Escitalopram Research Articles

Tratamentos farmacológicos para o transtorno de ansiedade social: existem novos parâmetros na atualidade?

CONTEXTO: O transtorno de ansiedade social (TAS), apesar da baixa taxa de detecção e do alto índice de comorbidades associadas, é considerado uma condição tratável. Apesar da resposta estabelecida a diversas classes de medicamentos, os algoritmos para o tratamento do TAS necessitam de atualização constante. OBJETIVO: Realizar revisão sistemática da literatura no que diz respeito à eficácia dos tratamentos farmacológicos relativos ao TAS, a partir de estudos controlados, conduzidos no período de 2005 a 2010. MÉTODO: Foram utilizados os indexadores eletrônicos PsycoInfo, Lilacs e Medline, utilizando-se as palavras-chave: "social phobia or social anxiety and treatment". RESULTADOS: De acordo com critérios de inclusão adotados, 29 artigos foram incluídos e analisados. Mostram-se eficazes para o tratamento do TAS as seguintes drogas, de acordo com a classe: a) ISRSs: escitalopram, fluvoxamina, citalopram, GR205171 e sertralina; b) ISRSN: venlafaxina; c) IMAOs: fenelzina, moclobemina; d) aminoácidos: d-cicloserina; f) anticonvulsivantes: tiagabina. CONCLUSÃO: Os ISRSs e os ISRSNs têm seu uso estabelecido e ainda continuam sendo considerados primeira opção de tratamento. Porém, destaca-se o potencial futuro da d-cicloserina e dos anticonvulsivantes, com necessidade de um número maior de estudos controlados que confirmem os achado iniciais. A ação das diferentes drogas em nível neurobiológico, bem como dos tratamentos associados, necessita ainda ser mais explorada.

Increased plasma corticosterone levels after periaqueductal gray stimulation-induced escape reaction or panic attacks in rats

The hypothalamo–pituitary–adrenal (HPA) axis is involved in stress, depression and anxiety. Controversy exists on HPA axis activation during panic attacks (PAs). We examined whether the HPA axis is involved in the escape or panic-like response in an animal model of PAs induced by electrical stimulation of the dorsolateral periaqueductal gray (dlPAG) in rats. Additionally, rats were also treated with chronic administration of buspirone (BUSP) and escitalopram (ESCIT), respectively; and they were stimulated in the open-field arena for panic-like reaction. Levels of stress hormone corticosterone were measured following 30min after escape or panic condition. Our results demonstrated that the levels of plasma corticosterone were significantly increased after the induction of escape or panic-like response in comparison with the sham animals. The levels of corticosterone were significantly decreased in the dlPAG stimulated groups after rats were treated chronically with the ESCIT but not the BUSP as compared to the saline treated animals. Importantly, the increase of corticosterone level after escape or panic-like response was paralleled by an increase of neuronal activation of c-Fos in both the parvocellular and magnocellular paraventricular nucleus of the hypothalamus. Moreover, the c-Fos data also showed a decrease in the number of positive cells particularly for the ESCIT as well as the BUSP in comparison with the saline stimulated animals. In conclusion, the present study clearly demonstrated that PA or escape response activates the HPA axis and it remains difficult to anticipate the mechanism underlying HPA axis during PAs and its relationship with 5-HT drugs.

Comparison of escitalopram vs. citalopram and venlafaxine in the treatment of major depression in Spain: clinical and economic consequences

