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.
Adult patients ...aged 19-94 years receiving vortioxetine for MDD at 72 hospitals and clinics in South Korea between 19
August 2014 and 18
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.
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),
=0.7989), sex (male: 15.95% 198/1,241 versus female: 17.85% 361/2,022,
=0.1623), or liver impairment (with liver impairment: 20.90% 14/67 versus without liver impairment: 17.05% 545/3,196,
=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,
<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,
<0.0001) and Digit Symbol Substitution Test (mean±SD: 4.83±9.81,
<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%,
=0.0511), sex (male: 77.45% versus female: 81.01%,
=0.0587), or liver impairment (with liver impairment: 67.57% versus without liver impairment: 79.85%,
=0.0663).
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.
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. Keywords: China, cognition, functioning, major depressive disorder, real-world evidence, vortioxetine
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.
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 (he 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 (≥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 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.
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.
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.
Escitalopram (10 to 20 mg/day) demonstrated a favorable safety and tolerability profile over 12-months treatment, with further improvement in patient response.
Abstract
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.
Short Summary: Two studies were used to evaluate the safety and persistence of nalmefene in the routine management of alcohol dependence in Europe as part of the overall risk management plan. Although adverse events appeared more common in over 65-year olds, there were no major differences in safety outcomes between the total population, and those with psychiatric and somatic comorbidities or those with a history of seizures. Findings were in line with those from previous clinical studies. The differing rates of persistence beyond 1 year (49% in the prospective study and < 5% in the multi-database retrospective cohort study) likely reflect the different study methodologies and serve to highlight the relevance of follow-up support.
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.
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.
The information in this review was gathered from published articles and abstracts.
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.
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.
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–Åsberg 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=1140) or GAD (n=1045) 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≤12) reached ‘normal’ quality of life enjoyment and satisfaction levels, whereas in GAD, 67% of remitters (HAMA≤7) reached ‘normal’ quality of life, enjoyment, and satisfaction. A strong correlation between the symptom-specific scales and the Q-LES-Q was observed. These analyses suggest that remission with scores of 6 on the MADRS and 5 on the HAMA correspond with a quality of life enjoyment and satisfaction found in community comparison patients (Q-LES-Q score of 58±10%). Treatment with escitalopram results in a significant improvement of quality of life enjoyment and satisfaction in patients with MDD or GAD. Both response and remission in patients with GAD and remission in patients with MDD are correlated with a ‘normal’ quality of life enjoyment and satisfaction.
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.
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.
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).
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.
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