Yawning as a Rare Side Effect With Increased Escitalopram Dose: A Case Report.

Yawning is a normal physiological process that occurs naturally in all human beings in different settings, such as hunger, drowsiness, or stress. It is typically harmless, but abnormal yawning can be seen in many medical conditions. In psychiatry, it frequently occurs in disorders like depression, insomnia, and anxiety due to disturbed sleep. It has also been observed as an adverse reaction of some drugs, like escitalopram, a selective serotonin reuptake inhibitor. Escitalopram is a widely prescribed, well-tolerated antidepressant and antianxiety drug that can induce a range of side effects, one of which is excessive yawning. Its excessive occurrence can be distressing for patients, affecting their socio-occupational functioning. Clinically, differentiating yawning induced by escitalopram treatment from that in depression can be a diagnostic hurdle. Awareness and recognition of this lesser known side effect can improve patient outcomes by allowing for timely adjustments and easing the discomfort.

Should rTMS be considered a first-line treatment for major depressive episodes in adults?

Treatment-resistant depression (TRD) is an epidemic with rising social, economic, and political costs. In a patient whose major depressive episode (MDE) persists through an adequate antidepressant trial, insurance companies often cover alternative treatments which may include repetitive transcranial magnetic stimulation (rTMS). RTMS is an FDA-cleared neuromodulation technique for TRD which is safe, efficacious, noninvasive, and well-tolerated. Recent developments in the optimization of rTMS algorithms and targeting have increased the efficacy of rTMS in treating depression, improved the clinical convenience of these treatments, and decreased the cost of a course of rTMS. In this opinion paper, we make a case for why conventional FDA-cleared rTMS should be considered as a first-line treatment for all adult MDEs. RTMS is compared to other first-line treatments including psychotherapy and SSRIs. These observations suggest that rTMS has similar efficacy, fewer side-effects, lower risk of serious adverse events, comparable compliance, the potential for more rapid relief, and cost-effectiveness. This suggestion, however, would be strengthened by further research with an emphasis on treatment-naive subjects in their first depressive episode, and trials directly contrasting rTMS with SSRIs or psychotherapy.

An Unexpected Phenomenon: A Case of Citalopram-Induced Dyskinesia.

Dyskinetic movements are characterized as hyperkinetic, repetitive movements of the extremities, facial, and oral musculature, most associated with prolonged dopamine D2 receptor blockade. In rare instances, dyskinetic movements can be brought on by selective serotonin reuptake inhibitor (SSRI) usage via an indirect D2 blockade mechanism, mimicking the D2 blockade observed with dopamine receptor blocking agents (DRBAs), such as in first-generation antipsychotics. This mimicked D2 blockade by SSRIs is said to be due to increased tonic inhibition by serotonin on dopaminergic neurons in the dopaminergic pathways of the brain, specifically the nigrostriatal pathway. In this case report, we look at a patient with a history of cerebral palsy who developed acute dyskinetic movements after short-term citalopram usage. The objective is to bring attention to the possible extrapyramidal side effects (EPS) of SSRI usage.

Vortioxetine improved schizophrenia-like behavioral deficits in a Poly I:C-induced maternal immune activation model of schizophrenia in rats.

BACKGROUND: Several studies provide clear evidence that exposure to various infections during pregnancy are linked with an increased risk for schizophrenia. In preclinical studies, administration of polyinosinic-polycytidylic acid (Poly I:C) in pregnant rodents can induce maternal immune activation leading to impairments in brain function in the offspring. OBJECTIVES: The aim of this study was to investigate the effect of vortioxetine, a multimodal selective serotonin reuptake inhibitor (SSRI), in the pathophysiology of Poly I:C-induced schizophrenia-like model in rats. METHODS: For this purpose, Poly I:C (8 mg/kg, ip) was injected into pregnant animals 14 days after mating, and tail blood was taken for determination of IL-6 levels after 2 h. At postnatal days 83-86, behavioral tests were performed. RESULTS: Our results revealed that Poly I:C caused impairments in prepulse inhibition, novel object recognition, social interaction, and open-field tests. Chronic administration of vortioxetine (2.5, 5, and 10 mg/kg, ip, postnatal days 69-83) caused significant improvements in these deficits. CONCLUSION: Overall, our findings indicate that vortioxetine may provide new therapeutic approaches for the treatment of schizophrenia. We think that increased serotonergic activity in frontal brain regions may provide the ameliorative effect of vortioxetine, especially on negative and cognitive symptoms. Therefore, it will be useful to determine the efficacy of vortioxetine with combined drugs with further studies.

