Escitalopram
Abstract Escitalopram is the therapeutically active S-enantiomer of RS-citalopram, a commonly prescribed SSRI. The R-enantiomer is essentially pharmacologically inactive. Escitalopram 10 or 20 mg/day produced significantly greater improvements in standard measurements of antidepressant effect (Montg...
Ausführliche Beschreibung
Autor*in: |
Waugh, John [verfasserIn] Goa, Karen L. [verfasserIn] |
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Format: |
E-Artikel |
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Sprache: |
Englisch |
Erschienen: |
2003 |
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Übergeordnetes Werk: |
Enthalten in: CNS drugs - Berlin [u.a.] : Springer, 1994, 17(2003), 5 vom: Apr., Seite 343-362 |
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Übergeordnetes Werk: |
volume:17 ; year:2003 ; number:5 ; month:04 ; pages:343-362 |
Links: |
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DOI / URN: |
10.2165/00023210-200317050-00004 |
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Katalog-ID: |
SPR033074348 |
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520 | |a Abstract Escitalopram is the therapeutically active S-enantiomer of RS-citalopram, a commonly prescribed SSRI. The R-enantiomer is essentially pharmacologically inactive. Escitalopram 10 or 20 mg/day produced significantly greater improvements in standard measurements of antidepressant effect (Montgomery-Åsberg Depression Rating Scale [MADRS], Clinical Global Impressions Improvement and Severity scales [CGI-I and CGI-S] and Hamilton Rating Scale for Depression [HAM-D]) in patients with major depressive disorder (MDD) than placebo in several 8-week, placebo-controlled, randomised, double-blind, multicentre studies. Symptom improvement was rapid, with some parameters improving within 1–2 weeks of starting escitalopram treatment. In addition, escitalopram showed earlier and clearer separation from placebo than RS-citalopram, at one-quarter to half the dosage, in 8-week, placebo-controlled trials; had significantly better efficacy than RS-citalopram in a subgroup of patients with moderate MDD in a 24-week trial; and produced sustained response and remission significantly faster than venlafaxine extended release in patients with MDD. Escitalopram reduced relapse rate compared with placebo and increased the percentage of patients in remission in long-term trials (up to 52 weeks). Consistently significant improvements for all efficacy parameters were also observed in patients with generalised anxiety disorder, social anxiety disorder and panic disorder treated with escitalopram for 8–12 weeks in individual, randomised, placebo-controlled, double-blind investigations. The good tolerability profile of escitalopram is predictable and similar to that of RS-citalopram. Such adverse events as nausea, ejaculatory problems, diarrhoea and insomnia are expected but, with the exception of ejaculatory problems and nausea, which is mild and transient, these were generally no more frequent than with placebo in fully published clinical trials. No adverse events not previously seen in acute trials were reported with long-term use. Conclusions: Escitalopram, the S-enantiomer of RS-citalopram, is a highly selectiveinhibitor for the serotonin transporter, ameliorates depressive symptoms in patients with MDD at half the RS-citalopram dosage, has a rapid onset of symptom improvement and has a predictable tolerability profile of generally mild adverse events. Like RS-citalopram, escitalopram is expected to have a low propensity for drug interactions, a potential benefit in the management of patients with comorbidities. In combination, these properties place escitalopram, like other SSRIs, as first-line therapy in patients with MDD. Escitalopram is indicated for use in patients with panic disorder in Europe and, should further evidence confirm early findings that escitalopram reduces anxiety, the drug may well find an additional role in the management of anxiety disorders. Pharmacodynamic Properties Escitalopram is the therapeutically active S-enantiomer of RS-citalopram, which is a highly selective and effective serotonin reuptake inhibitor. The antidepressant mechanism of escitalopram is presumed to be a result of stimulation of serotonergic neurotransmission in the CNS as a consequence of higher serotonin levels resulting from inhibition of the serotonin transporter. Escitalopram has no or very low affinity for a variety of other serotonin, dopamine, α- and β-adrenergic, histamine, muscarinic and benzodiazepine receptors. It also does not bind to or has low affinity for a range of ion channels including those for $ Na^{+} $], $ K^{+} $], $ Cl^{-} $] and $ Ca^{2+} $]. In rat models predictive of antidepressant activity, escitalopram demonstrated higher activity than RS- citalopram. The minimum effective dose was 4-fold lower with escitalopram than with RS-citalopram in reducing aggressive behaviour in the resident-intruder rat model and in reducing panic-like anxiety in rats after electrical stimulation of the dorsal peri-aquaductal grey matter. A trial using a conditioned fear model in rats found that escitalopram reversed suppression of exploratory activity more rapidly than a comparable dose of S-citalopram in RS-citalopram. This qualitative difference between S-citalopram and RS-citalopram was confirmed by another in vivo trial that showed higher extracellular serotonin concentrations in the frontal cortex of rats after injection with escitalopram than in rats treated with a racemic mixture of S-citalopram and R-citalopram, indicating inhibition of the S-enantiomer by the R-enantiomer in the racemate. Pharmacokinetic Properties Escitalopram shows linear and dose-proportional pharmacokinetics with steady—state plasma concentrations achieved in 1 week in healthy volunteers. The mean steady-state area under the plasma concentration-time curve (0–24h) after a dosage of 10 mg/day was 360.2 ng · h/mL in healthy volunteers. After a single dose of escitalopram 20mg, peak plasma concentrations were reached in 4–5 hours and were not affected by food intake. Absolute bioavailability of RS-citalopram is about 80% and binding to human plasma proteins of escitalopram is approximately 56%. The apparent volume of distribution of escitalopram after oral administration is 12–26 L/kg. The pharmacokinetic profile of the S-enantiomer is the same whether given as escitalopram 10mg or RS-citalopram 20mg. Escitalopram is transformed to two metabolites, S-demethylcitalopram and S-didemethylcitalopram, both of which are much less potent than the parent drug. Alernatively, the nitrogen atom may be oxidised to the N-oxide metabolite. Escitalopram is the predominant plasma compound. The primary isoenzymes involved in metabolising escitalopram are cytochrome P450 (CYP) 2C19, CYP3A4 and CYP2D6. Elimination of escitalopram is principally via hepatic and renal routes as metabolites. Oral clearance of escitalopram is 36 L/h (600 mL/min) and the elimination half-life (t1/2) is between 27 and 32 hours. There are no sex-related differences in escitalopram pharmacokinetics; however, escitalopram is eliminated more slowly in the elderly but maximum plasma concentration is unchanged thus increasing systemic exposure. In addition, oral clearance of RS-citalopram was reduced by 37% and t1/2; doubled in patients with hepatic impairment. Therapeutic Efficacy Antidepressive efficacy was observed in patients with major depressive disorder (MDD) in 8-week trials with significant improvements in Montgomery-Åsberg Depression Rating Scale (MADRS) scores in patients receiving escitalopram 10 or 20 mg/day versus those receiving placebo noted as early as 1–2 weeks after starting therapy. Follow-on studies found that escitalopram reduced the long-term risk of relapse and continued to reduce MADRS scores. Significant improvements ere also observed in all secondary efficacy parameters including the Hamilton Rating Scale for Depression (HAM-D) and the Clinical Global Impressions Improvement and Severity scales (CGI-I and CGI-S) scores, and at least half of patients receiving escitalopram responded to treatment. Escitalopram showed earlier and better efficacy than RS-citalopram in a subgroup of patients with moderate MDD after 24 weeks and produced sustained response and remission significantly more rapidly (p < 0.05) than venlafaxine extended release (XR) at several timepoints over 8 weeks in patients with this disorder. In addition, improvements in quality of life (QOL) were experienced in the one study to report this. Significantly greater reductions in Hamilton Rating Scale for Anxiety (HAM-A) scores were observed in 124 patients, meeting the DSM-IV criteria for generalised anxiety disorder (GAD), who received escitalopram than in 128 patients meeting the same criteria who received placebo for 8 weeks. Improvements were also observed in several secondary efficacy parameters in the patients receiving escitalopram. In a 12-week study in patients who met the DSM-IV criteria for social anxiety disorder (SAD), those receiving escitalopram (n = 181 ) showed greater reductions in all SAD measurement scores and in disability scores than those receiving placebo (n = 177). The primary efficacy parameter was changes in Liebowitz Social Anxiety Scale scores from baseline to week 12. Secondary efficacy parameters included CGI-I scores, changes in CGI-S scores and Sheehan Disability scores over the same period. Escitalopram was significantly more effective than placebo in the treatment of panic disorder for all efficacy parameters in a 10-week trial. Efficacy measurements included frequency of panic attacks, the Panic and Anticipatory Anxiety Scale, Panic and Agoraphobia Scale, HAM-A, CGI-I and CGI-S scores, the Patient Global Evaluation and a QOL questionnaire. Improvements were apparent by week 4 in patients with GAD or panic disorder. Pharmacoeconomics Two decision analytic studies carried out in Finland and Sweden found that, when used to treat MDD, escitalopram was more cost effective than RS-citalopram, fluoxetin... | ||
650 | 4 | |a Major Depressive Disorder |7 (dpeaa)DE-He213 | |
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650 | 4 | |a Major Depressive Disorder |7 (dpeaa)DE-He213 | |
650 | 4 | |a Social Anxiety Disorder |7 (dpeaa)DE-He213 | |
700 | 1 | |a Goa, Karen L. |e verfasserin |4 aut | |
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10.2165/00023210-200317050-00004 doi (DE-627)SPR033074348 (SPR)00023210-200317050-00004-e DE-627 ger DE-627 rakwb eng 610 ASE 44.40 bkl Waugh, John verfasserin aut Escitalopram 2003 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Escitalopram is the therapeutically active S-enantiomer of RS-citalopram, a commonly prescribed SSRI. The R-enantiomer is essentially pharmacologically inactive. Escitalopram 10 or 20 mg/day produced significantly greater improvements in standard measurements of antidepressant effect (Montgomery-Åsberg Depression Rating Scale [MADRS], Clinical Global Impressions Improvement and Severity scales [CGI-I and CGI-S] and Hamilton Rating Scale for Depression [HAM-D]) in patients with major depressive disorder (MDD) than placebo in several 8-week, placebo-controlled, randomised, double-blind, multicentre studies. Symptom improvement was rapid, with some parameters improving within 1–2 weeks of starting escitalopram treatment. In addition, escitalopram showed earlier and clearer separation from placebo than RS-citalopram, at one-quarter to half the dosage, in 8-week, placebo-controlled trials; had significantly better efficacy than RS-citalopram in a subgroup of patients with moderate MDD in a 24-week trial; and produced sustained response and remission significantly faster than venlafaxine extended release in patients with MDD. Escitalopram reduced relapse rate compared with placebo and increased the percentage of patients in remission in long-term trials (up to 52 weeks). Consistently significant improvements for all efficacy parameters were also observed in patients with generalised anxiety disorder, social anxiety disorder and panic disorder treated with escitalopram for 8–12 weeks in individual, randomised, placebo-controlled, double-blind investigations. The good tolerability profile of escitalopram is predictable and similar to that of RS-citalopram. Such adverse events as nausea, ejaculatory problems, diarrhoea and insomnia are expected but, with the exception of ejaculatory problems and nausea, which is mild and transient, these were generally no more frequent than with placebo in fully published clinical trials. No adverse events not previously seen in acute trials were reported with long-term use. Conclusions: Escitalopram, the S-enantiomer of RS-citalopram, is a highly selectiveinhibitor for the serotonin transporter, ameliorates depressive symptoms in patients with MDD at half the RS-citalopram dosage, has a rapid onset of symptom improvement and has a predictable tolerability profile of generally mild adverse events. Like RS-citalopram, escitalopram is expected to have a low propensity for drug interactions, a potential benefit in the management of patients with comorbidities. In combination, these properties place escitalopram, like other SSRIs, as first-line therapy in patients with MDD. Escitalopram is indicated for use in patients with panic disorder in Europe and, should further evidence confirm early findings that escitalopram reduces anxiety, the drug may well find an additional role in the management of anxiety disorders. Pharmacodynamic Properties Escitalopram is the therapeutically active S-enantiomer of RS-citalopram, which is a highly selective and effective serotonin reuptake inhibitor. The antidepressant mechanism of escitalopram is presumed to be a result of stimulation of serotonergic neurotransmission in the CNS as a consequence of higher serotonin levels resulting