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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 -
BMC Psychiatry Jun 2024Psychotic depression (PD) is characterized by the co-occurrence of emotional dysfunction and psychotic symptoms such as delusions and hallucinations with poor clinical...
Non-linear relationship between TSH and psychotic symptoms on first episode and drug naïve major depressive disorder patients: a large sample sized cross-sectional study in China.
INTRODUCTION
Psychotic depression (PD) is characterized by the co-occurrence of emotional dysfunction and psychotic symptoms such as delusions and hallucinations with poor clinical outcomes. TSH may involve in the development of PD. This study aims to explore relationship between TSH and PD.
METHODS
A total of 1718 outpatients diagnosed as FEDN MDD were recruited in this study. The relationship between PD and TSH was evaluated using multivariable binary logistic regression analysis. To assess the presence of non-linear associations, a two-piecewise linear regression model was employed. Furthermore, interaction and stratified analyses were conducted with respect to sex, education, marital status, comorbid anxiety, and suicide attempt.
RESULTS
Multivariable logistic regression analysis revealed that TSH was positively associated with the risk of PD after adjusting for confounders (OR = 1.26, 95% CI: 1.11 to 1.43; p < 0.05). Smoothing plots showed a nonlinear relationship between TSH and PD, with the inflection point of TSH being 4.94 mIU/L. On the right of the inflection point, for each unit increase in serum TSH level on the right side of the inflection point, the probability of PD increased substantially by 47% (OR = 1.47, 95% CI: 1.25 to 1.73, p < 0.001), while no significant association was observed on the left side of the inflection point (OR = 0.87, 95% CI: 0.67 to 1.14, p = 0.32).
CONCLUSION
Our investigation showed a nonlinear TSH-PD relationship in FEDN MDD patients, thus contributing to effective intervention strategies for psychotic symptoms in depression patients.
Topics: Humans; Male; Female; Cross-Sectional Studies; Adult; Thyrotropin; China; Depressive Disorder, Major; Psychotic Disorders; Middle Aged; Young Adult
PubMed: 38834989
DOI: 10.1186/s12888-024-05860-7 -
BMC Psychiatry Jun 2024Polypharmacy is common in older adults with psychiatric disorders, but no consensus has reached about the reliable indicators evaluating the benefits and risks of...
BACKGROUND
Polypharmacy is common in older adults with psychiatric disorders, but no consensus has reached about the reliable indicators evaluating the benefits and risks of drug-drug interactions (DDIs) in polypharmacy. We aimed to identify indicators suitable for evaluating the clinical significance of DDIs in polypharmacy in older adults with psychiatric disorders.
METHODS
The online tools were used to distribute and collect the questionnaires. The Delphi method was applied to analyze experts' opinions. The degree of authority and coordination of experts were analyzed using the coefficient of variation, coefficient of coordination, expert's judgment factor, familiarity with the study content factor, and Kendall coordination coefficient. Statistical analysis was conducted using the IBM SPSS® Statistics Package version 26.0.
RESULTS
After three rounds of expert consultation, five primary and eleven secondary indicators were identified. The primary "pharmacodynamic indicator" included "severity of adverse drug reactions", "duration of adverse drug reaction", "symptom relief", "time to onset of symptomatic relief", "number of days in hospital", and "duration of medication". The secondary "pharmacokinetic indicator" contained "dosage administered" and "dosing intervals". The primary "patient tolerance indicator" contained one secondary indicator of "patient tolerability". The primary indicator "patient adherence" contained one secondary indicator of "patient adherence to medication". The primary indicator "cost of drug combination" contained one secondary indicator of "readmission". These indicators were used to determine the clinical significance of DDIs during polypharmacy.
CONCLUSIONS
The clinical significance of drug combinations should be taken into account when polypharmacy is used in the elderly. The five primary indicators and eleven secondary indicators might be preferred to evaluate their risks and benefits. Medication management in this population requires a multidisciplinary team, in which nurses play a key role. Future research should focus on how to establish efficient multidisciplinary team workflows and use functional factors to assess DDIs in polypharmacy for psychiatric disorders.
Topics: Humans; Polypharmacy; Drug Interactions; Delphi Technique; Mental Disorders; Aged; Male; Female; Drug-Related Side Effects and Adverse Reactions; Middle Aged; Surveys and Questionnaires; Clinical Relevance
PubMed: 38834965
DOI: 10.1186/s12888-024-05872-3 -
BMJ Open Jun 2024Schizophrenia, a chronic mental problem, significantly impacts cognition, emotion and social functioning. Conventional pharmacotherapy faces challenges including...
