Clinical efficacy and achievement of a complete remission in depression: increasing interest in treatment with escitalopram

Such a prevalent disease as Major Depressive Disorder (MDD), associated with prominent impairment in physical and social functioning, implies as well an increased morbidity and mortality. Long-term treatments are required due to the frequent occurrence of relapses. Patient compliance is a core factor in both acute and continuation treatment, closely related to tolerability issues. We have partially reviewed the literature published on PubMed since 2004 which assess the relative antidepressant efficacy of escitalopram and comparator antidepressants in adult patients who met DSM-IV criteria for major depressive disorder (MDD). Clinically important differences exist between commonly prescribed antidepressants. These analyses are in favor of a superior efficacy and tolerability of long-term escitalopram treatment (10 to 20mg/day) compared with active controls, including selective serotonin re-uptake inhibitors (SSRIs) (paroxetine, citalopram, bupropion, fluoxetine, fluvoxamine, sertraline), serotonin/noradrenaline reuptake inhibitors (SNRIs) (venlafaxine, milnacipran and duloxetine) and noradrenergic and specific serotonergic antidepressants (NaSSAs) (mirtazapine). Cipriani et al. (2009) have performed a network meta-analysis of 12 new generation antidepressants. They have shown that clinically important differences exist between commonly prescribed antidepressants for both efficacy and acceptability in favor of escitalopram and sertraline in acute treatment, defined as 8-week treatment. Kasper et al. (2009) conducted a post-hoc pooled analysis of data from two 6-month randomized controlled trials that revealed superior efficacy and tolerability of escitalopram when compared with paroxetine. The pooled analysis of four randomized, double-blind, active comparator, 6-month trials in MDD, by Wade et al. (2009), showed that short-term outcomes may predict long-term treatment compliance and outcomes. A higher probability of achieving remission was associated with responding after 8 weeks and with completing 6 months of treatment. Furthermore, Week 24 complete remission (MADRS≤5) was significantly (P<0,01) higher for escitalopram (51.7%) than for the pooled comparators (45.6%). And after 6 months, fewer patients discontinued treatment with escitalopram (15.9%) than with the pooled comparators (23.9%) (P<0.001). This fragmentary review of the literature shows that it is necessary to adopt a stringent definition of remission in depression, especially in clinical trials; a MADRS total score less or equal to 10 to define remission, a MADRS total score less or equal to 5 to define complete remission, and moreover no MADRS single item greater than 1 to define symptom-free remission. In all these meta-analyses, the superiority of escitalopram compared with other antidepressants was confirmed for both acute and long-term treatment of MDD, especially in harshly depressed patients.     

Escitalopram is more effective than citalopram for the treatment of severe major depressive disorder

BACKGROUND: Escitalopram is a highly selective serotonin reuptake inhibitor (SSRI). It is the therapeutically active S-enantiomer of citalopram. It has been shown, compared with placebo, to be an effective and well-tolerated treatment for major depressive disorders (MDD) in both primary and specialist care settings. A recent meta-analysis has found that escitalopram-treated patients showed significant higher response rates and increased mean change from baseline in the Montgomery-Asberg Depression Rating Scale (MADRS) total scores at weeks 1 and 8 compared with citalopram-treated patients. Each of these active drugs shares similar safety profiles. Although the efficacy of newer antidepressants has been well established for the treatment of mild-to-moderate depression, there are very few studies concerning severe depression. OBJECTIVE: To determine if escitalopram is more effective than citalopram in patients with severe depression. METHODS: Data were pooled from three different clinical trials, each similar in design and inclusion/exclusion criteria, primary endpoints and assessment schedules. This analysis was exhaustive because it included all trials in which the maximum dose for escitalopram (20 mg) could be administered. According to the cut-off point taken to define severe depression based on the MADRS total score ( 30), 506 patients were considered as severely depressed patients and so included in this analysis. Among them, 169 received escitalopram, 171 received citalopram and 166 received the placebo. The primary efficacy parameter was the mean change from baseline to end of treatment in MADRS total score between escitalopram and citalopram groups, based on last-observation-carried-forward method. The change from baseline to endpoint of the Hamilton rating scale for Depression (HAM-D) and the Clinical Global Impression of Improvement and Severity (CGI-I and CGI-S) were also analysed as secondary criteria. Clinical response was defined by at least a 50% reduction in baseline MADRS total score or by at least a 60% reduction in baseline HAM-D score or by a score of 1 (very much improved) on the CGI scale, and remission by a MADRS total score pound 12. RESULTS: Results showed that the mean change from baseline in the MADRS total score was significantly higher in the escitalopram group compared with the citalopram group (- 17.3 vs - 13.8 respectively, p=0.003). This significant difference was observed as early as week 1 (p=0.01). Response rates were significantly higher for escitalopram than for citalopram (56% vs 41% respectively, p=0.007). A borderline significant difference was found for remission rate in the observed-cases analysis (43% vs 33% respectively, p=0.07). Analyses of the HAM-D, CGI-I and CGI-S scores revealed consistent results. DISCUSSION: This study shows that the new SSRI escitalopram has better efficacy in the treatment of severe depression than citalopram, its racemic parent. Mean differences between treatments groups were in favour of escitalopram for all scales. The benefits of escitalopram compared with citalopram, as demonstrated by both magnitude of effect and time of onset, are superior to the benefits of citalopram, an antidepressant drug with proven efficacy. This evidence clearly supports the use of escitalopram as a legitimate first-line treatment for MDD.     

