Selective Serotonin Reuptake Inhibitor Therapy Research Articles

The potential predictors for treatment-resistance depression after selective serotonin reuptake inhibitors therapy in Han Chinese: A resting-state functional magnetic resonance imaging study.

Selective serotonin reuptake inhibitors (SSRIs) are among the most important antidepressants. However, there is limited research on predicting the occurrence of treatment-resistant depression (TRD) after 5 years. Examining the predictive effect of TRD occurrence using resting-state fMRI in patients initiating SSRIs treatment at the onset of major depressive disorder (MDD) could potentially enhance TRD management. A total of 60 first-episode drug-naive MDD patients who met the criteria, along with 41 healthy controls of Han Chinese ethnicity, were recruited. All MDD patients received SSRIs as the initial treatment for relieving depressive symptoms. Resting-state fMRI scans were conducted for all subjects. Follow-up assessments were conducted over a period of five years, during which MDD patients were categorized into treatment-resistant depression (TRD) and non-treatment-resistant depression (NRD) groups based on disease progression. Amplitude of low-frequency fluctuations (ALFF), fractional amplitude of low-frequency fluctuations (fALFF), and Regional Homogeneity (ReHo) values were calculated and compared among the three groups. Additionally, receiver operating characteristic (ROC) curves were employed to identify potential predictors. After 5 years of follow-up, it was found that 43 MDD patients were classified as NRD, while 17 were classified as TRD. In comparison to TRD, NRD exhibited decreased ALFF in the left middle cingulum gyrus (MCG.L) and in the right middle frontal gyrus (MFG.R), as well as decreased ReHo in MCG.L. Furthermore, NRD showed increased fALFF in the left precuneus (PCUN.L). The area under the curve (AUC) values were as follows: 0.724 (MCG.L by ALFF), 0.732 (MFG.R), 0.767 (PCUN.L), 0.774 (MCG.L by ReHo), 0.878 (combined), 0.547 (HAMD), and 0.408 (HAMA) respectively. The findings suggest that PCUN.L, MFG.R, MCG.L, and the combined measures may indicate the possibility of developing TRD after 5 years when SSRIs are used as the initial therapy for relieving depressive symptoms in MDD patients.

SSRI Efficacy in Treating Major Depressive Disorder: Preliminary Findings

Background: Conflicting evidence on the relative effectiveness of second-generation antidepressants has made initial management of major depressive disorder (MDD) complex and frequently results in a trial-and-error-based approach to treatment. With recent literature suggesting serotonin plays no significant role in the etiology of depression, further investigation of selective serotonin reuptake inhibitors (SSRIs) as a firstline treatment of MDD is warranted.
 Methods: A retrospective chart review of patients 18 years or older visiting the Fort Wayne Family Medicine Center and completing a Patient Health Questionnaire (PHQ) or Generalized Anxiety Disorder scale (GAD) from January 2020 through May 2023 was performed. Comparative analysis of PHQ and GAD scores was performed to determine if any differences in treatment management outcomes were present between SSRI therapy and other treatment approaches.
 Results: 1,502 patients met the inclusion criteria. Due to time constraints, a sample of 45 patients (10 males, 35 females) was selected and preliminary results are as follows: After initiating treatment with an SSRI, 14 (42.4%) PHQ scores and 7 (24.1%) GAD scores demonstrated improved disease severity. After initiating treatment with another antidepressant class, 10 (31.3%) PHQ scores and 17 (48.6%) GAD scores demonstrated improved disease severity. There was no significant difference (p=0.351) in treatment outcomes between antidepressant class in terms of PHQ results, but a significant difference (p=0.044) was found between groups with regards to GAD results.
 Conclusions: This study describes preliminary findings on the current patterns of care for mental health within a primary care setting and demonstrates antidepressant classes appear equally efficacious in treating depression. However, anxiety management outcomes appear to be influenced by antidepressant class administered. Future analysis will include the entire available dataset and produce more robust results from which to improve patient-specific and community health outcomes.

