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3.
J Clin Psychiatry ; 85(2)2024 Jun 05.
Article in English | MEDLINE | ID: mdl-38836865

ABSTRACT

Objectives: 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.Methods: 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 ICD-10 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.Results: 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).Conclusions: 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.


Subject(s)
Stress Disorders, Post-Traumatic , United States Department of Veterans Affairs , Veterans , Humans , Female , Stress Disorders, Post-Traumatic/epidemiology , Stress Disorders, Post-Traumatic/drug therapy , Male , Veterans/statistics & numerical data , Veterans/psychology , Middle Aged , United States/epidemiology , Adult , Sex Factors , United States Department of Veterans Affairs/statistics & numerical data , Practice Guidelines as Topic , Aged , Practice Patterns, Physicians'/statistics & numerical data , Guideline Adherence/statistics & numerical data , Antidepressive Agents/therapeutic use , Antipsychotic Agents/therapeutic use
4.
Sci Rep ; 14(1): 12985, 2024 06 06.
Article in English | MEDLINE | ID: mdl-38839828

ABSTRACT

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.


Subject(s)
Cognition , Magnetic Resonance Imaging , Prefrontal Cortex , Psychotic Disorders , Humans , Prefrontal Cortex/metabolism , Prefrontal Cortex/physiopathology , Prefrontal Cortex/diagnostic imaging , Male , Female , Psychotic Disorders/metabolism , Psychotic Disorders/drug therapy , Psychotic Disorders/physiopathology , Adult , Young Adult , Glutamic Acid/metabolism , Antipsychotic Agents/therapeutic use , Antipsychotic Agents/pharmacology , Gyrus Cinguli/metabolism , Gyrus Cinguli/diagnostic imaging , Gyrus Cinguli/physiopathology
5.
BMC Med ; 22(1): 233, 2024 Jun 10.
Article in English | MEDLINE | ID: mdl-38853281

ABSTRACT

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.


Subject(s)
Antipsychotic Agents , Length of Stay , Schizophrenia , Substance-Related Disorders , Humans , Retrospective Studies , Schizophrenia/epidemiology , Schizophrenia/drug therapy , Male , Female , Adult , Substance-Related Disorders/epidemiology , Middle Aged , Antipsychotic Agents/therapeutic use , Comorbidity , Hospitalization/statistics & numerical data , Switzerland/epidemiology , Young Adult
7.
J Manag Care Spec Pharm ; 30(6): 549-559, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38824623

ABSTRACT

BACKGROUND: Schizophrenia and schizoaffective disorder require long-term antipsychotic treatment with antipsychotic medications, but poor medication adherence can lead to increased health care utilization and costs. Long-acting injectable antipsychotics (LAIs) offer potential therapeutic advantages in that they require less frequent dosing and improved medication adherence. South Carolina has the highest adoption of LAIs among US states, making it an ideal population for comparing the effectiveness of LAIs vs oral antipsychotics (OAPs) in treating schizophrenia or schizoaffective disorder. OBJECTIVE: To evaluate the effect of LAIs compared with OAPs on medication adherence, health care resource utilization, and costs among South Carolina Medicaid beneficiaries with schizophrenia or schizoaffective disorder. METHODS: South Carolina Medicaid beneficiaries with at least 1 claim for an LAI or OAP between January 1, 2015, and December 31, 2018, aged 18 to 65, with at least 2 claims with diagnoses of schizophrenia or schizoaffective disorder were included. Propensity scores (PSs) were calculated using logistic regression adjusting for confounders and predictors of the outcome. We estimated the "average treatment effect on the treated" by employing PS-weighted t-tests and chi-square tests. RESULTS: A total of 3,531 patients met the inclusion criteria, with 1,537 (44.5%) treated with LAIs and 1,994 (56.5%) treated with OAPs. In PS-weighted analyses, the LAI cohort had a greater proportion of days covered than the OAP cohort with a 365-day fixed denominator (69% vs 64%; P < 0.0001), higher medication possession ratio with a variable denominator while on therapy (85% vs 80%; P < 0.0001), and higher persistence (82% vs 64%; P < 0.0001). The average number of inpatient visits and emergency department visits did not significantly differ between cohorts (0.28 hospitalizations, P = 0.90; 3.68 vs 2.96 emergency department visits, P = 0.19). The number of outpatient visits, including visits for medication administration, were greater in the LAI cohort (23.1 [SD 24.2]) vs OAP (16.9 [SD 21.2]; P < 0.0001); however, including the costs for medication administration visits, outpatient costs (per member) were approximately $2,500 lower in the LAI cohort (P < 0.0001). The number of pharmacy visits was greater in the OAP cohort (LAI 21.0 [SD 17.0] vs OAP 23.0 [SD 15.0]; P = 0.006). All-cause total costs were greater in the LAI cohort ($26,025 [SD $29,909]) vs the OAP cohort ($17,291 [SD $25,261]; P < 0.0001) and were driven by the difference in pharmaceutical costs (LAI $15,273 [SD $16,183] vs OAP $4,696 [SD $10,371]; P < 0.0001). CONCLUSIONS: Among South Carolina Medicaid beneficiaries, treatment with LAIs for schizophrenia or schizoaffective disorder was associated with greater medication adherence rates. Patients using LAIs had higher drug costs and total costs, but lower outpatient and total nondrug costs compared with those using OAPs.


