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.     

A double-blind, randomized, parallel-group, flexible-dose study to evaluate the tolerability, efficacy and effects of treatment discontinuation with escitalopram and paroxetine in patients with major depressive disorder

This multinational, randomized, double-blind, flexible-dose study evaluated the short- and long-term antidepressant tolerability and efficacy of escitalopram and paroxetine. Tolerability was assessed by monitoring adverse events throughout the study, and discontinuation events during brief treatment interruption and tapered withdrawal. Discontinuation-emergent effects were evaluated in two separate double-blind periods. First, to mimic the consequences of non-compliance, patients were randomized to one of two treatment interruption periods (placebo-substitution for 3-5 days). Second, patients were randomized to a 1-2-week tapered withdrawal period randomly scheduled between weeks 28 and 31. The pre-specified primary efficacy endpoint was the mean change from baseline in total Montgomery-Asberg Depression Rating Scale (MADRS) score at week 8, using the principle of last observation carried forward. A total of 323 patients entered 8 weeks of double-blind treatment and received at least one flexible dose of escitalopram (10-20 mg/day) or paroxetine (20-40 mg/day). Patients who demonstrated evidence of a significant clinical improvement (Clinical Global Impression-Improvement of 1 or 2) at week 8 entered a 19-week, double-blind maintenance period during which they were treated with the same dose they received at week 8, followed by a 1-2-week tapered withdrawal period. A total of 89 patients (28%) withdrew during the study; significantly (P<0.01) more patients withdrew from the paroxetine group (34%) than from the escitalopram group (21%), and significantly (P<0.05) more paroxetine patients withdrew due to lack of efficacy. The mean MADRS total score improved for both treatment groups from baseline to week 8, with no statistical difference between groups. In severely depressed patients (baseline MADRS total score >or=30), escitalopram was superior (P<0.05) to paroxetine at week 27 (end of maintenance treatment). There was a high prevalence of sexual dysfunction at baseline: the mean Arizona Sexual Experience Scale (ASEX) score was approximately 20 points in both treatment groups. Mean total ASEX scores increased slightly above baseline values during the acute period and declined slightly below baseline values towards the end of the maintenance period. During taper and cessation of treatment, patients in the paroxetine group demonstrated significantly more discontinuation symptoms relative to escitalopram based on the Discontinuation Emergent Signs and Symptoms scores.     

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.     

The effect of escitalopram on sleep problems in depressed patients

The results from three 8-week escitalopram studies in major depressive disorder are presented with respect to efficacy and the effect on sleep quality, both in the full population and the subpopulation of patients with sleep problems at baseline.Analysis of pooled data from these randomized, double-blind, placebo-controlled, studies in which citalopram was the active reference, showed a significant improvement for escitalopram-treated patients (n = 52.0) in the Montgomery-Asberg depression rating scale (MADRS) item 4 ('reduced sleep') scores at weeks 6 and 8 compared with placebo (n=398; p < 0.01) and at weeks 4, 6 and 8 (n = 403; p < 0.05) compared with citalopram.Escitalopram-treated patients with sleep problems (MADRS item 4 score > or = 4; n = 254) at baseline showed a statistically significant improvement in mean MADRS item 4 scores at weeks 4, 6 and 8 compared with patients treated with placebo (n = 191; p < 0.05) or citalopram (n = 193; p < 0.01). These patients also showed a statistically significant (p < 0.05) and clinically relevant improvement in MADRS total score after escitalopram treatment compared with citalopram at weeks 1, 4, 6 and 8 (observed cases) and endpoint (-2.45; last observation carried forward [LOCF]). Statistical significance in favour of escitalopram versus placebo treatment was found at all visits, including endpoint (-4.2; LOCF).Thus, these post-hoc analyses suggest that escitalopram has a significant beneficial effect compared with placebo or citalopram in reducing sleep disturbance in patients suffering from major depressive disorder. The effect of escitalopram in improving 'reduced sleep' scores was clearly seen in patients with more severe sleep disturbance at baseline. A further prospective study is needed to establish this useful clinical effect in insomniac depressives.     

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.     

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

ABSTRACT

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-Åsberg Depression Rating Scale (MADRS) ≥ 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 ≤ 12) after 24 weeks was 75% for escitalopram and 67% for paroxetine (?p < 0.05). The results on the primary efficacy scale were supported by significantly greater differences in favour of escitalopram on the Hamilton Anxiety, Hamilton Depression and Clinical Global Impression-Improvement and -Severity scales. For very severely depressed patients (baseline MADRS ≥ 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.     

