Nicolas Despiegel

Efficacy of escitalopram in patients with severe depression: a pooled analysis

Escitalopram is an effective, well‐tolerated treatment for major depressive disorder in both primary and specialist settings. This analysis compared the efficacy of escitalopram with citalopram in the treatment of patients with severe depression [defined as a score of ≥30 Montgomery–Åsberg Depression Rating Scale (MADRS)]. Data from three clinical trials were used for this pooled analysis. A total of 506 severely depressed patients were included (169 received escitalopram, 171 citalopram and 166 placebo). Mean change from baseline in MADRS total scores (primary efficacy parameter) was significantly higher in the escitalopram‐treated group compared with the citalopram‐treated group (p = 0.003). There was a significant difference in response between escitalopram and citalopram (56 vs. 41%, respectively, p = 0.007). Results from secondary efficacy parameters (Hamilton rating for depression and Clinical Global Impression of Improvement and Severity scales) were consistent with previous results. The benefits in severe depression of escitalopram vs. citalopram were so demonstrated.

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 physicians 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 </=12) increased from 46% at baseline to 65% by Week 8 and 86% by Week 52. CONCLUSIONS Escitalopram (10 to 20 mg/day) demonstrated a favorable safety and tolerability profile over 12-months treatment, with further improvement in patient response.

Traitement des épisodes dépressifs sévères: escitalopram est plus efficace que citalopram

Resume La prise en charge therapeutique des patients atteints de depression severe reste encore un challenge pour les medecins. Par rapport a la forme legere ou moderee, la depression severe se caracterise souvent par une duree plus longue, une co-morbidite superieure, une plus faible probabilite de remission spontanee et un taux de rechute plus important. Par ailleurs, si l’efficacite des nouveaux antidepresseurs est bien etablie dans la depression legere a moderee, beaucoup moins d’etudes ont ete realisees dans la depression severe. Probablement parce que la depression severe n’est pas percue comme une entite a part, mais comme un continuum dans la clinique de cette pathologie, et aussi peut-etre en raison d’une absence de consensus clair sur la definition meme de cette severite. Apres avoir utilise les definitions basees sur la clinique et sur le mode de prise en charge, les auteurs semblent desormais privilegier l’utilisation des echelles cliniques avec un seuil specifique pour cette definition. En utilisant l’echelle MADRS (Montgomery-Asberg Depression Rating Scale) et la valeur seuil de 30 pour definir la severite de la depression, nous avons realise une analyse poolee avec les donnees des trois essais cliniques comparant l’efficacite du escitalopram a celle du citalopram. Les resultats montrent de facon constante une meilleure efficacite du escitalopram par rapport au citalopram, dans cette indication particuliere qu’est la depression severe.

Impact of Treatment Success on Health Service Use and Cost in Depression: Longitudinal Database Analysis

AbstractBackground: Research has consistently demonstrated a relationship between depression and increased levels of health service use over the short term. However, much less is known about how this relationship is influenced by the success, or otherwise, of depression management strategies, and the economic impact over the longer term. Objective: To investigate the economic impact of non-remission on health service use and costs over 12 months from the index episode in patients with depression. Methods: A naturalistic, longitudinal study was carried out using data from a large primary care UK general practice research database between 2001 and 2006. The records of 88935 patients aged ≥18 years, diagnosed with depression and in receipt of at least two antidepressant prescriptions (for amitriptyline, citalopram, escitalopram, fluoxetine, paroxetine, sertraline or venlafaxine) in the first 3 months after the index prescription were included. The main outcome measures were health service use and cost over the 12-month study period, by remission status, where remission is defined as patients not using antidepressants for at least 6 months after antidepressant treatment has ended. Results: Sociodemographic and clinical characteristics were similar for participants classified as in remission and those not in remission. Over 12 months from the index prescription, patients classified as non-remitters spent longer, on average, than patients classified as remitters on concomitant psychotropic medication (204 days vs 93 days, respectively), and had more contact with primary care services (17 vs 13 GP visits), secondary care psychiatrists and other specialists (47% vs 40%). Days in hospital, accident and emergency attendances and psychological therapy contacts did not differ between the groups. Total 12-month costs per participant were significantly lower for remitters (mean £656 vs £937; mean difference £317; p < 0.0001). Total costs fell over time for both groups, but at a faster rate for those in remission, and for those who remitted earlier after the index prescription than for those who remitted later. Conclusions: Successful cessation of antidepressant medication treatment in adults with depression can result in significant cost savings to the health service.

