Escitalopram Research Articles

Escitalopram ahead of the game in MDD

Escitalopram ahead of the game in MDD

Escitalopram [Cipralex; Lundbeck A/S] has been launched in France.

Escitalopram [Cipralex; Lundbeck A/S] has been launched in France.

P.2.010 Venlafaxine XR versus escitalopram treatment of major depressive disorder

Comorbid depression and anxiety may result in greater symptom severity and poorer treatment response than either condition alone. Selective serotonin reuptake inhibitors have been found to be effective in treating both depression and anxiety; however, pharmacodynamic and pharmacokinetic changes associated with aging warrant special attention in medication trials in older patients.The objective of this study was to assess the efficacy and tolerability of short-term (12-week) administration of escitalopram oxalate 10 to 20 mg/d for moderate to marked comorbid depression and anxiety in elderly patients.This open-label, flexible-dose (10–20 mg/d), pilot trial was conducted at the Psychiatry Service, Veterans Affairs Medical Center, Cincinnati, Ohio. Outpatients aged ≥65 years were included if they met the criteria for comorbid major depressive disorder (MDD) and generalized anxiety disorder (GAD), as defined in the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision, for ≥4 weeks and had a baseline Montgomery-sberg Depression Rating Scale (MADRS) score of >22 and a Hamilton Rating Scale for Anxiety (HAM-A) score of ≥18. All patients received escitalopram 10 to 20 mg/d. The primary efficacy variables were the mean changes from baseline in total MADRS and HAM-A scores at 12 weeks (last observation carried forward). The secondary efficacy end point was the change from baseline in Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36) 8 subscale scores. Adverse events were assessed at each visit (treatment weeks 1, 2, 3, 4, 6, 8, 10, and 12) with the use of open-ended questioning.Twenty patients were enrolled (mean [SD] age, 73.0 [4.8] years; 6 [30%] women; race: 17 [85%] white, 2 [10%] black, and 1 [5%] “other”). Seventeen (85%) of 20 patients completed the study; 3 (15%) withdrew: 1 (5%) due to lack of efficacy and 2 (10%) due to adverse events (dizziness and somnolence [1 (5%) patient each]). Statistically significant improvements from baseline to end point were found with escitalopram treatment (MADRS: t19 = 7.38, P < 0.001, effect size = 2.93; HAM-A: t19 = 4.19, P < 0.001, effect size = 1.83). Significant changes from baseline in scores on 4 (Social Functioning, Role Functioning-Emotional, Mental Health, and Energy/Fatigue) of the 8 subscales of the SF-36 were als of ound (all, P < 0.01).In this small study in elderly patients with comorbid MDD and GAD, treatment with escitalopram 10 to 20 mg/d for 12 weeks was associated with significant improvements in symptoms of depression and anxiety.

R-citalopram counteracts the antidepressant-like effect of escitalopram in a rat chronic mild stress model.

The selective serotonin (5-HT) reuptake inhibitor, citalopram, is a racemic mixture of the stereoisomers, S-(+)-citalopram (escitalopram) and R-(-)-citalopram (R-citalopram). R-citalopram has been shown to counteract the 5-HT enhancing properties of escitalopram in acute studies in animals. In the present study we report, for the first time, on an interaction between R-citalopram and escitalopram after repeated dosing in a rat chronic mild stress (CMS) model of depression. The effect of escitalopram (2.0, 3.9 and 7.8 mg/kg per day), R-citalopram (7.8 mg/kg per day) and escitalopram 3.9 mg/kg per day plus R-citalopram 7.8 mg/kg per day were studied and compared to the effect of citalopram (8.0 mg/kg per day), imipramine and R-fluoxetine (8.9 mg/kg per day). Significant effects relative to a vehicle-treated group were achieved from week 1 for escitalopram (3.9 and 7.8 mg/kg per day), from week 2 for citalopram (8.0 mg/kg per day), from week 3 for R-fluoxetine (8.9 mg/kg per day) and from week 4 for escitalopram (2.0 mg/kg per day) and imipramine (8.9 mg/kg per day). R-citalopram (7.8 mg/kg per day) and escitalopram (3.9 mg/kg per day) plus R-citalopram (7.8 mg/kg per day) did not differ significantly from vehicle. There were no drug-induced effects in non-stressed control groups. In conclusion, escitalopram showed a shorter time to response in the rat CMS model of depression than citalopram, which was faster acting than R-fluoxetine and imipramine. R-citalopram counteracted the effect of escitalopram. The mechanism of action of R-citalopram is, at the moment unclear, but may be relevant to the improved clinical antidepressant activity seen with escitalopram in comparison with citalopram, and may also indicate an earlier response to escitalopram compared to other selective serotonin reuptake inhibitors (SSRIs).

SSRI market to be led by escitalopram by 2005, says Forest

SSRI market to be led by escitalopram by 2005, says Forest

The development of new antidepressants: focus on duloxetine and escitalopram.

The development of new antidepressants: focus on duloxetine and escitalopram.

Escitalopram

Escitalopram oxalate (S-citalopram, Lexapro™), a selective serotonin re-uptake inhibitor antidepressant which is the S-enantiomer of citalopram, is in clinical development worldwide for the treatment of depression and anxiety disorders. Preclinical studies demonstrate that the therapeutic activity of citalopram resides in the S-isomer and that escitalopram binds with high affinity to the human serotonin transporter. Conversely, R-citalopram is ∼ 30-fold less potent than escitalopram at this transporter. Escitalopram has linear pharmacokinetics, so that plasma levels increase proportionately and predictably with increased doses and its half-life of 27 – 32 h is consistent with once-daily dosing. In addition, escitalopram has negligible effects on cytochrome P450 drug-metabolising enzymes in vitro, suggesting a low potential for drug–drug interactions. The efficacy of escitalopram in patients with major depressive disorder has been demonstrated in multiple short-term, placebo-controlled clinical trials, three of which included citalopram as an active control, as well as in a 36-week study evaluating efficacy in the prevention of depression relapse. In these studies, escitalopram was shown to have robust efficacy in the treatment of depression and associated symptoms of anxiety relative to placebo. Efficacy has also been shown in treating generalised anxiety disorder, panic disorder and social anxiety disorder. Results also suggest that, at comparable doses, escitalopram demonstrates clinically relevant and statistically significant superiority to placebo treatment earlier than citalopram. Analysis of the safety database shows a low rate of discontinuation due to adverse events, and there was no statistically significant difference between escitalopram 10 mg/day and placebo in the proportion of patients who discontinued treatment early because of adverse events. The most common adverse events associated with escitalopram which occurred at a rate greater than placebo include nausea, insomnia, ejaculation disorder, diarrhoea, dry mouth and somnolence. Only nausea occurred in > 10% of escitalopram-treated patients.