Escitalopram 10 mg/day is effective and well tolerated in a placebo-controlled study in depression in primary care

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 相似文献   

Escitalopram (S‐Enantiomer of Citalopram): Clinical Efficacy and Onset of Action Predicted from a Rat Model

Abstract: 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 Åsberg Depression Rating Scale (MADRS) scores ≥22 and ≤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.     

Escitalopram (S-enantiomer of citalopram): clinical efficacy and onset of action predicted from a rat model

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.     

Do equivalent doses of escitalopram and citalopram have similar efficacy? A pooled analysis of two positive placebo-controlled studies in major depressive disorder

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.     

A randomized, double-blind, 24-week study of escitalopram (10 mg/day) versus citalopram (20 mg/day) in primary care patients with major depressive disorder

OBJECTIVE: A randomized, double-blind, 24-week-fixed-dose study comparing the efficacy and safety of escitalopram to that of citalopram was safety was conducted in primary care patients with moderate to severe major depressive disorder (MDD). RESEARCH DESIGN AND METHODS: This was a randomized, double-blind, 24-week fixeddose study. Patients were randomly assigned to treatment with escitalopram 10 mg/day (n = 175) or citalopram 20 mg/day (n = 182). Clinical response was evaluated using the Montgomery-Asberg Depression Rating Scale (MADRS) and Clinical Global Impression-Severity (CGI-S) scale. The prospectively defined primary parameter of antidepressant efficacy was the change from baseline in the mean MADRS total score during the 24 weeks of double-blind treatment, using a repeated measures analysis of variance to compare the treatment groups over all assessment points simultaneously. RESULTS: Based on the primary parameter, escitalopram was at least as efficacious as citalopram. Based on the prospectively defined secondary parameter, mean change from baseline in the CGI-S score, escitalopram was statistically significantly superior to citalopram at Week 24. The importance of long-term treatment could be demonstrated, in that more than half (55% and 51%) of the patients who had not responded by Week 8 achieved remission by Week 24. Both escitalopram and citalopram were safe and well tolerated in acute and long-term treatment, and the overall adverse event profiles for the two drugs were similar. For the intent-to-treat population, there were statistically significantly fewer withdrawals in the escitalopram group than in the citalopram group, particularly after Week 8. CONCLUSION: Patients with MDD responded well to long-term treatment with either escitalopram or citalopram. This study demonstrated the importance of extending treatment of depression beyond 8 weeks.     

Escitalopram for treatment of night eating syndrome: a 12-week, randomized, placebo-controlled trial

The primary objective of this study was to examine the short-term effects of escitalopram on symptoms of night eating syndrome (NES) in a randomized controlled clinical trial. A total of 40 patients with NES were randomly assigned to double-blind treatment with escitalopram 20 mg (n = 20) or placebo (n = 20) for 12 weeks. Escitalopram was started at 10 mg/d with a dosage increase to 20 mg/d after 4 weeks; placebo dosing was identical. The primary end point was a mean change in total score of the Night Eating Questionnaire (NEQ). At 12 weeks, mean (SE) change in NEQ total score was -13.0 (1.6) and -10.6 (2.2) in the escitalopram and placebo groups, respectively (F(1,37) = 2.5, P = 0.124). There was a marginal interaction effect between response to escitalopram and race (F(1,34) = 4.0, P = 0.052), with a favorable effect for white patients (F(1,20) = 6.0, P = 0.024) but not for black patients (F(1,13) = 0.6, P = 0.453). Seven patients in the escitalopram group, compared with 6 patients in the placebo group, showed a 50% NEQ score reduction (P = 0.736). Sixteen patients in the escitalopram group and 12 patients in the placebo group no longer met NES criteria (P = 0.168). Twelve patients in the escitalopram group were classified as responders according to the Clinical Global Impression Improvement scale compared with 7 patients in the placebo group (P = 0.113). No significant between-group differences were found for weight, mood ratings, or adverse events. We conclude that escitalopram treatment for 12 weeks was not superior to placebo in reducing NES symptoms as measured by the NEQ.     