Subject(s)
Antipsychotic Agents , Delayed-Action Preparations , Medicaid , Medication Adherence , Patient Acceptance of Health Care , Schizophrenia , Humans , Antipsychotic Agents/economics , Antipsychotic Agents/administration & dosage , Antipsychotic Agents/therapeutic use , Medicaid/economics , Medicaid/statistics & numerical data , Schizophrenia/drug therapy , Schizophrenia/economics , Male , Female , Adult , Medication Adherence/statistics & numerical data , United States , Middle Aged , South Carolina , Administration, Oral , Young Adult , Patient Acceptance of Health Care/statistics & numerical data , Adolescent , Retrospective Studies , Aged , Injections , Health Care Costs/statistics & numerical data , Psychotic Disorders/drug therapy , Psychotic Disorders/economics
9.
Eur. j. psychiatry ; 38(2): [100229], Apr.-Jun. 2024.
Article in English | IBECS | ID: ibc-231864

ABSTRACT

Background and objectives Alterations in the molecular mechanisms of specific amino acids (AAs) may be implicated in the pathophysiology of schizophrenia (SZ). However, little is known about antipsychotic drugs influence on levels of AAs. This study aimed to further explore antipsychotics' effects on AAs and serum lipid levels in first-episode SZ. Methods Eighty subjects with the International Classification of Diseases, Tenth Edition (ICD-10) criteria-defined SZ were enrolled. The levels of 31 AAs were measured in plasma samples using ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Results Ten AAs (i.e., citrulline, sarcosine, tyrosine, leucine, proline, hydroxyproline, kynurenine, tryptophan, valine and isoleucine) were observed to be higher and three AAs (i.e., GABA, aminobutyric acid and asparaginic acid) were lower in 80 patients with first-episode SZ after various antipsychotics treatment. In addition, there were 1 out of 31 AAs altered after olanzapine treatment and there were only 2 out of 31 AAs altered after risperidone treatment. Furthermore, serum triglyceride (TG) was markedly upregulated after olanzapine treatment, while Apolipoprotein A1 (ApoA1) was generally upregulated after risperidone treatment in patients with first-episode SZ. Conclusions Taken together, antipsychotic treatment can affect the plasma levels of AAs in patients with first-episode SZ, and olanzapine and risperidone have differential effects on the levels of AAs. (AU)


Subject(s)
Humans , Male , Female , Adolescent , Young Adult , Adult , Middle Aged , Aged , Antipsychotic Agents/therapeutic use , Amino Acids , Schizophrenia/drug therapy , Prospective Studies
10.
BMC Health Serv Res ; 24(1): 574, 2024 May 03.
Article in English | MEDLINE | ID: mdl-38702737

