-
Behavioural Brain Research Jun 2024Major depressive disorder (MDD) affects millions of people worldwide, with women at a higher risk during the childbearing age. Vortioxetine (VOX) and Vilazodone (VLZ)...
Major depressive disorder (MDD) affects millions of people worldwide, with women at a higher risk during the childbearing age. Vortioxetine (VOX) and Vilazodone (VLZ) are newer antidepressants with improved therapeutic profile commonly used, but their safety during pregnancy and long-term effects on offspring are poorly understood due to paucity of literature in preclinical and clinical studies. This study aimed to investigate whether prenatal exposure to VOX and VLZ impacts depressive- and anxiety-like neurobehavioral alterations in offspring, focusing on neurotransmitter-mediated mechanisms. Pregnant Wistar dams received either VOX or VLZ, 1mg/day and 2mg/day of the drug orally from gestation day (GD) 6 to 21. The dams naturally delivered their offspring and reared until they reached postnatal day (PND) 21. Offspring of both sexes were tested for display of depressive-and anxiety-like behaviors from PND 56 to 70. After PND 70, offspring were sacrificed, and their brains were collected to estimate neurotransmitter levels. As per protocol, controls were maintained simultaneously for each experimental design. Prenatal exposure to VOX or VLZ induced an increased state of depressive- and anxiety-like behaviors in both male and female offspring. Additionally, neurotransmitter (serotonin, dopamine, and nor-epinephrine) levels in the prefrontal cortex region of the brain were substantially reduced in exposed offspring. No sex specific neurobehavioral and neurochemical implications were observed in the present study. Our findings suggest that prenatal exposure to VOX and VLZ disrupts neurochemical balance in the fetal brain, leading to long-lasting neurobehavioral impairments in offspring of both sexes.
PubMed: 38945303
DOI: 10.1016/j.bbr.2024.115128 -
Archives of Suicide Research : Official... Jun 2024Nearly 50,000 Americans die each year from suicide, despite suicide death being a rare event in the context of health risk assessment and modeling. Prior research has...
OBJECTIVE
Nearly 50,000 Americans die each year from suicide, despite suicide death being a rare event in the context of health risk assessment and modeling. Prior research has underscored the need for contextualizing suicide risk models in terms of their potential uses and generalizability. This sensitivity analysis makes use of the Maryland Suicide Data Warehouse (MSDW) and illustrates how results inform clinical decision support.
METHOD
A cohort of 1 million living control patients were extracted from the MSDW in addition to 1,667 patients who had died by suicide between the years 2016 and 2019 according to the Maryland Office of the Medical Examiner (OCME). Data were extracted and aggregated as part of a 4-year retrospective design. Binary logistic and two penalized regression models were deployed in a repeated fivefold cross-validation. Model performances were evaluated using sensitivity, positive predictive value (PPV), and F1, and model coefficients were ranked according to coefficient size.
RESULTS
Several features were significantly associated with patients having died by suicide, including male sex, depressive and anxiety disorder diagnoses, social needs, and prior suicidal ideation and suicide attempt. Cross-validated binary logistic regression outperformed either ridge or LASSO (least absolute shrinkage and selection operator) models but generally achieved low-to-moderate PPV and sensitivity across most thresholds and a peak F1 of 0.323.
CONCLUSIONS
Suicide death prediction is constrained by the context of use, which determines the best balance of precision and recall. Predictive models must be evaluated close to the level of intervention. They may not hold up to different needs at different levels of care.
PubMed: 38945167
DOI: 10.1080/13811118.2024.2363227 -
Maternal Postpartum Depression Screening and Early Intervention in the Neonatal Intensive Care Unit.Advances in Pediatrics Aug 2024Families with infants admitted to the neonatal intensive care unit (NICU) are at a markedly increased risk of developing postpartum depression (PPD) because of the... (Review)
Review
Families with infants admitted to the neonatal intensive care unit (NICU) are at a markedly increased risk of developing postpartum depression (PPD) because of the stressors they experience by having an infant in this intensive setting. Routine screening for PPD is not regularly performed for these families because many NICUs do not offer it and well-child visits are missed while the infant is hospitalized. Because the identification and treatment of PPD is often missed in these families, screening needs to be administered in the NICU to ensure improved outcomes.
