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Connie Sanchez - One of the best experts on this subject based on the ideXlab platform.
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A comparative review of Escitalopram, paroxetine, and sertraline: Are they all alike?
International clinical psychopharmacology, 2014Co-Authors: Connie Sanchez, Elin Heldbo Reines, Stuart A MontgomeryAbstract:It is known that newer antidepressants, such as the selective serotonin reuptake inhibitors (SSRIs), provide advantages in tolerability over antidepressants such as the tricyclics. However, even within the SSRI class, differences in efficacy or tolerability exist between the individual drugs. Among the three most widely prescribed SSRIs are paroxetine, sertraline, and Escitalopram. Escitalopram is commonly referred to as an SSRI, but also has well-documented allosteric properties, and thus can be further classed as an allosteric serotonin reuptake inhibitor. All three antidepressants are efficacious compared with placebo, but there is evidence that Escitalopram is more effective than a range of other antidepressants. There are no direct data to regard either paroxetine or sertraline as a superior antidepressant. Escitalopram is superior compared with paroxetine, which has a less favorable tolerability profile. Paroxetine is associated with cholinergic muscarinic antagonism and potent inhibition of CYP2D6, and sertraline has moderate drug interaction issues in comparison with Escitalopram. Overall, as an allosteric serotonin reuptake inhibitor that is somewhat different from classical SSRIs, Escitalopram is the first choice judged by combined efficacy and tolerability, and nonclinical data have offered possible mechanisms through which Escitalopram could be more efficacious, based on its interaction with orthosteric and allosteric binding sites at the serotonin transporter.
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Blockade of the high-affinity noradrenaline transporter (NET) by the selective 5-HT reuptake inhibitor Escitalopram: an in vivo microdialysis study in mice
British Journal of Pharmacology, 2013Co-Authors: Hai T. Nguyen, Connie Sanchez, Bruno P. Guiard, Alexandre Bacq, Denis J. David, Indira David, Gael Quesseveur, Sophie Gautron, Alain M. GardierAbstract:BACKGROUND AND PURPOSE Escitalopram, the S(+)-enantiomer of citalopram is the most selective 5-HT reuptake inhibitor approved. Although all 5-HT selective reuptake inhibitors (SSRIs) increase extracellular levels of 5-HT ([5-HT]ext). some also enhance, to a lesser extent, extracellular levels of noradrenaline ([NA]ext). However, the mechanisms by which SSRIs activate noradrenergic transmission in the brain remain to be determined. EXPERIMENTAL APPROACH This study examined the effects of Escitalopram, on both [5-HT]ext and [NA]ext in the frontal cortex (FCx) of freely moving wild-type (WT) and mutant mice lacking the 5-HT transporter (SERT-/-) by using intracerebral microdialysis. We explored the possibilities that Escitalopram enhances [NA]ext, either by a direct mechanism involving the inhibition of the low- or high-affinity noradrenaline transporters, or by an indirect mechanism promoted by [5-HT]ext elevation. The forced swim test (FST) was used to investigate whether enhancing cortical [5-HT]ext and/or [NA]ext affected the antidepressant-like activity of Escitalopram. KEY RESULTS In WT mice, a single systemic administration of Escitalopram produced a significant increase in cortical [5-HT]ext and [NA]ext. As expected, Escitalopram failed to increase cortical [5-HT]ext in SERT-/- mice, whereas its neurochemical effects on [NA]ext persisted in these mutants. In WT mice subjected to the FST, Escitalopram increased swimming parameters without affecting climbing behaviour. Finally, Escitalopram, at relevant concentrations, failed to inhibit cortical noradrenaline and 5-HT uptake mediated by low-affinity monoamine transporters. CONCLUSIONS AND IMPLICATIONS These experiments suggest that Escitalopram enhances, although moderately, cortical [NA]extin vivo by a direct mechanism involving the inhibition of the high-affinity noradrenaline transporter (NET).