A Randomized Controlled Trial Comparing the Quality of Life and Medication Adherence in Patients on Antidepressant Monotherapy.

Background and objectives The quality of life declines with the growing severity of major depressive disorder (MDD). In depressed people, medication adherence and the quality of life are mutually corrosive. These concerns spurred the investigation of relationships between treatment outcomes and adherence levels. Limited studies are looking at how vortioxetine, escitalopram, and vilazodone affect these parameters. We aimed to detect how the Short Form-36 (SF-36) had changed 16 weeks after the baseline. The connection between treatment results (as expressed by the Hamilton Depression Rating Scale or HDRS) and medication adherence (as reflected by the Morisky Medication Adherence Scale-8 or MMAS-8) was also explored. Methods An open-label, randomized, three-arm trial with 96 MDD patients was conducted. For 16 weeks, the participants were put into three groups per a 1:1:1 ratio and administered tablets of vilazodone (20-40 mg/day), escitalopram (10-20 mg/day), or vortioxetine (5-20 mg/day). There were two test drugs: vilazodone and vortioxetine; the control was escitalopram. Four weeks apart, follow-up appointments were set after the baseline visit. The HDRS, mental and physical components of SF-36, and MMAS-8 scores were evaluated in the per-protocol (PP) population. Reduced HDRS scores were indicative of improved depression symptoms. Higher MMAS-8 and SF-36 scores indicated high drug adherence and enhanced quality of life. Our analysis used the Kruskal-Wallis test, the Bonferroni correction, and the Sankey diagram. In the Clinical Trial Registry-India (CTRI), we recorded this study prospectively (2022/07/043808). Results One hundred nine (81.34%) of the 134 individuals we examined were eligible. The PP population consisted of 96 (88.07%) of them who wrapped up the 16-week study. The mean age of the group was 46.3 ± 6.2 years. For each of the three groups, the SF-36 physical component scores revealed a median difference of 24.5 (23.8-26.0), 24.0 (22.8-25.3), and 27.0 (25.0-29.0) (p = 0.001). Accordingly, the mental components of their SF-36 scores showed a median difference of 32.0 (31.0-33.3), 31.0 (29.8-34.3), and 36.0 (33.0-38.0) (p = 0.001). A median difference of -15.0 (-16.0 to -14.0), -16.0 (-17.0 to -15.0), and -16.0 (-17.0 to -15.8) was observed in the HDRS scores after 16 weeks, with respect to the baseline (p < 0.001). The median MMAS-8 scores at 16 weeks were 6.0 (6.0-7.0), 6.8 (6.0-7.0), and 7.5 (6.5-8.0) (p = 0.031). The Sankey diagram illustrated the connection between better treatment results, increased medication compliance, and decreased symptoms of depression. Conclusion In comparison to vilazodone and escitalopram, vortioxetine demonstrated a statistically significant decrease in HDRS scores and an improvement in the physical and mental component scores of the SF-36. Clinical improvements were evident in the individuals' drug adherence levels. Larger-scale studies are advised to investigate the effects of these medications on the quality of life, medication adherence, and treatment outcomes.

Individual differences in the boldness of female zebrafish are associated with alterations in serotonin function.

One of the most prevalent axes of behavioral variation in both humans and animals is risk taking, where individuals that are more willing to take risk are characterized as bold while those that are more reserved are regarded as shy. Brain monoamines (i.e. serotonin, dopamine and noradrenaline) have been found to play a role in a variety of behaviors related to risk taking. Using zebrafish, we investigated whether there was a relationship between monoamine function and boldness behavior during exploration of a novel tank. We found a correlation between serotonin metabolism (5-HIAA:5-HT ratio) and boldness during the initial exposure to the tank in female animals. The DOPAC:DA ratio correlated with boldness behavior on the third day in male fish. There was no relationship between boldness and noradrenaline. To probe differences in serotonergic function in bold and shy fish, we administered a selective serotonin reuptake inhibitor, escitalopram, and assessed exploratory behavior. We found that escitalopram had opposing effects on thigmotaxis in bold and shy female animals: the drug caused bold fish to spend more time near the center of the tank and shy fish spent more time near the periphery. Taken together, our findings indicate that variation in serotonergic function has sex-specific contributions to individual differences in risk-taking behavior.

