Efficacy Of Selective Serotonin Reuptake Inhibitors Research Articles

Comparing Selective Serotonin Reuptake Inhibitors (SSRIs) Alone and in Combination With Beta-Blockers for Treating Panic Disorders: A Prospective Cohort Study.

Background Panic disorders are prevalent psychiatric conditions affecting 1.6% to 2.2% of the global population. While selective serotonin reuptake inhibitors (SSRIs) are the first line of treatment, their initial exacerbation of symptoms presents challenges. Beta-blockers have shown promise in managing panic symptoms, but research comparing the efficacy of combined SSRI and beta-blocker therapy to SSRI monotherapy is limited, particularly in Saudi Arabia. Objective To assess the effectiveness of SSRIs combined with beta-blockers vs. SSRI monotherapy in improving panic disorder symptoms severity in patients at King Abdul-Aziz Hospital, Makkah, Saudi Arabia. Methods This prospective cohort study included 62 patients with panic disorder, divided into two groups: SSRI monotherapy (n=29) and SSRIs with beta-blockers (n=33). Panic disorder severity was assessed using the Panic Disorder Severity Scale (PDSS) after three months of treatment. Secondary outcomes included depression and anxiety symptoms, measured by the Patient Health Questionnaire (PHQ-9) and General Anxiety Disorder Scale (GAD-7), respectively.Statistical analysis involved Mann-Whitney U tests for comparing PDSS scores between the groups due to non-parametric distributionand Chi-square tests for categorical variables. Relative risks (RR) were calculated to assess the likelihood of abnormal PDSS, PHQ-9, and GAD-7 scores between the groups. Multivariable linear regression was used to adjust for potential confounding factors. Results No statistically significant difference in PDSS scores was found between SSRI monotherapy (median=6,interquartile range (IQR)=3-9) and combination therapy (median=8, IQR=3-13) groups (p=0.188). The relative risk of abnormal PDSS scores was 1.8 times higher in the combination therapy group (p=0.077). No significant differences in depression (p=0.386) or anxiety (p=0.182) symptoms were observed. Additionally, 66.7% of combination therapy patients had abnormal PDSS scores compared to 33.3% in the SSRI group. The mean PHQ-9 score was 11.08±6.93, and the mean GAD-7 score was 10.69±6.41 for the total sample. Conclusion This study found no significant difference in the effectiveness of SSRIs combined with beta-blockers vs. SSRI monotherapy for treating panic disorders. However, the trend towards higher PDSS scores in the combination therapy group suggests further investigation is needed. Study limitations included small sample size, single-center design, short follow-up period, and lack of randomization. Despite these, the study provided valuable insights into treatment approaches for panic disorders in the Saudi population. Larger, randomized controlled trials with longer follow-up periods and multi-center designs are recommended for future research.

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.

Neurotransmitter system gene variants as biomarkers for the therapeutic efficacy of rTMS and SSRIs in obsessive-compulsive disorder.

This study aims to examine the potential influence of RS4680 (COMT), RS16965628 (SLC6A4), and RS1019385 (GRIN2B) polymorphisms on the therapeutic response to repetitive transcranial magnetic stimulation (rTMS) and selective serotonin reuptake inhibitors (SSRIs) in individuals with obsessive-compulsive disorder (OCD). Thirty-six untreated outpatients diagnosed with OCD were recruited and allocated to active or sham rTMS groups for two weeks. The mean age of the participants was 31.61, with 17 males (47.22%) and 19 females (52.78%). Peripheral blood samples (5 mL) were collected from each participant using ethylenediaminetetraacetic acid (EDTA) vacuum tubes for genotyping purposes, clinical evaluation was taken place at baseline and second week. The A allele of RS4680, C allele of RS16965628, and GG allele of RS1019385 were identified as potential bio-markers for predicting treatment response to OCD treatments (rTMS & SSRIs). Those genes may serve as bio-markers for the combined treatment of rTMS and SSRIs in OCD. The finding hold promise for further research and the potential implementation of precision treatment of OCD. https://www.chictr.org.cn, identifier ChiCTR1900023641.

Correlation between serum tryptophan metabolism and treatment efficacy of dapoxetine in patients with premature ejaculation: A pilot study.

