Therapeutic Advances in Psychopharmacology最新文献

Background: Preliminary evidence suggests that classic psychedelics may be effective in the treatment of some psychiatric disorders, yet little remains known about their effects on health behavior and physical health.

Objectives: The purpose of this study was to investigate associations of lifetime classic psychedelic use and psychological insight during one's most insightful classic psychedelic experience with health behavior and physical health.

Methods: Using data representative of the US population with regard to sex, age, and ethnicity (N = 2822), this study examined associations of lifetime classic psychedelic use and psychological insight with health behavior and physical health.

Results: Lifetime classic psychedelic use was associated with more healthy tobacco-related and diet-related behavior (β = 0.05 and 0.09, respectively). Among lifetime classic psychedelic users (n = 613), greater Psychological Insight Questionnaire (PIQ) total scale, PIQ Avoidance and Maladaptive Patterns (AMP) subscale, and PIQ Goals and Adaptive Patterns (GAP) subscale scores were each associated with higher odds of more healthy exercise-related behavior [adjusted odds ratios (aOR) (95% confidence interval, CI = 1.38 (1.13-1.68), 1.38 (1.13-1.68), and 1.32 (1.10-1.60), respectively] and higher odds of having a healthy body mass index (BMI) [aOR (95% CI) = 1.32 (1.07-1.63), 1.36 (1.10-1.69), and 1.23 (1.01-1.50), respectively], and greater GAP subscale scores were associated with more healthy diet-related behavior (β = 0.10). All PIQ scales were positively associated with some health behavior improvements (overall, diet, exercise) attributed to respondents' most insightful classic psychedelic experience (β = 0.42, 0.18, and 0.17; β = 0.40, 0.19, and 0.17; and β = 0.40, 0.15, and 0.15, respectively), but only PIQ total scale and AMP subscale scores were positively associated with alcohol-related health behavior improvements (β = 0.13 and 0.16, respectively).

Conclusion: Although these results cannot demonstrate causality, they suggest that psychological insight during a classic psychedelic experience may lead to positive health behavior change and better physical health in some domains, in particular in those related to weight management.

Background: Cannabidiol (CBD) is a promising novel candidate treatment for psychosis. It has a more benign side effect profile than antipsychotic medications, and being treated with CBD is not perceived as being stigmatising. These observations suggest that patients with psychosis would find CBD to be a relatively acceptable treatment.

Objective: This study tested the above hypothesis by assessing the views of a sample of patients.

Methods: Patients with a psychotic disorder were invited to complete a survey exploring their expectations about the efficacy and side effects of CBD.

Results: Seventy patients completed the survey. The majority (86%) were willing to try CBD as a treatment. Most patients believed that CBD would improve their psychotic symptoms (69%) and that it would have fewer side effects than their current medication (64%; mainly antipsychotics). A minority of patients (10%) were concerned that CBD might exacerbate their psychotic symptoms. This, however, appeared to reflect confusion between the effects of CBD and those of cannabis.

Conclusion: Most patients with psychosis regard CBD as an acceptable treatment. Although CBD has not yet been approved as a treatment for psychosis, many patients are aware of it through the presence of CBD in cannabis and in health supplements. When added to the emerging evidence of its efficacy and the low risk of side effects, the high acceptability of CBD underlines its therapeutic potential.

