Amygdala activity after subchronic escitalopram administration in healthy volunteers: A pharmaco-functional magnetic resonance imaging study.

BACKGROUND: Selective serotonin reuptake inhibitors (SSRIs) are used for the treatment of several conditions including anxiety disorders, but the basic neurobiology of serotonin function remains unclear. The amygdala and prefrontal cortex are strongly innervated by serotonergic projections and have been suggested to play an important role in anxiety expression. However, serotonergic function in behaviour and SSRI-mediated neurobiological changes remain incompletely understood. AIMS: To investigate the neural correlates of subchronic antidepressant administration. METHODS: We investigated whether the 2- to 3-week administration of a highly selective SSRI (escitalopram) would alter brain activation on a task robustly shown to recruit the bilateral amygdala and frontal cortices in a large healthy volunteer sample. Participants performed the task during a functional magnetic resonance imaging acquisition before (n = 96) and after subchronic escitalopram (n = 46, days of administration mean (SD) = 15.7 (2.70)) or placebo (n = 40 days of administration mean (SD) = 16.2 (2.90)) self-administration. RESULTS: Compared to placebo, we found an elevation in right amygdala activation to the task after escitalopram administration without significant changes in mood. This effect was not seen in the left amygdala, the dorsomedial region of interest, the subgenual anterior cingulate cortex or the right fusiform area. There were no significant changes in connectivity between the dorsomedial cortex and amygdala or the subgenual anterior cingulate cortex after escitalopram administration. CONCLUSIONS: To date, this most highly powered study of subchronic SSRI administration indicates that, contrary to effects often seen in patients with anxiety disorders, subchronic SSRI treatment may increase amygdala activation in healthy controls. This finding highlights important gaps in our understanding of the functional role of serotonin.

Intermittent escitalopram treatment and reactive aggression in women with premenstrual irritability and anger: A crossover study.

BACKGROUND: SSRIs are the primary treatment for premenstrual mood symptoms and particularly effective in reducing reactive aggression in the forms of irritability and anger. The present study examined whether behavioral responses in laboratory measures of reactive aggression are influenced by medication with the SSRI escitalopram in women reporting high levels of premenstrual irritability/anger. METHODS: Participants (N = 34) rated the cardinal mood symptoms of premenstrual dysphoric disorder over three menstrual cycles. During the second and third cycles, participants received escitalopram (20 mg) or placebo in a single-blind, cross-over design. In the luteal phase of the intervention cycles, participants completed two aggression tasks: The Anger-Infused Ultimatum Game (AI-UG) and the Point Subtraction Aggression Paradigm (PSAP). Additionally, they rated expression and control of anger using the State-Trait Anger Expression Inventory-2 (STAXI-2) once in the luteal phase and once in the follicular phase. RESULTS: While irritability/anger was reduced in the treatment (vs. placebo) cycle, no effect of escitalopram was detected in the PSAP. Escitalopram decreased reactive aggressive behavior in the AI-UG but only for a subset of participants who experienced a sharp premenstrual rise in outwardly expressed anger and/or did not experience a premenstrual rise in inwardly expressed anger. LIMITATIONS: The participants' symptoms were based on the severity of only premenstrual irritability/anger, limiting the generalizability to the broader group of PMDD patients. CONCLUSION: The results suggest that the behavioral consequences of severe premenstrual irritability/anger are not easily captured by traditional measures of reactive aggression and underline the importance of considering individual differences in symptom expression.

Effects of prolonged escitalopram administration on long-term potentiation within the hippocampal CA1 area in rats under predictable and unpredictable chronic mild stress.