Topics: Humans; Depression, Postpartum; Female; Intensive Care Units, Neonatal; Infant, Newborn; Mass Screening; Risk Factors
PubMed: 38944489
DOI: 10.1016/j.yapd.2024.01.004 -
Journal of Affective Disorders Jun 2024Trying to better define Bipolar Disorder (BD) progression, different staging models have been conceptualized, each one emphasizing different aspects of illness. In a...
BACKGROUND
Trying to better define Bipolar Disorder (BD) progression, different staging models have been conceptualized, each one emphasizing different aspects of illness. In a previous article we retrospectively applied the main staging models to a sample of 100 bipolar patients at four time points over a ten-year observation. In the present study, focusing on Kupka & Hillegers's model, we aimed to assess the transition of the same sample through the different stages of illness and to explore the potential role of clinical variables on the risk of progression.
METHODS
Multistate Model using the mstate package in R and Markov model with stratified hazards were used for statistical analysis.
RESULTS
A high hazard of transition from stage 2 to 3 emerged, with a probability of staying in stage 2 decreasing to 14 % after 3 years. BD II and depressive predominant polarity were significantly associated with transition from stage 1 to 2, whereas the number of lifetime episodes >3 and the elevated predominant polarity with transition from stage 3 to 4.
CONCLUSION
Our results corroborated the evidence on BD progression and contributed to outline its trajectory over time. Further effort may help to define a standardized staging approach towards ever increasing tailored interventions.
PubMed: 38944295
DOI: 10.1016/j.jad.2024.06.094 -
Journal of Affective Disorders Jun 2024Transcranial magnetic stimulation (TMS) is an evidence-based approach to treatment- resistant Major Depressive Disorder (TRD). Sleep dysfunction is associated with poor...
BACKGROUND
Transcranial magnetic stimulation (TMS) is an evidence-based approach to treatment- resistant Major Depressive Disorder (TRD). Sleep dysfunction is associated with poor outcomes in TRD, however, the impacts of sleep dysfunction on TMS treatment has yet to be defined. This study examined the association between sleep dysfunction and improvement in depression symptoms with TMS treatment for TRD.
METHODS
A retrospective observational cohort study was conducted examining all Veterans receiving TMS treatments through the "VA TMS Clinical Pilot Program" over a three-year period. The Patient Health Questionnaire (PHQ-9) sleep item was utilized to assess sleep dysfunction. The association between sleep dysfunction improvements during TMS treatment with depression outcomes was analyzed.
RESULTS
94.3 % (N = 778) of Veterans reported baseline sleep dysfunction. Chi-square analysis demonstrated higher rates of depression remission at the completion of TMS treatment for those with sleep improvement at weeks 1, 3 and 6 (all p < .001). ANOVA comparing sleep improvements and end of treatment PHQ-8 score (modified to remove sleep item) found a statistically significant difference in mean improvements of depression scores at all 3 time points.
LIMITATIONS
Limitations include those that are inherent to retrospective studies, as well as limitations in using the PHQ-9 sleep item as the primary means to assess sleep dysfunction.
CONCLUSION
This study reports on the largest sample size to date examining the relationship between sleep dysfunction and TMS treatment outcomes for MDD, and found that improvement in sleep dysfunction was associated with greater reductions in end of treatment depression symptoms including higher depression remission rates.
PubMed: 38944289
DOI: 10.1016/j.jad.2024.06.077 -
Journal of Psychiatric Research Jun 2024Depression is a growing public health concern, and exercise is an adjunctive treatment modality to improve depression, but the optimal form of exercise and the optimal... (Review)
Review
Optimal exercise modality and dose to improve depressive symptoms in adults with major depressive disorder: A systematic review and Bayesian model-based network meta-analysis of RCTs.
