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Schizophrenia Research Jan 2024Catatonia is a neuropsychiatric disorder characterised by altered movement, speech, and behaviour. Clozapine is an established therapy for treatment-resistant...
Catatonia is a neuropsychiatric disorder characterised by altered movement, speech, and behaviour. Clozapine is an established therapy for treatment-resistant schizophrenia, but its role in catatonia has not been systematically examined. In this systematic review, we aimed to assess the evidence for clozapine as a treatment for catatonia. Full text original research articles in English where at least one patient with catatonia was treated with clozapine were included, provided catatonia did not occur solely in the context of neuroleptic malignant syndrome. Results were tabulated with calculations of summary statistics presented. Risk of bias was assessed with the Tool for Evaluating the Methodological Quality of Case Reports and Case Series. 182 patients were included, 81 from cohort studies and 101 from case reports or case series. 119/182 patients (65 %) had a specified underlying diagnosis of schizophrenia. Over 80 % of reported patients with catatonia had at least partial remission following treatment with clozapine across both cohort studies and case reports and case series. Among the case reports and series, 24/101 patients (23.8 %) followed clozapine withdrawal. Overall, 25 studies were of low quality, 60 of moderate quality and 8 of high quality. Our findings should be interpreted with caution, as the reliance on case reports, case series and small cohort studies is susceptible to reporting biases, regression to the mean and confounding by other treatments. Future research could use large healthcare databases to ascertain outcomes in those on clozapine with a history of catatonia given the difficulty and expense of conducting randomised controlled trials.
Topics: Humans; Clozapine; Catatonia; Antipsychotic Agents; Schizophrenia; Neuroleptic Malignant Syndrome
PubMed: 36117082
DOI: 10.1016/j.schres.2022.09.021 -
BMJ Open Feb 2024Postoperative nausea and vomiting (PONV) is a leading perioperative morbidity outcome following general anaesthesia. This systematic review aims to identify, appraise...
OBJECTIVES
Postoperative nausea and vomiting (PONV) is a leading perioperative morbidity outcome following general anaesthesia. This systematic review aims to identify, appraise and summarise the evidence synthesis studies of prophylactic interventions that reduce the incidence of paediatric PONV, thereby highlighting knowledge gaps and avenues of future research.
DESIGN
Systematic review using the AMSTAR-2 (A MeaSurement Tool to Assess Systematic Reviews 2) tool and the ROBIS (Risk Of Bias In Systematic reviews) tool.
DATA SOURCES
Seven major databases, including MEDLINE and EMBASE, from inception to 23 September 2022.
ELIGIBILITY CRITERIA FOR SELECTING STUDIES
Evidence synthesis studies of only randomised controlled trials that explored prophylactic interventions for PONV in children undergoing general anaesthesia.
DATA EXTRACTION AND SYNTHESIS
Following screening process by two reviewers, data were extracted from all eligible studies, including demographic parameters and details of interventions. Eligible studies were categorised into 'pharmacological' and 'non-pharmacological' groups and high-risk surgical groups of 'strabismus' and 'tonsillectomy' for qualitative synthesis.
RESULTS
There were 20 evidence synthesis reviews (17 meta-analyses, 2 systematic reviews, 1 network meta-analysis): 14 investigated pharmacological PONV prophylaxis in children, 5 investigated non-pharmacological interventions, 1 studied both pharmacological and non-pharmacological interventions. Monotherapy pharmacological prophylaxis agents, for example, dexamethasone (relative risk (RR) 0.49, 95% CI 0.41 to 0.58), 5-hydroxytryptamine (5-HT) antagonists (OR 0.12, 95% CI 0.07 to 0.20) and α-adrenoreceptor agonists (dexmedetomidine: RR 0.33, 95% CI 0.21 to 0.54), are more effective than placebo. A combination of pharmacological agents provided superior efficacy to monotherapy, particularly dexamethasone and 5-HT antagonists (RR 0.21, 95% credible interval 0.15 to 0.28). Acustimulation practice was consistently favourable in preventing PONV compared with placebo (RR 0.36, 95% CI 0.25 to 0.52).