Exposure to chronic stress impairs memory. Also, escitalopram's impact on memory remains paradoxical. Therefore, this study examined how prolonged escitalopram administration affects input-output (I/O) functions, paired-pulse ratio (PPR), and long-term potentiation (LTP) in the hippocampal CA1 area in rats that underwent predictable and unpredictable chronic mild stress (PCMS and UCMS, respectively). Male rats were randomly assigned to different groups of control (Co), sham (Sh), PCMS and UCMS (PSt and USt, respectively; 2 h/day, for 21 consecutive days), escitalopram (Esc; 10 mg/kg, i.p., for 21 days), as well as PCMS and UCMS with escitalopram (PSt-Esc and USt-Esc, respectively). The fEPSP slope, amplitude, and area under the curve (AUC) were assessed in the hippocampal CA1 area using I/O functions, PP responses, and LTP. Serum corticosterone (CORT) levels were quantified in all experimental animals. The slope, amplitude, and AUC of fEPSP in the I/O functions, and all three PP phases prior and subsequent to LTP induction significantly declined in the USt and PSt groups. Escitalopram significantly enhanced these parameters in the PSt-Esc, but not in the USt-Esc group. Serum CORT levels corroborated the electrophysiological findings among experimental groups. Both PCMS and UCMS impaired neural excitability, neurotransmission, and memory within the hippocampal CA1 area. Escitalopram improved memory impairment only under PCMS, potentially attributed to reduced serum CORT levels. However, no influence on neural excitability, neurotransmission, and memory was observed under UCMS. This suggests different escitalopram doses might be required to ameliorate simultaneous mechanisms in response to various types of chronic mild stress.

Serotonin syndrome caused by escitalopram in Parkinson's disease psychosis: a case report.

BACKGROUND: Serotonin syndrome and Parkinson's disease (PD) are two diseases whose symptoms partially overlap; this poses challenges in distinguishing them in clinical practice. Early manifestations such as tremor, akathisia, diaphoresis, hypertonia and hyperreflexia are common in mild-to-moderate serotonin syndrome and can also occur in PD. Without prompt recognition and treatment, serotonin syndrome can rapidly progress, potentially leading to severe complications such as multiple organ failure within hours. Given their disparate treatment strategies, accurate clinical distinction is crucial for effective treatment. This case study explores a patient with serotonin syndrome triggered by escitalopram in the context of PD psychosis (PDP), providing insights into diagnosis and treatment planning. CASE PRESENTATION: A 75-year-old Asian woman with a one-year history of PD, a two-month history of PDP, and a six-year history of depression presented with symptoms including hyperreflexia, tremor, hypertonia, impaired level of consciousness, and inappropriate behavior following a recent one-month adjustment in medication. Initially suspected of being drug-induced parkinsonism or worsening PD, therapeutic drug monitoring revealed warning levels of escitalopram. Subsequent diagnoses confirmed serotonin syndrome. This syndrome may result from increased cortical serotonin activity at the serotonin2A receptor due to dopamine and serotonin imbalances in PDP, compounded by increased dopamine-mediated serotonin release. Additionally, being an intermediate metabolizer of cytochrome P450 enzyme 2C19, the patient experienced excessive escitalopram accumulation, exacerbating her condition. CONCLUSIONS: This case underscores the critical need to differentiate between symptoms of serotonin syndrome and PD, particularly in manifestations like tremor and hypertonia. Careful consideration of receptor profiles in patients with PDP is essential when selecting antidepressants to mitigate the risk of serotonin syndrome.

Shugan Jieyu capsule effects on peripheral blood micro-124, micro-132, and brain-derived neurotrophic factor in patients with mild to moderate depression.

