Journal of Clinical Psychopharmacology最新文献

Purpose: To evaluate the risk of bleeding associated with the simultaneous administration of antidepressants (ADs) and direct oral anticoagulants (DOACs).

Methods: PubMed, Embase, and Scopus databases were searched for papers that focused on the concomitant administration of ADs and DOACs and presented data on the bleeding outcomes. The comparator group of interest consisted of subjects who received only DOACs. Besides the overall pooled analysis, irrespective of the primary disease condition, we were also interested in studies involving patients with atrial fibrillation (AF). We therefore included studies with relevant comparisons (AD with DOACs, compared to DOACs alone), regardless of the reported underlying condition. Thereafter, we conducted a sensitivity analysis to refine estimates specific to AF. Clinical trials and observational studies were eligible. Pooled effect sizes were reported as relative risk (RR) for studies with cohort design and as odds ratio (OR) for case-control studies.

Results: Ten studies were included. Overall pooled analysis showed that treatment with both DOAC and selective serotonin reuptake inhibitor and serotonin and norepinephrine reuptake inhibitor (SSRI/SNRI) was associated with significantly higher risk of major bleeding (cohort: RR 1.25, 95% CI: 1.07-1.47; case-control: OR 1.40, 95% CI: 1.15-1.69). The risk of intracranial bleeding was found to be increased when cohort studies were pooled (RR 1.44, 95% CI: 1.24-1.66), but not with pooling of case-control studies (OR 1.58, 95% CI: 0.43-5.75). The risk of gastrointestinal bleeding and transient ischemic attack (TIA)/ischemic stroke was comparable between the 2 groups (DOAC + SSRI/SNRI vs DOAC only group).

Conclusions: Our results indicate that combined SSRIs/SNRIs and DOAC treatment may be associated with increased incidence of major and intracranial bleeding, further emphasizing the importance of caution when considering their concomitant use.

Background: Clozapine is effective for treatment-resistant schizophrenia and bipolar disorder but is often discontinued due to adverse effects. This study compared early clozapine discontinuation rates and reasons in patients with mood and psychotic disorders.

Methods: Data from all individuals with mood or psychotic disorders who initiated clozapine for the first time at the inpatient psychiatric unit of Mayo Clinic, Rochester, Minnesota, between 2014 and 2022 were retrospectively analyzed. Early clozapine discontinuation, defined as discontinuation within 90 days of initiation, was the primary outcome. Cox proportional hazards regression was used to assess factors associated with discontinuation.

Results: Of 83 patients (mood group n = 37, psychosis group n = 46), those in the mood group were older (P = 0.022) and more likely to be nonsmokers (P = 0.034). The overall 90-day clozapine discontinuation rate was 45.7%. Early discontinuation was significantly higher in the mood group than in the psychosis group (hazard ratio = 2.41, 95% confidence interval = 1.26-4.64, P = 0.008). Other factors associated with early discontinuation were female sex (P = 0.033), older age (P = 0.026), and nonsmoking (P = 0.001). In multivariable analysis, smoking status was the only factor significantly inversely associated with early clozapine discontinuation (hazard ratio = 0.47, 95% confidence interval = 0.22-0.99, P = 0.048), while diagnostic group, sex, and age did not show significant associations (all P > 0.05). Discontinuations were primarily due to adverse drug reactions in both groups.

Conclusions: Nearly half of the patients discontinued clozapine early, with higher rates in the mood group. Studies should further explore potential pharmacodynamic and pharmacokinetic factors associated with discontinuation, including the influence of smoking. Careful monitoring and personalized management of side effects are crucial for optimizing clozapine therapy and improving treatment outcomes.

Abstract: Following a decades-long decline in psychedelic research resulting from social, political, and legislative factors, there has been greatly renewed interest in these compounds' ability to treat psychiatric disorders. Classic psychedelics, encompassing both natural and synthetic psychoactive compounds, are characterized by their action as agonists or partial agonists of serotonin 5-hydroxytryptamine 2A receptors. In this comprehensive review, we summarize the latest clinical trials of classic psychedelics on depression and anxiety, attending to the patient demographics and methodology of each study. Overall, studies published since 2020 affirm the potential for classic psychedelics to treat major depressive disorder, treatment-resistant depression, bipolar II, and anxiety-spectrum disorders. However, findings are limited by short follow-up durations and nonstandard dosing and study designs. Given that many of the studies identified were post hoc analyses or follow-up studies from a select few parent studies, it is recommended that more original research be undertaken, with more diverse and larger sample sizes, standardized methodologies including blinding assessment, and long-term follow-up to identify duration of benefits and adverse reactions. It is also important to consider the role of psychological support and the therapeutic alliance in the psychedelic treatment of psychiatric disorders.

Purpose/background: Clozapine is the recommended drug for treatment-resistant schizophrenia. Drug response could be affected by numerous factors such as age, sex, body mass index, co-medication, consumption of xanthine-containing beverages, smoking, and genetic variants of the enzymes involved in clozapine metabolism (CYP1A2, CYP3A4, and, to a lesser extent, CYP2C19 and CYP2D6). This study evaluated genetic and nongenetic variables that may affect clozapine plasma concentrations in Uruguayan patients with schizophrenia.

Methods/procedures: Demographic data including sex, age, ethnicity, body weight, smoking habit, concomitant medication, and xanthine consumption were collected through a data collection form. Clozapine and norclozapine concentrations were determined using an HPLC system equipped with a UV detector. Genetic variants were determined through next-generation sequencing using Illumina sequencing technology and a panel of DNA probes.

Findings/results: Fifty patients were included in the study. After evaluation, only tobacco use and obesity had a significant impact on clozapine exposure (P < 0.05). The high prevalence of the genetic variant CYP1A2*1F may account for the significant impact that tobacco smoking has on clozapine concentrations. Some common adverse effects observed in this study depend on clozapine plasma concentrations, such as constipation and sialorrhea.

Implications/conclusions: These types of studies provide the clinician with tools to optimize clozapine therapy, attempting to use the minimum effective dose and attenuating the burden of concentration-dependent adverse reactions.