ABSTRACT

BACKGROUND: Audit and feedback (A/F), which include initiatives like report cards, have an inconsistent impact on clinicians' prescribing behavior. This may be attributable to their focus on aggregate prescribing measures, a one-size-fits-all approach, and the fact that A/F initiatives rarely engage with the clinicians they target. METHODS: In this study, we describe the development and delivery of a report card that summarized antipsychotic prescribing to publicly-insured youth in Philadelphia, which was introduced by a Medicaid managed care organization in 2020. In addition to measuring aggregate prescribing behavior, the report card included different elements of care plans, including whether youth were receiving polypharmacy, proper medication management, and the concurrent use of behavioral health outpatient services. The A/F initiative elicited feedback from clinicians, which we refer to as an "audit and feedback loop." We also evaluate the impact of the report card by comparing pre-post differences in prescribing measures for clinicians who received the report card with a group of clinicians who did not receive the report card. RESULTS: Report cards indicated that many youth who were prescribed antipsychotics were not receiving proper medication management or using behavioral health outpatient services alongside the antipsychotic prescription, but that polypharmacy was rare. In their feedback, clinicians who received report cards cited several challenges related to antipsychotic prescribing, such as the logistical difficulties of entering lab orders and family members' hesitancy to change care plans. The impact of the report card was mixed: there was a modest reduction in the share of youth receiving polypharmacy following the receipt of the report card, while other measures did not change. However, we documented a large reduction in the number of youth with one or more antipsychotic prescription fill among clinicians who received a report card. CONCLUSIONS: A/F initiatives are a common approach to improving the quality of care, and often target specific practices such as antipsychotic prescribing. Report cards are a low-cost and feasible intervention but there is room for quality improvement, such as adding measures that track medication management or eliciting feedback from clinicians who receive report cards. To ensure that the benefits of antipsychotic prescribing outweigh its risks, it is important to promote quality and safety of antipsychotic prescribing within a broader care plan.


Subject(s)
Antipsychotic Agents , Medicaid , Practice Patterns, Physicians' , Humans , Antipsychotic Agents/therapeutic use , United States , Philadelphia , Adolescent , Practice Patterns, Physicians'/statistics & numerical data , Male , Female , Patient Care Planning , Polypharmacy
11.
Pak J Pharm Sci ; 37(1(Special)): 245-255, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38747276

ABSTRACT

Aripiprazole (ARI), an antipsychotic having low solubility and stability. To overcome this, formation of binary and ternary using inclusion complexes of Methyl-ß-cyclodextrin (MßCD) /Hydroxy propyl beta cyclodextrin (HPßCD) and L-Arginine (ARG)/ Lysine (LYS) are analyzed by dissolution testing and phase stability study along with their complexation efficacy and solubility constants made by physical mixing. Inclusion complexes with ARG were better than LYS and prepared by solvent evaporation and lyophilization method as well. They are characterized by Attenuated Total Reflection Fourier Transform Infrared Spectroscopy (AT-FTIR), X-ray powder diffractometry (XRD), Differential Scanning Calorimetry (DSC), Scanning electron microscopy (SEM) and Thermal gravimetric analysis (TGA). The bond shifting in AT-FTIR confirmed the molecular interactions between host and guest molecules. The SEM images also confirmed a complete change of drug morphology in case of ternary inclusion complexes prepared by lyophilization method for both the polymers. ARI: MßCD: ARG when used in the specific molar ratio of 1:1:0.27 by prepared by lyophilization method has 18 times best solubility while ARI:HPßCD:ARG was 7 times best solubility than pure drug making MßCD a better choice than HPßCD. Change in the molar ratio will cause loss of stability or solubility. Solvent evaporation gave significant level of solubility but less stability.


Subject(s)
2-Hydroxypropyl-beta-cyclodextrin , Arginine , Aripiprazole , Calorimetry, Differential Scanning , Lysine , Solubility , beta-Cyclodextrins , Aripiprazole/chemistry , Arginine/chemistry , beta-Cyclodextrins/chemistry , 2-Hydroxypropyl-beta-cyclodextrin/chemistry , Lysine/chemistry , Spectroscopy, Fourier Transform Infrared , X-Ray Diffraction , Freeze Drying , Antipsychotic Agents/chemistry , Drug Stability , Microscopy, Electron, Scanning , Drug Compounding , Chemistry, Pharmaceutical/methods
12.
J Clin Psychiatry ; 85(2)2024 May 15.
Article in English | MEDLINE | ID: mdl-38767930

