Goal setting and goal attainment in patients with major depressive disorder: a narrative review on shared decision making in clinical practice.

OBJECTIVE: Narrative review of the processes of goal setting and goal attainment scaling, as practical approaches to operationalizing and implementing the principles of shared decision making (SDM) in the routine care of people living with major depressive disorder (MDD). METHODS: We searched electronic databases for clinical studies published in English using key terms related to MDD and goal setting or goal attainment scaling. Two clinical studies of goal setting in MDD are considered in detail to exemplify the practicalities of the goal setting approach. RESULTS: While SDM is widely recommended for people living with mental health problems, there is general agreement that it has thus far been implemented variably. In other areas of medicine, the process of goal setting is an established way to engage the patient, facilitate motivation, and assist the recovery process. For people living with MDD, the concept of goal setting is in its infancy, and only few studies have evaluated its clinical utility. Two clinical studies of vortioxetine for MDD demonstrate the utility of goal attainment scaling as an appropriate outcome for assessing functional improvement in ways that matter to the patient. CONCLUSIONS: Goal setting is a pragmatic approach to turning the principles of SDM into realities of clinical practice and aligns with the principles of recovery that encompasses the notions of self-determination, self-management, personal growth, empowerment, and choice. Accumulating evidence supports the use of goal attainment scaling as an appropriate personalized outcome measure for use in clinical trials.

Shared decision making is a structured approach in which a doctor assists their patient in making informed choices about treatment that consider the patient's own preferences. However, while acknowledged as the ideal approach, many doctors working in the mental health area say it can be difficult to apply in their daily clinical practice. In other areas of medicine, such as physical rehabilitation, the structured process of patients setting treatment goals in dialogue with their doctor has been recommended as a practical way to put the principles of shared decision making into practice.In this paper, we reviewed the medical literature to better understand how goal setting can be used to improve the care of people with major depressive disorder. The available evidence supports goal setting as a powerful way to engage patients in healthcare decisions, and ultimately improve health-related outcomes. The goal setting process provides patients the opportunity to verbalize their own, tangible goals for treatment; and following some negotiation, receive endorsement of their goals from their doctor. Patients feel supported and are better motivated to continue with their treatment.While still in its infancy, the growing evidence base supporting goal setting for people with major depressive disorder is encouraging. For example, the Goal Attainment Scaling (GAS) method of evaluating treatment success has been suitably adapted for use in people living with depression (GAS-D) and provides an easy, structured format for discussing personal treatment goals, as well as a method for tracking success, both in clinical practice and research studies.

Long-term safety and efficacy, including anhedonia, of vortioxetine for major depressive disorder: findings from two open-label studies.

OBJECTIVE: Evaluate the long-term safety and efficacy of vortioxetine in the management of major depressive disorder (MDD) in two open-label one-year studies, including a post-hoc analysis of its effects on symptoms related to anhedonia. METHODS: Both studies were 52-week, open-label, flexible-dose extension studies to evaluate the safety and efficacy of vortioxetine in adult patients with MDD following prior double-blind studies. Patients in the first study (NCT00761306) were flexibly treated with vortioxetine 5 or 10 mg/day (N = 74), and patients in the second study (NCT01323478) received vortioxetine 15 or 20 mg/day (N = 71). RESULTS: The safety and tolerability profile of vortioxetine was similar between the two studies; treatment-emergent adverse events with the highest incidence were nausea, dizziness, headache, and nasopharyngitis. Across both studies, improvements achieved during the preceding double-blind studies period were maintained, and additional improvements were observed with open-label treatment. Patients showed a mean ± SD reduction (improvement) in Montgomery and Åsberg Depression Rating Scale (MADRS) total score from open-label baseline to Week 52 of 4.3 ± 9.2 points in the 5-10 mg study, and 10.9 ± 10.0 in the 15-20 mg study. Post-hoc MMRM analyses of MADRS anhedonia factor scores also showed continued improvements over long-term treatment; patients showed a mean ± SE reduction from an open-label baseline to Week 52 of 3.10 ± 0.57 points in the 5-10 mg study, and 5.62 ± 0.60 in the 15-20 mg study. CONCLUSIONS: Data from both studies confirm the safety and efficacy of flexibly dosed vortioxetine over 52 weeks of treatment and demonstrate that MADRS anhedonia factor scores continue to improve with long-term maintenance treatment.

