The impact of antidepressant treatment on the network structure of neurocognition and core emotional depressive symptoms among depressed individuals with a history of suicide attempt: An 8-week clinical study.

BACKGROUND: A more in-depth understanding of the relationship between depressive symptoms, neurocognition and suicidal behavior could provide insights into the prognosis and treatment of major depressive disorder (MDD) and suicide. We conducted a network analysis among depressed patients examining associations between history of suicide attempt (HSA), core emotional major depression disorder, and key neurocognitive domains. METHOD: Depressed patients (n = 120) aged 18-65 years were recruited from a larger randomized clinical trial conducted at the Douglas Institute in Montreal, Canada. They were randomly assigned to receive one of two antidepressant treatments (i.e., escitalopram or desvenlafaxine) for 8 weeks. Core emotional MDD and key neurocognitive domains were assessed pre-post treatment. RESULTS: At baseline, an association between history of suicide attempt (HSA) and phonemic verbal fluency (PVF) suggested that HSA patients reported lower levels of the latter. After 8 weeks of antidepressant treatment, HSA became conditionally independent from PVF. Similar results were found for both the HAM-D and the QIDS-SR core emotional MDD/neurocognitive networks. CONCLUSION: Network analysis revealed a pre-treatment relationship between a HSA and decreased phonemic VF among depressed patients, which was no longer present after 8 weeks of antidepressant treatment.

A genome-wide association study of escitalopram treatment outcomes in patients with major depressive disorder.

Major depressive disorder (MDD) is a common psychological condition, the consequences of which, such as suicide, can be severe. Escitalopram, a selective serotonin reuptake inhibitor, is a commonly used antidepressant in clinics. However, more than one-third of patients with MDD do not respond to this drug. Gene polymorphism may affect the efficacy of escitalopram, but the genetic architecture of the antidepressant response in patients with MDD remains unclear. We perform a genome-wide association study (GWAS) of the genetic effect on the outcome of escitalopram in patients with MDD. A total of 203 patients with MDD and 176 healthy control (HC) adults were recruited from Beijing Anding Hospital. Patients received 12 weeks of antidepressant treatment with escitalopram. The Quick Inventory of Depressive Symptomatology-Self-Report (QIDS-SR) or Hamilton depression scale (HAMD) were used to evaluate the severity of depression symptoms at the baseline and the end of 2 and 12 weeks of treatment. A total of 140 variants in MDD patients were identified by GWAS to have genome-wide significance (p < 5e - 8) compared with HCs. Similarly, 189 and 18 variants were identified to be associated with QIDS-SR and HAMD score changes in patients after antidepressant treatment (p < 1e - 5), including rs12602361, rs72799048, rs16842235, and rs2518256. In the two weeks QIDS-SR score study, the gene-level association for these variants and gene set enrichment analyses implicate the enrichment of genes involved in the synaptic plasticity process and nervous system development. Our results implicate the predictive capacity of the effect of escitalopram treatment, supporting a link between genetic basis and remission of depression.

Off-label higher doses of serotonin reuptake inhibitors in the treatment of obsessive-compulsive disorder: Safety and tolerability.

OBJECTIVE: To examine the long-term safety and tolerability of off-label high-dose serotonin reuptake inhibitors (OLHD-SRIs) in the treatment of obsessive-compulsive disorder (OCD). METHODS: A retrospective longitudinal study was performed on 105 randomly selected outpatients diagnosed with OCD and were treated with OLHD-SRIs for at least 6 months. Patients received sertraline >200 mg/day, escitalopram >20 mg/day, fluvoxamine >300 mg/day, and fluoxetine >60 mg/day, combined with exposure and response prevention therapy. Patients were divided into three dosing groups: sertraline equivalent dose (SED) ≤ 200 mg/day (n = 26, 24.7%), 201-400 mg/day (n = 51, 48.5%) and 401-650 mg/day (n = 28, 26.6%). Safety and tolerability were assessed with an electrocardiogram, blood biochemistry, complete blood count, and side-effects monitoring. RESULTS: SED ranged from 100 to 650 mg/day and the mean duration of OLHD-SRI treatment was 20.8 months. The most common side-effects reported were sexual dysfunction (n = 36, 34%), weight gain (n = 28, 27%), sedation (n = 27, 26%), hyperhidrosis (n = 20, 19%), and tremor (n = 11, 10%). Abnormal ECG was documented in one patient, and another patient experienced a first-time seizure, whereas elevated liver enzymes were seen in 4.8% of the sample (n = 5). None of the patients had serotonin syndrome or drug-induced liver injury. Side-effects did not differ among the three dosing groups. CONCLUSION: OLHD-SRIs appear to be safe and well tolerated in OCD patients in SED ≤ 650 mg/day doses and the side-effects did not differ between the three dosing groups.

