Efficacy and tolerability of venlafaxine versus specific serotonin reuptake inhibitors in treatment of major depressive disorder: a meta-analysis of published studies

Specific serotonin reuptake inhibitors (SSRIs) are considered as first-line treatment in major depressive disorder (MDD). There is evidence that venlafaxine may be more effective than several antidepressants in the treatment of MDD. This meta-analysis includes all published, randomized, double-blind, head-to-head trials, which compared venlafaxine and an SSRI in the treatment of MDD in adults. Twenty-six trials comparing venlafaxine with an SSRI were included (total participants: 5858). Meta-analysis using a random effect model showed that venlafaxine was superior to SSRIs in achieving remission [odds ratio (OR)=1.13, 95% confidence interval (CI)=1.0-1.28, P=0.05] and response (OR=1.17, 95% CI=1.03-1.34, P=0.02). Subgroup analysis found that venlafaxine had a significantly better response rate than fluoxetine (OR=1.28, 95% CI=1.05-1.55, P=0.01). There were no significant differences in response or remission between venlafaxine and other individual SSRIs. There was no significant difference in all cause discontinuation between venlafaxine and SSRIs (OR=1.10, 95% CI=0.97-1.25, P=0.15). Venlafaxine had significantly higher discontinuation due to adverse events compared with SSRIs (OR=1.41, 95% CI=1.10-1.79, P=0.006). The superior efficacy of venlafaxine over SSRIs is of clinical importance. However, higher rates of discontinuation due to adverse events for venlafaxine compared with SSRIs are a disadvantage. Findings of this meta-analysis that included only published studies were similar to those from meta-analysis that included unpublished data.     

Safety and tolerability of antidepressant co-treatment in acute major depressive disorder: results from a systematic review and exploratory meta-analysis

Introduction: Although antidepressant (AD) monotherapy is recommended first-line for major depressive disorder (MDD), AD + AD co-treatment is common.

Areas covered: We conducted the first systematic review searching PubMed/MEDLINE/PsycInfo/Embase from database inception until 1 June 2015 for acute randomized trials in ≥ 20 adults with MDD comparing AD monotherapy with AD + AD co-treatment that reported quantitative data on adverse events (AEs). Meta-analyzing 23 studies (n = 2435, duration = 6.6 weeks) AD monotherapy and AD + AD co-treatment were similar regarding intolerability-related discontinuation (risk ratio [RR] = 1.38, 95% CI = 0.89 – 1.10) and frequency of ≥ 1 AE (RR = 1.19, 95% CI = 0.95 – 1.49). Nevertheless, AD + AD co-treatment was associated with significantly greater burden regarding 4/25 AEs (tremor: RR = 1.55, 95% CI = 1.01 – 2.38; sweating: RR = 1.95, 95% CI = 1.13 –3.38, ≥ 7% weight gain: RR = 3.15, 95% CI = 1.34 – 7.41; weight gain = 2.17, 95% CI = 0.71 – 3.63 kg), but not more CNS, gastrointestinal, sexual or alertness-related AEs. However, 11/25 AEs (44.0%) were reported in only 1 – 2 studies. Adding noradrenergic and specific serotonergic antidepressants (NaSSA) or tricyclic antidepressants (TCA) to selective serotonin reuptake inhibitors (SSRIs) was specifically associated with more AEs.

Expert opinion: The potential for increased AEs with AD + AD co-treatment needs to be considered vis-à-vis unclear efficacy benefits of this strategy. In particular, NaSSAs and TCAs should be added to SSRIs with caution. Clearly, more data on side-effect burden of AD + AD co-treatment are needed.     

A meta-analysis of the efficacy of venlafaxine extended release 75–225 mg/day for the treatment of major depressive disorder

Objective: To evaluate the short-term efficacy of venlafaxine extended release (ER) 75–225?mg/day compared with placebo for treating major depressive disorder (MDD) and to examine associations between baseline characteristics and efficacy outcomes in MDD patients treated with venlafaxine ER 75–225?mg/day.