Safety and effectiveness of vortioxetine for major depressive disorder: Real-world evidence from a population-based study in South Korea.

Background: A post-marketing surveillance study was conducted to assess the real-world safety and effectiveness of vortioxetine for the treatment of major depressive disorder (MDD) in South Korea. Methods: Adult patients aged 19-94 years receiving vortioxetine for MDD at 72 hospitals and clinics in South Korea between 19th August 2014 and 18th August 2020 were included. Patients were followed for up to 24±2 weeks, at up to three visits. Adverse events (AEs) and effectiveness, assessed by both clinician and patient-reported measures, were analyzed. Results: A total of 3,263 patients (mean age: 51.28 years) were included in the safety set; 1,095 were aged ≥65 years. The majority of the safety set (61.97%) were female. The overall rate of any AEs and serious AEs were 17.13 and 1.56%, respectively. The majority of AEs were mild (88.32%). The rates of AEs did not differ statistically by age (≥65 years: 16.89% [185/1,095] versus <65 years: 17.25% [374/2,168)], p=0.7989), sex (male: 15.95% [198/1,241] versus female: 17.85% [361/2,022], p=0.1623), or liver impairment (with liver impairment: 20.90% [14/67] versus without liver impairment: 17.05% [545/3,196], p=0.4087). Effectiveness was assessed in 1,918 patients. By 24±2 weeks, there were significant clinical improvements from baseline, assessed by change in Montgomery-Asberg Depression Rating Scale total score (mean±standard deviation [SD]: -10.49±9.42 points, p <0.0001), the proportion of patients with improved symptoms using the Clinical Global Impression - Improvement scores (79.29%), and in both patient-reported measures, with a significant improvement in the Korean Version of the Perceived Deficits Questionnaire-Depression (mean±SD: -6.06±13.23, p <0.0001) and Digit Symbol Substitution Test (mean±SD: 4.83±9.81, p <0.0001) total scores from baseline. Similar to the safety profiles, the proportions of patients with improved symptoms compared with baseline using the Clinical Global Impression - Improvement scores did not differ by age (≥65 years: 82.09% versus <65 years: 78.32%, p=0.0511), sex (male: 77.45% versus female: 81.01%, p=0.0587), or liver impairment (with liver impairment: 67.57% versus without liver impairment: 79.85%, p=0.0663). Conclusion: Vortioxetine appears to be well-tolerated and effective for treating MDD patients in the real-world setting in South Korea, irrespective of age, sex, and liver impairment, reflecting the known profile of vortioxetine based on studies worldwide.

Effectiveness and Safety of Vortioxetine for Major Depressive Disorder in Real-World Clinical Practice: Results from the Single-Arm RELIEVE China Study.