The safety and efficacy of escitalopram and sertraline in post-stroke depression: a randomized controlled trial.

OBJECTIVES: This study aims to evaluate the safety and efficacy of escitalopram and sertraline in post-stroke depression (PSD) patients, to provide more reliable therapeutics for cardiovascular and psychiatric clinical practice. METHODS: We recruited 60 patients (aged 40-89 years old) with an ICD-10 diagnosis of PSD, who were then randomly assigned to two groups and treated with flexible doses of escitalopram (10 to 20 mg/day, n = 30) or sertraline (50 to 200 mg/day, n = 30) for consecutive 8 weeks, respectively. The 24-item Hamilton Depression Rating Scale (HAMD-24), the 14-item Hamilton Anxiety Rating Scale (HAMA-14), the Treatment Emergent Symptom Scale (TESS), the Montreal Cognitive Assessment Scale (MOCA), and the Activity of Daily Living scale (ADL) were used to assess patients before, during, and after treatment for depression, anxiety, adverse effects, cognitive function, and daily living activities. Repeated measures ANOVA, the Mann-Whitney U test, the chi-square test (χ2), or Fisher's exact test was employed to assess baseline demographics, response rate, adverse effects rate, and changes in other clinical variables. RESULTS: Significant reduction in HAMD-24 and HAMA-14 scores was evaluated at baseline, as well as 1, 3, 4, 6, and 8 weeks of drug intervention (p < 0.01). There was a significant group difference in post-treatment HAMD-24 scores (p < 0.05), but no difference was observed in HAMA-14 scores (p > 0.05). Further analysis showed a significant variance in the HAMD-24 scores between the two groups at the end of the first week (p < 0.01). The incidence of adverse effects in both patient groups was mild, but there was a statistically significant difference between the two groups (p < 0.05). The improvement in cognitive function and the recovery of daily living abilities were comparable between both groups (p > 0.05). CONCLUSION: Escitalopram and sertraline showed comparable efficacy for anxiety symptoms, cognitive function, and daily living abilities in PSD patients. In addition, escitalopram was more appropriate for alleviating depressive symptoms. To validate the conclusion, trials with a larger sample size are in demand in the future. The registration number is ChiCTR1800017373.

Comparing the effect of fluoxetine, escitalopram, and sertraline, on the level of BDNF and depression in preclinical and clinical studies: a systematic review.

Brain-derived neurotrophic factor (BDNF) dysfunction is one of the most important mechanisms underlying depression. It seems that selective serotonin reuptake inhibitors (SSRIs) improve depression via affecting BDNF level. In this systematic review, for the first time, we aimed to review the effect of three SSRIs including fluoxetine, escitalopram, and sertraline, on both depression and BDNF level in preclinical and clinical studies. PubMed electronic database was searched, and 193 articles were included in this study. After reviewing all manuscripts, only one important difference was found: subjects. We found that SSRIs induce different effects in animals vs. humans. Preclinical studies showed many controversial effects, while human studies showed only two effects: improvement of depression, with or without the improvement of BDNF. However, most studies used chronic SSRIs treatment, while acute SSRIs were not effectively used and evaluated. In conclusion, it seems that SSRIs are reliable antidepressants, and the improvement effect of SSRIs on depression is not dependent to BDNF level (at least in human studies).

Perspectives on the impact of vortioxetine on the treatment armamentarium of major depressive disorder.