Efficacy of escitalopram in the treatment of major depressive disorder compared with conventional selective serotonin reuptake inhibitors and venlafaxine XR: a meta-analysis

OBJECTIVE: Escitalopram is the most selective of the selective serotonin reuptake inhibitor (SSRI) antidepressants. Previous studies have suggested that escitalopram is superior to citalopram in efficacy. We conducted a meta-analysis of studies in which escitalopram was compared with other antidepressants to assess the relative efficacy of these agents. METHODS: Data from all randomized, double-blind studies in major depression in which escitalopram was compared with active controls (citalopram, fluoxetine, paroxetine, sertraline and venlafaxine XR [extended release]) were pooled. The 10 studies were conducted in both specialist settings and general practice. Patients met the criteria of the Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV), for major depressive disorder and were at least 18 years old. In all but 2 studies, patients were required to have a score of 22 or more on the Montgomery-Asberg Depression Rating Scale (MADRS). The primary outcome measure was the estimated difference in treatment effect in MADRS total score at the end of the study. Secondary outcome measures were the response to treatment (defined as a > or = 50% reduction in baseline MADRS total score) and remission rate (defined as MADRS total score < or = 12 at end of study). RESULTS: A total of 2687 patients were included in the analyses (escitalopram n = 1345, conventional SSRIs n = 1102, venlafaxine XR n = 240). Escitalopram was superior to all comparators in overall treatment effect, with an estimated difference in treatment effect of 1.07 points (95% confidence interval [CI] 0.42-1.73, p < 0.01), and in response (odds ratio [OR] 1.29, 95% CI 1.07-1.56, p < 0.01) and remission (OR 1.21, 95% CI 1.01-1.46, p < 0.05) rates. In analysis by medication class, escitalopram was significantly superior to the SSRIs and comparable to venlafaxine, although the overall results do not necessarily reflect a significant difference between escitalopram and individual SSRIs. These results were similar in the severely depressed population (patients with baseline MADRS > or = 30). The withdrawal rate due to adverse events was 6.7% for escitalopram compared with 9.1% for the comparators (p < 0.05). CONCLUSIONS: In this meta-analysis, escitalopram showed significant superiority in efficacy compared with the active controls.     

Qualitative changes in symptomatology as an effect of treatment with escitalopram in generalized anxiety disorder and major depressive disorder

The purpose of this article is to examine the similarities and differences between patients with Major Depressive Disorder (MDD) versus Generalized Anxiety Disorder (GAD) versus MDD with anxiety symptoms. Data were analysed from all randomized double-blind clinical studies with escitalopram that measured symptoms using either Hamilton Anxiety Scale (HAMA) or Montgomery-Asberg Depression Rating Scale (MADRS). The contribution of each item of a scale to the total score was calculated before and after treatment, in remitters. Most single items of the HAMA contribute nearly equally in patients with GAD. In patients with MDD, four symptoms (i.e. anxious mood, tension, insomnia and concentration) contribute to most to the HAMA total score. In patients with GAD, three symptoms (tension, sleep and concentration) contribute two-thirds of the MADRS total score. In contrast, most MADRS items contribute equally to the total score in patients with MDD. After treatment to remission, the profile of residual symptoms MDD or GAD was similar to the symptom profile before treatment. Anxiety symptoms are very common in patients with MDD or GAD, and the symptomatic pattern is similar. In both disorders, the symptomatic pattern of residual symptoms is similar to the pattern of symptoms before treatment.     