Primary premature ejaculation (PPE) is a common male neurobiological disorder. Currently, there is consensus that the impairment in central serotonin (5-HT) neurotransmission constitutes a key pathogenic factor in PPE. Selective serotonin reuptake inhibitors (SSRIs) serve as the primary pharmacological intervention; however, a comprehensive elucidation of their mechanism of action remains incomplete. Owing to significant individual variability in efficacy, SSRIs exhibit a high discontinuation rate. Hence, there is an urgent need to address the selection of SSRIs for PPE treatment. This study aims to investigate the characteristics of tryptophan (TRP) metabolism in patients with PPE and to assess its influence on the efficacy of SSRIs. The exploratory study included a total of 16 patients with PPE and 16 control subjects who were healthy men without any sexual dysfunction. Upon enrollment in the study, all participants underwent a thorough medical history review and physical examination. Subsequently, their serum levels of TRP, its metabolites, large neutral amino acids (LNAAs), and metabolite ratios were assessed using a liquid chromatography-mass spectrometry (LC-MS) assay. After a period of 4weeks of dapoxetine treatment, all patients with PPE underwent reassessment using the Premature Ejaculation Diagnostic Tool (PEDT) score and intravaginal ejaculatory latency time (IELT) test. The ratio of serum TRP to other LNAAs (TRP/LNAAs) in patients with PPE was found to be significantly lower compared to the control group (P<0.05). Conversely, the ratio of kynurenine to TRP (KYN/TRP) was observed to be significantly higher in the PPE patients compared to the control group (P<0.05). Including the serum TRP/LNAAs ratio and KYN/TRP ratio in the prediction model yielded the highest prediction efficiency for PPE. There was a significant negative correlation between the ratio of TRP/LNAAs before the treatment and the IELT after 4weeks of the treatment. Additionally, there was a significant positive correlation observed between the ratio of TRP/LNAAs before the treatment and the PEDT score after 4weeks of the treatment. This study demonstrates that the reduction in the TRP/LNAAs ratio and the elevation of the KYN/TRP ratio are significant characteristics associated with PPE. These findings suggest that diminished tryptophan availability in the brain and the activation of the kynurenine (KYN) pathway may play a role in the pathogenesis of PPE. The TRP/LNAAs ratio has potential as a reliable indicator of central serotonin (5-HT) levels. Considering the TRP/LNAAs ratio when selecting SSRIs for the treatment of PPE may enhance the response rate of this medication.

Predictive modeling of antidepressant efficacy based on cognitive neuropsychological theory

BackgroundWe aimed to develop a clinical predictive model based on the cognitive neuropsychological (CNP) theory and machine-learning to examine SSRI efficacy in the treatment of MDD. MethodsBaseline assessments including clinical symptoms (HAMD, HAMA, BDI, and TEPS scores), negative biases (NEO-PI-R-N and NCPBQ scores), sociodemographic characteristics (social support and SES), and a 5-min eye-opening resting-state EEG were completed by 69 participants with first-episode major depressive disorder (MDD) and 36 healthy controls. The clinical symptoms and negative bias were again assessed after an 8-week treatment of depression with selective serotonin reuptake inhibitors (SSRIs). A multi-modality machine-learning model was developed to predict the effectiveness of SSRI antidepressants. ResultsAt baseline, we observed significant differences between MDD patients and healthy controls in terms of social support, clinical symptoms, and negative bias characteristics (p < 0.001). A negative association was found (p < 0.05) between neuroticism and alpha asymmetry in both the central and central-parietal areas, as well as between negative cognitive processing bias and alpha asymmetry in the parietal region. Compared to responders, non-responders exhibited less negative cognitive processing bias and greater alpha asymmetry in both central and central-parietal regions. Importantly, we developed a multi-modality machine-learning model with 83 % specificity using the above salient features. ConclusionsResearch results support the CNP theory of depression treatment. To some extent, the multimodal clinical model constructed based on the CNP theory effectively predicted the efficacy of this treatment in this population. LimitationsSmall sample and only focus on the mechanisms of delayed-onset SSRI treatment.

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.&#x0D; 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.&#x0D; 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.&#x0D; 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.