INTRODUCTION: Major Depressive Disorder (MDD) is a mental health issue that significantly affects patients' quality of life and functioning. Despite available treatments, many patients continue to suffer due to incomplete symptom resolution and side effects. AREAS COVERED: This manuscript examines Vortioxetine's role in Major Depressive Disorder (MDD) treatment, highlighting its potential to reshape therapeutic strategies due to its unique Multimodal action and proven broad-spectrum efficacy in multiple depressive domains. A detailed examination of Vortioxetine's pharmacological aspects, including indications, dosage, pharmacodynamics, and pharmacokinetics, is provided, emphasizing its safety and effectiveness. The discussion extends to Vortioxetine's role in acute-phase treatment and maintenance of MDD and its profound impact on specialized depression domains. EXPERT OPINION: Vortioxetine is distinguished for its novel multimodal serotonin modulation mechanism, showcasing significant promise as an innovative treatment for MDD. Its efficacy, which is dose-dependent, along with a commendable tolerability profile, positions it as a potential leading option for initial treatment strategies. The discourse on dosage titration, particularly the strategy of initiating treatment at lower doses followed by gradual escalation, underscores the approach toward minimizing initial adverse effects while optimizing therapeutic outcomes, aligning with the principles of personalized medicine in psychiatric care.

The efficacy of citalopram or escitalopram in patients with asthma and major depressive disorder.

BACKGROUND: Major depressive disorder is common in people with asthma. Yet, few studies have evaluated depression treatment in those with asthma. OBJECTIVE: To explore the relationship between antidepressant use, depressive symptoms, and asthma control, pooled data from 3 randomized trials of either citalopram or escitalopram were assessed. METHODS: Linear fixed effects and binary logistic regression analyses were conducted with between-subject covariates including treatment group, (original) study, and demographics. The within-subject effect of visit, and a treatment group-visit (between-within) interaction effect, were also evaluated. Analyses were repeated in a high asthma exacerbation subgroup having at least 3 oral corticosteroid bursts in the previous 12 months. Outcomes included the Hamilton rating scale for depression (HAM-D17), the 7-item asthma control questionnaire (ACQ), and oral corticosteroid use (yes or no). RESULTS: In the pooled sample (n = 255), the antidepressant treatment group exhibited lower HAM-D17 overall (P ≤ .001) and a lower likelihood for oral corticosteroid use (P ≤ .001) relative to the placebo group. In the high-exacerbation subgroup (n = 96), treatment group participants had lower overall asthma control questionnaire (P = .004) and HAM-D17 scores (P ≤ .001), and a lower likelihood of oral corticosteroid use (P = .003), relative to placebo participants. All treatment group interaction effects were not significant. CONCLUSION: Citalopram or escitalopram exhibited efficacy in reducing depressive symptoms and the need for rescue oral corticosteroids in patients with asthma and major depressive disorder. Future work should determine whether selective serotonin reuptake inhibitors are effective at improving asthma outcomes in those with asthma who are not depressed. TRIAL REGISTRATION: Clinicaltrials.gov Identifier: NCT00621946 and NCT01324700 (one study was conducted before ClinicalTrials.gov requirements).

THERAPY OF POST-COVID DEPRESSION: A PROACTIVE PSYCHOSOMATIC APPROACH.

OBJECTIVE: Aim: Evaluation of the effectiveness of the early 8-week monotherapy with escitalopram as a form of proactive psychosomatic intervention for patients with post-COVID depression. PATIENTS AND METHODS: Materials and methods: 44 patients with post-COVID depression were involved in a proactive psychosomatic intervention in the form of an 8-week intake of escitalopram (Medogram, Medochemiе Ltd) for 2-8 weeks in the case of a diagnosis of severe depression. Hamilton Depression Scale (HAM-D), Somatic Symptom Scale (SSS-8), Quality of Life Scale (CQLS) were used to assess symptoms and status dynamics. RESULTS: Results: Patients with post-COVID depression after an 8-week course of escitalopram therapy showed a significant reduction in mental and somatic symptoms of depression and an improvement in quality of life. At the time of enrollment in the study, 12 (28.58%) individuals had mild depression, 15 (35.71%) had moderate depression, and 15 (35.71%) had severe depression. At the end of the 8th weeks of taking the drug in 24 (57.14%) there were no signs of depression on the HAM-D scale, in 18 people there were subclinical manifestations of depression. The effectiveness of escitalopram in reducing the symptoms of depression in this study was 66%. CONCLUSION: Conclusions: With the introduction of pharmacotherapy with escitalopram there was a significant reduction in mental and so¬matic symptoms of depression and an improvement in quality of life. Escitalopram (Medochemie Ltd) may be an effective drug for psychopharmacotherapy of depressive symptoms in patients who have had COVID-19. Further studies are promising its effective¬ness in the treatment of post-COVID depression.

Genotyping of patients treated with selective serotonin reuptake inhibitors. / Genotyping av pasienter behandlet med selektive serotoninreopptakshemmere.