Escitalopram prevents relapse in older patients with major depressive disorder.

OBJECTIVE: The present study investigated the efficacy and tolerability of escitalopram in the prevention of relapse of major depressive disorder (MDD) in older patients who had responded to acute treatment with escitalopram. METHOD: A total of 405 patients who were aged 65 years or older with a primary diagnosis of MDD (according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria) and a Montgomery-Asberg Depression Rating Scale (MADRS) total score of 22 or more received 12-week, open-label escitalopram 10 or 20 mg per day treatment. Remitters (MADRS 相似文献   

Stimulant Prescription Cautions: Addressing Misuse, Diversion and Malingering

Major depressive disorder (MDD) in children and adolescents is a public health problem that requires evidence-based management. Our objective is to review available studies, with a PubMed search, and briefly summarize safety and efficacy results of (mostly SSRI) antidepressants in children and adolescents with MDD. Fluoxetine and escitalopram are safe and effective in the treatment of MDD in children and adolescents both in reduction of symptoms, and in remission/response rates. However, response rates are lower than for non-OCD anxiety. Sertraline also had positive results in one study that pooled results from two studies. The number needed to treat (NNT) for MDD is 10, and the number needed to harm (NNH) for suicidality is 112. Methodological limitations in the studies include, mainly, high placebo response rates, associated with multiple study sites, younger patients, and lower MDD severity. Treatment should be maintained close to 1 year after remission, to prevent relapse. FDA-approved fluoxetine and escitalopram are safe and effective in the treatment of pediatric MDD. Sertraline also has some data supporting its efficacy and safety, but is not FDA-approved. The possible modest increase in suicidal ideation in some patients should be known by clinicians, but the risk/benefit ratio is 1 to 11.2 times favorable to using SSRIs in moderate to severe MDD.     

Use of bupropion in combination with serotonin reuptake inhibitors.

Incomplete symptom remission and sexual side effects are common problems for which bupropion often is added to treatment with selective serotonin and serotonin-norepinephrine reuptake inhibitors (SSRIs and SNRIs) for patients with major depressive disorder (MDD). This article reviews the literature on combining bupropion with SSRIs or SNRIs. We used MEDLINE to select studies that included patients diagnosed with MDD treated with any combination of bupropion and an SSRI or SNRI, either to enhance antidepressant response or to ameliorate antidepressant-associated sexual dysfunction. Bibliographies of located articles were searched for additional studies. Controlled and open-label studies support the effectiveness of bupropion in reversing antidepressant-associated sexual dysfunction, whereas open trials suggest that combination treatment with bupropion and an SSRI or SNRI is effective for the treatment of MDD in patients refractory to the SSRI, SNRI, or bupropion alone. The available data suggest that, although not an approved indication, the combination of bupropion and either an SSRI or an SNRI is generally well tolerated, can boost antidepressant response, and can reduce SSRI or SNRI-associated sexual side effects. Additional randomized controlled studies are needed to answer important questions, such as those regarding optimal dose and duration of treatment.     

Escitalopram in the long-term treatment of major depressive disorder.