INTRODUCTION
Schizophrenia, a chronic mental problem, significantly impacts cognition, emotion and social functioning. Conventional pharmacotherapy faces challenges including numerous side effects, low adherence to medication and substantial costs. In this context, group arts therapies (GATs) emerge as a promising complementary approach for symptom alleviation in schizophrenia patients. Nonetheless, the effectiveness and safety of GATs are yet to be firmly established. This study aims to systematically assess the therapeutic impact of all group-based artistic interventions as complementary treatments for schizophrenia, focusing on their potential benefits.
METHODS AND ANALYSIS
This study will search four English-language databases (PubMed, Web of Science, Cochrane Library and Embase), two Chinese databases (Wanfang Data and China National Knowledge Infrastructure) and three Korean databases (RISS, Korean Citation Index and DBpia) from their inception until October 2023. It will include all randomised controlled trials that compare GATs for schizophrenia with standard rehabilitation methods. The primary outcome is the improvement in patients' positive and negative symptoms. Methodologies such as bias risk assessment, data synthesis, sensitivity analysis and subgroup analysis will be implemented using Review Manager V.5.4. Study results with high heterogeneity will be merged using a random-effects model ( >50% or p<0.1). In cases where meta-analysis is not viable due to significant clinical and methodological heterogeneity, a qualitative summary of the findings will be provided.
ETHICS AND DISSEMINATION
The data used in this systematic review are anonymised, devoid of any private information, eliminating the requirement for ethical approval. Dissemination of the research findings will be conducted via peer-reviewed publications.
PROSPERO REGISTRATION NUMBER
CRD42023471583.
Topics: Humans; Schizophrenia; Systematic Reviews as Topic; Meta-Analysis as Topic; Art Therapy; Research Design; Psychotherapy, Group; Randomized Controlled Trials as Topic
PubMed: 38834330
DOI: 10.1136/bmjopen-2023-082076 -
Cureus May 2024MDMA (3,4-methylenedioxymethamphetamine), also known as Ecstasy, is a synthetic amphetamine with hallucinogenic and stimulant properties, which has become...
MDMA (3,4-methylenedioxymethamphetamine), also known as Ecstasy, is a synthetic amphetamine with hallucinogenic and stimulant properties, which has become increasingly favored as a substance for recreational use. Despite its deceptive reputation as "safe," chronic MDMA use is associated with neuropsychiatric complications, including psychosis. We describe a case of a 23-year-old woman with chronic MDMA use disorder and childhood trauma, who presented with severe psychosis and catatonic features. While initial diagnostic possibilities included drug-induced psychosis and mood disorders, the patient's history and presentation supported a diagnosis of bipolar I disorder with psychotic features, which was exacerbated by MDMA use. Conventional antipsychotics failed to improve psychotic symptoms and led to worsening of catatonia, requiring electroconvulsive therapy (ECT) for improvement. Socioeconomic barriers hindered follow-up care, leading to an Emergency Department (ED) admission shortly after discharge. This case highlights the intricate interplay between substance use, psychiatric illness, and trauma, and showcases ECT's efficacy in severe psychosis. It emphasizes the necessity for comprehensive mental health services, especially for vulnerable populations, and calls for further research into MDMA's psychiatric effects and optimal treatment approaches for individuals with co-occurring substance use and psychiatric disorders.
PubMed: 38832158
DOI: 10.7759/cureus.59641 -
Translational Psychiatry Jun 2024There is a lack of knowledge regarding the relationship between proneness to dimensional psychopathological syndromes and the underlying pathogenesis across major...
