scholarly journals Structural Changes in Hippocampal Subfields in Patients with Continuous Remission of Drug-Naive Major Depressive Disorder

2020 ◽  
Vol 21 (9) ◽  
pp. 3032 ◽  
Author(s):  
Asuka Katsuki ◽  
Keita Watanabe ◽  
LeHoa Nguyen ◽  
Yuka Otsuka ◽  
Ryohei Igata ◽  
...  

Objective: Hippocampal volume is reduced in patients with major depressive disorder (MDD) compared with healthy controls. The hippocampus is a limbic structure that has a critical role in MDD. The aim of the present study was to investigate the changes in the volume of the hippocampus and its subfields in MDD patients who responded to antidepressants and subsequently were in continuous remission. Subjects and Methods: Eighteen patients who met the following criteria were enrolled in the present study: the DSM-IV-TR criteria for MDD, drug-naïve at least 8 weeks or more, scores on the 17-items of Hamilton Rating Scale for Depression (HAMD) of 14 points or more, and antidepressant treatment response within 8 weeks and continuous remission for at least 6 months. All participants underwent T1-weighted structural MRI and were treated with antidepressants for more than 8 weeks. We compared the volumes of the hippocampus, including its subfields, in responders at baseline to the volumes at 6 months. The volumes of the whole hippocampus and the hippocampal subfields were measured using FreeSurfer v6.0. Results: The volumes of the left cornu Ammonis (CA) 3 (p = 0.016) and the granule cell layer of the dentate gyrus (GC-DG) region (p = 0.021) were significantly increased after 6 months of treatment compared with those at baseline. Conclusions: Increases in volume was observed in MDD patients who were in remission for at least 6 months.

CNS Spectrums ◽  
2020 ◽  
Vol 25 (2) ◽  
pp. 313-314
Author(s):  
Marlene P. Freeman ◽  
Maurizio Fava ◽  
Bryan Dirks ◽  
Manish K. Jha ◽  
Richard C. Shelton ◽  
...  

Abstract:Study Objectives:Sexual dysfunction occurs in 40%-60% of patients with major depressive disorder (MDD), due to either the illness itself and/or the effects of antidepressant treatment. The phase-2 CLARITY trial recently demonstrated the efficacy of adjunctive pimavanserin (PIM) for MDD when added to ongoing selective serotonin or serotonin–norepinephrine reuptake inhibitor (SSRI/SNRI) treatment. No new safety observations were reported in this study. This post-hoc analysis examines the potential impact of PIM treatment on sexual function.Method:Study methodology has been presented previously (APA 2019). Adult male and female patients with moderate-to-severe MDD were randomized to PIM 34 mg/day (n=51) or placebo (PBO, n=152) added to ongoing SSRI/SNRI treatment. Massachusetts General Hospital–Sexual Functioning Inventory (MGH-SFI) and Hamilton Depression Rating Scale, 17-item version (HAMD-17) item 14 (sexual interest) scores were examined by analysis of covariance.Results:Adjunctive PIM resulted in significantly greater 5-week reduction (improvement) relative to SSRI/SNRI treatment plus placebo on mean MGH-SFI scores (difference –0.634, SE 0.167; P<0.001; effect size [ES], Cohen’s d 0.614). Similarly, PIM resulted in greater improvement compared with placebo on individual MGH-SFI items that applied to both males and females: Interest in Sex (P=0.006; ES=0.483), Ability to Get Sexually Aroused/Excited (P=0.001; ES=0.560), Ability to Achieve Orgasm (P<0.001; ES=0.609), Overall Sexual Satisfaction (P=0.003; ES=0.524). HAMD-17 item 14 scores were also significantly more reduced (improved) with PIM (P<0.001; ES=0.574).Conclusions:These results underscore the potential of adjunctive PIM for improving sexual function in patients with MDD and inadequate response to SSRIs/SNRIs. Potential benefits should be confirmed in further studies.Funding Acknowledgements:ACADIA Pharmaceuticals Inc.


2020 ◽  
pp. 1-9 ◽  
Author(s):  
Le Xiao ◽  
Xuequan Zhu ◽  
Amy Gillespie ◽  
Yuan Feng ◽  
Jingjing Zhou ◽  
...  