Research design and methods: This meta-analysis included published and unpublished short-term, double-blind, placebo-controlled, Wyeth/Pfizer sponsored studies of venlafaxine ER at doses up to 225?mg/day in adults with MDD.

Clinical trial registration: All trials were conducted before trial registration became mandatory.

Main outcome measures: Change from baseline in the 17-item Hamilton Rating Scale for Depression (HAM-D₁₇) total score was analyzed over time using a mixed-effects model for repeated measures with terms for study, treatment group, visit, interaction between treatment group and visit, and baseline score as a covariate. Associations between baseline demographic and clinical characteristics and the probability of HAM-D₁₇ response and remission at week 8 were evaluated using logistic regression models, with terms for study, treatment group, and baseline characteristics in the models. Safety and tolerability was assessed based on adverse events (AEs) and discontinuations due to AEs.

Results: The full analysis set included 1087 patients from five studies that fulfilled selection criteria. Statistically significant separation between venlafaxine ER and placebo groups for HAM-D₁₇ total score was seen at week 2 and all subsequent assessments (p-values <.0001). There was no significant interaction between treatment and baseline HAM-D₁₇ total score. Probability of HAM-D₁₇ remission at week 8 decreased with increasing baseline HAM-D₁₇ total score (p?=?.0012; OR: 0.94); however, baseline HAM-D₁₇ total score did not predict response. Discontinuations due to AEs were reported for 9.4% of venlafaxine-ER-treated patients compared with 3.6% of placebo-treated patients.

Key limitations: Five studies met the criteria for inclusion. Several differences in design between included studies limited the analysis: one study did not include a week 3 assessment (the week 3 time point was therefore dropped from the analysis), one study had two venlafaxine ER dose arms, which were combined into one group for the meta-analysis, and mixed- and flexible-dose studies were pooled.

Conclusions: Venlafaxine ER 75–225?mg/day effectively reduced symptoms of depression in patients with MDD overall and in patients with either lower (≤23) or higher (>23) HAM-D₁₇ total score at baseline.     

Vortioxetine (Lu AA21004) in generalized anxiety disorder: Results of an 8-week,multinational, randomized,double-blind,placebo-controlled clinical trial

Vortioxetine is a multimodal antidepressant, with anxiolytic properties observed in preclinical studies. The goal of the current study was to evaluate the efficacy and tolerability of vortioxetine 5 mg vs placebo in adults with generalized anxiety disorder (GAD). Adults with a primary diagnosis of GAD (HAM-A total score ≥20 and MADRS score ≤16) received vortioxetine 5 mg or placebo for 8 weeks. The primary efficacy endpoint was reduction in HAM-A total scores from baseline after 8 weeks of treatment compared with placebo. Key secondary measurements were HAD anxiety subscore, CGI-I, SDS total score, HAM-A response rates, HAM-A total score for subjects whose baseline HAM-A total score was ≥25, and SF-36 social functioning subscore. HAM-A remission rates were also measured. Adverse events (AEs) were assessed throughout the study. In total, 301 subjects (mean age, 45.2 years; 31% male) were randomized (1:1) to receive vortioxetine 5 mg (n=150) or placebo (n=151). After 8 weeks of treatment, there was a statistically significant difference in reduction from baseline in HAM-A total score for the vortioxetine group (?14.30) compared with placebo recipients (?10.49) (P<0.001). Statistically significant differences were observed for all key secondary outcomes favoring vortioxetine treatment (vs placebo), using a mixed model for repeated measurements (MMRM) analysis. Active treatment resulted in a significantly higher rate of remission. Vortioxetine was well tolerated. The most common treatment-related AEs were nausea, headache, dizziness, and dry mouth. In sum, vortioxetine was safe and effective in treating adults with GAD in this multinational population.     

A review of the clinical efficacy,safety and tolerability of the antidepressants vilazodone,levomilnacipran and vortioxetine

Introduction: As a leading cause of disability, major depressive disorder (MDD) is characterized by reduced quality of life and altered functioning. Current pharmaceutical treatment options are limited in their success by modest effects and adverse events that often lead to discontinuation. One current trend in antidepressant development is to combine inhibition of the serotonin transporter with other pharmacological targets, including the norepinephrine transporter or different serotonin receptors.