BACKGROUND: Escitalopram has been proven safe and efficacious in the treatment of major depressive disorder (MDD) in short-term studies. The long-term clinical tolerability and response to treatment are presented from a 12-month open-label study with a total exposure time to escitalopram of 486 patient years. METHODS: Patients (n = 590) with MDD entered the study after completing one of two 8-week, double-blind, placebo-controlled, lead-in studies in primary care. Escitalopram was administered at doses of 10 or 20 mg/day (dose based on physician's clinical judgement) with an average exposure to escitalopram of 315 days. The primary efficacy parameter was the Montgomery Asberg Depression Rating Scale (MADRS) total score. RESULTS: The overall withdrawal rate was 26%; and the withdrawal rate due to adverse events was 9%. The most common adverse events were headache, back pain, upper respiratory tract infection, rhinitis and nausea, with an incidence ranging from 11% to 17%. No new types of adverse events were seen after the acute period of 8 weeks, and the incidence declined with time. At baseline (entry into the 12-month study), patients had a mean MADRS total score of 14.2, which decreased to 10.5 after 8 weeks and 7.2 after 52 weeks (LOCF). The percentage of patients in remission (MADRS total score 相似文献   

Are typical starting doses of the selective serotonin reuptake inhibitors sub-optimal? A meta-analysis of randomized,double-blind,placebo-controlled,dose-finding studies in major depressive disorder

The purpose of this meta-analysis is to examine the relationship between selective serotonin reuptake inhibitor (SSRI) starting dose and treatment outcome in major depressive disorder (MDD). Medline/Pubmed, EMBASE, the Cochrane database, as well as a number of online clinical trial registries were searched for double-blind, placebo-controlled, fixed-dose trials comparing different starting doses of SSRIs for MDD. Data from nine trials (n=2340) were combined using a random-effects model. Patients randomized to receive the usual starting dose (10 mg escitalopram; 20 mg fluoxetine, paroxetine, citalopram; 50 mg sertraline and fluvoxamine) were less likely to respond than patients who received higher starting doses (RR=0.9; P=0.04; response rate 50.8 vs. 54.8%). The rate of discontinuation due to adverse events was lower among the usual starting dose group (9.8%) compared to the higher starting dose group (16.5%).Initiating treatment with SSRIs at doses higher than those typically used in clinical trials/settings is associated with higher response rates but also higher rates of discontinuation due to intolerance. Developing treatment strategies allowing clinicians to deliver higher initial SSRI doses while enhancing the tolerability of treatment may represent an alternative approach to improving the efficacy of treatment of MDD.     

Effects of selective serotonin reuptake and dual serotonergic-noradrenergic reuptake treatments on memory and mental processing speed in patients with major depressive disorder

Patients with major depressive disorder (MDD) usually suffer from altered cognitive functions of episodic memory, working memory, mental processing speed and motor response. Diverse studies suggest that different antidepressant agents may improve cognitive functions in patients with MDD. The aim of this work is to study the effects of serotonergic reuptake inhibitors (SSRIs) and serotonergic-noradrenergic reuptake inhibitors (SNRIs) treatments to improve the performance on memory tasks and mental processing speed in MDD. Seventy-three subjects meeting criteria for major depressive disorder were assessed with the Hamilton depression rating scale and a neuropsychological battery. The subjects were medicated with escitalopram (n = 36) or duloxetine (n = 37) for 24 weeks. At the end of the trial, the subjects were assessed again with the same neuropsychological battery used prior to the treatment. Both treatments improved importantly the episodic memory and to a lesser extent, working memory, mental processing speed and motor performance. Our results suggest that cognition is partially independent from improvement in clinical symptoms. Both groups achieved remission rates in the HAM-D-17 after 24 weeks of treatment, but SNRI was superior to SSRI at improving episodic and working memory. Our work indicates that the superiority of SNRI over the SSRI at episodic memory improvement is clinically relevant.     

Safety and efficacy of oral escitalopram as continuation treatment of intravenous citalopram in patients with major depressive disorder

The objective of this open-label, multicentre study was to evaluate the safety and efficacy of treatment with escitalopram (10 or 20 mg/day) for 6 weeks following a switch from intravenous citalopram treatment (20 or 40 mg/day) in patients presenting with a major depressive episode. A total of 173 patients were included, 147 (85%) of whom completed the study. The mean Montgomery-Asberg Depression Rating Scale (MADRS) total score at inclusion (last citalopram dose) was 31.6 +/- 9.9. The MADRS score decreased to 23.4 +/- 10.5 after 3 days of oral treatment with escitalopram and was 12.7 +/- 9.3 at the end of the study. The scores on the Clinical Global Impression (CGI) and Patient Global Evaluation scales also improved: at the end of the study, the response rates were 67% on the MADRS (defined as >or=50% decrease from MADRS baseline score) and 68% on the CGI-I (defined as CGI-I 相似文献   

Comparison of escitalopram and citalopram efficacy: A meta-analysis

OBJECTIVE Escitalopram is a new selective serotonin reuptake inhibitor (SSRI) indicated for the treatment of major depressive disorder (MDD) and panic disorder. Escitalopram is the therapeutically active enantiomer of citalopram. Its efficacy in the treatment of MDD was compared to that of citalopram.