Background: Major depressive disorder (MDD) affects >163 million people worldwide and is a leading cause of disability in China. Functional impairment occurs alongside cognitive symptoms, anxiety, and depression, reducing quality of life and productivity in patients with MDD. Purpose: The multimodal antidepressant vortioxetine has demonstrated efficacy in relieving depressive and functional symptoms of MDD in randomized controlled trials (RCTs). The RELIEVE China study aimed to investigate the real-world effectiveness of vortioxetine in China. Patients and Methods: This was an observational, prospective cohort study in patients with MDD initiating treatment with vortioxetine at physician's discretion in China. Participants were followed up for 24 weeks and assessed at 3 time points: baseline, week 8, and week 24. The primary objective was to assess the change from baseline to weeks 8 and 24 in functional impairment as measured by Sheehan Disability Scale (SDS) total score. Additional assessments included SDS subdomains, measures of depression severity, anxiety, and cognition. The safety and tolerability of vortioxetine were also examined. Results: In total, 859 patients were included in the analysis. A consistent and significant improvement in functional impairment was observed during the study, with baseline mean SDS total score (16.7 points) decreasing by 5.42 (SE, 0.22) and 8.71 (SE, 0.226) points at week 8 and week 24, respectively (P<0.0001). Improvements in other functioning, cognitive, and anxiety assessments were also observed (all P<0.0001). A total of 74.7% of patients had responded, and 63.9% had reached remission at week 24. The tolerability profile of vortioxetine in this real-world population was consistent with the established tolerability profile for this drug. Conclusion: This study demonstrated the short- and long-term effectiveness and tolerability of vortioxetine for patients with MDD in a real-world setting in China. These findings are consistent with the efficacy and safety profile observed during RCTs.

Efficacy and safety of vortioxetine in treatment of patients with major depressive disorder and common co-morbid physical illness.

BACKGROUND: The multimodal antidepressant vortioxetine is effective in reducing somatic symptoms in patients with major depressive disorder (MDD), but little is known about its effects in reducing depressive symptoms in patients with common comorbid physical illnesses. METHODS: This was a pooled analysis of 13 randomized, placebo-controlled trials which evaluated the efficacy (using the Montgomery-Åsberg Depression Rating Scale [MADRS]) and safety of vortioxetine (5-20 mg/day) in adult patients with MDD. We evaluated stable somatic comorbid conditions that were verified by a diagnosis and had sufficient database representation. RESULTS: Of the 5982 patients included in the database, 963 (16.1%) patients had a diagnosis of cardiovascular disease, 152 (2.5%) had diabetes mellitus and 26 (0.4%) had chronic obstructive pulmonary disorder (COPD). At Week 8, adjusted mean[95%CI] treatment differences (vortioxetine vs. placebo) on MADRS total scores were -2.7[-4.2, -1.3] (p = 0.0002) points for the cardiovascular disease, -4.0[-7.7, -0.4] (p = 0.03) for the diabetes, and -6.2[-21.3, 8.9] (p = 0.36) for the COPD groups. The rate and pattern of adverse events were similar across the sub-groups with comorbidities and was consistent with that expected for vortioxetine treatment. LIMITATIONS: The primary studies were not designed to investigate the relationship between vortioxetine and comorbidities, nor were the post hoc analyses powered to detect group differences. CONCLUSIONS: Patients with MDD and comorbid cardiovascular disease or diabetes respond to vortioxetine in a similar way to the broader MDD population. Vortioxetine was generally safe and well tolerated and without unexpected adverse events in these subpopulations, most of whom are taking multiple concomitant medications.

Safety and Persistence of Nalmefene Treatment for Alcohol Dependence. Results from Two Post-authorisation Safety Studies.

AIMS: Two post-authorisation studies assessed the safety and persistence of patients' use of nalmefene. METHODS: The START study (EUPAS5678) was a non-interventional, multi-country, prospective, 18-month (8 follow-up visits) cohort study including outpatients initiating nalmefene for the first time. The multi-database retrospective cohort study (MDRC, EUPAS14083) included baseline and follow-up data from German, Swedish and UK healthcare databases. Both studies permitted 'all comers' without explicit exclusion criteria; predefined subgroups of interest included the elderly (≥65 years) as well as patients with significant psychiatric and/or somatic comorbidities. RESULTS: START study: Overall, the mean duration of nalmefene treatment was 10.3 ± 7.3 months (N = 1348), with 49.0% of patients treated for ≥1 year; frequent reasons for treatment discontinuation were 'goal reached' and 'drug cost'. The most frequently reported adverse drug reactions (ADRs) were nausea (4.7%), dizziness (3.2%) and insomnia (2.0%). ADR rates appeared higher in the elderly subpopulation (18.6% reported ≥1 ADR vs. 12.0% in the total population) but were not higher in the other predefined subgroups.MDRC study: The database follow-up analysis followed 2892 patients over 18 months for whom the duration of nalmefene treatment was between 2 and 3 months and <5% of patients used nalmefene for ≥1 year. CONCLUSIONS: Despite the inclusion of a wider patient population (e.g. elderly patients and those with relevant co-morbidities), the safety and tolerability profile of nalmefene given in routine practice was consistent with previous clinical studies. The differing rates of persistence beyond 1 year likely reflect the different methodologies and highlight the relevance of psychosocial support at follow-up visits.

