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.     

Prospective, multicentre, randomized, double-blind study of the efficacy of escitalopram versus citalopram in outpatient treatment of major depressive disorder

Pre-clinical studies, active-control clinical trials and meta-analyses indicate that escitalopram (S-citalopram) might be more effective than citalopram, the racemic mixture of S- and R-citalopram. The present study aimed to confirm the superior efficacy of escitalopram over citalopram. A double-blind, randomized clinical trial was performed in which general practitioners and psychiatrists compared fixed doses of escitalopram (20 mg/day) with citalopram (40 mg/day) over 8 weeks in outpatients with major depressive disorder (MDD) [baseline Montgomery-Asberg Depression Rating Scale (MADRS) score > or =30]. Primary efficacy parameter was change from baseline to last assessment in the MADRS total score. Out of 138 (aged 44.1+/-10.9 years; initial MADRS score 36.3+/-4.8) and 142 (aged 46.2+/-11.1 years; initial MADRS score 35.7+/-4.4) evaluable patients who were randomized to escitalopram and citalopram, respectively, six and 15 withdrew prematurely (P=0.05). The MADRS score decreased more in the escitalopram than in the citalopram arm (-22.4+/-12.9 versus -20.3+/-12.7; P<0.05). There were more treatment responders with escitalopram (76.1%) than with citalopram (61.3%, P<0.01). Adjusted remitter rates were 56.1% and 43.6%, respectively (P<0.05). Tolerability was similar in both groups. This randomized double-blind trial confirms that escitalopram has a superior effect to citalopram in MDD.     

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.     

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.     

Escitalopram (10-20 mg/day) is effective and well tolerated in a placebo-controlled study in depression in primary care

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.     

A randomized, double-blind, placebo-controlled study of citalopram in adolescents with major depressive disorder

In a European, multicenter, double-blind study, 244 adolescents, 13 to 18 years old, with major depression were randomized to treatment with citalopram (n = 124) or placebo (n = 120). One third of the patients in both groups withdrew from the study. No significant differences in improvement of scores from baseline to week 12 between citalopram and placebo were found. The response rate was 59% to 61% in both groups according to the Schedule for Affective Disorders and Schizophrenia for school-aged children-Present episode version (Kiddie-SADS-P) (depression and anhedonia scores < or =2) and Montgomery Asberg Depression Rating Scale (MADRS) (> or =50% reduction). Remission (MADRS score < or =12) was achieved by 51% of patients with citalopram and 53% with placebo. A post hoc analysis revealed that more than two thirds of all patients received psychotherapy during this study. For those patients not receiving psychotherapy, there was a higher percentage of Kiddie-SADS-P responders with citalopram (41%) versus placebo (25%) and a significantly higher percentage of MADRS responders and remitters with citalopram (52% and 45%, respectively) versus placebo (22% and 19%, respectively). Mild to moderate treatment-emergent adverse events were reported in 75% citalopram and 71% of placebo patients, most commonly headache, nausea, and insomnia. Serious adverse events occurred in 14% to 15% in both groups. Suicide attempts, including suicidal thoughts and tendencies, were reported by 5 patients in the placebo group and by 14 patients in the citalopram group (not significant) with no pattern with respect to duration of treatment, time of onset, or dosage. In contrast, the suicidal ideation (Kiddie-SADS-P) single item showed worsening more frequently in the placebo (18%) than in the citalopram group (8%).     

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).     

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.     

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.     

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 dose-response revisited: an alternative psychometric approach to evaluate clinical effects of escitalopram compared to citalopram and placebo in patients with major depression