ABSTRACT

Schizophrenia is a major mental illness that is managed with long-term antipsychotic medication as a standard of care. Antipsychotic medications, however, are associated with many subjective and objective adverse effects. These adverse effects have driven the study of risk-mitigation strategies such as targeted intermittent therapy and dose reduction and drug discontinuation. Randomized controlled trials (RCTs) of these strategies have been synthesized in meta-analysis; both strategies have been associated with no functional benefits and with an increased risk of relapse. The RCTs, however, have been criticized because, in many, patients were abruptly switched to the target dose or too rapidly tapered, thereby predisposing the RCT to failure of the intervention. Two important RCTs examined gradual individualized dose reduction and discontinuation. One, conducted in first-episode psychosis patients who were free from positive symptoms for 6 months, found that, at 18-month follow-up, dose reduction was associated with a higher risk of relapse (number needed to harm [NNH] = 5) and with no functional benefits. However, after return to routine clinical care, at a 7-year follow-up, the dose reduction group had better functional outcomes and similar clinical outcomes relative to the maintenance treatment group. The other RCT, conducted in patients with relapsing psychosis, found that, at a 2-year follow-up, dose reduction was associated with a higher risk of relapse (NNH = 5) and with no improvements in social, cognitive, quality of life, satisfaction, and other domains. Many large nationwide observational studies have found that antipsychotic discontinuation by patients with first-episode psychosis and schizophrenia is associated with increased relapse, rehospitalization, suicide mortality, cardiovascular mortality, and all-cause mortality. There is also the ethical matter that attempts to identify the few who may benefit from antipsychotic dose reduction and discontinuation may compromise the health and stability of the many who require long-term maintenance treatment.


Subject(s)
Antipsychotic Agents , Psychotic Disorders , Schizophrenia , Humans , Antipsychotic Agents/administration & dosage , Antipsychotic Agents/therapeutic use , Antipsychotic Agents/adverse effects , Schizophrenia/drug therapy , Psychotic Disorders/drug therapy , Drug Tapering , Randomized Controlled Trials as Topic , Recurrence
13.
J Clin Psychiatry ; 85(2)2024 May 15.
Article in English | MEDLINE | ID: mdl-38767931

ABSTRACT

Objective: The objective of this study was to examine the relationship between clozapine use and hematologic malignancies, using national administrative data from the United States Veterans Health Administration (VHA).Methods: This case-control study of veterans with schizophrenia matched cases with incident hematologic malignancy to 10 controls without hematologic malignancy by gender, age, and time since first schizophrenia diagnosis from October 1999, the beginning of VHA data archives, to June 2022. Schizophrenia diagnoses were identified using International Classification of Diseases, Ninth Revision, code 295.x and International Statistical Classification of Diseases, Tenth Revision, codes F20.x and F25.x from inpatient hospitalization and outpatient encounter data. Additional inclusion criteria were age 18-85 years, no prior history of malignancy, and at least 1 year of antipsychotic exposure. Clozapine exposure was assessed using 3 metrics: any exposure, years of exposure, and cumulative defined daily doses (DDD). Conditional multivariable logistic regression was used to adjust for nonmatched confounding variables.Results: A total of 2,306 veterans with schizophrenia were identified with an incident diagnosis of hematologic malignancy and matched to 23,043 controls. Any prior clozapine exposure was more commonly observed among cases (5.3%) than controls (4.1%) and was significantly different after adjustment (odds ratio [OR], 1.31; 95% CI, 1.08-1.60). Risk was dose-dependent, where cumulative clozapine exposures from 3,000 to 4,999 DDD (OR, 1.78; 95% CI, 1.13-2.79) and ≥5,000 DDD (OR, 1.81; 95% CI, 1.24-2.64) were significantly associated with malignancy risk. Similarly, clozapine exposure of 5 or more years was associated with malignancy risk (OR, 1.88; 95% CI, 1.43-2.47).Conclusion: Consistent with prior report, this study observed an increased risk of hematologic malignancy associated with clozapine exposure. These findings suggest patients receiving clozapine use, particularly those with long-term use, should be closely monitored for hematologic malignancy.