Areas covered: In a span of < 3 years, the FDA approved three new antidepressants for the treatment of MDD: vilazodone in January 2011, levomilnacipran in July 2013 and vortioxetine in September 2013. This article reviews the efficacy, safety and tolerability of these three drugs mainly from the Phase III trial data.

Expert opinion: All three drugs are effective in the treatment of MDD, but data comparing them to other antidepressants is currently lacking. Vilazodone was proposed to produce a more rapid onset and have fewer sexual side effects but neither effect has been conclusively shown. Levomilnacipran appears to be effective in improving functional impairment, including both social and work functioning. Vortioxetine is currently the only drug of the three with proven efficacy in elderly patients. It also appears to have cognitive enhancing properties which are largely independent of improved depressive symptoms. Overall, these drugs represent a promising step forward in antidepressant drug development.     

Remission of major depressive disorder without adverse events: a comparison of escitalopram versus serotonin norepinephrine reuptake inhibitors

Abstract

Objective:

An antidepressant’s tolerability, generally captured as the frequency and severity of adverse events (AEs), is often as important as its efficacy in determining treatment success. This study used a composite outcome – remission of major depressive disorder (MDD) without AEs?– to compare the benefit–risk profiles of escitalopram versus the norepinephrine reuptake inhibitors (SNRIs) duloxetine and venlafaxine extended release (XR).     

Vortioxetine: a New Treatment for Major Depressive Disorder

Introduction: Vortioxetine is a structurally novel medication that has recently been approved for treatment of major depressive disorder (MDD). This medication is a serotonin reuptake inhibitor that also has a number of other potentially relevant effects on serotoninergic receptors, which may differentiate the drug’s effects from those of current first-line antidepressants, such as selective serotonin reuptake inhibitors (SSRIs) and serotonin norepinephrine reuptake inhibitors (SNRIs).

Areas Covered: This article will review the basic clinical pharmacology of vortioxetine, summarize the major clinical trials that were performed prior to approval by the US Food and Drug Administration (FDA), discuss relevant post-marketing studies of this drug, and offer expert commentary on the significance of this new agent in clinical practice. Pre-approval studies were identified as all randomized, placebo-controlled studies of vortioxetine listed on clinicaltrials.gov. Other referenced studies were identified via a MEDLINE database literature search in August 2015 using the key search terms, vortioxetine and Lu AA21004, combined with additional terms that included pharmacological profile, pharmacokinetics, drug interactions, adverse effects, side effects, safety, major depression, and major depressive disorder. We identified relevant systematic reviews, meta-analyses, randomized trials and preclinical studies of importance.

Expert Opinion: Results of placebo-controlled trials suggest efficacy and an overall safety profile comparable to existing first-line antidepressants. The most common side effects are nausea, vomiting and constipation. Results of several studies indicate that vortioxetine may have therapeutic effects on cognition (e.g., memory and executive functioning) that exceed that of standard antidepressants. Disadvantages include cost and the current paucity of long-term efficacy data from large clinical trials. The authors suggest that vortioxetine is currently a good second-line antidepressant option and shows promise, pending additional long-term data, to become a first-line antidepressant option.     

Vortioxetine: a review of efficacy,safety and tolerability with a focus on cognitive symptoms in major depressive disorder

Introduction: Vortioxetine is a pharmacodynamically novel antidepressant that exerts effects on various neurotransmitters including serotonin, noradrenaline, dopamine, glutamate, histamine and acetylcholine. Its efficacy in the symptomatic management of major depressive disorder (MDD) has been established in several short- and long-term trials. Vortioxetine has also demonstrated independent pro-cognitive effects in adults with MDD.

Areas covered: This report provides a concise review of the pharmacology, efficacy and safety of vortioxetine as they pertain to cognition.