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Escitalopram, an antidepressant with an allosteric effect at the serotonin transporter—a review of current understanding of its mechanism of action
Psychopharmacology, 2012Co-Authors: Huailing Zhong, Nasser Haddjeri, Connie SanchezAbstract:Rationale Escitalopram is a widely used antidepressant for the treatment of patients with major depression. It is the pure S-enantiomer of racemic citalopram. Several clinical trials and meta-analyses indicate that Escitalopram is quantitatively more efficacious than many other antidepressants with a faster onset of action. Objective This paper reviews current knowledge about the mechanism of action of Escitalopram. Results The primary target for Escitalopram is the serotonin transporter (SERT), which is responsible for serotonin (or 5-hydroxytryptamine [5-HT]) reuptake at the terminals and cell bodies of serotonergic neurons. Escitalopram and selective serotonin reuptake inhibitors bind with high affinity to the 5-HT binding site (orthosteric site) on the transporter. This leads to antidepressant effects by increasing extracellular 5-HT levels which enhance 5-HT neurotransmission. SERT also has one or more allosteric sites, binding to which modulates activity at the orthosteric binding site but does not directly affect 5-HT reuptake by the transporter. In vitro studies have shown that through allosteric binding, Escitalopram decreases its own dissociation rate from the orthosteric site on the SERT. R-citalopram, the nontherapeutic enantiomer in citalopram, is also an allosteric modulator of SERT but can inhibit the actions of Escitalopram by interfering negatively with its binding. Both nonclinical studies and some clinical investigations have demonstrated the cellular, neurochemical, neuroadaptive, and neuroplastic changes induced by Escitalopram with acute and chronic administration. Conclusions The findings from binding, neurochemical, and neurophysiological studies may provide a mechanistic rationale for the clinical difference observed with Escitalopram compared to other antidepressant therapies.
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Escitalopram versus citalopram: the surprising role of the R-enantiomer
Psychopharmacology, 2004Co-Authors: Connie Sanchez, Elin Heldbo Reines, Klaus Peter Bogeso, Bjarke Ebert, Claus BraestrupAbstract:Rationale Citalopram is a racemate consisting of a 1:1 mixture of the R (−)- and S (+)-enantiomers. Non-clinical studies show that the serotonin reuptake inhibitory activity of citalopram is attributable to the S -enantiomer, Escitalopram. A series of recent non-clinical and clinical studies comparing Escitalopram and citalopram to placebo found that equivalent doses of these two drugs, i. e. containing the same amount of the S -enantiomer, showed better effect for Escitalopram. These results suggested that the R -citalopram in citalopram inhibits the effect of the S -enantiomer. Objective To review the pharmacological and non-clinical literature that describes the inhibition of Escitalopram by R -citalopram, as well as the implications of this inhibition for the clinical efficacy of Escitalopram compared to citalopram. Methods The information in this review was gathered from published articles and abstracts. Results In appropriate neurochemical, functional, and behavioural non-clinical experiments, Escitalopram shows greater efficacy and faster onset of action than comparable doses of citalopram. The lower efficacy of citalopram in these studies is apparently due to the inhibition of the effect of the S -enantiomer by the R -enantiomer, possibly via an allosteric interaction with the serotonin transporter. Data from randomised clinical trials consistently show better efficacy with Escitalopram than with citalopram, including higher rates of response and remission, and faster time to symptom relief. Conclusion The R -enantiomer present in citalopram counteracts the activity of the S -enantiomer, thereby providing a possible basis for the pharmacological and clinical differences observed between citalopram and Escitalopram.
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the s enantiomer of r s citalopram increases inhibitor binding to the human serotonin transporter by an allosteric mechanism comparison with other serotonin transporter inhibitors
European Neuropsychopharmacology, 2003Co-Authors: Fenghua Chen, Connie Sanchez, Mads Breum Larsen, Ove WiborgAbstract:Abstract The interaction of the S - and R -enantiomers (Escitalopram and R -citalopram) of citalopram, with high- and low-affinity binding sites in COS-1 cell membranes expressing human SERT (hSERT) were investigated. Escitalopram affinity for hSERT and its 5-HT uptake inhibitory potency was in the nanomolar range and approximately 40-fold more potent than R -citalopram. Escitalopram considerably stabilised the [ 3 H]-Escitalopram/SERT complex via an allosteric effect at a low-affinity binding site. The stereoselectivity between Escitalopram and R -citalopram was approximately 3:1 for the [ 3 H]-Escitalopram/hSERT complex. The combined effect of Escitalopram and R -citalopram was additive. Paroxetine and sertraline mainly stabilised the [ 3 H]-paroxetine/hSERT complex. Fluoxetine, duloxetine and venlafaxine have only minor effects. 5-HT stabilised the [ 125 I]-RTI-55, [ 3 H]-MADAM, [ 3 H]-paroxetine, [ 3 H]-fluoxetine and [ 3 H]-venlafaxine/SERT complex to some extent. Thus, Escitalopram shows a unique interaction with the hSERT compared with other 5-HT reuptake inhibitors (SSRIs) and, in addition to its 5-HT reuptake inhibitory properties, displays a pronounced effect via an affinity-modulating allosteric site.
Rico Nil - One of the best experts on this subject based on the ideXlab platform.
