Journal of Clinical Psychopharmacology最新文献

Purpose/background: Cognitive impairment severely disrupts functioning and recovery in schizophrenia. Methylphenidate extended-release (ER) shows promise for cognition in attention-deficit/hyperactivity disorder but has limited, inconsistent evidence in schizophrenia. This study investigates low-dose methylphenidate ER's effects on cognitive and functional outcomes in schizophrenia, addressing a critical therapeutic gap.

Methods/procedures: In an 8-week, open-label, randomized crossover trial, 24 stable adults with Diagnostic and Statistical Manual of Mental Disorders, 5th edition, diagnosis of schizophrenia spectrum disorder received 4 weeks of methylphenidate ER or treatment-as-usual (TAU), with crossover at week 4, and follow-up at week 12. The primary outcome was improvement in functional capacity, measured by the Virtual Reality Functional Capacity Assessment Tool (VRFCAT), while secondary outcomes included cognitive performance, assessed by the Brief Assessment of Cognition in Schizophrenia (BACS), and symptom severity evaluated by Positive and Negative Symptoms Scale (PANSS).

Findings/results: VRFCAT scores improved significantly over time; in the first period (baseline to week 4), the medication-first arm showed improvement versus the TAU-first arm, with overall gains from baseline to week 8 of 303.47 seconds and 159.91 seconds , respectively, sustained post medication. BACS showed significant improvements in the TAU-first arm during the medication phase for Symbol Coding and Tower of London. PANSS-6 improved significantly while on study medication, notably in delusions and social withdrawal, without psychosis exacerbation. At 2-month follow-up, 75% resumed methylphenidate ER.

Implications/conclusions: While results are interpreted cautiously due to the open-label design and small sample size, this trial suggests low-dose methylphenidate ER may enhance functional capacity, specific cognitive domains, and symptoms in schizophrenia without exacerbating psychosis.

Background: Methylphenidate is a central nervous system stimulant commonly used in the treatment of attention deficit hyperactivity disorder (ADHD). While it is known to improve sustained attention, its effects on individuals without clinical conditions remain controversial. This integrative review investigates the impact of MPH in nontherapeutic settings, with a focus on cognitive and behavioral outcomes and potential side effects.

Methods: A systematic search was conducted across multiple electronic databases, including PubMed, EMBASE, Scopus, Web of Science, and PsycINFO, covering studies published from 2010 to 2021, according to a previously published protocol.

Results: A total of 33 studies were included. While findings indicate that a single dose of methylphenidate may improve attention and readiness in cognitive tasks and may enhance the efficiency of visual and motor processing, the literature about its effects on working memory, inhibitory response, food consumption, and subjective mood alteration remains controversial. Also, methylphenidate shows some increase in heart rate and blood pressure.

Conclusion: This review highlights robust evidence regarding the effects of methylphenidate on attention and readiness, in addition to minimal overall cardiovascular impact. Also, it reveals a significant lack of research on the chronic effects of the medication and lack of standardization in the methods used to measure the stimulant's effects. Limitations include the lack of a meta-analysis and a potentially restrictive search strategy, which may have reduced the number of studies analyzed.

Purpose/background: Treatment-emergent bleeding is a well-known risk with serotonergic antidepressants. Studies assessing this risk based on varying serotonergic binding affinity are limited. This report was conducted to address this gap in the literature by evaluating antidepressant-associated bleeding risks based on binding affinity to the serotonin transporter (SERT).

Methods/procedures: A sample of bleeding events from 267 patients that occurred between January 1, 2018 and January 1, 2020, within a single Veterans Affairs (VA) Health Care System was retrospectively evaluated. The primary endpoint was the percentage of veterans experiencing a bleeding event while prescribed an antidepressant with high (Ki ≤1), intermediate (Ki >1 to <10), or low (Ki ≥10) SERT binding affinity.

Findings/results: Approximately 56% of veterans who developed a bleed were prescribed an antidepressant with high SERT binding affinity compared with 17.2% and 26.6% among those receiving antidepressants with intermediate and low SERT binding affinity, respectively (P < 0.0001). The most common bleeding types were hematuria, upper gastrointestinal bleeds, and hematologic dyscrasias.

Implications/conclusions: The results suggest that veterans receiving antidepressants with high binding affinity to SERT are at a significantly higher risk of bleeding. Larger randomized prospective trials are necessary to fully elucidate these findings.

Background: Treatment-resistant depression (TRD), a clinical subtype of major depressive disorder (MDD), is associated with greater severity and functional impairment, representing a significant challenge in psychiatric care. Recent studies suggest that the use of psychedelics can provide rapid and substantial improvement in the severity of depressive symptoms. Therefore, the aim of this systematic review is to evaluate and synthesize the evidence on the efficacy of psychedelics in the treatment of TRD.

Methods: Studies were included if they enrolled participants diagnosed with TRD, used scales to assess depression severity, reported effect sizes or provided metrics for calculating effect sizes of the intervention, and involved single-blind, double-blind, or open-label trials, including single-arm studies.

Results: Fifteen articles were included in this systematic review, 10 of which were randomized double-blind controlled trials (RCTs) and 5 open-label clinical trials. All studies were summarized and analyzed, providing a current overview of the scientific literature on the therapeutic potential of typical and atypical psychedelics in TRD.

Conclusions: The use of psychedelics in the treatment of treatment-resistant depression represents an alternative and complementary therapeutic approach to traditional treatments, suggesting efficacy across different classes of these substances.

Purpose: Trazodone is metabolized by CYP3A4 to the active metabolite meta-chlorophenylpiperazine (mCPP), which is associated with various adverse drug reactions (ADRs). mCPP is further inactivated by CYP2D6. Despite the knowledge of trazodone metabolism, the evidence regarding the impact of pharmacogenetics remains limited. This study aimed to examine the association between pharmacogenetic variants in genes involved in the metabolism of trazodone and the occurrence of ADRs during trazodone treatment.

Methods: We performed an explorative observational study using available data and serum samples from 2 ongoing pharmacogenetic studies. For patients treated with trazodone, we analyzed information on trazodone tolerability, genetic variants in CYP2D6, CYP3A5, and ABCB1, as well as co-medications to assess potential drug-drug-gene interactions (phenoconversion). Serum levels of mCPP and trazodone were measured in a subset of patients.

Results: Data from 98 patients were analyzed. Reduced CYP2D6 activity was associated with an increased risk of ADRs during trazodone therapy. After accounting for phenoconversion and adjusting for sex, trazodone dose, and CYP3A5 phenotype, CYP2D6 poor metabolizers were found to be more likely to develop ADRs compared with normal metabolizers (OR: 8.96; 95% CI=1.67-48.08). No association with ADRs was found for genetic variants in CYP3A5 and ABCB1. Subgroup analysis revealed that reduced CYP2D6 activity was associated with a higher mCPP-to-trazodone ratio and a greater tendency for ADRs.

Conclusions: Our findings suggest that mCPP could contribute to trazodone-related ADRs, especially in individuals with reduced CYP2D6 metabolism. Larger clinical studies are needed to confirm that CYP2D6 genotyping could contribute to preventing ADRs in clinical practice.