-
PloS One 2024The Mental Welfare Commission for Scotland published a report into the death of a young person, with recommendations for the Royal College of Psychiatry in Scotland...
INTRODUCTION
The Mental Welfare Commission for Scotland published a report into the death of a young person, with recommendations for the Royal College of Psychiatry in Scotland Child and Adolescent Faculty; to explore if there were barriers to the use of Clozapine in young people in Scotland.
METHODS
A mixed-methods study was performed using a cross-sectional survey of clinicians working in child and adolescent psychiatry across Scotland, to determine attitudes towards clozapine use and the perceived barriers and facilitators to clozapine treatment.
RESULTS
Results suggest that there may be a lack of clearly defined pathways within and between services, as well as a lack of resources provided for the necessary monitoring of a young person started on clozapine. Multiple respondents felt unskilled in clozapine initiation and had not accessed formal training. The most frequently mentioned themes for improving facilitation of clozapine prescription were that of increased resources and training.
DISCUSSION
National policymakers including the Mental Welfare Commission, NHS Education for Scotland, and NHS Scotland should consider these findings to address the potential underutilisation of clozapine for people aged under 18 in services across Scotland. A review of current service provision should take place, with consideration of whether the facilitators to clozapine prescription which our study has highlighted could be implemented more effectively. This may help reduce identified barriers and increase clozapine prescription to those who would benefit from it, potentially improving outcomes for young people with treatment-resistant psychosis.
Topics: Humans; Clozapine; Scotland; Adolescent; Cross-Sectional Studies; Male; Female; Psychiatry; Antipsychotic Agents; Surveys and Questionnaires; Attitude of Health Personnel; Practice Patterns, Physicians'; Adult; Child; Psychiatrists
PubMed: 38900758
DOI: 10.1371/journal.pone.0304996 -
PloS One 2024Recent studies on classic psychedelics have suggested that their use is associated with psychological strengths and resilience, thereby conferring users a type of...
Recent studies on classic psychedelics have suggested that their use is associated with psychological strengths and resilience, thereby conferring users a type of psychological protection relative to non-users. However, this idea has been brought into question by recent findings suggesting that lifetime users of lysergic acid diethylamide (LSD) report worse mental health during stressful experiences. The current study addresses these mixed findings by examining whether LSD use prior to a stressful experience buffers against the psychological distress experienced in the wake of the stressful experience. This study draws on openly-available data from the National Survey on Drug Use and Health (2008-2019) on 5,067,553 (weighted) unemployed, job seeking individuals experiencing job loss. Using purposeful respondent exclusion criteria to establish temporal precedence of the variables under investigation, this study offers a straightforward test of whether LSD use confers psychological resilience to naturalistic users. LSD use prior to job loss was associated with a higher likelihood of severe psychological distress following job loss, regardless of whether sociodemographic variables were controlled for or not. In sum, this study fails to find evidence for LSD-conferred psychological resilience in naturalistic users in the wake of a stressful experience.
Topics: Humans; Lysergic Acid Diethylamide; Resilience, Psychological; Male; Female; Adult; Unemployment; Middle Aged; Hallucinogens; Young Adult; Stress, Psychological; Adolescent; Psychological Distress
PubMed: 38900707
DOI: 10.1371/journal.pone.0304991 -
Pain Research & Management 2024Common postoperative complications following surgery, particularly acute appendicitis surgery, include postoperative pain and vomiting, which can cause discomfort and... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Common postoperative complications following surgery, particularly acute appendicitis surgery, include postoperative pain and vomiting, which can cause discomfort and delay recovery time.
METHODS
A randomized double-blinded placebo-controlled clinical trial was conducted with 80 cases of acute appendicitis of American Society of Anesthesiologists (ASA) physical status I or II and aged 18-60 y/o scheduled for appendectomy under general anesthesia. Patients were randomly divided into two equal groups: group A received 4 mg of ondansetron IV (2 ml) and group B received 2 ml of normal slain IV (placebo). Pain according to VAS, nausea and vomiting according to clinical symptoms, shivering and sedation according to the Bedside Shivering Assessment Scale (BSAS), and the Ramsay Sedation Scale (RSS) at 2, 6, 12, and 24 hours after surgery were evaluated and compared between the groups.