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a 24 week randomized double blind placebo controlled study of Escitalopram for the prevention of generalized social anxiety disorder
The Journal of Clinical Psychiatry, 2005Co-Authors: S A Montgomery, Henrik Loft, Rico Nil, Natalie Durrpal, Jeanphilippe BoulengerAbstract:OBJECTIVE Escitalopram has proven efficacy in the short-term treatment of generalized social anxiety disorder (SAD). The present relapse prevention study investigated relapse rates during a 24-week, randomized, double-blind, placebo-controlled period in patients with generalized SAD who had responded to 12-week open-label treatment with Escitalopram. METHOD A total of 517 patients with a primary diagnosis of generalized SAD (per DSM-IV criteria) and a Liebowitz Social Anxiety Scale (LSAS) total score of > or = 70 received 12 weeks of open-label treatment with flexible doses (10-20 mg/day) of Escitalopram. Of these patients, 371 responded (Clinical Global Impressions-Improvement scale [CGI-I] score of 1 or 2) and were randomly assigned to 24 weeks of double-blind treatment with escitalo-pram (10 or 20 mg/day) (N = 190) or placebo (N = 181), continuing with the dose level administered at the end of the open-label period. Relapse was defined as either an increase in LSAS total score of > or = 10 or withdrawal due to lack of efficacy, as judged by the investigator. The study was conducted from January 2001 to June 2002. RESULTS Survival analysis of relapse and time to relapse showed a significant advantage for Escitalopram compared to placebo (log-rank test: p < .001). The risk of relapse was 2.8 times higher for placebo-treated patients than for Escitalopram-treated patients (p < .001), resulting in significantly fewer Escitalopram-treated patients relapsing (22% vs. 50%), at both doses. Escitalopram was well tolerated during double-blind treatment of generalized SAD, and only 2.6% of the Escitalopram-treated patients withdrew because of adverse events. The overall discontinuation rate, excluding relapses, was 13.2% for patients treated with Escitalopram and 8.3% for patients treated with placebo. CONCLUSION Escitalopram was effective and well tolerated in the long-term treatment of generalized SAD.
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Escitalopram in the treatment of social anxiety disorder randomised placebo controlled flexible dosage study
British Journal of Psychiatry, 2005Co-Authors: Siegfried Kasper, Henrik Loft, Dan J. Stein, Rico NilAbstract:Background Selective serotonin reuptake inhibitors are effective in the treatment of social anxiety disorder and are currently regarded as the pharmacotherapy of choice. Aims To investigate the efficacy and tolerability of Escitalopram in the treatment of generalised social anxiety disorder. Method Patients with generalised social anxiety disorder were randomised to receive placebo ( n =177) or 10-20 mg Escitalopram ( n =181) in a 12-week, double-blind trial. The primary outcome measure was the mean change from baseline to last assessment in the Liebowitz Social Anxiety Scale (LSAS) total score. Results The study showed a statistically superior therapeutic effect for Escitalopram compared with placebo on the LSAS total score ( P =0.005). There were significantly more responders to treatment for Escitalopram than for placebo (54% v . 39%; P <0.01). The clinical relevance of these findings was supported by significant reduction in the work and social components of the Sheehan Disability Scale and by the good tolerability of Escitalopram treatment. Conclusions Escitalopram was efficacious and well tolerated in the treatment of generalised social anxiety disorder.
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efficacy and tolerability of Escitalopram in 12 and 24 week treatment of social anxiety disorder randomised double blind placebo controlled fixed dose study
Depression and Anxiety, 2004Co-Authors: M Malcolm D Lader, Karina Stender, Vera Burger, Rico NilAbstract:Selective serotonin reuptake inhibitors are the pharmacological treatment of choice for the treatment of social anxiety disorder (SAD). The efficacy and tolerability of fixed doses of Escitalopram were compared to those of placebo in the long-term treatment of generalised SAD, using paroxetine as an active reference. Patients with a DSM-IV diagnosis of SAD between 18–65 years of age were randomised to 24 weeks of double-blind treatment with placebo (n = 166), 5 mg Escitalopram (n = 167), 10 mg Escitalopram (n = 167), 20 mg Escitalopram (n = 170), or 20 mg paroxetine (n = 169). Based on the primary efficacy parameter, Liebowitz Social Anxiety Scale (LSAS) total score at Week 12 (LOCF), a significantly superior therapeutic effect compared to placebo was seen for 5 and 20 mg Escitalopram and for all doses for the OC analyses. Further improvement in LSAS scores was seen at Week 24 (OC and LOCF), with significant superiority over placebo for all doses of Escitalopram, and 20 mg Escitalopram was significantly superior to 20 mg paroxetine. Response to treatment (assessed by a Clinical Global Impression-Improvement score ≤2) was significantly higher for all active treatments than for placebo at Week 12. Clinical relevance was supported by a significant decrease in all the Sheehan disability scores, and the good tolerability of Escitalopram treatment. It is concluded that doses of 5–20 mg Escitalopram are effective and well tolerated in the short- and long-term treatment of generalised SAD. Depression and Anxiety 00:000–000, 2004. © 2004 Wiley-Liss, Inc.