BACKGROUND: To assess the effectiveness of Shugan Jieyu capsules on peripheral blood miR-124, miR-132, and brain-derived neurotrophic factor (BDNF) levels in patients with mild to moderate depression following coronary artery intervention [percutaneous coronary intervention (PCI)] for coronary heart disease. AIM: To evaluate the therapeutic efficacy of Shugan Jieyu capsules and their effects on the peripheral blood levels of miR-124, miR-132, and BDNF in patients with mild to moderate depression following PCI for coronary heart disease. METHODS: Patients with mild-to-moderate depression of the liver-qi stagnation type after PCI for coronary heart disease at the 305th Hospital of the People's Liberation Army were enrolled from June 2022 to November 2023 and randomly assigned to two groups: Experimental (treated with Shugan Jieyu capsules) and control (treated with escitalopram oxalate tablets). This study compared the antidepressant effects of these treatments using 17-item Hamilton Rating Scale for Depression (HAMD-17) scores, metabolic equivalents, low-density lipoprotein cholesterol, BDNF, high-sensitivity C-reactive protein levels, miR-124 and miR-132 levels, distribution of immune-related lymphocyte subsets, and traditional Chinese medicine syndrome scores before and after 6 weeks of treatment. RESULTS: No significant difference was observed in any index between the two groups before treatment (P > 0.05). After treatment, the total efficacy rates were 93.33% and 90.00% in the experimental and control groups, respectively. Experimental group had significantly lower scores for the main and secondary syndromes compared to the control group (P < 0.05). No significant difference was observed in the metabolic equivalents between the two groups before and after treatment (P > 0.05). The levels of low-density lipoprotein cholesterol, high-sensitivity C-reactive protein, and miR-132 were significantly lower, whereas those of miR-124, BDNF, CD3+T lymphocytes, CD3+CD4+T helper lymphocytes, and CD3+CD4+/CD3+CD8+ cells were significantly higher in the experimental group compared to the control group (P < 0.05). The incidence of adverse reactions during experimental group was significantly lower than that in control group (P < 0.05). CONCLUSION: Shugan Jieyu capsules have good efficacy in patients with mild-to-moderate depression after PCI, and its mechanism may contribute to the regulation of miR-124, miR-132, BDNF levels, and lymphoid immune cells.

Investigation of the immunological effects of escitalopram oxalate in the breast cancer co-culture model.

Background: During breast cancer treatment, approximately half of the patients are prescribed psychotropic medication, such as selective serotonin reuptake inhibitors (SSRIs). Escitalopram oxalate is an SSRI used as an antidepressant. Objectives: In this study, by creating a breast cancer microenvironment with THP-1, MCF-7 and MDA-MB-231 breast cancer co-culture models were created. Methods: MCF-7, MDA-MB-231, and THP-1 cell lines to determine the concentration range of the cytotoxic effect of escitalopram oxalate MTS and MTT test were used. IC50 values were determined by the xCELLigence real-time cell analysis (RTCA) system. Apoptotic activities and cytokine levels were determined by flow cytometry. Results: In the xCELLigence real-time analysis made according to the results, the IC50 value of escitalopram oxalate was measured as 13.7 µM for MCF-7 and 10.9 µM for MDA-MB-231. The IC50 value was measured as 54.6 µM for MCF-7 and 58.4 µM for MDA-MB-231 in xCELLigence analysis with tamoxifen. According to the MTS test results, the IC50 value of tamoxifen for THP-1 was 92.03 µM and the IC50 value for escitalopram oxalate was 95.32 µM. In the co-culture model, the immunological effects of escitalopram oxalate on MCF-7 cells were 2.8%, 11.1%, 15.6%, 10.6%, and 12.1% for interleukin (IL)-1ß, IL-6, IL-8, IL-10, and TNF-α, respectively, while MDA effects on MB-231 cells, respectively, were 2.1%, 15.9%, 16.2%, 8.8%, and 11.8%. Conclusions: According to the results obtained, it was concluded that the immunological effects of escitalopram oxalate are more effective than tamoxifen and that it can be used as an adjunctive agent in breast cancer treatment.

The effect of escitalopram in treating mild to moderate depressive disorder and improving the quality of life in patients undergoing coronary artery bypass grafting - a double-blind randomized clinical trial.