RESULTS
There was a significant decline in the severity of pain only at 2 hours after surgery between the ondansetron and control groups (5.3 ± 1.0 vs. 6.0 ± 1.0; =0.01), not showing a difference between the groups at 6, 12, and 24 hours after appendectomy. Postoperative nausea and vomiting at 2 (5% vs. 25%; =0.03) and 6 (7.5% vs. 27.5%; =0.04) hours after appendectomy in the ondansetron group. At different times, the ondansetron and control groups did not differ in terms of pethidine consumption or sedation.
CONCLUSIONS
In conclusion, our study found that ondansetron was effective in reducing postoperative vomiting after acute appendicitis surgery. However, it did not show a clinically significant effect on postoperative pain. This trial is registered with IRCT20230722058883N1.
Topics: Humans; Double-Blind Method; Ondansetron; Adult; Male; Female; Pain, Postoperative; Appendicitis; Young Adult; Middle Aged; Adolescent; Postoperative Nausea and Vomiting; Appendectomy; Pain Measurement; Antiemetics; Treatment Outcome; Time Factors
PubMed: 38899063
DOI: 10.1155/2024/6429874 -
Biological & Pharmaceutical Bulletin 2024Although carboplatin (CBDCA) is classified as a moderately emetogenic agent, the majority of guidelines recommend the use of a neurokinin-1 receptor antagonist in...
Although carboplatin (CBDCA) is classified as a moderately emetogenic agent, the majority of guidelines recommend the use of a neurokinin-1 receptor antagonist in addition to a 5-hydroxytryptamine type 3 receptor antagonist with dexamethasone (DEX) for CBDCA-containing chemotherapy because of its higher emetogenic risk. However, the additional efficacy of aprepitant (APR) in CBDCA-containing treatment remains controversial, and data on multiple-day treatments are limited. Etoposide (ETP) was administered on days 1-3 in the CBDCA + ETP regimen, and it is important to evaluate suitable antiemetic therapy for the regimen. Therefore, we evaluated the efficacy of additional APR in CBDCA + ETP. Patients were divided into two groups and retrospectively evaluated. One was the control group, which was prophylactically administered palonosetron (PALO) and DEX, and the other was the APR group, which received APR orally with PALO and DEX. The primary endpoint was complete response (CR) between the groups. The overall CR rates were 75.0 and 76.4% in the control and APR groups, respectively, with no significant difference (p = 1.00). In the acute phase, it was 88.9 and 97.2%, respectively, and 86.1 and 79.2% in the delayed phase, respectively, without significant differences (p = 0.10 and 0.38, respectively). The incidence and severity of nausea, vomiting, and anorexia were not significantly different between the two groups in the acute and delayed phases. Our findings suggest that combining APR with PALO and DEX does not improve the CR rate in CBDCA + ETP therapy.
Topics: Aprepitant; Carboplatin; Humans; Dexamethasone; Palonosetron; Male; Etoposide; Antiemetics; Female; Middle Aged; Vomiting; Aged; Nausea; Retrospective Studies; Adult; Drug Therapy, Combination; Antineoplastic Combined Chemotherapy Protocols; Quinuclidines; Morpholines; Antineoplastic Agents; Isoquinolines; Treatment Outcome
PubMed: 38897969
DOI: 10.1248/bpb.b24-00046 -
The Korean Journal of Pain Jun 2024has bioactive constituents and has been used for therapeutic actions. The present study was undertaken to investigate the mechanisms underlying pain-relieving effects...
BACKGROUND
has bioactive constituents and has been used for therapeutic actions. The present study was undertaken to investigate the mechanisms underlying pain-relieving effects of the hydroethanolic extract of C. scolymus (HECS).