from inhibition of the serotonin transporter. Escitalopram has no or very low affinity for a variety of other serotonin, dopamine, α- and β-adrenergic, histamine, muscarinic and benzodiazepine receptors. It also does not bind to or has low affinity for a range of ion channels including those for $ Na^{+} $], $ K^{+} $], $ Cl^{-} $] and $ Ca^{2+} $]. In rat models predictive of antidepressant activity, escitalopram demonstrated higher activity than RS- citalopram. The minimum effective dose was 4-fold lower with escitalopram than with RS-citalopram in reducing aggressive behaviour in the resident-intruder rat model and in reducing panic-like anxiety in rats after electrical stimulation of the dorsal peri-aquaductal grey matter. A trial using a conditioned fear model in rats found that escitalopram reversed suppression of exploratory activity more rapidly than a comparable dose of S-citalopram in RS-citalopram. This qualitative difference between S-citalopram and RS-citalopram was confirmed by another in vivo trial that showed higher extracellular serotonin concentrations in the frontal cortex of rats after injection with escitalopram than in rats treated with a racemic mixture of S-citalopram and R-citalopram, indicating inhibition of the S-enantiomer by the R-enantiomer in the racemate. Pharmacokinetic Properties Escitalopram shows linear and dose-proportional pharmacokinetics with steady—state plasma concentrations achieved in 1 week in healthy volunteers. The mean steady-state area under the plasma concentration-time curve (0–24h) after a dosage of 10 mg/day was 360.2 ng · h/mL in healthy volunteers. After a single dose of escitalopram 20mg, peak plasma concentrations were reached in 4–5 hours and were not affected by food intake. Absolute bioavailability of RS-citalopram is about 80% and binding to human plasma proteins of escitalopram is approximately 56%. The apparent volume of distribution of escitalopram after oral administration is 12–26 L/kg. The pharmacokinetic profile of the S-enantiomer is the same whether given as escitalopram 10mg or RS-citalopram 20mg. Escitalopram is transformed to two metabolites, S-demethylcitalopram and S-didemethylcitalopram, both of which are much less potent than the parent drug. Alernatively, the nitrogen atom may be oxidised to the N-oxide metabolite. Escitalopram is the predominant plasma compound. The primary isoenzymes involved in metabolising escitalopram are cytochrome P450 (CYP) 2C19, CYP3A4 and CYP2D6. Elimination of escitalopram is principally via hepatic and renal routes as metabolites. Oral clearance of escitalopram is 36 L/h (600 mL/min) and the elimination half-life (t1/2) is between 27 and 32 hours. There are no sex-related differences in escitalopram pharmacokinetics; however, escitalopram is eliminated more slowly in the elderly but maximum plasma concentration is unchanged thus increasing systemic exposure. In addition, oral clearance of RS-citalopram was reduced by 37% and t1/2; doubled in patients with hepatic impairment. Therapeutic Efficacy Antidepressive efficacy was observed in patients with major depressive disorder (MDD) in 8-week trials with significant improvements in Montgomery-Åsberg Depression Rating Scale (MADRS) scores in patients receiving escitalopram 10 or 20 mg/day versus those receiving placebo noted as early as 1–2 weeks after starting therapy. Follow-on studies found that escitalopram reduced the long-term risk of relapse and continued to reduce MADRS scores. Significant improvements ere also observed in all secondary efficacy parameters including the Hamilton Rating Scale for Depression (HAM-D) and the Clinical Global Impressions Improvement and Severity scales (CGI-I and CGI-S) scores, and at least half of patients receiving escitalopram responded to treatment. Escitalopram showed earlier and better efficacy than RS-citalopram in a subgroup of patients with moderate MDD after 24 weeks and produced sustained response and remission significantly more rapidly (p < 0.05) than venlafaxine extended release (XR) at several timepoints over 8 weeks in patients with this disorder. In addition, improvements in quality of life (QOL) were experienced in the one study to report this. Significantly greater reductions in Hamilton Rating Scale for Anxiety (HAM-A) scores were observed in 124 patients, meeting the DSM-IV criteria for generalised anxiety disorder (GAD), who received escitalopram than in 128 patients meeting the same criteria who received placebo for 8 weeks. Improvements were also observed in several secondary efficacy parameters in the patients receiving escitalopram. In a 12-week study in patients who met the DSM-IV criteria for social anxiety disorder (SAD), those receiving escitalopram (n = 181 ) showed greater reductions in all SAD measurement scores and in disability scores than those receiving placebo (n = 177). The primary efficacy parameter was changes in Liebowitz Social Anxiety Scale scores from baseline to week 12. Secondary efficacy parameters included CGI-I scores, changes in CGI-S scores and Sheehan Disability scores over the same period. Escitalopram was significantly more effective than placebo in the treatment of panic disorder for all efficacy parameters in a 10-week trial. Efficacy measurements included frequency of panic attacks, the Panic and Anticipatory Anxiety Scale, Panic and Agoraphobia Scale, HAM-A, CGI-I and CGI-S scores, the Patient Global Evaluation and a QOL questionnaire. Improvements were apparent by week 4 in patients with GAD or panic disorder. Pharmacoeconomics Two decision analytic studies carried out in Finland and Sweden found that, when used to treat MDD, escitalopram was more cost effective than RS-citalopram, fluoxetin... Major Depressive Disorder (dpeaa)DE-He213 Anxiety Disorder (dpeaa)DE-He213 Venlafaxine (dpeaa)DE-He213 Major Depressive Disorder (dpeaa)DE-He213 Social Anxiety Disorder (dpeaa)DE-He213 Goa, Karen L. verfasserin aut Enthalten in CNS drugs Berlin [u.a.] : Springer, 1994 17(2003), 5 vom: Apr., Seite 343-362 (DE-627)327645172 (DE-600)2043806-0 1179-1934 nnns volume:17 year:2003 number:5 month:04 pages:343-362 https://dx.doi.org/10.2165/00023210-200317050-00004 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA SSG-OPC-PHA SSG-OPC-ASE GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_266 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 44.40 ASE AR 17 2003 5 04 343-362 |
spelling |
10.2165/00023210-200317050-00004 doi (DE-627)SPR033074348 (SPR)00023210-200317050-00004-e DE-627 ger DE-627 rakwb eng 610 ASE 44.40 bkl Waugh, John verfasserin aut Escitalopram 2003 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Escitalopram is the therapeutically active S-enantiomer of RS-citalopram, a commonly prescribed SSRI. The R-enantiomer is essentially pharmacologically inactive. Escitalopram 10 or 20 mg/day produced significantly greater improvements in standard measurements of antidepressant effect (Montgomery-Åsberg Depression Rating Scale [MADRS], Clinical Global Impressions Improvement and Severity scales [CGI-I and CGI-S] and Hamilton Rating Scale for Depression [HAM-D]) in patients with major depressive disorder (MDD) than placebo in several 8-week, placebo-controlled, randomised, double-blind, multicentre studies. Symptom improvement was rapid, with some parameters improving within 1–2 weeks of starting escitalopram treatment. In addition, escitalopram showed earlier and clearer separation from placebo than RS-citalopram, at one-quarter to half the dosage, in 8-week, placebo-controlled trials; had significantly better efficacy than RS-citalopram in a subgroup of patients with moderate MDD in a 24-week trial; and produced sustained response and remission significantly faster than venlafaxine extended release in patients with MDD. Escitalopram reduced relapse rate compared with placebo and increased the percentage of patients in remission in long-term trials (up to 52 weeks). Consistently significant improvements for all efficacy parameters were also observed in patients with generalised anxiety disorder, social anxiety disorder and panic disorder treated with escitalopram for 8–12 weeks in individual, randomised, placebo-controlled, double-blind investigations. The good tolerability profile of escitalopram is predictable and similar to that of RS-citalopram. Such adverse events as nausea, ejaculatory problems, diarrhoea and insomnia are expected but, with the exception of ejaculatory problems and nausea, which is mild and transient, these were generally no more frequent than with placebo in fully published clinical trials. No adverse events not previously seen in acute trials were reported with long-term use. Conclusions: Escitalopram, the S-enantiomer of RS-citalopram, is a highly selectiveinhibitor for the serotonin transporter, ameliorates depressive symptoms in patients with MDD at half the RS-citalopram dosage, has a rapid onset of symptom improvement and has a predictable tolerability profile of generally mild adverse events. Like RS-citalopram, escitalopram is expected to have a low propensity for drug interactions, a potential benefit in the management of patients with comorbidities. In combination, these properties place escitalopram, like other SSRIs, as first-line therapy in patients with MDD. Escitalopram is indicated for use in patients with panic disorder in Europe and, should further evidence confirm early findings that escitalopram reduces anxiety, the drug may well find an additional role in the management of anxiety disorders. Pharmacodynamic Properties Escitalopram is the therapeutically active S-enantiomer of RS-citalopram, which is a highly selective and effective serotonin reuptake inhibitor. The antidepressant mechanism of escitalopram is presumed to be a result of stimulation of serotonergic neurotransmission in the CNS as a consequence of higher serotonin levels resulting from inhibition of the serotonin transporter. Escitalopram has no or very low affinity for a variety of other serotonin, dopamine, α- and β-adrenergic, histamine, muscarinic and benzodiazepine receptors. It also does not bind to or has low affinity for a range of ion channels including those for $ Na^{+} $], $ K^{+} $], $ Cl^{-} $] and $ Ca^{2+} $]. In rat models predictive of antidepressant activity, escitalopram demonstrated higher activity than RS- citalopram. The minimum effective dose was 4-fold lower with escitalopram than with RS-citalopram in reducing aggressive behaviour in the resident-intruder rat model and in reducing panic-like anxiety in rats after electrical stimulation of the dorsal peri-aquaductal grey matter. A trial using a conditioned fear model in rats found that escitalopram reversed suppression of exploratory activity more rapidly than a comparable dose of S-citalopram in RS-citalopram. This qualitative difference between S-citalopram and RS-citalopram was confirmed by another in vivo trial that showed higher extracellular serotonin concentrations in the frontal cortex of rats after injection with escitalopram than in rats treated with a racemic mixture of S-citalopram and R-citalopram, indicating inhibition of the S-enantiomer by the R-enantiomer in the racemate. Pharmacokinetic Properties Escitalopram shows linear and dose-proportional pharmacokinetics with steady—state plasma concentrations achieved in 1 week in healthy volunteers. The mean steady-state area under the plasma concentration-time curve (0–24h) after a dosage of 10 mg/day was 360.2 ng · h/mL in healthy volunteers. After a single dose of escitalopram 20mg, peak plasma concentrations were reached in 4–5 hours and were not affected by food intake. Absolute bioavailability of RS-citalopram is about 80% and binding to human plasma proteins of escitalopram is approximately 56%. The apparent volume of distribution of escitalopram after oral administration is 12–26 L/kg. The pharmacokinetic profile of the S-enantiomer is the same whether given as escitalopram 10mg or RS-citalopram 20mg. Escitalopram is transformed to two metabolites, S-demethylcitalopram and S-didemethylcitalopram, both of which are much less potent than the parent drug. Alernatively, the nitrogen atom may be oxidised to the N-oxide metabolite. Escitalopram is the predominant plasma compound. The primary isoenzymes involved in metabolising escitalopram are cytochrome P450 (CYP) 2C19, CYP3A4 and CYP2D6. Elimination of escitalopram is principally via hepatic and renal routes as metabolites. Oral clearance of escitalopram is 36 L/h (600 mL/min) and the elimination half-life (t1/2) is between 27 and 32 hours. There are no sex-related differences in escitalopram pharmacokinetics; however, escitalopram is eliminated more slowly in the elderly but maximum plasma concentration is unchanged thus increasing systemic exposure. In addition, oral clearance of RS-citalopram was reduced by 37% and t1/2; doubled in patients with hepatic impairment. Therapeutic Efficacy Antidepressive efficacy was observed in patients with major depressive disorder (MDD) in 8-week trials with significant improvements in Montgomery-Åsberg Depression Rating Scale (MADRS) scores in patients receiving escitalopram 10 or 20 mg/day versus those receiving placebo noted as early as 1–2 weeks after starting therapy. Follow-on studies found that escitalopram reduced the long-term risk of relapse and continued to reduce MADRS scores. Significant improvements ere also observed in all secondary efficacy parameters including the Hamilton Rating Scale for Depression (HAM-D) and the Clinical Global Impressions Improvement and Severity scales (CGI-I and CGI-S) scores, and at least half of patients receiving escitalopram responded to treatment. Escitalopram showed earlier and better efficacy than RS-citalopram in a subgroup of patients with moderate MDD after 24 weeks and produced sustained response and remission significantly more rapidly (p < 0.05) than venlafaxine