to be effective for behavioral and psychological symptoms of dementia (BPSD).
METHODS
This retrospective study investigated the effectiveness and safety of pharmacotherapy including antipsychotics in outpatients or inpatients with BPSD.
RESULTS
Of all Alzheimer-type dementia (AD) patients with BPSD initiating treatment between March and August 2011, a total of 102 patients available for 12-month follow-up comprised the subjects in this chart review. Of these, 68 (66.7%) continued treatment in the ambulatory or inpatient setting, with their MMSE scores improved from 17.3 ± 3.6 at baseline to 18.3 ± 3.53, 17.9 ± 3.80 and 17.0 ± 4.14 after 3, 6 and 12 months, respectively. In contrast, their NPI scores were significantly different from 11.7 ± 11.2 at baseline to 4.86 ± 5.40, 3.56 ± 4.65 and 2.27 ± 3.77 after 3, 6 and 12 months, respectively. Of the 36 inpatients available for follow-up, 27 (75%) on concurrent antipsychotics (chlorpromazine [CP] equivalent, 162.2 mg) at baseline remained on concurrent antipsychotics (CP equivalent, 212.5 mg) after 12 months, while, of the 66 outpatients available for follow-up, 13 (19.7%) on concurrent antipsychotics (CP equivalent, 93.4 mg) at baseline remained on concurrent antipsychotics (CP equivalent, 113.0 mg) after 12 months.
CONCLUSIONS
Study results confirmed the effectiveness and safety of the study treatment in Japanese AD patients with BPSD for up to 12 months. How best to incorporate antipsychotics into the treatment of BPSD in clinical settings lies in the hands of us Japanese clinicians.
PubMed: 38845733
DOI: 10.14789/jmj.JMJ22-0024-OA -
Scientific Reports Jun 2024One third of people with psychosis become antipsychotic treatment-resistant and the underlying mechanisms remain unclear. We investigated whether altered cognitive...
One third of people with psychosis become antipsychotic treatment-resistant and the underlying mechanisms remain unclear. We investigated whether altered cognitive control function is a factor underlying development of treatment resistance. We studied 50 people with early psychosis at a baseline visit (mean < 2 years illness duration) and follow-up visit (1 year later), when 35 were categorized at treatment-responsive and 15 as treatment-resistant. Participants completed an emotion-yoked reward learning task that requires cognitive control whilst undergoing fMRI and MR spectroscopy to measure glutamate levels from Anterior Cingulate Cortex (ACC). Changes in cognitive control related activity (in prefrontal cortex and ACC) over time were compared between treatment-resistant and treatment-responsive groups and related to glutamate. Compared to treatment-responsive, treatment-resistant participants showed blunted activity in right amygdala (decision phase) and left pallidum (feedback phase) at baseline which increased over time and was accompanied by a decrease in medial Prefrontal Cortex (mPFC) activity (feedback phase) over time. Treatment-responsive participants showed a negative relationship between mPFC activity and glutamate levels at follow-up, no such relationship existed in treatment-resistant participants. Reduced activity in right amygdala and left pallidum at baseline was predictive of treatment resistance at follow-up (67% sensitivity, 94% specificity). The findings suggest that deterioration in mPFC function over time, a key cognitive control region needed to compensate for an initial dysfunction within a social-emotional network, is a factor underlying development of treatment resistance in early psychosis. An uncoupling between glutamate and cognitive control related mPFC function requires further investigation that may present a future target for interventions.
Topics: Humans; Prefrontal Cortex; Male; Female; Psychotic Disorders; Adult; Magnetic Resonance Imaging; Cognition; Young Adult; Glutamic Acid; Antipsychotic Agents; Gyrus Cinguli
PubMed: 38839828
DOI: 10.1038/s41598-024-63474-1 -
Journal of Psychosocial Nursing and... Jun 2024
Topics: Humans; Bipolar Disorder; United States; United States Food and Drug Administration; Drug Approval; Antipsychotic Agents; Antimanic Agents
PubMed: 38838336
DOI: 10.3928/02793695-20240422-79 -
CNS Drugs Jul 2024BACKGROUND AND OBJECTIVES: Clozapine is the medication of choice for treatment-resistant schizophrenia. However, it has a complex metabolism and unexplained...
