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JAMA Network Open Jun 2024Long-acting injectable antipsychotics (LAIs) can help decrease the rate of nonadherence to medications in patients with schizophrenia, but these drugs are underutilized...
IMPORTANCE
Long-acting injectable antipsychotics (LAIs) can help decrease the rate of nonadherence to medications in patients with schizophrenia, but these drugs are underutilized in clinical practice, especially in Asian countries. One strategy for the early prescription of LAIs is to administer the drugs during patients' first admission, when they have more time to absorb medication-related knowledge.
OBJECTIVE
To estimate the prevalence of and risk factors for in-hospital use of LAIs among first-admission patients with schizophrenia in Taiwan and to examine the association of early discontinuation with readmission risk among patients receiving LAIs.
DESIGN, SETTING, AND PARTICIPANTS
This cohort study included data from a claims database for patients with a first admission for schizophrenia at psychiatric wards in Taiwan from 2004 to 2017. Eligible patients were diagnosed with schizophrenia or schizoaffective disorder at discharge and aged between 15 and 64 years. Data analysis was performed from April to September 2022.
EXPOSURE
In-hospital use of LAIs with or without early discontinuation.
MAIN OUTCOME AND MEASURES
Readmission for any psychotic disorder following discharge from first admission, with risk estimated via multivariable survival regression analysis, including the Cox proportional hazards (CPH) model and accelerated failure time (AFT) model.
RESULTS
Of the 56 211 patients with a first admission for schizophrenia (mean [SD] age, 38.1 [12.1] years; 29 387 men [52.3%]), 46 875 (83.4%) did not receive any LAIs during admission, 5665 (10.1%) received LAIs with early discontinuation, and 3671 (6.5%) received LAIs without early discontinuation. The prevalence of receiving LAIs increased by 4%, from 15.3% (3863 of 25 251 patients) to 19.3% (3013 of 15 608 patients) between 2004-2008 and 2013-2017. After controlling for sex, year, prior antipsychotic use, age at first admission, and length of stay, the CPH regression analysis revealed that the readmission risk increased among patients receiving LAIs with early discontinuation (adjusted hazard ratio [aHR], 1.25; 95% CI, 1.21-1.30) but decreased among patients receiving LAIs without early discontinuation (aHR, 0.88; 95% CI, 0.84-0.92) compared with patients not receiving LAIs. Results remained similar for the AFT model.
CONCLUSIONS AND RELEVANCE
The incidence of in-hospital use of LAIs among patients with a first admission for schizophrenia has remained low. In this study, early discontinuation of LAIs was associated with readmission risk-specifically, early discontinuation with a higher risk while the lack of early discontinuation with a lower risk compared with treatment with oral antipsychotics alone-which suggests our results have implications for improving the efficacy of LAI administration among patients with a first admission for schizophrenia.
Topics: Humans; Schizophrenia; Antipsychotic Agents; Patient Readmission; Male; Taiwan; Female; Adult; Middle Aged; Delayed-Action Preparations; Risk Factors; Adolescent; Young Adult; Cohort Studies; Medication Adherence; Hospitalization; Injections; Proportional Hazards Models
PubMed: 38884998
DOI: 10.1001/jamanetworkopen.2024.17006 -
Psychiatry and Clinical... Mar 2024Thiol-disulfide homeostasis (TDH), one of the most important antioxidants, is involved in the non-enzymatic removal of reactive oxygen molecules in the body and is one...
BACKGROUND
Thiol-disulfide homeostasis (TDH), one of the most important antioxidants, is involved in the non-enzymatic removal of reactive oxygen molecules in the body and is one of the many methods to measure the level of oxidative stress (OS). In the present study, TDH is investigated in adolescent depression, and its relationship to clinical variables is examined.
METHODS
Thirty-two (50.0%) patients diagnosed with major depressive disorder (MDD) and without psychotropic drug use and 32 (50.0%) healthy controls were included in the present study. The subjects MDD and control groups were between 13 and 18 years old. Participants completed the DSM-5 Level-2 scales for depression and irritability. A colorimetric method proposed by Erel and Neselioglu was used to analyze the TDH parameters of serum samples.
RESULTS
Biochemical analyses of samples from the MDD and control groups showed significant differences between the groups in native thiol (SH) levels ( = .002), disulfide (SS) levels ( = .021), disulfide/total thiol (SS/ToSH) ( = .009), and disulfide/native thiol (SS/SH) ( = .003) levels. Analysis of receiver operating characteristic showed that the area under the curve values with "acceptable discrimination potential" for the TDH parameters were significantly able to discriminate individuals with MDD from healthy controls.