Challenges in measuring and valuing productivity costs, and their relevance in mood disorders

Lost productivity is often excluded from economic evaluations, which may lead to an underestimation of the societal benefits of treatment. However, there are multiple challenges in reliably estimating and reporting productivity losses. This article explores the main challenges, ie, selecting an appropriate valuation method (ie, human capital, friction cost, or multiplier), avoiding double counting, and accounting for equity. It also discusses the use of presenteeism instruments and their application in clinical trials, with a specific focus on their relevance in individuals with mood disorders. Further research and discussion is required on the development of reliable techniques for measuring and valuing productivity changes due to presenteeism.

Escitalopram and Duloxetine in Major Depressive Disorder: A Pharmacoeconomic Comparison Using UK Cost Data

AbstractBackground: Selective serotonin reuptake inhibitors (SSRIs) and serotoninnoradrenaline 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-Åsberg Depression Rating Scale (MADRS) score ≥26 and Clinical Global Impression Severity (CGI-S) score ≥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 ≥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 ≥50%) and remission (MADRS score ≤12) rates at week 24. Cost outcomes were assessed from the societal perspective. Healthcare resource use and sick leave were evaluated using a health economic assessment questionnaire. Unit costs of healthcare services were obtained from standard UK sources (£, year 2006 values).Results: Over the total 24-week study period, escitalopram was associated with significant cost savings compared with duloxetine (total per-patient monthly cost £188 vs £334, respectively). In the primary CEA, escitalopram dominated duloxetine (i.e. was more effective on the disability scale and less costly). Treatment with escitalopram resulted in significantly lower mean sick leave duration per patient over 24 weeks than duloxetine (30.7 days vs 62.2 days).In multivariate analyses, escitalopram as a treatment choice was associated with a 54% reduction in sick leave duration (p < 0.001). Treatment with escitalopram also resulted in 49% lower total costs than treatment with duloxetine (p = 0.002). Absenteeism accounted for about two-thirds of the overall cost. Early clinical improvement (mean change in MADRS total score, response and remission) had an independent significant impact on the sick leave duration, after controlling for key co-variates.Conclusions: Escitalopram was associated with significantly lower duration of sick leave and significant savings in the total cost compared with duloxetine; it dominated duloxetine when effectiveness was assessed on the SDS scale. Indirect costs due to sick leave accounted for the most substantial portion of the total cost and should, therefore, be an important consideration when pharmacoeconomic comparisons between treatments are made from the societal perspective. The link between decrease in absenteeism and early (8-week) clinical improvement suggested in the additional analyses may explain the reduced sick leave observed with escitalopram, given its superior short-term efficacy compared with duloxetine (demonstrated in the underlying clinical trial).

The use and performance of productivity scales to evaluate presenteeism in mood disorders.

OBJECTIVE Mood disorders are associated with a high societal cost, mainly due to presenteeism. The objective of this study was to review the use of 10 instruments that rate presenteeism in mood disorders and to provide recommendations regarding the appropriateness of instruments in different study settings. METHODS A systematic review of the literature was conducted to identify scales used to measure presenteeism, including the World Health Organization Health and Work Performance Questionnaire, the Lam Employment Absence and Productivity Scale, the Sheehan Disability Scale, the Work Limitation Questionnaire, and Work Productivity and Activity Impairment questionnaire. Study characteristics and major results (by symptom level, by treatment arm, correlation to other scales, and use of monetization) were data extracted. RESULTS Twenty-nine studies were identified. The Sheehan Disability Scale, the Work Limitation Questionnaire, and Health and Work Performance Questionnaire were the most commonly used instruments. The majority (60%) of scales demonstrated higher presenteeism in individuals with mood disorders than in individuals without. The Lam Employment Absence and Productivity Scale, the Sheehan Disability Scale, and the Work Limitation Questionnaire showed that presenteeism increased with increasing severity of disease. Few studies reported results on presenteeism by treatment, with only small between-treatment differences observed. Good correlations between presenteeism instruments and clinical or quality-of-life scales were reported. Three studies converted results from presenteeism scales into monetary units. CONCLUSIONS Limited experiential evidence exists comparing the performance of presenteeism scales in mood disorders. Therefore, recommendations for inclusion of a presenteeism tool must be driven by instrument properties (ease of administration, amenability to monetization) and the study type. Future research should focus on the responsiveness of the instrument and on how mood disorders impact self-reported assessment.