There is a lack of knowledge regarding the relationship between proneness to dimensional psychopathological syndromes and the underlying pathogenesis across major psychiatric disorders, i.e., Major Depressive Disorder (MDD), Bipolar Disorder (BD), Schizoaffective Disorder (SZA), and Schizophrenia (SZ). Lifetime psychopathology was assessed using the OPerational CRITeria (OPCRIT) system in 1,038 patients meeting DSM-IV-TR criteria for MDD, BD, SZ, or SZA. The cohort was split into two samples for exploratory and confirmatory factor analyses. All patients were scanned with 3-T MRI, and data was analyzed with the CAT-12 toolbox in SPM12. Psychopathological factor scores were correlated with gray matter volume (GMV) and cortical thickness (CT). Finally, factor scores were used for exploratory genetic analyses including genome-wide association studies (GWAS) and polygenic risk score (PRS) association analyses. Three factors (paranoid-hallucinatory syndrome, PHS; mania, MA; depression, DEP) were identified and cross-validated. PHS was negatively correlated with four GMV clusters comprising parts of the hippocampus, amygdala, angular, middle occipital, and middle frontal gyri. PHS was also negatively associated with the bilateral superior temporal, left parietal operculum, and right angular gyrus CT. No significant brain correlates were observed for the two other psychopathological factors. We identified genome-wide significant associations for MA and DEP. PRS for MDD and SZ showed a positive effect on PHS, while PRS for BD showed a positive effect on all three factors. This study investigated the relationship of lifetime psychopathological factors and brain morphometric and genetic markers. Results highlight the need for dimensional approaches, overcoming the limitations of the current psychiatric nosology.
Topics: Humans; Male; Female; Adult; Magnetic Resonance Imaging; Bipolar Disorder; Depressive Disorder, Major; Schizophrenia; Psychotic Disorders; Gray Matter; Middle Aged; Genome-Wide Association Study; Factor Analysis, Statistical; Brain; Psychopathology; Multifactorial Inheritance; Cerebral Cortex
PubMed: 38830892
DOI: 10.1038/s41398-024-02936-6 -
Journal of Psychiatric Research May 2024Emotional deficits in psychosis are prevalent and difficult to treat. In particular, much remains unknown about facial expression abnormalities, and a key reason is that...
Emotional deficits in psychosis are prevalent and difficult to treat. In particular, much remains unknown about facial expression abnormalities, and a key reason is that expressions are very labor-intensive to code. Automatic facial coding (AFC) can remove this barrier. The current study sought to both provide evidence for the utility of AFC in psychosis for research purposes and to provide evidence that AFC are valid measures of clinical constructs. Changes of facial expressions and head position of participants-39 with schizophrenia/schizoaffective disorder (SZ), 46 with other psychotic disorders (OP), and 108 never psychotic individuals (NP)-were assessed via FaceReader, a commercially available automated facial expression analysis software, using video recorded during a clinical interview. We first examined the behavioral measures of the psychotic disorder groups and tested if they can discriminate between the groups. Next, we evaluated links of behavioral measures with clinical symptoms, controlling for group membership. We found the SZ group was characterized by significantly less variation in neutral expressions, happy expressions, arousal, and head movements compared to NP. These measures discriminated SZ from NP well (AUC = 0.79, sensitivity = 0.79, specificity = 0.67) but discriminated SZ from OP less well (AUC = 0.66, sensitivity = 0.77, specificity = 0.46). We also found significant correlations between clinician-rated symptoms and most behavioral measures (particularly happy expressions, arousal, and head movements). Taken together, these results suggest that AFC can provide useful behavioral measures of psychosis, which could improve research on non-verbal expressions in psychosis and, ultimately, enhance treatment.
PubMed: 38830297
DOI: 10.1016/j.jpsychires.2024.05.056 -
JCPP Advances Jun 2024Due to limitations of categorical definitions of mental illness, there is a need for quantitative empirical investigations of the dimensional structure of...
BACKGROUND
Due to limitations of categorical definitions of mental illness, there is a need for quantitative empirical investigations of the dimensional structure of psychopathology. Using exploratory bifactor methods, this study investigated a comprehensive and representative structure of psychopathology in children to better understand how psychotic-like experiences (PLEs), autism spectrum disorder (ASD) symptoms, impulsivity, and sensitivity to reward and punishment, may be integrated into extant general factor models of psychopathology.
METHODS
We used seven child-report and three parent-report instruments capturing diverse mental health symptoms in 11,185 children aged 9-10 from the Adolescent Brain Cognitive Development (ABCD) Study. We built on previous modeling frameworks by conducting both split sample and full sample factor analytic approaches that harnessed recent methodological advances in bifactor exploratory structural equation modeling (B-ESEM) to examine a wide range of psychopathology measures not previously integrated into a single analysis. Validity of psychopathology dimensions was examined by investigating associations with sex, age, cognition, imaging measures, and medical service usage.