CONCLUSION
Thiol-disulfide homeostasis, one of the OS parameters, was found to be impaired in adolescents with depression. Our results suggest that TDH may contribute to the etiopathogenesis of adolescent MDD and that TDH may be a novel approach to assess OS in adolescent depression.
PubMed: 38883887
DOI: 10.5152/pcp.2024.23744 -
Heliyon Jun 2024Cervical intraepithelial neoplasia (CIN) encompasses a range of cervical lesions that are closely linked to cervical invasive carcinoma. Early detection and timely...
BACKGROUND
Cervical intraepithelial neoplasia (CIN) encompasses a range of cervical lesions that are closely linked to cervical invasive carcinoma. Early detection and timely treatment of CIN are crucial for preventing the progression of the disease. However, no bibliometric analysis has been conducted in this area. This research aimed to employ bibliometric analysis to summarize the current research hotspots and estimate future research trends in the CIN field.
METHODS
Publications related to CIN (2013-2023) were retrieved from the Science-Citation-Index-Expanded-of-Web-of-Science-Core-Collection. CiteSpace, VOSviewer, and the bibliometric-Online-Analysis-Platform-of-Literature-Metrology were employed to analyze the yearly research output, collaborating institutions or countries, leading researchers, principal journals, co-referenced sources, and emerging keywords.
RESULTS
In total, 4677 articles on CIN that were published from 2013 to 2023 and met our criteria were extracted. Major publishing platforms were predominantly USA until 2017 when China emerged as the leading source of publications about CIN. The USA was the leading nation in international collaborations. The National-Cancer-Institute (NCI) was the institution with the most publications. Schiffman Mark produced the highest number of articles, with a total of 92. Ten major clusters were identified through co-cited keyword clustering, including prevalence, human papillomavirus, DNA methylation, p16, methylation, conization, HPV genotyping tests (VALGENT), deep learning, vaginal microbiome, and immunohistochemistry. Keyword burst analysis showed that photodynamic therapy and deep learning emerged as prominent research focal points with significant impact in resent three years.
CONCLUSION
Global publications on CIN research showed a relatively stable trend over the past eleven years. Current research hotspots are deep learning and photodynamic therapy. This research offered organized data and insightful guidance for future studies, which may help better prevent, screen, and treat CIN.
PubMed: 38882369
DOI: 10.1016/j.heliyon.2024.e32114 -
Drug Design, Development and Therapy 2024The Baihe Dihuang decoction (BDD) is a representative traditional Chinese medicinal formula that has been used to treat anxiety disorders for thousands of years. This...
PURPOSE
The Baihe Dihuang decoction (BDD) is a representative traditional Chinese medicinal formula that has been used to treat anxiety disorders for thousands of years. This study aimed to reveal mechanisms of anxiolytic effects of BDD with multidimensional omics.
METHODS
First, 28-day chronic restraint stress (CRS) was used to create a rat model of anxiety, and the open field test and elevated plus maze were used to assess anxiety-like behavior. Enzyme-linked immunosorbent assay (ELISA), hematoxylin-eosin staining, and immunofluorescence staining were used to evaluate inflammatory response. Besides, 16S rRNA gene sequencing assessed fecal microbiota composition and differential microbiota. Non-targeted metabolomics analysis of feces was performed to determine fecal biomarkers, and targeted metabolomics was used to observe the levels of hippocampus neurotransmitters. Finally, Pearson correlation analysis was used to examine relationships among gut microbiota, fecal metabolites, and neurotransmitters.
RESULTS
BDD significantly improved anxiety-like behaviors in CRS-induced rats and effectively ameliorated hippocampal neuronal damage and abnormal activation of hippocampal microglia. It also had a profound effect on the diversity of microbiota, as evidenced by significant changes in the abundance of 10 potential microbial biomarkers at the genus level. Additionally, BDD led to significant alterations in 18 fecal metabolites and 12 hippocampal neurotransmitters, with the majority of the metabolites implicated in amino acid metabolism pathways such as D-glutamine and D-glutamate, alanine, arginine and proline, and tryptophan metabolism. Furthermore, Pearson analysis showed a strong link among gut microbiota, metabolites, and neurotransmitters during anxiety and BDD treatment.
CONCLUSION
BDD can effectively improve anxiety-like behaviors by regulating the gut-brain axis, including gut microbiota and metabolite modification, suppression of hippocampal neuronal inflammation, and regulation of neurotransmitters.