Introduction: Chronic depression and anxiety can be a risk factor for coronary aArtery bypass grafting (CABG) and is an emerging factor after coronary artery disease when the patient is admitted to the hospital and after surgery. We aimed to assess the effect of Escitalopram in treating mild to moderate depressive disorder and improving the quality of life in patients undergoing CABG. Methods: In this randomized clinical trial, 50 patients undergoing CABG referred to Tehran Heart Hospital from January 2021 to May 2021 and were suffering from mild to moderate depression were randomly assigned to one of the two groups of Escitalopram or placebo. The level of depression was assessed based on Beck's depression inventory and the quality-of-life status and its domains were assessed based on the SF-36 questionnaire in 2 groups. Measurements were obtained at baseline and at four and eight weeks after treatment. Chi-square, Fisher's exact, paired, and Wilcoxon tests or ANOVA were used as appropriate. Results: There was no significant difference between the level of depression between the two study groups at baseline (P=0.312). There was no significant difference between the quality of life and its domains in the two study groups at baseline (P=0.607). However, the most important effect of Escitalopram was reducing depression scores in the intervention group at weeks 4 and 8 after treatment compared to the placebo group (P<0.001). The quality of life and its domains were significantly higher in the Escitalopram group eight weeks after treatment (P=0.004). The amount of drug side effects at 2 and 4 weeks after treatment had no significant difference between the groups (P>0.05). Conclusion: Escitalopram was effective in treating mild to moderate depressive disorder and improving quality of life in patients undergoing CABG. Clinical trial registration: https://irct.behdasht.gov.ir/, identifier IRCT20140126016374N2.

[Antidepressants in psychiatric practice]. / Antidepressanty v psikhiatricheskoi praktike.

The choice of antidepressants for depression or neurotic disorder is analyzed in the article. Drugs of the group of selective serotonin reuptake inhibitors are used for various mental disorders more often than other antidepressants according to clinical recommendations. Drugs of other groups (selective serotonin and norepinephrine reuptake inhibitors, tricyclic antidepressants, tetracyclic antidepressants, monoamine oxidase inhibitors) are used when the effectiveness of selective serotonin reuptake inhibitors is insufficient or the severity of the mental disorder is significant. The duration of therapy, if well tolerated, can range from several months to many years. Antidepressants from Canonpharma Production are successfully used in clinical practice: Sertraline Canon, Fluoxetine Canon, Escitalopram Canon, Duloxetine Canon, Mirtazapine Canon, Agomelatine Canon. These drugs have different mechanisms of action. They are used for various depression and other mental disorders. All antidepressants from Canonpharma Production have been tested for bioequivalence to the original drugs. This fact increases confidence in these medicines. Some features of the use of these antidepressants based on clinical recommendations and personal experience are discussed in the article.

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.

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.

Feeling blue to seeing red: A case of escitalopram-induced epistaxis.

Selective serotonin reuptake inhibitors are associated with an increased risk of bleeding, most commonly intracranial and gastric bleeding, especially in conjunction with anticoagulant use. Although uncommon, escitalopram is associated with epistaxis in a dose-dependent manner. Dosage reduction may be sufficient in management.

Escitalopram moderately outperforms citalopram towards anti-neuroinflammation and neuroprotection in 6-hydroxydopamine-induced mouse model of Parkinson's disease.

Citalopram and escitalopram are structurally close-related antidepressants and both forms are widely used in the world. We aimed to comparatively evaluate the anti-neuroinflammatory and neuroprotective effects of escitalopram and citalopram in Parkinson's disease (PD) mouse model. Mice were randomly divided into six groups and received 6-hydroxydopamine (6-OHDA) or vehicle administration. The mice were then treated with escitalopram, citalopram or saline for consecutive 7 days. Behaviors, neuroinflammation, neurotransmitters, and neurotoxicity were assessed. Results showed that citalopram but not escitalopram worsened body weight loss and increased freezing time in the PD mice. Both drugs had no impact on the anxiety-like behaviors but ameliorated the depressive-like behaviors as in elevated plus maze and sucrose splash tests. Escitalopram but not citalopram ameliorated motor discoordination in the PD mice as in rotarod test. In accordance, escitalopram but not citalopram attenuated the 6-OHDA-induced nigrostriatal dopaminergic loss. Further mechanistic investigations showed that both drugs mitigated activations of microglia and astrocytes and/or levels of pro-inflammatory cytokines in the PD mice, but escitalopram showed appreciably better effects in the substantia nigra. Neurotransmitter examination in the prefrontal cortex suggested that the two drugs had comparable effects on the disturbed neurotransmitters in the PD mice, but citalopram was prone to disrupt certain normal homeostasis. In conclusion, escitalopram is moderately superior than citalopram to suppress neuroinflammation and to protect against dopaminergic neuronal death and motor discoordination in the 6-OHDA-induced PD mice. Our findings imply that escitalopram shall be prescribed with priority over citalopram to treat PD patients with depression as escitalopram may meanwhile provide greater additional benefits to the patients.