Management of anhedonia after epilepsy surgery

Anhedonia is clinically defined as difficulty or inability to feel pleasure or to be motivated to perform activities that were previously pleasurable. Anhedonia is a core feature of depressive disorders but can be present in other conditions such as substance use and anxiety disorders. Herein we report the case of a 34-year-old female who developed marked anhedonia after left cortico-amygdalohippocampectomy. Despite optimal seizure control, the person struggled with anhedonia and other depressive symptoms. After ruling out medico-neurologic complications, she was prescribed with a selective serotonin reuptake inhibitor and cognitive-behavioral therapy. Anhedonia can be a challenging neuropsychiatric presentation that requires ruling out the effects of antiseizure medications, neurosurgery, and other drugs before prescribing antidepressants.

Severe alcohol use disorder after initiation of selective serotonin reuptake inhibitor therapy.

Severe alcohol use disorder after initiation of selective serotonin reuptake inhibitor therapy.

Default Mode Network Hypoalignment of Function to Structure Correlates With Depression and Rumination

BackgroundRecent studies have begun to examine how signals in the brain correspond to the underlying white matter structure using tools from the field of graph signal processing to quantify brain function alignment to brain network topology. Here, we applied this framework for the first time toward a transdiagnostic cohort of individuals with internalizing psychopathologies, including mood and anxiety disorders, to uncover how such alignment within the default mode network (DMN) is related to depression and rumination symptoms. MethodsBoth diffusion-weighted and resting-state functional magnetic resonance imaging were obtained from participants at baseline (n = 60 patients, n = 19 healthy control participants). Patients were randomized to 12 weeks of treatment with either a selective serotonin reuptake inhibitor or cognitive behavioral therapy, and symptom scales were readministered posttreatment (n = 46 patients at follow-up). Using graph signal processing methodology, we quantified the alignment of functional signals to their underlying white matter structural networks. ResultsWe found that signal alignment within the posterior DMN was decreased in patients with internalizing psychopathologies compared with healthy control participants and was inversely (negatively) correlated with baseline depression and rumination scales. Signal alignment within the posterior DMN was also correlated with the ratio of total within-DMN to extra-DMN functional connectivity for these regions. ConclusionsThese findings are consistent with previous literature regarding pathological promiscuity of posterior DMN connectivity and provide the first graph signal processing–based analyses in a transdiagnostic cohort of patients with internalizing psychopathologies.

Real world experience of Endoxifen augmentation therapy in a case of resistant OCD

About 40%–60% of obsessive-compulsive disorder patients do not achieve full remission even when treated with selective serotonin reuptake inhibitor and cognitive behavioural therapy. Here, we describe a case of a 30-year-old female suffering from OCD, who was not improved even after fluoxetine 80 mg per day and behavioural therapy and was successfully treated with low dose fluoxetine (60 mg/day) and Endoxifen (8 mg/day).

Late-life depression: Epidemiology, phenotype, pathogenesis and treatment before and during the COVID-19 pandemic.

Late-life depression (LLD) is one of the most common mental disorders among the older adults. Population aging, social stress, and the COVID-19 pandemic have significantly affected the emotional health of older adults, resulting in a worldwide prevalence of LLD. The clinical phenotypes between LLD and adult depression differ in terms of symptoms, comorbid physical diseases, and coexisting cognitive impairments. Many pathological factors such as the imbalance of neurotransmitters, a decrease in neurotrophic factors, an increase in β-amyloid production, dysregulation of the hypothalamic-pituitary-adrenal axis, and changes in the gut microbiota, are allegedly associated with the onset of LLD. However, the exact pathogenic mechanism underlying LLD remains unclear. Traditional selective serotonin reuptake inhibitor therapy results in poor responsiveness and side effects during LLD treatment. Neuromodulation therapies and complementary and integrative therapies have been proven safe and effective for the treatment of LLD. Importantly, during the COVID-19 pandemic, modern digital health intervention technologies, including socially assistive robots and app-based interventions, have proven to be advantageous in providing personal services to patients with LLD.

