International Clinical Psychopharmacology最新文献

The aim of this analysis was to examine the impact of treatment with lurasidone on a broad range of symptoms during an acute episode of schizophrenia. In patients with an acute exacerbation of schizophrenia treated with lurasidone in a 6-week, double-blind, placebo-controlled trial, a mixed-effect model for repeated measures was used to analyze weekly change in both the five Marder Factors and the 30 individual items of the Positive and Negative Syndrome Scale (PANSS). Treatment with lurasidone was associated with significant endpoint improvement on all five Marder PANSS factors with effect sizes ranging from 0.22 to 0.44. Significant early (week 2), sustained improvement was observed on four of the five Marder Factors, with significant improvement occurring by week 4 on the Marder Negative Symptom factor. In addition to significant improvement on five out of eight Marder Positive Symptom items, the following non-Positive PANSS items were notable for being especially responsive to lurasidone treatment in terms of significant early improvement and endpoint effect sizes >0.3: anxiety, tension, preoccupation, active social avoidance, and conceptual disorganization. The results of this non-USA study confirm results from previous studies indicating that lurasidone is an effective antipsychotic medication.

Treatment adherence is the cornerstone of the management of psychiatric disorders in the prevention of acute symptom exacerbation, relapse, and hospitalization. Patients are usually treated with psychotropic polypharmacy, including complex regimens, which may contribute to nonadherence. In this real-world acute setting study, we used direct [therapeutic drug monitoring (TDM)] and indirect (emergency room and acute ward clinical judgments) measures to assess adherence in 145 patients with severe mental illnesses. Logistic regressions were used to predict adherence and agreement between adherence measures. The adherence estimates were predicted by sociodemographic and clinical factors and differed across methods: 24.8% for TDM, 55.9 and 50.4% for emergency room and acute ward clinical judgments, respectively. TDM aligned with clinical judgments in about 50% of cases, whereas the agreement between independent clinical judgments reached 84.9%. The concordance on adherence estimates between methods was influenced by sociodemographics, lifestyle, and clinical factors. Our findings underscore a discrepancy between different methods of adherence estimation. These methods capture distinct aspects of adherence and differ in their applicability and reliability, especially in acute settings. Future studies, integrating direct and indirect adherence estimates, are warranted to improve the accuracy of treatment adherence estimation for decision-making in managing exacerbation of psychiatric disorders.

Cognitive dysfunction is a core feature of schizophrenia spectrum disorders and a major determinant of functional outcomes. This study aimed to: (a) systematically review randomized controlled trials (RCTs) evaluating the cognitive effects of third-generation antipsychotics (TGAs: brexpiprazole, cariprazine, lumateperone, and lurasidone) and xanomeline-trospium; and (b) perform a network meta-analysis (NMA) including additional second-generation antipsychotics with potential procognitive effects. A systematic literature search identified eligible RCTs, which were combined with trials on aripiprazole, olanzapine, quetiapine, risperidone, and ziprasidone from a previous meta-analysis. A frequentist NMA (random-effects model) was conducted using standardized mean differences (SMDs) in pre-post cognitive scores. Associations between cognitive outcomes, follow-up duration, and SMDs for psychotic symptoms were examined; metaregression controlled for age and psychosis severity. Fourteen RCTs (n = 2464) met the inclusion criteria. Lurasidone (Hedges' g = 0.46) and xanomeline (g = 0.30) outperformed placebo in improving global cognitive performance, whereas quetiapine (g = 0.64) and cariprazine (g = 0.20) had the most favorable impacts on attention. Cognitive SMDs were unrelated to follow-up duration or improvements in psychotic symptoms. Age and baseline psychosis severity did not influence cognitive response. In conclusion, selected second and TGAs, including M1/M4 receptor agonists such as xanomeline, may offer promising treatment options for cognitive dysfunction. Further research should personalize pharmacological strategies based on cognitive profiles.

