Therapeutic Advances in Psychopharmacology最新文献

Background: Postoperative delirium (POD) is associated with higher risks of postoperative complications ‌and‌ mortality (2- to 3-fold increase). Studies investigating the effect of intraoperative ketamine on POD risk have yielded conflicting results. This study aimed to assess the effects of intraoperative ketamine and its more potent version, esketamine, on POD.

Design: Systematic review and meta-analysis.

Objective: To evaluate the effect of intraoperative ketamine/esketamine on the incidence of POD.

Methods: We adhered to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, and searched the PubMed, Embase, Medline (Ovid), Cochrane, Scopus, and Web of Science databases for the MeSH terms "ketamine" and "emergence delirium" from database inception to July 10, 2024. The primary outcome was POD incidence following general anesthesia. Data were analyzed using a common effects model, with between-study heterogeneity tested using the I ² statistic, and relative risk (RR) with 95% confidence intervals (CIs) for dichotomous data was used as the effect measure.

Results: A total of 18 studies with a total of 1571 participants met eligibility criteria. A meta-analysis of all studies suggests that the intraoperative use of ketamine/esketamine may reduce the incidence of POD (RR = 0.71, 95% CI: 0.56, 0.90, p < 0.01). In the drug subgroup, esketamine demonstrated enhanced efficacy in preventing POD compared to ketamine (RR = 0.59, 95% CI: 0.38, 0.90, p = 0.02). In addition, subanesthetic doses of ketamine/esketamine (⩽0.5 mg/kg) contributed to POD prevention (RR = 0.52, 95% CI: 0.34, 0.79, p < 0.01), whereas higher doses (>0.5 mg/kg) showed no statistically significant effect (RR = 0.89, 95% CI: 0.66, 1.21, p = 0.46). Further analysis revealed additional benefits of ketamine/esketamine in reducing POD incidence in cardiac surgery (RR = 0.46, 95% CI: 0.31, 0.68, p < 0.01), in the elderly (RR = 0.68, 95% CI: 0.52, 0.91, p < 0.01), and in the first 24 h post-surgery (RR = 0.52, 95% CI: 0.29, 0.94, p = 0.03).

Conclusion: Our findings suggest that perioperative administration of ketamine/esketamine had a protective effect against the incidence of POD, with esketamine demonstrating superior efficacy compared to ketamine. The treatment effect exhibited a dose-response relationship, with subanesthetic doses showing greater efficacy. Furthermore, ketamine/esketamine may offer additional benefits for patients with specific risk factors.

Background: Poor adherence to antipsychotic medications is the leading cause of relapses and hospitalizations in patients with schizophrenia, resulting in worse functional outcomes and quality of life. Long-acting injectable (LAI) antipsychotics are an effective therapeutic option to improve adherence, but they are often underutilized, particularly during inpatient care.

Objective: To investigate the predictive factors for LAI utilization among inpatients with schizophrenia and to assess whether initiating a LAI antipsychotic treatment during hospitalization reduces the risk of readmission.

Design: Observational prospective study.

Methods: Patients were evaluated at admission, discharge, and after 3 months. Two comparisons were performed: patients who initiated a LAI during the hospitalization versus those who continued with oral antipsychotics, and readmitted versus not-readmitted patients within 3 months. Factors statistically associated with LAI initiation or readmission were entered as independent variables in two backward logistic regression models, having "LAI initiation" and "rehospitalization at three months" as outcomes.

Results: One hundred two patients were included. Twelve were lost at follow-up. Forty-two (44%) initiated an LAI during the admission. Subjects who received LAI were significantly younger, more educated, and less adherent to treatment. Thirty (33%) patients were readmitted within 3 months after discharge. Re-hospitalized subjects had more psychiatric hospitalizations in the past and a lower rate of LAI antipsychotic treatment initiation during the studied hospitalization: 5/39 (13%) patients prescribed a LAI antipsychotic were readmitted within 3 months, compared with 25/51 (49%) prescribed an oral antipsychotic medication (OR = 0.19; p = 0.002).

Conclusion: Introducing LAI antipsychotic treatment during a psychiatric hospitalization may reduce the risk of early readmissions, thus facilitating the improvement of the course of the illness and the patient's quality of life.