extended release (XR) at several timepoints over 8 weeks in patients with this disorder. In addition, improvements in quality of life (QOL) were experienced in the one study to report this. Significantly greater reductions in Hamilton Rating Scale for Anxiety (HAM-A) scores were observed in 124 patients, meeting the DSM-IV criteria for generalised anxiety disorder (GAD), who received escitalopram than in 128 patients meeting the same criteria who received placebo for 8 weeks. Improvements were also observed in several secondary efficacy parameters in the patients receiving escitalopram. In a 12-week study in patients who met the DSM-IV criteria for social anxiety disorder (SAD), those receiving escitalopram (n = 181 ) showed greater reductions in all SAD measurement scores and in disability scores than those receiving placebo (n = 177). The primary efficacy parameter was changes in Liebowitz Social Anxiety Scale scores from baseline to week 12. Secondary efficacy parameters included CGI-I scores, changes in CGI-S scores and Sheehan Disability scores over the same period. Escitalopram was significantly more effective than placebo in the treatment of panic disorder for all efficacy parameters in a 10-week trial. Efficacy measurements included frequency of panic attacks, the Panic and Anticipatory Anxiety Scale, Panic and Agoraphobia Scale, HAM-A, CGI-I and CGI-S scores, the Patient Global Evaluation and a QOL questionnaire. Improvements were apparent by week 4 in patients with GAD or panic disorder. Pharmacoeconomics Two decision analytic studies carried out in Finland and Sweden found that, when used to treat MDD, escitalopram was more cost effective than RS-citalopram, fluoxetin... Major Depressive Disorder (dpeaa)DE-He213 Anxiety Disorder (dpeaa)DE-He213 Venlafaxine (dpeaa)DE-He213 Major Depressive Disorder (dpeaa)DE-He213 Social Anxiety Disorder (dpeaa)DE-He213 Goa, Karen L. verfasserin aut Enthalten in CNS drugs Berlin [u.a.] : Springer, 1994 17(2003), 5 vom: Apr., Seite 343-362 (DE-627)327645172 (DE-600)2043806-0 1179-1934 nnns volume:17 year:2003 number:5 month:04 pages:343-362 https://dx.doi.org/10.2165/00023210-200317050-00004 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA SSG-OPC-PHA SSG-OPC-ASE GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_266 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 44.40 ASE AR 17 2003 5 04 343-362 |
allfields_unstemmed |
10.2165/00023210-200317050-00004 doi (DE-627)SPR033074348 (SPR)00023210-200317050-00004-e DE-627 ger DE-627 rakwb eng 610 ASE 44.40 bkl Waugh, John verfasserin aut Escitalopram 2003 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Escitalopram is the therapeutically active S-enantiomer of RS-citalopram, a commonly prescribed SSRI. The R-enantiomer is essentially pharmacologically inactive. Escitalopram 10 or 20 mg/day produced significantly greater improvements in standard measurements of antidepressant effect (Montgomery-Åsberg Depression Rating Scale [MADRS], Clinical Global Impressions Improvement and Severity scales [CGI-I and CGI-S] and Hamilton Rating Scale for Depression [HAM-D]) in patients with major depressive disorder (MDD) than placebo in several 8-week, placebo-controlled, randomised, double-blind, multicentre studies. Symptom improvement was rapid, with some parameters improving within 1–2 weeks of starting escitalopram treatment. In addition, escitalopram showed earlier and clearer separation from placebo than RS-citalopram, at one-quarter to half the dosage, in 8-week, placebo-controlled trials; had significantly better efficacy than RS-citalopram in a subgroup of patients with moderate MDD in a 24-week trial; and produced sustained response and remission significantly faster than venlafaxine extended release in patients with MDD. Escitalopram reduced relapse rate compared with placebo and increased the percentage of patients in remission in long-term trials (up to 52 weeks). Consistently significant improvements for all efficacy parameters were also observed in patients with generalised anxiety disorder, social anxiety disorder and panic disorder treated with escitalopram for 8–12 weeks in individual, randomised, placebo-controlled, double-blind investigations. The good tolerability profile of escitalopram is predictable and similar to that of RS-citalopram. Such adverse events as nausea, ejaculatory problems, diarrhoea and insomnia are expected but, with the exception of ejaculatory problems and nausea, which is mild and transient, these were generally no more frequent than with placebo in fully published clinical trials. No adverse events not previously seen in acute trials were reported with long-term use. Conclusions: Escitalopram, the S-enantiomer of RS-citalopram, is a highly selectiveinhibitor for the serotonin transporter, ameliorates depressive symptoms in patients with MDD at half the RS-citalopram dosage, has a rapid onset of symptom improvement and has a predictable tolerability profile of generally mild adverse events. Like RS-citalopram, escitalopram is expected to have a low propensity for drug interactions, a potential benefit in the management of patients with comorbidities. In combination, these properties place escitalopram, like other SSRIs, as first-line therapy in patients with MDD. Escitalopram is indicated for use in patients with panic disorder in Europe and, should further evidence confirm early findings that escitalopram reduces anxiety, the drug may well find an additional role in the management of anxiety disorders. Pharmacodynamic Properties Escitalopram is the therapeutically active S-enantiomer of RS-citalopram, which is a highly selective and effective serotonin reuptake inhibitor. The antidepressant mechanism of escitalopram is presumed to be a result of stimulation of serotonergic neurotransmission in the CNS as a consequence of higher serotonin levels resulting from inhibition of the serotonin transporter. Escitalopram has no or very low affinity for a variety of other serotonin, dopamine, α- and β-adrenergic, histamine, muscarinic and benzodiazepine receptors. It also does not bind to or has low affinity for a range of ion channels including those for $ Na^{+} $], $ K^{+} $], $ Cl^{-} $] and $ Ca^{2+} $]. In rat models predictive of antidepressant activity, escitalopram demonstrated higher activity than RS- citalopram. The minimum effective dose was 4-fold lower with escitalopram than with RS-citalopram in reducing aggressive behaviour in the resident-intruder rat model and in reducing panic-like anxiety in rats after electrical stimulation of the dorsal peri-aquaductal grey matter. A trial using a conditioned fear model in rats found that escitalopram reversed suppression of exploratory activity more rapidly than a comparable dose of S-citalopram in RS-citalopram. This qualitative difference between S-citalopram and RS-citalopram was confirmed by another in vivo trial that showed higher extracellular serotonin concentrations in the frontal cortex of rats after injection with escitalopram than in rats treated with a racemic mixture of S-citalopram and R-citalopram, indicating inhibition of the S-enantiomer by the R-enantiomer in the racemate. Pharmacokinetic Properties Escitalopram shows linear and dose-proportional pharmacokinetics with steady—state plasma concentrations achieved in 1 week in healthy volunteers. The mean steady-state area under the plasma concentration-time curve (0–24h) after a dosage of 10 mg/day was 360.2 ng · h/mL in healthy volunteers. After a single dose of escitalopram 20mg, peak plasma concentrations were reached in 4–5 hours and were not affected by food intake. Absolute bioavailability of RS-citalopram is about 80% and binding to human plasma proteins of escitalopram is approximately 56%. The apparent volume of distribution of escitalopram after oral administration is 12–26 L/kg. The pharmacokinetic profile of the S-enantiomer is the same whether given as escitalopram 10mg or RS-citalopram 20mg. Escitalopram is transformed to two metabolites, S-demethylcitalopram and S-didemethylcitalopram, both of which are much less potent than the parent drug. Alernatively, the nitrogen atom may be oxidised to the N-oxide metabolite. Escitalopram is the predominant plasma compound. The primary isoenzymes involved in metabolising escitalopram are cytochrome P450 (CYP) 2C19, CYP3A4 and CYP2D6. Elimination of escitalopram is principally via hepatic and renal routes as metabolites. Oral clearance of escitalopram is 36 L/h (600 mL/min) and the elimination half-life (t1/2) is between 27 and 32 hours. There are no sex-related differences in escitalopram pharmacokinetics; however, escitalopram is eliminated more slowly in the elderly but maximum plasma concentration is unchanged thus increasing systemic exposure. In addition, oral clearance of RS-citalopram was reduced by 37% and t1/2; doubled in patients with hepatic impairment. Therapeutic Efficacy Antidepressive efficacy was observed in patients with major depressive disorder (MDD) in 8-week trials with significant improvements in Montgomery-Åsberg Depression Rating Scale (MADRS) scores in patients receiving escitalopram 10 or 20 mg/day versus those receiving placebo noted as early as 1–2 weeks after starting therapy. Follow-on studies found that escitalopram reduced the long-term risk of relapse and continued to reduce MADRS scores. Significant improvements ere also observed in all secondary efficacy parameters including the Hamilton Rating Scale for Depression (HAM-D) and the Clinical Global Impressions Improvement and Severity scales (CGI-I and CGI-S) scores, and at least half of patients receiving escitalopram responded to treatment. Escitalopram showed earlier and better efficacy than RS-citalopram in a subgroup of patients with moderate MDD after 24 weeks and produced sustained response and remission significantly more rapidly (p < 0.05) than venlafaxine extended release (XR) at several timepoints over 8 weeks in patients with this disorder. In addition, improvements in quality of life (QOL) were experienced in the one study to report this. Significantly greater reductions in Hamilton Rating Scale for Anxiety (HAM-A) scores were observed in 124 patients, meeting the DSM-IV criteria for generalised anxiety disorder (GAD), who received escitalopram than in 128 patients meeting the same criteria who received placebo for 8 weeks. Improvements were also observed in several secondary efficacy parameters in the patients receiving escitalopram. In a 12-week study in patients who met the DSM-IV criteria for social anxiety disorder (SAD), those receiving escitalopram (n = 181 ) showed greater reductions in all SAD measurement scores and in disability scores than those receiving placebo (n = 177). The primary efficacy parameter was changes in Liebowitz Social Anxiety Scale scores from baseline to week 12. Secondary efficacy parameters included CGI-I scores, changes in CGI-S scores and Sheehan Disability scores over the same period. Escitalopram was significantly more effective than placebo in the treatment of panic disorder for all efficacy parameters in a 10-week trial. Efficacy measurements included frequency of panic attacks, the Panic and Anticipatory Anxiety Scale, Panic and Agoraphobia Scale, HAM-A, CGI-I and CGI-S scores, the Patient Global Evaluation and a QOL questionnaire. Improvements were apparent by week 4 in patients with GAD or panic disorder. Pharmacoeconomics Two decision analytic studies carried out in Finland and Sweden found that, when used to treat MDD, escitalopram was more cost effective than RS-citalopram, fluoxetin... Major Depressive Disorder (dpeaa)DE-He213 Anxiety Disorder (dpeaa)DE-He213 Venlafaxine (dpeaa)DE-He213 Major Depressive Disorder (dpeaa)DE-He213 Social Anxiety Disorder (dpeaa)DE-He213 Goa, Karen L. verfasserin aut Enthalten in CNS drugs Berlin [u.a.] : Springer, 1994 17(2003), 5 vom: Apr., Seite 343-362 (DE-627)327645172 (DE-600)2043806-0 1179-1934 nnns volume:17 year:2003 number:5 month:04 pages:343-362 https://dx.doi.org/10.2165/00023210-200317050-00004 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA SSG-OPC-PHA SSG-OPC-ASE GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_266 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 44.40 ASE AR 17 2003 5 04 343-362 |
allfieldsGer |