Selective Serotonin Reuptake Inhibitors and Symptoms of Depression in Patients on Chronic Hemodialysis: A Systematic Review.

Objective: The use of selective serotonin reuptake inhibitors (SSRIs) is common among hemodialysis patients who receive treatment for depression. However, studies on the efficacy of SSRIs in patients on chronic hemodialysis are few and have led to conflicting results. The present systematic review aims to evaluate, in randomized, controlled studies (RCSs), the efficacy of SSRI administration in reducing symptoms of depression in patients on chronic hemodialysis when compared with placebo or psychological interventions. Method: Research was run on December 2023 in the following databases: Ovid MEDLINE (1985 to present); Ovid EMBASE (1985 to present); Cochrane Library (Wiley); and PubMed (1985 to present). The primary outcome was the frequency and severity of the symptoms of depression assessed through the Beck Depression Inventory (BDI) or the Hamilton Depression Rating Scale (HAMD). The secondary outcome was the prevalence of adverse events. Results: Seven studies totaling 433 patients were included. The number of patients in each individual study ranged from 13 to 120. The length of studies ranged from 8 weeks to 6 months. Heterogeneous data precluded informative meta-analysis. Three studies compared sertraline with a placebo. Of these, two demonstrated that sertraline was better than the placebo in reducing the symptoms of depression while one showed no statistically significant differences between sertraline and the placebo. One study, comparing fluoxetine with a placebo showed that the symptoms of depression did not differ significantly at 8 weeks. In another study, escitalopram administration led to a significantly greater reduction in the Hamilton Depression Rating Scale score compared to a placebo, as well as in the Hamilton Anxiety Rating Scale score. In one study, citalopram and psychological interventions were both effective in reducing the symptoms of depression and anxiety and, in another study, sertraline was modestly more effective than CBT at 12 weeks in reducing the symptoms of depression. Conclusions: SSRIs may be effective in reducing the symptoms of depression in patients on chronic hemodialysis. SSRI administration, at the dosage used in the studies included in the present systematic review, seems safe in most hemodialysis patients. However, the paucity of studies and the limited number of patients included in the trials may suggest that further randomized, controlled studies are needed to determine if SSRIs may be used routinely in daily clinical practice in such a population.

Effectiveness of vortioxetine for winter depression in bipolar disorder: A case report.

Background: We present a case report on the efficacy of the short-term application of vortioxetine in managing winter depression in patients with seasonal bipolar disorder (BP). Standard treatment strategies for BP may not adequately address seasonal depressive symptoms during winter in patients with seasonal BP patterns. Depressive symptoms during winter may be linked to seasonal changes in serotonin transporter binding, such as a decrease in synaptic serotonin levels, necessitating alternative approaches. Although antidepressants, including vortioxetine, are effective in treating seasonal monopolar depression, their efficacy and safety in treating depression in patients with seasonal BP patterns remain unclear. Case Presentation: This case report focuses on a 44-year-old male patient diagnosed with seasonal BP who had recurrent depressive episodes, specifically during winter. Notably, the patient had a significant decrease in recurrent episodes after short-term seasonal vortioxetine use without inducing mania or rapid cycling. Conclusion: Our study highlights the potential effectiveness of a seasonal, short-term treatment strategy with antidepressants, including vortioxetine, for winter depression in individuals with BP.

Cutaneous Small-Vessel Vasculitis Induced by Escitalopram: A Case-Based Brief Review of the Literature.

A 65-year-old male with multiple comorbidities and recently diagnosed with diabetic kidney disease developed upper and lower extremity rash following escitalopram initiation for his depressive mood. Clinical assessment and skin biopsy confirmed cutaneous small-vessel vasculitis (CSVV), prompting drug discontinuation and oral methylprednisolone therapy. The resolution of the rash was achieved within a week. This rare case of CSVV induced by escitalopram highlights the importance of timely recognition and management of drug-induced CSVV and adds to the limited literature on selective serotonin reuptake inhibitor-associated CSVV.

The Impact of Development on Antidepressant and Placebo Response in Anxiety Disorders: A Bayesian Hierarchical Meta-Analytic Examination of Randomized Controlled Trials in Children, Adolescents, and Adults.