Expert opinion: The significant impact of cognitive dysfunction in MDD has achieved increased consideration among researchers over the past decade. Vortioxetine is the first antidepressant agent to demonstrate meaningful clinical efficacy in the improvement of cognition in adults with MDD, independent of improvement in affective symptomatology. These results provide the impetus for further study into the potential pro-cognitive effects of vortioxetine in other conditions wherein cognitive dysfunction is prominent.     

Escitalopram in the treatment of major depressive disorder: A meta-analysis

ABSTRACT

Objective: To assess the relative antidepressant efficacy of escitalopram and comparator antidepressants.

Research design and methods: A meta-analysis was performed using studies in major depressive disorder (MDD) comparing escitalopram with active controls, including selective serotonin reuptake inhibitors [SSRIs] (citalopram, fluoxetine, paroxetine, sertraline) and serotonin/noradrenaline reuptake inhibitors [SNRIs] (venlafaxine, duloxetine). Adult patients had to meet DSM-IV criteria for MDD.

Main outcome measures: The primary outcome measure was the treatment difference in Montgomery–Åsberg Depression Rating Scale (MADRS) total score at week?8. Secondary outcome measures were response and remission (MADRS total score ≤?12) rates.

Results: Individual patient data (N?=?4549) from 16 randomized controlled trials were included in the analyses (escitalopram n?=?2272, SSRIs n?=?1750, SNRIs n?=?527). Escitalopram was significantly more effective than comparators in overall treatment effect, with an estimated mean treatment difference of 1.1?points on the MADRS (p?<?0.0001), and in responder (63.7?vs. 58.3%, p?<?0.0001) and remitter (53.1?vs. 49.4%, p?<?0.0059) analyses. Escitalopram was significantly superior to SSRIs, with an estimated difference in response of 62.1?vs. 58.4% and remission of 51.6?vs. 49.0%. In comparison to SNRIs, the estimated difference in response was 68.3?vs. 59.0% (p?=?0.0007) and for remission the difference was 57.8?vs. 50.5% (p?=?0.0088). These results were similar for severely depressed patients (baseline MADRS ≥?30). Sensitivity analyses were performed with data from articles reporting Hamilton Rating Scale for Depression (HAMD) scores. The 8-week withdrawal rate due to adverse events was 5.4% for escitalopram and 7.9% for the comparators (p?<?0.01). This difference was accounted for by statistically significant higher attrition rates in the SNRI comparisons. This work may be limited by the clinical methodology underlying meta-analytic studies, in particular, the exclusion of trials that fail to meet predetermined criteria for inclusion.

Conclusions: In this meta-analysis, superior efficacy of escitalopram compared to SSRIs and SNRIs was confirmed, although the superiority over SSRIs was largely explained by differences between escitalopram and citalopram.     

A meta-analysis of clinical trials comparing milnacipran, a serotonin--norepinephrine reuptake inhibitor, with a selective serotonin reuptake inhibitor for the treatment of major depressive disorder.

CONTEXT: Over the past few years, a number of studies have emerged suggesting that the treatment of major depressive disorder (MDD) with antidepressants which enhance both noradrenergic as well as serotonergic neurotransmission may result in higher response or remission rates than treatment with antidepressants which selectively enhance serotonergic neurotransmission. OBJECTIVE: The objective of this paper was to compare response rates among patients with MDD treated with either milnacipran, an antidepressant thought to simultaneously enhance both noradrenergic and serotonergic neurotransmission, or a selective serotonin reuptake inhibitor (SSRI). DATA SOURCES: Medline/Pubmed were searched. No year of publication or language limits were used. STUDY SELECTION: Double-blind, randomized clinical trials comparing milnacipran with an SSRI for the treatment of MDD. DATA EXTRACTION: Data were extracted with the use of a pre-coded form. DATA SYNTHESIS: Analyses were performed comparing response rates between the two antidepressant agents. Data from 6 reports involving a total of 1082 outpatients with MDD were identified and combined using a random-effects model. Patients randomized to treatment with milnacipran were as likely to experience clinical response as patients randomized to treatment with an SSRI according to the MADRS (RR = 1.04, 95% CI: 0.88-1.23, p = 0.533) or the HDRS (RR = 1.06, 95% CI: 0.90-1.24, p = 0.456) for the random effects model. Simply pooling MADRS-based response rates between the two agents revealed a 58.9% response rate for milnacipran and a 58.3% response rate for the SSRIs. Similarly, HDRS-based response rates were 59.7% and 57.5%. There was also no difference in overall discontinuation rates (RR = 0.93; 95% CI: 0.76-1.14; p = 0.506), the rate of discontinuation due to adverse events (RR = 0.77; 95% CI: 0.55-1.1; p = 0.157), or the rate of discontinuation due to inefficacy (RR = 0.98; 95% CI: 0.7-1.38; p = 0.95) between the two groups. CONCLUSIONS: These results suggest that milnacipran and the SSRIs do not differ with respect to their overall efficacy in the treatment of MDD.     