Obstructive sleep apnea (OSA) is a prevalent sleep disorder linked to significant daytime sleepiness and mood disturbances. Continuous positive airway pressure (CPAP) therapy is the standard treatment for OSA, but its effects on mental health outcomes, are not well understood. This study aimed to evaluate the impact of CPAP on daytime sleepiness, depressive symptoms, and anxiety symptoms while assessing how improvements vary with age. A total of 98 participants diagnosed with OSA were included in this study. Pretreatment and posttreatment scores for daytime sleepiness [Epworth Sleepiness Scale (ESS)], depression [Patient Health Questionnaire (PHQ)], and anxiety [Generalized Anxiety Disorder (GAD)] were collected. Improvements were calculated as the difference between pretreatment and posttreatment scores. Age, sex, ethnicity, apnea-hypopnea index, and CPAP compliance, were analyzed. Significant improvements were observed across all age groups after CPAP treatment: ESS scores improved by a mean of 5.6 points ( P  < 0.001), PHQ scores improved by 6.3 points ( P  < 0.001), and GAD scores improved by 1.1 points ( P  = 0.002). CPAP therapy effectively reduced daytime sleepiness, depression, and anxiety in patients with OSA, with significant age-related differences in outcomes. Younger individuals benefited most from treatment.

Schizophrenia is a serious psychiatric condition requiring continuous treatment with antipsychotic medications available in different formulations, including oral antipsychotics (OAPs) and long-acting injectables (LAIs). This narrative review aims to comprehensively outline the advantages and disadvantages of OAPs and LAIs to support clinicians in choosing different formulations based on the presentation of clinical symptoms. An electronic search of the PubMed database was performed in June 2024, and additional articles were retrieved from the references or personal knowledge of the authors. Relevant advantages of OAPs identified in the literature include dosing flexibility, ease of discontinuation, lower cost, autonomy of patient administration, shorter time to steady-state, and wide choice of molecules, including risk of nonadherence, plasma level fluctuations, food and drug interactions, and polypharmacy. LAIs' advantages include improved adherence leading to reduced relapse rates and hospitalizations, patient convenience, and stable drug levels while disadvantages include discomfort of injection, possible stigma, less manageable drug interactions, organization of administration centers, and patient preference possibly contrary to physician preference. When treating schizophrenia, it is critical to consider patients' needs, preferences, and history of medication adherence. Combining patient education with individualized treatment plans may optimize outcomes and improve the quality of life.

This study aims to elucidate current trends in clinical practice for managing depression in elderly patients, focusing on the utilization of pharmacotherapeutics and integrated care models to improve patient outcomes. A comprehensive survey was conducted among physicians from various European countries to gather insights into prescribing habits, treatment patterns, and the impact of comorbidities on therapeutic choices, with a focus on trazodone. The participants included psychiatrists, general practitioners, and neurologists actively involved in elderly depression care. The findings reveal a preference among physicians for using antidepressants like trazodone, due to efficacy and tolerability. Selective serotonin reuptake inhibitors and serotonin-noradrenaline reuptake inhibitors were also commonly prescribed, while tricyclic antidepressants and monoamine oxidase inhibitors were less favored. Psychiatric conditions and sleep disturbances significantly influenced treatment decisions. The survey underscored the importance of multidisciplinary management and the crucial role of caregivers in the treatment process. Effective management of depression in the elderly demands a precision approach that incorporates a thorough understanding of pharmacology, comorbidities, and a collaborative approach to maximize the effects of treatment while trying to minimize polypharmacy and the co-occurring side effects. The study highlights the need for tailored treatment strategies that address the complex needs of the elderly to enhance their quality of life and treatment outcomes.