In continuation of a previous psychometric analysis of dose-response data for citalopram in depression, the corresponding study data for escitalopram is of interest, since escitalopram is the active enantiomer of citalopram and because citalopram was used as the active control. Revisiting those corresponding data, the psychometric properties of the Montgomery-Asberg Depression Scale (MADRS) and the Hamilton Depression Scale (HAMD) were investigated by focusing on the unidimensional HAMD6 and MADRS6. Effect sizes were calculated and compared for two dosages of escitalopram (10 mg and 20 mg daily) and between each of these two dosages and 40 mg citalopram daily. The results showed that the three depression scales MADRS6, MADRS10 and HAMD6 were psychometrically acceptable (coefficient of homogeneity of 0.40 or higher). In the severely depressed patients (MADRS10> or =30) a rather clear dose-response relationship for escitalopram was seen on all three scales after 6 and 8 wk of therapy. Thus, the effect size for 10 mg escitalopram ranged from 0.28 to 0.38 while the effect sizes for 20 mg escitalopram ranged from 0.57 to 0.77. This difference was statistically significant (p<0.01). The effect size for 40 mg citalopram ranged from 0.36 to 0.47, which is within the range found for 40 mg citalopram in our previous dose-response analysis of citalopram after 6 wk of therapy. The numerically largest difference between 20 mg escitalopram and 40 mg citalopram was seen after 8 wk of therapy for MADRS10 (effect size 0.71 vs. 0.37). An item analysis identified 'suicidal thoughts' to be the most discriminating item in this respect. These results for the severely depressed patients were confirmed by the patients self-reported quality of life evaluation. When all included patients were analysed, however, no clear dose-response relationship was seen. In conclusion, a dose-response relationship for escitalopram was seen in the severely depressed patients on all outcome scales after 6 and 8 wk of treatment. After 8 wk of treatment 20 mg escitalopram was superior to 40 mg citalopram, but not after 2 wk of treatment.     

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 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 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   

Remission, dropouts, and adverse drug reaction rates in major depressive disorder: a meta-analysis of head-to-head trials

OBJECTIVE: To summarize remission rates and dropouts due to adverse drug reactions (ADRs) or lack of efficacy (LoE) of serotonin-norepinephrine reuptake inhibitors (SNRIs), selective serotonin-reuptake inhibitors (SSRIs), and tricyclic antidepressants (TCAs) in treating major depressive disorder. METHODS: We searched MEDLINE, EMBASE, IPA, and the Cochrane International Library from 1980-2005. Meta-analysis summarized outcomes from head-to-head randomized clinical trials comparing >or= 2 drugs from three antidepressants classes (SNRIs, and/or SSRIs, and/or TCAs) followed by >or= 6 weeks of treatment. Remission was a final Hamilton Depression Rating Scale (HAMD) score 0.05 for SNRIs versus TCAs; p < 0.001 for TCAs versus SSRIs and SNRIs versus SSRIs). When categorized as inpatients (n = 582) and outpatients (n = 1613), SNRIs had the highest remission rates (52.0% for 144 inpatients and 49.3% for 559 outpatients). SNRIs had lowest overall dropouts (26.1%), followed by SSRIs (28.4%), and TCAs (35.7%). Dropouts due to ADRs and LoE were 10.3% and 6.2% for SNRIs, 8.3% and 7.2% for SSRIs, and 19.8% and 9.9% for TCAs, respectively (p > 0.05 for ADR dropouts only). One limitation was the inclusion of only venlafaxine-XR; results may not be the same for immediate release forms. In addition, few studies reported remission rates. CONCLUSIONS: SNRIs had the highest efficacy remission rates (statistically significant for inpatients and outpatients), and the lowest overall dropout rates, suggesting clinical superiority in treating major depression.     

Cost-effectiveness analysis of escitalopram: a new SSRI in the first-line treatment of major depressive disorder in Austria

OBJECTIVES: To compare the cost-effectiveness of escitalopram, a new selective serotonin reuptake inhibitor (SSRI), with (generic) citalopram in the first-line treatment of major depressive disorder (MDD) in Austria. METHODS: A two-path decision analytic model with a 6-month horizon was adapted to the Austrian setting using Austrian clinical guidelines. All patients (aged >or= 18 years) started at the primary successfully treated patient was lower ( currency 115) for care path and were referred to specialist care in the secondary care path in case of insufficient response. Model inputs included drug-specific probabilities from head-to-head trial data, literature and expert opinion. The main outcome measure was success (i.e., remission defined as Montgomery-Asberg Depression Rating Scale (MADRS) score 相似文献   