METHODS
The antinociceptive activity of HECS was assessed through formalin and acetic acid-induced writhing tests at doses of 50, 100 and 200 mg/kg intraperitoneally. Additionally, naloxone (non-selective opioid receptors antagonist, 2 mg/kg), atropine (non-selective muscarinic receptors antagonist, 1 mg/kg), chlorpheniramine (histamine HH-receptor antagonist, 20 mg/kg), cimetidine (histamine H-receptor antagonist, 12.5 mg/kg), flumazenil (GABA/BDZ receptor antagonist, 5 mg/kg) and cyproheptadine (serotonin receptor antagonist, 4 mg/kg) were used to determine the systis implicated in HECS-induced analgesia. Impact of HECS on locomotor activity was executed by open-field test. Determination of total phenolic content (TPC) and total flavonoid content (TFC) was done. Evaluation of antioxidant activity was conducted iploying 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging assay.
RESULTS
HECS (50, 100 and 200 mg/kg) significantly indicated dose dependent antinociceptive activity against pain-related behavior induced by formalin and acetic acid ( < 0.001). Pretreatment with naloxone, atropine and flumazenil significantly reversed HECS-induced analgesia. Antinociceptive effect of HECS riained unaffected by chlorpheniramine, cimetidine and cyproheptadine. Locomotor activity was not affected by HECS. TPC and TFC of HECS were 59.49 ± 5.57 mgGAE/g dry extract and 93.39 ± 17.16 mgRE/g dry extract, respectively. DPPH free radical scavenging activity (IC) of HECS was 161.32 ± 0.03 μg/mL.
CONCLUSIONS
HECS possesses antinociceptive activity which is mediated via opioidergic, cholinergic and GABAergic pathways.
PubMed: 38881282
DOI: 10.3344/kjp.23355 -
Journal of Pharmacological Sciences Aug 2024We examined the inhibitory effects of α-linolenic acid (ALA) on the contractions of pig coronary arteries. ALA concentration-dependently inhibited the contractions...
We examined the inhibitory effects of α-linolenic acid (ALA) on the contractions of pig coronary arteries. ALA concentration-dependently inhibited the contractions elicited by U46619 and prostaglandin F without affecting those elicited by 80 mM KCl, histamine, acetylcholine, and serotonin. ALA rightward shifted the concentration-response curve of U46619, and Schild plot analysis revealed that ALA competitively antagonized U46619. Furthermore, ALA inhibited the increase in intracellular Ca concentration caused by TP receptor stimulation but not that caused by FP receptor stimulation. These results suggest that ALA behaves as a selective antagonist of TP receptors in coronary arteries.
Topics: Animals; Coronary Vessels; alpha-Linolenic Acid; Swine; 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; Calcium; Receptors, Thromboxane; Dose-Response Relationship, Drug; Male; Dinoprost; Muscle Contraction
PubMed: 38880549
DOI: 10.1016/j.jphs.2024.06.001 -
European Journal of Internal Medicine Jun 2024Alcohol use disorder (AUD) is among the leading causes of morbidity and mortality worldwide, and over 95 million people live with alcohol dependence globally. The...
BACKGROUND
Alcohol use disorder (AUD) is among the leading causes of morbidity and mortality worldwide, and over 95 million people live with alcohol dependence globally. The estimated heritability of AUD is 50-60 %, and multiple genes are thought to contribute to various endophenotypes of the disease. Previous clinical trials support a precision medicine approach using ondansetron (AD04, a 5-HT3 antagonist) by segregating AUD populations by the bio-genetic endophenotype of specific serotonergic genotypes and the bio-psychosocial endophenotype of the severity of drinking or both. By targeting the modulation of biogenetic signaling within the biopsychosocial context of AUD, low-dose AD04 holds promise in reducing alcohol consumption among affected individuals while minimizing adverse effects.
