Journal of Clinical Psychopharmacology最新文献

Purpose/background: In the United States, clozapine is the only antipsychotic approved for preventing suicide in schizophrenia. Using the worldwide pharmacovigilance database (VigiBase), 2 studies explore fatal outcomes during suicide and other adverse drug reactions (ADRs) in adults treated with clozapine.

Methods: The first study (from inception until January 15, 2023) focused on 17,624 fatal outcomes in 6 groups after stratification by sex and age group (young, 18 to 44 y; middle-aged, 45 to 64 y; and geriatric, above 64 y). Fatal ADR outcomes were ranked by frequency; overrepresentation/underrepresentation was determined by univariate odds ratios (OR), 95% CIs, and adjusted ORs. The second study (from inception until January 1, 2024) tested differences between 752 completed suicides (cases) and 692 nonfatal suicide attempts (controls) using logistic regression.

Findings/results: In young males, the prevalence of completed suicide within fatal outcome labels was 9.2% (299/3223), second only after the unspecific label, "death"; it was significantly overrepresented when compared with females (adjusted OR=1.5 (CI 1.1-1.9; P=0.004). In the comparison of completed versus attempted suicides, the adjusted ORs were (1) 2.1 (CI: 1.7-2.7) for male sex, (2) 1.5 (CI: 1.2-2.0) for the middle-aged and 3.2 (CI: 1.6-6.3) for the geriatric groups, and (3) 7.5 (CI: 5.2-10.9) for the United States.

Implications/conclusions: The literature and this new data indicate that, for saving the lives of young males treated with clozapine, the most important focus should be on preventing completed suicide and avoiding clozapine nonadherence. In VigiBase, the proportion of fatal outcomes during US suicide attempts was 70% (261/375); other studies are needed.

Purpose/background: Atomoxetine is a selective norepinephrine reuptake inhibitor prescribed for the management of attention-deficit hyperactivity disorder (ADHD). Untreated ADHD can significantly damage a woman's well-being and often worsens during postpartum. As a result, physicians often recommend continued medication therapy during pregnancy and postpartum; however, there is limited data evaluating the safety of atomoxetine's transfer into human milk.

Methods: The InfantRisk Center's Human Milk Biorepository collected milk samples from 10 lactating participants who were treated with atomoxetine 40 to 100 mg daily. The concentrations of atomoxetine in milk were quantified using liquid chromatography-tandem mass spectrometry.

Results: The mean atomoxetine concentration in milk was 12 ng/mL at an adjusted daily dose of 80 mg, resulting in a relative infant dose (RID) of 0.19%. To estimate a worst-case scenario, the maximum concentration of 39 ng/mL was used to simulate a worst-case scenario RID of 0.65%. There were no reported adverse effects in the breastfed infants.

Conclusions: The transfer of atomoxetine into human milk is minimal, with a 0.19% RID, well below the 5% safety threshold for psychoactive medications. The minimal transfer suggests that maternal atomoxetine use poses a very low risk to breastfed infants, making it a suitable choice for medication management of ADHD in lactating women.

Purpose: To identify factors affecting valbenazine efficacy and change in tardive dyskinesia (TD) symptoms after valbenazine discontinuation using post hoc analysis of the J-KINECT study evaluating valbenazine efficacy and safety in patients with TD.

Methods: J-KINECT comprised a 6-week, placebo-controlled, double-blind period; a 42-week valbenazine extension period; and a 4-week follow-up period. Predictors for valbenazine efficacy were analyzed using multiple regression analysis for change in Abnormal Involuntary Movement Scale (AIMS) total score and logistic regression analysis for ≥50% improvement in AIMS total score, from baseline to week 6. For factors predicting changes in TD symptoms after valbenazine discontinuation, multiple regression analysis examined the change in AIMS total score from weeks 48 to 52.

Results: Factors associated with valbenazine efficacy (decrease in AIMS total score at week 6) were baseline AIMS total score and interaction terms of valbenazine dose and baseline AIMS total score (adjusted R2 =0.318). Valbenazine dose was significantly associated with ≥50% improvement in AIMS total score from baseline to week 6 [odds ratio (95% confidence interval)=1.02 (1.01, 1.03), P <0.001]. Factors associated with exacerbation of TD symptoms (increase in AIMS total score) 4 weeks after valbenazine discontinuation were baseline anticholinergic use and atypical antipsychotic use (adjusted R2 =0.182).

Conclusions: Although multiple regression analysis did not identify strong predictors of valbenazine efficacy and change in TD symptoms after valbenazine discontinuation, valbenazine dose was associated with meaningful improvement in TD. Rather than indicating efficacy in patients with specific factors, the data suggest a possible dose-dependent trend in improvement with valbenazine.

Purpose/background: Schizophrenia is often associated with nonadherence to oral antipsychotic therapy, which increases the risk of relapse, hospitalization, and higher health care costs. To overcome this challenge, long-acting injectable (LAI) antipsychotics, such as paliperidone palmitate, offer a solution by reducing relapse rates. Also, the bioequivalent formulations can enhance treatment accessibility while maintaining efficacy and safety. The present study assessed the bioequivalence of a test paliperidone palmitate extended-release injectable suspension (PP-ERIS), Vegapali, compared with the reference formulation, Invega Sustenna.

Methods/procedures: A multicenter, randomized, multiple-dose, open-label, parallel-arm pharmacokinetic (PK) study was conducted including patients with schizophrenia or schizoaffective disorder receiving monthly intramuscular injections of the test or reference formulation for 7 months. Plasma samples were collected predose and postdose to determine steady-state PK parameters, including C max,ss and AUC τ,ss . The bioequivalence was confirmed if the 90% CIs for the test/reference geometric mean ratios were within 80.00% to 125.00%. Safety assessments also included adverse event (AE) monitoring and clinical evaluations.

Findings/results: The PK analysis demonstrated that the 90% CIs for Cmax,ss and AUCτ,ss were within the required bioequivalence range. Both formulations exhibited comparable systemic exposure, and AE incidence was consistent with the known safety profile of paliperidone palmitate.

Implications/conclusions: The test formulation, Vegapali, proved to be bioequivalent to the reference product, supporting its use as an alternative LAI treatment for schizophrenia. This finding guarantees the therapeutic equivalence of both formulations, expanding access to effective and sustained treatment options for schizophrenia management.