Pharmacotherapy of major depressive disorder in adolescents

Importance of the field: At any one time, major depressive disorder (MDD) affects 4 – 6% of adolescents. When untreated, MDD leads to a high immediate and subsequent suicide risk, long-term chronicity and a poor psychosocial outcome. Whereas psychotherapy can be effective in mild depression, it seems to be less effective in moderate and severe depression. However, although the use of antidepressants increased markedly during the 1990s, in recent years it has decreased as a result of concerns regarding the emergence of suicidality during antidepressant treatment.

Areas covered in this review: Are antidepressants truly effective? What is the relationship between different treatments for depression – psychotherapy and pharmacotherapy – alone or in combination? Can antidepressants increase the risk of suicide in some adolescents? Can antidepressants reduce suicide risk in suicidal adolescents?

What the reader will gain: There is evidence that selective serotonin reuptake inhibitors (SSRIs) can improve adolescent depression better than placebo, although the magnitude of the antidepressant effect is ‘small to moderate’, because of a high placebo response. The SSRI with the best rate of response compared to placebo is fluoxetine. The increased risk of suicidality in adolescents, compared to adults, is weak but consistent across most studies. However, epidemiological studies do not support a relationship between use of antidepressants and suicide rate.

Take home message: A cautious and well-monitored use of antidepressant medications is a first-line treatment option in adolescents with moderate to severe depression. Low rates of remission with current treatment strategies indicate that further research in both psychotherapy and pharmacotherapy is warranted.     

Results of a real-world study on vortioxetine in patients with major depressive disorder in South East Asia (REVIDA)

Objective: The REVIDA study aimed to assess the evolution of major depression symptoms in South East Asian (SEA) patients treated with vortioxetine for major depression in real-world clinical practice.

Methods: This non-interventional study was conducted from August 2016 to April 2017. A total of 138 patients (aged 18–65 years) with an active episode of major depression were recruited from Malaysia, Philippines, Singapore and Thailand. Vortioxetine was initiated on the first visit and patients were followed for 3 months. Depression severity was assessed using the PHQ-9 questionnaire (patient assessed) and CGI-S scale (physician assessed); cognitive function was assessed with the PDQ-D questionnaire; work productivity and activity impairment (WPAI) was assessed with the WPAI questionnaire.

Results: At baseline, 89.9% of patients were moderately to severely depressed (PHQ-9 score ≥10). During the 3 month treatment period, mean?±?SD PHQ-9 score decreased from 18.7?±?5.7 to 5.0?±?5.3, mean?±?SD CGI-S score decreased from 4.4?±?0.7 to 2.2?±?1.1 and mean?±?SD PDQ-D score decreased from 42.1?±?18.8 to 13.4?±?13.0. By Month 3, response and remission rates reached 80.8% and 59.0%, respectively. Work productivity loss decreased from 73.6% to 30.5%, while activity impairment decreased from 71.5% to 24.6%. Positive correlations were observed between PHQ-9, PDQ-D, and WPAI work productivity loss and activity impairment. By Month 3, 82.0% of patients were either not depressed or only mildly depressed (PHQ-9 score ≤9).

Conclusion: In real-world clinical settings, vortioxetine was effective in reducing depression severity and improving cognitive function and work productivity in SEA patients with major depression.     

