Therapeutic Advances in Psychopharmacology最新文献

Approximately 15% of pregnant women experience postpartum depression (PPD). Even with currently available antidepressant treatments, many women will continue to be impaired by symptoms. Psychedelic therapy offers a promising transdiagnostic therapeutic strategy for several mental health disorders, and early results from current trials suggest that serotonergic psychedelics may represent a viable therapeutic approach for PPD. However, there is marked variability in the therapeutic response to psychedelic therapy, and the benefit-risk ratio in this population is not yet clear. To inform the rationale for the use of serotonergic psychedelics in the treatment of PPD, this review summarises the existing knowledge of immune, endocrine and neural pathways underpinning PPD and explores how serotonergic psychedelics interact with these pathways in the context of maternal motivation, bonding and caregiving behaviours. Finally, special considerations for psychedelic therapy in the postpartum period are outlined and future perspectives explored. Despite the rationale and encouraging early findings, further research is required to determine efficacy and safety profiles. Future studies, particularly longitudinal trials, should include adaptations and safeguards tailored to the unique physiological, psychological and caregiving contexts of the postpartum period.

[This corrects the article DOI: 10.1177/20451253251342628.].

What is this summary about? Antipsychotics are a type of medicine used to treat the symptoms of schizophrenia. These medicines come in various forms, including long-acting injectables (LAIs), which are taken every few weeks or months. There may be differences amongst doctors in how they approach treatment of people who are in the early phase of schizophrenia and experiencing symptoms for the first time. For instance, there may be differences in how the doctors prescribe antipsychotics, or in how they judge that their patient has recovered enough to function in their daily lives (also known as functional recovery). This summary is based on two articles that reported results from a special process called the Delphi technique. This aimed to gain agreement from a group of experts on how LAI antipsychotics should be used for people living with early phase schizophrenia. Another aim was to gain agreement on what functional recovery looks like and how it can be assessed. Based on expert agreement obtained through the Delphi technique, people with early schizophrenia could benefit from LAI antipsychotics. It was also agreed that LAIs may help people living with early phase schizophrenia reach functional recovery. Functional recovery can be represented by key aspects including depression, aggressive behavior, and social interactions. In the future, it would be useful to develop a survey or questionnaire that could assess all these key aspects.

Background: Chronic cognitive overload strains working memory and activates the body's stress response via the hypothalamic-pituitary-adrenocortical axis, potentially causing stress-related health issues. Over-the-counter herbals, including lemon balm extract, are gaining popularity for stress management, possibly due to their lack of side effects.

Objectives: To examine whether Zensera™, a lemon balm extract, produced mood and cognitive improvements throughout the day, 106 young healthy adults, with moderate stress complaints, were tested to compare the effects of 300 mg Zensera™ to a matched placebo during periods of cognitive overload.

Design: An acute, parallel groups, randomised, double-blind, placebo-controlled design was implemented with cognitive function, mood, heart rate and blood pressure measured at baseline and at 1, 3 and 5 h post-treatment.

Methods: Overall subjective calmness (primary aim) and fatigue (secondary) were captured at the beginning and end of the test day. Other transient mood measures were captured throughout the day, before and after high cognitive demand sessions.

Results: For the primary outcome, no changes in overall calmness emerged. Zensera™ elicited improved performance on the hardest executive function trials at 5 h, and multiple regression confirmed that increased performance on the hardest attention network tasks was predicted by increased calmness and contentment at 5 h. Finally, Zensera™ helped restore feelings of transient calmness following the impact of cognitive demand, which was not seen for the placebo.

Conclusion: Overall, these findings provide evidence for acute protective effects of Zensera™ in stressed adults, with benefits for challenging executive function tasks and enhanced calmness recovery following cognitive effort. Further research exploring the impact of Zensera™ for chronic stress is warranted.

Trial registration: The study was registered on clinicaltrials.gov under the code NCT06183372: https://clinicaltrials.gov/study/NCT06183372) where the trial protocol and statistical analysis plan can be accessed.

