Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Escitalopram is the active S-enantiomer of citalopram. In a chronic mild stress model of depression in rats, treatments with both escitalopram and citalopram were effective; however, a faster time to onset of efficacy compared to vehicle treatment was observed for escitalopram-treated (5 mg/kg/day) than for citalopram-treated (10 mg/kg/day) rats at Week 1. To study the predictability of this observation in the clinic, we analysed 4-week data from an 8-week, double-blind, randomised, placebo-controlled, flexible-dose study that compared escitalopram and citalopram to placebo in primary care patients with major depressive disorder (baseline Montgomery and Asberg Depression Rating Scale (MADRS) scores > or =22 and < or =40). Since the flexible dosing started after Week 4, analysis of 4-week data ensured that the patients received fixed doses of 10 mg/day escitalopram (155 patients), 20 mg/day citalopram (160 patients), or placebo (154 patients). The efficacy analysis showed a significantly superior therapeutic effect for escitalopram versus placebo from Week 1 onwards (observed cases) with an adjusted mean change in MADRS at Week 4 (last observation carried forward) of 2.7 points (P=0.002). By comparison, 20 mg/day citalopram did not demonstrate a statistically significant effect compared to placebo. Escitalopram was well tolerated with an adverse event profile similar to that of citalopram. The preclinical observation that escitalopram possesses a faster time to onset of efficacy than citalopram was also seen in primary care patients with major depressive disorder. Thus, escitalopram is efficacious in depression and the effect occurs earlier than for citalopram.
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PMID:Escitalopram (S-enantiomer of citalopram): clinical efficacy and onset of action predicted from a rat model. 1188 63

Escitalopram, a selective serotonin reuptake inhibitor (SSRI), was compared to placebo in a study of patients with major depressive disorder (DSM-IV) who had baseline Montgomery-Asberg Depression Rating Scale (MADRS) total scores >or=22 and <or=40. After a 1-week, single-blind placebo period, patients were randomized to receive escitalopram 10 mg/day (n=191) or placebo (n=189) in an 8-week, double-blind period. The primary efficacy analysis of adjusted mean change in MADRS total score from baseline showed a statistically significantly larger effect for escitalopram than for placebo with a treatment difference at week 8 (last observation carried forward, LOCF) of 2.7 points (SE 0.85; P=0.002). In further by-week efficacy analyses, the effect of escitalopram was consistently larger than that of placebo (P<0.05) beginning at week 1 (Clinical Global Impression-Improvement score), week 2 (MADRS score) or week 3 (Clinical Global Impression-Severity score). Escitalopram was very well tolerated with a low overall withdrawal rate similar to that for placebo. Nausea was the only adverse event reported significantly more in escitalopram-treated patients than in placebo-treated patients, although it was infrequent and transient. Escitalopram 10 mg/day had a statistically significantly better antidepressant effect than placebo as early as week 1, and was safe and very well tolerated.
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PMID:Escitalopram 10 mg/day is effective and well tolerated in a placebo-controlled study in depression in primary care. 1198 49

Selective serotonin reuptake inhibitors, the antidepressants most widely prescribed today, exert specific action against various anxiety disorders and have an excellent acceptability profile. In addition, anxiety problems are commonly seen in depression, in the form of either characterised anxiety disorders or associated anxious symptoms. Such symptoms of anxiety result in increased risk of suicide and appear to be associated with development of more severe and chronic depressive disorders. Because of the adverse effects associated with anxiolytics, in particular benzodiazepines, their indications have been restricted. Consequently, first-line drug therapy for anxiety symptoms associated with depression involves selection of an antidepressant having anxiolytic properties. Specific serotonin reuptake inhibitors are commonly favoured at present since they have a less pronounced sedative effect than the tricyclic antidepressants (e.g. amitriptyline, maprotiline). Escitalopram, the active enantiomer of citalopram, has demonstrated efficacy and rapidity of action upon depressive symptoms seen in major depressive episodes. Global analysis of three studies comparing citalopram and escitalopram with a placebo in depressive disorders allowed specific investigation of the activity of these molecules upon the anxiety component of depressive disorders. Anxiety was quantitatively evaluated using item 6 (inner tension) of the MADRS, and for two of the three studies, using the anxiety sub-score of the HAM-D as well as the HAM-A total score. The results for the two active molecules demonstrate significant superiority in comparison with the placebo. Furthermore, in the case of escitalopram, this improvement appeared significant as of the first week of treatment (p<0.05); by the end of the second week of treatment, the degree of significance was even more pronounced (p<0.001). The tolerability profile of these two active substances was very good. These studies thus demonstrate the efficacy of escitalopram against anxiety symptoms associated with depression, together with particularly interesting rapidity of action. Use of an antidepressant with proven activity against anxiety accompanying depression avoids the need for co-prescription of tranquillizers, which themselves are not devoid of adverse effects.
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PMID:[Effects of escitalopram on anxiety symptoms in depression]. 1238 49