10.2165/00023210-200317050-00004 doi (DE-627)SPR033074348 (SPR)00023210-200317050-00004-e DE-627 ger DE-627 rakwb eng 610 ASE 44.40 bkl Waugh, John verfasserin aut Escitalopram 2003 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Escitalopram is the therapeutically active S-enantiomer of RS-citalopram, a commonly prescribed SSRI. The R-enantiomer is essentially pharmacologically inactive. Escitalopram 10 or 20 mg/day produced significantly greater improvements in standard measurements of antidepressant effect (Montgomery-Åsberg Depression Rating Scale [MADRS], Clinical Global Impressions Improvement and Severity scales [CGI-I and CGI-S] and Hamilton Rating Scale for Depression [HAM-D]) in patients with major depressive disorder (MDD) than placebo in several 8-week, placebo-controlled, randomised, double-blind, multicentre studies. Symptom improvement was rapid, with some parameters improving within 1–2 weeks of starting escitalopram treatment. In addition, escitalopram showed earlier and clearer separation from placebo than RS-citalopram, at one-quarter to half the dosage, in 8-week, placebo-controlled trials; had significantly better efficacy than RS-citalopram in a subgroup of patients with moderate MDD in a 24-week trial; and produced sustained response and remission significantly faster than venlafaxine extended release in patients with MDD. Escitalopram reduced relapse rate compared with placebo and increased the percentage of patients in remission in long-term trials (up to 52 weeks). Consistently significant improvements for all efficacy parameters were also observed in patients with generalised anxiety disorder, social anxiety disorder and panic disorder treated with escitalopram for 8–12 weeks in individual, randomised, placebo-controlled, double-blind investigations. The good tolerability profile of escitalopram is predictable and similar to that of RS-citalopram. Such adverse events as nausea, ejaculatory problems, diarrhoea and insomnia are expected but, with the exception of ejaculatory problems and nausea, which is mild and transient, these were generally no more frequent than with placebo in fully published clinical trials. No adverse events not previously seen in acute trials were reported with long-term use. Conclusions: Escitalopram, the S-enantiomer of RS-citalopram, is a highly selectiveinhibitor for the serotonin transporter, ameliorates depressive symptoms in patients with MDD at half the RS-citalopram dosage, has a rapid onset of symptom improvement and has a predictable tolerability profile of generally mild adverse events. Like RS-citalopram, escitalopram is expected to have a low propensity for drug interactions, a potential benefit in the management of patients with comorbidities. In combination, these properties place escitalopram, like other SSRIs, as first-line therapy in patients with MDD. Escitalopram is indicated for use in patients with panic disorder in Europe and, should further evidence confirm early findings that escitalopram reduces anxiety, the drug may well find an additional role in the management of anxiety disorders. Pharmacodynamic Properties Escitalopram is the therapeutically active S-enantiomer of RS-citalopram, which is a highly selective and effective serotonin reuptake inhibitor. The antidepressant mechanism of escitalopram is presumed to be a result of stimulation of serotonergic neurotransmission in the CNS as a consequence of higher serotonin levels resulting from inhibition of the serotonin transporter. Escitalopram has no or very low affinity for a variety of other serotonin, dopamine, α- and β-adrenergic, histamine, muscarinic and benzodiazepine receptors. It also does not bind to or has low affinity for a range of ion channels including those for $ Na^{+} $], $ K^{+} $], $ Cl^{-} $] and $ Ca^{2+} $]. In rat models predictive of antidepressant activity, escitalopram demonstrated higher activity than RS- citalopram. The minimum effective dose was 4-fold lower with escitalopram than with RS-citalopram in reducing aggressive behaviour in the resident-intruder rat model and in reducing panic-like anxiety in rats after electrical stimulation of the dorsal peri-aquaductal grey matter. A trial using a conditioned fear model in rats found that escitalopram reversed suppression of exploratory activity more rapidly than a comparable dose of S-citalopram in RS-citalopram. This qualitative difference between S-citalopram and RS-citalopram was confirmed by another in vivo trial that showed higher extracellular serotonin concentrations in the frontal cortex of rats after injection with escitalopram than in rats treated with a racemic mixture of S-citalopram and R-citalopram, indicating inhibition of the S-enantiomer by the R-enantiomer in the racemate. Pharmacokinetic Properties Escitalopram shows linear and dose-proportional pharmacokinetics with steady—state plasma concentrations achieved in 1 week in healthy volunteers. The mean steady-state area under the plasma concentration-time curve (0–24h) after a dosage of 10 mg/day was 360.2 ng · h/mL in healthy volunteers. After a single dose of escitalopram 20mg, peak plasma concentrations were reached in 4–5 hours and were not affected by food intake. Absolute bioavailability of RS-citalopram is about 80% and binding to human plasma proteins of escitalopram is approximately 56%. The apparent volume of distribution of escitalopram after oral administration is 12–26 L/kg. The pharmacokinetic profile of the S-enantiomer is the same whether given as escitalopram 10mg or RS-citalopram 20mg. Escitalopram is transformed to two metabolites, S-demethylcitalopram and S-didemethylcitalopram, both of which are much less potent than the parent drug. Alernatively, the nitrogen atom may be oxidised to the N-oxide metabolite. Escitalopram is the predominant plasma compound. The primary isoenzymes involved in metabolising escitalopram are cytochrome P450 (CYP) 2C19, CYP3A4 and CYP2D6. Elimination of escitalopram is principally via hepatic and renal routes as metabolites. Oral clearance of escitalopram is 36 L/h (600 mL/min) and the elimination half-life (t1/2) is between 27 and 32 hours. There are no sex-related differences in escitalopram pharmacokinetics; however, escitalopram is eliminated more slowly in the elderly but maximum plasma concentration is unchanged thus increasing systemic exposure. In addition, oral clearance of RS-citalopram was reduced by 37% and t1/2; doubled in patients with hepatic impairment. Therapeutic Efficacy Antidepressive efficacy was observed in patients with major depressive disorder (MDD) in 8-week trials with significant improvements in Montgomery-Åsberg Depression Rating Scale (MADRS) scores in patients receiving escitalopram 10 or 20 mg/day versus those receiving placebo noted as early as 1–2 weeks after starting therapy. Follow-on studies found that escitalopram reduced the long-term risk of relapse and continued to reduce MADRS scores. Significant improvements ere also observed in all secondary efficacy parameters including the Hamilton Rating Scale for Depression (HAM-D) and the Clinical Global Impressions Improvement and Severity scales (CGI-I and CGI-S) scores, and at least half of patients receiving escitalopram responded to treatment. Escitalopram showed earlier and better efficacy than RS-citalopram in a subgroup of patients with moderate MDD after 24 weeks and produced sustained response and remission significantly more rapidly (p < 0.05) than venlafaxine extended release (XR) at several timepoints over 8 weeks in patients with this disorder. In addition, improvements in quality of life (QOL) were experienced in the one study to report this. Significantly greater reductions in Hamilton Rating Scale for Anxiety (HAM-A) scores were observed in 124 patients, meeting the DSM-IV criteria for generalised anxiety disorder (GAD), who received escitalopram than in 128 patients meeting the same criteria who received placebo for 8 weeks. Improvements were also observed in several secondary efficacy parameters in the patients receiving escitalopram. In a 12-week study in patients who met the DSM-IV criteria for social anxiety disorder (SAD), those receiving escitalopram (n = 181 ) showed greater reductions in all SAD measurement scores and in disability scores than those receiving placebo (n = 177). The primary efficacy parameter was changes in Liebowitz Social Anxiety Scale scores from baseline to week 12. Secondary efficacy parameters included CGI-I scores, changes in CGI-S scores and Sheehan Disability scores over the same period. Escitalopram was significantly more effective than placebo in the treatment of panic disorder for all efficacy parameters in a 10-week trial. Efficacy measurements included frequency of panic attacks, the Panic and Anticipatory Anxiety Scale, Panic and Agoraphobia Scale, HAM-A, CGI-I and CGI-S scores, the Patient Global Evaluation and a QOL questionnaire. Improvements were apparent by week 4 in patients with GAD or panic disorder. Pharmacoeconomics Two decision analytic studies carried out in Finland and Sweden found that, when used to treat MDD, escitalopram was more cost effective than RS-citalopram, fluoxetin... Major Depressive Disorder (dpeaa)DE-He213 Anxiety Disorder (dpeaa)DE-He213 Venlafaxine (dpeaa)DE-He213 Major Depressive Disorder (dpeaa)DE-He213 Social Anxiety Disorder (dpeaa)DE-He213 Goa, Karen L. verfasserin aut Enthalten in CNS drugs Berlin [u.a.] : Springer, 1994 17(2003), 5 vom: Apr., Seite 343-362 (DE-627)327645172 (DE-600)2043806-0 1179-1934 nnns volume:17 year:2003 number:5 month:04 pages:343-362 https://dx.doi.org/10.2165/00023210-200317050-00004 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA SSG-OPC-PHA SSG-OPC-ASE GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_266 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 44.40 ASE AR 17 2003 5 04 343-362 |
allfieldsSound |
10.2165/00023210-200317050-00004 doi (DE-627)SPR033074348 (SPR)00023210-200317050-00004-e DE-627 ger DE-627 rakwb eng 610 ASE 44.40 bkl Waugh, John verfasserin aut Escitalopram 2003 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Escitalopram is the therapeutically active S-enantiomer of RS-citalopram, a commonly prescribed SSRI. The R-enantiomer is essentially pharmacologically inactive. Escitalopram 10 or 20 mg/day produced significantly greater improvements in standard measurements of antidepressant effect (Montgomery-Åsberg Depression Rating Scale [MADRS], Clinical Global Impressions Improvement and Severity scales [CGI-I and CGI-S] and Hamilton Rating Scale for Depression [HAM-D]) in patients with major depressive disorder (MDD) than placebo in several 8-week, placebo-controlled, randomised, double-blind, multicentre studies. Symptom improvement was rapid, with some parameters improving within 1–2 weeks of starting escitalopram treatment. In addition, escitalopram showed earlier and clearer separation from placebo than RS-citalopram, at one-quarter to half the dosage, in 8-week, placebo-controlled trials; had significantly better efficacy than RS-citalopram in a subgroup of patients with moderate MDD in a 24-week trial; and produced sustained response and remission significantly faster than venlafaxine extended release in patients with MDD. Escitalopram reduced relapse rate compared with placebo and increased the percentage of patients in remission in long-term trials (up to 52 weeks). Consistently significant improvements for all efficacy parameters were also observed in patients with generalised anxiety disorder, social anxiety disorder and panic disorder treated with escitalopram for 8–12 weeks in individual, randomised, placebo-controlled, double-blind investigations. The good tolerability profile of escitalopram is predictable and similar to that of RS-citalopram. Such adverse events as nausea, ejaculatory problems, diarrhoea and insomnia are expected but, with the exception of ejaculatory problems and nausea, which is mild and transient, these were generally no more frequent than with placebo in fully published clinical trials. No adverse events not previously seen in acute trials were reported with long-term use. Conclusions: Escitalopram, the S-enantiomer of RS-citalopram, is a highly selectiveinhibitor for the serotonin transporter, ameliorates depressive symptoms in patients with MDD at half the RS-citalopram dosage, has a rapid onset of symptom improvement and has a predictable tolerability profile of generally mild adverse events. Like RS-citalopram, escitalopram is expected to have a low propensity for drug interactions, a potential benefit in the management of patients with comorbidities. In combination, these properties place escitalopram, like other SSRIs, as first-line therapy in patients with MDD. Escitalopram is indicated for use in patients with panic disorder in Europe and, should further evidence confirm early findings that escitalopram reduces anxiety, the drug may well find an additional role in the management of anxiety disorders. Pharmacodynamic Properties Escitalopram is the therapeutically active S-enantiomer of RS-citalopram, which is a highly selective and effective serotonin reuptake inhibitor. The antidepressant mechanism of escitalopram is presumed to be a result of stimulation of serotonergic neurotransmission in the CNS as a consequence of higher serotonin levels resulting from inhibition of the serotonin transporter. Escitalopram has no or very low affinity for a variety of other serotonin, dopamine, α- and β-adrenergic, histamine, muscarinic and benzodiazepine receptors. It also does not bind to or has low affinity for a range of ion channels including those for $ Na^{+} $], $ K^{+} $], $ Cl^{-} $] and $ Ca^{2+} $]. In rat models predictive of antidepressant activity, escitalopram demonstrated higher activity than RS- citalopram. The minimum effective dose was 4-fold lower with escitalopram than with RS-citalopram in reducing aggressive behaviour in the resident-intruder rat model and in reducing panic-like anxiety in rats after electrical stimulation of the dorsal peri-aquaductal grey matter. A trial using a conditioned fear model in rats found that escitalopram reversed suppression of exploratory activity more rapidly than a comparable dose of S-citalopram in RS-citalopram. This qualitative difference between S-citalopram and RS-citalopram was confirmed by another in vivo trial that showed higher extracellular serotonin concentrations in the frontal cortex of rats after injection with escitalopram than in rats treated with a racemic mixture of S-citalopram and R-citalopram, indicating inhibition of the S-enantiomer by the R-enantiomer in the racemate. Pharmacokinetic Properties Escitalopram shows linear and dose-proportional pharmacokinetics with steady—state plasma concentrations achieved in 1 week in healthy volunteers. The mean steady-state area under the plasma concentration-time curve (0–24h) after a dosage of 10 mg/day was 360.2 ng · h/mL in healthy volunteers. After a single dose of escitalopram 20mg, peak plasma concentrations were reached in 4–5 hours and were not affected by food intake. Absolute bioavailability of RS-citalopram is about 80% and binding to human plasma proteins of escitalopram is approximately 56%. The apparent volume of distribution of escitalopram after oral administration is 12–26 L/kg. The pharmacokinetic profile of the S-enantiomer is the same whether given as escitalopram 10mg or RS-citalopram 20mg. Escitalopram is transformed to two metabolites, S-demethylcitalopram and