Emulating a Target Trial of Dynamic Treatment Strategies for Major Depressive Disorder Using Data From the STAR∗D Randomized Trial

BackgroundClinical guidelines recommend adding a second drug for patients with major depressive disorder who have a partial response and switching antidepressants for those who show no response or intolerance. This guidelines-based strategy was compared with other strategies for the management of unresponsive depression. MethodsA total of 1436 individuals experiencing treatment failure with citalopram and still requiring antidepressant therapy were identified in the STAR∗D (Sequenced Treatment Alternatives to Relieve Depression) trial. A (hypothetical) target trial was then designed and emulated. The following strategies for decision making were compared: sequential monotherapy, sequential dual non–selective serotonin reuptake inhibitor therapy (SD), and a guidelines-based strategy. The primary outcome was symptomatic remission defined as a Hamilton Depression Rating Scale score ≤7 or 2 consecutive scores ≤5 on the 16-item Quick Inventory of Depressive Symptomatology–Clinician Rated. Secondary outcomes were serious events (hospitalizations, suicide, and mortality). Inverse probability weighting was used to control for possible confounding. ResultsA total of 971 patients were eligible for our emulation. Patients initiating SD had the lowest levels of depression at baseline. The estimated 9-month probability of remission was 43.5% for the sequential monotherapy group, 47.6% for the SD group, and 53.2% for the guidelines-based strategy group. Compared with the sequential monotherapy group, the difference in 9-month probability of remission was −4.2% (95% CI, −15.6 to 4.6) for the SD group and −9.7% (−19.3 to 1.9) for the guidelines-based strategy group. The 9-month relative risks of remission were 1.09 (0.90 to 1.38) and 1.22 (0.96 to 1.46), respectively. Results were consistent across sensitivity analyses. The 9-month relative risks of serious events were 0.77 (0.38 to 1.40) and 0.62 (0.33 to 1.00), respectively. ConclusionsUsing the guidelines-based strategy was associated with an increased probability of remission and a lower risk of serious adverse events. The potential implications are substantial given the large number of patients experiencing treatment failure to antidepressants.

Associations between Autoimmunity and Depression: Serum IL-6 and IL-17 Have Directly Impact on the HAMD Scores in Patients with First-Episode Depressive Disorder.

Objective The study is aimed at evaluating the immune-activation state before and after treatment in patients with first-episode depressive disorder (FDD) with evaluating the ILs and CRP levels and further clarifying the association between autoimmunity and the etiology and pathogenesis of FDD. Methods We designed a case-control study. FDD patients and healthy subjects were enrolled in the FDD group and control group. Serum IL-6, IL-17, and CRP were measured before and after selective serotonin reuptake inhibitor (SSRI) therapy, as well as Hamilton rating scale for depression (HAMD) and life event scale (LES) scores. The correlations between IL-6 and IL-17 and HAMD and LES scores were analysed, and multiple linear regression analysis was performed for HAMD score. Results 40 FDD patients and 40 healthy subjects were included in the FDD and control group from October 2009 to September 2012. Before treatment, the IL-6 (28.99 ± 5.51, P < 0.001) and IL-17 (41.15 ± 4.80, P < 0.001) in the FDD group were significantly higher than the control group (16.84 ± 3.78 and 21.68 ± 3.72, respectively). The C-reactive protein (CRP) level in two groups was comparable (P = 0.879). After treatment, the IL-6 (18.69 ± 5.07, P < 0.001) and IL-17 (30.67 ± 3.47, P < 0.001) levels and HAMD scores (6.73 ± 4.15) in the FDD group were significantly decreased than before treatment (P < 0.001, respectively). CRP level was slightly increased after treatment without statistically significant (P = 0.239). The HAMD score correlated with IL-6 (r = 0.638, P < 0.001) and IL-17 (r = 0.927, P < 0.001); the total LES and negative LES also correlated with IL-6 (r = 0.226, P < 0.05) (r = 0.366, P <0.001) and IL-17 (r = 0.348, P < 0.001) (r = 0.493, P < 0.001). Multiple linear regression analysis showed that both of the IL-6 and IL-17 had direct impact on HAMD score. Conclusion The autoimmunity status was overactivated in FDD patients, and serum IL-6 and IL-17 levels had direct impact on the HAMD score. Patients who experienced more negative life events had higher activation level of autoimmunity status and HAMD scores, and serum IL-6 and IL-17 levels can be decreased by SSRI treatment.