Abstract Background This study aimed to examine the efficacy of combining paroxetine and mirtazapine v. switching to mirtazapine, for patients with major depressive disorder (MDD) who have had an insufficient response to SSRI monotherapy (paroxetine) after the first 2 weeks of treatment. Methods This double-blind, randomized, placebo-controlled, three-arm study recruited participants from five hospitals in China. Eligible participants were aged 18–60 years with MDD of at least moderate severity. Participants received paroxetine during a 2-week open-label phase and patients who had not achieved early improvement were randomized to paroxetine, mirtazapine or paroxetine combined with mirtazapine for 6 weeks. The primary outcome was improvement on the Hamilton Rating Scale for Depression 17-item (HAMD-17) scores 6 weeks after randomization. Results A total of 204 patients who showed early non-response to paroxetine monotherapy were randomly assigned to receive either mirtazapine and placebo (n = 68), paroxetine and placebo (n = 68) or mirtazapine and paroxetine (n = 68), with 164 patients completing the outcome assessment. At week 8, the least squares (LS) mean change of HAMD-17 scores did not significantly differ among the three groups, (12.98 points) in the mirtazapine group, (12.50 points) in the paroxetine group and (13.27 points) in the mirtazapine plus paroxetine combination group. Participants in the paroxetine monotherapy group were least likely to experience adverse effects. Conclusions After 8 weeks follow-up, paroxetine monotherapy, mirtazapine monotherapy and paroxetine/mirtazapine combination therapy were equally effective in non-improvers at 2 weeks. The results of this trial do not support a recommendation to routinely offer additional treatment or a switch in treatment strategies for MDD patients who do not show early improvement after 2 weeks of antidepressant treatment.


2021 ◽  
Vol 3 ◽  
Author(s):  
Anzar Abbas ◽  
Colin Sauder ◽  
Vijay Yadav ◽  
Vidya Koesmahargyo ◽  
Allison Aghjayan ◽  
...  

Objectives: Multiple machine learning-based visual and auditory digital markers have demonstrated associations between major depressive disorder (MDD) status and severity. The current study examines if such measurements can quantify response to antidepressant treatment (ADT) with selective serotonin reuptake inhibitors (SSRIs) and serotonin–norepinephrine uptake inhibitors (SNRIs).Methods: Visual and auditory markers were acquired through an automated smartphone task that measures facial, vocal, and head movement characteristics across 4 weeks of treatment (with time points at baseline, 2 weeks, and 4 weeks) on ADT (n = 18). MDD diagnosis was confirmed using the Mini-International Neuropsychiatric Interview (MINI), and the Montgomery–Åsberg Depression Rating Scale (MADRS) was collected concordantly to assess changes in MDD severity.Results: Patient responses to ADT demonstrated clinically and statistically significant changes in the MADRS [F(2, 34) = 51.62, p &lt; 0.0001]. Additionally, patients demonstrated significant increases in multiple digital markers including facial expressivity, head movement, and amount of speech. Finally, patients demonstrated significantly decreased frequency of fear and anger facial expressions.Conclusion: Digital markers associated with MDD demonstrate validity as measures of treatment response.


2019 ◽  
Vol 215 (2) ◽  
pp. 494-501 ◽  
Author(s):  
Ole Köhler-Forsberg ◽  
Erik Roj Larsen ◽  
Henriette N. Buttenschøn ◽  
Marcella Rietschel ◽  
Joanna Hauser ◽  
...  