Background: Suicidal ideation, attempts, and deaths present a major and tragic public health concern. Recent trials of psilocybin therapy (PT) have shown promise in treating treatment-resistant depression and have found a reduction in suicidal ideation. Given the growth of PT research, there is a need to further understand its effect on suicidal ideation, attempts, and deaths.

Objective: To assess and synthesize evidence on the effects of PT on suicidal ideation, attempts, and deaths in psychiatric patients.

Design: PRISMA-compliant systematic review and meta-analysis.

Data source: MEDLINE, EMBASE, Cochrane, and PsychINFO.

Method: Databases were searched for randomized controlled trials of PT in adults with psychiatric diagnoses that reported suicide outcomes (ideation, attempts, and deaths). Abstract and full-text screening were conducted, and suicide outcomes were extracted. Meta-analysis was performed with a random effects model to assess changes in suicide outcomes compared to control through the standardized mean difference (SMD). Assessment of heterogeneity, risk of bias, and subgroup analysis was completed.

Results: Nine studies were included (N = 593; 335 psilocybin & 258 control). Two studies were excluded from meta-analysis because suicide-related outcomes data were not available. Participants with PT experienced a small and significant decrease in suicidal ideation compared to control (k = 7, SMD = -0.24, 95% CI -0.42 to -0.06, p = 0.008, I ² = 0%). There was no publication bias found. Subgroup analysis found no significant differences between groups. No study reported suicide attempts or suicide deaths. Two studies had a high risk of bias.

Conclusion: Psilocybin therapy may reduce suicidal ideation in adults with psychiatric diagnoses. Current studies are limited by small sample size, lack of follow-up data, and assessment of blinding.

Trial registration: CRD42023445706.

Background: Extrapyramidal symptoms (EPS) in association with the long-acting, injectable, atypical antipsychotic aripiprazole once monthly (AOM) have been observed in clinical trials, but information on EPS requiring treatment with anticholinergic drugs in clinical practice is limited.

Objectives: The objective of this European post-authorisation safety study (PASS) was to assess the risk of EPS-related events, as defined by dispensings of anticholinergic drugs, linked to the use of AOM in routine clinical practice.

Design: This European cohort study was based on healthcare databases from Germany (German Pharmacoepidemiological Research Database GePaRD), Italy (Caserta and Palermo healthcare claims databases), and Sweden (National health registers). New users of AOM were followed from their first dispensing for a maximum of 2 years.

Methods: Primary study outcome was an EPS-related event, defined as the first dispensing of an anticholinergic drug. The crude incidence rate (IR) and the cumulative incidence of EPS-related events were estimated. Cox proportional hazard regression modelling was performed to further investigate the effect of potential risk factors for the occurrence of EPS-related events.

Results: A total of N = 1748 patients were eligible for inclusion into the primary study populations (Germany N = 629; Italy N = 519; Sweden N = 600). IRs of EPS-related events per 100 patient years were highest in Italy (IR = 18.4; 95% confidence interval (CI) 15.3-22.1), followed by Sweden (IR = 7.7; 95% CI 5.8-10.2) and Germany (IR = 3.4; 95% CI 2.4-4.6). Rates were highest during the first 30 days after treatment initiation. Cumulative incidences after 2 years of treatment were 27.8% (Italy), 11.5% (Sweden), and 10.0% (Germany). Diabetes and previous antipsychotic drug use were identified as risk factors for EPS-related events.

Conclusion: In this observational study, incidence rates of EPS-related events, defined as the first dispensing of an anticholinergic drug during follow-up, were compatible with the known safety profile of AOM but showed substantial regional variation.

Trial registration: EU PAS number EUPAS21056.

Background: Long-acting injectable (LAI) antipsychotics can improve treatment adherence in patients with schizophrenia. Despite their benefits, LAIs are underused in China compared to other countries. Little real-world evidence describes the impact of switching from oral to LAI antipsychotics on adherence and healthcare utilization in clinical practice in China, which could help address this gap.

Objectives: To understand utilization of LAI and to assess the impact of switching from oral to LAI antipsychotics on adherence and healthcare utilization.