Study objective:Population based study to determine the clinical consequences and economic impact of using escitalopram (ESC) vs. citalopram (CIT) and venlafaxine (VEN) in patients who initiate treatment for a new episode of major depression (MD) in real life conditions of outpatient practice.Methods:Observational, multicenter, retrospective study conducted using computerized medical records (administrative databases) of patients treated in six primary care centers and two hospitals between January 2003 and March 2007. Study population: patients >20 years of age diagnosed with a new episode of MD who initiate treatment with ESC, CIT or VEN who had not received any antidepressant treatment within the previous 6 months, and were followed for 18 months or more. Main variables: socio-demographic variables, remission (defined as a patient completing 6 months of therapy), comorbidity, annual health care costs (medical visits, diagnostic and therapeutic tests, hospitalizations, emergency room and psychoactive drugs prescribed) and non-health care costs (productivity losses at work, mainly sick leave and disability). Statistical analyses: logistic regression and ANCOVA models.Results:A total of 965 patients (ESC = 131; CIT = 491; VEN = 343) were identified and met study criteria. ESC-treated patients were younger, with a higher proportion of males, and had a lower specific comorbidity (p < 0.01). ESC-treated patients achieved higher remission rates compared to CIT (58.0% vs. 38.3%) or VEN patients (32.4%), p < 0.001, and had lower productivity work losses compared to VEN patients (32.7 vs. 43.8 days), p = 0.042. No differences in productivity work losses were observed between ESC and CIT patients. Compared to the ESC group, higher costs in average/unit of psychoactive drugs were found in the VEN group (€643.00), p = 0.003, whereas no differences were observed between the ESC and CIT groups (€294.70 vs. €265.20). In the corrected model, total costs (health care and non-health care cost) were lower with ESC (€2276.20) compared to CIT (€3093.80), p = 0.047 and VEN (€3801.20), p = 0.045.Conclusions:ESC appears to be dominant in the treatment of new MD episodes when compared to CIT and VEN, resulting in higher remission rates and lower total costs.

A comparative study of escitalopram angumentation with psychoanalysis in the treatment of refractory depression

Objective To investigate the efficacy of escitalopram combined with psychoanalysis in the treatment of refractory depression. Methods A total of 63 patients were randomly divided into escitalopram group ( n = 32) and escitalopram combined with psychoanalysis group( n = 31 ). All patients were evaluated with Hamilton depression Rating Scale(HAMD). Results After treatment,the scores of HAMD in two groups were both significantly lower than those before treatment. In the 8th ( ( HAMD ( 17.35 ± 2.98 ) ), 12th ( ( HAMD (9. 26 ±3.46) )weekend of treatment, the scores of HAMD in study group were significanlly lower than those in control group(8 th:21.97 ± 3.26; 12 th: 15.28 ± 3. 18 ). There were no significant differences in side effects between study group and control group. Conclusion Escitalopram angumented with psychoanalysis takes effects better than escitalopram single and doesn't increase side effects in the treatment of refractory depression. Key words: Escitalopram; Psychoanalysis; Refractory depression

Zero Order Spectrophotometric Method for Estimation of Escitalopram Oxalate in Tablet Formulations

A new, simple, fast and reliable zero order spectrophotometric method has been developed for determination of Escitalopram Oxalate in bulk and tablet dosage forms. The quantitative determination of drug was carried out using the zero order values (absorbance) measured at 238 nm. Calibration graph constructed at 238 nm was linear in concentration range of 2-20 µg/ml with correlation coefficient 0.9999. The method was found to be precise, accurate, specific, and validated as per ICH guidelines and can be used for determination of Escitalopram Oxalate in tablet formulations.

Escitalopram

Escitalopram (escitalopram oxalate; Cipralex, Lexapro), a selective serotonin reuptake inhibitor (SSRI) indicated for the treatment of major depressive disorder (MDD), demonstrates a highly selective and potent, dose-dependent inhibition of the human serotonin transporter, inhibiting serotonin reuptake into presynaptic nerve terminals and thus increasing serotonergic activity in the CNS. With regard to primary endpoints (such as improved scores on the Montgomery-Asberg Depression Rating Scale [MADRS] and the Hamilton Depression Rating Scale [HAM-D]), escitalopram was generally more effective than placebo, at least as effective as citalopram, and generally at least as effective as other comparator drugs, including the SSRIs fluoxetine, paroxetine and sertraline, the serotonin-noradrenaline (norepinephrine) reuptake inhibitors (SNRIs) venlafaxine extended release and duloxetine, and the aminoketone bupropion in adult patients with MDD in short-term, well designed trials. Moreover, it demonstrated a rapid onset of antidepressant action. Escitalopram was also found to be cost effective in several studies, dominating other SSRIs and venlafaxine extended release. Maintenance therapy is commonly required to prevent recurrence of depression. Long-term trials corroborated short-term results, with escitalopram demonstrating greater efficacy than placebo in relapse prevention. Additionally, escitalopram was at least as effective as citalopram, paroxetine and duloxetine in long-term comparative trials. Escitalopram has a predictable tolerability profile with generally mild to moderate and transient adverse events, and a low propensity for drug interactions. Sexual dysfunction with escitalopram treatment appeared to occur to a similar or lower extent to that with paroxetine (another SSRI), to a similar or greater extent to that with the SNRI duloxetine, and to a greater extent than that with the aminoketone bupropion. Thus, escitalopram is an effective and generally well tolerated treatment for moderate to severe MDD. Escitalopram, like other SSRIs, is an effective first-line option in the management of patients with MDD.