Bupropion: a review of its use in the management of major depressive disorder

Bupropion is presumed to be a dopamine-norepinephrine reuptake inhibitor and is an effective antidepressant. It is available as three oral formulations: (i) bupropion immediate release (IR) [Wellbutrin] administered three times daily; (ii) bupropion sustained release (SR) [Wellbutrin SR] administered twice daily; and (iii) bupropion extended/modified release (XR) [Wellbutrin XL/Wellbutrin XR] administered once daily. All three formulations are bioequivalent in terms of systemic exposure to bupropion. Oral three-times-daily bupropion IR was effective and generally well tolerated in the treatment of major depressive disorder (MDD). It was as efficacious and as well tolerated as some tricyclic antidepressants (TCAs) and the selective serotonin reuptake inhibitor (SSRI) fluoxetine. Moreover, it was associated with less somnolence and weight gain than some TCAs. Twice-daily bupropion SR was also efficacious and generally well tolerated in the treatment of MDD. It was as effective as and had a generally similar tolerability profile to some SSRIs, but had the advantage of less somnolence and sexual dysfunction. The efficacy of bupropion XR in terms of primary efficacy measures was established in two of six well designed placebo-controlled studies. Bupropion XR also demonstrated efficacy in terms of some secondary outcomes in five of these studies. Additionally, bupropion XR was similar, in terms of the primary efficacy outcomes, to the SSRI escitalopram in two placebo-controlled trials and to the serotonin-norepinephrine reuptake inhibitor (SNRI) venlafaxine extended release (XR) in two trials (one of which was placebo-controlled), but not in a third placebo-controlled trial where venlafaxine XR was better than bupropion XR. It was generally as well tolerated as escitalopram and venlafaxine XR, but was associated with less sexual dysfunction than escitalopram. Available clinical data suggest that bupropion is an effective and generally well tolerated option in the treatment of MDD, with the newer formulations having the advantage of reduced frequency of daily administration.     

Vortioxetine: a novel antidepressant for the treatment of major depressive disorder

Introduction: Vortioxetine is a novel antidepressant drug approved for the treatment of major depressive disorder (MDD) in adults. It is formulated into tablets and has a dose range of 5–20 mg. The recommended starting dose is 10 mg administered orally once daily without the need for food.

Areas covered: This review focuses on the preclinical and clinical discovery of vortioxetine. It analyzes the pharmacological, neurochemical, and behavioral mechanisms of the medication and how these contribute to its potential therapeutic advantages as described in published preclinical and clinical studies and product labels.

Expert opinion: Vortioxetine displays high affinity for serotonin transporter (SERT), and serotonin 5-HT₃, 5HT_1A, 5HT₇ receptors. Functional studies show that vortioxetine acts as a SERT blocker, a 5-HT₃, 5-HT₇ receptor antagonist, and a 5-HT_1A receptor agonist. The drug is active in animal models predictive of antipsychotic and antidepressant activities and demonstrates procognitive effects in several animal models that assessed memory, cognition, and executive functions. Short- and long-term clinical trials demonstrated the clinical efficacy of vortioxetine in treating depressive symptoms and cognitive deficits in MDD patients. It also displays fairly benign safety and tolerability profiles. Vortioxetine’s unique psychopharmacological properties might contribute to an improved clinical outcome in MDD patient populations.     

An updated review of antidepressants with marked serotonergic effects in obsessive–compulsive disorder

Introduction: Since the recognition of the effectiveness of clomipramine in treating obsessive–compulsive disorder (OCD), a number of recent empirical studies have confirmed a key role of the serotonergic (5-HT) system in the pathophysiology of OCD. The current study presents a review of the existing double-blind studies testing 5-HT antidepressants in OCD.

Areas covered: A systematic review was performed to identify double-blind, placebo-controlled, randomized clinical trials investigating the efficacy of antidepressants with marked 5-HT effects [clomipramine, selective serotonin reuptake inhibitors (SSRIs), venlafaxine, desvenlafaxine, duloxetine, mirtazapine, agomelatine, vortioxetine and vilazodone] in the short-term treatment of OCD. The search provided 29 studies investigating eight different 5-HT antidepressants. While the findings show reliable efficacy of clomipramine and SSRIs in the treatment of OCD symptoms, no double-blind studies were identified investigating the efficacy of desvenlafaxine, duloxetine, mirtazapine, agomelatine, vortioxetine or vilazodone.