Escitalopram oxalate (S-citalopram, Lexapro), a selective serotonin re-uptake inhibitor antidepressant which is the S-enantiomer of citalopram, is in clinical development worldwide for the treatment of depression and anxiety disorders. Preclinical studies demonstrate that the therapeutic activity of citalopram resides in the S-isomer and that escitalopram binds with high affinity to the human serotonin transporter. Conversely, R-citalopram is approximately 30-fold less potent than escitalopram at this transporter. Escitalopram has linear pharmacokinetics, so that plasma levels increase proportionately and predictably with increased doses and its half-life of 27 - 32 h is consistent with once-daily dosing. In addition, escitalopram has negligible effects on cytochrome P450 drug-metabolising enzymes in vitro, suggesting a low potential for drug-drug interactions. The efficacy of escitalopram in patients with major depressive disorder has been demonstrated in multiple short-term, placebo-controlled clinical trials, three of which included citalopram as an active control, as well as in a 36-week study evaluating efficacy in the prevention of depression relapse. In these studies, escitalopram was shown to have robust efficacy in the treatment of depression and associated symptoms of anxiety relative to placebo. Efficacy has also been shown in treating generalised anxiety disorder, panic disorder and social anxiety disorder. Results also suggest that, at comparable doses, escitalopram demonstrates clinically relevant and statistically significant superiority to placebo treatment earlier than citalopram. Analysis of the safety database shows a low rate of discontinuation due to adverse events, and there was no statistically significant difference between escitalopram 10 mg/day and placebo in the proportion of patients who discontinued treatment early because of adverse events. The most common adverse events associated with escitalopram which occurred at a rate greater than placebo include nausea, insomnia, ejaculation disorder, diarrhoea, dry mouth and somnolence. Only nausea occurred in > 10% of escitalopram-treated patients.
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PMID:Escitalopram. 1238 7

Escitalopram is a new antidepressant drug, available for clinical use in many countries. This review describes the properties of escitalopram, summarizes the results of randomized controlled trials, and suggests that escitalopram has advantages over citalopram in the treatment of depression.
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PMID:Escitalopram: efficacy and tolerability in the treatment of depression. 1247 11

Escitalopram was compared to placebo in moderately to severely depressed patients in primary care with citalopram as the active reference. Patients were randomized to receive flexible doses of 10-20 mg/day escitalopram (n=155), 20-40 mg/day citalopram (n=160), or placebo (n=154) over an 8-week double-blind period. The primary efficacy parameter was the change from baseline to last assessment in the Montgomery-Asberg Depression Rating Scale total score. Escitalopram produced a statistically significant therapeutic difference of 2.9 points (P=0.002) compared to placebo, and escitalopram was consistently and statistically significantly more efficacious than placebo from week 1 onwards. Analysis of Clinical Global Impression-Severity and Clinical Global Impression-Improvement confirmed the primary efficacy results. By week 8, significantly more patients had responded to treatment with escitalopram than with citalopram (P=0.021) or placebo (P=0.009). Escitalopram was as well tolerated as citalopram and had a similar adverse event profile. Both escitalopram- and citalopram-treated patients had placebo-level adverse event withdrawal rates (3% and 4%, respectively). This study demonstrates the consistent antidepressant efficacy and excellent tolerability of escitalopram 10-20 mg/day in primary care patients with major depressive disorder.
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PMID:Escitalopram (10-20 mg/day) is effective and well tolerated in a placebo-controlled study in depression in primary care. 1281 55