The benefit of selective serotonin reuptake inhibitors (SSRIs) in improving quality of life (QoL) has been investigated in randomized-controlled trials (RCTs) with equivocal results. This study explored whether SSRIs could improve QoL in individuals with medical, psychiatric, and neuropsychiatric conditions. RCTs were searched in PubMed, Embase, Scopus, Ovid, and Google Scholar. Data were synthesized via a meta-analysis. Subgroup and meta-regression analyses were performed. The sample size was 9,070. Compared with placebo, SSRIs showed statistically significant improvements in QoL in cancer ( d  = 0.30), major depressive disorder ( d  = 0.27), premenstrual dysphoric disorder ( d  = 0.38), type 2 diabetes mellitus ( d  = 0.48), persistent depressive disorder ( d  = 0.32), and menopausal symptoms ( d  = 0.40). Paroxetine exhibited the highest effect size. No significant improvements were noted in chronic obstructive pulmonary disease ( d  = 0.65, P  = 0.09), congestive heart failure ( d  = 0.46, P  = 0.27), and irritable bowel syndrome ( d  = 0.26, P  = 0.127). The reduction in depressive symptoms improved QoL. Small-study effects, high attrition rates, and demographic imbalances are limiting factors to recommend SSRIs to improve QoL. Future research should focus on QoL domains and pharmacological properties of each SSRI.

Treatment-resistant depression (TRD) has great clinical importance because it has the highest disability burden of all depressive conditions. We investigated the prevalence of TRD and identified the risk and protective factors associated with antidepressant resistance among adult patients with major depressive disorder (MDD). A total of 176 132 adult patients with MDD were selected from the Taiwan National Health Insurance Research Database between 2001 and 2010 and followed for 1 year. TRD was defined as nonresponse to at least two antidepressants, and treatment-resistant tendency was defined as nonresponse to at least the first antidepressant. General physical condition measured by the Charlson Comorbidity Index (CCI), psychiatric comorbidities, and economic status were assessed. Only 2.6% ( n  = 4608) of the adults with MDD met the TRD criteria, but 26.4% ( n  = 46 491) were classified as having treatment-resistant tendency. The following psychiatric comorbidities were related to TRD: anxiety disorders [odds ratio (OR): 1.88], substance use disorders (OR: 1.73), alcohol use disorders (OR: 1.27), and personality disorders (OR: 2.12). In addition, a more severe physical condition (higher CCI) increased the likelihood of TRD (OR: 1.12). Psychiatric comorbidities and poor general physical condition may increase the likelihood of antidepressant treatment failure.

Depression is a common comorbidity in Parkinson's disease (PD), significantly reducing patients' quality of life. This mini-review examines pharmacological and nonpharmacological therapies for managing depression in PD, analyzing their benefits, and limitations. Pharmacological options include tricyclic antidepressants, selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), levodopa, dopaminergic agonists, and monoamine oxidase B inhibitors. Nonpharmacological strategies involve brief psychodynamic therapy, cognitive-behavioral therapy (CBT), physical exercise, phytomedicine, massage therapy, music therapy, phototherapy, yoga, repetitive transcranial magnetic stimulation (rTMS), transcranial direct current stimulation, electroconvulsive therapy (ECT), and deep brain stimulation. SSRIs, SNRIs, and some dopamine agonists have shown effectiveness and good tolerability, especially when combined with CBT or rTMS. For severe or refractory cases, ECT remains a viable option. Although many of these therapies show promise, the limited number and scale of studies for each treatment restrict the strength of current evidence. Further large-scale, multicenter randomized-controlled trials are essential to validate these preliminary findings and establish evidence-based guidelines. In addition, the potential benefits of social support and brief psychodynamic therapy in the context of PD-related depression require further exploration to provide holistic care strategies for this population.

Neutropenia and the more severe, potentially life-threatening agranulocytosis are recognized side effects of clozapine that require regular, mandatory, and life-long blood monitoring. However, most cases of haematological adverse effects occur in the first few months of treatment; therefore, there are now increasing calls for the termination of the mandatory monitoring after this initial period. In this report, we present a patient with treatment-resistant schizophrenia who was successfully treated with clozapine yet developed neutropenia after 9 years. This soon evolved into agranulocytosis requiring the use of granulocyte colony-stimulating factor and eventual clozapine cessation. Such late-onset cases of agranulocytosis are isolated and rare but should not impede the drive to relax mandatory clozapine haematological monitoring, but patients and carers must be aware of potential symptoms of agranulocytosis.