RESULTS
All four factor analytic models showed excellent fit and similar structure within informant. PLEs loaded most highly onto a general psychopathology factor, suggesting that they may reflect non-specific risk for mental illness. ASD symptoms loaded separately from attention/hyperactivity symptoms. Symptoms of impulsivity and sensitivity to reward and punishment loaded onto specific factors, distinct from externalizing and internalizing factors. All identified factors were associated with clinically relevant risk factors, providing preliminary evidence for their construct validity.
CONCLUSION
By integrating diverse child-report and parent-report psychopathology measures for children in the ABCD sample, we deliver data on the quantitative structure of psychopathology for an exceptionally large set of measurements and discuss implications for the field.
PubMed: 38827988
DOI: 10.1002/jcv2.12228 -
Therapeutic Advances in... 2024This case report examines the possible correlation between the clozapine/norclozapine ratio and the occurrence of constipation and paralytic ileus. We present the case...
This case report examines the possible correlation between the clozapine/norclozapine ratio and the occurrence of constipation and paralytic ileus. We present the case of a 42-year-old patient diagnosed with schizoaffective disorder undergoing clozapine therapy. Despite intensive treatment with clozapine, haloperidol, valproic acid and biweekly electroconvulsive therapy sessions for over a year, florid psychotic symptoms and fluctuating mood swings persisted. Therefore, valproic acid was replaced by carbamazepine, a potent inducer of several CYP450-enzymes. To maintain clozapine plasma levels, fluvoxamine, a CYP1A2-inhibitor, was introduced at a dose of 25 mg before this switch. After addition of carbamazepine, there was a significant decline in clozapine levels, necessitating an increase in fluvoxamine dosage to 50 mg. Five weeks later the patient was admitted to a general hospital with a diagnosis of paralytic ileus. Treatment with enemas proved effective. Drug concentration analysis revealed a 2.5-fold increase in norclozapine levels in the weeks preceding hospital admission, resulting in an inverted clozapine/norclozapine ratio. Treatment with clozapine, carbamazepine and fluvoxamine was continued as the patient demonstrated clinical improvement on carbamazepine. Concurrently, an intensive laxative regimen was initiated. Two weeks later, the patient was readmitted to the general hospital due to suspected paralytic ileus and faecal vomiting, once again displaying an inverted clozapine/norclozapine ratio. We discuss potential mechanisms contributing to the occurrence of the paralytic ileus in this patient, including the antagonism of muscarinic M3 receptors by both clozapine and norclozapine, as well as the agonism of delta-opioid receptors by norclozapine. This case highlights the potential significance of both the clozapine/norclozapine ratio and absolute norclozapine levels as risk factors for constipation and paralytic ileus in patients on clozapine therapy.
PubMed: 38827014
DOI: 10.1177/20451253241255487 -
Psychiatry Research Aug 2024This study examined trajectories of suicide-risk and their relationship to symptoms, recovery, and quality of life over time. Data was obtained from the Recovery after...
This study examined trajectories of suicide-risk and their relationship to symptoms, recovery, and quality of life over time. Data was obtained from the Recovery after an Initial Schizophrenia Episode Early Treatment Program (RAISE-ETP) study. 404 individuals with first-episode psychosis (FEP) completed measures of suicide-risk, depression, positive symptoms, recovery, and quality of life at baseline, 6mo, 12mo, 18mo, and 24mo. Latent class analysis was used to identify temporal trajectories of suicide-risk. General linear mixed models for repeated measures were used to examine the relationship between the latent trajectories of suicide-risk and clinical variables. Results identified three latent trajectories of suicide-risk (low-risk, worsening, and improving). The low-risk and improving classes experienced improvements in depression, positive symptoms, quality of life, and recovery over time. The worsening class experienced improvements in positive symptoms and quality of life, but no change in depression or recovery. These results suggest that some individuals with FEP are at risk for persistent depression and worsening suicide-risk during treatment despite experiencing improvements in positive symptoms and quality of life. These findings have important clinical implications, as persistent depression and worsening suicide-risk might be masked by the primary focus on positive symptoms and quality of life in most FEP clinics.
Topics: Humans; Psychotic Disorders; Female; Male; Adult; Young Adult; Quality of Life; Depression; Adolescent; Suicide; Schizophrenia
PubMed: 38823163
DOI: 10.1016/j.psychres.2024.115978