A comparative study of the efficacy of acute and continuation treatment with escitalopram versus duloxetine in patients with major depressive disorder

ABSTRACT

Objective: This study evaluated the efficacy and tolerability of escitalopram and duloxetine in the treatment of major depressive disorder (MDD).

Research design and methods: Patients were randomised to 24 weeks of double-blind treatment with fixed doses of escitalopram (20?mg) (n = 143) or duloxetine (60?mg) (n = 151). 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).

Main outcome measures; Results: At week 8, the mean change from baseline in total MADRS score was –19.5 for patients treated with escitalopram (n = 141) and –17.4 for patients treated with duloxetine (n = 146), a difference of 2.1 points (?p < 0.05). At week 8, the proportion of responders (≥?50% decrease in MADRS) was 69% (escitalopram) and 58% (duloxetine) (?p < 0.05) and remission (MADRS ≤?12) rates were 56% (escitalopram) and 48% (duloxetine) (NS). For the primary endpoint, the mean change from baseline in total MADRS score at week 24 was –23.4 for patients treated with escitalopram and –21.7 for patients treated with duloxetine, a difference of 1.7 points (?p = 0.055, one-sided). The difference in mean change from baseline in MADRS total score favoured escitalopram at weeks 1, 2, 4, 8, 12 and 16 (?p < 0.05). The overall withdrawal rates were 22% (escitalopram) and 25% (duloxetine) (NS). The withdrawal rate due to adverse events was lower for escitalopram (9%) compared to duloxetine (17%) (?p < 0.05) and significantly more patients treated with duloxetine reported insomnia (12.6% vs. 4.9%) and constipation (8.6% vs. 2.8%).

Conclusion: Escitalopram was superior to duloxetine in acute treatment and at least as efficacious and better tolerated in long-term treatment of MDD.     

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.     

Efficacy and safety of escitalopram versus citalopram in major depressive disorder: a 6-week, multicenter, randomized, double-blind, flexible-dose study

Rationale

S-citalopram (escitalopram) is the very active moiety of citalopram. It has been shown in many studies to be an effective and safe antidepressant for treating major depressive disorder (MDD).

Objective

The aim of our study was to compare the efficacy and safety of escitalopram vs citalopram in Chinese MDD patients.

Methods

In the double-blind study, 240 MDD patients were randomly assigned to treatment for 6 weeks either with escitalopram (10?C20?mg/d) or citalopram (20?C40?mg/d). The primary efficacy measurement was the change of 17-item Hamilton Depression Rating Scale (HAMD-17) total score from baseline to the end of study. The secondary efficacy measurements were response and remission rates. The adverse events (AEs) were recorded by the investigator.

Results

Two hundred and three (85%) patients completed the trial. The average dose was 13.9?mg/d in the escitalopram group and 27.6?mg/d in the citalopram group. No significant differences were found between the two groups in the change in HAMD-17 total score, response, and remission rate. These results were similar in severe MDD patients. No significant differences were found between the two groups in AEs. No serious AEs were observed in this study.

Conclusions

The study suggests that escitalopram 10?C20?mg/d are as effective and safe as citalopram 20?C40?mg/d in the short-term treatment for Chinese MDD patients.     

Escitalopram and duloxetine in the treatment of major depressive disorder: a pooled analysis of two trials

Pooled analyses have shown that escitalopram has superior effectiveness versus all comparators, including selective serotonin reuptake inhibitors and venlafaxine. Recent studies have compared escitalopram with duloxetine. Data from two randomized, double-blind studies that compared escitalopram (10-20 mg/day) and duloxetine (60 mg/day) were pooled and analysed for all patients and for the subsample of severely depressed patients [baseline Montgomery-Asberg Depression Rating Scale (MADRS) score > or =30]. Escitalopram (n=280) was superior to duloxetine (n=284) with respect to mean change from baseline in MADRS score at weeks 1, 2, 4 and 8 with a mean treatment difference at week 8 of 2.6 points (P<0.01). Similar results were seen for severely depressed patients, with a mean treatment difference of 3.7 points (P<0.01). Response and remission rates at week 8 were significantly higher for patients treated with escitalopram [response 67.1% for escitalopram compared with 53.2% for duloxetine, P<0.001; remission (MADRS< or =12) 54.3% for escitalopram compared with 44.4% for duloxetine, P<0.05]. The numbers needed to treat based on response and remission rates, in favour of escitalopram, were 8 and 11, respectively, for all patients (6 and 7, respectively, for severely depressed patients). Significantly fewer (P<0.001) patients (all cause and owing to adverse events) withdrew from the escitalopram group. This pooled analysis shows that over an 8-week treatment period, escitalopram (10-20 mg/day) is superior in both effectiveness and tolerability compared with duloxetine (60 mg/day).     