S-didemethylcitalopram, both of which are much less potent than the parent drug. Alernatively, the nitrogen atom may be oxidised to the N-oxide metabolite. Escitalopram is the predominant plasma compound. The primary isoenzymes involved in metabolising escitalopram are cytochrome P450 (CYP) 2C19, CYP3A4 and CYP2D6. Elimination of escitalopram is principally via hepatic and renal routes as metabolites. Oral clearance of escitalopram is 36 L/h (600 mL/min) and the elimination half-life (t1/2) is between 27 and 32 hours. There are no sex-related differences in escitalopram pharmacokinetics; however, escitalopram is eliminated more slowly in the elderly but maximum plasma concentration is unchanged thus increasing systemic exposure. In addition, oral clearance of RS-citalopram was reduced by 37% and t1/2; doubled in patients with hepatic impairment. Therapeutic Efficacy Antidepressive efficacy was observed in patients with major depressive disorder (MDD) in 8-week trials with significant improvements in Montgomery-Åsberg Depression Rating Scale (MADRS) scores in patients receiving escitalopram 10 or 20 mg/day versus those receiving placebo noted as early as 1–2 weeks after starting therapy. Follow-on studies found that escitalopram reduced the long-term risk of relapse and continued to reduce MADRS scores. Significant improvements ere also observed in all secondary efficacy parameters including the Hamilton Rating Scale for Depression (HAM-D) and the Clinical Global Impressions Improvement and Severity scales (CGI-I and CGI-S) scores, and at least half of patients receiving escitalopram responded to treatment. Escitalopram showed earlier and better efficacy than RS-citalopram in a subgroup of patients with moderate MDD after 24 weeks and produced sustained response and remission significantly more rapidly (p < 0.05) than venlafaxine extended release (XR) at several timepoints over 8 weeks in patients with this disorder. In addition, improvements in quality of life (QOL) were experienced in the one study to report this. Significantly greater reductions in Hamilton Rating Scale for Anxiety (HAM-A) scores were observed in 124 patients, meeting the DSM-IV criteria for generalised anxiety disorder (GAD), who received escitalopram than in 128 patients meeting the same criteria who received placebo for 8 weeks. Improvements were also observed in several secondary efficacy parameters in the patients receiving escitalopram. In a 12-week study in patients who met the DSM-IV criteria for social anxiety disorder (SAD), those receiving escitalopram (n = 181 ) showed greater reductions in all SAD measurement scores and in disability scores than those receiving placebo (n = 177). The primary efficacy parameter was changes in Liebowitz Social Anxiety Scale scores from baseline to week 12. Secondary efficacy parameters included CGI-I scores, changes in CGI-S scores and Sheehan Disability scores over the same period. Escitalopram was significantly more effective than placebo in the treatment of panic disorder for all efficacy parameters in a 10-week trial. Efficacy measurements included frequency of panic attacks, the Panic and Anticipatory Anxiety Scale, Panic and Agoraphobia Scale, HAM-A, CGI-I and CGI-S scores, the Patient Global Evaluation and a QOL questionnaire. Improvements were apparent by week 4 in patients with GAD or panic disorder. Pharmacoeconomics Two decision analytic studies carried out in Finland and Sweden found that, when used to treat MDD, escitalopram was more cost effective than RS-citalopram, fluoxetin... Major Depressive Disorder (dpeaa)DE-He213 Anxiety Disorder (dpeaa)DE-He213 Venlafaxine (dpeaa)DE-He213 Major Depressive Disorder (dpeaa)DE-He213 Social Anxiety Disorder (dpeaa)DE-He213 Goa, Karen L. verfasserin aut Enthalten in CNS drugs Berlin [u.a.] : Springer, 1994 17(2003), 5 vom: Apr., Seite 343-362 (DE-627)327645172 (DE-600)2043806-0 1179-1934 nnns volume:17 year:2003 number:5 month:04 pages:343-362 https://dx.doi.org/10.2165/00023210-200317050-00004 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA SSG-OPC-PHA SSG-OPC-ASE GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_266 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 44.40 ASE AR 17 2003 5 04 343-362 |
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Enthalten in CNS drugs 17(2003), 5 vom: Apr., Seite 343-362 volume:17 year:2003 number:5 month:04 pages:343-362 |
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Enthalten in CNS drugs 17(2003), 5 vom: Apr., Seite 343-362 volume:17 year:2003 number:5 month:04 pages:343-362 |
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<?xml version="1.0" encoding="UTF-8"?><collection xmlns="http://www.loc.gov/MARC21/slim"><record><leader>01000caa a22002652 4500</leader><controlfield tag="001">SPR033074348</controlfield><controlfield tag="003">DE-627</controlfield><controlfield tag="005">20230519194315.0</controlfield><controlfield tag="007">cr uuu---uuuuu</controlfield><controlfield tag="008">201007s2003 xx |||||o 00| ||eng c</controlfield><datafield tag="024" ind1="7" ind2=" "><subfield code="a">10.2165/00023210-200317050-00004</subfield><subfield code="2">doi</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-627)SPR033074348</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(SPR)00023210-200317050-00004-e</subfield></datafield><datafield tag="040" ind1=" " ind2=" "><subfield code="a">DE-627</subfield><subfield code="b">ger</subfield><subfield code="c">DE-627</subfield><subfield code="e">rakwb</subfield></datafield><datafield tag="041" ind1=" " ind2=" "><subfield code="a">eng</subfield></datafield><datafield tag="082" ind1="0" ind2="4"><subfield code="a">610</subfield><subfield code="q">ASE</subfield></datafield><datafield tag="084" ind1=" " ind2=" "><subfield code="a">44.40</subfield><subfield code="2">bkl</subfield></datafield><datafield tag="100" ind1="1" ind2=" "><subfield code="a">Waugh, John</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="245" ind1="1" ind2="0"><subfield code="a">Escitalopram</subfield></datafield><datafield tag="264" ind1=" " ind2="1"><subfield code="c">2003</subfield></datafield><datafield tag="336" ind1=" " ind2=" "><subfield code="a">Text</subfield><subfield code="b">txt</subfield><subfield code="2">rdacontent</subfield></datafield><datafield tag="337" ind1=" " ind2=" "><subfield code="a">Computermedien</subfield><subfield code="b">c</subfield><subfield code="2">rdamedia</subfield></datafield><datafield tag="338" ind1=" " ind2=" "><subfield code="a">Online-Ressource</subfield><subfield code="b">cr</subfield><subfield code="2">rdacarrier</subfield></datafield><datafield tag="520" ind1=" " ind2=" "><subfield code="a">Abstract Escitalopram is the therapeutically active S-enantiomer of RS-citalopram, a commonly prescribed SSRI. The R-enantiomer is essentially pharmacologically inactive. Escitalopram 10 or 20 mg/day produced significantly greater improvements in standard measurements of antidepressant effect (Montgomery-Åsberg Depression Rating Scale [MADRS], Clinical Global Impressions Improvement and Severity scales [CGI-I and CGI-S] and Hamilton Rating Scale for Depression [HAM-D]) in patients with major depressive disorder (MDD) than placebo in several 8-week, placebo-controlled, randomised, double-blind, multicentre studies. Symptom improvement was rapid, with some parameters improving within 1–2 weeks of starting escitalopram treatment. In addition, escitalopram showed earlier and clearer separation from placebo than RS-citalopram, at one-quarter to half the dosage, in 8-week, placebo-controlled trials; had significantly better efficacy than RS-citalopram in a subgroup of patients with moderate MDD in a 24-week trial; and produced sustained response and remission significantly faster than venlafaxine extended release in patients with MDD. Escitalopram reduced relapse rate compared with placebo and increased the percentage of patients in remission in long-term trials (up to 52 weeks). Consistently significant improvements for all efficacy parameters were also observed in patients with generalised anxiety disorder, social anxiety disorder and panic disorder treated with escitalopram for 8–12 weeks in individual, randomised, placebo-controlled, double-blind investigations. The good tolerability profile of escitalopram is predictable and similar to that of RS-citalopram. Such adverse events as nausea, ejaculatory problems, diarrhoea and insomnia are expected but, with the exception of ejaculatory problems and nausea, which is mild and transient, these were generally no more frequent than with placebo in fully published clinical trials. No adverse events not previously seen in acute trials were reported with long-term use. Conclusions: Escitalopram, the S-enantiomer of RS-citalopram, is a highly selectiveinhibitor for the serotonin transporter, ameliorates depressive symptoms in patients with MDD at half the RS-citalopram dosage, has a rapid onset of symptom improvement and has a predictable tolerability profile of generally mild adverse events. Like RS-citalopram, escitalopram is expected to have a low propensity for drug interactions, a potential benefit in the management of patients with comorbidities. In combination, these properties place escitalopram, like other SSRIs, as first-line therapy in patients with MDD. Escitalopram is indicated for use in patients with panic disorder in Europe and, should further evidence confirm early findings that escitalopram reduces anxiety, the drug may well find an additional role in the management of anxiety disorders. Pharmacodynamic Properties Escitalopram is the therapeutically active S-enantiomer of RS-citalopram, which is a highly selective and effective serotonin reuptake inhibitor. The antidepressant mechanism of escitalopram is presumed to be a result of stimulation of serotonergic neurotransmission in the CNS as a consequence of higher serotonin levels resulting from inhibition of the serotonin transporter. Escitalopram has no or very low affinity for a variety of other serotonin, dopamine, α- and β-adrenergic, histamine, muscarinic and benzodiazepine receptors. It also does not bind to or has low affinity for a range of ion channels including those for $ Na^{+} $], $ K^{+} $], $ Cl^{-} $] and $ Ca^{2+} $]. In rat models predictive of antidepressant activity, escitalopram demonstrated higher activity than RS- citalopram. The minimum effective dose was 4-fold lower with escitalopram than with RS-citalopram in reducing aggressive behaviour in the resident-intruder rat model and in reducing panic-like anxiety in rats after electrical stimulation of the dorsal peri-aquaductal grey matter. A trial using a conditioned fear model in rats found that escitalopram reversed suppression of exploratory activity more rapidly than a comparable dose of S-citalopram in RS-citalopram. This qualitative difference between S-citalopram and RS-citalopram was confirmed by another in vivo trial that showed higher extracellular serotonin concentrations in the frontal cortex of rats after injection with escitalopram than in rats treated with a racemic mixture of S-citalopram and R-citalopram, indicating inhibition of the S-enantiomer by the R-enantiomer in the racemate. Pharmacokinetic Properties Escitalopram shows linear and dose-proportional pharmacokinetics with steady—state plasma concentrations achieved in 1 week in healthy volunteers. The mean steady-state area under the plasma concentration-time curve (0–24h) after a dosage of 10 mg/day was 360.2 ng · h/mL in healthy volunteers. After a single dose of escitalopram 20mg, peak plasma concentrations were reached in 4–5 hours and were not affected by food intake. Absolute bioavailability of RS-citalopram is about 80% and binding to human plasma proteins of escitalopram is approximately 56%. The apparent volume of distribution of escitalopram after oral administration is 12–26 L/kg. The pharmacokinetic profile of the S-enantiomer is the same whether given as escitalopram 10mg or RS-citalopram 20mg. Escitalopram is transformed to two metabolites, S-demethylcitalopram and S-didemethylcitalopram, both of which are much less potent than the parent drug. Alernatively, the nitrogen atom may be oxidised to the N-oxide metabolite. Escitalopram is the predominant plasma compound. The primary isoenzymes involved in metabolising escitalopram are cytochrome P450 (CYP) 2C19, CYP3A4 and CYP2D6. Elimination of escitalopram is principally via hepatic and renal routes as metabolites. Oral clearance of escitalopram is 36 L/h (600 mL/min) and the elimination half-life (t1/2) is between 27 and 32 hours. There are no sex-related differences in escitalopram pharmacokinetics; however, escitalopram is eliminated more slowly in the elderly but maximum plasma concentration is unchanged thus increasing systemic exposure. In addition, oral clearance of RS-citalopram was reduced by 37% and t1/2; doubled in patients with hepatic impairment. Therapeutic Efficacy Antidepressive efficacy was observed in patients with major depressive disorder (MDD) in 8-week trials with significant improvements in Montgomery-Åsberg Depression Rating Scale (MADRS) scores in patients receiving escitalopram 10 or 20 mg/day versus those receiving placebo noted as early as 1–2 weeks after starting therapy. Follow-on studies found that escitalopram reduced the long-term risk of relapse and continued to reduce MADRS scores. Significant improvements ere also observed in all secondary efficacy parameters including the Hamilton Rating Scale for Depression (HAM-D) and the Clinical Global Impressions Improvement and Severity scales (CGI-I and CGI-S) scores, and at least half of patients receiving escitalopram responded to treatment. Escitalopram showed earlier and better efficacy than RS-citalopram in a subgroup of patients with moderate MDD after 24 weeks and produced sustained response and remission significantly more rapidly (p < 0.05) than venlafaxine extended release (XR) at several timepoints over 8 weeks in patients with this disorder. In addition, improvements in quality of life (QOL) were experienced in the one study to report this. Significantly greater reductions in Hamilton Rating Scale for Anxiety (HAM-A) scores were observed in 124 patients, meeting the DSM-IV criteria for generalised anxiety disorder (GAD), who received escitalopram than in 128 patients meeting the same criteria who received placebo for 8 weeks. Improvements were also observed in several secondary efficacy parameters in the patients receiving escitalopram. In a 12-week study in patients who met the DSM-IV criteria for social anxiety disorder (SAD), those receiving escitalopram (n = 181 ) showed greater reductions in all SAD measurement scores and in disability scores than those receiving placebo (n = 177). The primary efficacy parameter was changes in Liebowitz Social Anxiety Scale scores from baseline to week 12. Secondary efficacy parameters included CGI-I scores, changes in CGI-S scores and Sheehan Disability scores over the same period. Escitalopram was significantly more effective than placebo in the treatment of panic disorder for all efficacy parameters in a 10-week trial. Efficacy measurements included frequency of panic attacks, the Panic and Anticipatory Anxiety Scale, Panic and Agoraphobia Scale, HAM-A, CGI-I and CGI-S scores, the Patient Global Evaluation and a QOL questionnaire. Improvements were apparent by week 4 in patients with GAD or panic disorder. Pharmacoeconomics Two decision analytic studies carried out in Finland and Sweden found that, when used to treat MDD, escitalopram was more cost effective than RS-citalopram, fluoxetin...