Comparative study between escitalopram and paroxetine in the treatment of depression

Objective To observe the clinical efficacy and safety of escitalporam in the treatment of depression. Methods 68 patients with depression randomly devided into escitalopram group and paroxetine group for 6 weeks. clinical efficacy was evaluated using Hamilton depression scale(HAMD) and Hamilton anxiety scale (HAMA) and treatment emergent symptoms scales(TESS)were used to evaluate the advense effects. Results The effective rate of escitalopram was94. 1% and paroxetine group was91.1%. Escitalopram group showed a highter response rate compared with paroxetine group after one week treatment. Conclusion Escitalopram is an effective and safe drug in the treatment of depression. Key words: Escitalopram; Paroxetine; Depression

Early-life stress and antidepressants modulate peripheral biomarkers in a gene–environment rat model of depression

Background Availability of peripheral biomarkers for depression could aid diagnosis and help to predict treatment response. The objective of this work was to analyse the peripheral biomarker response in a gene–environment interaction model of depression. Genetically selected Flinders Sensitive Line (FSL) rats were subjected to maternal separation (MS), since early-life trauma is an important antecedent of depression. An open-ended approach based on a proteomic analysis of serum was combined with the evaluation of depression-associated proteins. Methods Rats experienced MS and chronically received escitalopram (ESC) or nortryptiline (NOR). Serum proteins were compared by two-dimensional gel electrophoresis. Corticosterone, cytokines, BDNF and C-reactive protein (CRP) were measured by immunoassays. Results Comparing FSL with the control Flinders Resistant Line (FRL), Apo-AI and Apo-AIV, α1-macroglobulin, glutathione peroxidase and complement-C3 were significantly modulated. Significant increases were detected in leptin, interleukin (IL) 1α and BDNF. CRP levels were significantly reduced. The impact of early-life stress was assessed by comparing FSL + MS versus FSL. Apo-E, α1-macroglobulin, complement-C3, transferrin and hemopexin were significantly modulated. The effect of stress in antidepressant response was then evaluated. In the comparison FSL + ESC + MS versus FSL + ESC, albumin, α1-macroglobulin, glutathione peroxidase and complement-C3 were modulated and significant reductions were detected in IL4, IL6, IL10, CRP and BDNF. By comparing FSL + NOR + MS versus FSL + NOR proteins like Apo-AIV, pyruvate dehydrogenase, α1-macroglobulin, transferrin and complement-C3 showed different levels. Conclusions Lipid metabolism and immunity proteins were differently expressed in FSL in comparison with FRL. Exposure to MS induced changes in inflammation and transport proteins which became apparent in response to antidepressant treatments. Modulated proteins could suggest biomarker studies in humans.

Clinical lessons from GENDEP for the treatment of depression

In GENDEP, a European multicentre pharmacogenomic study http://gendep.iop.kcl.ac.uk/results.php, subjects with major depression were treated with escitalopram (ESC) or nortriptyline (NOR), in a part-randomised potential crossover design, and prospectively rated for response and ADRs with measures including the MADRS, HDRS, BDI, UKU, and ASEC (a self-report measure developed for GENDEP, Uher et al, in press). Factor analysis and Item Response Theory applied to the three measures of depression employed in the study generated three symptom dimensions. Mixed linear regression models showed no difference between ESC and NOR on the three original scales, but symptom dimensions revealed drug-specific advantages: observed mood and cognitive symptoms improved more with ESC than with NOR; neurovegetative symptoms improved more with NOR than with ESC. CYP2C19 genotypic category significantly predicted steady-state (week 8) ESC concentration. Analysis of baseline weight as a predictor revealed that lower BMI predicted better response to NOR. There was good agreement between the UKU and the ASEC, and urinary symptoms, dry mouth, blurred vision, and orthostatic hypotension predicted discontinuation of either drug.