Organic cation transporter 2 contributes to SSRI antidepressant efficacy by controlling tryptophan availability in the brain

Selective serotonin reuptake inhibitors (SSRI) are common first-line treatments for major depression. However, a significant number of depressed patients do not respond adequately to these pharmacological treatments. In the present preclinical study, we demonstrate that organic cation transporter 2 (OCT2), an atypical monoamine transporter, contributes to the effects of SSRI by regulating the routing of the essential amino acid tryptophan to the brain. Contrarily to wild-type mice, OCT2-invalidated mice failed to respond to prolonged fluoxetine treatment in a chronic depression model induced by corticosterone exposure recapitulating core symptoms of depression, i.e., anhedonia, social withdrawal, anxiety, and memory impairment. After corticosterone and fluoxetine treatment, the levels of tryptophan and its metabolites serotonin and kynurenine were decreased in the brain of OCT2 mutant mice compared to wild-type mice and reciprocally tryptophan and kynurenine levels were increased in mutants’ plasma. OCT2 was detected by immunofluorescence in several structures at the blood-cerebrospinal fluid (CSF) or brain-CSF interface. Tryptophan supplementation during fluoxetine treatment increased brain concentrations of tryptophan and, more discreetly, of 5-HT in wild-type and OCT2 mutant mice. Importantly, tryptophan supplementation improved the sensitivity to fluoxetine treatment of OCT2 mutant mice, impacting chiefly anhedonia and short-term memory. Western blot analysis showed that glycogen synthase kinase-3β (GSK3β) and mammalian/mechanistic target of rapamycin (mTOR) intracellular signaling was impaired in OCT2 mutant mice brain after corticosterone and fluoxetine treatment and, conversely, tryptophan supplementation recruited selectively the mTOR protein complex 2. This study provides the first evidence of the physiological relevance of OCT2-mediated tryptophan transport, and its biological consequences on serotonin homeostasis in the brain and SSRI efficacy.

Incidence of adverse events and comparative tolerability of selective serotonin reuptake inhibitors, and serotonin and norepinephrine reuptake inhibitors for the treatment of anxiety, obsessive-compulsive, and stress disorders: a systematic review and network meta-analysis.

Selective serotonin reuptake inhibitors (SSRIs) and serotonin and norepinephrine reuptake inhibitors (SNRIs) show similar efficacy as treatments for anxiety, obsessive-compulsive, and stress-related disorders. Hence, comparisons of adverse event rates across medications are an essential component of clinical decision-making. We aimed to compare patterns of adverse events associated with SSRIs and SNRIs in the treatment of children and adults diagnosed with these disorders through a network meta-analysis. We searched MEDLINE, PsycINFO, Embase, Cochrane, websites of regulatory agencies, and international registers from inception to 09 September 2022, for randomized controlled trials assessing the efficacy of SSRIs or SNRIs. We analyzed the proportion of participants experiencing at least one adverse event and incidence rates of 17 specific adverse events. We estimated incidence rates and odds ratios through network meta-analysis with random effects and three-level models. We analyzed 799 outcome measures from 80 studies (n = 21 338). Participants in medication groups presented higher rates of adverse events (80.22%, 95% CI 76.13-83.76) when compared to placebo groups (71.21%, 67.00-75.09). Nausea was the most common adverse event (25.71%, CI 23.96-27.54), while weight change was the least common (3.56%, 1.68-7.37). We found higher rates of adverse events of medications over placebo for most medications, except sertraline and fluoxetine. We found significant differences between medications for overall tolerability and for autonomic, gastrointestinal, and sleep-related symptoms. Adverse events are a common reason that patients discontinue SSRIs and SNRIs. Results presented here guide clinical decision-making when clinicians weigh one medication over another. This might improve treatment acceptability and compliance.

A systematic review and meta-analysis on the efficacy outcomes of selective serotonin reuptake inhibitors in depression in Alzheimer’s disease