Background: Understanding how development influences medication and placebo responses in anxiety disorders could inform treatment decisions, including age-specific first- versus second-line psychopharmacological interventions. Objective: To meta-analytically compare the trajectory of selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), and placebo response in youth and adults with anxiety disorders. Methods: Weekly symptom severity data were extracted from prospective, randomized, parallel-group, placebo-controlled trials of SSRIs and SNRIs in children, adolescents, and adults with anxiety disorders (generalized, separation, and social anxiety disorders as well as panic disorder). Treatment response was modeled for the standardized change in continuous measures of anxiety using a Bayesian hierarchical model. Change in symptom severity was evaluated as a function of time, and post hoc analyses were conducted to determine the sensitivity of these results across sample heterogeneity and alternative functional forms. Results: Data were included from 11 trials of youth (SSRI, κ = 7; SNRI, κ = 4) and 71 studies of adults (SSRI, κ = 46; SNRI, κ = 25). In total, 1067 youth participated in SSRI trials and 1024 in SNRI trials. In total, 10,826 adults participated in SSRI trials (placebo, n = 5367; SSRI n = 5,459) and 6232 in SNRI trials (placebo, n = 3,128; SNRI n = 3,094). A logarithmic model best described the response. Placebo response was similar in youth and adults (mean difference = -1.98 ± 6.21, 95% credible interval [CrI]: -10.2 to 14.2, p = 0.750), and statistically significant improvement from baseline emerged by week 2 in both adults (mean difference: -18.34 + 1.017, 95% CrI: -20.3 to 16.3, p < 0.001) and youth (mean difference: -23.74 + 3.736, 95% CrI: -31.1 to -16.4, p < 0.001). SSRIs produced similar improvements for youth and adults (p = 0.129), but SNRIs produced slower improvement in youth than adults (p = 0.018). Conclusions: Antidepressant-related improvement occurs early in youth and adults with anxiety disorders. SSRI response is similar in adults and youth; however, SNRIs produce greater responses in adults than youth, potentially representing a developmental effect.

Altered Serotonin 1B Receptor Binding After Escitalopram for Depression Is Correlated With Treatment Effect.

BACKGROUND: Major depressive disorder (MDD) is commonly treated with selective serotonin reuptake inhibitors (SSRIs). SSRIs inhibit the serotonin transporter (5-HTT), but the downstream antidepressant mechanism of action of these drugs is poorly understood. The serotonin 1B (5-HT1B) receptor is functionally linked to 5-HTT and 5-HT1B receptor binding and 5-HT1B receptor mRNA is reduced in the raphe nuclei after SSRI administration in primates and rodents, respectively. The effect of SSRI treatment on 5-HT1B receptor binding in patients with MDD has not been examined previously. This positron emission tomography (PET) study aimed to quantify brain 5-HT1B receptor binding changes in vivo after SSRI treatment for MDD in relation to treatment effect. METHODS: Eight unmedicated patients with moderate to severe MDD underwent PET with the 5-HT1B receptor radioligand [11C]AZ10419369 before and after 3 to 4 weeks of treatment with the SSRI escitalopram 10 mg daily. Depression severity was assessed at time of PET and after 6 to 7 weeks of treatment with the Montgomery-Åsberg Depression Rating Scale. RESULTS: We observed a significant reduction in [11C]AZ10419369 binding in a dorsal brainstem (DBS) region containing the median and dorsal raphe nuclei after escitalopram treatment (P = .036). Change in DBS [11C]AZ10419369 binding correlated with Montgomery-Åsberg Depression Rating Scale reduction after 3-4 (r = 0.78, P = .021) and 6-7 (r = 0.94, P < .001) weeks' treatment. CONCLUSIONS: Our findings align with the previously reported reduction of 5-HT1B receptor binding in the raphe nuclei after SSRI administration and support future studies testing change in DBS 5-HT1B receptor binding as an SSRI treatment response marker.

Treating Depression in Dementia Patients: A Risk or Remedy-A Narrative Review.