Serotonin syndrome (SS) and hyponatremia are severe, potentially life-threatening adverse reactions to serotonergic medications. Their concurrent manifestation is rare but clinically significant due to overlapping pathophysiological mechanisms. This report describes the fatal outcome of a 30-year-old female who presented to the Emergency Department with agitation following self-administration of duloxetine 60 mg, in addition to ongoing amitriptyline therapy and possible L-tryptophan supplementation. During hospitalization, she was treated with intravenous chlorphenamine for a suspected allergic reaction. Subsequently, she developed severe neurological deterioration, malignant arrhythmia, and profound acute hyponatremia (serum sodium 114 mmol/L), culminating in brain death within 48 h. The synergistic pharmacodynamic and pharmacokinetic interactions between duloxetine, amitriptyline, and chlorphenamine-three agents with serotonin reuptake inhibition properties-were implicated in precipitating SS and syndrome of inappropriate antidiuresis (SIAD)-induced hyponatremia. This combination resulted in extensive cerebral edema and cardiopulmonary arrest. The case highlights the diagnostic challenge posed by overlapping SS and hyponatremia manifestations, particularly when compounded by incomplete pharmacological histories and inappropriate drug administration. Clinicians should maintain high vigilance for SS and hyponatremia in patients receiving serotonergic agents, especially when multiple such drugs are co-administered. Comprehensive medication anamnesis, prompt electrolyte monitoring, and avoidance of pharmacodynamic duplication are essential to prevent similar outcomes.

Background: Ketamine is a rapid-acting antidepressant with robust evidence, but unclear predictors of therapeutic response.

Objectives: Based on previous knowledge, hemodynamic parameters and acute altered state of consciousness have been hypothesized as potential correlates of subsequent antidepressant outcome.

Design: A post hoc analysis was performed using the data from an open-label study, in which 39 patients with depression received a single intravenous infusion of ketamine (0.54 mg/kg). Antidepressant response was defined as ⩾50% reduction in the Montgomery-Åsberg Depression Rating Scale (MADRS) at day 7.

Methods: Systolic and diastolic blood pressure (SBP and DBP), heart rate, Clinician-Administered Dissociative States Scale (CADSS) and Brief Psychiatric Rating Scale (BPRS) were assessed during the infusion, alongside plasma levels of ketamine and norketamine. Data were analyzed using mixed-effects models and correlation and regression techniques.

Results: Responders exhibited significantly higher SBP and DBP during ketamine infusion compared with nonresponders. The degree of dissociation or psychotomimetic symptoms during the infusion did not differ significantly between responders and nonresponders. Antipsychotic (AP) augmentation was associated with worse antidepressant outcome as well as with lower infusion-related blood pressure values. CADSS and BPRS did not differ between AP users and nonusers. None of the parameters correlated with plasma levels of ketamine or norketamine.

Conclusion: Higher blood pressure during ketamine administration was associated with better antidepressant outcome, supporting the hypothesis concerning sympathetic activation in treatment responders. Psychological parameters (as measured by CADSS and BPRS) were not linked to subsequent outcomes and did not resolve inconsistencies in previous studies. Concomitant antipsychotic medication attenuated ketamine's antidepressant effects.

Trial registration: EudraCT 2018-001539-39.

Background: Bipolar disorder (BD) is associated with a higher prevalence of chronic kidney disease (CKD) and increased mortality, yet individuals with both BD and CKD are less likely to receive kidney replacement therapy (KRT). Sodium-glucose cotransporter-2 inhibitors (SGLT2is) provide renal protection in diabetes, but their long-term effects in this high-risk population remain unknown.

Objectives: To evaluate whether SGLT2i use reduces the risk of KRT and all-cause mortality in adults with BD and mild-to-moderate CKD (stage ⩽ 3).

Design: Observational cohort study with propensity score matching (PSM).

Method: In this study using TriNetX (2009-2024) real-world database, 89,369 adults with BD and mild-to-moderate CKD were classified as SGLT2i users (n = 12,736) or nonusers (n = 76,633). Primary outcomes were progression to KRT and all-cause mortality over 5 years. Adjusted hazard ratios (aHRs) were estimated using Cox proportional hazards models, and 1:1 PSM reduced confounding. Subgroup analyses examined sex, race/ethnicity, diabetes status, CKD stage, and mood stabilizer use.