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.     

Escitalopram and duloxetine in major depressive disorder: a pharmacoeconomic comparison using UK cost data

BACKGROUND: Selective serotonin reuptake inhibitors (SSRIs) and serotonin-noradrenaline reuptake inhibitors (SNRIs) are approved for the treatment of major depressive disorder (MDD). The allosteric SSRI escitalopram has been shown to be at least as clinically effective as the SNRIs venlafaxine and duloxetine in MDD, with a better tolerability profile. In addition, escitalopram has been shown to be cost saving compared with venlafaxine. OBJECTIVE: To evaluate the cost effectiveness of escitalopram versus duloxetine in the treatment of MDD, and to identify key cost drivers. METHODS: The pharmacoeconomic evaluation was conducted alongside a 24-week, double-blind, multinational randomized study (escitalopram 20 mg/day and duloxetine 60 mg/day) in outpatients with MDD, aged 18-65 years, with Montgomery-Asberg Depression Rating Scale (MADRS) score >or=26 and Clinical Global Impression Severity (CGI-S) score >or=4, and baseline duration of the current depressive episode of 12 weeks to 1 year.The analysis was conducted on the full analysis set (FAS), which included all patients with >or=1 valid post-baseline health economic assessment. Effectiveness outcomes of the cost-effectiveness analyses (CEA) included the change in Sheehan Disability Scale (SDS) score (primary CEA), treatment response (MADRS score decrease >or=50%) and remission (MADRS score 相似文献   

Onset of action of escitalopram compared with other antidepressants: results of a pooled analysis

In general, antidepressant drugs are regarded as too slow acting. Most patients who benefit from treatment require more than 2 weeks of therapy to respond to treatment. An efficacious and well-tolerated antidepressant drug with an earlier onset of effect would be of greater interest to clinicians and patients. To study the onset of effect of escitalopram, a selective serotonin reuptake inhibitor (SSRI), data were pooled from controlled randomized clinical double-blind trials comparing this drug with other antidepressant drugs (SSRIs and venlafaxine XR) in major depressive disorder (MDD), with assessments of the primary efficacy parameter [mean change in the Montgomery-Asberg Depression Rating Scale (MADRS) total score from baseline, using last observation carried forward]. The mean change in MADRS total scores was significantly higher for escitalopram-treated patients than for patients treated with the comparators on day 7 (-3.9 versus -3.4, respectively, P = 0.029). This difference remained significant and in favour of escitalopram at all subsequent assessments. Using secondary outcomes (Clinical Global Impression of Improvement and Severity scales and early improvement), the results consistently showed a statistically significantly faster onset of effect of escitalopram compared to other antidepressants. In conclusion, by using the MADRS scale and pooling data from the escitalopram clinical trials in MDD comparing escitalopram with other active antidepressant drugs, escitalopram was shown to be a fast-acting antidepressant with a more rapid onset of effect than the comparators, particularly other SSRIs.     

A probabilistic cost-effectiveness analysis of escitalopram, generic citalopram and venlafaxine as a first-line treatment of major depressive disorder in the UK

OBJECTIVES: To determine if escitalopram is cost-effective in the UK when compared with venlafaxine and generic citalopram in primary care treatment of Major Depressive Disorder (MDD). METHODS: A pre-existing cost-effectiveness model was adapted to reflect the practice in the UK. Adult patients (> 18 years) with MDD [baseline scores >/= 18 and 相似文献   

Escitalopram in the treatment of major depressive disorder: A meta-analysis

ABSTRACT

Objective: To assess the relative antidepressant efficacy of escitalopram and comparator antidepressants.

Research design and methods: A meta-analysis was performed using studies in major depressive disorder (MDD) comparing escitalopram with active controls, including selective serotonin reuptake inhibitors [SSRIs] (citalopram, fluoxetine, paroxetine, sertraline) and serotonin/noradrenaline reuptake inhibitors [SNRIs] (venlafaxine, duloxetine). Adult patients had to meet DSM-IV criteria for MDD.

Main outcome measures: The primary outcome measure was the treatment difference in Montgomery–Åsberg Depression Rating Scale (MADRS) total score at week?8. Secondary outcome measures were response and remission (MADRS total score ≤?12) rates.