BACKGROUND: The diagnosis of depression in dementia patients leads to an increase in the burden of the disease. To treat depression in this patient group, antidepressants are frequently used; however, there is not any proof of their therapeutic effectiveness, and their use may be potentially harmful. This narrative review aims to summarize the existing evidence regarding the role of antidepressants in treating depression in dementia patients. MAIN TEXT: A search was conducted in the PubMed, Excerpta Medica database (EMBASE), and Cochrane databases for randomized controlled trials and meta-analyses wherein antidepressants were given to dementia sufferers to address depression. Fifteen randomized controlled trials and seven meta-analyses were identified. Most well-designed blinded placebo-controlled trials reported a lack of effectiveness of antidepressants in treating depression in dementia patients. Among the seven metanalyses, two reported good efficacy of Selective serotonin reuptake inhibitors (SSRIs). However, two major Cochrane reviews reported little or no effectiveness and increased side effects of antidepressants in dementia patients. CONCLUSION: There is robust evidence regarding the lack of efficacy of antidepressants in treating depression in dementia patients. However, further well-designed Randomized controlled trials (RCTs,) using scales with good validity and reliability to diagnose depression in dementia patients, sufficient sample sizes, and detailed adverse effect profiles may help determine the rationale for their use.

Antidepressant-related microstructural changes in the external capsule.

Several magnetic resonance imaging (MRI) studies have reported that antidepressant medications are strongly linked to brain microstructural alterations. Notably, external capsule alterations have been reported to be a biological marker for therapeutic response. However, prior studies did not investigate whether a change in the neurite density or directional coherence of white matter (WM) fibers underlies the observed microstructural alterations. This MRI-based case-control study examined the relationship between patients' current use of antidepressant medications and advanced measurements of external capsule WM microstructure derived from multishell diffusion imaging using neurite orientation dispersion and density imaging (NODDI). The study compared a group of thirty-five participants who were taking antidepressant medications comprising selective serotonin reuptake inhibitors (SSRIs) (n = 25) and serotonin and norepinephrine reuptake inhibitors (SNRIs) with a control group of thirty-five individuals matched in terms of age, sex, race, and atherosclerotic cardiovascular risk factors. All participants were selected from the Dallas Heart Study phase 2, a multi-ethnic, population-based cohort study. A series of multiple linear regression analyses were conducted to predict microstructural characteristics of the bilateral external capsule using age, sex, and antidepressant medications as predictor variables. There was significantly reduced neurite density in the bilateral external capsules of patients taking SSRIs. Increased orientation dispersion in the external capsule was predominantly seen in patients taking SNRIs. Our findings suggest an association between specific external capsule microstructural changes and antidepressant medications, including reduced neurite density for SSRIs and increased orientation dispersion for SNRIs.

Premenstrual syndrome: new insights into etiology and review of treatment methods.

Premenstrual syndrome (PMS) is a common disorder affecting women of reproductive age, with an estimated global prevalence of 47.8%, with severe symptoms occurring in 3-8%, significantly affecting daily functioning. GABA conductance and changes in neurosteroid levels, particularly allopregnanolone, are suspected to play a substantial role in the disorder's etiology. In this paper, we provide an overview of recent reports on the etiology and recognized therapeutic approaches, encompassing both pharmacological and non-pharmacological interventions. Our examination includes studies on SSRIs, hormonal agents, neurosteroids, supplementation, and therapeutic roles. We aim to determine the most favorable treatment regimen by comparing medication effects and alternative methods. The treatment of PMS is crucial for enhancing the quality of life for affected women. Medications used in PMS treatment should be individually selected to achieve the best therapeutic effect, considering the clinical situation of the patients.

Development of a multivariate prediction model for antidepressant resistant depression using reward-related predictors.

Introduction: Individuals with depression who do not respond to two or more courses of serotonergic antidepressants tend to have greater deficits in reward processing and greater internalizing symptoms, yet there is no validated self-report method to determine the likelihood of treatment resistance based on these symptom dimensions. Methods: This online case-control study leverages machine learning techniques to identify differences in self-reported anhedonia and internalizing symptom profiles of antidepressant non-responders compared to responders and healthy controls, as an initial proof-of-concept for relating these indicators to medication responsiveness. Random forest classifiers were used to identify a subset from a set of 24 reward predictors that distinguished among serotonergic medication resistant, non-resistant, and non-depressed individuals recruited online (N = 393). Feature selection was implemented to refine model prediction and improve interpretability. Results: Accuracies for full predictor models ranged from .54 to .71, while feature selected models retained 3-5 predictors and generated accuracies of .42 to .70. Several models performed significantly above chance. Sensitivity for non-responders was greatest after feature selection when compared to only responders, reaching .82 with 3 predictors. The predictors retained from feature selection were then explored using factor analysis at the item level and cluster analysis of the full data to determine empirically driven data structures. Discussion: Non-responders displayed 3 distinct symptom profiles along internalizing dimensions of anxiety, anhedonia, motivation, and cognitive function. Results should be replicated in a prospective cohort sample for predictive validity; however, this study demonstrates validity for using a limited anhedonia and internalizing self-report instrument for distinguishing between antidepressant resistant and responsive depression profiles.