Elin Heldbo Reines - One of the best experts on this subject based on the ideXlab platform.
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A comparative review of Escitalopram, paroxetine, and sertraline: Are they all alike?
International clinical psychopharmacology, 2014Co-Authors: Connie Sanchez, Elin Heldbo Reines, Stuart A MontgomeryAbstract:It is known that newer antidepressants, such as the selective serotonin reuptake inhibitors (SSRIs), provide advantages in tolerability over antidepressants such as the tricyclics. However, even within the SSRI class, differences in efficacy or tolerability exist between the individual drugs. Among the three most widely prescribed SSRIs are paroxetine, sertraline, and Escitalopram. Escitalopram is commonly referred to as an SSRI, but also has well-documented allosteric properties, and thus can be further classed as an allosteric serotonin reuptake inhibitor. All three antidepressants are efficacious compared with placebo, but there is evidence that Escitalopram is more effective than a range of other antidepressants. There are no direct data to regard either paroxetine or sertraline as a superior antidepressant. Escitalopram is superior compared with paroxetine, which has a less favorable tolerability profile. Paroxetine is associated with cholinergic muscarinic antagonism and potent inhibition of CYP2D6, and sertraline has moderate drug interaction issues in comparison with Escitalopram. Overall, as an allosteric serotonin reuptake inhibitor that is somewhat different from classical SSRIs, Escitalopram is the first choice judged by combined efficacy and tolerability, and nonclinical data have offered possible mechanisms through which Escitalopram could be more efficacious, based on its interaction with orthosteric and allosteric binding sites at the serotonin transporter.
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The cardiovascular safety profile of Escitalopram
European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology, 2013Co-Authors: Michael E. Thase, Elin Heldbo Reines, Klaus Larsen, Sidney H. KennedyAbstract:Abstract The cardiovascular effects of Escitalopram were examined in a large group of participants in double-blind, randomized, placebo-controlled studies. Escitalopram ( n =3298) was administered at doses between 5 and 20 mg/day. Patients were treated in acute (8–12 weeks) and long-term (24 weeks) studies. Assessment of cardiovascular safety included heart rate, blood pressure (BP), treatment-emergent adverse events (TEAEs) and electrocardiograms (ECGs). In the short-term, there was a small, but statistically significant 2 beats per minute decrease in heart rate with Escitalopram compared with placebo. The difference compared to placebo in systolic or diastolic BP was not clinically or statistically significant. Valid ECG assessments at both baseline and last assessment were available for 2407 Escitalopram patients and 1952 placebo patients. Escitalopram–placebo differences in mean changes in ECG values were not clinically meaningful. The mean difference to placebo in the corrected QT [Fridericia's (QTcF)] interval was 3.5 ms (all Escitalopram doses); 1.3 ms (Escitalopram 10 mg) and 1.7 ms (Escitalopram 20 mg) ( p =0.2836 for 10 versus 20 mg). One out of 2407 Escitalopram patients had a QTcF interval >500 ms and a change from baseline >60 ms. The incidence and types of cardiac-associated adverse events were similar between patients treated for 8–12 weeks with placebo (2.2%) or Escitalopram (1.9%) and for 24 weeks with placebo (2.7%) or Escitalopram (2.3%). Analyses of data from long-term studies and studies of the elderly showed similar results. In conclusion, these data demonstrate that Escitalopram, like other SSRIs, has a statistically significant effect on heart rate and no clinically meaningful effect on ECG values, BP, with a placebo-level incidence of cardiac-associated adverse events.
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Escitalopram versus citalopram: the surprising role of the R-enantiomer
Psychopharmacology, 2004Co-Authors: Connie Sanchez, Elin Heldbo Reines, Klaus Peter Bogeso, Bjarke Ebert, Claus BraestrupAbstract:Rationale Citalopram is a racemate consisting of a 1:1 mixture of the R (−)- and S (+)-enantiomers. Non-clinical studies show that the serotonin reuptake inhibitory activity of citalopram is attributable to the S -enantiomer, Escitalopram. A series of recent non-clinical and clinical studies comparing Escitalopram and citalopram to placebo found that equivalent doses of these two drugs, i. e. containing the same amount of the S -enantiomer, showed better effect for Escitalopram. These results suggested that the R -citalopram in citalopram inhibits the effect of the S -enantiomer. Objective To review the pharmacological and non-clinical literature that describes the inhibition of Escitalopram by R -citalopram, as well as the implications of this inhibition for the clinical efficacy of Escitalopram compared to citalopram. Methods The information in this review was gathered from published articles and abstracts. Results In appropriate neurochemical, functional, and behavioural non-clinical experiments, Escitalopram shows greater efficacy and faster onset of action than comparable doses of citalopram. The lower efficacy of citalopram in these studies is apparently due to the inhibition of the effect of the S -enantiomer by the R -enantiomer, possibly via an allosteric interaction with the serotonin transporter. Data from randomised clinical trials consistently show better efficacy with Escitalopram than with citalopram, including higher rates of response and remission, and faster time to symptom relief. Conclusion The R -enantiomer present in citalopram counteracts the activity of the S -enantiomer, thereby providing a possible basis for the pharmacological and clinical differences observed between citalopram and Escitalopram.