Effect of Low-Dose Statins in Addition to Standard Therapy on Brain Perfusion and Neurocognitive Performance in Patients with Major Depressive Disorder

Introduction: Major depressive disorder (MDD) is a prevalent condition which has a well-known association with ischemic cardiomyopathy, probably explained by an inflammatory mediator mechanism. Statins, besides reducing cholesterol production, have pleiotropic effects including anti-inflammatory activity. The goal was to evaluate the effect of statins as an addition to standard therapy on mood status, brain perfusion, and neurocognitive performance in MDD. Methods: We studied 20 MDD patients with brain single-photon emission tomography and Cambridge Neuropsychological Test Automated Battery (CANTAB), half randomized to 10 mg of Rosuvastatin or placebo, in addition to selective serotonin reuptake inhibitors (SSRIs) therapy and being reevaluated 3 months later. The images were compared using Statistical Parametric Mapping; clinical scores (Hamilton Depression Score with 17 items and Beck’s Depression Inventory) as well as neurocognitive parameters were applied as covariances (CoV) to estimate regional cerebral blood flow (rCBF) changes with both therapies. Results: Clinical scores decreased in both groups (p = 0.0001); Beck’s presented a larger decrease with statins. We observed significantly rCBF changes expressed as significant larger clusters of voxels (p < 0.05) in the pre/subgenual anterior cingulate plus orbitofrontal cortex and a small area in the posterior cingulate gyrus in the statins group, whereas it was not observed with placebo, when using clinical scores as CoV. A similar pattern of rCBF changes was present with emotions recognition, attentional, paired associates learning, spatial planning, and working memory tasks. Conclusion: Short-term use of low-dose statins in MDD patients under SSRIs results in important rCBF changes in key mood associated areas to improvement in neurocognitive performance. These findings, even though demonstrated in a small sample, could open a new therapeutic tool in the comprehensive management of this disorder.

EEG microstates as markers of major depressive disorder and predictors of response to SSRIs therapy

BackgroundMajor depressive disorder (MDD) is associated with abnormal neural activities and brain connectivity. EEG microstate is a voltage topology map that reflects transient activations of the brain network. A limited number of studies on EEG microstate in MDD have focused on differences between patients and healthy controls. However, EEG microstate changes in MDD patients before and after drug treatment have not been evaluated. We assessed EEG microstate characteristics and evaluated changes in brain network dynamics in MDD patients before and after drug treatment. Moreover, we evaluated the neuro-electrophysiological mechanisms of antidepressant therapies. Methods64-channel resting EEG was obtained from 101 patients with first-episode untreated depression (0 week) and 45 healthy controls (HC) from January to December 2020. MDD patients were treated with selective serotonin reuptake inhibitors (SSRI). EEG data for 51 MDD patients who had completed an 8-week follow-up was collected. After pre-processing, EEG data from different groups were subjected to microstate analysis, and the atomize and agglomerate hierarchical clustering (AAHC) was into 4 microstates. Next, EEG signals from each patient were fitted using templates of 4 microstates. Finally, microstate indices were collected and analyzed. ResultsGlobal clustering generated 4 microstates (A, B, C, D) in all subjects, which explained 65–84% of the global variance. Compared to HC, the duration of microstate D reduced while those of microstates A and B increased in MDD patients. After the 8-week treatment period, the duration and coverage of microstate D increased, the frequency of microstate A and transition probability of microstate D to A reduced, while transition probability of microstate B to D and D to B increased in MDD patients. There were no differences in microstate features between HC and MDD at 8 weeks. In patients with first-episode untreated depression, lower average durations of microstate D, relatively higher frequencies of microstate C and lower transition probabilities of microstate D to B correlated with better effects after 8 weeks. The higher occurrence and proportion of microstate C at 8 weeks was positively correlated with the HAMD score and reduction rate. The same observation was reached for the transition probability of microstate A to C. However, the transition probability of microstate D to B showed a negative correlation with the HAMD score at 8 weeks. ConclusionMicrostate D is a potential electrophysiological trait of MDD and can predict treatment outcomes of SSRIs. Therefore, EEG microstate analysis may not only be an objective method for evaluating treatment outcomes of depression, but is also a potential new approach for exploring the neuro-electrophysiological mechanisms of antidepressant therapy.Public title: Multidimensional diagnosis, individualized treatment and management techniques based on clinic-pathological characteristics of depressive disorder; Registration number: ChiCTR1900026600; Date of registration: 2019-10-15; URL: http://www.chictr.org.cn/index.aspx