CONCLUSION
Monotherapy pharmacological prophylaxis is more effective than placebo in reducing the incidence of paediatric PONV, with the efficacy increased further by using combination pharmacotherapy. Further research must compare multiple treatment arms of pharmacological and non-pharmacological prophylaxes for PONV to identify the optimal multimodal prophylaxis regimen.
PROSPERO REGISTRATION NUMBER
CRD42021236698.
Topics: Child; Humans; Antiemetics; Dexamethasone; Incidence; Postoperative Nausea and Vomiting; Serotonin; Systematic Reviews as Topic; Meta-Analysis as Topic
PubMed: 38388499
DOI: 10.1136/bmjopen-2022-070775 -
Neuropsychopharmacology : Official... Oct 2023Lysergic acid diethylamide (LSD) is a potent classic serotonergic psychedelic, which facilitates a variety of altered states of consciousness. Here we present the first... (Meta-Analysis)
Meta-Analysis
Lysergic acid diethylamide (LSD) is a potent classic serotonergic psychedelic, which facilitates a variety of altered states of consciousness. Here we present the first meta-analysis establishing dose-response relationship estimates of the altered states of consciousness induced by LSD. Data extracted from articles identified by a systematic literature review following PRISMA guidelines were obtained from the Altered States Database. The psychometric data comprised ratings of subjective effects from standardized and validated questionnaires: the Altered States of Consciousness Rating Scale (5D-ASC, 11-ASC) and the Mystical Experience Questionnaire (MEQ30). We performed meta-regression analyses using restricted cubic splines for data from studies with LSD doses of up to 200 μg base. Most scales revealed a sigmoid-like increase of effects, with a plateauing at around 100 μg. The most strongly modulated factors referred to changes in perception and illusory imagination, followed by positively experienced ego-dissolution, while only small effects were found for Anxiety and Dread of Ego Dissolution. The considerable variability observed in most factors and scales points to the role of non-pharmacological factors in shaping subjective experiences. The established dose-response relationships may be used as general references for future experimental and clinical research on LSD to compare observed with expected subjective effects and to elucidate phenomenological differences between psychedelics.
Topics: Humans; Lysergic Acid Diethylamide; Hallucinogens; Consciousness; Anxiety; Anxiety Disorders
PubMed: 37161078
DOI: 10.1038/s41386-023-01588-2 -
CNS Drugs Dec 2023The renewed interest in psychedelic research provides growing evidence of potentially unique effects on various aspects of reward processing systems. Using the Research...
BACKGROUND AND OBJECTIVES
The renewed interest in psychedelic research provides growing evidence of potentially unique effects on various aspects of reward processing systems. Using the Research Domain Criteria (RDoC) framework, as proposed by the National Institute of Mental Health, we aim to synthesize the existing literature concerning the impact of lysergic acid diethylamide (LSD) on the RDoC's Positive Valence Systems (PVS) domain, and to identify potential avenues for further research.
METHODS
Two LSD-related terms (lysergic acid diethylamide and LSD) and 13 PVS-related terms (reward, happiness, bliss, motivation, reinforcement learning, operant, conditioning, satisfaction, decision making, habit, valence, affect, mood) were used to search electronic databases such as PubMed, Scopus, PsychINFO, and Web of Science for relevant articles. A manual search of the reference list resulted in nine additional articles. After screening, articles and data were evaluated and included based on their relevance to the objective of investigating the effects of LSD on the PVS. Articles and data were excluded if they did not provide information about the PVS, were observational in nature, lacked comparators or reference groups, or were duplicates. A risk of bias assessment was performed using the National Toxicology Program's Office of Health Assessment and Translation (NTP OHAT) risk of bias (RoB) tool. Data from the included articles were collected and structured based on the RDoC bio-behavioral matrix, specifically focusing on the PVS domain and its three constituent constructs: reward responsiveness, reward learning, and reward valuation.