Treatment with an SSRI antidepressant restores hippocampo-hypothalamic corticosteroid feedback and reverses insulin resistance in low-birth-weight rats

Low birth weight (LBW) is associated with type 2 diabetes and depression, which may be related to prenatal stress and insulin resistance as a result of chronic hypothalamic-pituitary-adrenal (HPA) axis hyperactivity. We examined whether treatment with a selective serotonin reuptake inhibitor [escitalopram (ESC)] could downregulate HPA axis activity and restore insulin sensitivity in LBW rats. After 4-5 wk of treatment, ESC-exposed LBW (SSRI-LBW) and saline-treated control and LBW rats (Cx and LBW) underwent an oral glucose tolerance test or a hyperinsulinemic euglycemic clamp to assess whole body insulin sensitivity. Hepatic phosphoenolpyruvate carboxykinase (PEPCK) mRNA expression and red skeletal muscle PKB Ser(473) phosphorylation were used to assess tissue-specific insulin sensitivity. mRNA expression of the hypothalamic mineralocorticoid receptor was fivefold upregulated in LBW (P < 0.05 vs. Cx), accompanied by increased corticosterone release during restraint stress and total 24-h urinary excretion (P < 0.05 vs. Cx), whole body insulin resistance (P < 0.001 vs. Cx), and impaired insulin suppression of hepatic PEPCK mRNA expression (P < 0.05 vs. Cx). Additionally, there was a tendency for reduced red muscle PKB Ser(473) phosphorylation. The ESC treatment normalized corticosterone secretion (P < 0.05 vs. LBW), whole body insulin sensitivity (P < 0.01) as well as postprandial suppression of hepatic mRNA PEPCK expression (P < 0.05), and red muscle PKB Ser(473) phosphorylation (P < 0.01 vs. LBW). We conclude that these data suggest that the insulin resistance and chronic HPA axis hyperactivity in LBW rats can be reversed by treatment with an ESC, which downregulates HPA axis activity, lowers glucocorticoid exposure, and restores insulin sensitivity in LBW rats.

Another Inch Closer to Personalized Pharmacotherapy

Researchers are avidly pursuing genetic explanations of why individuals respond differently to antidepressants. Investigators in the Genome-Based Therapeutic Drugs for Depression (GENDEP) study conducted a genome-wide exploration of 706 genetically unrelated European participants with unipolar major depression who received 12 weeks of escitalopram (which selectively inhibits the serotonin transporter without affecting norepinephrine reuptake) or nortriptyline (which has an 100-times-greater affinity for the …

Colorimetric Method for the Estimation of Escitalopram Oxalate in Tablet Dosage Form

A colorimetric method for the analysis of escitalopram oxalate in pure form and in tablets has been developed based on the formation of chloroform soluble ion associates with bromocresol green acidic dye. The extract of ion associates exhibited absorption maxima at 417 nm obeying Beer's law in the range of 2-10 µg/ml. The method is simple, precise and accurate with recovery of 98-102% and does not require any separation of soluble excipients from tablet dosage form.

HPTLC method for simultaneous analysis of escitalopram oxalate and clonazepam in pharmaceutical preparations

A simple, rapid, precise, and accurate high-performance thin-layer chromatographic (HPTLC) method has been established and validated for simultaneous analysis of escitalopram oxalate (ESC) and clonazepam (CLO) in pharmaceutical preparations. Separation was achieved on a aluminum HPTLC plates coated with 0.2 mm layers of silica gel 60 F 254 with methanol-toluene-triethylamine 1:3.5:0.1 ( v/v ) as mobile phase. Densitometric quantification was performed at 253 nm by reflectance scanning. The R F values of ESC and CLO were 0.36 and 0.49, respectively. The linearity of the method was investigated in the range 50–150 μg mL −1 for ESC and 5–15 μg mL −1 for CLO. Percentage recoveries for ESC and CLO were 100.41 and 99.54%, respectively, by height and 100.21% and 99.99% by area. The method was validated for precision, accuracy, specificity, and ruggedness.

Does Dual Antidepressant Therapy as Initial Treatment Hasten and Increase Remission from Depression?

