Pharmacopsychiatry最新文献

Objective: We examined associations between caffeine intake, urinary caffeine biomarkers, and depressive symptoms across age groups.

Methods: We analyzed the National Health and Nutrition Examination Survey from 2005 to 2018 data from 30,817 adults aged≥18 years, categorized as younger (18-39 y), middle-aged (40-59 y), and older (≥ 60 y). Dietary caffeine, assessed using two 24-hour recalls, was modeled continuously and categorically (< 100, 100 to<200, and≥200 mg/d). Urinary caffeine and metabolites were measured in a 2009-2014 subsample (n=4,378). A nine-item Patient Health Questionnaire score of≥10 was considered to indicate depressive symptoms. Survey-weighted multivariable models estimated associations and caffeine-by-age interactions.

Results: The adjusted dietary caffeine and age interaction was significant for a nine-item Patient Health Questionnaire score of≥10 (F[4,77]=2.912, p=0.027), but not for the total nine-item Patient Health Questionnaire score (p=0.522). Among older adults, high versus low intake was associated with greater odds of a nine-item Patient Health Questionnaire score of≥10 (adjusted odds ratio=1.64, 95% confidence interval: 1.23-2.20). The spline model similarly showed an age interaction (F[2,80]=3.782, p=0.027), with predicted probabilities increasing mostly among older adults. Higher log urinary caffeine was associated with greater odds of a nine-item Patient Health Questionnaire score of≥10 among older adults (adjusted odds ratio=1.24, 95% confidence interval: 1.07-1.42; false discovery rate-adjusted p=0.012), although the global age interaction was not significant (false discovery rate-adjusted p=0.470). No adjusted urinary biomarker association with the total nine-item Patient Health Questionnaire score was significant.

Conclusion: Associations were outcome-specific: age modified the association between dietary caffeine and the presence of depressive symptoms, but not mean symptom severity. Among older adults, high intake was associated with greater odds of depressive symptoms.

Introduction: Anhedonia has been proposed as a marker of poor functional outcomes in schizophrenia. A model that omits baseline functioning estimates a different quantity from one that includes it: the former assesses whether anhedonia identifies patients who function worse later, and the later assesses whether it adds prognostic information beyond baseline functioning. We estimated both associations using data from the Clinical Antipsychotic Trials of Intervention Effectiveness trial.

Methods: We reanalysed the Clinical Antipsychotic Trials of Intervention Effectiveness Phase 1/1A Main Trial schizophrenia sample (759 rated and decisive model 672). We moved from the first quantity to the second quantity by removing the Heinrichs-Carpenter Quality of Life Scale anhedonia item from the outcome and then adding the baseline function. We repeated the test on the three Quality of Life Scale subscales without the item, screened all 21 items the same way, set anhedonia against 15 other baseline features, and tested independent outcomes, drug interactions and attrition.

Results: Baseline anhedonia predicted the 21-item Quality of Life Scale total at 12 months (standardised β=0.309, p=4.2×10^-15). Removing the item from the outcome measure did not change the association (β=0.301). Adding the baseline function collapsed it (β=0.022, p=0.58). All 21 items behaved the same way: 21 were significant in models with no baseline term, 21 with the item also removed, and 0 once baseline function was adjusted. Anhedonia ranked 13th of 21 items, 13th of 16 features, and predicted no independent outcomes.

Conclusion: Baseline single-item anhedonia in Clinical Antipsychotic Trials of Intervention Effectiveness marks concurrent clinical and functional burden. It carries no incremental prognostic value beyond the baseline function.

Introduction: Antipsychotic-induced weight gain and metabolic disturbance are common in schizophrenia, but liability varies across agents. Aripiprazole has a relatively favorable metabolic profile, yet evidence on aripiprazole once-monthly, its long-acting injectable formulation, remains limited. We hypothesized that switching from a higher liability antipsychotic would yield a greater weight reduction than switching from a lower liability agent.

Methods: This 16-week, prospective, open-label, multicenter study enrolled patients with stable schizophrenia. Participants were stratified by the metabolic liability of their prior oral antipsychotic (high vs. low). Participants received aripiprazole once-monthly 400 mg intramuscularly every 4 weeks, with cross-titration of the prior agent. Anthropometric and metabolic parameters were assessed every 4 weeks from baseline. Weight changes at week 16 were the principal outcome, and all analyses were exploratory. Mixed models for repeated measures evaluated changes over time, adjusting for covariates.