BACKGROUND: Selective serotonin reuptake inhibitors (SSRIs) are used by over 180,000 people in Norway. The enzymes CYP2D6 and CYP2C19 are key in the metabolism of SSRI antidepressants. The serotonin transporter coded by SLC6A4 may be significant for the efficacy of the drugs. MATERIAL AND METHOD: All patients who had undergone genotyping for CYP2D6, CYP2C19 and SLC6A4 at the Centre for Psychopharmacology in 2020 were included, irrespective of indication. For those patients where data were available, CYP2C19 genotype was linked to serum concentration measurement of escitalopram, which is the most commonly used SSRI drug. RESULTS: Out of 3,492 patients, 432 (12.4 %) had a combination of genotypes of CYP2D6, CYP2C19 and SLC6A4 considered to lead to the most favourable metabolism and efficacy of SSRI antidepressants. The dose requirement in patients with poor CYP2C19 metabolism was more than halved to achieve the same concentration of escitalopram compared to patients with normal metabolism. INTERPRETATION: Our findings demonstrate the low prevalence of the most favourable genotype combination for response to SSRIs. Genotype combinations probably contribute to the wide variation between individuals in the efficacy of these drugs and the fact that treatment does not produce the desired outcome in many patients.

Identification of Endocannabinoid Predictors of Treatment Outcomes in Major Depressive Disorder: A Secondary Analysis of the First Canadian Biomarker Integration Network in Depression (CAN-BIND 1) Study.

INTRODUCTION: An increasing number of studies are examining the link between the endocannabinoidome and major depressive disorder (MDD). We conducted an exploratory analysis of this system to identify potential markers of treatment outcomes. METHODS: The dataset of the Canadian Biomarker Integration Network in Depression-1 study, consisting of 180 patients with MDD treated for eight weeks with escitalopram followed by eight weeks with escitalopram alone or augmented with aripiprazole was analyzed. Association between response Montgomery-Asberg Depression Rating Scale (MADRS; score reduction≥50%) or remission (MADRS score≤10) at weeks 8 and 16 and single nucleotide polymorphisms (SNPs), methylation, and mRNA levels of 33 endocannabinoid markers were examined. A standard genome-wide association studies protocol was used for identifying SNPs, and logistic regression was used to assess methylation and mRNA levels. RESULTS: Lower methylation of CpG islands of the diacylglycerol lipase alpha gene (DAGLA) was associated with non-remission at week 16 (DAGLA; OR=0.337, p<0.003, q=0.050). Methylation of DAGLA was correlated with improvement in Clinical Global Impression (p=0.026), Quick Inventory of Depressive Symptomatology (p=0.010), and Snaith-Hamilton Pleasure scales (p=0.028). We did not find any association between SNPs or mRNA levels and treatment outcomes. DISCUSSION: Methylation of DAGLA is a promising candidate as a marker of treatment outcomes for MDD and needs to be explored further.

Modulatory effect of long-term treatment with escitalopram and clonazepam on the expression of anxiety-related neuropeptides: neuromedin U, neuropeptide S and their receptors in the rat brain.

BACKGROUND: Newly identified multifunctional peptidergic modulators of stress responses: neuromedin U (NMU) and neuropeptide S (NPS) are involved in the wide spectrum of brain functions. However, there are no reports dealing with potential molecular relationships between the action of diverse anxiolytic or antidepressant drugs and NMU and NPS signaling in the brain. The present work was therefore focused on local expression of the aforementioned stress-related neuropeptides in the rat brain after long-term treatment with escitalopram and clonazepam. METHODS: Studies were carried out on adult, male Sprague-Dawley rats that were divided into 3 groups: animals injected with saline (control) and experimental individuals treated with escitalopram (at single dose 5 mg/kg daily), and clonazepam (at single dose 0.5 mg/kg). All individuals were sacrificed under anaesthesia and the whole brain excised. Total mRNA was isolated from homogenized samples of amygdala, hippocampus, hypothalamus, thalamus, cerebellum and brainstem. Real time-PCR method was used for estimation of related NPS, NPS receptor (NPSR), NMU, NMU and receptor 2 (NMUR2) mRNA expression. The whole brains were also sliced for general immunohistochemical assessment of the neuropeptides expression. RESULTS: Chronic administration of clonazepam resulted in an increase of NMU mRNA expression and formation of NMU-expressing fibers in the amygdala, while escitalopram produced a significant decrease in NPSR mRNA level in hypothalamus. Long-term escitalopram administration affects the local expression of examined neuropeptides mRNA in a varied manner depending on the brain structure. CONCLUSIONS: Pharmacological effects of escitalopram may be connected with local at least partially NPSR-related alterations in the NPS/NMU/NMUR2 gene expression at the level selected rat brain regions. A novel alternative mode of SSRI action can be therefore cautiously proposed.