BackgroundDepressive symptoms are the most common neuropsychiatric symptoms in patients with Alzheimer’s disease (AD). However, despite being common, no definite consensus recommendations exist for the management of depression in AD.ObjectiveTo assess the effects of selective serotonin reuptake inhibitors (SSRIs) on the alleviation of depressive symptoms in patients with AD.Material and methodsMedline, Scopus, Web of Science, Google Scholar, and PsychINFO were electronically searched from inception until October 2022. Response to therapy and mean depression scores between the treatment (or before) and placebo (or after) groups were the primary outcomes. For depression scores, the standard mean deviation and accompanying 95% confidence interval were determined. The risk of bias was determined using the funnel plot, trim and fill, Egger’s and Begg’s analyses.ResultsSSRIs attenuated depressive symptoms in patients with AD (0.905 SMD, 95%CI, 0.689 to 1.121, p < 0.000). At individual SSRI level, escitalopram, paroxetine, and sertraline significantly alleviated depressive symptoms in AD patients (0.813 SMD, 95%CI, 0.207 to 1.419, p = 0.009, 1.244 SMD, 95%CI, 0.939 to 1.548, p < 0.000, and 0.818 SMD, 95%CI, 0.274 to 1.362, p < 0.000). The funnel plot, trim and fill, Begg’s test (p = 0.052), and Egger’s test (p = 0.148), showed no significant risk of publication bias.ConclusionOur meta-analysis supports the use of SSRIs for the alleviation of depression in patients with AD. However, we recommend larger randomized clinical trials that would compare the efficacy of different SSRIs in AD patients with depression.

Symptom-level effects of SSRIs in depression studies in a large-scale study programme: efficacy, effects of baseline severity, impact on suicidality, and more

Abstract Conclusions about the efficacy of antidepressants, such as the selective serotonin reuptake inhibitors (SSRIs), in clinical trials have generally been based on analyses of total sum scores on psychometric rating scales, mainly the Hamilton Depression Rating Scale (HDRS). However, this rating scale has several drawbacks, such as multidimensionality and a tendency of several items to pick up side-effects. Therefore, analyses that only rely on global drug treatment effects on the HDRS and similar scales risk misrepresenting important properties of any drugs investigated. This presentation concerns the findings of a research project investigating item-level effects of SSRIs in treating depression in a material encompassing 8262 patients having participated in pre- and post-marketing industry-sponsored studies concering paroxetine, sertraline or citalopram. This has been a fruitful endeavour, having resulted in numerous research papers. Though our main focus at the outset was to investigate if a comparatively low efficacy of SSRIs in clinical trials was an artefact related to the use of HDRS sum scores as the main outcome (which was indeed the case), we have also used this material to investigate a number of other important questions relating to the influence of SSRIs on the various symptoms experienced by patients with depression. Major findings discussed in the presentation include: i) confirmation of early (but not widely known) reports that SSRIs significantly reduce core depression symptoms already after a week of treatment ii) strong evidence for SSRIs being equally effective in treating core depressive symptoms in mild as well as severe depression, earlier reported differences apparently being explained by differences in terms of effects (and prevalence) of non-core symptoms iii) SSRIs do not seem to exacerbate suicidality as measured by the relevant item of the HDRS scale - indeed, both average scores as well as likelihood of worsening are significantly reduced already at week 1. The implications of these, and other, findings are discussed in relation to both the role of SSRIs in the clinic as well as pre-clinical research into e.g. the mode of action of these drugs. Disclosure of Interest None Declared

The effect of SSRIs on fear learning: a systematic review and meta-analysis.

Selective serotonin reuptake inhibitors (SSRIs) are considered first-line medication for anxiety-like disorders such as panic disorder, generalized anxiety disorder, and post-traumatic stress disorder. Fear learning plays an important role in the development and treatment of these disorders. Yet, the effect of SSRIs on fear learning are not well known. We aimed to systematically review the effect of six clinically effective SSRIs on acquisition, expression, and extinction of cued and contextual conditioned fear. We searched the Medline and Embase databases, which yielded 128 articles that met the inclusion criteria and reported on 9 human and 275 animal experiments. Meta-analysis showed that SSRIs significantly reduced contextual fear expression and facilitated extinction learning to cue. Bayesian-regularized meta-regression further suggested that chronic treatment exerts a stronger anxiolytic effect on cued fear expression than acute treatment. Type of SSRI, species, disease-induction model, and type of anxiety test used did not seem to moderate the effect of SSRIs. The number of studies was relatively small, the level of heterogeneity was high, and publication bias has likely occurred which may have resulted in an overestimation of the overall effect sizes. This review suggests that the efficacy of SSRIs may be related to their effects on contextual fear expression and extinction to cue, rather than fear acquisition. However, these effects of SSRIs may be due to a more general inhibition of fear-related emotions. Therefore, additional meta-analyses on the effects of SSRIs on unconditioned fear responses may provide further insight into the actions of SSRIs.