METHODS A quantitative meta-analysis was applied to 1262 patients in four randomised clinical trials; the comparison was based on response rate and mean change from baseline in the Montgomery–Åsberg depression rating scale (MADRS) total score at week 8. Complementary analyses were performed on early MADRS change from baseline (week 1), in very severely depressed patients (baseline MADRS total score ≥35) and on the influence of the level of severity at baseline.

RESULTS Compared with citalopram, escitalopram-treated patients showed significantly higher response rates and increased mean change from baseline in MADRS at weeks 1 and 8. The superiority of escitalopram over citalopram was more pronounced in very severely depressed patients. This superiority was further shown to increase with degree of severity of the depression. The robustness of meta-analysis results was supported by sensitivity analyses. The clinical superiority of escitalopram versus citalopram is consistent with the results of preclinical pharmacological studies.

CONCLUSION Escitalopram was shown to be an effective therapeutic treatment for MDD, presenting significant advantages over citalopram.     

Effective dose of escitalopram in moderate versus severe DSM-IV major depression

INTRODUCTION: Data from the three available placebo-controlled trials with fixed doses of escitalopram in the acute therapy of DSM-IV major depressive disorder (MDD) were pooled. The hypothesis tested was that escitalopram 10 mg/d might be an effective dose in moderate MDD, whereas escitalopram 20 mg/d might be needed in severe depression. METHODS: The Montgomery-Asberg Depression Scale with all 10 items was used at baseline to differentiate between moderate (score range 22 to 29) and severe (scores > or = 30) major depression. The MADRS (6) was selected as the primary efficacy parameter, using a standardised effect size of 0.40 as indicator of clinically significant response. RESULTS: After 8 weeks of therapy, escitalopram 10 mg was superior to placebo, with a standardised effect size above 0.40 for patients with moderate depression, but not for those with severe depression. In contrast, 20 mg escitalopram was superior to placebo, with a standardised effect size above 0.40 in severe depression, but not in moderate depression. The MADRS (6) showed response (standardised effect sizes above 0.40) for moderate depression after two weeks of treatment with 10 mg escitalopram and in severely depressed patients after 4 weeks with 20 mg escitalopram. CONCLUSION: Escitalopram 10 mg/d was the optimal dose for the treatment of moderate DSM-IV MDD, while escitalopram 20 mg/d was an effective dose in patients with moderate to severe depression.     

5HT1A-mediated stimulation of cortisol release in major depression: use of non-invasive cortisol measurements to predict clinical response

The purpose of the present study was to explore 5HT1A-mediated cortisol release in major depressive disorder (MDD) patients in order to determine whether the degree of 5HT1A-receptor sensitivity can predict response to treatment with selective serotonin reuptake inhibitors (SSRIs). We examined whether the sensitivity of the 5HT1A receptor, as measured by the difference in salivary cortisol levels immediately before and 90 min following the administration of a single dose of the 5HT1A-selective agonist buspirone, predicted treatment outcome following an 8-week, fixed-dose, open trial of the SSRI escitalopram in 17 outpatients with MDD. Change in cortisol levels before and 90 min after the administration of buspirone were not found to predict treatment outcome, whether defined as clinical response (50% or greater reduction in symptom severity), or remission of symptoms. In conclusion, in the present study, we did not find that the change in salivary cortisol levels following the administration of a 5HT1A-selective agonist predicted treatment outcome following an 8-week, fixed-dose, open-label trial of the SSRI escitalopram among outpatients with MDD. Although the 5HT1A-desensetization hypothesis is still a valid one, the results of the present study could not provide any evidence in support.     