Subject(s)
Antipsychotic Agents , Clozapine , Hematologic Neoplasms , Schizophrenia , Veterans , Humans , Schizophrenia/drug therapy , Schizophrenia/epidemiology , Clozapine/adverse effects , Male , Female , Middle Aged , Hematologic Neoplasms/epidemiology , Hematologic Neoplasms/chemically induced , Veterans/statistics & numerical data , Case-Control Studies , United States/epidemiology , Antipsychotic Agents/adverse effects , Aged , Adult , Young Adult , Aged, 80 and over , United States Department of Veterans Affairs/statistics & numerical data , Adolescent , Risk Factors
14.
Clin Cardiol ; 47(5): e24278, 2024 May.
Article in English | MEDLINE | ID: mdl-38767024

ABSTRACT

Olanzapine, an atypical antipsychotic medication, has gained prominence in the treatment of schizophrenia and related psychotic disorders due to its effectiveness and perceived safety profile. However, emerging evidence suggests a potential link between olanzapine use and adverse cardiovascular effects, including cardiomyopathy. This narrative review explores the mechanisms, clinical implications, and management strategies associated with olanzapine-induced cardiomyopathy. A comprehensive review of the literature was conducted to investigate the relationship between olanzapine and cardiomyopathy. The search included epidemiological studies, clinical case reports, and mechanistic research focusing on the pathophysiology of olanzapine-induced cardiomyopathy. The review also examined treatment strategies for managing this potential complication. Olanzapine-induced cardiomyopathy is hypothesized to be associated with metabolic disturbances and receptor antagonism. The metabolic effects of olanzapine, such as weight gain, insulin resistance, and dyslipidemia, share similarities with obesity-related cardiomyopathy. Additionally, olanzapine's antagonism of certain receptors may contribute to cardiovascular stress. The review highlighted that patients with new-onset heart failure and significant weight gain while on olanzapine should be closely monitored for signs of cardiomyopathy. Early detection and prompt withdrawal of olanzapine, along with initiation of goal-directed medical therapy, are crucial for mitigating this potentially life-threatening condition. The relationship between olanzapine and cardiomyopathy is complex and not yet fully understood. However, the potential for significant cardiovascular risk necessitates vigilance among healthcare providers. Early identification and management of olanzapine-induced cardiomyopathy can improve patient outcomes. Further research is needed to elucidate the precise mechanisms behind this adverse effect and to develop optimized treatment strategies for patients requiring antipsychotic therapy.


Subject(s)
Antipsychotic Agents , Cardiomyopathies , Obesity , Olanzapine , Humans , Olanzapine/adverse effects , Antipsychotic Agents/adverse effects , Cardiomyopathies/chemically induced , Cardiomyopathies/diagnosis , Obesity/complications , Schizophrenia/drug therapy , Diagnosis, Differential , Risk Factors
15.
Epidemiol Psychiatr Sci ; 33: e31, 2024 May 23.
Article in English | MEDLINE | ID: mdl-38779809