Design: This is a retrospective, 1-year mirror-image study using electronic health records (2012-2019) from a psychiatric specialized hospital and the psychiatry department in a general hospital in China. The observation period was 1 year before and after LAI initiation in patients already receiving oral antipsychotics.

Methods: Adult patients (aged 18-65) who initiated LAIs after receiving oral antipsychotics, with schizophrenia diagnosis at least 12 months before LAI initiation were included. The date of LAI initiation was designated as the index date. Adherence to antipsychotics was assessed by the proportion of days covered. Schizophrenia-related healthcare utilization comprised the percentage of patients who had admissions, the duration of inpatient stays, the number of inpatient visits, and outpatient visits. Wilcoxon signed-rank test and McNemar's test were used for before-after comparison.

Results: Overall, 98 and 59 eligible patients were included in two hospitals, respectively. Treatment adherence (proportion of days covered) after switching increased significantly from 46% to 61% (p < 0.01) and 32% to 58% (p < 0.01), respectively. The frequency of hospital admissions (and cumulative admission days) reduced from 10.2% to 4.1% (6 days to 2 days, p = 0.11), and 55.9% to 10.2% (11 days to 2 days, p < 0.01), respectively. Outpatient visits increased from 5 to 6 visits (p = 0.10), and 7 to 9 visits (p < 0.01), respectively.

Conclusion: Consistent benefits of LAIs in enhancing treatment adherence and optimizing healthcare utilization were observed in two representative hospitals having different clinical settings and patient characteristics.

Background: Post-traumatic stress disorder (PTSD) is a prevalent mental illness with a high disability rate. The neurobiological abnormalities in PTSD suggest that drug therapy may have certain therapeutic effects. According to the recommendations of clinical guidelines for PTSD, the current clinical preference is for selective serotonin reuptake inhibitors (SSRIs) or serotonin and norepinephrine reuptake inhibitors (SNRIs). Nevertheless, the efficacy of other types of drugs remains uncertain, which impacts the selection of personalized treatment for patients.

Objectives: The aim of this meta-analysis was to assess the efficacy and acceptability of drugs with different pharmacological mechanisms in alleviating PTSD symptoms by comparing the response rates and dropout rates of different drug treatment groups in randomized clinical trials.

Design: Systematic review and meta-analysis.

Methods: We searched and analyzed 52 reports that described the efficacy and acceptability of medication for PTSD. Among these, 49 trials used the dropout rate as an acceptability indicator, and 52 trials used the response rate as an efficacy indicator.

Results: In the 49 trials with the dropout rate as the indicator, the dropout rate was 29% (95% confidence interval, 0.26-0.33; n = 3870). In the 52 trials with the response rate as the indicator, the response rate was 39% (95% confidence interval, 0.33-0.45; n = 3808). After drug treatment, the core symptoms of PTSD were significantly improved. This meta-analysis indicated that there was no significant difference between antidepressants and antipsychotics in improving clinical symptoms and acceptability. However, antidepressants may have a slight advantage in efficacy, although with a higher dropout rate.

Conclusion: Drug treatment is an effective rehabilitation method for PTSD patients, and individualized drug management should be considered.

Trial registration: This systematic evaluation scheme has been registered with PROSPERO (protocol ID: CRD42023462662).

Post-traumatic stress disorder (PTSD) and associated trauma and stressor-related disorders are common and debilitating, presenting significant treatment challenges due to their complex interplay of biological, cognitive, affective, somatic and social factors. Current treatments, while advancing and effective, yield limited efficacy for many individuals, underscoring the need for novel therapeutic approaches. This review explores the multifaceted nature of PTSD, emphasising its intricate predisposing and maintaining factors and explores the potential of psilocybin, a classical psychedelic, as a therapeutic agent. This review synthesises recent literature on the safety, efficacy and proposed mechanisms of action and change of psychedelic therapies for psychiatric conditions associated with traumatic stress, including treatment-resistant depression, end-of-life anxiety and anorexia nervosa. Correspondingly, it proposes a conceptual framework for psilocybin treatment in PTSD, framing the condition as a complex, maladaptive interpretive framework that is both predetermined and over-determined. A clinical narrative illustrates how psilocybin's unique psychopharmacological properties and catalysed subjective effects may facilitate therapeutic progress by disrupting this rigid and restricting framework. Finally, we offer recommendations for the safe administration of psilocybin for traumatised patients in medical research settings, emphasising the importance of rigorous and trauma-informed protocols and comprehensive patient care.