Depression is a growing public health concern, and exercise is an adjunctive treatment modality to improve depression, but the optimal form of exercise and the optimal dose are still unclear. This systematic review examined the efficacy of four major types of exercise (aerobic, resistance, mixed, and mind-body) on depression, as well as the dose-response relationship between total and specific exercise and depressive symptoms. We included randomized controlled trials that included participants aged 18 years or older with a diagnosis of major depressive disorder or a depressive symptom score above a threshold as determined by a validated screening measure, implemented one or more exercise therapy groups, and assessed depressive symptoms at baseline and follow-up. Forty-six studies (3164 patients) were included in the meta-analysis. Aerobic (standardised mean difference (SMD) = -0.93; 95% CI: -1.25 to -0.62) and mind-body exercise (SMD) = -0.81; 95% CI: -1.19 to -0.42) improved depressive symptoms better compared to controls, followed by mixed (SMD = -0.77; 95% CI: -1.20 to -0.34) and resistance exercise (SMD = -0.76; 95% CI: -1.24 to -0.28). This dose-response meta-analysis showed a U-shaped curve between exercise dose and depressive symptoms. The minimum effective dose was estimated to be 320 metabolic equivalent (METs) -min per week and the optimal response was 860 METs-min per week. These findings lead us to advocate that clinicians carefully select the appropriate dose of exercise based on the patient's individual characteristics and needs, in conjunction with psychological care interventions.
PubMed: 38944017
DOI: 10.1016/j.jpsychires.2024.06.031 -
Progress in Molecular Biology and... 2024Researchers are interested in drug repurposing or drug repositioning of existing pharmaceuticals because of rising costs and slower rates of new medication development.... (Review)
Review
Researchers are interested in drug repurposing or drug repositioning of existing pharmaceuticals because of rising costs and slower rates of new medication development. Other investigations that authorized these treatments used data from experimental research and off-label drug use. More research into the causes of depression could lead to more effective pharmaceutical repurposing efforts. In addition to the loss of neurotransmitters like serotonin and adrenaline, inflammation, inadequate blood flow, and neurotoxins are now thought to be plausible mechanisms. Because of these other mechanisms, repurposing drugs has resulted for treatment-resistant depression. This chapter focuses on therapeutic alternatives and their effectiveness in drug repositioning. Atypical antipsychotics, central nervous system stimulants, and neurotransmitter antagonists have investigated for possible repurposing. Nonetheless, extensive research is required to ensure their formulation, effectiveness, and regulatory compliance.
Topics: Drug Repositioning; Humans; Depression; Antidepressive Agents; Animals
PubMed: 38942546
DOI: 10.1016/bs.pmbts.2024.03.037 -
Journal of Affective Disorders Jun 2024Early symptomatic improvement may predict treatment response in bipolar I disorder. Cariprazine has demonstrated early treatment effects in bipolar I depression and...
Early improvement with cariprazine as a predictor of antidepressant, anxiolytic, and antimanic response in bipolar I mania and depression: A pooled post hoc analysis of randomized cariprazine trials.
BACKGROUND
Early symptomatic improvement may predict treatment response in bipolar I disorder. Cariprazine has demonstrated early treatment effects in bipolar I depression and mania studies; therefore, we assessed whether early improvement with cariprazine predicts eventual treatment response.
METHODS
Post hoc analyses used pooled data from randomized, double-blind, placebo-controlled bipolar I depression (NCT02670538, NCT02670551) and mania (NCT00488618, NCT01058096, NCT01058668) trials. In depression studies (cariprazine 1.5 mg/d, 3 mg/d, or placebo), early improvement in Montgomery-Åsberg Depression Rating Scale (MADRS) and Hamilton Anxiety Rating Scale (HAM-A) total scores (≥25 % improvement at day 15) and subsequent depressive/anxiety symptom response status (≥50 % improvement at week 6) were assessed. In mania studies (cariprazine 3-12 mg/d or placebo), early improvement in Young Mania Rating Scale (YMRS) total scores (≥25 % improvement at day 7) and manic symptom response status (≥50 % improvement at week 3) were assessed.
RESULTS
Patients with bipolar I depression and early MADRS improvement were approximately 4- to 6-times as likely to achieve MADRS or HAM-A response than those without early improvement; patients with early HAM-A improvement were approximately 3- to 4-times as likely to achieve MADRS or HAM-A response. A subset of patients without early improvement with cariprazine 1.5 mg/d (20-31 %) subsequently responded following up-titration. Patients with mania and early YMRS improvement were approximately 5 times more likely to have manic symptom response than those without early improvement.
