Verification of successful maintenance by serum drug level during a guided antipsychotic reduction to reach minimum effective dose (GARMED) trial.

BACKGROUND: Inconsistent results regarding the risk of relapse and better subjective outcomes of previous antipsychotic dose reduction trials in patients with remitted psychosis have not been verified using therapeutic drug monitoring (TDM). This study examined plasma drug concentrations of a dose-tapering trial which exhibited the potential of successful maintenance under lower antipsychotic dosages. METHODS: A 2-year open-label randomized prospective trial recruited remitted patients to undergo guided antipsychotic tapering. Blood samples were collected at baseline, annually, and after each dose reduction. Plasma aripiprazole/dehydroaripiprazole concentrations were determined using LC-MS/MS. The relationship between the dose and serum drug levels was examined using Spearman's correlation. Divided at 120 ng/mL, relapse rate, global function, quality of life, and psychopathology were compared between high- and low- drug level groups. RESULTS: A total of 126 blood samples were collected, after excluding13 samples due of non-adherence. The correlation coefficients between dosage and drug level were 0.853 (aripiprazole) and 0.864 (dehydroaripiprazole), and the dose and concentration plots were parallel along the tapering trajectories, except patients with non-adherence. The concentration-to-dose ratio of aripiprazole in this cohort, 17.79 ± 7.23 ng/mL/mg, was higher than that in Caucasian populations. No significant differences were observed in the clinical outcomes between the high- and low-level groups. Remarkably, 12 of 15 patients maintained remission at plasma aripiprazole concentrations of <120 ng/mL. CONCLUSIONS: The lower-than-expected doses reached in our antipsychotic tapering trial were substantiated to provide adequate prophylactic effects by TDM results in a subset of patients treated with aripiprazole, even considering the differences in pharmacogenomics between ethnicities.

Effectiveness of cognitive behavioural-based interventions for adults with attention-deficit/hyperactivity disorder extends beyond core symptoms: A meta-analysis of randomized controlled trials.

OBJECTIVES: To provide an updated systematic review of randomized controlled studies for the efficacy of cognitive behavioural therapy (CBT) in treating adults with attention-deficit/hyperactivity disorder (ADHD). DESIGN: Meta-analysis. METHODS: PROSPERO registration: CRD42021273633. The methods used aligned with the PRISMA guidelines. Database searches identified CBT treatment outcome studies eligible for conducted meta-analysis. Treatment response was summarized by calculating the standardized mean differences for changes in outcome measures for adults with ADHD. Measures included core and internalizing symptoms and were assessed on the basis of self-reporting and investigator evaluation. RESULTS: Twenty-eight studies met the inclusion criteria. This meta-analysis indicates that CBT for adults with ADHD was effective in reducing both core and emotional symptoms. Decreases in depression and anxiety were predicted by the reduction of core ADHD symptoms. An increase in self-esteem and quality of life were also observed for adults with ADHD who were received CBT. Adults who received either individual or group therapy significantly exhibited a greater reduction of symptoms than those who received active control intervention, received treatment as usual, or were on the treatment waitlist. Traditional CBT was equally effective in reducing core ADHD symptoms but outperformed other CBT approaches in reducing emotional symptoms among adults with ADHD. CONCLUSIONS: This meta-analysis offers cautiously optimistic support for the efficacy of CBT in treating adults with ADHD. The additional reduction of emotional symptoms demonstrates the potential of CBT in adults with ADHD who are at higher risk for depression and anxiety comorbidities.

Impacts of early clinical exposure on undergraduate student professionalism-a qualitative study.

INTRODUCTION: Early clinical exposure (ECE), or authentic human contact in a social or clinical context during preclinical training, has been adopted by many medical schools. This study aims to investigate how medical students' sense of professionalism changed after ECE intervention, with the aim of informing curriculum design to enhance student awareness of the importance of medical professionalism. METHOD: Focus groups of ECE students were held to collect data for the study. All participants read interview guidelines before starting. During the focus groups, the students discussed their medical obligations as perceived throughout the course, which offered a choice between four different ECE tracks. They were then asked to report their understanding of the situations they encountered during the course and reflect on their implications. RESULTS: Six focus groups of 22 students in total from a medical school in northern Taiwan were held shortly after the students completed an ECE course in September 2019. From their responses, 10 categories relating to medical professionalism were deduced categorized under 5 major dimensions. An additional 8 sub-dimensions on attitudes and 2 sub-dimensions on personal well-being were also identified as new categories separate from but related to medical professionalism. After the ECE intervention, about 59% of participants redefined their understanding of medical professionalism. CONCLUSION: ECE and intensive interaction with key stakeholders, including patients and their families, help students in the early stages of medical education form and cultivate a sense of medical professionalism. However, the relationship between participants' personalities, motivations, and clinical activities requires further investigation.

Neutropenia after the coadministration of clozapine and nirmatrelvir-ritonavir in a patient with SARS-CoV-2 infection: A case report with a literature review.

Background: Schizophrenia is considered one of the major risk factors for mortality from SARS-CoV-2 infection. Early antiviral treatment is important to decrease the risk of mortality. Currently, Paxlovid (nirmatrelvir-ritonavir) has been widely used in SARS-CoV-2 patients with risk factors. However, drug-drug interactions with anti-psychotics are prominent and complicated. Case presentation: We report a clozapine-treated patient with SARS-CoV-2 infection who developed neutropenia after coadministration with Paxlovid. In this case, clozapine was used for over 15 years, without neutropenia development. However, severe neutropenia (absolute neutrophil count = 523/µl) developed 3 days after the coadministration of Paxlovid 2 doses per day, valproic acid 1,000 mg per day and clozapine 100 mg per day. The development of neutropenia may be attributed to the complicated interaction among Paxlovid, SARS-CoV-2 infection, valproic acid, fluvoxamine and clozapine. Conclusions: Neutropenia is a rare but life-threatening event if a concomitant infection occurs. The risk may increase during SARS-CoV-2 infection and the coadministration of clozapine and Paxlovid. Although the exact causes of neutropenia in this patient are not fully clear, the white blood cell count and absolute neutrophil count should be closely monitored during the administration of Paxlovid in clozapine-treated patients with SARS-CoV-2 infection.