RESULTS
We reviewed 28 clinical studies with 477 participants. Lysergic acid diethylamide, assessed at self-report (23 studies), molecular (5 studies), circuit (4 studies), and paradigm (3 studies) levels, exhibited dose-dependent mood improvement (20 short-term and 3 long-term studies). The subjective and neural effects of LSD were linked to the 5-HT receptor (molecular). Animal studies (14 studies) suggested LSD could mildly reinforce conditioned place preference without aversion and reduce responsiveness to other rewards. Findings on reward learning were inconsistent but hinted at potential associative learning enhancements. Reward valuation measures indicated potential reductions in effort expenditure for other reinforcers.
CONCLUSION
Our findings are consistent with our previous work, which indicated classical psychedelics, primarily serotonin 2A receptor agonists, enhanced reward responsiveness in healthy individuals and patient populations. Lysergic acid diethylamide exhibits a unique profile in the reward learning and valuation constructs. Using the RDoC-based framework, we identified areas for future research, enhancing our understanding of the impact of LSD on reward processing. However, applying RDoC to psychedelic research faces limitations due to diverse study designs that were not initially RDoC-oriented. Limitations include subjective outcome measure selection aligned with RDoC constructs and potential bias in synthesizing varied studies. Additionally, some human studies were open-label, introducing potential bias compared to randomized, blinded studies.
Topics: Animals; Humans; Hallucinogens; Lysergic Acid Diethylamide; Serotonin Receptor Agonists; Affect; Self Report
PubMed: 37999867
DOI: 10.1007/s40263-023-01044-1 -
Frontiers in Pharmacology 2023Cancer is a neoplastic transformation that affects tissue. Among the many complications associated with cancer treatment, managing the distressing side effects of...
Cancer is a neoplastic transformation that affects tissue. Among the many complications associated with cancer treatment, managing the distressing side effects of chemotherapy-induced nausea and vomiting (CINV) is of main concern. Ondansetron is a selective serotonin 5-HT3 receptor antagonist that has emerged as an essential medication against CINV in adult cancer patients. Ondansetron efficacy and tolerability have made it a primary medication in CINV prophylaxis and treatment regimens. The study aims to offer a detailed overview of ondansetron's effectiveness, safety, and impact on patients' lives, ultimately contributing to the ongoing research to enhance the quality of cancer care. On 4 September 2023, a search was conducted of the ClinicalTrials.gov database using the search terms "cancer," "ondansetron," and "Zofran." Inclusion and exclusion criteria were defined to select relevant clinical trials. Included trials were completed with results and interventional studies that assessed the preventive effects of ondansetron on CINV in adult cancer patients. A total of 23 clinical trials were identified, with only 13 of them focusing on investigating the preventive effects of ondansetron on CINV in adult cancer patients. The collective findings from these trials showed an effective management of CINV using ondansetron. Through a comprehensive overview of clinical trials, the use of ondansetron in adult cancer patients represents a significant improvement in CINV management.
PubMed: 38074143
DOI: 10.3389/fphar.2023.1310455 -
Therapeutic Drug Monitoring Apr 2024Therapeutic drug monitoring of clozapine in children and adolescents has received insufficient attention. Calculation of concentration-to-dose (C/D) ratios from trough...
A Systematic Review of Clozapine Concentration-Dose Ratio from Therapeutic Drug Monitoring Studies in Children and Adolescents Treated with Clozapine for Mental Disorders.
BACKGROUND
Therapeutic drug monitoring of clozapine in children and adolescents has received insufficient attention. Calculation of concentration-to-dose (C/D) ratios from trough steady-state concentrations estimate drug clearance.