Drug treatment for panic disorder with or without agoraphobia: systematic review and network meta-analysis of randomised controlled trials.

OBJECTIVE: To identify drug classes and individual selective serotonin reuptake inhibitors (SSRIs) with high rates of remission and low risk of adverse events in the treatment of panic disorder with or without agoraphobia. DESIGN: Systematic review and network meta-analysis. DATA SOURCES: Embase, Medline, and ClinicalTrials.gov from inception to 17 June 2021. ELIGIBILITY CRITERIA FOR STUDY SELECTION: Randomised controlled trials that included adults aged ≥18 years with a diagnosis of panic disorder, compared drugs used to treat the panic disorder, and measured the outcomes of interest, including remissions, dropouts, and adverse events. METHODS: Risk of bias in the included studies was assessed using the revised Cochrane risk of bias tool for randomised trials. Direct meta-analyses were performed using random effects models. A two stage network meta-analysis with surface under the cumulative ranking curve (SUCRA) was used to estimate the comparative efficacy of drug classes and individual SSRIs. RESULTS: 87 studies including a total of 12 800 participants and 12 drug classes were eligible for inclusion. Almost all the studies (86/87) had some concern or were at high risk of bias. Network meta-analysis of remission with consistent results indicated that tricyclic antidepressants, benzodiazepines, monoamine oxidase inhibitors, SSRIs, and serotonin-noradrenaline reuptake inhibitors (SNRIs) were associated with significantly higher remission rates than placebo, with risk ratios of 1.39 (95% confidence interval 1.26 to 1.54), 1.47 (1.36 to 1.60), 1.30 (1.00 to 1.69), 1.38 (1.26 to 1.50), and 1.27 (1.12 to 1.45), respectively. SUCRAs identified benzodiazepines (84.5%, mean rank=2.4), tricyclic antidepressants (68.7%, 3.8), and SSRIs (66.4%, 4.0) as the top three best treatments for remission. However, tricyclic antidepressants, benzodiazepines, and SSRIs were also significantly associated with increased risk of adverse events compared with placebo, with risk ratios of 1.79 (1.47 to 2.19), 1.76 (1.50 to 2.06), and 1.19 (1.01 to 1.41), respectively. Consistency assumption of adverse events was upheld but could still be present on removal of studies with high percentages of women participants and those with agoraphobia. A SUCRA cluster ranking plot considering both remission and adverse events among all drug classes indicated that SSRIs were associated with high remission and low risk of adverse events. Among individual SSRIs, sertraline and escitalopram provided high remission with an acceptable risk of adverse events. CONCLUSION: The findings suggest that SSRIs provide high rates of remission with low risk of adverse events for the treatment of panic disorder. Among SSRIs, sertraline and escitalopram were associated with high remission and low risk of adverse events. The findings were, however, based on studies of moderate to very low certainty levels of evidence, mostly as a result of within study bias, inconsistency, and imprecision of the findings reported. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42020180638.

Serum amyloid P component level is associated with clinical response to escitalopram treatment in patients with major depressive disorder.

Serum amyloid P component (SAP) is a universal constituent of human amyloid deposits, which has been implicated in Alzheimer's disease and major depressive disorder (MDD). However, the relationship between SAP level and depression severity remains obscure. The aims of this study were to investigate how SAP is involved in depression and to explore the association between SAP level and antidepressant treatment response. Patients with MDD (n = 85) who received escitalopram monotherapy for 8-12 weeks were selected from a multicenter open-label randomized clinical trial. The same number of healthy controls was recruited. Depression severity was measured according to the Hamilton Depression Rating Scale (HAMD-17) at baseline and weeks 4, 8, and 12. The plasma levels of SAP were measured at baseline, week 2 and week 12. As a result, baseline levels of SAP were significantly higher in depressed patients than in control subjects (p < 0.001). SAP levels at baseline were negatively associated with depression severity after escitalopram treatment (p < 0.05), and the changes in SAP levels from baseline to week 12 were highly correlated with the severity of depressive symptoms based on the HAMD-17 score (p < 0.05). Interestingly, treatment with escitalopram significantly decreased the plasma levels of SAP in females, but not in males. Altogether, our results suggest that SAP not only involved in the pathobiology of depression but also mediates the action of antidepressant medications.