Background Epigenetic modulators have been proposed as promising new drug targets to treat adverse remodeling in heart failure. Here, we evaluated the potential of 4 epigenetic drugs, including the recently developed histone deacetylase 6 (HDAC6) inhibitor JS28, to prevent endothelin-1 induced pathological gene expression in cardiac myocytes and analyzed the chromatin binding profile of the respective inhibitor targets. Methods and Results Cardiac myocytes were differentiated and puromycin-selected from mouse embryonic stem cells and treated with endothelin-1 to induce pathological gene expression (938 differentially expressed genes, q<0.05). Dysregulation of gene expression was at least in part prevented by epigenetic inhibitors, including the pan-BRD (bromodomain-containing protein) inhibitor bromosporine (290/938 genes), the BET (bromodomain and extraterminal) inhibitor JQ1 (288/938), the broad-spectrum HDAC inhibitor suberoylanilide hydroxamic acid (227/938), and the HDAC6 inhibitor JS28 (210/938). Although the 4 compounds were similarly effective toward pathological gene expression, JS28 demonstrated the least adverse effects on physiological gene expression. Genome-wide chromatin binding profiles revealed that HDAC6 binding sites were preferentially associated with promoters of genes involved in RNA processing. In contrast, BRD4 binding was associated with genes involved in core cardiac myocyte functions, for example, myocyte contractility, and showed enrichment at enhancers and intronic regions. These distinct chromatin binding profiles of HDAC6 and BRD4 might explain the different effects of their inhibitors on pathological versus physiological gene expression. Conclusions In summary, we demonstrated, that the HDAC6 inhibitor JS28 effectively prevented the adverse effects of endothelin-1 on gene expression with minor impact on physiological gene expression in cardiac myocytes. Selective HDAC6 inhibition by JS28 appears to be a promising strategy for future evaluation in vivo and potential translation into clinical application.

Tardive dyskinesia (TD) is a movement disorder that can develop with the use of dopamine receptor-blocking agents and is most commonly caused by antipsychotics. The use of antipsychotics is expanding, which may lead to an increased number of patients experiencing TD. To summarise the current knowledge of the epidemiology and risk factors for TD in Japan, we reviewed articles related to the current state of knowledge around TD identified through a PubMed search, and held a roundtable discussion of experts in Japan on 9 September 2021 to form the basis of the opinion presented within this review. The true prevalence of TD among patients treated with antipsychotics is not well characterised; it is reported to be between 15% and 50% globally and between 6.5% and 7.7% in Japan. Potential barriers to timely treatment of TD include the stigma surrounding mental health issues and the lack of data regarding TD in Asian patients. This review summarises the current knowledge of the epidemiology, challenges to TD diagnosis and risk factors for TD in Japan. Recent strategies for symptom monitoring and early diagnosis, as well as consensus recommendations are included. Achieving a high level of awareness of TD among physicians who treat patients with psychiatric disorders is of great importance and physicians should ensure that patients with psychiatric disorders receiving antipsychotics are proactively monitored for signs of TD.

Plain language summary: Plain Language Summary (In Japanese).

Visual summary: Visual Summary (In Japanese).

Background: Clozapine is associated with a diverse range of side effects. In addition, patients prescribed clozapine commonly suffer with medical comorbidities.

Objectives: This study aimed to characterise patients prescribed clozapine who required medical admission, understand reasons for admission, identify areas for interventions to prevent future admission and describe clozapine management during the inpatient stay.

Design: We conducted a retrospective analysis of patients prescribed clozapine who were admitted to a general medical hospital in a 12-month period.

Method: Data were collected using electronic drug charts and notes.

Results: In total, 114 clozapine patients were hospitalised. Twenty-eight patients (25%) were admitted because of infection, 12 (11%) were elective admissions and 12 (11%) had gastrointestinal problems. Most patients admitted were Black (54%) and half were female. Few changes were made to clozapine dosing on admission or during the inpatient stay. Most patients had been taking clozapine for many years at the point of admission, the majority were able to continue taking it for the duration of their medical treatment and were discharged on the same dose they were taking prior to admission. Clozapine plasma concentrations were not consistently measured with only 18 (16%) patients having one or more plasma concentrations determined during their admission. The median clozapine plasma concentration on admission was 0.48 mg/L (nor-clozapine 0.21 mg/L), with a range of 0.09 to 3.9 mg/L. Three patients were admitted to the intensive care unit during their admission; all were discharged on clozapine. Four patients died; one from lung adenocarcinoma, one bowel obstruction, one cardiac arrest and one chest sepsis. In total, 27 patients (23%) had their clozapine stopped on admission, 6 (22% of this group) unintentionally.

Conclusions: Our study found that the most common reason for admission for patients taking clozapine was infection. Plasma concentrations were not measured routinely despite clozapine having a narrow therapeutic index and enhanced potential for toxicity in the medically unwell patient.