Prevention of relapse in generalized anxiety disorder by escitalopram treatment

Escitalopram has demonstrated a robust and dose-dependent efficacy in the treatment of generalized anxiety disorder (GAD) for up to 3 months. In the present study, the efficacy and tolerability of escitalopram in the prevention of relapse in GAD was investigated. A total of 491 patients with a primary diagnosis of GAD and a Hamilton Anxiety (HAMA) total score>or=20 received 12 wk of open-label treatment with a fixed dose of escitalopram (20 mg/d). Of these, 375 patients responded (HAMA total scoreor=15, or lack of efficacy, as judged by the investigator. The results of the primary analysis showed a clear beneficial effect of escitalopram relative to placebo on the time to relapse of GAD (log-rank test, p<0.001). The risk of relapse was 4.04 times higher for placebo-treated patients than for escitalopram-treated patients; the proportion of patients who relapsed was statistically significantly higher in the placebo group (56%) than in the escitalopram group (19%) (p<0.001). Escitalopram was well tolerated and 7% of the escitalopram-treated patients withdrew due to adverse events, vs. 8% of the placebo patients. The incidence of discontinuation symptoms with escitalopram during tapered withdrawal was low; the symptoms primarily being dizziness (10-12%), nervousness (2-6%), and insomnia (2-6%). Escitalopram 20 mg/d significantly reduced the risk of relapse and was well tolerated in patients with GAD.     

Escitalopram

Escitalopram oxalate (S-citalopram, Lexapro), a selective serotonin re-uptake inhibitor antidepressant which is the S-enantiomer of citalopram, is in clinical development worldwide for the treatment of depression and anxiety disorders. Preclinical studies demonstrate that the therapeutic activity of citalopram resides in the S-isomer and that escitalopram binds with high affinity to the human serotonin transporter. Conversely, R-citalopram is 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.     

艾司西酞普兰与氟西汀治疗抑郁症对照研究

目的比较艾司西酞普兰与氟西汀治疗抑郁症的疗效和安全性。方法随机将77例符合CCMD-3抑郁发作的住院患者分为艾司西酞普兰组和氟西汀组,艾司西酞普兰组剂量10～20mg／d,氟西汀组20～40mg／d,疗程6周。疗效采取汉密尔顿抑郁量表（HAMD）和汉密尔顿焦虑量表（HAMA）评定,不良反应和安全性用TESS和实验室检查评定。结果两组总体疗效相当,艾司西酞普兰组有效率为87．2％,治愈率为48．7％,氟西汀组有效率为86．8％,治愈率4为7．4％,两组疗效比较差异无显著性。但1周末时HAMD评分及减分率两组间差异有显著性,说明艾司西酞普兰起效快;艾司西酞普兰组不良反应发生率明显少于氟西汀组,差异有统计学意义。结论艾司西酞普兰是安全、有效的抗抑郁药。     

Escitalopram in the treatment of multisomatoform disorder: a double-blind, placebo-controlled trial

Despite the prevalence of multisomatoform disorder (MSD), there are few controlled trials of its pharmacotherapy. The aim of this study was to compare the efficacy and safety of escitalopram (10-20 mg/day) with that of placebo in treating patients with MSD over a 12-week period. Fifty-one outpatients aged from 18 to 65 years, with multiple medically unexplained symptoms, were recruited. The primary efficacy measure was a change on the Patient Health Questionnaire-15 scores from baseline to endpoint. Secondary efficacy endpoints included the Clinical Global Impression-Improvement score, the psychic and somatic subscales of the Hamilton Anxiety Scale, Montgomery-Asberg Depression Rating Scale, the Visual Analogue Pain Rating Scale, the Scale for the Assessment of Illness Behaviour and the Sheehan Disability Scale. On the primary analysis of covariance, escitalopram-treated patients had significantly greater reductions in Patient Health Questionnaire scores (P<0.0001) compared with placebo at week 12. Significant separation from placebo occurred from week 6 onwards. Escitalopram was superior to placebo on all secondary outcome endpoints, with the exception of the Scale for the Assessment of Illness Behaviour. The medication was well tolerated. In conclusion, in this 12-week, randomized, placebo-controlled study, escitalopram (10-20 mg/day) was both effective and well tolerated in the treatment of patients with MSD. Compared with placebo, escitalopram was associated with lower symptom scores, increased response and remission rates, and improved functioning.     