A first improvement in the treatment of depression was achieved in 1970-80 with the development of selective serotonin reuptake inhibitors (SSRI) because these drugs, which are as potent antidepressants as the tricyclics, are devoid of most of the secondary effects of the latter drugs (orthostatic hypotension, weight gain, dry mouth, etc, mainly caused by their capacity to block alpha1-adrenergic, H1 histaminergic and muscarinic receptors). However, SSRI did not solve all the problems inherent to the treatment of depression because (i) approximately 30% of depressed patients do not respond to these drugs, and (ii) their antidepressant effect becomes really significant only after 3-4 weeks of treatment, like that observed with tricyclics. A further improvement in the development of antidepressant drugs has recently been made with the synthesis of the S enantiomer of citalopram, called Escitalopram. Indeed, this active enantiomer is the most selective among all SSRI available to date, including citalopram. In addition, the potency of Escitalopram to inhibit serotonin reuptake (K(i)=2,1 nM) and to induce antidepressant-like effects in relevant animal paradigms (forced swimming test; chronic mild stress; stress-induced ultrasonic vocalization) is markedly increased as compared with citalopram and other SSRI. In particular, in the forced swimming test, which is especially relevant for assessing the potential antidepressant properties of drugs, Escitalopram was shown to be at least 15 fold more potent than any other SSRI to delay helplessness-induced immobility of rats. Even more interestingly, under chronic treatment conditions, Escitalopram was found to be significantly more rapid than any other antidepressant (tricyclics such as imipramine, SSRI such as fluoxetine) to restore sucrose intake in rats subjected to chronic mild stress, suggesting a reduced delay in its antidepressant action. This was indeed fully confirmed in humans as only 1-2 weeks of treatment with Escitalopram was enough to significantly reduce MADRS score in depressed subjects, compared to 3-4 weeks with any other antidepressant drug. These unique properties led to further investigations of the pharmacological profile of Escitalopram. It thus appeared that, at equipotent doses, the S enantiomer was significantly more efficient than citalopram (racemate) to increase the extracellular levels of serotonin within the frontal cortex of freely moving rats bearing a locally implanted microdialysis probe. Further experiments showed that R-citalopram counteracted the capacity of Escitalopram to enhance extracellular 5-HT levels, thereby explaining why the racemate had only a limited action in this regard. In addition, behavioural studies (stress-induced ultrasonic vocalization test) also showed that R-citalopram exerts effects opposite to those (antidepressant--and anxiolytic--like effects) of Escitalopram. The reason for these differences between the two enantiomers might concern the secondary molecular targets at which citalopram acts, but with affinities at least two orders of magnitude less than for the serotonin transporter. Indeed, R-citalopram has a 7-10-fold higher affinity for H1 histaminergic (K(i)=180 nM) and alpha1-adrenergic (K(i)=560 nM) receptors than Escitalopram (respective K(is) > or = 2 000 nM), and this difference might contribute not only to the better selectivity of the latter enantiomer for its therapeutically relevant target (i.e. the serotonin transporter) but also to its improved capacity to enhance central 5-HT neurotransmission. On the other hand, the global affinity of Escitalopram (K(i)=200-430 nM) for both subtypes of sigma receptors (sigma1 and sigma2) is higher than that of R-citalopram (and of the racemate citalopram; K(i)=200-1 500 nM), and this might also strengthen the antidepressant and anxiolytic effects of the S enantiomer because behavioural studies showed that selective sigma1 and sigma2 agonists are endowed with both antidepressant--and anxiolytic-like properties in relevant animal models. However, to date, the exact nature (agonist or antagonist) of the action of Escitalopram at sigma receptors is not known yet, and this question has to be addressed in future investigations. Altogether, these data open novel perspectives for both a better treatment of depressive disorders and a better knowledge of the neurobiological mechanisms underlying antidepressant therapy, and, possibly, depression itself.
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PMID:[Mechanisms of action of antidepressants: new data from Escitalopram]. 1287 51