ABSTRACT

AIMS: Accumulating studies have assessed mortality risk associated with mood-stabilizers, the mainstay treatment for bipolar disorder (BD). However, existing data were mostly restricted to suicide risk, focused on lithium and valproate and rarely adequately adjusted for potential confounders. This study aimed to assess comparative mortality risk with all, natural and unnatural causes between lithium, valproate and three frequently prescribed second-generation antipsychotics (SGA), with adjustment for important confounders. METHODS: This population-based cohort study identified 8137 patients with first-diagnosed BD, who had exposed to lithium (n = 1028), valproate (n = 3580), olanzapine (n = 797), quetiapine (n = 1975) or risperidone (n = 757) between 2002 and 2018. Data were retrieved from territory-wide medical-record database of public healthcare services in Hong Kong. Propensity-score (PS)-weighting method was applied to optimize control for potential confounders including pre-existing chronic physical diseases, substance/alcohol use disorders and other psychotropic medications. PS-weighted Cox proportional-hazards regression was conducted to assess risk of all-, natural- and unnatural-cause mortality related to each mood-stabilizer, compared to lithium. Three sets of sensitivity analyses were conducted by restricting to patients with (i) length of cumulative exposure to specified mood-stabilizer ≥90 days and its medication possession ratio (MPR) ≥90%, (ii) MPR of specified mood-stabilizer ≥80% and MPR of other studied mood-stabilizers <20% and (iii) monotherapy. RESULTS: Incidence rates of all-cause mortality per 1000 person-years were 5.9 (95% confidence interval [CI]: 4.5-7.6), 8.4 (7.4-9.5), 11.1 (8.3-14.9), 7.4 (6.0-9.2) and 12.0 (9.3-15.6) for lithium-, valproate-, olanzapine-, quetiapine- and risperidone-treated groups, respectively. BD patients treated with olanzapine (PS-weighted hazard ratio = 2.07 [95% CI: 1.33-3.22]) and risperidone (1.66 [1.08-2.55]) had significantly higher all-cause mortality rate than lithium-treated group. Olanzapine was associated with increased risk of natural-cause mortality (3.04 [1.54-6.00]) and risperidone was related to elevated risk of unnatural-cause mortality (3.33 [1.62-6.86]), relative to lithium. The association between olanzapine and increased natural-cause mortality rate was consistently affirmed in sensitivity analyses. Relationship between risperidone and elevated unnatural-cause mortality became non-significant in sensitivity analyses restricted to low MPR in other mood-stabilizers and monotherapy. Valproate- and lithium-treated groups did not show significant differences in all-, natural- or unnatural-cause mortality risk. CONCLUSION: Our data showed that olanzapine and risperidone were associated with higher mortality risk than lithium, and further supported the clinical guidelines recommending lithium as the first-line mood-stabilizer for BD. Future research is required to further clarify comparative mortality risk associated with individual SGA agents to facilitate risk-benefit evaluation of alternative mood-stabilizers to minimize avoidable premature mortality in BD.


Subject(s)
Antimanic Agents , Antipsychotic Agents , Bipolar Disorder , Propensity Score , Quetiapine Fumarate , Valproic Acid , Humans , Bipolar Disorder/drug therapy , Bipolar Disorder/mortality , Antipsychotic Agents/therapeutic use , Antipsychotic Agents/adverse effects , Female , Male , Adult , Middle Aged , Valproic Acid/therapeutic use , Antimanic Agents/therapeutic use , Cohort Studies , Quetiapine Fumarate/therapeutic use , Quetiapine Fumarate/adverse effects , Olanzapine/therapeutic use , Hong Kong/epidemiology , Risperidone/therapeutic use , Risperidone/adverse effects , Lithium/therapeutic use , Cause of Death
16.
BMJ Case Rep ; 17(5)2024 May 06.
Article in English | MEDLINE | ID: mdl-38719244

ABSTRACT

Brexpiprazole is a relatively new drug that has no published research or applications within the paediatric population. Brexpiprazole targets multiple receptors and can manifest as multisystem symptoms when ingested in supratherapeutic quantities. In this report, we discuss the case of a child in early childhood who presented with delayed neurological and cardiac symptoms 24 hours after accidental ingestion of brexpiprazole. Due to delayed onset, this case highlights that a high index of suspicion and prolonged observation are necessary to appropriately manage brexpiprazole overdose or accidental ingestion.


Subject(s)
Quinolones , Thiophenes , Humans , Thiophenes/adverse effects , Quinolones/adverse effects , Quinolones/poisoning , Male , Drug Overdose , Child, Preschool , Antipsychotic Agents/adverse effects , Female
17.
Soins Psychiatr ; 45(352): 42-43, 2024.
Article in French | MEDLINE | ID: mdl-38719360

ABSTRACT

A 59-year-old man who had been presenting with a variety of neuropsychiatric symptoms for several weeks. Despite repeated visits to somatic emergencies, as well as a thorough work-up including complementary examinations and specialist opinions, no organic diagnosis was established. The patient was treated symptomatically with neuroleptics and benzodiazepines, which led to a significant improvement in symptoms.


Subject(s)
Antipsychotic Agents , Benzodiazepines , Humans , Male , Middle Aged , Antipsychotic Agents/therapeutic use , Diagnosis, Differential , Benzodiazepines/therapeutic use
18.
Dan Med J ; 71(5)2024 Apr 11.
Article in English | MEDLINE | ID: mdl-38704837

ABSTRACT

Current evidence for pharmacological treatment of mania during hospitalisation is insufficient as there are no larger well-designed randomised trials of comparative medical treatments of mania during inpatient stays. Moreover, there is considerable variation in pharmacological medication in clinical practice during hospitalisation for mania. Based on a hospital data overview, a systematic search of the literature and a three-day consensus meeting, this narrative review proposed an algorithm for optimised pharmacological treatment of mania during hospitalisation and its subsequent scientific evaluation.