Escitalopram

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

Evidence based review of escitalopram in treating major depressive disorder in primary care

The study aimed to summarize clinical data for escitalopram in the treatment of major depressive disorder in primary care. Medline, Embase and Cochrane databases were searched for randomized controlled trials of escitalopram (10-20 mg/day for 8 weeks) versus other antidepressants in therapeutic doses or placebo. Patients were required to have had moderate/severe depression, with Montgomery-Asberg Depression Rating Scale (MADRS) scores recorded at baseline and 8 weeks. Outcomes examined were remission rates (MADRS/=50% decrease from baseline in MADRS at week 8). Data were combined using a random effects meta-analytic model. Of the 15 studies identified, 11 were rejected (five not primary care, four duplicate reports, one lacked 8-week MADRS scores, one not depression) and four were accepted (n=1472 patients). The four studies had nine arms, four for escitalopram (n=654), two for citalopram (n=333), one for venlafaxine-XR (n=142) and two for placebo (n=343). Remission rates for escitalopram were superior to placebo (48.7% versus 37.6%, P=0.003) and citalopram (52.8% versus 43.5%, P=0.003) but similar to venlafaxine-XR (P=0.97). Response rates were superior to placebo (48.7% versus 43.1%, P<0.001) and citalopram (62.5% versus 49.5%, P=0.001) but not venlafaxine-XR (P=0.52). Adverse events were comparable among active drugs (P<0.05). Remission rates for escitalopram were superior to placebo (48.7% versus 37.6%, P=0.003) and citalopram (52.8% versus 43.5%, P=0.003) but similar to venlafaxine-XR (P=0.97). Response rates were superior to placebo (48.7% versus 43.1%, P<0.001) and citalopram (62.5% versus 49.5%, P=0.001) but not venlafaxine-XR (P=0.52). Adverse events were comparable among active drugs (P>0.05). Remission and response rates of escitalopram in primary care are clinically superior to placebo and citalopram, but similar to venlafaxine-XR. Further head-to-head trials are warranted to verify these findings. A pharmacoeconomic analysis is also required to determine whether these clinical advantages for the patients translate into economic advantages for the health care system.     

Combining escitalopram with gaboxadol provides no additional benefit in the treatment of patients with severe major depressive disorder

The aim of this proof-of-concept study was to compare the efficacy of escitalopram (20 mg/d) in combination with fixed doses of gaboxadol to escitalopram (20 mg) in the treatment of patients with severe major depressive disorder (MDD). Adult patients were randomized to 8 wk of double-blind treatment with fixed doses of placebo (n=71), escitalopram (20 mg, n=140), escitalopram (20 mg)+gaboxadol (5 mg) (n=139), or escitalopram (20 mg)+gaboxadol (10 mg) (n=140). The pre-defined primary analysis of efficacy was an analysis of covariance (ANCOVA) of change from baseline to endpoint (week 8) in Montgomery-?sberg Depression Rating Scale (MADRS) total score using last observation carried forward (LOCF). There was no statistically significant difference in the mean change from baseline in MADRS total score between the 20 mg escitalopram+10 mg gaboxadol group and the 20 mg escitalopram group [difference=-0.45 MADRS points (95% CI -2.5 to 1.6, p=0.6619, full analysis set (FAS), LOCF, ANCOVA)] at week 8. The mean treatment differences to placebo at week 8 were -5.6 (95% CI -8.0 to -3.1, p<0.0001) (20 mg escitalopram), -5.1 (95% CI -7.5 to -2.7, p<0.0001) (20 mg escitalopram+5 mg gaboxadol), and -6.0 (95% CI -8.4 to -3.6, p<0.0001) (20 mg escitalopram+10 mg gaboxadol). The most common adverse events reported in the active treatment groups for which the incidence was higher than that in the placebo group, comprised nausea, anxiety and insomnia. There were no clinically relevant efficacy differences between a combination of escitalopram and gaboxadol compared to escitalopram alone in the treatment of severe MDD. All active treatment groups were superior in efficacy to placebo and were well tolerated.     

Escitalopram versus placebo in the treatment of dysthymic disorder

Numerous studies have assessed the acute efficacy of antidepressants, including selective serotonin reuptake inhibitors, in treating dysthymic disorder; however, escitalopram, the S-enantiomer of citalopram, has not been studied. Thirty-six outpatients with Structured Clinical Interview for DSM-III-R-diagnosed dysthymic disorder, aged 23-65 years (mean±SD=44.7±11 years), were randomly assigned to double-blind escitalopram (maximum dose 20?mg/day) versus placebo for 12 weeks. Inclusion criteria included age 18-65 years and Hamilton Depression Rating Scale (HDRS) score≥12. We hypothesized that escitalopram would be superior to placebo in the HDRS-24 item total score at week 12. We also hypothesized the superiority of escitalopram over placebo for secondary measures, including the percentage of participants classified as responders and remitters, as well as social functioning (Social Adjustment Scale), clinical global impression-improvement, Global Assessment of Functioning Scale. Participants' baseline HDRS-24 averaged 23.4±5.9. Final HDRS-24 scores at last observation carried forward did not differ significantly between escitalopram-treated (mean±SD=10.88±5.83) and placebo-treated individuals (mean±SD=16.4±6.34) (F=2.82, degrees of freedom=1,32, P=0.10). Significant differences favoring active medication were found on the Social Adjustment Scale and the Clinical Global Impression Severity and Global Assessment of Functioning Scale, but not in the percentages of responders or remitters. A larger study sample or higher escitalopram dose may show more significant placebo-medication differences.     