Results: SGLT2i use was associated with lower risk of KRT (aHR 0.47 (95% CI, 0.42-0.53)) and all-cause mortality (aHR 0.69 (95% CI, 0.65-0.73); both p < 0.001). Protective effects were consistent across subgroups, including individuals receiving lithium, lamotrigine, valproate, or antipsychotics. After PSM (10,967 matched pairs), 5-year KRT-free survival was 94.61% versus 90.99%, and overall survival was 78.67% versus 67.53% (both p < 0.001). Given the observational design, the possibility of residual or unmeasured confounding canot be excluded.

Conclusion: SGLT2i therapy in individuals with BD and mild-to-moderate CKD is associated with substantially lower risks of KRT and all-cause mortality. Prospective trials are needed to confirm these findings.

Background: Psychiatric patients have a high risk of obesity, frequently due to psychotropic medication-induced weight gain. However, real-world comparative data on antiobesity medications (AOMs) in this population remain rare.

Objectives: To compare short-term weight-loss efficacy, adverse events (AEs), and early discontinuation (ED) among psychiatric outpatients taking liraglutide (LIRA), naltrexone/bupropion, phentermine-topiramate (PT), or metformin (MET).

Design: Retrospective observational cohort study.

Methods: We conducted a 12-week retrospective chart review of 117 psychiatric outpatients with International Classification of Diseases, 10th Revision, F01-F99 diagnoses. Percent weight change over time was analyzed using linear mixed-effects models. AEs and ED were compared across treatment groups.

Results: Compared with MET, LIRA was associated with a greater percent weight reduction (estimate -3.45%, 95% confidence interval (CI) -5.35 to -1.55, p < 0.001), with a significant treatment-by-time interaction at 12 weeks (p = 0.019). Female sex and full-time employment were associated with attenuated weight loss, and the number of concomitant psychotropic medications with moderate weight-gain risk showed a trend toward greater weight reduction (p = 0.066). No significant differences were observed in AE incidence across AOMs. ED rates differed by drug type (p = 0.017), being lowest in the MET group (39.1%) and highest in the PT group (72.2%).

Conclusion: In this real-world psychiatric cohort, LIRA was associated with greater short-term weight loss than MET without an increased observed frequency of AEs. ED rates varied across AOMs. These findings should be interpreted cautiously, given the observational design and short follow-up period, and require confirmation in larger, long-term studies.

Background: Lithium, the gold standard treatment of bipolar disorder (BD), is thought to cause nephropathy in long-term users. However, the role of confounding variables linked to BD in exerting this adverse effect remains unclear.

Objectives: This paper evaluates kidney function in patients with affective disorders who are taking lithium compared to patients not on lithium treatment.

Design: This article is a systematic review and meta-analysis.

Data sources and methods: A comprehensive search of publications up to October 2023 within Cochrane, Embase, PubMed, Scopus, Web of Science, and CINAHL databases was performed. Three assessors screened and extracted data from eligible observational studies. Risk of bias assessment was done with the ROBINS-E tool. Eligible studies were comparative studies of adult patients with diagnoses of affective disorders, including BD on lithium, with control groups not on lithium, reporting kidney function outcomes.

Results: Mean estimated Glomerular filtration rate (eGFR) showed less favorable outcomes in the lithium group compared to the non-lithium group (n = 1622, MD = -11.14 ml/min/1.73 m², 95% CI: -16.61, -5.68, I ² = 86%). The mean annual eGFR decline comparison favored the non-lithium group (n = 13,280, MD = 0.13 ml/min/1.73 m², 95% CI: 0.06, 0.20,I ² = 0%). Serum creatinine concentration (mg/dl) was found to be higher in the lithium compared to non-lithium groups (n = = 1704, MD = 0.05, 95% CI: 0.03, 0.07,I ² = 3%). New or progressing chronic kidney disease events were not found to be statistically different between the lithium and control groups (n = = 17,740, OR = 2.16, 95% CI: 0.59, 7.94,I ² = 99%). The high heterogeneity in this meta-analysis limits the reliability and interpretability of our results.

Conclusion: Kidney function, as measured by eGFR, was decreased in the lithium-taking groups versus the non-lithium groups. Continuous monitoring and discussion of risks and benefits with patients, especially those with a baseline of reduced kidney function, is imperative.

Trial registration: This review was registered prospectively with PROSPERO (CRD42024517414).