Results: Individual patient data (N?=?4549) from 16 randomized controlled trials were included in the analyses (escitalopram n?=?2272, SSRIs n?=?1750, SNRIs n?=?527). Escitalopram was significantly more effective than comparators in overall treatment effect, with an estimated mean treatment difference of 1.1?points on the MADRS (p?<?0.0001), and in responder (63.7?vs. 58.3%, p?<?0.0001) and remitter (53.1?vs. 49.4%, p?<?0.0059) analyses. Escitalopram was significantly superior to SSRIs, with an estimated difference in response of 62.1?vs. 58.4% and remission of 51.6?vs. 49.0%. In comparison to SNRIs, the estimated difference in response was 68.3?vs. 59.0% (p?=?0.0007) and for remission the difference was 57.8?vs. 50.5% (p?=?0.0088). These results were similar for severely depressed patients (baseline MADRS ≥?30). Sensitivity analyses were performed with data from articles reporting Hamilton Rating Scale for Depression (HAMD) scores. The 8-week withdrawal rate due to adverse events was 5.4% for escitalopram and 7.9% for the comparators (p?<?0.01). This difference was accounted for by statistically significant higher attrition rates in the SNRI comparisons. This work may be limited by the clinical methodology underlying meta-analytic studies, in particular, the exclusion of trials that fail to meet predetermined criteria for inclusion.

Conclusions: In this meta-analysis, superior efficacy of escitalopram compared to SSRIs and SNRIs was confirmed, although the superiority over SSRIs was largely explained by differences between escitalopram and citalopram.     

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   

Effectiveness and acceptability of sertraline and citalopram in major depressive disorder: pragmatic randomized open-label comparison

OBJECTIVE: Citalopram and sertraline are widely prescribed selective serotonin reuptake inhibitors (SSRIs). There is no conclusive evidence to show superiority of citalopram or sertraline in terms of efficacy or tolerability. Hence this study was designed to compare short term efficacy and safety of citalopram and sertraline in major depressive disorder (MDD) in Indian patients. METHODS: In an open, randomized study, 100 patients were divided into two groups. In Group A (n = 50) patients received citalopram (20-60 mg/day) for 6 weeks. In Group B (n = 50) patients received sertraline (50-150 mg/day) for 6 weeks. Patients were evaluated at baseline and then at 1, 2, 3, 4, 5, and 6 weeks. RESULTS: There was significant improvement in Hamilton depression rating scale (HDRS), Montgomery and Asberg depression rating scale (MADRS) and Amritsar depressive inventory (ADI) scores (p < 0.05) with both the drugs. However, the decrease in score was more with citalopram (p < 0.05). Onset of action of citalopram was earlier as compared to sertraline (p < 0.05). The number of responders and remitters was also more with citalopram (p < 0.05). No serious adverse event was reported in either of the groups. CONCLUSION: Citalopram had shown better efficacy, earlier onset of action and more number of responders and remitters as compared to sertraline in MDD in Indian patients.     

Efficacy of extended release quetiapine fumarate monotherapy in patients with major depressive disorder: a pooled analysis of two 6-week, double-blind, placebo-controlled studies

Prospectively planned pooled analysis evaluating the efficacy of quetiapine extended release (XR) monotherapy in major depressive disorder (MDD). Data were pooled from two 6-week, randomized, double-blind, placebo-controlled studies of quetiapine XR in outpatients with MDD. The primary endpoint was Montgomery-?sberg Depression Rating Scale (MADRS) total score change from randomization at week 6. Other evaluations were MADRS response/remission, Hamilton Rating Scale for Anxiety, and subgroup analyses. A total of 968 patients were randomized to quetiapine XR, 150 mg/day (n=315), 300 mg/day (n=323), or placebo (n=330). The mean MADRS total score reductions from randomization were significant at week 6 with quetiapine XR, 150 mg/day (-14.7; P<0.001) and 300 mg/day (-14.7; P<0.001) versus placebo (-11.1), with significant reductions versus placebo from week 1 onward. Response rates (week 6): 52.7% (P<0.001) quetiapine XR 150 mg/day and 49.5% (P<0.001) quetiapine XR 300 mg/day versus placebo (33.0%). MADRS remission (score≤8; week 6): 23.5% (P=0.208) quetiapine XR 150 mg/day and 28.8% (P<0.01) quetiapine XR 300 mg/day versus placebo (19.4%). Quetiapine XR (both doses) significantly improved eight of 10 MADRS items versus placebo at week 6. The therapeutic effect of quetiapine XR was neither limited to nor driven by factors such as sex, age, or severity of depression. In patients with MDD, quetiapine XR (150 and 300 mg/day) monotherapy reduced depressive symptoms, with significant improvements compared with placebo from week 1 onward.     

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.