Acupuncture combined with SSRIs in the treatment of perimenopausal depressive disorder: A protocol for systematic review and meta-analysis.

Background:Perimenopausal depressive disorder (PDD) is an affective disorder involving endocrine, neurological, immune, which seriously endangers the physical and mental health of human. Selective serotonin reuptake inhibitors (SSRIs) are the current first-line clinical treatment, have limited efficacy and serious side effects. Acupuncture combined with SSRIs therapy has been widely used clinically because it increases efficacy and reduces side effects. There is a lack of high-quality evidence to assess its efficacy and safety. This study evaluated the effectiveness and safety of acupuncture combined with SSRIs in the treatment of PDD by meta-analysis.Methods:All randomized controlled trials articles about acupuncture combined with SSRIs treatment of PDD will be searched in databases, such as PubMed, Cochrane Library, Web of Science, China National Knowledge Infrastructure, Wan Fang, Wei Pu from the construction of the library to December 16, 2021. According to Cochrane 5.1 Handbook criteria, two researchers independently screened the literature, extracted data, and evaluated the quality of included studies. Meta-analysis was performed by using RevMan 5.4 and STATA 16.0 software.Results:This study will summarize the current evidence to evaluate the effectiveness and safety of acupuncture combined with SSRIs for the treatment of PDD.Conclusion:The results of this study will provide clinicians with new treatment ideas and bring benefits to most patients.Registration number:INPLASY2021120080 (DOI number: 10.37766/inplasy2021.12.0080).

Selective Serotonin Reuptake Inhibitors for the Prevention of Post-Stroke Depression: A Systematic Review and Meta-Analysis.

There are controversial data on the efficacy and safety profile of selective serotonin reuptake inhibitors (SSRIs) to prevent post-stroke depression (PSD). We performed a systematic search in MEDLINE and SCOPUS databases to identify randomized-controlled trials questioning the use of early SSRI therapy in the post-stroke population and its effect on PSD incidence. We included 6 studies with 6560 participants. We extracted the data on PSD occurrence in association with the treatment arm (SSRI versus placebo), as reported by each study. For safety analysis, we extracted the information on adverse events. A random-effects model was used to calculate the pooled relative risk estimates. Early SSRI therapy was associated with a significant reduction of PSD occurrence compared to placebo (10.4% versus 13.8%; relative risk: 0.75 [95% CI, 0.66–0.86]; absolute risk reduction: 3.4%). SSRI therapy increases the risk of bone fracture (RR 2.28 [95% CI, 1.58–3.30]) and nausea (RR 2.05 [95% CI, 1.10–3.82]) in the post-stroke population. Considering the risk-benefit ratio of early SSRI therapy in the post-stroke population, future research should identify high-risk patients for PSD to improve the risk-benefit consideration of this therapy for use in clinical practice.

An Investigation into the Association Between Dopamine Receptor D1 Multilocus Genetic Variation, Multiparametric Magnetic Resonance Imaging, and Antidepressant Treatment.