Topics: Animals; Rats; Anti-Anxiety Agents; Drugs, Chinese Herbal; Male; Metabolomics; Disease Models, Animal; Rats, Sprague-Dawley; Gastrointestinal Microbiome; Stress, Psychological; Anxiety; Restraint, Physical; Hippocampus
PubMed: 38882046
DOI: 10.2147/DDDT.S458983 -
Drug Design, Development and Therapy 2024Over the past decade, the idea of targeting the endocannabinoid system to treat anxiety disorders has received increasing attention. Previous studies focused more on... (Review)
Review
Over the past decade, the idea of targeting the endocannabinoid system to treat anxiety disorders has received increasing attention. Previous studies focused more on developing cannabinoid receptor agonists or supplementing exogenous cannabinoids, which are prone to various adverse effects due to their strong pharmacological activity and poor receptor selectivity, limiting their application in clinical research. Endocannabinoid hydrolase inhibitors are considered to be the most promising development strategies for the treatment of anxiety disorders. More recent efforts have emphasized that inhibition of two major endogenous cannabinoid hydrolases, monoacylglycerol lipase (MAGL) and fatty acid amide hydrolase (FAAH), indirectly activates cannabinoid receptors by increasing endogenous cannabinoid levels in the synaptic gap, circumventing receptor desensitization resulting from direct enhancement of endogenous cannabinoid signaling. In this review, we comprehensively summarize the anxiolytic effects of MAGL and FAAH inhibitors and their potential pharmacological mechanisms, highlight reported novel inhibitors or natural products, and provide an outlook on future directions in this field.
Topics: Humans; Anti-Anxiety Agents; Amidohydrolases; Monoacylglycerol Lipases; Animals; Endocannabinoids; Enzyme Inhibitors; Anxiety Disorders
PubMed: 38882045
DOI: 10.2147/DDDT.S462785 -
Epilepsy & Behavior Reports 2024Patients with epilepsy often present with concurrent psychiatric disorders, posing unique challenges for healthcare providers. This review explores the intricate...
Patients with epilepsy often present with concurrent psychiatric disorders, posing unique challenges for healthcare providers. This review explores the intricate relationship between psychiatric comorbidities, epilepsy, and psychotropic medications to inform clinical decision-making. The bidirectional association between epilepsy and psychiatric conditions complicates treatment, with psychiatric symptoms preceding or following seizure onset. The review discusses the seizure risks associated with antidepressants, CNS stimulants, and antipsychotics, shedding light on both historical perspectives and recent empirical evidence. Antidepressants, particularly tricyclic antidepressants (TCAs), are known to pose seizure risks, while newer agents like selective serotonin reuptake inhibitors (SSRIs) exhibit lower incidences and even potential anticonvulsant effects. Contrary to common beliefs, CNS stimulants used in attention-deficit/hyperactivity disorder (ADHD) treatment show efficacy without significantly increasing seizure risk. However, the association between ADHD and seizures warrants careful consideration. Among antipsychotics, clozapine stands out for its heightened seizure risks, especially during titration and at high doses, necessitating close monitoring and individualized approaches. Understanding the nuanced seizure risks associated with different psychotropic medications is crucial for optimizing patient care and minimizing iatrogenic seizures in this vulnerable population. By recognizing the complexities of psychiatric comorbidities in epilepsy and considering the unique challenges they pose, healthcare providers can make informed decisions to enhance patient safety and treatment outcomes. This review offers practical insights to guide clinicians in navigating the intricate landscape of managing psychiatric comorbidities in patients with epilepsy.
PubMed: 38881884
DOI: 10.1016/j.ebr.2024.100679 -
The Journal of International Medical... Jun 2024Pregabalin is a prescription medicine that has recently been approved for individuals who suffer from fibromyalgia, neuropathic pain, anxiety disorder, or epilepsy.... (Review)
Review
Pregabalin is a prescription medicine that has recently been approved for individuals who suffer from fibromyalgia, neuropathic pain, anxiety disorder, or epilepsy. Pregabalin has the side effects of dizziness, sleepiness, and angioedema. Pregabalin-induced rhabdomyolysis has been rarely reported, with only four reports to date. We report two cases of rhabdomyolysis after pregabalin treatment. A man aged older than 90 years presented with exhaustion, muscle aches, and a high serum creatine kinase concentration after taking 75 mg of pregabalin on the first day of treatment. A woman in her 90s with long-term use of pregabalin presented with considerably elevated serum creatine kinase concentrations. Both patients had a long history of taking statins. Pregabalin therapy was stopped, high-volume intravenous fluids were administered, and serum electrolytes were frequently checked. Alkalinisation was performed with excellent outcomes. The Naranjo Adverse Drug Reaction scale and previous research suggest an association between pregabalin and rhabdomyolysis. Clinicians should be alert to the possibility of rhabdomyolysis occurring with the use of pregabalin, especially when taking statins.