Acute Efficacy and Safety of Escitalopram Versus Desvenlafaxine and Vortioxetine in the Treatment of Depression With Cognitive Complaint: A Rater-Blinded Randomized Comparative Study

Objective This study aimed to compare the efficacy and safety of escitalopram, vortioxetine, and desvenlafaxine for acute treatment of major depressive disorder (MDD) with cognitive complaint (CC). Methods A total of 129 patients with MDD who also complained of CC were randomized evenly to either escitalopram, vortioxetine, or desvenlafaxine group and underwent a multi-center, six-week, rater-blinded, and head-to-head comparative trial. Differences in depressive symptoms following treatment were measured using the Hamilton Depression Rating Scale (HAMD) and the Montgomery-Åsberg Depression Rating Scale (MADRS). Subjective cognitive function and the presence of adverse events were assessed. Results The three antidepressant treatment groups did not show significant differences in the improvement of depressive symptoms as measured by HAMD and MADRS. Desvenlafaxine treatment was associated with a superior treatment response rate in depressive symptoms compared to vortioxetine or escitalopram treatment. However, no significant differences were found in the remission rate of depressive symptoms. The three antidepressant treatment groups did not show significant differences in the improvement of CC. Adverse profiles of each treatment group were tolerable, with no significant differences. Conclusion In acute antidepressant treatment for MDD with CC, escitalopram, vortioxetine, and desvenlafaxine presented similar efficacy in relief of depressive symptoms; however, desvenlafaxine was associated with a superior treatment. Further studies are needed to confirm these results by investigating the therapeutic efficacy and safety profile of long-term antidepressant treatment of MDD with CC (Clinical Trial Registry, http://cris.nih.go.kr/cris/en/: KCT0002173).     

促肾上腺皮质激素释放激素受体1基因多态与抗抑郁药物疗效的关联研究

目的探讨促肾上腺皮质激素释放激素受体1(corticotropin-releasing hormone receptor1,CRHR1)基因多态性与选择性5-羟色胺再摄取抑制剂(Selective Serotonin Reuptake Inhibitors,SSRIs)、5-羟色胺和去甲肾上腺素再摄取抑制剂(Serotonin and Norepinephrine Reuptake Inhibitors,SNRIs)抗抑郁疗效差异的相关性。方法对符合美国精神障碍诊断与统计手册第4版(Diagnostic and Statistical Manual of Mental Disorders,Fourth Edi-tion,DSM-Ⅳ)抑郁症诊断标准的271例抑郁症患者予以单一新型抗抑郁药(SSRIs或SNRIs)常规剂量治疗至少6周,以治疗前后17项汉密尔顿抑郁量表(Hamilton Depression Scale,HAMD)总分减分率作为评估疗效的指标。采用TaqMan探针法检测CRHR1基因上4个单核苷酸多态性(Single Nucleotide Polymorphism,SNP)的基因型,比较有效组(HAMD-17减分率≥50%)和无效组(HAMD-17减分率<50%)之间4个位点基因型及多位点组成单倍型的不同。结果治疗4周末:CRHR1基因rs17689966位点A等位基因及AA基因型携带者在治疗无效组的频率均显著高于有效组(88.0%vs.77.0%,P=0.004;75.8%vs.59.0%,P=0.004)。有3种单倍型在有效组和无效组之间的分布差异有统计学意义,分别是T-A/T-G(rs242924-rs17689966:86.6%vs.74.7%,P=0.002;8.1%vs.15.5%,P=0.018),G-T-G(rs4458044-rs rs242924-rs17689966:8.2%vs.15.5%,P=0.019)。治疗6周末:CRHR1基因4个SNPs的基因型、等位基因频率及单倍型分析在不同疗效患者组间分布差异均无统计学意义(均P>0.05)。结论CRHR1基因多态性可能与SSRIs、SNRIs类药物的早期疗效相关。     

CLOCK may Predict the Response to Fluvoxamine Treatment in Japanese Major Depressive Disorder Patients