METHODS
A systematic electronic literature search was conducted in 3 article databases from inception until January 10, 2023, and articles reporting clozapine concentrations in children and adolescents were retrieved. The pharmacokinetic quality of the studies was assessed, and clozapine C/D ratios were calculated using the sample mean clozapine dose and concentration.
RESULTS
Of the 37 articles of potential interest, only 7 reported clozapine trough and steady-state concentrations. After excluding case reports and a study confounded by fluvoxamine, 4 studies on psychosis from Europe and the United States were included. The clozapine C/D ratios were similar to published adult values and ranged from 0.82 to 1.24 with a weighted mean of 1.08 ng/mL per mg/d. The weighted means were 334 mg/d for the dose and 380 ng/mL for the concentration. The stratified analysis of the weighted mean clozapine C/D ratios from 2 studies showed lower values in 52 male (1.05 ng/mL per mg/d) than in 46 female (1.46 ng/mL per mg/d) children and adolescents, with values similar to those reported for European adult nonsmokers. Two female adolescents had high clozapine C/D ratios (2.54 ng/mL per mg/d), an Asian American patient with borderline obesity and a patient with intellectual disability with low dosage (mean = 102 mg/d) and concentration (mean = 55 ng/mL).
CONCLUSIONS
Reports on clozapine therapeutic drug monitoring in children and adolescents are limited in number and quality. Future studies should focus on basic pharmacokinetic issues, such as stratification by sex, smoking, and relevant comedications with inductive or inhibitory properties.
Topics: Adult; Child; Male; Humans; Female; Adolescent; Clozapine; Antipsychotic Agents; Drug Monitoring; Mental Disorders; Psychotic Disorders
PubMed: 38018845
DOI: 10.1097/FTD.0000000000001154 -
BMC Psychiatry Jan 2024The utilization of once-monthly paliperidone palmitate (PP1M) in schizophrenia treatment has increased due to its enhanced adherence and convenience. However, there is...
BACKGROUND
The utilization of once-monthly paliperidone palmitate (PP1M) in schizophrenia treatment has increased due to its enhanced adherence and convenience. However, there is limited evidence on patient characteristics that may influence treatment outcomes when switching from oral antipsychotics (OAPs) to PP1M therapy. This systematic review aims to identify such patient characteristics and explore potential beneficial factors to aid healthcare professionals in clinical practice.
METHODS
A systematic literature search was conducted in the PubMed, Embase, and Cochrane Library databases up to July 19, 2022. Studies related to patients with schizophrenia who had been previously treated with OAPs and switched to PP1M were identified and included. Outcomes included the Positive and Negative Syndrome Scale (PANSS) total score, the clinical Global Impressions - Severity (CGI-S) score, the Personal and Social Performance (PSP) total score, and hospitalisation rate. Data were independently extracted and analysed. The results were presented through a narrative synthesis.
RESULTS
Eleven studies with a total of 4150 patients were included, identifying nine potential characteristics. The most commonly reported characteristics was patient's prior treatment with OAPs, followed by the stage of disease, duration of illness (DI), ethnicity, reason for switching to PP1M, history of hospitalisation, time of start injection of PP1M, the PANSS and PSP total score at baseline. Patients in the acute stage, with a shorter DI, a less than 1-week time interval to PP1M injection, and a lower PANSS total score at baseline may have a trend on providing better improvements on PANSS total score. Acute stage and shorter DI also showed potential trends in reducing CGI-S score. Early initiation of PP1M, switching for reasons other than lack of efficacy, and a higher PSP score at baseline exhibited potential trends towards better PSP total score improvements.
CONCLUSION
Our findings may suggest that patients in acute stage, with a shorter duration of illness, with early initiation of PP1M injection, and lower PANSS or PSP scores may trend towards better clinical results when transitioning to PP1M from OAPs. Further research is necessary to validate these potential associations and identify any unexplored characteristics. Such investigations are crucial for providing comprehensive clinical recommendations and informing treatment strategies in this context.