The complex clinical response to selective serotonin reuptake inhibitors in depression: a network perspective

The clinical response to selective serotonin reuptake inhibitors (SSRIs) in depression takes weeks to be fully developed and is still not entirely understood. This study aimed to determine the direct and indirect effects of SSRIs relative to a placebo control condition on clinical symptoms of depression. We included data of 8262 adult patients with major depression participating in 28 industry-sponsored US Food and Drug Administration (FDA) registered trials on the efficacy of SSRIs. Clinical symptoms of depression were assessed by the 17 separate items of the Hamilton Depression Rating Scale (HDRS) after 1, 2, 3, 4 and 6 weeks of treatment. Network estimation techniques showed that SSRIs had quick and strong direct effects on the two affective symptoms, i.e., depressed mood and psychic anxiety; direct effects on other symptoms were weak or absent. Substantial indirect effects were found for all four cognitive symptoms, which showed larger reductions in the SSRI condition but mainly in patients reporting larger reductions in depressed mood. Smaller indirect effects were found for two arousal/somatic symptoms via the direct effect on psychic anxiety. Both direct and indirect effects on sleep problems and most arousal/somatic symptoms were weak or absent. In conclusion, our study revealed that SSRIs primarily caused reductions in affective symptoms, which were related to reductions in mainly cognitive symptoms and some specific arousal/somatic symptoms. The results can contribute to disclosing the mechanisms of action of SSRIs, and has the potential to facilitate early detection of responders and non-responders in clinical practice.

Role of 5-HT1A-mediated upregulation of brain indoleamine 2,3 dioxygenase 1 in the reduced antidepressant and antihyperalgesic effects of fluoxetine during maintenance treatment.

The reduced antidepressant and antihyperalgesic effects of selective serotonin reuptake inhibitors (SSRIs) such as fluoxetine during maintenance treatment has been reported, but little is known about the molecular mechanism of this phenomenon. In three comorbid pain and depression animal models (genetic predisposition, chronic social stress, arthritis), we showed that the fluoxetine's antidepressant and antihyperalgesic effects were reduced during the maintenance treatment. Fluoxetine exposure induced upregulation of the 5-hydroxytryptamine 1A (5-HT1A) auto-receptor and indoleamine 2,3 dioxygenase 1 (IDO1, a rate-limiting enzyme of tryptophan metabolism) in the brainstem dorsal raphe nucleus (DRN), which shifted the tryptophan metabolism away from the 5-HT biosynthesis. Mechanistically, IDO1 upregulation was downstream to fluoxetine-induced 5-HT1A receptor expression because 1) antagonism of the 5-HT1A receptor with WAY100635 or 5-HT1A receptor knockout blocked the IDO1 upregulation, and 2) inhibition of IDO1 activity did not block the 5-HT1A receptor upregulation following fluoxetine exposure. Importantly, inhibition of either the 5-HT1A receptor or IDO1 activity sustained the fluoxetine's antidepressant and antihyperalgesic effects, indicating that 5-HT1A-mediated IDO1 upregulation in the brainstem DRN contributed to the reduced antidepressant and antihyperalgesic effects of fluoxetine. These results suggest a new strategy to improving the therapeutic efficacy of SSRI during maintenance treatment.

Current and emerging treatment options for premature ejaculation.

Premature ejaculation (PE) is a prevalent male sexual dysfunction. Current standard treatment regimens include behavioural therapies, topical anaesthetics, dapoxetine and other selective serotonin reuptake inhibitors (SSRIs). Most of the pharmacotherapeutic options target neurotransmitters (such as serotonin and oxytocin) that have a role in the ejaculation mechanism. However, these treatments are mildly effective and only provide a temporary delay in the ejaculation latency time, and PE recurs when the treatment is stopped. Thus, a treatment for PE is urgently needed and research is ongoing to find the ideal PE therapy. The efficacy and safety of topical anaesthetics and SSRIs in delaying ejaculation have been confirmed in many well-designed controlled trials. Both preclinical and clinical studies on new-generation SSRIs are ongoing. Moreover, promising results came from clinical trials in which the efficacy of on-demand PE therapies targeting neurotransmitters other than serotonin, such as α1-adrenoceptor antagonists and oxytocin antagonists, was assessed. Surgical intervention and neuromodulation have been proposed as potential treatment options for PE; however, current PE guidelines do not recommend these treatments owing to safety concerns.