Comparative effectiveness of antidepressants on geriatric depression: Real-world evidence from a population-based study.

BACKGROUND: There is little real-world evidence about effectiveness of different antidepressants on geriatric depression. METHODS: We used population-based claims data in Taiwan between 1997 and 2013 to include older patients (≥ 60 years of age) who were diagnosed with depression and started to use antidepressants. All patients were followed up until discontinuation of antidepressant use or the end of the study period. Treatment outcomes were set as the risk of switching to another antidepressant, receiving augmentation therapy, and psychiatric hospitalization. We used cox proportional hazards regression models to calculate hazard ratios with 95% confidence intervals (CIs) and adjust for several confounding factors (aHRs). RESULTS: During the study period, a total of 207,946 elderly patients with depression received one of the following 11 antidepressants: sertraline, fluoxetine, paroxetine, escitalopram, citalopram, fluvoxamine, venlafaxine, duloxetine, moclobemide, mirtazapine, and bupropion. Compared to the patients treated with sertraline, those treated with fluvoxamine / venlafaxine had significantly but modestly higher risks of switching (aHR [95% CI]: 1.16 [1.11-1.21] / 1.10 [1.06-1.14]), augmentation (1.06 [1.02-1.10] / 1.08 [1.05-1.12]), and hospitalization (1.28 [1.03-1.58] / 1.37 [1.16-1.62]). Otherwise, the remaining 9 antidepressants yielded no consistent result in the three outcomes. LIMITATIONS: This study is a multi-arm and active controlled trial, lacking a placebo group. CONCLUSION: As treating geriatric depression, no individual antidepressant posed consistently better effectiveness in the outcomes of switching antidepressant, receiving augmentation, and psychiatric hospitalization than any other one, whereas clinicians should be cautious when prescribing fluvoxamine and venlafaxine.

Protocol for Escitalopram and Language Intervention for Subacute Aphasia (ELISA): A randomized, double blind, placebo-controlled trial.

In this forthcoming multicenter, prospective, randomized, double-blind placebo-controlled trial, we will investigate the augmentative effects of a selective serotonin reuptake inhibitor, escitalopram, on language therapy in individuals with post-stroke aphasia. We hypothesize that, when combined with language therapy, daily escitalopram will result in greater improvement than placebo in an untrained picture naming task (Philadelphia Naming Test short form) administered one week after the end of language therapy. We also will examine whether escitalopram's effect on language is independent of its effect on depression, varies with lesion location, or is associated with increased functional connectivity within the left hemisphere. Finally, we will examine whether individuals with BDNF met alleles show reduced response to treatment and reduced changes in connectivity. We expect to enroll 88 participants over four years. Participants are given escitalopram or placebo within one week of their stroke for 90 days and receive fifteen 45-minute computer-delivered sessions of language treatment beginning 60 days from the start of drug therapy. Patients then complete a comprehensive assessment of language at one, five, and twenty weeks after the last language therapy session. ELISA is the first randomized, controlled trial evaluating the effect of a selective serotonin reuptake inhibitor on the improvement of language in people with aphasia undergoing language treatment during the acute to subacute post-stroke period. Trial registration: The trial is registered with ClinicalTrials.gov NCT03843463.

Sensory Adaptation Training or Escitalopram for IBS With Constipation and Rectal Hypersensitivity: A Randomized Controlled Trial.