Combining genetic variants with neuroimaging phenotypes may facilitate understanding of the biological mechanisms for the etiology and pharmacology of antidepressant treatment of major depressive disorder (MDD). To explore the latent pathway of dopamine gene-hierarchical brain network-antidepressant treatment. Retrospective. One hundred and sixty-eight MDD inpatients divided into responders (N=98) or nonresponders (N=70) based on the treatment outcome of antidepressant. Diffusion tensors imaging and resting-state functional magnetic resonance imaging at 3.0T using echo-planar sequence. Four genetic variations of the dopamine receptor D1 (DRD1) were genotyped. Strengths of rich-club, feeder, and local connections were calculated based on the rich-club organizations of structural and functional brain networks at baseline and following 4 weeks of selective serotonin reuptake inhibitor (SSRI) therapy. Logistic and linear regressions were used to analyze the impact of DRD1 multilocus genetic profile score on the treatment response of SSRI, and their associations with strengths of rich-club, feeder, and local connections. Mediation models were developed to explore the mediation role of rich-club organizations on the relationship between DRD1 and SSRI therapy response. A P value <0.05 was considered to be statistically significant. Multiple genetic variations of DRD1 were significantly related to the strengths of feeder connections both in structural and functional networks, and to the treatment response of SSRI. Furthermore, the strength of the structural feeder connection significantly modulated the effect of DRD1 variants on SSRI treatment outcome. DRD1 displayed close connections both with SSRI treatment outcome and rich-club organizations of structural and functional data. Moreover, structural feeder connection played a mediating role in the relationship between DRD1 and antidepressant therapy. 3 TECHNICAL EFFICACY STAGE: 4.

Combining selective serotonin reuptake inhibitors and cognitive behavioral therapy in youth with depression and anxiety

BackgroundTreatment studies of children and adolescents with internalizing disorders suggest that the combination of a selective serotonin reuptake inhibitor (SSRI) and cognitive behavioral therapy (CBT) consistently produces greater improvement than either treatment alone. We sought to determine how response to combined treatment varies across disorders (anxiety versus depression), and by specific patient characteristics. MethodsThree large National Institutes of Health-funded trials of children and adolescents with major depression (n = 2) and anxiety disorders (n = 1) were evaluated, each comparing CBT + SSRI to SSRI only, Bayesian Hierarchical Models (BHMs) were used, for endpoint response, time course of response and predictors of response in participants who received SSRI or SSRI+CBT. ResultsSSRI+CBT significantly decreased symptoms by week 4 (p<0.001) across disorders. This improvement continued at week 8 and 12 (p<0.001); however, the additive benefit of CBT over SSRI monotherapy was not statistically significant until week 12 (p<0.001). The fastest response to SSRI+CBT was for patients who were younger, with milder baseline anxiety/depression symptoms and depressive disorders. The slowest response for SSRI+CBT was for boys, adolescents, minoritized children, those with severe symptoms and externalizing disorders. LimitationsLimitations included inconsistent moderators, variation in the number of observations over time and a lack of genetic or pharmacokinetic variables related to SSRI exposure across studies. ConclusionsThe superiority of SSRI+CBT for youth with depression and anxiety is further supported. For purposes of rapid and greater relief, combination treatment is the superior approach across anxiety and depression and is robust to a range of participant characteristics. However, the added value of CBT (with an SSRI) occurs late in treatment. These findings represent a step towards understanding heterogeneity of treatment response and raise the possibility that interventions could be better tailored or adapted based on patient characteristics.

Impact of Updating Pharmacogenetic Results: Lessons Learned from the PREDICT Program.

Pharmacogenomic (PGx) evidence for selective serotonin reuptake inhibitors (SSRIs) continues to evolve. For sites offering testing, maintaining up-to-date interpretations and implementing new clinical decision support (CDS) driven by existing results creates practical and technical challenges. Vanderbilt University Medical Center initiated panel testing in 2010, added CYP2D6 testing in 2017, and released CDS for SSRIs in 2020. We systematically reinterpreted historic CYP2C19 and CYP2D6 genotypes to update phenotypes to current nomenclature and to launch provider CDS and patient-oriented content for SSRIs. Chart review was conducted to identify and recontact providers caring for patients with current SSRI therapy and new actionable recommendations. A total of 15,619 patients’ PGx results were reprocessed. Of the non-deceased patients reprocessed, 21% (n = 3278) resulted in CYP2C19*1/*17 reinterpretations. Among 289 patients with an actionable recommendation and SSRI medication prescription, 31.8% (n = 92) did not necessitate contact of a clinician, while 43.2% (n = 125) resulted in clinician contacted, and for 25% (n = 72) no appropriate clinician was able to be identified. Maintenance of up-to-date interpretations and recommendations for PGx results over the lifetime of a patient requires continuous effort. Reprocessing is a key strategy for maintenance and expansion of PGx content to be periodically considered and implemented.