METHODS
This was a phase III, 6-month, 25-site, randomized, placebo-controlled clinical trial using AD04 to treat DSM-V-categorized AUD individuals who were pre-stratified into the endophenotypes of heavy or very heavy drinking individuals and possessed a pre-defined profile of genetic variants related to the serotonin transporter and serotonin-3AB receptor. Participants (N = 303) presented moderate to severe AUD, >80 % were men, mostly in their fifties, and >95 % were of European descent. Low-dose AD04 (approx. 033 mg twice daily) or a matching placebo was administered twice daily for 6 months. Brief Behavioral Compliance Enhancement Treatment (BBCET [53]) was administered every two weeks to enhance medication compliance and clinic attendance.
RESULTS
There was a significant reduction in the monthly percentage of heavy drinking days, PHDD (-46·7 % (2·7 %), 95 %CI: -52·1 % to -41·2 % vs. -38·1 % (2·9 %), 95 %CI: -43·8 % to -32·5 %, respectively; LS mean difference=-8·5 %; p = 0.03) among AD04-treated vs. placebo-receiving heavy drinking individuals at month 6. Heavy drinking individuals were also less likely to be diagnosed with AUD [Month 1: -32·0 % (2·8 %), 95 %CI: -37·5 % to -26·5 % vs. -23·2 % (2·9 %), 95 %CI: -28·9 to -17·5 %; LS mean difference= -8·8 %; p = 0·026)], and improved on the WHO quality of life BREF scale with a significant effect for at least a 1-level downward shift (OR = 3.4; 95 % CI: 1·03-11·45, p = 0·044). Importantly, heavy drinking individuals, as distinct from very heavy drinking individuals, were the bio-psychosocial endophenotype more predictive of therapeutic response to AD04. AD04 had an exceptional safety and tolerability profile, like the placebo's.
CONCLUSIONS
In this Phase 3 clinical trial, AD04 was shown to be a promising treatment for currently drinking heavy drinking individuals with AUD who also possess a specific genotypic profile in the serotonin transporter and serotonin-3AB receptor complex. Using AD04 to reduce the harm of AUD in heavy drinking individuals who are currently drinking, without the necessity of abstinence or detoxification from alcohol use, is an important advance in the field of precision medicine. AD04's adverse events profile, which was like placebo, should enhance accessibility and acceptance of modern medical treatment for AUD by lowering the incorrect but commonly perceived stigma of personal failure.
PubMed: 38876929
DOI: 10.1016/j.ejim.2024.06.001 -
Toxicology Letters Jun 2024Several fungi belonging to the genus Psilocybe, also called "magic mushrooms", contain the hallucinogenic drugs psilocybin and psilocin. They are chemically related to...
Several fungi belonging to the genus Psilocybe, also called "magic mushrooms", contain the hallucinogenic drugs psilocybin and psilocin. They are chemically related to serotonin (5-HT). In addition to being abused as drugs, they are now also being discussed or used as a treatment option for depression. Here, we hypothesized that psilocybin and psilocin may act also on cardiac serotonin receptors and studied them in vitro in atrial preparations of our transgenic mouse model with cardiac myocytes-specific overexpression of the human 5-HT receptor (5-HT-TG) as well as in human atrial preparations. Both psilocybin and psilocin enhanced the force of contraction in isolated left atrial preparations from 5-HT-TG, increased the beating rate in isolated spontaneously beating right atrial preparations from 5-HT-TG and augmented the force of contraction in the human atrial preparations. The inotropic and chronotropic effects of psilocybin and psilocin at 10 µM were smaller than that of 1 µM 5-HT on the left and right atria from 5-HT-TG, respectively. Psilocybin and psilocin were inactive in WT. In the human atrial preparations, inhibition of the phosphodiesterase III by cilostamide was necessary to unmask the positive inotropic effects of psilocybin or psilocin. The effects of 10 µM psilocybin and psilocin were abrogated by 10 µM tropisetron or by 1 µM GR125487, a more selective 5-HT receptor antagonist. In summary, we demonstrated that psilocin and psilocybin act as agonists on cardiac 5-HT receptors.