UNLABELLED
BACKGROUND AND OBJECTIVES: Clozapine is the medication of choice for treatment-resistant schizophrenia. However, it has a complex metabolism and unexplained interindividual variability. The current work aims to develop a pharmacokinetic model of clozapine and norclozapine in non-smokers and assess the impact of demographic and genetic predictors.
METHODS
Healthy volunteers were recruited in a population pharmacokinetic study. Blood samples were collected at 30 min and 1, 2, 3, 5 and 8 h following a single flat dose of clozapine (12.5 mg). The clozapine and norclozapine concentrations were measured via high-performance liquid chromatography-ultraviolet method. A semi-physiological pharmacokinetic model of clozapine and norclozapine was developed using nonlinear mixed-effects modeling. Clinical and genetic predictors were evaluated, including CYP1A2 (rs762551) and ABCB1 (rs2032582), using restriction fragment length polymorphism.
RESULTS
A total of 270 samples were collected from 33 participants. The data were best described using a two-compartment model for clozapine and a two-compartment model for norclozapine with first-order absorption and elimination and pre-systemic metabolism. The estimated (relative standard error) clearance of clozapine and norclozapine were 27 L h (31.5 %) and 19.6 L h (30%), respectively. Clozapine clearance was lower in sub-Saharan Africans (n = 4) and higher in Caucasians (n = 9) than Asians (n = 20). Participants with CYP1A2 (rs762551) (n = 18) and ABCB1 (rs2032582) (n = 12) mutant alleles had lower clozapine clearance in the univariate analysis.
CONCLUSIONS
This is the first study to develop a semi-physiological pharmacokinetic model of clozapine and norclozapine accounting for the pre-systemic metabolism. Asians required lower doses of clozapine as compared with Caucasians, while clozapine pharmacokinetics in sub-Saharan Africans should be further investigated in larger trials.
Topics: Clozapine; Humans; Adult; Male; Antipsychotic Agents; Female; Cytochrome P-450 CYP1A2; Young Adult; Models, Biological; Healthy Volunteers; ATP Binding Cassette Transporter, Subfamily B; Middle Aged
PubMed: 38836990
DOI: 10.1007/s40263-024-01092-1 -
The Journal of Clinical Psychiatry Jun 2024Women veterans are more likely than men veterans to receive medications that Department of Veterans Affairs clinical practice guidelines recommend against to treat...
Women veterans are more likely than men veterans to receive medications that Department of Veterans Affairs clinical practice guidelines recommend against to treat posttraumatic stress disorder (PTSD). To understand this difference, we examined potential confounders in incident prescribing of guideline discordant medications (GDMs) in veterans with PTSD. Veterans receiving care for PTSD during 2020 were identified using Veterans Health Administration administrative data. PTSD diagnosis was established by the presence of at least 1 coded outpatient encounter or inpatient hospitalization during the calendar year 2020. Incident GDM prescribing was assessed during 2021, including benzodiazepines, antipsychotics, select anticonvulsants, and select antidepressants. Log-binomial regression was used to estimate the difference in risk for GDM initiation between men and women, adjusted for patient, prescriber, and facility-level covariates, and to identify key confounding variables. Of 704,699 veterans with PTSD, 16.9% of women and 10.1% of men initiated a GDM, an increased risk of 67% for women [relative risk (RR) = 1.67; 95% CI, 1.65-1.70]. After adjustment, the gender difference decreased to 1.22 (95% CI, 1.20-1.24) in a fully specified model. Three key confounding variables were identified: bipolar disorder (RR = 1.60; 95% CI, 1.57-1.63), age (<40 years: RR = 1.20 [1.18-1.22]; 40-54 years: RR = 1.13 [1.11-1.16]; ≥65 years: RR = 0.64 [0.62-0.65]), and count of distinct psychiatric medications prescribed in the prior year (RR = 1.14; 1.13-1.14). Women veterans with PTSD were 67% more likely to initiate a GDM, where more than half of this effect was explained by bipolar disorder, age, and prior psychiatric medication. After adjustment, women veterans remained at 22% greater risk for an incident GDM, suggesting that other factors remain unidentified and warrant further investigation.