Simultaneous Benzodiazepine and SSRI Initiation in Young People With Anxiety Disorders.

Objective: There are potential risks and benefits of combining benzodiazepine (BZD) and selective serotonin reuptake inhibitor (SSRI) therapy at anxiety disorder treatment onset. We investigated how often adolescents and young adults with anxiety disorders simultaneously initiate BZD treatment with SSRI treatment and examined whether SSRI treatment duration varies by simultaneous BZD initiation.Methods: In a United States commercial claims database (January 2008-December 2016), we identified adolescents (10-17 years) and young adults (18-24 years) with ICD-9-CM/ICD-10-CM anxiety disorder diagnoses initiating SSRI treatment, without past-year SSRI and BZD treatment. We defined simultaneous initiation as filling a new BZD prescription on the date of SSRI initiation. We estimated time to SSRI treatment discontinuation and used stabilized inverse probability of treatment weighting for adjusted estimates.Results: The study included 94,399 adolescents and 130,971 young adults initiating SSRI treatment with an anxiety disorder. Four percent of adolescents and 17% of young adults simultaneously initiated BZD treatment, varying by age, anxiety disorder, comorbidities, health care utilization, and provider type. Simultaneous BZD initiation among SSRI initiators declined from 2008 to 2016. SSRI treatment duration was similar in initiators of simultaneous therapy vs SSRI monotherapy: ≥ 6 months in adolescents (55% vs 56%, respectively) and in young adults (39% vs 40%). Nine percent of simultaneous initiators continued BZDs for ≥ 6 months.Conclusions: Simultaneous initiation of BZD and SSRI treatment is relatively common in young adults with anxiety disorders and was not associated with longer SSRI persistence. Given risks of BZD treatment, potential benefits and risks of adding a BZD at SSRI treatment initiation must be carefully weighed.

Abnormal levels of mitochondrial proteins in plasma neuronal extracellular vesicles in major depressive disorder

To characterize neuronal mitochondrial abnormalities in major depressive disorder (MDD), functional mitochondrial proteins (MPs) extracted from enriched plasma neuron-derived extracellular vesicles (NDEVs) of MDD participants (n = 20) were quantified before and after eight weeks of treatment with a selective serotonin reuptake inhibitor (SSRI). Pretreatment baseline NDEV levels of the transcriptional type 2 nuclear respiratory factor (NRF2) which controls mitochondrial biogenesis and many anti-oxidant gene responses, regulators of diverse neuronal mitochondrial functions cyclophilin D (CYPD) and mitofusin-2 (MFN2), leucine zipper EF-hand containing transmembrane 1 protein (LETM1) component of a calcium channel/calcium channel enhancer, mitochondrial tethering proteins syntaphilin (SNPH) and myosin VI (MY06), inner membrane electron transport complexes I (subunit 6) and III (subunit 10), the penultimate enzyme of nicotinamide adenine dinucleotide (NAD) generation nicotinamide mononucleotide adenylytransferase 2 (NMNAT2), and neuronal mitochondrial metabolic regulatory and protective factors humanin and mitochondrial open-reading frame of the 12S rRNA-c (MOTS-c) all were significantly lower than those of NDEVs from matched controls (n = 10), whereas those of pro-neurodegenerative NADase Sterile Alpha and TIR motif-containing protein 1 (SARM1) were higher. The baseline NDEV levels of transcription factor A mitochondrial (TFAM) and the transcriptional master-regulator of mitochondrial biogenesis PPAR γ coactivator-1α (PGC-1α) showed no differences between MDD participants and controls. Several of these potential biomarker proteins showed substantially different changes in untreated MDD than those we reported in untreated first-episode psychosis. NDEV levels of MPs of all functional classes, except complex I-6, NRF2 and PGC-1α were normalized in MDD participants who responded to SSRI therapy (n = 10) but not in those who failed to respond (n = 10) by psychiatric evaluation. If larger studies validate NDEV MP abnormalities, they may become useful biomarkers and identify new drug targets.