</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Major Depressive Disorder</subfield><subfield code="7">(dpeaa)DE-He213</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Anxiety Disorder</subfield><subfield code="7">(dpeaa)DE-He213</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Venlafaxine</subfield><subfield code="7">(dpeaa)DE-He213</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Major Depressive Disorder</subfield><subfield code="7">(dpeaa)DE-He213</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Social Anxiety Disorder</subfield><subfield code="7">(dpeaa)DE-He213</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Goa, Karen L.</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="773" ind1="0" ind2="8"><subfield code="i">Enthalten in</subfield><subfield code="t">CNS drugs</subfield><subfield code="d">Berlin [u.a.] : Springer, 1994</subfield><subfield code="g">17(2003), 5 vom: Apr., Seite 343-362</subfield><subfield code="w">(DE-627)327645172</subfield><subfield code="w">(DE-600)2043806-0</subfield><subfield code="x">1179-1934</subfield><subfield code="7">nnns</subfield></datafield><datafield tag="773" ind1="1" ind2="8"><subfield code="g">volume:17</subfield><subfield code="g">year:2003</subfield><subfield code="g">number:5</subfield><subfield code="g">month:04</subfield><subfield code="g">pages:343-362</subfield></datafield><datafield tag="856" ind1="4" ind2="0"><subfield code="u">https://dx.doi.org/10.2165/00023210-200317050-00004</subfield><subfield code="z">lizenzpflichtig</subfield><subfield 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Waugh, John |
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Escitalopram |
abstract |
Abstract Escitalopram is the therapeutically active S-enantiomer of RS-citalopram, a commonly prescribed SSRI. The R-enantiomer is essentially pharmacologically inactive. Escitalopram 10 or 20 mg/day produced significantly greater improvements in standard measurements of antidepressant effect (Montgomery-Åsberg Depression Rating Scale [MADRS], Clinical Global Impressions Improvement and Severity scales [CGI-I and CGI-S] and Hamilton Rating Scale for Depression [HAM-D]) in patients with major depressive disorder (MDD) than placebo in several 8-week, placebo-controlled, randomised, double-blind, multicentre studies. Symptom improvement was rapid, with some parameters improving within 1–2 weeks of starting escitalopram treatment. In addition, escitalopram showed earlier and clearer separation from placebo than RS-citalopram, at one-quarter to half the dosage, in 8-week, placebo-controlled trials; had significantly better efficacy than RS-citalopram in a subgroup of patients with moderate MDD in a 24-week trial; and produced sustained response and remission significantly faster than venlafaxine extended release in patients with MDD. Escitalopram reduced relapse rate compared with placebo and increased the percentage of patients in remission in long-term trials (up to 52 weeks). Consistently significant improvements for all efficacy parameters were also observed in patients with generalised anxiety disorder, social anxiety disorder and panic disorder treated with escitalopram for 8–12 weeks in individual, randomised, placebo-controlled, double-blind investigations. The good tolerability profile of escitalopram is predictable and similar to that of RS-citalopram. Such adverse events as nausea, ejaculatory problems, diarrhoea and insomnia are expected but, with the exception of ejaculatory problems and nausea, which is mild and transient, these were generally no more frequent than with placebo in fully published clinical trials. No adverse events not previously seen in acute trials were reported with long-term use. Conclusions: Escitalopram, the S-enantiomer of RS-citalopram, is a highly selectiveinhibitor for the serotonin transporter, ameliorates depressive symptoms in patients with MDD at half the RS-citalopram dosage, has a rapid onset of symptom improvement and has a predictable tolerability profile of generally mild adverse events. Like RS-citalopram, escitalopram is expected to have a low propensity for drug interactions, a potential benefit in the management of patients with comorbidities. In combination, these properties place escitalopram, like other SSRIs, as first-line therapy in patients with MDD. Escitalopram is indicated for use in patients with panic disorder in Europe and, should further evidence confirm early findings that escitalopram reduces anxiety, the drug may well find an additional role in the management of anxiety disorders. Pharmacodynamic Properties Escitalopram is the therapeutically active S-enantiomer of RS-citalopram, which is a highly selective and effective serotonin reuptake inhibitor. The antidepressant mechanism of escitalopram is presumed to be a result of stimulation of serotonergic neurotransmission in the CNS as a consequence of higher serotonin levels resulting from inhibition of the serotonin transporter. Escitalopram has no or very low affinity for a variety of other serotonin, dopamine, α- and β-adrenergic, histamine, muscarinic and benzodiazepine receptors. It also does not bind to or has low affinity for a range of ion channels including those for $ Na^{+} $], $ K^{+} $], $ Cl^{-} $] and $ Ca^{2+} $]. In rat models predictive of antidepressant activity, escitalopram demonstrated higher activity than RS- citalopram. The minimum effective dose was 4-fold lower with escitalopram than with RS-citalopram in reducing aggressive behaviour in the resident-intruder rat model and in reducing panic-like anxiety in rats after electrical stimulation of the dorsal peri-aquaductal grey matter. A trial using a conditioned fear model in rats found that escitalopram reversed suppression of exploratory activity more rapidly than a comparable dose of S-citalopram in RS-citalopram. This qualitative difference between S-citalopram and RS-citalopram was confirmed by another in vivo trial that showed higher extracellular serotonin concentrations in the frontal cortex of rats after injection with escitalopram than in rats treated with a racemic mixture of S-citalopram and R-citalopram, indicating inhibition of the S-enantiomer by the R-enantiomer in the racemate. Pharmacokinetic Properties Escitalopram shows linear and dose-proportional pharmacokinetics with steady—state plasma concentrations achieved in 1 week in healthy volunteers. The mean steady-state area under the plasma concentration-time curve (0–24h) after a dosage of 10 mg/day was 360.2 ng · h/mL in healthy volunteers. After a single dose of escitalopram 20mg, peak plasma concentrations were reached in 4–5 hours and were not affected by food intake. Absolute bioavailability of RS-citalopram is about 80% and binding to human plasma proteins of escitalopram is approximately 56%. The apparent volume of distribution of escitalopram after oral administration is 12–26 L/kg. The pharmacokinetic profile of the S-enantiomer is the same whether given as escitalopram 10mg or RS-citalopram 20mg. Escitalopram is transformed to two metabolites, S-demethylcitalopram and S-didemethylcitalopram, both of which are much less potent than the parent drug. Alernatively, the nitrogen atom may be oxidised to the N-oxide metabolite. Escitalopram is the predominant plasma compound. The primary isoenzymes involved in metabolising escitalopram are cytochrome P450 (CYP) 2C19, CYP3A4 and CYP2D6. Elimination of escitalopram is principally via hepatic and renal routes as metabolites. Oral clearance of escitalopram is 36 L/h (600 mL/min) and the elimination half-life (t1/2) is between 27 and 32 hours. There are no sex-related differences in escitalopram pharmacokinetics; however, escitalopram is eliminated more slowly in the elderly but maximum plasma concentration is unchanged thus increasing systemic exposure. In addition, oral clearance of RS-citalopram was reduced by 37% and t1/2; doubled in patients with hepatic impairment. Therapeutic Efficacy Antidepressive efficacy was observed in patients with major depressive disorder (MDD) in 8-week trials with significant improvements in Montgomery-Åsberg Depression Rating Scale (MADRS) scores in patients receiving escitalopram 10 or 20 mg/day versus those receiving placebo noted as early as 1–2 weeks after starting therapy. Follow-on studies found that escitalopram reduced the long-term risk of relapse and continued to reduce MADRS scores. Significant improvements ere also observed in all secondary efficacy parameters including the Hamilton Rating Scale for Depression (HAM-D) and the Clinical Global Impressions Improvement and Severity scales (CGI-I and CGI-S) scores, and at least half of patients receiving escitalopram responded to treatment. Escitalopram showed earlier and better efficacy than RS-citalopram in a subgroup of patients with moderate MDD after 24 weeks and produced sustained response and remission significantly more rapidly (p < 0.05) than venlafaxine extended release (XR) at several timepoints over 8 weeks in patients with this disorder. In addition, improvements in quality of life (QOL) were experienced in the one study to report this. Significantly greater reductions in Hamilton Rating Scale for Anxiety (HAM-A) scores were observed in 124 patients, meeting the DSM-IV criteria for generalised anxiety disorder (GAD), who received escitalopram than in 128 patients meeting the same criteria who received placebo for 8 weeks. Improvements were also observed in several secondary efficacy parameters in the patients receiving escitalopram. In a 12-week study in patients who met the DSM-IV criteria for social anxiety disorder (SAD), those receiving escitalopram (n = 181 ) showed greater reductions in all SAD measurement scores and in disability scores than those receiving placebo (n = 177). The primary efficacy parameter was changes in Liebowitz Social Anxiety Scale scores from baseline to week 12. Secondary efficacy parameters included CGI-I scores, changes in CGI-S scores and Sheehan Disability scores over the same period. Escitalopram was significantly more effective than placebo in the treatment of panic disorder for all efficacy parameters in a 10-week trial. Efficacy measurements included frequency of panic attacks, the Panic and Anticipatory Anxiety Scale, Panic and Agoraphobia Scale, HAM-A, CGI-I and CGI-S scores, the Patient Global Evaluation and a QOL questionnaire. Improvements were apparent by week 4 in patients with GAD or panic disorder. Pharmacoeconomics Two decision analytic studies carried out in Finland and Sweden found that, when used to treat MDD, escitalopram was more cost effective than RS-citalopram, fluoxetin... |
abstractGer |