Results: Among the 151 participants (100 low-risk and 51 high-risk participants), weight, body mass index, and waist circumference decreased significantly in the high-risk group only, and more high-risk patients reached clinically meaningful improvement. Most lipid and glycemic indices changed little, although low-density lipoprotein cholesterol and total cholesterol decreased in both groups. Psychiatric symptoms remained stable. In a subgroup switched from oral aripiprazole (n=73), anthropometric and metabolic parameters were all unchanged.

Discussion: In patients previously exposed to high-metabolic-risk antipsychotics, switching to aripiprazole once-monthly was associated with short-term reductions in weight and central adiposity-consistent with the reversal of the prior agents' metabolic burden-while psychiatric stability was maintained. Longer-term studies are needed to confirm their durability and clinical significance.

Introduction: This study investigated the antisuicidal effects of repeated intravenous ketamine in patients with treatment-resistant depression and explored associations between suicidal ideation and temporal changes in selected plasma biomarkers to identify potential biomarkers.

Methods: This secondary analysis of an open-label trial included outpatients with treatment-resistant depression who received four intravenous ketamine infusions (0.5 mg/kg) over 2 weeks. Suicidal ideation was assessed at baseline and post-intervention using the Montgomery-Åsberg Depression Rating Scale (item 10), Quick Inventory of Depressive Symptomatology-Self Report (item 12), and Columbia Suicide Severity Rating Scale. Eleven targeted plasma biomarkers were quantified via liquid chromatography-mass spectrometry. Associations between suicidal ideation scores and biomarker changes were evaluated using Pearson's and Spearman's correlation coefficients, with p-values adjusted for multiple comparisons using the false discovery rate procedure.

Results: Repeated ketamine infusions were associated with modest reductions in suicide-related item scores on the Montgomery-Åsberg Depression Rating Scale item 10 (1.5±1.5 to 1.0±1.3, p=0.01) and Quick Inventory of Depressive Symptomatology-Self Report item 12 (1.3±0.9 to 0.8±0.9, p=0.01). Columbia Suicide Severity Rating Scale scores numerically decreased (1.1±1.3 to 0.8±1.2, p=0.17) without reaching statistical significance. In unadjusted analyses, improved Columbia Suicide Severity Rating Scale scores showed nominal associations with increased levels of citric acid (r=- 0.40, p=0.03) and kynurenic acid (ρ=- 0.37, p=0.04), although these did not survive false discovery rate correction.

Discussion: Repeated ketamine infusions were associated with modest reductions in suicide-related item scores on the Montgomery-Åsberg Depression Rating Scale and Quick Inventory of Depressive Symptomatology-Self Report. While no definitive biomarkers were identified after false discovery rate correction, these nominal associations are purely hypothesis-generating and require larger validation trials.

Abstract: In this review, a comprehensive overview of the brain regions, neurotransmitters and hormones involved in mood and emotions is provided. Their relevance to rhythmic changes in mood is highlighted and vice versa the influence of the circadian clock on emotion and mood, which is apparent across model organisms. The relevance of the clock especially in mood disorders major depressive disorder and bipolar disorder is a major focus with special attention given to the relationship between treatments of mood disorders and the phasing of clock and physiological rhythms. This review is meant to provide readers starting to orient themselves in the field of circadian clocks and mood disorders with a concise overview of the most relevant points and help dive deeper into specialized materials.

Introduction: Antipsychotic medications are essential in treating psychotic disorders; yet, large-scale studies examining individual patient preferences are lacking. The current study explores variations in patient perspectives on antipsychotic treatment.

Methods: Data were derived from the online decision aid Personal Antipsychotic Choice Index in the Netherlands. This freely available 30-item questionnaire assessed preferred treatment effectiveness, side effects, administration routes, and demographics, psychosis history, and antipsychotic use. Non-parametric tests compared responses by sex, age, and D₂-receptor affinity of used medication.