Effects of selective serotonin reuptake inhibitors on endocrine system (Review).

Selective serotonin reuptake inhibitors (SSRIs) are typically prescribed for treating major depressive disorder (MDD) due to their high efficacy. These drugs function by inhibiting the reuptake of serotonin [also termed 5-hydroxytryptamine (5-HT)], which raises the levels of 5-HT in the synaptic cleft, leading to prolonged activation of postsynaptic 5-HT receptors. Despite the therapeutic benefits of SSRIs, this mechanism of action also disturbs the neuroendocrine response. Hypothalamic-pituitary-adrenal (HPA) axis activity is strongly linked to both MDD and the response to antidepressants, owing to the intricate interplay within the serotonergic system, which regulates feeding, water intake, sexual drive, reproduction and circadian rhythms. The aim of the present review was to provide up-to-date evidence for the proposed effects of SSRIs, such as fluoxetine, citalopram, escitalopram, paroxetine, sertraline and fluvoxamine, on the endocrine system. For this purpose, the literature related to the effects of SSRIs on the endocrine system was searched using the PubMed database. According to the available literature, SSRIs may have an adverse effect on glucose metabolism, sexual function and fertility by dysregulating the function of the HPA axis, pancreas and gonads. Therefore, considering that SSRIs are often prescribed for extended periods, it is crucial to monitor the patient closely with particular attention to the function of the endocrine system.

The Emergence of Mania After Initiating Escitalopram for Anxiety Disorder.

The abrupt transition into mania, known as a bipolar switch, poses a significant challenge in the treatment of mental illnesses. We present a case of a 22-year-old Hispanic female with generalized anxiety disorder (GAD) and autism spectrum disorder (ASD) who developed mania within five days after initiating escitalopram 5 mg. The patient had no reported history of bipolar disorder prior to this episode, and an extensive medical workup ruled out organic causes. The patient was in the acute inpatient psychiatric unit for 25 days and returned to baseline after discontinuation of escitalopram and initiating divalproex and olanzapine. This case underscores the potential risk of a bipolar switch with antidepressant use and highlights the importance of vigilant monitoring and considering underlying bipolarity in such patients.

Brexpiprazole for Agitation Associated With Dementia Due to Alzheimer's Disease.

Alzheimer's disease (AD) is a prevalent neurodegenerative disease characterized by progressive cognitive and functional decline. Nearly all patients with AD develop neuropsychiatric symptoms (NPSs). Agitation is one of the most distressing and challenging NPS. Brexpiprazole is an oral antipsychotic and is the first approved pharmacologic agent in the United States for the treatment of agitation associated with dementia due to AD. Its effect is thought to be from its partial serotonin 5-HT1A and dopamine D2 receptor agonist activity and serotonin 5-HT2A receptor antagonism. Brexpiprazole is a maintenance medication, and it should not be used "as needed" or as a "PRN" treatment for breakthrough agitation. Brexpiprazole is a major substrate of CYP2D6 and CYP3A4. Dose adjustments may be required for drug interactions or impaired renal or hepatic function. Clinical trials found brexpiprazole 2 to 3 mg/d demonstrated significant improvements in agitation, with brexpiprazole showing an approximate 5-point greater reduction on change in the Cohen-Mansfield Agitation Inventory total score at week 12 from baseline compared with placebo. Brexpiprazole is generally well tolerated and safe, and common adverse reactions when used for this indication include dizziness, headaches, insomnia, nasopharyngitis, somnolence, and urinary tract infections. Like other antipsychotics used for agitation in AD, brexpiprazole is associated with higher mortality rates compared with placebo. In a long-term care setting, there are several considerations for its use. Benefits include an oral agent that is well tolerated and clinical data showing statistically significant effects on agitation. However, brexpiprazole has not been studied in head-to-head clinical trials against other antipsychotics, and there are differing opinions if the agitation score reductions translate to a clinically meaningful difference. The approval of brexpiprazole signals favorably for upcoming agents for this indication, including escitalopram and dextromethorphan-bupropion. Both escitalopram and dextromethorphan-bupropion are currently undergoing clinical trials.