艾司西酞普兰与西酞普兰治疗抑郁症的对照研究

目的评价艾司西酞普兰治疗抑郁症的有效性和安全性。方法选择126例抑郁症患者,试验组63例,口服艾司西酞普兰:1-2周口服10 mg,3-6周剂量可调10-20 mg;对照组63例,口服西酞普兰:1-2周口服20 mg,3-6周剂量可调20-40 mg。疗程6周,以十七项汉密尔顿抑郁量表(HAMD-17)、汉密尔顿焦虑量表(HAMA)和临床总体印象量表(CGI)进行疗效评价;以不良事件、实验室检查和心电图检查等评价安全性。结果共106例患者完成研究,试验组52例,对照组54例。试验组与对照组6周末有效率(82.7%vs 88.9%,P=0.484)、痊愈率(36.5%vs.27.8%,P=0.360),2组差异无统计学意义(P>0.05)。HAMA和CGI的评分在各时间点2组相比差异无统计学意义(P>0.05)。试验组与对照组不良反应发生率(17.5%vs 30.2%,P=0.07)差异无统计学意义。结论艾司西酞普兰治疗抑郁症安全有效,与西酞普兰相当,不良反应较轻。     

Escitalopram in obsessive–compulsive disorder: a randomized,placebo-controlled,paroxetine-referenced,fixed-dose, 24-week study

ABSTRACT

Objective: A randomized, placebo-controlled fixed-dose trial was undertaken to determine the efficacy and tolerability of escitalopram in obsessive–compulsive disorder (OCD), using paroxetine as the active reference.

Research design and methods: A total of 466 adults with OCD from specialized clinical centres, psychiatric hospital departments, psychiatric practices, or general practice were randomized to one of four treatment groups: escitalopram 10?mg/day (n = 116), escitalopram 20?mg/day (n = 116), paroxetine 40?mg/day (n = 119), or placebo (n = 115) for 24 weeks. The primary efficacy endpoint was the mean change in the Yale–Brown Obsessive–Compulsive Scale (Y?BOCS) total score from baseline to week 12. Secondary efficacy endpoints included remission (defined as Y?BOCS total score ≤10), NIMH?OCS, and CGI?S and CGI?I scores at weeks 12 and 24. Tolerability was based on the incidence of adverse events, and on changes in vital signs (blood pressure and pulse).

Main outcome measures; Results: Escitalopram 20?mg/day was superior to placebo on the primary and all secondary outcome endpoints, including remission. Escitalopram 10?mg/day and paroxetine 40?mg/day were also effective on the primary scale as well as some other outcome measures. In the escitalopram 20?mg/day group, the improvement in Y?BOCS total score was significantly better than in the placebo group as early as week 6. The most common AEs in the active treatment groups were nausea (19–27%), headache (17–22%), and fatigue (12–19%). More paroxetine-treated patients withdrew due to adverse events than escitalopram- or placebo-treated patients.

Conclusion: Given that escitalopram 20?mg/day was associated with an earlier onset, higher response and remission rates, improved functioning, and better tolerability than the reference drug, escitalopram deserves to be considered as one of the first-line agents in the pharmacotherapy of OCD for longer-term treatment periods.     

Escitalopram : a review of its use in the management of major depressive and anxiety disorders

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-Asberg 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 selective inhibitor 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.     