Patient Response Trajectories in Major Depressive Disorder.

Objective: To investigate whether the efficacy of antidepressants can be understood in terms of patient response-trajectory classes. Experimental Design: Patient-level data were analysed from 1357 adults with MDD randomised to either escitalopram 20 mg/day (n = 676) or placebo (n = 681) in five 8-week randomised placebo-controlled trials. Growth mixture models (GMMs) were used to identify the response trajectories; longitudinal latent class analysis (LLCA) was used to corroborate the findings. Principal Observations: Three classes of response were identified for escitalopram and placebo based on the trajectory of the patients' Montgomery-Åsberg Depression Rating Scale (MADRS) total scores during treatment. All three classes had similar mean baseline MADRS scores, but the change from baseline after 8 weeks differed: -4.2 MADRS points for non-responders, -18.4 MADRS points for slow responders, and -26.7 points for fast responders. The proportions of non-responders, slow responders and fast responders were 53%, 38% and 9%, respectively, with placebo and 27%, 58% and 14%, respectively, with escitalopram. Receiver operating curve analysis showed that a cut-off of ≥43% improvement from baseline to week 2 predicted fast responders, and a cut-off of ≥28% improvement from baseline to week 4 predicted responders (fast or slow). There were no clinically useful differences at baseline that predicted the trajectory class to which a patient would belong. Conclusions: The presence of fast-, slow- and non-responder classes has a clear clinical relevance for guiding treatment decisions; individual patients can be classified by the change in their MADRS score from baseline at 2 or 4 weeks.

Suicidal ideation and behavior in adults with major depressive disorder treated with vortioxetine: post hoc pooled analyses of randomized, placebo-controlled, short-term and open-label, long-term extension trials.

OBJECTIVES: This study aimed to evaluate the risk of suicidal ideation and behavior associated with vortioxetine treatment in adults with major depressive disorder (MDD). METHODS: Suicide-related events were evaluated post hoc using 2 study pools: one short-term pool of 10 randomized, placebo-controlled studies (6-8 weeks) and another long-term pool that included 3 open-label extension studies (52 weeks). Evaluation of suicide-related events was performed using Columbia-Suicide Severity Rating Scale (C-SSRS) scores and treatment-emergent adverse events (TEAEs) data. RESULTS: At baseline, the percentage of patients reporting any C-SSRS ideation or behavior events in short-term studies was similar between placebo (14.7%), vortioxetine (19.8%, 13.0%, 11.2%, and 13.7% for 5-, 10-, 15-, and 20-mg groups, respectively), and duloxetine active reference (13.2%) and did not change throughout the 6- to 8-week treatment period for placebo (17.0%), vortioxetine (19.3%, 13.5%, 12.6%, and 15% for 5-, 10-, 15-, and 20-mg groups, respectively), or duloxetine (11.3%). The incidence of suicide-related events for TEAEs in the short-term pool was 0.4% for placebo, 0.2% or 1.0% for vortioxetine 5 mg or 10 mg, and 0.7% each for vortioxetine 15 mg and 20 mg, as well as duloxetine. After 52-week treatment with vortioxetine, suicidal ideation based on C-SSRS was 9.8%, C-SSRS suicidal behavior was 0.2%, and the incidence of suicide-related events based on TEAEs was <1%. There were no completed suicides in any study. CONCLUSIONS: Vortioxetine is not associated with increased risk of suicidal ideation or behavior in MDD patients.