LIMITATIONS
Post hoc analysis; relatively short study durations; flexible-dosing (mania studies).
CONCLUSIONS
Early symptom improvement with cariprazine may inform therapeutic decisions for patients with bipolar I disorder.
PubMed: 38942209
DOI: 10.1016/j.jad.2024.06.100 -
Journal of Affective Disorders Jun 2024Cariprazine has emerged as a promising augmenting treatment agent for unipolar depression and as a monotherapy option for bipolar depression. We evaluated cariprazine's...
BACKGROUND
Cariprazine has emerged as a promising augmenting treatment agent for unipolar depression and as a monotherapy option for bipolar depression. We evaluated cariprazine's efficacy in treating acute major depressive episodes in individuals with major depressive disorder (MDD) or bipolar disorder.
METHODS
A systematic review was conducted on MEDLINE, Embase, PyscInfo, Scopus and Web of Science, ClinicalTrials.gov and ScanMedicine. Study quality was assessed using the RoB 2 tool. Pairwise and dose-response meta-analyses were conducted with RStudio. Evidence quality was assessed with GRADE.
RESULTS
Nine RCTs meeting inclusion criteria encompassed 4877 participants. Cariprazine, compared to placebo, significantly reduced the MADRS score (MD = -1.49, 95 % CI: -2.22 to -0.76) and demonstrated significantly higher response (RR = 1.21, 95 % CI: 1.12 to 1.30) and remission (RR = 1.19, 95 % CI: 1.06 to 1.34) rates. Subgroup analysis unveiled statistically significant reductions in MADRS score in MDD (MD = -1.15, 95 % CI: -2.04 to -0.26) and bipolar I disorder (BDI) (MD = -2.53, 95 % CI: -3.61 to -1.45), higher response rates for both MDD (RR = 1.19, 95 % CI: 1.08 to 1.31) and BDI (RR = 1.27, 95 % CI: 1.10 to 1.46), and higher remission rates only for BDI (RR = 1.41, 95 % CI: 1.24 to 1.60). A higher rate of treatment discontinuation due to adverse events was observed.
LIMITATIONS
Reliance solely on RCTs limits generalisability; strict criteria might not reflect real-world diversity.
CONCLUSIONS
Cariprazine demonstrates efficacy in treating major depressive episodes, although variations exist between MDD and BDI and tolerability may be an issue.
PubMed: 38942207
DOI: 10.1016/j.jad.2024.06.099 -
Journal of Affective Disorders Jun 2024Heart rate variability (HRV) is often reduced in patients with major depressive disorder (MDD) and is linked to symptoms. However, prior studies have mainly focused on...
BACKGROUND
Heart rate variability (HRV) is often reduced in patients with major depressive disorder (MDD) and is linked to symptoms. However, prior studies have mainly focused on short-term HRV, with limited exploration of the 24-h HRV circadian rhythm, despite its ability to comprehensively capture overall HRV distribution and dynamic fluctuations. In this study, we investigated the circadian rhythms of 24-h HRV indices in patients with MDD and their associations with symptom severity.
METHODS
We recorded 24-h electrocardiograms in 73 patients with MDD (53 in major depressive episode and 20 in remission period) and 31 healthy controls. An extended cosine model was used to model the circadian rhythm of six HRV indices by five parameters: the mesor, amplitude, duty cycle, curve smoothness, and acrophase. Symptom severity was evaluated using the Hamilton Depression Scale and Hamilton Anxiety Scale.
RESULTS
Compared with the control group, patients with MDD had a significantly smaller SampEn mesor, higher HF duty cycle, and lower heart rate (HR) duty cycle. They also had a significantly higher curve smoothness for HR, RMSSD, and HF. The mesor for SampEn, along with the curve smoothness for HR and ln RMSSD, were associated with certain symptoms in patients with MDD.
LIMITATIONS
The cross-sectional design and psychiatric treatment of most patients with MDD limited our findings.
CONCLUSION
Patients with MDD exhibit abnormal HRV circadian rhythms that are associated with symptoms. Moreover, 24-h ECG monitoring may potentially serve as an adjunct value to objectively evaluate clinical symptoms in these patients.
PubMed: 38942206
DOI: 10.1016/j.jad.2024.06.102