Health-related quality of life (HRQOL) among patients with Generalised Anxiety Disorder: evaluation conducted alongside an escitalopram relapse prevention trial

ABSTRACT Background: Improving health-related quality of life (HRQoL) should be a treatment goal for patients with Generalised Anxiety Disorder (GAD). Objectives: To assess the impact of treatment with escitalopram on HRQoL as well as the effect of relapse on HRQoL and work productivity. Methods: This study was conducted alongside a double-blind, placebo-controlled, relapse prevention multinational clinical trial. Relapse was defined as a Hamilton Anxiety Scale (HAMA) ≥ 15. Treatment responders (HAMA ≤ 10) after 12 weeks of open-label treatment (10 mg/day escitalopram for Week 1 followed by 20 mg/day thereafter) were included. The study dataset comprised patients (n = 329) from French, Canadian, German and Swedish centres. HRQoL was assessed using the SF-36 scale, and data on sick leave and on-the-job productivity as measured by the Work Limitation Questionnaire and the work efficacy and work satisfaction visual analogue scales (VAS) scales were collected at baseline, randomization (Week 12), Weeks 36, 60 and at last assessment. For future health economic analysis, quality adjusted life years were calculated from the SF-36 results. Results: At baseline, GAD patients reported significantly impaired quality of life compared with the general population. During the 12-week open-label treatment period, treatment responders reported significant improvements in HRQoL on all dimensions of the SF-36 ( p < 0.001) and on-the-job productivity ( p < 0.001), whereas sick leave decreased but did not reach statistical significance. After randomization, relapsed patients reported significantly lower QoL than non-relapsed patients on all 4 SF-36 mental health dimensions ( p < 0.001). Relapsed patients reported slightly lower on-the-job productivity than non-relapsed patients and scored lower on the work efficacy and work satisfaction VAS scales. Conclusion: GAD adversely affects patient functioning and daily life. Short-term treatment with escitalopram reverses this impairment to population norms. GAD relapse is associated with a deterioration of HRQoL and work productivity.

The 6-month persistence on SSRIs and associated economic burden.

Abstract Objectives: To assess persistence on SSRIs (most prescribed antidepressants) and associated healthcare costs in a naturalistic setting. Methods: For this retrospective cohort study based on a US reimbursement claims database, all adults with a claim for a SSRI (citalopram, escitalopram, fluoxetine, paroxetine or sertraline) related to a diagnosis of depression were included. Patients should have had no previous reimbursement for any antidepressant within the previous 6 months. Non-persistence was defined as failing to renew prescription within 30 days in the 6-month period after the index date. Results: In the 45,481 patients included, persistence decreased from 95.5% at 1 month, to 52.6% at 2 months, 37.6% at 3 months and 18.9% at 6 months. Among factors associated with higher 6-month persistence were age 18–34 years, physician’s specialty, treatment with escitalopram, absence of abuse history and psychotropic prescription history. During the 6-month after index date, healthcare costs tended to be higher in non-persistent than in persistent patients although not significantly (RR = 1.05, adjusted p = 0.055). Conclusion: Despite some limitations associated with the use of computerized administrative claims data (residual unmeasured confounding), these results highlight a generally low persistence rate at 6 months. Special attention should be given to persistence on treatment, with consideration of potential antidepressant impact.

Cost-Effectiveness Analysis of Escitalopram Compared with Paroxetine in Treatment of Generalized Anxiety Disorder in the United Kingdom

Background: Generalized anxiety disorder (GAD) is associated with substantial economic burden. Objective: To assess, from a societal perspective, the cost-effectiveness of escitalopram and paroxetine in the treatment of GAD in the UK. Method: A decision analytic model with a 9 month time horizon was adapted to the UK setting. Model inputs included drug- and nondrug-specific probabilities from head-to-head trial data, published literature, and expert opinion. Main outcome measures were success (response after 12 wk of treatment and no relapse during the following 24 wk) and costs. Resource use was based on National Institute for Health and Clinical Excellence guidance for GAD patient management, and estimated unit costs came from standard national sources. Human capital approach was used to estimate costs of absence from work. The analysis was performed from the societal perspective. Results: Escitalopram-treated patients were associated with 14.4% higher first-line treatment success and significantly lower discontinuation rates due to adverse events than were those treated with paroxetine. Treatment with escitalopram yielded lower expected costs with greater effectiveness compared with paroxetine. These clinical advantages led to less sick leave and resource use as a result of lower switch rates and use of secondary care. Total expected 9 month costs were £1408 (