Abstract Escitalopram is the therapeutically active S-enantiomer of RS-citalopram, a commonly prescribed SSRI. The R-enantiomer is essentially pharmacologically inactive. Escitalopram 10 or 20 mg/day produced significantly greater improvements in standard measurements of antidepressant effect (Montgomery-Åsberg Depression Rating Scale [MADRS], Clinical Global Impressions Improvement and Severity scales [CGI-I and CGI-S] and Hamilton Rating Scale for Depression [HAM-D]) in patients with major depressive disorder (MDD) than placebo in several 8-week, placebo-controlled, randomised, double-blind, multicentre studies. Symptom improvement was rapid, with some parameters improving within 1–2 weeks of starting escitalopram treatment. In addition, escitalopram showed earlier and clearer separation from placebo than RS-citalopram, at one-quarter to half the dosage, in 8-week, placebo-controlled trials; had significantly better efficacy than RS-citalopram in a subgroup of patients with moderate MDD in a 24-week trial; and produced sustained response and remission significantly faster than venlafaxine extended release in patients with MDD. Escitalopram reduced relapse rate compared with placebo and increased the percentage of patients in remission in long-term trials (up to 52 weeks). Consistently significant improvements for all efficacy parameters were also observed in patients with generalised anxiety disorder, social anxiety disorder and panic disorder treated with escitalopram for 8–12 weeks in individual, randomised, placebo-controlled, double-blind investigations. The good tolerability profile of escitalopram is predictable and similar to that of RS-citalopram. Such adverse events as nausea, ejaculatory problems, diarrhoea and insomnia are expected but, with the exception of ejaculatory problems and nausea, which is mild and transient, these were generally no more frequent than with placebo in fully published clinical trials. No adverse events not previously seen in acute trials were reported with long-term use. Conclusions: Escitalopram, the S-enantiomer of RS-citalopram, is a highly selectiveinhibitor for the serotonin transporter, ameliorates depressive symptoms in patients with MDD at half the RS-citalopram dosage, has a rapid onset of symptom improvement and has a predictable tolerability profile of generally mild adverse events. Like RS-citalopram, escitalopram is expected to have a low propensity for drug interactions, a potential benefit in the management of patients with comorbidities. In combination, these properties place escitalopram, like other SSRIs, as first-line therapy in patients with MDD. Escitalopram is indicated for use in patients with panic disorder in Europe and, should further evidence confirm early findings that escitalopram reduces anxiety, the drug may well find an additional role in the management of anxiety disorders. Pharmacodynamic Properties Escitalopram is the therapeutically active S-enantiomer of RS-citalopram, which is a highly selective and effective serotonin reuptake inhibitor. The antidepressant mechanism of escitalopram is presumed to be a result of stimulation of serotonergic neurotransmission in the CNS as a consequence of higher serotonin levels resulting from inhibition of the serotonin transporter. Escitalopram has no or very low affinity for a variety of other serotonin, dopamine, α- and β-adrenergic, histamine, muscarinic and benzodiazepine receptors. It also does not bind to or has low affinity for a range of ion channels including those for $ Na^{+} $], $ K^{+} $], $ Cl^{-} $] and $ Ca^{2+} $]. In rat models predictive of antidepressant activity, escitalopram demonstrated higher activity than RS- citalopram. The minimum effective dose was 4-fold lower with escitalopram than with RS-citalopram in reducing aggressive behaviour in the resident-intruder rat model and in reducing panic-like anxiety in rats after electrical stimulation of the dorsal peri-aquaductal grey matter. A trial using a conditioned fear model in rats found that escitalopram reversed suppression of exploratory activity more rapidly than a comparable dose of S-citalopram in RS-citalopram. This qualitative difference between S-citalopram and RS-citalopram was confirmed by another in vivo trial that showed higher extracellular serotonin concentrations in the frontal cortex of rats after injection with escitalopram than in rats treated with a racemic mixture of S-citalopram and R-citalopram, indicating inhibition of the S-enantiomer by the R-enantiomer in the racemate. Pharmacokinetic Properties Escitalopram shows linear and dose-proportional pharmacokinetics with steady—state plasma concentrations achieved in 1 week in healthy volunteers. The mean steady-state area under the plasma concentration-time curve (0–24h) after a dosage of 10 mg/day was 360.2 ng · h/mL in healthy volunteers. After a single dose of escitalopram 20mg, peak plasma concentrations were reached in 4–5 hours and were not affected by food intake. Absolute bioavailability of RS-citalopram is about 80% and binding to human plasma proteins of escitalopram is approximately 56%. The apparent volume of distribution of escitalopram after oral administration is 12–26 L/kg. The pharmacokinetic profile of the S-enantiomer is the same whether given as escitalopram 10mg or RS-citalopram 20mg. Escitalopram is transformed to two metabolites, S-demethylcitalopram and S-didemethylcitalopram, both of which are much less potent than the parent drug. Alernatively, the nitrogen atom may be oxidised to the N-oxide metabolite. Escitalopram is the predominant plasma compound. The primary isoenzymes involved in metabolising escitalopram are cytochrome P450 (CYP) 2C19, CYP3A4 and CYP2D6. Elimination of escitalopram is principally via hepatic and renal routes as metabolites. Oral clearance of escitalopram is 36 L/h (600 mL/min) and the elimination half-life (t1/2) is between 27 and 32 hours. There are no sex-related differences in escitalopram pharmacokinetics; however, escitalopram is eliminated more slowly in the elderly but maximum plasma concentration is unchanged thus increasing systemic exposure. In addition, oral clearance of RS-citalopram was reduced by 37% and t1/2; doubled in patients with hepatic impairment. Therapeutic Efficacy Antidepressive efficacy was observed in patients with major depressive disorder (MDD) in 8-week trials with significant improvements in Montgomery-Åsberg Depression Rating Scale (MADRS) scores in patients receiving escitalopram 10 or 20 mg/day versus those receiving placebo noted as early as 1–2 weeks after starting therapy. Follow-on studies found that escitalopram reduced the long-term risk of relapse and continued to reduce MADRS scores. Significant improvements ere also observed in all secondary efficacy parameters including the Hamilton Rating Scale for Depression (HAM-D) and the Clinical Global Impressions Improvement and Severity scales (CGI-I and CGI-S) scores, and at least half of patients receiving escitalopram responded to treatment. Escitalopram showed earlier and better efficacy than RS-citalopram in a subgroup of patients with moderate MDD after 24 weeks and produced sustained response and remission significantly more rapidly (p < 0.05) than venlafaxine extended release (XR) at several timepoints over 8 weeks in patients with this disorder. In addition, improvements in quality of life (QOL) were experienced in the one study to report this. Significantly greater reductions in Hamilton Rating Scale for Anxiety (HAM-A) scores were observed in 124 patients, meeting the DSM-IV criteria for generalised anxiety disorder (GAD), who received escitalopram than in 128 patients meeting the same criteria who received placebo for 8 weeks. Improvements were also observed in several secondary efficacy parameters in the patients receiving escitalopram. In a 12-week study in patients who met the DSM-IV criteria for social anxiety disorder (SAD), those receiving escitalopram (n = 181 ) showed greater reductions in all SAD measurement scores and in disability scores than those receiving placebo (n = 177). The primary efficacy parameter was changes in Liebowitz Social Anxiety Scale scores from baseline to week 12. Secondary efficacy parameters included CGI-I scores, changes in CGI-S scores and Sheehan Disability scores over the same period. Escitalopram was significantly more effective than placebo in the treatment of panic disorder for all efficacy parameters in a 10-week trial. Efficacy measurements included frequency of panic attacks, the Panic and Anticipatory Anxiety Scale, Panic and Agoraphobia Scale, HAM-A, CGI-I and CGI-S scores, the Patient Global Evaluation and a QOL questionnaire. Improvements were apparent by week 4 in patients with GAD or panic disorder. Pharmacoeconomics Two decision analytic studies carried out in Finland and Sweden found that, when used to treat MDD, escitalopram was more cost effective than RS-citalopram, fluoxetin... |
abstract_unstemmed |
Abstract Escitalopram is the therapeutically active S-enantiomer of RS-citalopram, a commonly prescribed SSRI. The R-enantiomer is essentially pharmacologically inactive. Escitalopram 10 or 20 mg/day produced significantly greater improvements in standard measurements of antidepressant effect (Montgomery-Åsberg Depression Rating Scale [MADRS], Clinical Global Impressions Improvement and Severity scales [CGI-I and CGI-S] and Hamilton Rating Scale for Depression [HAM-D]) in patients with major depressive disorder (MDD) than placebo in several 8-week, placebo-controlled, randomised, double-blind, multicentre studies. Symptom improvement was rapid, with some parameters improving within 1–2 weeks of starting escitalopram treatment. In addition, escitalopram showed earlier and clearer separation from placebo than RS-citalopram, at one-quarter to half the dosage, in 8-week, placebo-controlled trials; had significantly better efficacy than RS-citalopram in a subgroup of patients with moderate MDD in a 24-week trial; and produced sustained response and remission significantly faster than venlafaxine extended release in patients with MDD. Escitalopram reduced relapse rate compared with placebo and increased the percentage of patients in remission in long-term trials (up to 52 weeks). Consistently significant improvements for all efficacy parameters were also observed in patients with generalised anxiety disorder, social anxiety disorder and panic disorder treated with escitalopram for 8–12 weeks in individual, randomised, placebo-controlled, double-blind investigations. The good tolerability profile of escitalopram is predictable and similar to that of RS-citalopram. Such adverse events as nausea, ejaculatory problems, diarrhoea and insomnia are expected but, with the exception of ejaculatory problems and nausea, which is mild and transient, these were generally no more frequent than with placebo in fully published clinical trials. No adverse events not previously seen in acute trials were reported with long-term use. Conclusions: Escitalopram, the S-enantiomer of RS-citalopram, is a highly selectiveinhibitor for the serotonin transporter, ameliorates depressive symptoms in patients with MDD at half the RS-citalopram dosage, has a rapid onset of symptom improvement and has a predictable tolerability profile of generally mild adverse events. Like RS-citalopram, escitalopram is expected to have a low propensity for drug interactions, a potential benefit in the management of patients with comorbidities. In combination, these properties place escitalopram, like other SSRIs, as first-line therapy in patients with MDD. Escitalopram is indicated for use in patients with panic disorder in Europe and, should further evidence confirm early findings that escitalopram reduces anxiety, the drug may well find an additional role in the management of anxiety disorders. Pharmacodynamic Properties Escitalopram is the therapeutically active S-enantiomer of RS-citalopram, which is a highly selective and effective serotonin reuptake inhibitor. The antidepressant mechanism of escitalopram is presumed to be a result of stimulation of serotonergic neurotransmission in the CNS as a consequence of higher serotonin levels resulting from inhibition of the serotonin transporter. Escitalopram has no or very low affinity for a variety of other serotonin, dopamine, α- and β-adrenergic, histamine, muscarinic and benzodiazepine receptors. It also does not bind to or has low affinity for a range of ion channels including those for $ Na^{+} $], $ K^{+} $], $ Cl^{-} $] and $ Ca^{2+} $]. In rat models predictive of antidepressant activity, escitalopram demonstrated higher activity than RS- citalopram. The minimum effective dose was 4-fold lower with escitalopram than with RS-citalopram in reducing aggressive behaviour in the resident-intruder rat model and in reducing panic-like anxiety in rats after electrical stimulation of the dorsal peri-aquaductal grey matter. A trial using a conditioned fear model in rats found that escitalopram reversed suppression of exploratory activity more rapidly than a comparable dose of S-citalopram in RS-citalopram. This qualitative difference between S-citalopram and RS-citalopram was confirmed by another in vivo trial that showed higher extracellular serotonin concentrations in the frontal cortex of rats after injection with escitalopram than in rats treated with a racemic mixture of S-citalopram and R-citalopram, indicating inhibition of the S-enantiomer by the R-enantiomer in the racemate. Pharmacokinetic Properties Escitalopram shows linear and dose-proportional pharmacokinetics with steady—state plasma concentrations achieved in 1 week in healthy volunteers. The mean steady-state area under the plasma concentration-time curve (0–24h) after a dosage of 10 mg/day was 360.2 ng · h/mL in healthy volunteers. After a single dose of escitalopram 20mg, peak plasma concentrations were reached in 4–5 hours and were not affected by food intake. Absolute bioavailability of RS-citalopram is about 80% and binding to human plasma proteins of escitalopram is approximately 56%. The apparent volume of distribution of escitalopram after oral administration is 12–26 L/kg. The pharmacokinetic profile of the S-enantiomer is the same whether given as escitalopram 10mg or RS-citalopram 20mg. Escitalopram is transformed to two metabolites, S-demethylcitalopram and S-didemethylcitalopram, both of which are much less potent than the parent drug. Alernatively, the nitrogen atom may be oxidised to the N-oxide metabolite. Escitalopram is the predominant plasma compound. The primary isoenzymes involved in metabolising escitalopram are cytochrome P450 (CYP) 2C19, CYP3A4 and CYP2D6. Elimination of escitalopram is principally via hepatic and renal routes as metabolites. Oral clearance of escitalopram is 36 L/h (600 mL/min) and the elimination half-life (t1/2) is between 27 and 32 hours. There are no sex-related differences in escitalopram pharmacokinetics; however, escitalopram is eliminated more slowly in the elderly but maximum plasma concentration is unchanged thus increasing systemic exposure. In addition, oral clearance of RS-citalopram was reduced by 37% and t1/2; doubled in patients with hepatic impairment. Therapeutic Efficacy Antidepressive efficacy was observed in patients with major depressive disorder (MDD) in 8-week trials with significant improvements in Montgomery-Åsberg