CLINICO-BIOCHEMICAL STUDY OF SAFETY AND TOLERABILITY OF SELECTIVE SEROTONIN REUPTAKE INHIBITORS (SSRIs) IN A TERTIARY MEDICAL COLLEGE IN WEST BENGAL

INTRODUCTION:Selective serotonin reuptake inhibitors (SSRIs) are a class of drugs that selectively increase the levels of serotonin in the synaptic cleft by blocking its uptake by serotoninergic neurons. They are now extensively used to treat various psychiatric disorders like depression, panic disorders, obsessive compulsive disorders and are now being evaluated in the treatment of a number of other psychiatric disorders like bulimia nervosa and social phobia. In this scenario we try to elucidate the serum electrolyte level, serum serotonin level, renal function test and platelet count to check out the changes as in different papers demonstrated that there are variations in different parameters of renal function occurred with chronic administration of SSRI. Objectives: To evaluate serum electrolyte level, serum serotonin level, renal function tests and platelet count of patients with major depressive disorder on chronic SSRI therapy and screen for any adverse drug reactions (if any) Materials and Methods: A cross-sectional observational study conducted in the Department of Psychiatry, Department of Biochemistry and Department of Pharmacology of Medical College and Hospital, Kolkata . The study protocol was approved by the Institutional Ethics Committee. Written consent was obtained from the subjects included in the study. Results and Discussion: After evaluating the biochemical parameters, it was observed that long term (more than 6 months) SSRI therapy can cause decline Platelet count (29.76%) and Serum Sodium Levels i.e. Hyponatremia (29.76%); whereas the serum serotonin levels (17.86%) were found to be elevated. Further, a negative correlation of -0.605 was observed between the serum sodium levels (in subjects with hyponatremia) and the duration for which the subjects were taking SSRI whereas a positive correlation of +0.407 was observed between the serum serotonin levels (in subjects with above normal serum serotonin levels) and the duration for which the subjects were taking SSRI. A number of adverse drug effects were reported. 28 subjects (33.33%) reported at least any one of the following symptoms like Headache, Sedation, Dizziness, Anxiety, Agitation. 12 subjects (14.28%) reported having recurring suicidal thoughts. 21 subjects (25.00%) reported GIT Problems like nausea/ vomiting/ constipation/ dyspepsia. 13 subjects (15.48%) reported reduction in sleep time while 20 subjects (23.81%) reported reduction in appetite. Sexual Problems like decreased libido, ejaculation difculty or impotence was reported by 19 subjects (22.62%). 25 subjects (29.76%) reported that they had gained weight after the therapy. Discontinuation Symptoms were reported by 59 subjects (70.24%). Conclusion: The hemogram of patients on SSRI therapy should be monitored from time to time and their biochemical parameters should be evaluated to prevent any untoward adverse effects in the subjects. The patients on SSRI therapy should be closely monitored for adverse effects like sexual problems, GITproblems, CNS manifestations, suicidal thoughts, discontinuation symptoms among others.

The Potential Role of Pharmacogenomics in Optimizing Drug Regimens for Older People with Major Depressive Disorder.

Major depressive disorder (MDD) is a mood disorder common in older individuals. While many clinical guidelines endorse the use of selective serotonin reuptake inhibitors (SSRIs) as first-line therapy in the treatment of MDD, the use of SSRIs in older populations can result in medication-related adverse events. The use of pharmacogenomic (PGx) testing as a personalized tool to determine optimal SSRI therapy could offer a means to decrease morbidity and improve overall quality of life in older people. This manuscript will review the epidemiology and criteria of MDD according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), discuss the prevalence of MDD in older individuals, review the clinical treatment guidelines for the use of SSRIs in MDD, provide a brief overview of PGx testing, and present evidence for SSRI therapy modifications based on PGx testing.