Topics: Humans; Female; Stress Disorders, Post-Traumatic; Male; Veterans; Middle Aged; United States; Adult; Sex Factors; United States Department of Veterans Affairs; Practice Guidelines as Topic; Aged; Practice Patterns, Physicians'; Guideline Adherence; Antidepressive Agents; Antipsychotic Agents
PubMed: 38836865
DOI: 10.4088/JCP.23m15174 -
The Mental Health Clinician Jun 2024Clozapine is the only antipsychotic approved for treatment-resistant schizophrenia, but without appropriate monitoring, it can be associated with potentially fatal...
INTRODUCTION
Clozapine is the only antipsychotic approved for treatment-resistant schizophrenia, but without appropriate monitoring, it can be associated with potentially fatal outcomes. An International Adult Clozapine Titration Guideline categorizes patients into normal or slow metabolizers. Categorization provides clozapine titration schedules and recommends regular c-reactive protein (CRP) and clozapine concentration monitoring to reduce the risk of adverse drug reactions (ADRs). The impact of the guideline on clozapine ADRs has not been evaluated.
METHODS
A retrospective chart review assessed clozapine titrations, laboratory monitoring, ADRs, and discontinuations for clozapine-naive adult inpatients at a single center from January 1, 2013, to June 1, 2022. Each patient's cumulative weekly clozapine dosage was compared with their guideline recommended dosage to create a percent accordance. Linear logistic regression evaluated the relationship between titration speed and the presence of an ADR, while descriptive statistics analyzed laboratory monitoring.
RESULTS
Forty-three patients were included, with the majority being White males with schizophrenia. An inverse relationship existed between the last inpatient week clozapine dose percent accordance and the probability of an ADR. Nonobese patients were less likely than obese patients to experience an ADR (odds ratio = 0.17; 95% CI, 0.03-0.99). CRP and clozapine concentration monitoring was suboptimal.
DISCUSSION
Based on our small retrospective review of primarily White males, more aggressive clozapine titrations did not increase ADRs. Future studies with more diverse samples are needed and should focus on specific ADRs, which may have increased occurrence with rapid titrations. Obese patients were at higher risk of ADRs, correlating with the guideline-recommended slower titrations for these patients.
PubMed: 38835819
DOI: 10.9740/mhc.2024.06.204 -
Psychiatry Research Aug 2024An association between psychiatric medications and falls and fractures in people taking them has been demonstrated, but which class or medication leads to the greatest... (Meta-Analysis)
Meta-Analysis Comparative Study Review
An association between psychiatric medications and falls and fractures in people taking them has been demonstrated, but which class or medication leads to the greatest risk of falls or fractures should be further investigated. The aim of this study was to compare and rank the magnitude of risk of falls and fractures due to different psychiatric medications. Eight databases were searched for this meta-analysis and evaluated using a frequency-based network meta-analysis. The results included a total of 28 papers with 14 medications from 5 major classes, involving 3,467,314 patients. The results showed that atypical antipsychotics were the class of medications with the highest risk of falls, and typical antipsychotics were the class of medications with the highest risk of resulting in fractures. Quetiapine ranked first in the category of 13 medications associated with risk of falls, and class Z drugs ranked first in the category of 6 medications associated with risk of fractures. The available evidence suggests that atypical antipsychotics and typical antipsychotics may be the drugs with the highest risk of falls and fractures, respectively. Quetiapine may be the medication with the highest risk of falls, and class Z drugs may be the medication with the highest risk of fractures.
Topics: Humans; Accidental Falls; Antipsychotic Agents; Fractures, Bone; Network Meta-Analysis
PubMed: 38833938
DOI: 10.1016/j.psychres.2024.115974