The selective serotonin reuptake inhibitor sertraline alters learning from aversive reinforcements in patients with depression: evidence from a randomized controlled trial.

BACKGROUND: Selective serotonin reuptake inhibitors (SSRIs) are first-line pharmacological treatments for depression and anxiety. However, little is known about how pharmacological action is related to cognitive and affective processes. Here, we examine whether specific reinforcement learning processes mediate the treatment effects of SSRIs. METHODS: The PANDA trial was a multicentre, double-blind, randomized clinical trial in UK primary care comparing the SSRI sertraline with placebo for depression and anxiety. Participants (N = 655) performed an affective Go/NoGo task three times during the trial and computational models were used to infer reinforcement learning processes. RESULTS: There was poor task performance: only 54% of the task runs were informative, with more informative task runs in the placebo than in the active group. There was no evidence for the preregistered hypothesis that Pavlovian inhibition was affected by sertraline. Exploratory analyses revealed that in the sertraline group, early increases in Pavlovian inhibition were associated with improvements in depression after 12 weeks. Furthermore, sertraline increased how fast participants learned from losses and faster learning from losses was associated with more severe generalized anxiety symptoms. CONCLUSIONS: The study findings indicate a relationship between aversive reinforcement learning mechanisms and aspects of depression, anxiety, and SSRI treatment, but these relationships did not align with the initial hypotheses. Poor task performance limits the interpretability and likely generalizability of the findings, and highlights the critical importance of developing acceptable and reliable tasks for use in clinical studies. FUNDING: This article presents research supported by NIHR Program Grants for Applied Research (RP-PG-0610-10048), the NIHR BRC, and UCL, with additional support from IMPRS COMP2PSYCH (JM, QH) and a Wellcome Trust grant (QH).

Serum brain-derived neurotrophic factor, Val66Met polymorphism and open-label SSRI treatment response in Major Depressive Disorder.

BACKGROUND: Brain-derived neurotrophic factor (BDNF) has been implicated in the therapeutic action of antidepressants and possibly in the pathophysiology of Major Depressive Disorder (MDD). Clinical studies of peripheral blood levels of BDNF in MDD have provided conflicting results, and there are also conflicting reports regarding the predictive value of peripheral BDNF levels for antidepressant treatment response. The present study investigated the association between serum BDNF levels, the BDNF Val66Met polymorphism (rs6265), clinical characteristics and SSRI treatment response. METHODS: This open-label clinical trial included 99 physically healthy, unmedicated MDD participants and 70 healthy controls. Following a baseline assessment, 53 of the MDD participants completed an eight-week, open-label course of SSRI antidepressant treatment. Serum BDNF levels and Hamilton Rating Scale for Depression (HDRS) ratings were examined at baseline and after eight weeks of treatment. Antidepressant response was defined as a decrease in HDRS ratings of > 50% from baseline to the end-of-treatment. Finally, serum BDNF levels and SSRI treatment response were compared between MDD participants who were heterozygous or homozygous for the Met allele ("Met-carriers") and individuals homozygous for the Val allele. RESULTS: Serum BDNF levels at baseline were significantly higher in the unmedicated MDD participants compared to healthy controls (15.90 ng/ml vs 13.75 ng/ml, t (167) = -2.041, p = 0.043). In a post-hoc analysis, this difference was seen in the female but not male participants (16.85 ng/ml vs 14.06 ng/ml, t (91) = -2.067, p = 0.042; 14.86 ng/ml vs 13.31 ng/ml, t (74) = -0.923, p = 0.359). Baseline serum BDNF levels were not associated with treatment responder status or with absolute change in depression ratings over the course of 8-week SSRI treatment (p = 0.599). In both Responders and Non-responders, no significant changes in serum BDNF levels were found over the 8-week period of SSRI-treatment (16.32 ng/ml vs 16.23 ng/ml, t (18) = 0.060, p = 0.953; 16.04 ng/ml vs 15.61 ng/ml, t (29) = 0.438, p = 0.665, respectively). Further, no differences were found in serum BDNF levels prior to treatment between MDD Met-carriers and MDD Val/Val homozygotes (15.32 ng/ml vs 16.36 ng/ml, t (85) = 0.747, p = 0.457), and no differences were found in post-treatment serum BDNF (F1,42= 0.031, p = 0.862). However, MDD Val/Val homozygotes showed significantly greater antidepressant responses at week 8 than did MDD Met-carriers (F1,46 = 4.366, p = 0.043). CONCLUSION: Our results do not support sufficient reliability of using peripheral BDNF to characterize depression or to predict antidepressant response in clinical use. The role of sex in moderating BDNF differences in depression, and the role of BDNF gene polymorphisms in predicting antidepressant response, remain to be further investigated. We conclude that, while central nervous system BDNF is likely involved in antidepressant efficacy and in aspects of MDD pathophysiology, its reflection in serum BDNF levels is of limited diagnostic or prognostic utility.