Management of Depression in Adolescents in Japan.

Objectives: In Japan, there are currently no approved antidepressant treatments for pediatric patients with depression. This study aimed to estimate the prevalence of depression among adolescents under medical care in Japan, the pharmacological treatments used, and the perceived unmet needs among the medical specialties treating depression in the pediatric population. Methods: The study was conducted in November 2014 as an internet survey among physicians in clinical practice. It included a sample of 731 physicians with the potential to treat adolescent patients with depression and 161 physicians who had treated at least one adolescent with depression with pharmacotherapy in the previous 12 months. Of the sample of 161 treating physicians, 60 were internal medicine specialists, 73 were psychiatrists, and 28 were certified specialists from the Japanese Society of Child and Adolescent Psychiatry, Japanese Society of Psychosomatic Medicine Pediatrics, or Japanese Society of Pediatric Psychiatry and Neurology. The participants completed questionnaires concerning their patient population with depression, drug-treated population, and drugs prescribed. Results: Estimates of prevalence data indicated that there were ∼550,000 adolescent patients with depression in Japan (10% of the patient population with depression) under medical care of different medical specialties; ∼64% of these patients were receiving pharmacotherapy. Pharmacotherapy for adolescents with depression was prescribed mainly by psychiatrists (62% of prescriptions for these patients). The most common first-choice agent was sertraline (23% of respondents) followed by anxiolytics (17%) and fluvoxamine (13%), while antipsychotics were the preferred choice for 7%. Conclusion: The study indicates a high prevalence of depression among adolescents in Japan. These patients are seen by different medical specialties; the use of pharmacotherapy is relatively common and comprises various drug classes, including antidepressants, anxiolytics, and antipsychotics. This study shows that there is a medical need for approved treatments for adolescents with depression in Japan.

Efficacy of escitalopram in the treatment of social anxiety disorder: A meta-analysis versus placebo.

Escitalopram is the most selective of the serotonin reuptake inhibitor (SSRI) antidepressants. We conducted a meta-analysis of placebo-controlled studies where escitalopram was used to treat patients with social anxiety disorder (SAD). Data from all randomised, double-blind placebo-controlled studies in SAD with escitalopram from both specialist settings and general practice were used. Patients met the DSM-IV criteria for SAD, were ≥18 years old, and had a Liebowitz Social Anxiety Scale (LSAS) ≥60. The primary outcome measure was the estimated treatment difference in LSAS total score at Week 12. Secondary outcome measures included the estimated treatment difference in the Clinical Global Impression-Severity (CGI-S) score at Week 12. A total of 1598 patients from 3 randomised controlled trials were included in the analyses. Escitalopram (n=1061) was superior to placebo (n=537), with an estimated treatment difference on the LSAS of -9.2 points (95%CI: [-14.4; -4.0], p<0.01) (escitalopram 5mg/day), -4.6 points (95%CI: [-8.1; -1.0], p<0.01) (escitalopram 10mg/day), -10.1 points (95%CI: [-13.7; -6.5], p<0.01) (escitalopram 20mg/day) and -7.3 points (95%CI: [-12.3; -2.2], p<0.01) (escitalopram 10-20mg/day). For the CGI-S, the corresponding values were -0.55 points (95%CI: [-0.79; -0.31], p<0.01) (escitalopram 5mg/day), -0.26 points (95%CI: [-0.42; -0.10], p<0.01) (escitalopram 10mg/day), -0.48 points (95%CI: [-0.64; -0.31], p<0.01) (escitalopram 20mg/day) and -0.29 points (95%CI: [-0.51; -0.07], p<0.05) (escitalopram 10-20mg/day). The withdrawal rate due to adverse events was 7.2% for escitalopram, compared with 4.3% for placebo (p<0.05). In this meta-analysis, all doses of escitalopram showed significant superiority in efficacy versus placebo in the treatment of patients with SAD.

The safety and tolerability of vortioxetine: Analysis of data from randomized placebo-controlled trials and open-label extension studies.