S-citalopram (escitalopram) mediates the serotonin reuptake inhibitory effect of the racemate, R,S-citalopram. The effect of escitalopram (0.5-3.9 mg/kg) was investigated in a rat conditioned fear stress model of anxiety and compared to the effects of R-citalopram (1.0-7.8 mg/kg), R,S-citalopram (4.0 and 8.0 mg/kg), and escitalopram (2.0 mg/kg)+R-citalopram (7.8 mg/kg). Diazepam (0.95 mg/kg) and buspirone (4.6 mg/kg) were included as positive controls. During an acquisition session, rats were allowed to freely explore a novel cage for 9 min. During that time, they received two inescapable footshocks through an electrifiable grid floor. Groups of nonshocked control rats were run in parallel. During an expression session on the next day, rats were treated with drug or vehicle 30 min before they were reintroduced into the test cage for a 9-min period this time without receiving footshocks and the total distance travelled was recorded. The distance travelled by vehicle-treated rats was markedly suppressed compared to a vehicle-treated group of nonshocked controls. Escitalopram produced a dose-dependent inhibition of the conditioned suppression of exploratory behaviour (minimal effective dose 1.0 mg/kg). Interestingly R,S-citalopram 4.0 and 8.0 mg/kg produced significantly smaller effect than escitalopram 2.0 and 4.0 mg/kg, receptively. R-citalopram, 7.8 mg/kg, produced a significant effect. However, in spite of this, R-citalopram (7.8 mg/kg) significantly inhibited the effect of escitalopram (2.0 mg/kg). The activity in drug-treated nonshocked groups was similar to the vehicle-treated group, except for the buspirone-treated group where a significant reduction was observed. The finding that R-citalopram inhibits the effect of escitalopram may be relevant to the improved clinical efficacy seen with escitalopram compared to R,S-citalopram in the treatment of anxiety and depression.
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PMID:R-citalopram counteracts the effect of escitalopram in a rat conditioned fear stress model of anxiety. 1295 34

Escitalopram is the S-enantiomer of the racemic compound citalopram, a selective serotonin reuptake inhibitor (SSRI) widely used for the treatment of depression. This review describes the current body of pharmacologic and clinical evidence supporting the use of escitalopram for the treatment of depression and anxiety. Preclinical studies have confirmed that it is primarily this molecule that provides the inhibition of serotonin reuptake responsible for the antidepressant effect of citalopram, with minimal-to-nonexistent affinity for other receptor sites. Clinical trials of escitalopram in depressed patients indicate that escitalopram, 10 mg/day, is as effective as 40 mg/day of its parent compound, citalopram, with an excellent safety and tolerability profile. Because of its increased selectivity, escitalopram represents a refinement in SSRI therapy for symptoms of depression and anxiety. This article also explores the implications of a more selective SSRI on the management of depressed patients in the primary care clinical practice.
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PMID:Escitalopram: A New SSRI for the Treatment of Depression in Primary Care. 1501 11

Escitalopram is the S-enantiomer of citalopram. In this study, we compared the efficacy of equivalent dosages of escitalopram and citalopram in the treatment of moderate to severe major depressive disorder (MDD), based on data from two, pooled, randomized, double-blind, placebo-controlled studies of escitalopram in which citalopram was the active reference. The primary efficacy parameter was the mean change from baseline in the Montgomery Asberg Depression Rating Scale (MADRS) total score. Significant differences in favour of escitalopram were observed for the MADRS [P<0.05, observed cases (OC)/last observation carried forward (LOCF)] and Clinical Global Improvement-Severity of Illness scores (CGI-S; P<0.05, OC/LOCF). Escitalopram separated from placebo at week 1 on the primary efficacy parameter, whereas citalopram first separated from placebo at week 6. An analysis of time to response showed that escitalopram-treated patients responded significantly faster to treatment than citalopram-treated patients (P<0.01). More patients responded to and achieved remission with escitalopram than to citalopram (P<0.05, OC). The HAMD scale was only used in the fixed-dose study, where escitalopram-treated patients had a significant reduction in HAMD-17 total score at week 8 compared to citalopram-treated patients (P<0.05, OC/LOCF). In the pooled subpopulation of severely ill patients (MADRS> or = 30), escitalopram-treated patients showed greater improvement than citalopram-treated patients (P<0.05, LOCF/OC). Escitalopram showed consistently superior efficacy compared to citalopram in the treatment of moderate to severe MDD on all efficacy parameters, and was similarly well tolerated.
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PMID:Do equivalent doses of escitalopram and citalopram have similar efficacy? A pooled analysis of two positive placebo-controlled studies in major depressive disorder. 1510 57


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