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Escitalopram 10 mg day is effective and well tolerated in a placebo controlled study in depression in primary care
International Clinical Psychopharmacology, 2003Co-Authors: Ulla M Lepola, Henrik Loft, Elin Heldbo ReinesAbstract:Escitalopram was compared to placebo in moderately to severely depressed patients in primary care with citalopram as the active reference. Patients were randomized to receive flexible doses of 10-20 mg/day Escitalopram (n=155), 20-40 mg/day citalopram (n=160), or placebo (n=154) over an 8-week double-blind period. The primary efficacy parameter was the change from baseline to last assessment in the Montgomery-Asberg Depression Rating Scale total score. Escitalopram produced a statistically significant therapeutic difference of 2.9 points (P=0.002) compared to placebo, and Escitalopram was consistently and statistically significantly more efficacious than placebo from week 1 onwards. Analysis of Clinical Global Impression-Severity and Clinical Global Impression-Improvement confirmed the primary efficacy results. By week 8, significantly more patients had responded to treatment with Escitalopram than with citalopram (P=0.021) or placebo (P=0.009). Escitalopram was as well tolerated as citalopram and had a similar adverse event profile. Both Escitalopram- and citalopram-treated patients had placebo-level adverse event withdrawal rates (3% and 4%, respectively). This study demonstrates the consistent antidepressant efficacy and excellent tolerability of Escitalopram 10-20 mg/day in primary care patients with major depressive disorder.
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Escitalopram s enantiomer of citalopram clinical efficacy and onset of action predicted from a rat model
Pharmacology & Toxicology, 2001Co-Authors: Stuart A Montgomery, Elin Heldbo Reines, Connie Sanchez, Henrik Loft, Mariusz PappAbstract:Escitalopram is the active S-enantiomer of citalopram. In a chronic mild stress model of depression in rats, treatments with both Escitalopram and citalopram were effective; however, a faster time to onset of efficacy compared to vehicle treatment was observed for Escitalopram-treated (5 mg/kg/day) than for citalopram-treated (10 mg/kg/day) rats at Week 1. To study the predictability of this observation in the clinic, we analysed 4-week data from an 8-week, double-blind, randomised, placebo-controlled, flexible-dose study that compared Escitalopram and citalopram to placebo in primary care patients with major depressive disorder (baseline Montgomery and Asberg Depression Rating Scale (MADRS) scores > or =22 and < or =40). Since the flexible dosing started after Week 4, analysis of 4-week data ensured that the patients received fixed doses of 10 mg/day Escitalopram (155 patients), 20 mg/day citalopram (160 patients), or placebo (154 patients). The efficacy analysis showed a significantly superior therapeutic effect for Escitalopram versus placebo from Week 1 onwards (observed cases) with an adjusted mean change in MADRS at Week 4 (last observation carried forward) of 2.7 points (P=0.002). By comparison, 20 mg/day citalopram did not demonstrate a statistically significant effect compared to placebo. Escitalopram was well tolerated with an adverse event profile similar to that of citalopram. The preclinical observation that Escitalopram possesses a faster time to onset of efficacy than citalopram was also seen in primary care patients with major depressive disorder. Thus, Escitalopram is efficacious in depression and the effect occurs earlier than for citalopram.
Henrik Loft - One of the best experts on this subject based on the ideXlab platform.