The safety and tolerability of vortioxetine in adults with major depressive disorder was assessed. Tolerability was based on the nature, incidence and severity of treatment-emergent adverse events (TEAEs) during acute (6/8) week treatment in 11 randomized, double-blind placebo-controlled short-term studies in major depressive disorder: six with an active reference. Symptoms following discontinuation were assessed through the Discontinuation-Emergent Signs and Symptoms checklist in three studies. Long-term (⩽52 weeks) tolerability was evaluated in five open-label extension studies. Patients (n =5701) were acutely treated with either placebo (n=1817), vortioxetine (5-20mg/day; n=3018), venlafaxine XR (225mg/day; n=113) or duloxetine (60mg/day; n=753). The withdrawal rate due to TEAEs during treatment with vortioxetine (5-20mg/day) was 4.5-7.8%, compared with placebo (3.6%), venlafaxine XR (14.2%) or duloxetine (8.8%). Common TEAEs (incidence ⩾5% and >2 × placebo) with vortioxetine (5-20mg/day) were nausea (20.9-31.2%) and vomiting (2.9-6.5%). For vortioxetine (5-20mg/day), the incidence of TEAEs associated with insomnia was 2.0-5.1% versus 4.0% for placebo, and with sexual dysfunction 1.6-1.8% versus 1.0% for placebo. Discontinuation symptoms as assessed by the mean Discontinuation-Emergent Signs and Symptoms total score after abrupt discontinuation were comparable to placebo in the first and second week. Vortioxetine had no effect relative to placebo on clinical laboratory parameters, body weight, heart rate or blood pressure. Vortioxetine showed no clinically relevant effect on ECG parameters, including the QTcF interval. In long-term treatment, no new types of TEAEs were seen; the mean weight gain was 0.7-0.8kg. Thus, vortioxetine (5-20mg/day) appears safe and generally well tolerated in the treatment of major depressive disorder.

A comparative review of escitalopram, paroxetine, and sertraline: Are they all alike?

It is known that newer antidepressants, such as the selective serotonin reuptake inhibitors (SSRIs), provide advantages in tolerability over antidepressants such as the tricyclics. However, even within the SSRI class, differences in efficacy or tolerability exist between the individual drugs. Among the three most widely prescribed SSRIs are paroxetine, sertraline, and escitalopram. Escitalopram is commonly referred to as an SSRI, but also has well-documented allosteric properties, and thus can be further classed as an allosteric serotonin reuptake inhibitor. All three antidepressants are efficacious compared with placebo, but there is evidence that escitalopram is more effective than a range of other antidepressants. There are no direct data to regard either paroxetine or sertraline as a superior antidepressant. Escitalopram is superior compared with paroxetine, which has a less favorable tolerability profile. Paroxetine is associated with cholinergic muscarinic antagonism and potent inhibition of CYP2D6, and sertraline has moderate drug interaction issues in comparison with escitalopram. Overall, as an allosteric serotonin reuptake inhibitor that is somewhat different from classical SSRIs, escitalopram is the first choice judged by combined efficacy and tolerability, and nonclinical data have offered possible mechanisms through which escitalopram could be more efficacious, based on its interaction with orthosteric and allosteric binding sites at the serotonin transporter.

The cardiovascular safety profile of escitalopram.