Topics: Humans; Pregabalin; Rhabdomyolysis; Female; Male; Aged, 80 and over; Analgesics; Creatine Kinase
PubMed: 38879799
DOI: 10.1177/03000605241257776 -
The Lancet. Psychiatry Jul 2024Many patients with schizophrenia have symptoms that do not respond to antipsychotics. This condition is called treatment-resistant schizophrenia and has not received... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Many patients with schizophrenia have symptoms that do not respond to antipsychotics. This condition is called treatment-resistant schizophrenia and has not received specific attention as opposed to general schizophrenia. Psychological and psychosocial interventions as an add-on treatment to pharmacotherapy could be useful, but their role and comparative efficacy to each other and to standard care in this population are not known. We investigated the efficacy, acceptability, and tolerability of psychological and psychosocial interventions for patients with treatment-resistant schizophrenia.
METHODS
In this systematic review and network meta-analysis (NMA), we searched for published and unpublished randomised controlled trials (RCTs) through a systematic database search in BIOSIS, CINAHL, Embase, LILACS, MEDLINE, PsychInfo, ClinicalTrials.gov, and the WHO International Clinical Trials Registry Platform for articles published from inception up to Jan 31, 2020. We also searched the Cochrane Schizophrenia Group registry for studies published from inception up to March 31, 2022, and PubMed and Cochrane CENTRAL for studies published from inception up to July 31, 2023. We included RCTs that included patients with treatment-resistant schizophrenia. The primary outcome was overall symptoms. We did random-effects pairwise meta-analyses and NMAs to calculate standardised mean differences (SMDs) or risk ratios with 95% CIs. No people with lived experience were involved throughout the research process. The study protocol was registered in PROSPERO, CRD42022358696.
FINDINGS
We identified 30 326 records, excluding 24 526 by title and abstract screening. 5762 full-text articles were assessed for eligibility, of which 5540 were excluded for not meeting the eligibility criteria, and 222 reports corresponding to 60 studies were included in the qualitative synthesis. Of these, 52 RCTs with 5034 participants (1654 [33·2%] females and 3325 [66·8%] males with sex indicated) comparing 20 psychological and psychosocial interventions provided data for the NMA. Mean age of participants was 38·05 years (range 23·10-48·50). We aimed to collect ethnicity data, but they were scarcely reported. According to the quality of evidence, cognitive behavioural therapy for psychosis (CBTp; SMD -0·22, 95% CI -0·35 to -0·09, 35 trials), virtual reality intervention (SMD -0·41, -0·79 to -0·02, four trials), integrated intervention (SMD -0·70, -1·18 to -0·22, three trials), and music therapy (SMD -1·27, -1·83 to -0·70, one study) were more efficacious than standard care in reducing overall symptoms. No indication of publication bias was identified.
INTERPRETATION
We provide robust findings that CBTp can reduce the overall symptoms of patients with treatment-resistant schizophrenia, and therefore clinicians can prioritise this intervention in their clinical practice. Other psychological and psychosocial interventions showed promising results but need further investigation.
FUNDING
DAAD-ASFE.
Topics: Humans; Network Meta-Analysis; Psychosocial Intervention; Schizophrenia, Treatment-Resistant; Randomized Controlled Trials as Topic; Psychotherapy; Antipsychotic Agents; Treatment Outcome; Schizophrenia
PubMed: 38879276
DOI: 10.1016/S2215-0366(24)00136-6 -
BMC Psychiatry Jun 2024Accumulating evidence supports the idea that inflammation may contribute to the pathophysiology of major depressive disorder (MDD). Duloxetine, a...
OBJECTIVE
Accumulating evidence supports the idea that inflammation may contribute to the pathophysiology of major depressive disorder (MDD). Duloxetine, a serotonin-norepinephrine reuptake inhibitor, exhibits anti-inflammatory effects both in vitro and in vivo. In this study, we investigated the impact of duloxetine on changes in serum proinflammatory cytokine levels among individuals diagnosed with MDD.