Subject(s)
Algorithms , Hospitalization , Mania , Humans , Mania/drug therapy , Antipsychotic Agents/therapeutic use , Antimanic Agents/therapeutic use , Bipolar Disorder/drug therapy , Bipolar Disorder/therapy
19.
Cells ; 13(9)2024 Apr 29.
Article in English | MEDLINE | ID: mdl-38727298

ABSTRACT

The antipsychotic drug clozapine demonstrates superior efficacy in treatment-resistant schizophrenia, but its intracellular mode of action is not completely understood. Here, we analysed the effects of clozapine (2.5-20 µM) on metabolic fluxes, cell respiration, and intracellular ATP in human HL60 cells. Some results were confirmed in leukocytes of clozapine-treated patients. Neuroreceptor inhibition under clozapine reduced Akt activation with decreased glucose uptake, thereby inducing ER stress and the unfolded protein response (UPR). Metabolic profiling by liquid-chromatography/mass-spectrometry revealed downregulation of glycolysis and the pentose phosphate pathway, thereby saving glucose to keep the electron transport chain working. Mitochondrial respiration was dampened by upregulation of the F0F1-ATPase inhibitory factor 1 (IF1) leading to 30-40% lower oxygen consumption in HL60 cells. Blocking IF1 expression by cotreatment with epigallocatechin-3-gallate (EGCG) increased apoptosis of HL60 cells. Upregulation of the mitochondrial citrate carrier shifted excess citrate to the cytosol for use in lipogenesis and for storage as triacylglycerol in lipid droplets (LDs). Accordingly, clozapine-treated HL60 cells and leukocytes from clozapine-treated patients contain more LDs than untreated cells. Since mitochondrial disturbances are described in the pathophysiology of schizophrenia, clozapine-induced mitohormesis is an excellent way to escape energy deficits and improve cell survival.


Subject(s)
Clozapine , Mitochondria , Humans , Clozapine/pharmacology , Clozapine/analogs & derivatives , Mitochondria/metabolism , Mitochondria/drug effects , HL-60 Cells , Antipsychotic Agents/pharmacology , Apoptosis/drug effects , Adenosine Triphosphate/metabolism , Schizophrenia/drug therapy , Schizophrenia/metabolism , Schizophrenia/pathology , Leukocytes/drug effects , Leukocytes/metabolism , Endoplasmic Reticulum Stress/drug effects , Cellular Reprogramming/drug effects , Metabolic Reprogramming
20.
Arch Psychiatr Nurs ; 49: 113-117, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38734446

ABSTRACT

INTRODUCTION: Patients on antipsychotic medications are at higher risk of developing metabolic syndrome; nevertheless, metabolic screening for patients on antipsychotics is suboptimal. METHODS: This project developed and implemented AMP (Antipsychotic Metabolic screening Protocol), a nurse-driven protocol on inpatient psychiatric units that allowed nursing staff to collect all components of a metabolic screening. Nurses working on units with AMP were surveyed pre- and post-implementation on perception of AMP and empowerment. RESULTS: AMP significantly increased overall metabolic screening as well as the most frequently missing component (lipid panel). The screening rates pre-intervention were similar to those found in the literature (on average, only two-thirds of patients were screened). However, AMP improved the rate such that nine out of every ten patients on the units were screened. Nurses had a negative perception and no change in empowerment from AMP implementation. CONCLUSIONS: AMP can be used to increase metabolic screening for patients on antipsychotics. Further research is needed to better understand adoptability of nurse-driven protocols in the psychiatric inpatient setting as well as other applications, such as smoking cessation or safety sitters.


Subject(s)
Antipsychotic Agents , Inpatients , Mass Screening , Metabolic Syndrome , Humans , Antipsychotic Agents/therapeutic use , Metabolic Syndrome/diagnosis , Psychiatric Nursing , Surveys and Questionnaires , Female , Male , Nursing Staff, Hospital/psychology
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