Negative Prognostic Associations of Selective Serotonin Reuptake Inhibitors Use in Hospitalized COVID-19 Patients and Potential Contribution of Cardiovascular Comorbidities.

INTRODUCTION: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a causative agent of coronavirus disease 2019 (COVID-19), a very contagious systemic disease dominantly affecting the respiratory tract. Recent findings oppose earlier suggestions that selective serotonin reuptake inhibitors (SSRIs) might be protective during acute SARS-CoV-2 infection, prompting the current study. METHODS: The institutional registry of a tertiary referral center was retrospectively evaluated for SSRI use and associated clinical outcomes among hospitalized COVID-19 patients with mostly severe and critical disease. RESULTS: Among 1,558 patients, there were 78 (5%) exposed to SSRI during hospitalization. SSRI users in comparison to non-users did not significantly differ in their demographic characteristics, comorbidity profile or the severity of COVID-19 symptoms and associated inflammatory response at admission. In multivariate analyses adjusted for clinically meaningful variables, SSRI use was significantly associated with higher risks of death, mechanical ventilation, intensive care unit treatment, and bacteremia, whereas no significant relationship with risks of venous, arterial thrombosis, and major bleeding was present. Patients with less severe initial COVID-19 presentation, lower inflammatory burden, higher platelet count, lower cumulative comorbidity burden, presence of hyperlipidemia, atrial fibrillation, chronic heart failure and nonexposed to acetylsalicylic-acid had higher mortality associated with SSRI use. CONCLUSIONS: Findings of the current study validate findings of higher mortality but also report higher tendency for respiratory deterioration, intensive care unit treatment, and bacteremia associated with SSRI use among hospitalized COVID-19 patients. These findings also suggest the potential contribution of cardiovascular comorbidities to detrimental clinical course of SSRI exposed patients.

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.

Combined effect of CYP2C19 and CYP2D6 genotypes on escitalopram serum concentration and its metabolic ratio in a European patient population.

AIMS: The aim of the present study was to investigate the impact of CYP2D6 genotype on exposure and metabolism of escitalopram in patients stratified by CYP2C19 genotype in a large real-world population. METHODS: Patients were included from a therapeutic drug monitoring service if they had measured serum concentration of escitalopram and the metabolite, N-desmethyl escitalopram, and performed CYP2C19 and CYP2D6 genotyping. Patients were divided into 16 combined genotype-predicted phenotype subgroups (poor [PM], intermediate [IM], normal [NM] and ultrarapid metabolizers [UM]) of CYP2C19/CYP2D6. The concentration-to-dose (CD) ratio and metabolite-to-parent ratio (metabolic ratio) of escitalopram were compared across subgroups using the Kruskal-Wallis test followed by Dunn's test with CYP2D6 NMs as the reference group. RESULTS: A total of 5067 patients were included in the study. A stepwise increase in escitalopram CD ratio by decreasing CYP2D6 activity was observed in all CYP2C19 subgroups, except for in CYP2C19 UMs. The percentage differences in escitalopram CD ratio between CYP2D6 PMs and NMs were 24% in CYP2C19 NMs (P < .001), 28% in CYP2C19 IMs (P < .001) and 31% in CYP2C19 PMs (P = .04). As for the CD ratio, CYP2D6 genotype effect on metabolic ratio increased stepwise by decreasing CYP2C19 metabolism. CONCLUSIONS: CYP2D6 genotype is of significant importance for the individual variation in escitalopram pharmacokinetics. The most relevant increase in escitalopram concentration is seen in individuals with decreased and/or absent CYP2C19 activity. By combining CYP2C19 and CYP2D6 genotypes, the optimal dose for patients may be predicted with greater precision than for CYP2C19 genotype alone.