Only 30%-40% of depressed patients remit after 8 weeks of treatment with an antidepressant. We hypothesized that beginning treatment with two antidepressants would improve remission rates. Relatively treatment-naive depressed outpatients (with DSM-IV diagnoses of major depressive disorder, dysthymic disorder, or depression not otherwise specified) were initially treated with a combination of escitalopram (ESC) plus bupropion (BUP), using rapid dose escalation to ESC 40 mg/day plus BUP 400 to 450 mg/day by study day 15 in an open-label, 8-week study. Remission was defined as a score < or =7 on the 17-item Hamilton Rating Scale for Depression (HAM-D17) at the end of the study. Recruitment occurred between July, 2003, and June, 2006, and the final patient completed the protocol in July, 2006. Fifty-five patients signed informed consent, 49 of whom received at least one dose of study medication. Of the 49 patients, 28 (57%) were women and 30 (61%) had a current diagnosis of major depressive disorder; the mean age was 38+/-12 years, and the mean pre-treatment HAM-D17 score was 16+/-4. Sixteen (33%) of the patients remitted by study week 2, and 31 (63%) by week 8. Nine patients (18%) dropped out prior to their week 8 visit, 5 of them because of side effects. The lack of a comparison group and the use of non-blind raters are drawbacks of this study. This open-label study suggests that increased numbers of patients may benefit from dual therapy with ESC plus BUP and that the benefit may perhaps include an increased likelihood of early response. Registry: ClinicalTrials.gov: http://www.clinicaltrials.gov/NCT00296712 (Journal of Psychiatric Practice. 2009;15:337-345).

Electrophysiological studies in the rat brain on the basis for aripiprazole augmentation of antidepressants in major depressive disorder

Aripiprazole (ARI) is an atypical antipsychotic approved by the Food and Drug Administration for use in major depressive disorder as an adjunct to antidepressants. However, the precise mechanisms responsible for the effectiveness of ARI augmentation are not fully understood. The current study was aimed at examining the effects of ARI administration alone and in combination with the selective serotonin reuptake inhibitors (SSRI) escitalopram (ESC) on the firing of serotonin (5-HT), norepinephrine (NE), and dopamine (DA) neurons. Electrophysiological experiments were carried out in anesthetized Sprague-Dawley rats. ESC was delivered via subcutaneously implanted osmotic minipumps at a dose of 10 mg/kg/day. ARI was subcutaneously injected daily at a dose of 2 mg/kg/day. Both drugs were administered for 2 and 14 days alone and in combination. Control rats received physiological saline in analogous regimens. Two-day ESC administration resulted in a significant decrease in the firing rate of 5-HT, NE, and DA neurons. Following 14 days of ESC administration, 5-HT firing returned to the baseline. The firing rate of NE and DA neurons remained significantly decreased. ARI administered for 2 or 14 days significantly increased the firing rate of 5-HT neurons by 36% and 48%, respectively, but not those of DA and NE neurons. Desensitization of somatodendritic 5-HT autoreceptors was observed after 2 days of ARI administration. The combination of the two drugs reversed the inhibitory action of ESC on the firing rate of 5-HT, NE, and DA neurons. The present study showed that addition of ARI to an SSRI regimen reverses the inhibitory action of the SSRI on monoaminergic neuronal firing.

The comparison study of efficacy and cognitive function between escitalopram and fluoxetine in the patients with depression

Objective To compare the effects of escitalopram and fluoxetine on clinical efficacy and cognitive function in depression patients.Methods Total 60 cases of patients with depression were randomly divided into escitalopram group(30 cases) and fluoxetine group(30 cases) . Carried on the clinical check experiment, two groups of medicine therapeutic dose respectively was 10'20 mg/d and 20'40 mg/d,and the treatment course was 8 weeks. Using HAMD17 and CGI-SI to evaluate efficient; using WCST and vocabulary fluency test to evaluate cognitive function of the two groups and using Treatment Emergent Symptom Scale and the laboratory test to evaluate adverse events. Results At 1st week, the response rate ( 20.00%) of escitalopram group were higher than this of fluoxertine group (3.33% )(χ2=4.04, P 0.05). Compare the scores in the two groups before and after treatment, vocabulary fluency test and the total numbers of test, continuous errors and random errors in WCST had improved( t =1.70'6.00,P 0.05). There was no significant difference between the two groups in vocabulary fluency test and WCST tests( t =0.02'0.49,P >0.05). The comparison of the adverse events frequence rates of escitalopram group and fluoxertine group had no statistical difference (χ2=0.07,P >0.05). Conclusion Escitalopram and fluoxetine have similar therapeutic efficacy and can improve cognition function of depressive patient. Escitalopram has a faster efficient time than fluoxertine which can release the symptoms promptly. Key words: Escitalopram; Fluoxetine; Depression; Cognitive function