Intravenous augmentative citalopram versus clomipramine in partial/nonresponder depressed patients: a short-term, low dose, randomized, placebo-controlled study

The aim of the present study was to evaluate the efficacy of short-term low-dose intravenous augmentative citalopram (10 mg/d) versus clomipramine (25 mg/d) versus placebo in a sample of patients with MDE and partial or no response to selective serotonin reuptake inhibitors (SSRIs). Fifty-four patients with a Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision, MDE and partial or no response to SSRIs per os (21-item Hamilton Depression Rating Scale [HAM-D21] score reduction, <50% or < or =25%, respectively, compared with pretreatment scores) were selected and randomized to citalopram (n = 18), clomipramine (n = 18), or placebo (n = 18) intravenous augmentation. The augmentation regimen lasted 5 days during which patients were maintained on their previous treatment with oral SSRIs. Analyses of variance with repeated measures on HAM-D(21), collected daily in blind-raters design, were performed to detect any change of depressive symptoms between the 3 groups. In addition, the number of responders and remitters was computed in the 3 groups of treatment. At end point, a significant treatment effect (F= 4.57; P = 0.015) and time-by-treatment effect (F = 11.22; P < 0.0001) were found on HAM-D21 total scores in favor of citalopram and clomipramine versus placebo, with a superiority of citalopram over clomipramine on overall symptoms (P = 0.05) as well as on anxiety-somatization symptoms (P = 0.027). The number of responders was significantly superior in the active treatment groups versus the placebo group ([chi](2)(2) = 16.36; P < 0.0001). The same result was found, considering the number of remitters ([chi](2)(2) = 13.50; P < 0.0001). Present findings suggest that both clomipramine and citalopram intravenous augmentation at low doses and for a short period are well tolerated and superior to placebo in major depressives with partial or no response to oral SSRIs with a possible superiority of citalopram over clomipramine with regard to anxiety-somatization symptoms. The lack of double-blind conditions and the limited sample size may limit the confidence in the reported results, and larger randomized controlled trials are warranted to confirm the present findings.     

The efficacy and safety of aripiprazole as adjunctive therapy in major depressive disorder: a second multicenter, randomized, double-blind, placebo-controlled study

Nonresponse to one or more antidepressants is common and an important public health problem. This study evaluated the efficacy and safety of adjunctive aripiprazole or placebo to standard antidepressant therapy (ADT) in patients with major depressive disorder who showed an inadequate response to at least 1 and up to 3 historical and 1 additional prospective ADT. The study comprised a 7-28-day screening, an 8-week prospective treatment, and a 6-week randomization phase. During prospective treatment, patients experiencing a major depressive episode (17-item Hamilton Rating Scale for Depression total score > or = 18) received single-blind adjunctive placebo plus clinicians' choice of ADT (escitalopram, fluoxetine, paroxetine controlled-release, sertraline, or venlafaxine extended-release). Subjects with inadequate response were randomized to adjunctive placebo (n = 190) or adjunctive aripiprazole (n = 191) (starting dose 5 mg/d, dose adjustments 2-20 mg/d, mean end-point dose of 11.0 mg/d). The primary efficacy endpoint was the mean change in Montgomery-Asberg Depression Rating Scale total score from end of prospective treatment phase to end of randomized treatment phase (last observation carried forward). Mean change in Montgomery-Asberg Depression Rating Scale total score was significantly greater with adjunctive aripiprazole than placebo (-8.5 vs -5.7; P = 0.001). Remission rates were significantly greater with adjunctive aripiprazole than placebo (25.4% vs 15.2%; P = 0.016) as were response rates (32.4% vs 17.4%; P < 0.001). Adverse events occurring in 10% of patients or more with adjunctive placebo or aripiprazole were akathisia (4.2% vs 25.9%), headache (10.5% vs 9.0%), and fatigue (3.7% vs 10.1%). Incidence of adverse events leading to discontinuation was low (adjunctive placebo [1.1%] vs adjunctive aripiprazole [3.7%]). Aripiprazole is an effective and safe adjunctive therapy as demonstrated in this short-term study for patients who are nonresponsive to standard ADT.     

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.     

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.