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a 24 week randomized double blind placebo controlled study of Escitalopram for the prevention of generalized social anxiety disorder
The Journal of Clinical Psychiatry, 2005Co-Authors: S A Montgomery, Henrik Loft, Rico Nil, Natalie Durrpal, Jeanphilippe BoulengerAbstract:OBJECTIVE Escitalopram has proven efficacy in the short-term treatment of generalized social anxiety disorder (SAD). The present relapse prevention study investigated relapse rates during a 24-week, randomized, double-blind, placebo-controlled period in patients with generalized SAD who had responded to 12-week open-label treatment with Escitalopram. METHOD A total of 517 patients with a primary diagnosis of generalized SAD (per DSM-IV criteria) and a Liebowitz Social Anxiety Scale (LSAS) total score of > or = 70 received 12 weeks of open-label treatment with flexible doses (10-20 mg/day) of Escitalopram. Of these patients, 371 responded (Clinical Global Impressions-Improvement scale [CGI-I] score of 1 or 2) and were randomly assigned to 24 weeks of double-blind treatment with escitalo-pram (10 or 20 mg/day) (N = 190) or placebo (N = 181), continuing with the dose level administered at the end of the open-label period. Relapse was defined as either an increase in LSAS total score of > or = 10 or withdrawal due to lack of efficacy, as judged by the investigator. The study was conducted from January 2001 to June 2002. RESULTS Survival analysis of relapse and time to relapse showed a significant advantage for Escitalopram compared to placebo (log-rank test: p < .001). The risk of relapse was 2.8 times higher for placebo-treated patients than for Escitalopram-treated patients (p < .001), resulting in significantly fewer Escitalopram-treated patients relapsing (22% vs. 50%), at both doses. Escitalopram was well tolerated during double-blind treatment of generalized SAD, and only 2.6% of the Escitalopram-treated patients withdrew because of adverse events. The overall discontinuation rate, excluding relapses, was 13.2% for patients treated with Escitalopram and 8.3% for patients treated with placebo. CONCLUSION Escitalopram was effective and well tolerated in the long-term treatment of generalized SAD.
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Escitalopram in the treatment of social anxiety disorder randomised placebo controlled flexible dosage study
British Journal of Psychiatry, 2005Co-Authors: Siegfried Kasper, Henrik Loft, Dan J. Stein, Rico NilAbstract:Background Selective serotonin reuptake inhibitors are effective in the treatment of social anxiety disorder and are currently regarded as the pharmacotherapy of choice. Aims To investigate the efficacy and tolerability of Escitalopram in the treatment of generalised social anxiety disorder. Method Patients with generalised social anxiety disorder were randomised to receive placebo ( n =177) or 10-20 mg Escitalopram ( n =181) in a 12-week, double-blind trial. The primary outcome measure was the mean change from baseline to last assessment in the Liebowitz Social Anxiety Scale (LSAS) total score. Results The study showed a statistically superior therapeutic effect for Escitalopram compared with placebo on the LSAS total score ( P =0.005). There were significantly more responders to treatment for Escitalopram than for placebo (54% v . 39%; P <0.01). The clinical relevance of these findings was supported by significant reduction in the work and social components of the Sheehan Disability Scale and by the good tolerability of Escitalopram treatment. Conclusions Escitalopram was efficacious and well tolerated in the treatment of generalised social anxiety disorder.
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Escitalopram 10 mg day is effective and well tolerated in a placebo controlled study in depression in primary care
International Clinical Psychopharmacology, 2003Co-Authors: Ulla M Lepola, Henrik Loft, Elin Heldbo ReinesAbstract:Escitalopram was compared to placebo in moderately to severely depressed patients in primary care with citalopram as the active reference. Patients were randomized to receive flexible doses of 10-20 mg/day Escitalopram (n=155), 20-40 mg/day citalopram (n=160), or placebo (n=154) over an 8-week double-blind period. The primary efficacy parameter was the change from baseline to last assessment in the Montgomery-Asberg Depression Rating Scale total score. Escitalopram produced a statistically significant therapeutic difference of 2.9 points (P=0.002) compared to placebo, and Escitalopram was consistently and statistically significantly more efficacious than placebo from week 1 onwards. Analysis of Clinical Global Impression-Severity and Clinical Global Impression-Improvement confirmed the primary efficacy results. By week 8, significantly more patients had responded to treatment with Escitalopram than with citalopram (P=0.021) or placebo (P=0.009). Escitalopram was as well tolerated as citalopram and had a similar adverse event profile. Both Escitalopram- and citalopram-treated patients had placebo-level adverse event withdrawal rates (3% and 4%, respectively). This study demonstrates the consistent antidepressant efficacy and excellent tolerability of Escitalopram 10-20 mg/day in primary care patients with major depressive disorder.
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Escitalopram s enantiomer of citalopram clinical efficacy and onset of action predicted from a rat model
Pharmacology & Toxicology, 2001Co-Authors: Stuart A Montgomery, Elin Heldbo Reines, Connie Sanchez, Henrik Loft, Mariusz PappAbstract:Escitalopram is the active S-enantiomer of citalopram. In a chronic mild stress model of depression in rats, treatments with both Escitalopram and citalopram were effective; however, a faster time to onset of efficacy compared to vehicle treatment was observed for Escitalopram-treated (5 mg/kg/day) than for citalopram-treated (10 mg/kg/day) rats at Week 1. To study the predictability of this observation in the clinic, we analysed 4-week data from an 8-week, double-blind, randomised, placebo-controlled, flexible-dose study that compared Escitalopram and citalopram to placebo in primary care patients with major depressive disorder (baseline Montgomery and Asberg Depression Rating Scale (MADRS) scores > or =22 and < or =40). Since the flexible dosing started after Week 4, analysis of 4-week data ensured that the patients received fixed doses of 10 mg/day Escitalopram (155 patients), 20 mg/day citalopram (160 patients), or placebo (154 patients). The efficacy analysis showed a significantly superior therapeutic effect for Escitalopram versus placebo from Week 1 onwards (observed cases) with an adjusted mean change in MADRS at Week 4 (last observation carried forward) of 2.7 points (P=0.002). By comparison, 20 mg/day citalopram did not demonstrate a statistically significant effect compared to placebo. Escitalopram was well tolerated with an adverse event profile similar to that of citalopram. The preclinical observation that Escitalopram possesses a faster time to onset of efficacy than citalopram was also seen in primary care patients with major depressive disorder. Thus, Escitalopram is efficacious in depression and the effect occurs earlier than for citalopram.