Faster Serotonin Clearance in CA3 Region of Hippocampus and Antidepressant-like Effect of Decynium-22 in Juvenile Mice Are Putatively Linked to Increased Plasma Membrane Monoamine Transporter Function: Implications for Efficacy of Antidepressants in Juveniles.

Selective serotonin reuptake inhibitors (SSRIs) are less efficacious in treating depression in children than in adults. SSRIs block serotonin uptake via the high-affinity, low-capacity serotonin transporter. However, the low-affinity, high-capacity organic cation transporter 3 (OCT3) and plasma membrane monoamine transporter (PMAT) are emerging as important players in serotonin uptake. We hypothesized that OCT3 and/or PMAT are functionally upregulated in juveniles, thereby buffering SSRIs’ ability to enhance serotonergic neurotransmission. Unlike in adult mice, we found the OCT/PMAT blocker, decynium-22, to have standalone antidepressant-like effects in juveniles. Using in vivo high-speed chronoamperometry, we found that juveniles clear serotonin from the CA3 region of the hippocampus ~2-fold faster than adult mice. Cell density did not differ between ages, suggesting that faster serotonin clearance in juveniles is unrelated to faster diffusion through the extracellular matrix. Western blot and immunohistochemistry showed that juvenile mice have modestly greater expression of PMAT than adults, whereas OCT3 expression in the CA3 region of the hippocampus was similar between ages. Together, these data suggest that faster serotonin clearance and antidepressant-like effects of decynium-22 in juvenile mice may be due to functionally upregulated PMAT. Faster serotonin clearance via PMAT in juveniles may contribute to reduced therapeutic efficacy of SSRIs in children relative to adults.

The Impact of SSRI Use on the Clinical Outcome and Prognosis of COVID-19 Patients: A Single-Center Prospective Study

Background: Recent studies have found a link between the usage of selective serotonin reuptake inhibitors (SSRIs) and a lower mortality rate in COVID-19 cases. Objective: The goal of current research was evaluating the effectiveness of SSRI drugs on improvement of COVID-19 patients. Methods: This prospective case-control study, compared SSRI-treated patients with matched control patients not treated with SSRIs at Masih Daneshvari Hospital on a population of 350 patients diagnosed with COVID-19 from March 15th 2021 to March 16th 2022. Results: ICU admission rates were significantly more in the control group than in the case group (44.8% vs. 25.9%; p-value=0.0002; Odds Ratio (OR)= 2.32). Intubation was reported for more cases in the control group than the case group (26.7% vs. 11.4%; p-value=0.0002; OR=2.84). Mortality rate was found to be significantly more in the control group than the case group (23.0% vs. 10.8%; p-value=0.0002; OR=2.46). Furthermore, the subgroup analyses on Fluvoxamine and Sertraline showed that Hospitalization period, ICU admission rates, and intubation were all reported to be significantly smaller in each case subgroups as against the control group. Conclusion: Our assessments underlined the potential efficacy of SSRIs in improving COVID-19 patients’ prognosis, since the use of SSRIs were shown to be associated with shorter hospital stay and ICU stay, lower ICU admission rates and intubation rates, and ultimately decreased mortality rates.

Safety and Efficacy of SSRIs in Improving Poststroke Recovery: A Systematic Review and Meta-Analysis.