BackgroundFor patients with major depressive disorder (MDD) experiencing side-effects or non-response to their first antidepressant, little is known regarding the effect of switching between a tricyclic antidepressant (TCA) and a selective serotonin reuptake inhibitor (SSRI).AimsTo compare the switch between the TCA nortriptyline and the SSRI escitalopram.MethodAmong 811 adults with MDD treated with nortriptyline or escitalopram for up to 12 weeks, 108 individuals switched from nortriptyline to escitalopram or vice versa because of side-effects or non-response (trial registration: EudraCT No.2004-001723-38 (https://eudract.ema.europa.eu/) and ISRCTN No.03693000 (http://www.controlled-trials.com)). Patients were followed for up to 26 weeks after switching and response was measured with the Montgomery–Åsberg Depression Rating scale (MADRS). We performed adjusted mixed-effects linear regression models with full information maximum likelihood estimation reporting β-coefficients with 95% CIs.ResultsSwitching antidepressants resulted in a significant decrease in MADRS scores. This was present for switchers from escitalopram to nortriptyline (n = 36, β = −0.38, 95% CI −0.51 to −0.25, P<0.001) and from nortriptyline to escitalopram (n = 72, β = −0.34, 95% CI −0.41 to −0.26, P<0.001). Both switching options resulted in significant improvement among individuals who switched because of non-response or side-effects. The results were supported by analyses on other rating scales and symptom dimensions.ConclusionsThese results suggest that switching from a TCA to an SSRI or vice versa after non-response or side-effects to the first antidepressant may be a viable approach to achieve response among patients with MDD.Declarations of interestK.J.A. holds an Alberta Centennial Addiction and Mental Health Research Chair, funded by the Government of Alberta. K.J.A. has been a member of various advisory boards, received consultancy fees and honoraria, and has received research grants from various companies including Johnson and Johnson Pharmaceuticals Research and Development and Bristol-Myers Squibb Pharmaceuticals Limited. D.S. has served on advisory boards for, and received unrestricted grants from, Lundbeck and AstraZeneca. A.F. and P.M. have received honoraria for participating in expert panels for Lundbeck and GlaxoSmithKline.


2020 ◽  
Author(s):  
Isaac Galatzer-Levy ◽  
Anzar Abbas ◽  
Vijay Yadav ◽  
Vidya Koesmahargyo ◽  
Allison Aghjayan ◽  
...  

Objectives: Multiple machine learning-based visual and auditory digital markers have demonstrated associations between Major Depressive Disorder (MDD) status and severity. The current study examines if such measurements can quantify response to antidepressant treatment (ADT) with selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine uptake inhibitors (SNRIs). Methods: Visual and auditory markers were acquired through an automated smartphone task that measures facial, vocal, and head movement characteristics across the first five weeks of treatment (with timepoints at 1, 3, and 5 weeks) on ADT (n = 12). The Montgomery-Asberg Depression Rating Scale (MADRS) was collected concordantly through clinical interviews to confirm diagnosis and assess changes in MDD severity. Results: Patient responses to ADT demonstrated clinically and statistically significant changes in the MADRS F(2,34) = 51.62, p <.0001. Additionally, patients demonstrated significant increases in multiple digital markers including facial expressivity, head movement, and amount of speech. Finally, patients demonstrated significant decreased frequency of fear and anger facial expressions. Conclusion: Digital markers associated with MDD demonstrate validity as measures of treatment response.


Biomedicines ◽  
2021 ◽  
Vol 9 (10) ◽  
pp. 1428
Author(s):  
Yi-Yung Hung ◽  
Chen-Kai Chou ◽  
Yi-Chien Yang ◽  
Hung-Chun Fu ◽  
El-Wui Loh ◽  
...  

The intracellular microRNAs that negatively regulate Toll-like receptor 4 signaling pathways in peripheral blood mononuclear cells are associated with major depressive disorder (MDD). However, that the distribution of these microRNAs in exosomes could be a biomarker of central nervous system diseases is just beginning to be explored. In the present study, we isolated serum exosomes from patients with MDD and healthy controls to explore the levels of exosomal microRNAs, including let-7e, miR-21-5p, miR-223, miR-145, miR-146a, and miR-155. We also investigated the changes of these exosomal microRNAs after antidepressant treatment and their association with clinical changes in scores on the Hamilton Depression Rating Scale. An ANCOVA adjusted by age, sex, BMI, and smoking showed higher expression levels of miR-146a (p = 0.006) in patients with MDD compared to controls. Patients who achieved remission showed significantly lower let-7e, miR-21-5p, miR-145, miR-146a, and miR-155 levels before treatment and increased levels after antidepressant treatment compared with the non-remission group. Through receiver operating characteristic (ROC) analysis, let-7e, miR-145, and miR-146a showed acceptable discrimination between the remission and non-remission groups, whereas miR-21-5p and miR-155 showed poor discrimination. These findings demonstrate that exosomal microRNAs may play essential roles in predicting antidepressants response.


Sign in / Sign up

Export Citation Format

Share Document