Weakened effective connectivity between salience network and default mode network during resting state in adolescent depression.

Adolescent major depressive disorder (MDD) is associated with altered resting-state connectivity between the default mode network (DMN) and the salience network (SN), which are involved in self-referential processing and detecting and filtering salient stimuli, respectively. Using spectral dynamical causal modelling, we investigated the effective connectivity and input sensitivity between key nodes of these networks in 30 adolescents with MDD and 32 healthy controls while undergoing resting-state fMRI. We found that the DMN received weaker inhibition from the SN and that the medial prefrontal cortex and the anterior cingulate cortex showed reduced self-inhibition in MDD, making them more prone to external influences. Moreover, we found that selective serotonin reuptake inhibitor (SSRI) intake was associated with decreased and increased self-inhibition of the SN and DMN, respectively, in patients. Our findings suggest that adolescent MDD is characterized by a hierarchical imbalance between the DMN and the SN, which could affect the integration of emotional and self-related information. We propose that SSRIs may help restore network function by modulating excitatory/inhibitory balance in the DMN and the SN. Our study highlights the potential of prefrontal-amygdala interactions as a biomarker and a therapeutic target for adolescent depression.

Access to a tailored mobile application enhances medication adherence among young users of antidepressants.

Introduction: Patients' adherence to antidepressants is generally reported to be poor. This study examined whether users of selective serotonin reuptake inhibitors (SSRIs) and serotonin and norepinephrine reuptake inhibitors (SNRIs) enhance medication adherence following access to a mobile application (app) tailored for this patient group. The study addresses the implementation phase of medication adherence. Methods: The study was a single group pre-post intervention design. Data were collected using the validated OsloMet Adherence-to-medication Survey tool (OMAS-37) before and after app access. Pre-app access survey (Survey 1) was conducted via social media and online newspapers, encompassing 445 SSRI/SNRI users aged 18 years and above. Post-app access survey (Survey 2) was sent to 103 SSRI/SNRI users from Survey 1. Wilcoxon Signed Rank Test compared pre- and post-intervention adherence measurements. Pearson's chi-square tests and Fisher's exact tests compared study population categories. Results: Forty-two SSRI/SNRI users, median age 26 (IQR 17), 93% identifying as female, used the app while using the same antidepressant during the 2-month period between gaining access to the app and Survey 2. There was a statistically significant reduction in non-adherence score post-app access (z = 3.57, n = 42, p < 0.001) with medium effect size (r = 0.39), indicating enhanced adherence. Total non-adherence score decreased by 39% from pre-to post-access, and there was a 12% decrease in users scoring equivalent with poor adherence (score <2) post-access. Twenty-nine of 37 non-adherence causes improved, with three showing statistical significance. Of 42 responders, 50% (n = 21) indicated using the app one to two times, while 50% (n = 21) more than three times. Approximately 69% (n = 28) found it useful, and 43% (n = 18) felt safer in their use of antidepressants after access to the app. No significant preference was observed for the app over alternative sources of information. Discussion: Enhanced medication adherence was observed among antidepressant users following access to the tailored app. Further studies are warranted to evaluate the app applicability to a broader range of antidepressants users or other patient groups, encompassing those in the initiation phase of medication adherence. The app is intended as an easily accessible supplement to the information and advice provided by prescribing physicians and dispensing pharmacists.