Efficacy and tolerability of extended release quetiapine fumarate monotherapy in the acute treatment of generalized anxiety disorder: a randomized, placebo controlled and active-controlled study

The main objective of this study was to evaluate efficacy and tolerability of once-daily extended release quetiapine fumarate (quetiapine XR) monotherapy in generalized anxiety disorder (GAD). This was a 8 week randomized, 2-week follow-up, double-blind, placebo-controlled, and active-controlled study. Patients were randomized to quetiapine XR 150 (n=219) or 300 mg/day (n=207); escitalopram, 10 mg/day (n=213); or placebo (n=215). The primary endpoint was the change from randomization at week 8 in Hamilton Anxiety Rating (HAM-A) total score. Week 8 mean HAM-A total score was significantly reduced from randomization with quetiapine XR 150 mg/day (-13.9, P<0.001), 300 mg/day (-12.3, P<0.05) and escitalopram (-12.3, P<0.05) versus placebo (-10.7); significant improvements with quetiapine XR (150 and 300 mg/day) versus placebo (P<0.001) were also shown at day 4. At week 8, significant improvements versus placebo were observed in HAM-A psychic [quetiapine XR (both doses) and escitalopram] and somatic (quetiapine XR 150 mg/day and escitalopram) cluster scores and HAM-A response and remission rates (quetiapine XR 150 mg/day). Most common adverse events were dry mouth, somnolence and sedation (quetiapine XR), headache, and nausea (escitalopram). In patients with GAD, quetiapine XR (150 and 300 mg/day) demonstrated significant efficacy at week 8 with symptom improvement as early as day 4. We concluded that quetiapine XR safety and tolerability results were consistent with the known profile of quetiapine.     

A comparative study of the efficacy of long-term treatment with escitalopram and paroxetine in severely depressed patients

OBJECTIVE: This randomised, double-blind, fixed-dose study evaluated the efficacy of escitalopram and paroxetine in the long-term treatment of severely depressed patients with major depressive disorder (MDD). RESEARCH DESIGN AND METHODS: Patients with a primary diagnosis of MDD and baseline Montgomery-Asberg Depression Rating Scale (MADRS) >or= 30 were randomised to 24 weeks of double-blind treatment with fixed doses of either escitalopram (20 mg) (n = 232) or paroxetine (40 mg) (n = 227). The primary analysis of efficacy was an analysis of covariance (ANCOVA) of change from baseline to endpoint (Week 24) in MADRS total score (last observation carried forward, LOCF). MAIN OUTCOME MEASURES; RESULTS: At endpoint (24 weeks), the mean change from baseline in MADRS total score was -25.2 for patients treated with escitalopram (n = 228) and -23.1 for patients with paroxetine (n = 223), resulting in a difference of 2.1 points (p < 0.05). The difference in the change in the MADRS total score (LOCF) was significantly in favour of escitalopram from Week 8 onwards. The proportion of remitters (MADRS or= 35), there was a difference of 3.4 points at endpoint in the MADRS total score in favour of escitalopram (p < 0.05). The overall withdrawal rate for patients treated with escitalopram (19%) was significantly lower than with paroxetine (32%) (p < 0.01). The withdrawal rate due to adverse events was significantly lower for escitalopram (8%) compared to paroxetine (16%) (p < 0.05). There were no significant differences in the incidence of individual adverse events during treatment. CONCLUSION: Escitalopram is significantly more effective than paroxetine in the long-term treatment of severely depressed patients.     

Cost-effectiveness of escitalopram vs. citalopram in major depressive disorder

Clinical trials have shown better efficacy of escitalopram over citalopram, and review-based economic models the cost-effectiveness of escitalopram vs. citalopram (brand and generic). No head-to-head clinical trial has, however, evaluated the cost-effectiveness of both drugs so far. The aim of this study was to assess the relative cost-effectiveness of escitalopram compared with citalopram in patients with major depressive disorder. An economic evaluation was conducted alongside a double-blind randomized clinical trial conducted by general practitioners and psychiatrists comparing fixed doses of escitalopram (20 mg/day) or citalopram (40 mg/day) over 8 weeks in ambulatory care patients with major depressive disorder (baseline Montgomery-Asberg Depression Rating Scale score > or =30). Resources use was recorded using a standardized form recording use of healthcare services and days of sick leave for the 2-month prestudy period and for the 8-week study period. Statistically significant improvements were observed in patients treated with escitalopram. Mean per-patient costs for the escitalopram group, compared with the citalopram group, were 41% lower (96 euro vs. 163 euro; P<0.05) from a healthcare perspective. Differences were mostly related to lower hospitalization costs for escitalopram compared with citalopram recipients, assuming a parity price between escitalopram and citalopram. Bootstrapped distributions of the cost-effectiveness ratios also showed better effectiveness and lower costs for escitalopram compared with citalopram. Escitalopram is significantly more effective than citalopram, and is associated with lower healthcare costs. This prospective economic analysis demonstrated that escitalopram is a cost-effective first-line treatment option for major depressive disorder.