The cardiovascular effects of escitalopram were examined in a large group of participants in double-blind, randomized, placebo-controlled studies. Escitalopram (n=3298) was administered at doses between 5 and 20mg/day. Patients were treated in acute (8-12 weeks) and long-term (24 weeks) studies. Assessment of cardiovascular safety included heart rate, blood pressure (BP), treatment-emergent adverse events (TEAEs) and electrocardiograms (ECGs). In the short-term, there was a small, but statistically significant 2 beats per minute decrease in heart rate with escitalopram compared with placebo. The difference compared to placebo in systolic or diastolic BP was not clinically or statistically significant. Valid ECG assessments at both baseline and last assessment were available for 2407 escitalopram patients and 1952 placebo patients. Escitalopram-placebo differences in mean changes in ECG values were not clinically meaningful. The mean difference to placebo in the corrected QT [Fridericia's (QTcF)] interval was 3.5 ms (all escitalopram doses); 1.3 ms (escitalopram 10mg) and 1.7 ms (escitalopram 20mg) (p=0.2836 for 10 versus 20 mg). One out of 2407 escitalopram patients had a QTcF interval >500 ms and a change from baseline >60 ms. The incidence and types of cardiac-associated adverse events were similar between patients treated for 8-12 weeks with placebo (2.2%) or escitalopram (1.9%) and for 24 weeks with placebo (2.7%) or escitalopram (2.3%). Analyses of data from long-term studies and studies of the elderly showed similar results. In conclusion, these data demonstrate that escitalopram, like other SSRIs, has a statistically significant effect on heart rate and no clinically meaningful effect on ECG values, BP, with a placebo-level incidence of cardiac-associated adverse events.

Satisfaction with medication is correlated with outcome but not persistence in patients treated with placebo, escitalopram, or serotonin-norepinephrine reuptake inhibitors: a post hoc analysis.

OBJECTIVE: To test whether satisfaction with taking medication, assessed using item 15 of the Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q), is associated with clinical outcome and persistence with treatment. METHOD: In this post hoc analysis, data were analyzed from 4 randomized placebo-controlled studies of patients with major depressive disorder treated with escitalopram (650 patients taking escitalopram and 534 taking placebo), together with data from 2 randomized trials of escitalopram versus venlafaxine or duloxetine (235 patients taking escitalopram and 233 taking a serotonin-norepinephrine reuptake inhibitor). The studies were published between 2002 and 2007. Instruments included the Q-LES-Q, which was assessed at baseline and week 8, and the Montgomery-Asberg Depression Rating Scale (MADRS), which was assessed at baseline and weeks 1, 2, 4, 6, and 8. RESULTS: At baseline, the mean ± SD MADRS total score was 30.0 ± 4.6, and the mean Q-LES-Q item 15 score was 2.9 ± 0.9. At week 8, the MADRS response rates of placebo-treated patients with a low, moderate, or high satisfaction with medication at baseline were 30%, 37%, and 46%, respectively (mixed model repeated measures [MMRM]). The corresponding MADRS response rates for escitalopram-treated patients with a low, moderate, or high satisfaction at baseline were 56%, 60%, and 67%, respectively (MMRM). Baseline satisfaction with medication was not significantly correlated with time to withdrawal (all reasons). The change in satisfaction with medication from baseline to endpoint was significantly correlated with symptomatic improvement on the MADRS (P < .001). CONCLUSIONS: Baseline satisfaction with medication after 1 week of placebo run-in is a moderator of treatment outcome but not of persistence of treatment in the acute treatment phase of depressed outpatients. Patient attitude toward medication should be taken into account before treatment is initiated.

Impact of escitalopram treatment on Quality of Life Enjoyment and Satisfaction Questionnaire scores in major depressive disorder and generalized anxiety disorder.

Administration of the same Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q) in major depressive disorder (MDD) and in generalized anxiety disorder (GAD) before and after treatment allowed us to compare quality of life enjoyment and satisfaction in these two disorders and to compare outcome based on symptoms versus functioning. Q-LES-Q and symptom-specific Montgomery-Asberg Depression Rating Scale (MADRS) and Hamilton Anxiety Scale (HAMA) data from eight randomized, 8-week, double-blind, placebo-controlled clinical trials with escitalopram were used. MDD (n=1,140) or GAD (n=1,045) patients report a substantial degree of quality of life enjoyment and satisfaction impairment (baseline scores 64% and 76% of community norm, respectively). Treatment resulted in statistically and clinically significant improvement in quality of life enjoyment and satisfaction. The improvement was greater in patients treated with escitalopram than with placebo. In MDD, the majority of remitters (MADRS

Escitalopram therapy for major depression and anxiety disorders.