Results: Of 23,733 completed questionnaires, 8,743 individuals with at least one psychotic episode were included (mean age: 38.8 and male: 58.8%). Psychotic symptom efficacy was rated most important (75.4%) followed by cognitive (61.9%) and depressive (49.5%) symptom efficacy (both p<0.001). Women rated psychotic and depressive symptom efficacy more important than men (p=0.003 and p<0.001), while adolescents prioritized cognitive symptom efficacy over adults (p=0.004). Extrapyramidal symptoms (73.2%) and weight gain (68.0%) were least acceptable side effects, particularly among women (both p<0.001). Men found sexual dysfunction less tolerable than women (p<0.001). Daily tablets were considered most acceptable (91.0%), followed by weekly tablets (40.1%), injectables (32.7%), and drops (27.9%). Patients using low D₂-affinity agents were more willing to accept dizziness (p=0.002) and hypersalivation (p<0.001) than high-affinity users, who in turn accepted sexual dysfunction and menstrual problems more often (both p<0.001).

Discussion: Patient preferences regarding antipsychotic medication vary widely. Incorporating these perspectives through shared decision-making may improve trust and adherence.

Introduction: Electrocardiographic changes indicating a significantly increased risk of adverse cardiac effects, such as heart-rate corrected QT interval prolongation, are rare during antidepressant treatment; however, systematic analyses are lacking. Therefore, our study aimed at investigating the relationship between heart-rate corrected QT interval changes and both dosage and serum levels of escitalopram and venlafaxine in a well-characterized study sample.

Methods: Two hundred seven depressed patients received escitalopram (10-20 mg/d) for 4 weeks. Non-responders were switched to high-dose venlafaxine (150-375 mg/d) for an additional 4 weeks of treatment. Serum concentrations were measured weekly and electrocardiograms were recorded at baseline, day 28 and day 56. Risk factors for heart-rate corrected QT interval prolongation were included as covariates in the analysis.

Results: Escitalopram did not significantly affect heart-rate corrected QT intervals. Switching to high-dose venlafaxine resulted in a significant increase of mean QT intervals from day 29 to day 56 (p=0.007), more pronounced in men (interaction p=0.038). Heart-rate corrected QT interval prolongation occurred in 5% of patients after escitalopram and 12% after venlafaxine; notably, 12 patients experienced critical prolongations, all with higher rates of known risk factors. No correlation between serum concentrations and heart-rate corrected QT intervals were observed.

Discussion: Our findings indicate that escitalopram does not affect heart-rate corrected QT intervals, whereas venlafaxine is associated with a modest but significant heart-rate corrected QT interval prolongation, particularly in males. Although infrequent, critical prolongations highlight the need for individualized risk assessment, especially in patients with risk factors. The lack of correlation with serum concentrations suggests that pharmacokinetic monitoring alone may not reliably predict cardiac risk. Our results underscore the importance of electrocardiogram monitoring with attention to sex-specific and clinical risk profiles.

Background: As accumulating evidence suggests the antisuicidal properties of ketamine, elucidating its underlying mechanisms and predictors of treatment response has become crucial. Whether a combination of clinical markers can enhance the prediction of the antisuicidal response to ketamine remains unclear.

Methods: Using data from our previous randomized placebo-controlled and open-label trials, this post hoc analysis evaluated 67 patients with treatment-resistant depression and prominent suicidal ideation who received a single ketamine infusion of 0.5 mg/kg. A classification and regression tree model was used to identify the combinations of clinical and demographic characteristics at baseline that can predict the antisuicidal response to ketamine infusion.

Results: Combinations of clinical predictors, including mild or moderate depression severity, a shorter duration of the current episode, no more than four trials of antidepressant failures, low or moderate current suicide risks, and a history of suicide attempts, offered superior predictive power for the rapid and sustained antisuicidal effects of sub-anesthetic ketamine infusion, outperforming the predictive power of any individual predictor.

Conclusions: Clinicians can use our findings to identify individuals who are most likely to benefit from the antisuicidal effects of ketamine. Further research is required to corroborate these findings.

Social media abstract: CART found combined baseline markers, including mild/moderate depression, shorter episode, ≤4 failed antidepressants, low/moderate suicide risk, and prior attempts, predict rapid/sustained antisuicidal response of sub-anesthetic ketamine in TRD.