Background: Psychiatric emergencies include agitation, substance-related (e.g., withdrawal) symptoms, and suicidal as well as self-harming behavior and require interdisciplinary management. Drug treatment of geriatric patients in emergency situations may be complicated by adverse drug reactions (ADRs).

Objectives: This study aimed to investigate prescriptions of potentially inappropriate medications (PIMs) and potential drug-drug interactions (DDIs) in the context of geriatric psychiatric emergencies in the emergency department (ED).

Design: Retrospective single-center study.

Methods: The medication lists of 87 consecutively acquired geriatric patient cases receiving pharmacological treatment between January 2018 and December 2022 in a psychiatric emergency department were analyzed. Herein, utilizing the PRISCUS 2.0 list and the Fit fOR The Aged (FORTA) classification, prescriptions of PIMs were assessed, and DDIs were classified with the aid of the drug interaction program AiDKlinik® (Arzneimittel-Informations-Dienste, Dosing GmbH, Heidelberg, Germany).

Results: A total of 94 drugs were administered during treatment in the ED. The total number of drugs per patient was on average 5.9 1 (median: 5; interquartile range: 4) hereafter. 77.7% of the newly prescribed drugs were PIMs according to the PRISCUS 2.0 list, while 18.1% were designated as therapeutic alternatives to PIMs. 70.2% and 22.3% of the newly recommended drugs were FORTA category C and D drugs, respectively. An average of 0.8 (median: 0; interquartile range: 1) potential DDIs existed before psychiatric ED treatment, and 0.9 (median: 0; interquartile range: 2) potential DDIs thereafter (p = 0.002). Coercive measures-such as administration of medication against the patient's will-were rarely required in the study population.

Conclusion: The majority of all drug prescriptions for the treatment of geriatric psychiatric emergencies were categorized as PIMs according to the PRISCUS 2.0 list and the FORTA classification. However, it should be noted that these PIM classification systems were not specifically designed for geriatric psychiatric settings. The number of potential DDIs was significantly higher after drug administration in the ED than before, which should prompt the monitoring of certain clinical parameters in the further course of treatment.

Background: Long-term use of antidepressant drugs is widespread despite guidelines recommending limited duration. General practitioners (GPs) play a central role in reviewing and discontinuing antidepressants, although they hesitate to initiate a discussion about the long-term use. The potential role of pharmacists in this process is underexplored, despite their pharmaceutical expertise and accessibility.

Objectives: To explore community pharmacists' perspectives on the discontinuation of long-term use of antidepressants, and the barriers and facilitators to their involvement in this process.

Design: Qualitative study.

Methods: Semi-structured interviews were conducted with 14 Belgian community pharmacists until data saturation. Interviews were recorded, transcribed, and thematically analyzed.

Results: Four themes emerged. (1) "Antidepressants at the pharmacy: a persistent taboo" showed pharmacists' hesitancy to initiate discontinuation discussions due to societal stigma and fear of being perceived as nosy. (2) "Balancing risks vs benefits" highlights that pharmacists were primarily concerned about relapse in stable patients but recognized that a patient request from a patient experiencing side effects may facilitate discontinuation. (3) "Is this my role?," pharmacists viewed GPs as the primary decision-makers in discontinuation, limiting their role to supporting GP treatment decisions. Key facilitators for discontinuation included a GP's decision to stop and a motivated patient. Regular reviews by the pharmacist could also facilitate the discontinuation process. (4) Optimizing pharmacists' role' with a strong need for GP collaboration, and acknowledging a need to optimize knowledge and skills to support antidepressant discontinuation.

Conclusion: Our study reveals that pharmacists viewed GPs as pivotal in the discontinuation process, as they make the decisions, while they see their role as supportive, following the doctor's decision. However, they faced significant barriers to discontinuing long-term antidepressants, including fear of relapse, societal taboo, and unclear responsibilities. More education, confidence building, and better collaboration with GPs could empower pharmacists to play a proactive role, improving the antidepressant discontinuation process.