INTRODUCTION: Rectal hypersensitivity is an important pathophysiological dysfunction in irritable bowel syndrome with predominant constipation (IBS-C), whose treatment remains challenging. In a randomized controlled trial, we compared the efficacy and safety of a novel sensori-behavioral treatment, sensory adaptation training (SAT) with escitalopram. METHODS: Patients with IBS-C (Rome III) with rectal hypersensitivity received 6 biweekly sessions of SAT or escitalopram 10 mg daily for 3 months. SAT was performed by repetitive gradual distension of 10-cm long highly compliant rectal balloon above tolerability thresholds using barostat. Treatment effects on sensory thresholds and symptoms were compared. Coprimary outcome measures were those achieving improvements in rectal hypersensitivity (≥20% increase in ≥2/3 sensory thresholds) and pain (≥30% decrease). RESULTS: We randomized 49 patients; 26 received SAT and 23 escitalopram. SAT significantly improved desire to defecate (Δ 13.5 ± 2.3 vs 2.2 ± 1.1 mm Hg, P = 0.0006) and maximum tolerability (Δ 14.8 ± 1.9 vs 1.6 ± 0.9 mm Hg, P < 0.0001) thresholds compared with escitalopram. There were significantly greater percentage of hypersensitivity responders with SAT than escitalopram (69% vs 17%, P < 0.001), but not pain responders (58% vs 44%, P = 0.4). Daily pain scores did not differ between groups (P = 0.8) or escitalopram (P = 0.06) but decreased with SAT (P = 0.0046) compared with baseline. SAT significantly increased rectal compliance (P < 0.019) and complete spontaneous bowel movements per week than escitalopram (P = 0.04). Five withdrew from adverse events with escitalopram and none with SAT. DISCUSSION: SAT was significantly more efficacious in improving hypersensitivity and bowel symptoms in IBS-C than escitalopram. SAT is a promising novel treatment for IBS with rectal hypersensitivity.

Antidepressant-like effect of dehydrozingerone from Zingiber officinale by elevating monoamines in brain: in silico and in vivo studies.

BACKGROUND: Dehydrozingerone (DHZ) is an active ingredient of Zingiber officinale and structural half analogue of curcumin. In the present study, DHZ was evaluated for monoamine oxidase (MAO) inhibitory activity in silico and antidepressant activity in vivo. METHOD: The binding affinity of DHZ with MAO-A (PDB ID: 2Z5Y) was assessed using Schrodinger's Maestro followed by free energy calculation, pharmacokinetic property prediction using Qikprop and Molecular dynamics simulation using Desmond. In vivo antidepressant activity of DHZ was evaluated on C57 BL/6 male mice using Escilatopram as the standard antidepressant. Open field test (OFT), forced swimming test (FST) and tail suspension test (TST) were used to evaluate the antidepressant effect of the drugs on days 1 and 7. Following the behavioural study, neurotransmitters (noradrenaline, dopamine and serotonin) were estimated using liquid chromatography-mass spectrometry. RESULTS: DHZ demonstrated a greater binding affinity for the MAO-A enzyme compared to moclobemide in silico. Immobility in TST and FST were significantly (p < 0.05) reduced in vivo with 100mg/kg DHZ as compared to respective controls. DHZ treatment was more effective 1 h post treatment compared to vehicle control. A significant increase in levels of neurotransmitters was observed in mice brain homogenate in response to DHZ treatment, reassuring its antidepressant-like potential. CONCLUSION: DHZ demonstrated MAO-A inhibition in silico, and the increased neurotransmitter levels in the brain in vivo were associated with an antidepressant-like effect.

The efficacy of escitalopram in major depressive disorder: a multicenter randomized, placebo-controlled double-blind study.

The aim of the study was to conduct a multicenter randomized double-blinded placebo-controlled clinical study to evaluate the efficacy of a generic form of escitalopram in treating major depressive disorder (MDD). A total of 390 MDD patients admitted to hospitals in six cities in China were randomized to receive the generic version of escitalopram, the proprietary form of escitalopram (Lexapro) or placebo. During the 8-week treatment, the Hamilton rating scale for depression-17 (HAM-D17), Hamilton Anxiety Rating Scale (HAMA), Montgomery-Åsberg Depression Rating Scale (MADRS), Clinical Global Impressions scale (CGI), current visual analogue scale pain levels (VAS-P1) and Sheehan Disability Scale (SDS) assessments were performed at week 0, 1, 2, 4, 6 and 8 to evaluate treatment responses. HAM-D17, MADRS, HAMA and CGI-S levels of patients who received escitalopram or Lexapro decreased steadily during 8 weeks' treatment, whereas the placebo group showed a relatively smaller reduction of these levels (P < 0.001). SDS and VAS-P1 both decreased after treatment with generic escitalopram or proprietary escitalopram Lexapro. Our results indicated that both the generic escitalopram and proprietary escitalopram Lexapro had potent efficacy in treating MDD.