PubMed: 38876450
DOI: 10.1016/j.toxlet.2024.06.006 -
BMC Psychiatry Jun 2024Clozapine is an off-label drug used in most countries to prevent suicide in individuals with schizophrenia. However, few studies have reported real-world prescription... (Observational Study)
Observational Study
BACKGROUND
Clozapine is an off-label drug used in most countries to prevent suicide in individuals with schizophrenia. However, few studies have reported real-world prescription practices. This study aimed to explore the association between a history of suicidal behavior and clozapine prescribing during eight weeks of hospitalization for individuals with early-stage schizophrenia.
METHODS
This observational cohort study used routine health data collected from a mental health hospital in Beijing, China. The study included 1057 inpatients who had schizophrenia onset within 3 years. History of suicidal behavior was coded from reviewing medical notes according to the Columbia Suicide Severity Rating Scale. Information on antipsychotic use during hospitalization was extracted from the prescription records. Time to clozapine use was analyzed using Cox regression models adjusted for sociodemographic and clinical covariates.
RESULTS
The prevalence rates of self-harm, suicidal behavior, and suicide attempt were 12.3%, 7.5%, and 5.4%, respectively. A history of self-harm history was positively associated with clozapine uses upon admission (4.1% vs. 0.8%, exact p = 0.009). Among those who had not used clozapine and had no clozapine contraindication, A history of suicidal behavior increased the possibility of switch to clozapine within 56 days after admission (Hazard Ratio[95% CI], 6.09[2.08-17.83]) or during hospitalization (4.18[1.62-10.78]).
CONCLUSION
The use of clozapine for early-stage schizophrenia was more frequent among those with suicidal behavior than among those without suicidal behavior in China, although the drug instructions do not label its use for suicide risk.
Topics: Humans; Clozapine; Schizophrenia; Male; Female; Adult; Antipsychotic Agents; China; Suicide, Attempted; Cohort Studies; Self-Injurious Behavior; Suicidal Ideation; Hospitalization; Young Adult; Middle Aged
PubMed: 38867174
DOI: 10.1186/s12888-024-05893-y -
BMC Psychiatry Jun 2024To analyze the economic benefits of paliperidone palmitate in the treatment of schizophrenia.
BACKGROUND
To analyze the economic benefits of paliperidone palmitate in the treatment of schizophrenia.
METHODS
We collected 546 patients who met the diagnostic criteria for schizophrenia according to the 《International Statistical Classification of Diseases and Related Health Problems,10th》(ICD-10). We gathered general population data such as gender, age, marital status, and education level, then initiated treatment with paliperidone palmitate. Then Follow-up evaluations were conducted at 1, 3, 6, 9, and 12 months after the start of treatment to assess clinical efficacy, adverse reactions, and injection doses. We also collected information on the economic burden before and after 12 months of treatment, as well as the number of outpatient visits and hospitalizations in the past year to analyze economic benefits.
RESULTS
The baseline patients totaled 546, with 239 still receiving treatment with paliperidone palmitate 12 months later. After 12 months of treatment, the number of outpatient visits per year increased compared to before (4 (2,10) vs. 12 (4,12), Z=-5.949, P < 0.001), while the number of hospitalizations decreased (1 (1,3) vs. 1 (1,2), Z = 5.625, P < 0.001). The inpatient costs in the direct medical expenses of patients after 12 months of treatment decreased compared to before (5000(2000,12000) vs. 3000 (1000,8050), P < 0.05), while there was no significant change in outpatient expenses and direct non-medical expenses (transportation, accommodation, meal, and family accompanying expenses, etc.) (P > 0.05); the indirect costs of patients after 12 months of treatment (lost productivity costs for patients and families, economic costs due to destructive behavior, costs of seeking non-medical assistance) decreased compared to before (300(150,600) vs. 150(100,200), P < 0.05).
CONCLUSION
Palmatine palmitate reduces the number of hospitalizations for patients, as well as their direct and indirect economic burdens, and has good economic benefits.
Topics: Humans; Paliperidone Palmitate; Schizophrenia; Male; Female; Antipsychotic Agents; Adult; Middle Aged; Hospitalization; Cohort Studies; Cost of Illness; Treatment Outcome
PubMed: 38867159
DOI: 10.1186/s12888-024-05874-1