Topics: Humans; Antipsychotic Agents; Paliperidone Palmitate; Schizophrenia; Administration, Oral; Treatment Outcome
PubMed: 38243208
DOI: 10.1186/s12888-024-05508-6 -
Schizophrenia Research Jun 2024As access to an essential part of clozapine research from the former Union of Soviet Socialist Republics (USSR) states is very limited, quality aspects have not gained...
OBJECTIVE
As access to an essential part of clozapine research from the former Union of Soviet Socialist Republics (USSR) states is very limited, quality aspects have not gained attention so far, and harmonization with modern research standards remains unclear.
METHODS
We performed a systematic search in PubMed, Embase and scientific indexes from former USSR states for articles published in Russian language till January 2023 (PROSPERO Reg. Number CRD42023386737) and assessed their quality using the modified Strengthening the reporting of observational studies in epidemiology (STROBE)-Checklist. We compared quality aspects for papers published before and after 2000.
RESULTS
A total of 60 papers were considered. Conflicts of interests and funding sources were reported in 5 and 3 (8 % and 5 %) studies respectively; ethical approval was warranted in two studies (3 %). Statistical analysis was performed in 57 (95 %) studies, but statistical methods were described in 21 (35 %) studies. When comparing studies before and after 2000, there was a trend towards improvement for several aspects, with the only significant differences being the objectives' specification (43 vs 83 %, p < 0.003) and the reporting of statistical methodology (0.0 vs 46 %, p < 0.001), which were more frequently available in papers after 2000.
CONCLUSIONS
Clozapine papers in Russian language suffered from severe methodological drawbacks limiting generalizability. Changes regarding standardization, transparency, ethics, and good scientific practice are urgently required. Using reporting checklists and predefining protocols are the first steps towards quality upgrade and accelerate the integration of science from the former USSR states into the world scientific system.
Topics: Clozapine; Humans; Antipsychotic Agents; USSR; Biomedical Research; Schizophrenia
PubMed: 37977975
DOI: 10.1016/j.schres.2023.10.040 -
The International Journal of... Mar 2024The efficacy of pharmacological and nutritional interventions in individuals at clinical high risk for psychosis (CHR-P) remains elusive. This study aims to investigate... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The efficacy of pharmacological and nutritional interventions in individuals at clinical high risk for psychosis (CHR-P) remains elusive. This study aims to investigate the efficacy of pharmacological and nutritional interventions in CHR-P and whether these interventions can enhance the efficacy of psychological treatments.
METHODS
We systematically reviewed data from 5 databases until July 24, 2021: PubMed, Web of Science, EMBASE, China National Knowledge Infrastructure, and WanFang Data. The primary outcome was the transition to psychosis. Network meta-analyses were conducted at 3 time points (6, 12, and ≥24 months) considering both pharmacological/nutritional interventions alone and its combination with psychotherapy.
RESULTS
Out of 11 417 identified references, 21 studies were included, comprising 1983 participants. CHR-P participants receiving omega-3 polyunsaturated fatty acids treatment were associated with a lower probability of transition compared with placebo/control at 6 months (odds ratio [OR] = 0.07, 95% confidence interval [CI] = .01 to .054), 12 months (OR = 0.14, 95% CI = .03 to .66), and ≥24 months (OR = 0.16, 95% CI = .05 to .54). Moreover, risperidone plus psychotherapy was associated with a lower likelihood of transition at 6 months compared with placebo/control plus psychotherapy, but this result was not sustained over longer durations.
CONCLUSION
Omega-3 polyunsaturated fatty acids helped in preventing transitions to psychosis compared with controls.
PROSPERO REGISTRATION NUMBER
CRD42021256209.
Topics: Humans; Network Meta-Analysis; Psychotic Disorders; Fatty Acids, Omega-3; Risperidone; Odds Ratio
PubMed: 38408281
DOI: 10.1093/ijnp/pyae014