Anjana Bose - One of the best experts on this subject based on the ideXlab platform.
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treatment of generalized anxiety disorder with Escitalopram pooled results from double blind placebo controlled trials
Journal of Affective Disorders, 2005Co-Authors: Wayne K Goodman, Anjana Bose, Qin WangAbstract:Abstract Background Escitalopram 10 mg/day is an effective and well-tolerated antidepressant. Three randomized controlled trials recently evaluated the safety and efficacy of Escitalopram in the treatment of generalized anxiety disorder (GAD). Methods The trial designs were virtually identical, allowing data to be pooled across studies. Male and female outpatients, ages 18–80 years, with DSM-IV-defined GAD were randomized to double-blind treatment with Escitalopram or placebo for 8 weeks. Escitalopram dose was fixed at 10 mg/day for the first 4 weeks, after which increases to 20 mg/day were permitted. The primary efficacy variable was the mean change from baseline in total Hamilton Anxiety Scale (HAMA) score. Results Approximately 850 patients were randomized to double-blind treatment. In each individual study, Escitalopram was significantly superior to placebo ( p p Limitations The studies included in this analysis were of short-term duration and excluded patients with significant medical and psychiatric comorbidities, such as major depressive disorder. Conclusion Results from the individual trials and the pooled analysis demonstrate that Escitalopram is effective and well tolerated for the treatment of GAD.
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a double blind comparison of Escitalopram and paroxetine in the long term treatment of generalized anxiety disorder
Annals of Clinical Psychiatry, 2005Co-Authors: Robert J Bielski, Anjana Bose, Chungchi ChangAbstract:Background. This study compared the efficacy and tolerability of Escitalopram, a newer SSRI, with paroxetine in the treatment of generalized anxiety disorder (GAD).Methods. Patients with DSM-IV-defined GAD were randomized to receive 24 weeks of double-blind flexible-dose treatment with either Escitalopram (10–20 mg/day) or paroxetine (20–50 mg/day), followed by a 2-week, double-blind, down-titration period. Mean change from baseline to endpoint (LOCF) in Hamilton Anxiety Scale (HAMA) scores was the primary efficacy variable.Results. Mean baseline HAMA scores for the Escitalopram (N=60) and paroxetine (N=61) groups were 23.7 and 23.4, respectively. After 24 weeks of treatment, mean changes in HAMA scores were −15.3 and −13.3 for Escitalopram and paroxetine, respectively (p=0.13). Significantly fewer patients withdrew from Escitalopram than paroxetine treatment due to adverse events (6.6% vs. 22.6%; p=0.02). The frequency of treatment-emergent adverse events was higher with paroxetine vs. Escitalopram: over...
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Escitalopram continuation treatment prevents relapse of depressive episodes.
The Journal of clinical psychiatry, 2004Co-Authors: Mark Hyman Rapaport, Anjana Bose, Hongjie ZhengAbstract:Background: Current guidelines for antidepressant use recommend 4 to 6 months of continuation treatment to prevent relapse of depression following symptom resolution. This study evaluates the efficacy and safety of continuation Escitalopram treatment. Method: Outpatients diagnosed with DSM-IV major depressive disorder (male or female, aged 18 to 81 years) who had completed 8 weeks of randomized double-blind treatment with Escitalopram, citalopram, or placebo entered an 8-week flexible-dose, open-label phase in which all patients received Escitalopram (10-20 mg/day). This study was initiated November 3, 1999, and completed April 5, 2001. Patients who met responder criteria (score of ≤ 12 on the Montgomery-Asberg Depression Rating Scale [MADRS]) were randomly assigned in a 2:1 ratio to Escitalopram (at the dose each patient was receiving at the end of the open-label phase) or placebo for 36 weeks of double-blind treatment. The primary efficacy variable was time to depression relapse (defined as MADRS score ≥ 22 or discontinuation due to an insufficient therapeutic response) from the start of the double-blind treatment phase. Results: A total of 502 patients received open-label Escitalopram treatment and had at least 1 MADRS assessment. A total of 274 evaluable subjects entered the double-blind treatment phase; 93 received placebo and 181 received Escitalopram. Time to depression relapse was significantly longer (p =.013) and the cumulative rate of relapse was significantly lower in patients who received Escitalopram (26% Escitalopram vs. 40% placebo; hazard ratio = 0.56; p =.01). Escitalopram-treated subjects had significantly lower depression ratings than those of placebo-treated patients. Escitalopram continuation treatment was safe and well tolerated. Discontinuation rates due to adverse events were 7% for the placebo group and 4% for the Escitalopram-treated group. Conclusion: Continuation treatment with Escitalopram is effective in preventing relapse into an episode of major depressive disorder.