BACKGROUND: Randomized controlled clinical trials have demonstrated that escitalopram is efficacious in a range of mood and anxiety disorders, but the individual trials are insufficiently large to allow a full exploration of its tolerability. OBJECTIVE: To assess the tolerability and safety of escitalopram through analysis of all randomized controlled clinical trials in major depressive disorder and anxiety disorders. METHODS: Analyses of tolerability were based on data from all available randomized, double-blind, controlled studies completed by December 2006 in which escitalopram was compared with placebo or active compounds (citalopram, fluoxetine, paroxetine, sertraline, venlafaxine). Adverse events (AEs) that occurred more frequently with escitalopram than with placebo were listed, and tolerability and safety were evaluated. RESULTS: Nausea was the only AE with an incidence greater than or equal to 10% and 5 percentage points greater than with placebo during short-term treatment. In general, AEs were mild to moderate in severity. AEs related to sexual dysfunction were similarly frequent with escitalopram and citalopram, but were higher with paroxetine. No suicide occurred among escitalopram-treated patients, and there were no significant differences between escitalopram and placebo in incidence of suicidal behavior, measured by self-harm and suicidal thoughts. The 8 week withdrawal rate due to AEs was higher with escitalopram than with placebo (7.3% vs 2.8%; p < 0.001) but lower than with paroxetine (6.6% vs 9.0%; p < 0.01) or venlafaxine (6.1% vs 13.2%; p < 0.01) (Fisher's Exact test, 2 tailed). Compared with paroxetine, escitalopram resulted in significantly fewer discontinuation symptoms (average increase in Discontinuation Emergent Signs and Symptoms Scale of 1.6 vs 3.9; p < 0.01). There were no clinically relevant changes in clinical laboratory values in patients treated with escitalopram. Mean weight change after 6 months of treatment with escitalopram (0.58 +/- 2.63 kg) was similar to that with placebo (0.15 +/- 2.33 kg). The incidence of cardiovascular events was similar to that with placebo. The risk of AEs was no higher in special patient populations, such as the elderly (> or =65 y of age) or those with hepatic dysfunction. CONCLUSIONS: Based on data from randomized controlled trials involving more than 4000 escitalopram-treated patients, escitalopram (10-20 mg/day) is safe and well tolerated in short- and long-term 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

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

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

Escitalopram versus citalopram: the surprising role of the R-enantiomer.

RATIONALE: Citalopram is a racemate consisting of a 1:1 mixture of the R(-)- and S(+)-enantiomers. Non-clinical studies show that the serotonin reuptake inhibitory activity of citalopram is attributable to the S-enantiomer, escitalopram. A series of recent non-clinical and clinical studies comparing escitalopram and citalopram to placebo found that equivalent doses of these two drugs, i.e. containing the same amount of the S-enantiomer, showed better effect for escitalopram. These results suggested that the R-citalopram in citalopram inhibits the effect of the S-enantiomer. OBJECTIVE: To review the pharmacological and non-clinical literature that describes the inhibition of escitalopram by R-citalopram, as well as the implications of this inhibition for the clinical efficacy of escitalopram compared to citalopram. METHODS: The information in this review was gathered from published articles and abstracts. RESULTS: In appropriate neurochemical, functional, and behavioural non-clinical experiments, escitalopram shows greater efficacy and faster onset of action than comparable doses of citalopram. The lower efficacy of citalopram in these studies is apparently due to the inhibition of the effect of the S-enantiomer by the R-enantiomer, possibly via an allosteric interaction with the serotonin transporter. Data from randomised clinical trials consistently show better efficacy with escitalopram than with citalopram, including higher rates of response and remission, and faster time to symptom relief. CONCLUSION: The R-enantiomer present in citalopram counteracts the activity of the S-enantiomer, thereby providing a possible basis for the pharmacological and clinical differences observed between citalopram and escitalopram.

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.