Recent studies have shown that selective serotonin reuptake inhibitors (SSRIs) have circadian properties, suggesting that the antidepressive action of SSRIs may also be attributable to circadian mechanisms. Another study reported an association between clock gene (CLOCK) and improvements in insomnia symptoms from SSRIs treatment. Therefore, we examined the association between CLOCK and the efficacy of fluvoxamine treatment in 121 patients with Japanese major depressive disorder (MDD). The MDD patients in this study had scores of 12 or higher on the 17 items of the Structured Interview Guide for Hamilton Rating Scale for Depression (SIGH-D). We defined a therapeutic response as a decrease of more than a 50% in baseline SIGH-D within 8 weeks, and clinical remission as a SIGH-D score of less than seven at 8 weeks. We selected three tagging SNPs in CLOCK for the subsequent statistical association analysis. We detected a significant association between rs3736544, a synonymous polymorphism in exon 20, and the fluvoxamine therapeutic response in MDD in the allele/genotype-wise analyses. In addition, remission with fluvoxamine was also significantly associated with rs3736544. These associations remained significant after Bonferroni correction. Moreover, haplotype analysis findings supported these significant associations, which appeared to be due mainly to rs3736544, in the fluvoxamine therapeutic remission. Our results indicate that CLOCK genotype may be a predictor of fluvoxamine treatment response in Japanese MDD. However, our sample size was small, and a replication study using larger samples may be required for conclusive results. Taro Kishi and Tsuyoshi Kitajima contributed equally to this work.     

A Danish cost-effectiveness model of escitalopram in comparison with citalopram and venlafaxine as first-line treatments for major depressive disorder in primary care

The objective of this study was to model the cost-effectiveness of escitalopram in comparison with generic citalopram and venlafaxine in primary care treatment of major depressive disorder (baseline scores 22-40 on the Montgomery-Asberg Depression Rating Scale, MADRS) in Denmark. A three-path decision analytic model with a 6-month horizon was used. All patients started at the primary care path and were referred to outpatient or inpatient secondary care in the case of insufficient response to treatment. Model inputs included drug-specific probabilities derived from systematic literature review, ad-hoc survey and expert opinion. Main outcome measures were remission defined as MADRS < or = 12 and treatment costs. Analyses were conducted from healthcare system and societal perspectives. The human capital approach was used to estimate societal cost of lost productivity. Costs were reported in 2004 DDK. The expected overall 6-month remission rate was higher for escitalopram (64.1%) than citalopram (58.9%). From both perspectives, the total expected cost per successfully treated patient was lower for escitalopram (DKK 22,323 healthcare, DKK 72,399 societal) than for citalopram (DKK 25,778 healthcare, DKK 87,786 societal). Remission rates and costs were similar for escitalopram and venlafaxine. Robustness of the findings was verified in multivariate sensitivity analyses. For patients in primary care, escitalopram appears to be a cost-effective alternative to (generic) citalopram, with greater clinical benefit and cost-savings, and similar in cost-effectiveness to venlafaxine.     

A Danish cost-effectiveness model of escitalopram in comparison with citalopram and venlafaxine as first-line treatments for major depressive disorder in primary care

The objective of this study was to model the cost-effectiveness of escitalopram in comparison with generic citalopram and venlafaxine in primary care treatment of major depressive disorder (baseline scores 22–40 on the Montgomery–Åsberg Depression Rating Scale, MADRS) in Denmark. A three-path decision analytic model with a 6-month horizon was used. All patients started at the primary care path and were referred to outpatient or inpatient secondary care in the case of insufficient response to treatment. Model inputs included drug-specific probabilities derived from systematic literature review, ad-hoc survey and expert opinion. Main outcome measures were remission defined as MADRS≤12 and treatment costs. Analyses were conducted from healthcare system and societal perspectives. The human capital approach was used to estimate societal cost of lost productivity. Costs were reported in 2004 DDK. The expected overall 6-month remission rate was higher for escitalopram (64.1%) than citalopram (58.9%). From both perspectives, the total expected cost per successfully treated patient was lower for escitalopram (DKK 22,323 healthcare, DKK 72,399 societal) than for citalopram (DKK 25,778 healthcare, DKK 87,786 societal). Remission rates and costs were similar for escitalopram and venlafaxine. Robustness of the findings was verified in multivariate sensitivity analyses. For patients in primary care, escitalopram appears to be a cost-effective alternative to (generic) citalopram, with greater clinical benefit and cost-savings, and similar in cost-effectiveness to venlafaxine.