Effects of escitalopram on the regulation of brain‐derived neurotrophic factor and nerve growth factor protein levels in a rat model of chronic stress

Escitalopram (ES-CIT) is a widely used, highly specific antidepressant. Until now there has been very little evidence on how this drug under pathological conditions affects an important feature within the pathophysiology of stress-related disorders such as depression: the endogenous neurotrophins. By using a well-characterized rat model in which chronic stress induces depressive-like behavior, the levels of neurotrophins brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) were determined in representative brain regions and serum using a highly sensitive improved fluorometric two-site ELISA system. There was a significant increase of BDNF in the left and right cortices after stress treatment (twofold increase) that was reversed by application of ES-CIT. An ES-CIT-dependent NGF reduction in stressed rats was detectable in the right cortex only (P = 0.027). The left hippocampus revealed significantly higher amounts of BDNF (2.5-fold increase) protein than the right hippocampus. These interhemispheric differences were unrelated to stress or ES-CIT treatment in all animals. BDNF and NGF of the frontal cortex, cerebellum, and serum did not change between the study groups. There was a negative correlation between body weight and serum BDNF, independent of stress or ES-CIT treatment. In conclusion, BDNF and NGF show substantial changes in this rodent model of chronic social stress, which is susceptible to antidepressant treatment with ES-CIT and therefore may constitute a neurobiological correlate for the disease.

Escitalopram, Sertraline Lead Class for Depression

Escitalopram, Sertraline Lead Class for Depression

Column Liquid Chromatography-Ultraviolet and Column Liquid Chromatography/Mass Spectrometry Evaluation of Stress Degradation Behavior of Escitalopram Oxalate

The objective of this work was to study the degradation behavior of escitalopram oxalate under different International Conference on Harmonization (ICH)-recommended stress conditions by column liquid chromatography (LC)-UV and LC/mass spectrometry (LC/MS) and to establish a validated stability-indicating LC assay method. Escitalopram oxalate was subjected to stress conditions of hydrolysis, oxidation, photolysis, and thermal decomposition. Extensive degradation was found to occur in alkaline medium. Mild degradation was observed in acidic and oxidative conditions. Escitalopram oxalate was stable to neutral, photolytic, and thermal stress. Successful separation of the drug from degradation products formed under stress conditions was achieved on a PerfectSil-100 ODS-3 column [C18 (5 microm, 25 cm x 4.6 mm id)] using methanol-0.01 M acetate buffer pH 3.8 adjusted with acetic acid (45 + 55) as the mobile phase. The flow rate was 1 ml/min, and the detection wavelength was 239 nm. The method was validated according to ICH guidelines. Major degradation products formed in hydrolysis and oxidative conditions were isolated, and structural elucidation of degradation products was done by LCIMS and infrared spectrometry studies. The major hydrolysis degradation product was confirmed as 1-(3-dimethylaminopropyl)-1-(4-fluoro- phenyl)-1,3dihydroisobenzofuran-5-carboxylic acid, and the major oxidative degradation product was confirmed as 1-{[3-dimethylamino(oxide)- propyl]-1-(4-fluro-phenyl)}-1,3-dihydro-isobenzofuran- 5-carbonitrile.

Medication for Depression and Anxiety: Don't Give Up Easily

Antidepressants “take time” to work in patients with major depressive disorder (MDD) and might take even longer in patients with anxiety disorders. But how long? When should clinicians switch medications? To learn more, researchers examined a pooled clinical trial database of 4357 patients receiving escitalopram for MDD (14 studies), generalized anxiety disorder (GAD; 6 studies), or social anxiety …