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Escitalopram in the treatment of generalized anxiety disorder double blind placebo controlled flexible dose study
Depression and Anxiety, 2004Co-Authors: R Jonathan T M D Davidson, Andrew Korotzer, Anjana Bose, Hongjie ZhengAbstract:Escitalopram has been shown in clinical trials to improve anxiety symptoms associated with depression, panic disorder, and social anxiety disorder. This study was designed to evaluate the efficacy and tolerability of Escitalopram in the treatment of generalized anxiety disorder (GAD). Outpatients (18 years or older) who met DSM-IV criteria for GAD, with baseline Hamilton Rating Scale for Anxiety (HAMA) scores > or = 18, were randomly assigned to double blind treatment with Escitalopram (10 mg/day for the first 4 weeks and then flexibly dosed from 10-20 mg/day) or placebo for 8 weeks, following a 1-week, single-blind, placebo lead-in period. The primary efficacy variable was the mean change from baseline in total HAMA score at Week 8. The Escitalopram group (N = 158) showed a statistically significant, and clinically relevant, greater improvement at endpoint compared with placebo (N = 157) in all prospectively defined efficacy parameters. Significant improvement in HAMA total score and HAMA psychic anxiety subscale score for the Escitalopram-treated group vs. the placebo-treated group was observed beginning at Week 1 and at each study visit thereafter. Mean changes from baseline to Week 8 on the HAMA total score using a last-observation-carried-forward (LOCF) approach were -11.3 for Escitalopram and -7.4 for placebo (P<.001). Response rates at Week 8 were 68% for Escitalopram and 41% for placebo (P<.01) for completers, and 58% for Escitalopram and 38% for placebo LOCF values (P<.01). Treatment with Escitalopram was well tolerated, with low rates of reported adverse events and an incidence of discontinuation due to adverse events not statistically different from placebo (8.9% vs. 5.1%; P=.27). Escitalopram 10-20 mg/day is effective, safe, and well tolerated in the treatment of patients with GAD.
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fixed dose trial of the single isomer ssri Escitalopram in depressed outpatients
The Journal of Clinical Psychiatry, 2002Co-Authors: William J Burke, Ivan Gergel, Anjana BoseAbstract:Background Escitalopram is the single isomer responsible for the serotonin reuptake inhibition produced by the racemic antidepressant citalopram. The present randomized, double-blind, placebo-controlled, fixed-dose multicenter trial was designed to evaluate the efficacy and tolerability of Escitalopram in the treatment of major depressive disorder. Method Outpatients with an ongoing DSM-IV major depressive episode (N = 491) were randomly assigned to placebo, Escitalopram, 10 mg/day, Escitalopram, 20 mg/day, or citalopram, 40 mg/day, and entered an 8-week double-blind treatment period following a 1-week single-blind placebo lead-in. Clinical response was evaluated by the Montgomery-Asberg Depression Rating Scale (MADRS), the 24-item Hamilton Rating Scale for Depression (HAM-D), the Clinical Global Impressions (CGI) scales, the Hamilton Rating Scale for Anxiety (HAM-A), and patient-rated quality-of-life scales. Results Escitalopram, at both doses, produced significant improvement at study endpoint relative to placebo on all measures of depression; significant separation of Escitalopram from placebo was observed within I week of double-blind treatment. Citalopram treatment also significantly improved depressive symptomatology compared with placebo; however, Escitalopram, 10 mg/day, was at least as effective as citalopram, 40 mg/day, at endpoint. Anxiety symptoms and quality of life were also significantly improved by Escitalopram compared with placebo. The incidence of discontinuations due to adverse events for the Escitalopram 10 mg/day group was not different from the placebo group (4.2% vs. 2.5%; p = .50), and not different for the Escitalopram 20 mg/day group and the citalopram 40 mg/day group (10.4% vs. 8.8%; p = .83). Conclusion Escitalopram, a single isomer SSRI, is well-tolerated and has demonstrated antidepressant efficacy at a dose of 10 mg/day.