METHODS
A cohort of 23 drug-naïve individuals diagnosed with MDD and 23 healthy controls were included in this study. The severity of depressive symptoms was evaluated using the 24-item Hamilton Depression Scale (HAMD-24). A panel of 7 proinflammatory cytokines, including interleukin-1β (IL-1β), IL-2, IL-6, IL-8, IL-12, tumor necrosis factor-α (TNF-α), and interferon-γ (IFN-γ), were quantified using multiplex Luminex assays. The levels of serum cytokines in healthy controls and patients with MDD were compared at baseline. All patients received duloxetine at a dosage range of 40-60 mg/day for a duration of 4 weeks. The HAMD-24 scores and serum cytokine levels were compared before and after duloxetine treatment.
RESULTS
Compared with healthy controls, patients with MDD had significantly greater levels of IL-2, IL-6, IL-8, IL-12, TNF-α, and IFN-γ (P < 0.05). Moreover, there was a significant decrease in HAMD-24 scores observed pre- and post-treatment (t = 13.161, P < 0.001). Furthermore, after 4 weeks of treatment, the serum levels of IL-8 (t = 3.605, P = 0.002), IL-12 (t = 2.559, P = 0.018), and IFN-γ (t = 3.567, P = 0.002) decreased significantly. However, there were no significant differences in other cytokines, including IL-1β, IL-2, IL-6, and TNF-α, before and after treatment (P > 0.05).
CONCLUSIONS
These findings present compelling evidence, potentially for the first time, indicating that duloxetine treatment may effectively reduce the serum concentrations of IL-8, IL-12, and IFN-γ in individuals diagnosed with MDD. However, the precise mechanisms underlying this effect remain unclear and warrant further investigation.
Topics: Humans; Duloxetine Hydrochloride; Depressive Disorder, Major; Female; Male; Cytokines; Adult; Middle Aged; Antidepressive Agents; Case-Control Studies; Inflammation
PubMed: 38877455
DOI: 10.1186/s12888-024-05910-0 -
BMC Public Health Jun 2024Overdose-related suicide attempts represent a significant portion of self-harm presentations in the psychiatric emergency department (ED). Identifying specific patient...
BACKGROUND
Overdose-related suicide attempts represent a significant portion of self-harm presentations in the psychiatric emergency department (ED). Identifying specific patient characteristics associated with these attempts holds promise for pinpointing drug classes with elevated risk and paving the way for tailored suicide prevention interventions. This study aims to examine the demographic profiles of ED patients who had experienced overdose-related suicide attempts.
METHODS
This retrospective study was conducted at Beijing Anding Hospital, Capital Medical University, from January 2020 to December 2021. Patients with psychiatric drug overdose suicide attempts presenting to the psychiatric ED were included. Sociodemographic characteristics and the specific classes of drugs involved were collected, and analysed descriptively.
RESULTS
This study examined 252 overdose patients, excluding 51 patients treated with alcohol or nonpsychiatric drugs, and a total 201 cases were included. The mean age of the patients was 28 ± 16 years (median 23, range 12-78), and 82% (n = 165) of the sample were females. Notably, nearly half (45%) of the patients were aged ≤ 20 years. While the number of cases decreased with increasing age, a significant increase was observed in 2021 compared to 2020. Benzodiazepines (BZDs) were the most frequently implicated substance class (n = 126, 63%), followed by antidepressants (n = 96, 48%), antipsychotics (n = 44, 22%), Z-drugs (n = 43, 21%), and mood stabilizers (n = 36, 18%). For adolescents, antidepressants (n = 52, 71%) overtook BZDs (n = 38, 52%) as the most common drug. The monthly distribution of cases revealed peaks in April and November. Furthermore, 21% (n = 42) of patients ingested more than two psychotropic medications concurrently. Finally, approximately half (n = 92) of the patients required inpatient admission for further treatment. Comparisons between hospitalized and nonhospitalized patients did not reveal any significant differences.
CONCLUSIONS
The present study revealed a greater prevalence of suicide overdose attempts among young females receiving prescriptions for antidepressants and/or BZDs. This finding suggests a potential need for enhanced monitoring of suicidal behaviour in this specific population when prescribing psychotropic medications. These findings contribute to the growing body of knowledge regarding drug overdose suicide attempts in psychiatric emergency settings and underscore the importance of further research to develop targeted prevention interventions.
Topics: Humans; Female; Adult; Suicide, Attempted; Male; Retrospective Studies; Drug Overdose; Adolescent; Young Adult; Middle Aged; Aged; Child; Beijing; Emergency Service, Hospital; Antidepressive Agents
PubMed: 38877447
DOI: 10.1186/s12889-024-19095-4