An observational study to evaluate the awareness of drug treatment, prescription pattern, adverse drug reactions, and adherence in patients of major depressive disorder.

Aims: Due to the paucity of studies in and out of India that dealt with treatment awareness of major depressive disorder (MDD), we decided to assess the awareness of MDD patients, and since adherence and awareness are linked to each other, we assessed adherence too. Prescription pattern studies identify changes in prescriptions due to poor initial response or adverse drug reactions (ADRs), which may result in dose reduction or switching medications and delay remission. Therefore, the study assessed the ADR pattern. Methodology: A cross-sectional questionnaire-based study was carried out on 200 MDD patients with treatment records for at least 3 months after getting approval from the Institutional Ethics Committee and consent from the patients. The data obtained were entered in Microsoft Excel and analyzed using descriptive statistics. Results: The mean age was 44.65 ± 12.02 years, and females were 70%. Maximum patients (98%) were aware of the consequence of stopping the drugs suddenly, and only 12.5% were aware of the onset of response to treatment. Escitalopram was the most common antidepressant prescribed (43.77%), and 67 ADRs out of 136 were attributable to it. Weakness and fatigue were the most common ADRs. The majority (97) of the ADRs were possibly related to antidepressants, and 65% of patients showed optimal adherence to medications. Conclusions: This study sheds light on the treatment awareness and adherence of MDD patients in India and highlights the need for educating patients about treatment response. It also emphasizes the importance of monitoring ADRs and adjusting prescription patterns accordingly to improve treatment outcomes.

A Randomized Controlled Trial Comparing Efficacy and Safety of Antidepressant Monotherapy.

BACKGROUND AND OBJECTIVES: The majority of mainstream antidepressants lack the promise of complete amelioration of symptoms. Other pitfalls include the latency period and side effects. These issues prompted investigations concerning the various roles of serotonin (5-HT) neurotransmissions in the etiology of depression. In this study, each study participant received vilazodone, vortioxetine, and escitalopram monotherapy for major depressive disorder (MDD) for 16 weeks. After that, the subject's scores on the Hamilton Depression Rating Scale (HDRS)-17 item version and the Montgomery Åsberg Depression Rating Scale (MADRS) were evaluated. In the study population, we kept track of the incidence of adverse events. METHODS: Ninety-six patients with MDD participated in this open-label, randomized, three-arm study. Participants were allotted into three groups according to a 1:1:1 ratio and given vilazodone (20-40 mg/day), vortioxetine (5-20 mg/day), or escitalopram (10-20 mg/day) for 16 weeks. Vortioxetine and vilazodone are test medications, with escitalopram serving as the control. After the baseline visit, follow-up appointments were scheduled every four weeks. Per-protocol (PP) and intent-to-treat (ITT) populations served as means for efficacy and safety evaluations, respectively. We prospectively registered this research in the Clinical Trial Registry, India (CTRI) (2022/07/043808). RESULTS: Out of the 134 patients we screened, 109 (81.34%) were eligible. Ninety-six (88.07%) of them completed the 16-week trial. In the PP population (n = 96), we analyzed efficacy. They had a mean age of 46.3 ± 6.2 years. At baseline, each group's median HDRS score was 30.0 (p = 0.964). Following 16 weeks of antidepressant therapy, these scores dropped to 15.0, 14.0, and 13.0 (p = 0.002). Baseline MADRS scores for all groups were 36.0 (p = 0.741). They had corresponding values of 20.0, 18.0, and 17.0 at 16 weeks (p < 0.001). Regarding both efficacy endpoints, the post-hoc analysis with the Bonferroni correction demonstrated statistically significant differences (p < 0.001). We performed the safety assessments within our ITT population (n = 109). Ninety-six adverse events were recorded. Nonetheless, none of them seemed serious. Still, five participants opted out because of their side effects. Vomiting and nausea were the most frequent side effects. CONCLUSION: Compared to escitalopram and vilazodone, vortioxetine demonstrated a statistically significant reduction in HDRS and MADRS scores. It also had fewer and milder side effects. We recommend conducting studies involving a broader population to investigate the antidepressant effects of these medications further.