Depression Rating Scale (MADRS) scores in patients receiving escitalopram 10 or 20 mg/day versus those receiving placebo noted as early as 1–2 weeks after starting therapy. Follow-on studies found that escitalopram reduced the long-term risk of relapse and continued to reduce MADRS scores. Significant improvements ere also observed in all secondary efficacy parameters including the Hamilton Rating Scale for Depression (HAM-D) and the Clinical Global Impressions Improvement and Severity scales (CGI-I and CGI-S) scores, and at least half of patients receiving escitalopram responded to treatment. Escitalopram showed earlier and better efficacy than RS-citalopram in a subgroup of patients with moderate MDD after 24 weeks and produced sustained response and remission significantly more rapidly (p < 0.05) than venlafaxine extended release (XR) at several timepoints over 8 weeks in patients with this disorder. In addition, improvements in quality of life (QOL) were experienced in the one study to report this. Significantly greater reductions in Hamilton Rating Scale for Anxiety (HAM-A) scores were observed in 124 patients, meeting the DSM-IV criteria for generalised anxiety disorder (GAD), who received escitalopram than in 128 patients meeting the same criteria who received placebo for 8 weeks. Improvements were also observed in several secondary efficacy parameters in the patients receiving escitalopram. In a 12-week study in patients who met the DSM-IV criteria for social anxiety disorder (SAD), those receiving escitalopram (n = 181 ) showed greater reductions in all SAD measurement scores and in disability scores than those receiving placebo (n = 177). The primary efficacy parameter was changes in Liebowitz Social Anxiety Scale scores from baseline to week 12. Secondary efficacy parameters included CGI-I scores, changes in CGI-S scores and Sheehan Disability scores over the same period. Escitalopram was significantly more effective than placebo in the treatment of panic disorder for all efficacy parameters in a 10-week trial. Efficacy measurements included frequency of panic attacks, the Panic and Anticipatory Anxiety Scale, Panic and Agoraphobia Scale, HAM-A, CGI-I and CGI-S scores, the Patient Global Evaluation and a QOL questionnaire. Improvements were apparent by week 4 in patients with GAD or panic disorder. Pharmacoeconomics Two decision analytic studies carried out in Finland and Sweden found that, when used to treat MDD, escitalopram was more cost effective than RS-citalopram, fluoxetin... |
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title_short |
Escitalopram |
url |
https://dx.doi.org/10.2165/00023210-200317050-00004 |
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author2 |
Goa, Karen L. |
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Goa, Karen L. |
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doi_str |
10.2165/00023210-200317050-00004 |
up_date |
2024-07-03T16:28:02.378Z |
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<?xml version="1.0" encoding="UTF-8"?><collection xmlns="http://www.loc.gov/MARC21/slim"><record><leader>01000caa a22002652 4500</leader><controlfield tag="001">SPR033074348</controlfield><controlfield tag="003">DE-627</controlfield><controlfield tag="005">20230519194315.0</controlfield><controlfield tag="007">cr uuu---uuuuu</controlfield><controlfield tag="008">201007s2003 xx |||||o 00| ||eng c</controlfield><datafield tag="024" ind1="7" ind2=" "><subfield code="a">10.2165/00023210-200317050-00004</subfield><subfield code="2">doi</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-627)SPR033074348</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(SPR)00023210-200317050-00004-e</subfield></datafield><datafield tag="040" ind1=" " ind2=" "><subfield code="a">DE-627</subfield><subfield code="b">ger</subfield><subfield code="c">DE-627</subfield><subfield code="e">rakwb</subfield></datafield><datafield tag="041" ind1=" " ind2=" "><subfield code="a">eng</subfield></datafield><datafield tag="082" ind1="0" ind2="4"><subfield code="a">610</subfield><subfield code="q">ASE</subfield></datafield><datafield tag="084" ind1=" " ind2=" "><subfield code="a">44.40</subfield><subfield code="2">bkl</subfield></datafield><datafield tag="100" ind1="1" ind2=" "><subfield code="a">Waugh, John</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="245" ind1="1" ind2="0"><subfield code="a">Escitalopram</subfield></datafield><datafield tag="264" ind1=" " ind2="1"><subfield code="c">2003</subfield></datafield><datafield tag="336" ind1=" " ind2=" "><subfield code="a">Text</subfield><subfield code="b">txt</subfield><subfield code="2">rdacontent</subfield></datafield><datafield tag="337" ind1=" " ind2=" "><subfield code="a">Computermedien</subfield><subfield code="b">c</subfield><subfield code="2">rdamedia</subfield></datafield><datafield tag="338" ind1=" " ind2=" "><subfield code="a">Online-Ressource</subfield><subfield code="b">cr</subfield><subfield code="2">rdacarrier</subfield></datafield><datafield tag="520" ind1=" " ind2=" "><subfield code="a">Abstract Escitalopram is the therapeutically active S-enantiomer of RS-citalopram, a commonly prescribed SSRI. The R-enantiomer is essentially pharmacologically inactive. Escitalopram 10 or 20 mg/day produced significantly greater improvements in standard measurements of antidepressant effect (Montgomery-Åsberg Depression Rating Scale [MADRS], Clinical Global Impressions Improvement and Severity scales [CGI-I and CGI-S] and Hamilton Rating Scale for Depression [HAM-D]) in patients with major depressive disorder (MDD) than placebo in several 8-week, placebo-controlled, randomised, double-blind, multicentre studies. Symptom improvement was rapid, with some parameters improving within 1–2 weeks of starting escitalopram treatment. In addition, escitalopram showed earlier and clearer separation from placebo than RS-citalopram, at one-quarter to half the dosage, in 8-week, placebo-controlled trials; had significantly better efficacy than RS-citalopram in a subgroup of patients with moderate MDD in a 24-week trial; and produced sustained response and remission significantly faster than venlafaxine extended release in patients with MDD. Escitalopram reduced relapse rate compared with placebo and increased the percentage of patients in remission in long-term trials (up to 52 weeks). Consistently significant improvements for all efficacy parameters were also observed in patients with generalised anxiety disorder, social anxiety disorder and panic disorder treated with escitalopram for 8–12 weeks in individual, randomised, placebo-controlled, double-blind investigations. The good tolerability profile of escitalopram is predictable and similar to that of RS-citalopram. Such adverse events as nausea, ejaculatory problems, diarrhoea and insomnia are expected but, with the exception of ejaculatory problems and nausea, which is mild and transient, these were generally no more frequent than with placebo in fully published clinical trials. No adverse events not previously seen in acute trials were reported with long-term use. Conclusions: Escitalopram, the S-enantiomer of RS-citalopram, is a highly selectiveinhibitor for the serotonin transporter, ameliorates depressive symptoms in patients with MDD at half the RS-citalopram dosage, has a rapid onset of symptom improvement and has a predictable tolerability profile of generally mild adverse events. Like RS-citalopram, escitalopram is expected to have a low propensity for drug interactions, a potential benefit in the management of patients with comorbidities. In combination, these properties place escitalopram, like other SSRIs, as first-line therapy in patients with MDD. Escitalopram is indicated for use in patients with panic disorder in Europe and, should further evidence confirm early findings that escitalopram reduces anxiety, the drug may well find an additional role in the management of anxiety disorders. Pharmacodynamic Properties Escitalopram is the therapeutically active S-enantiomer of RS-citalopram, which is a highly selective and effective serotonin reuptake inhibitor. The antidepressant mechanism of escitalopram is presumed to be a result of stimulation of serotonergic neurotransmission in the CNS as a consequence of higher serotonin levels resulting from inhibition of the serotonin transporter. Escitalopram has no or very low affinity for a variety of other serotonin, dopamine, α- and β-adrenergic, histamine, muscarinic and benzodiazepine receptors. It also does not bind to or has low affinity for a range of ion channels including those for $ Na^{+} $], $ K^{+} $], $ Cl^{-} $] and $ Ca^{2+} $]. In rat models predictive of antidepressant activity, escitalopram demonstrated higher activity than RS- citalopram. The minimum effective dose was 4-fold lower with escitalopram than with RS-citalopram in reducing aggressive behaviour in the resident-intruder rat model and in reducing panic-like anxiety in rats after electrical stimulation of the dorsal peri-aquaductal grey matter. A trial using a conditioned fear model in rats found that escitalopram reversed suppression of exploratory activity more rapidly than a comparable dose of S-citalopram in RS-citalopram. This qualitative difference between S-citalopram and RS-citalopram was confirmed by another in vivo trial that showed higher extracellular serotonin concentrations in the frontal cortex of rats after injection with escitalopram than in rats treated with a racemic mixture of S-citalopram and R-citalopram, indicating inhibition of the S-enantiomer by the R-enantiomer in the racemate. Pharmacokinetic Properties Escitalopram shows linear and dose-proportional pharmacokinetics with steady—state plasma concentrations achieved in 1 week in healthy volunteers. The mean steady-state area under the plasma concentration-time curve (0–24h) after a dosage of 10 mg/day was 360.2 ng · h/mL in healthy volunteers. After a single dose of escitalopram 20mg, peak plasma concentrations were reached in 4–5 hours and were not affected by food intake. Absolute bioavailability of RS-citalopram is about 80% and binding to human plasma proteins of escitalopram is approximately 56%. The apparent volume of distribution of escitalopram after oral administration is 12–26 L/kg. The pharmacokinetic profile of the S-enantiomer is the same whether given as escitalopram 10mg or RS-citalopram 20mg. Escitalopram is transformed to two metabolites, S-demethylcitalopram and S-didemethylcitalopram, both of which are much less potent than the parent drug. Alernatively, the nitrogen atom may be oxidised to the N-oxide metabolite. Escitalopram is the predominant plasma compound. The primary isoenzymes involved in metabolising escitalopram are cytochrome P450 (CYP) 2C19, CYP3A4 and CYP2D6. Elimination of escitalopram is principally via hepatic and renal routes as metabolites. Oral clearance of escitalopram is 36 L/h (600 mL/min) and the elimination half-life (t1/2) is between 27 and 32 hours. There are no sex-related differences in escitalopram pharmacokinetics; however, escitalopram is eliminated more slowly in the elderly but maximum plasma concentration is unchanged thus increasing systemic exposure. In addition, oral clearance of RS-citalopram was reduced by 37% and t1/2; doubled in patients with hepatic impairment. Therapeutic Efficacy Antidepressive efficacy was observed in patients with major depressive disorder (MDD) in 8-week trials with significant improvements in Montgomery-Åsberg Depression Rating Scale (MADRS) scores in patients receiving escitalopram 10 or 20 mg/day versus those receiving placebo noted as early as 1–2 weeks after starting therapy. Follow-on studies found that escitalopram reduced the long-term risk of relapse and continued to reduce MADRS scores. Significant improvements ere also observed in all secondary efficacy parameters including the Hamilton Rating Scale for Depression (HAM-D) and the Clinical Global Impressions Improvement and Severity scales (CGI-I and CGI-S) scores, and at least half of patients receiving escitalopram responded to treatment. Escitalopram showed earlier and better efficacy than RS-citalopram in a subgroup of patients with moderate MDD after 24 weeks and produced sustained response and remission significantly more rapidly (p < 0.05) than venlafaxine extended release (XR) at several timepoints over 8 weeks in patients with this disorder. In addition, improvements in quality of life (QOL) were experienced in the one study to report this. Significantly greater reductions in Hamilton Rating Scale for Anxiety (HAM-A) scores were observed in 124 patients, meeting the DSM-IV criteria for generalised anxiety disorder (GAD), who received escitalopram than in 128 patients meeting the same criteria who received placebo for 8 weeks. Improvements were also observed in several secondary efficacy parameters in the patients receiving escitalopram. In a 12-week study in patients who met the DSM-IV criteria for social anxiety disorder (SAD), those receiving escitalopram (n = 181 ) showed greater reductions in all SAD measurement scores and in disability scores than those receiving placebo (n = 177). The primary efficacy parameter was changes in Liebowitz Social Anxiety Scale scores from baseline to week 12. Secondary efficacy parameters included CGI-I scores, changes in CGI-S scores and Sheehan Disability scores over the same period. Escitalopram was significantly more effective than placebo in the treatment of panic disorder for all efficacy parameters in a 10-week trial. Efficacy measurements included frequency of panic attacks, the Panic and Anticipatory Anxiety Scale, Panic and Agoraphobia Scale, HAM-A, CGI-I and CGI-S scores, the Patient Global Evaluation and a QOL questionnaire. Improvements were apparent by week 4 in patients with GAD or panic disorder. 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|
score |
7.400773 |