BackgroundSeveral studies investigated the role of selective serotonin reuptake inhibitors (SSRIs) in improving poststroke recovery; thus, we have decided to conduct this systematic review and meta‐analysis to investigate the efficacy and safety of SSRIs in poststroke recovery.Methods and ResultsIn this meta‐analysis we searched the following databases: PubMed, Cochrane, Scopus, and Google Scholar. The studies were included if they were placebo‐controlled trials in design and reported SSRIs’ effects on poststroke depression, anxiety, disability, dependence, motor abilities, and cognitive functions. The quality of the included studies was assessed using the revised Cochrane risk‐of‐bias tool for randomized trials. The search yielded 44 articles that included 16 164 patients, and about half of the participants were treated with SSRIs. Our results showed that SSRIs had a significant effect on preventing depression (weighted mean difference [WMD], −7.05 [95% CI, −11.78 to −2.31]), treating depression according to the Hamilton Rating Scale for Depression score (WMD, −1.45 [95% CI, −2.77 to −0.14]), anxiety (relative risk, 0.23 [95% CI, 0.09–0.61]), dependence (WMD, 8.86 [95% CI, 1.23–16.48]), motor abilities according to National Institutes of Health Stroke Scale score (WMD, −0.79 [95% CI, −1.42 to −0.15]), and cognitive functions (WMD, 1.00 [95% CI, 0.12–1.89]). On the other hand, no significant effect of SSRIs on disability was observed. Additionally, we found that treating with SSRIs increased the risk of seizures (relative risk, 1.44 [95% CI, 1.13–1.83]), whereas there was no difference in the incidence of gastrointestinal symptoms or bleeding between SSRIs and a placebo.ConclusionsOur study showed that SSRIs are effective in preventing and treating depression, and improving anxiety, motor function, cognitive function, and dependence in patients after stroke. These benefits were only reproducible with the citalopram subanalysis but not fluoxetine. Further well‐conducted placebo‐controlled trials are needed to investigate the safety and efficacy of citalopram among patients after stroke.RegistrationURL: www.crd.york.ac.uk/prospero/; Unique identifier: CRD42021285766.

Citalopram Did Not Significantly Improve Anxiety in Children with Autism Spectrum Disorder Undergoing Treatment for Core Symptoms: Secondary Analysis of a Trial to Reduce Repetitive Behaviors.

Objective: Anxiety disorders are among the most common co-occurring conditions in autism spectrum disorder (ASD). Despite their prevalence and impact, there are no randomized controlled trials (RCTs) aimed at evaluating the efficacy of selective serotonin reuptake inhibitors (SSRIs) for anxiolysis in this population, who may have a different biological basis for anxiety. Methods: Secondary analyses of the STAART double-blind, placebo-controlled RCT of citalopram in children with ASD examined whether citalopram reduced anxiety measured on the parent-reported Child and Adolescent Symptom Inventory-4 (CASI-4) as the primary outcome. An intention-to-treat analysis involving all 149 participants used multiple imputations for missing data and included baseline stratification factors of age group and site, among others. We prespecified as clinically significant a 33% reduction in anxiety in citalopram versus placebo, coinciding with 80% power. We tested whether communicative ability on the Vineland Communication score moderated treatment effect and explored whether initial anxiety was associated with greater adverse events, which could impact on dose titration and achieving optimal dose. Results: Both groups showed substantial reduction in anxiety. Citalopram was associated with a nonsignificant 16.5% greater reduction (observed coefficient = -0.181, bootstrap standard error = 0.126, p = 0.151, confidence interval = -0.428 to 0.066). Anxiety reports were significantly lower in children with reduced communicative ability, but communicative ability did not moderate the treatment effect (interaction p = 0.294). Initial anxiety levels were not associated with increased adverse effects (interaction ps 0.162-0.954). Conclusion: Citalopram did not statistically significantly improve anxiety in children with ASD. Clinicians should be cautious in their use of SSRIs for this indication. There remains a need for well-powered clinical trials testing the efficacy of SSRIs among autistic children with anxiety disorders.

Pediatric Psychopharmacology for Depressive and Anxiety Disorders.

Anxiety and depressive disorders are the most common psychiatric illnesses among children and adolescents. These disorders are associated with impairments in social, family, and educational functioning. This article summarizes the evidence base for psychopharmacologic interventions; the developmental pharmacology of selective serotonin reuptake inhibitors (SSRIs) and serotonin norepinephrine reuptake inhibitors (SNRIs); and pharmacokinetic and pharmacodynamic differences between youths and adults that call for differences in dosage and affect response and tolerability. The authors also review the efficacy and tolerability of SSRIs and SNRIs in children and adolescents with depressive and anxiety disorder diagnoses, as well as data related to duration of therapy and SSRI/SNRI discontinuation in this population. Taken together, the current evidence suggests that SSRIs are the first-line psychopharmacologic intervention for youths with depressive and anxiety disorders, with SNRIs having a more limited role. These medications are safe and well tolerated, although emerging data and developmental pharmacologic concepts may help clinicians to choose from available SSRIs and to improve the efficacy and tolerability of these medications in children and adolescents.

Management of Psychiatric Disorders in Patients with Hepatic and Gastrointestinal Diseases.

Management of Psychiatric Disorders in Patients with Hepatic and Gastrointestinal Diseases.