Expert opinion: While our results support the effectiveness of older antidepressants with marked 5-HT effects in OCD, it also suggests that newer agents should be tested more comprehensively.     

Brand-Name Antidepressants Outperform Their Generic Counterparts in Preventing Hospitalization for Depression: The Real-World Evidence from Taiwan

BackgroundGeneric antidepressants are approved on the market based on evidence of bioequivalence to their brand-name versions. We aimed to assess whether generic antidepressants exert equal effectiveness as their brand-name counterparts for treating patients with depressive disorders.MethodsIn a nationwide, population-based cohort in Taiwan from 1997 through 2013, patients with a diagnosis of a depressive disorder aged between 18 and 65 years who were new users of antidepressant drugs were classified into either the brand-name group or the generic group. All patients were followed up until medication discontinuation or the end of the study period. We assessed the risk for hospitalization as a primary outcome and augmentation therapy, daily dose, medication discontinuation, or switching to another antidepressant as secondary outcomes.ResultsA total of 277 651 brand-name users (35.8% male; mean age: 41.2 years) and 270 583 generic users (35.8% male; mean age: 41.0 years) were divided into 10 different antidepressant groups (fluoxetine, sertraline, paroxetine, escitalopram, citalopram, venlafaxine, mirtazapine, moclobemide, imipramine, and bupropion). We found that patients treated with the generic form of sertraline, paroxetine, escitalopram, venlafaxine, mirtazapine, and bupropion demonstrated significantly higher risks of psychiatric hospitalization (adjusted hazard ratios ranged from 1.20–2.34), compared to their brand-name counterparts. The differences between brand-name antidepressants and their generic counterparts in secondary outcomes varied across different drugs.ConclusionsCompared to most generic antidepressants, brand-name drugs exhibited more protective effects on psychiatric hospitalization for depressive patients. These findings could serve as an important reference for clinicians when encountering patients with depressive disorder.     

Impact of adherence to antidepressants on healthcare outcomes and costs among patients with type 2 diabetes and comorbid major depressive disorder

Objective: To evaluate the association between adherence to antidepressants and an effect on clinical outcomes and healthcare costs in patients with major depressive disorder (MDD) and comorbid type 2 diabetes (T2D).

Methods: This retrospective study used MarketScan claims data from January 2012 to March 2014. Study entry was the first claim for an antidepressant and a diagnosis code for MDD and T2D in the prior 6 months. Adherence and persistence with antidepressant therapy in the first 180 days were defined as medication possession ratio (MPR)?≥?80% and length of therapy (LOT), with no treatment gap of >15 days, respectively. T2D control (HbA1c <7%), oral diabetes medication adherence, and healthcare costs were measured in the 12 month post-index period. The impact of antidepressant adherence and persistence on outcomes was assessed using multivariable analyses.

Results: Among the 1361 patients included, the mean age was 59 years and 55% were women. About one-third of the patients were adherent (35.9%, mean MPR?=?40%), persistent (32.0%, average LOT?=?100 days), and adherent/persistent (31.2%) on antidepressants. Being adherent, persistent, or adherent/persistent to antidepressants was associated with a two-fold improvement in adherence to oral diabetes medications. Of those with HbA1c data (n?=?121), adherence or adherence/persistence to antidepressants was associated with patients being five times more likely to have T2D control (odds ratio [OR]: 4.95; 95% confidence interval [CI]: 1.39, 17.59, p?=?.0134). Comparison between antidepressant-persistent and non-persistent patients was not significant. Mean difference in adjusted all-cause annual costs showed lower costs among antidepressant-adherent and adherent/persistent patients (adherent: -$350, 95% CI: -$462, -$247; adherent/persistent: -$1165; 95% CI: -$1280, -$1060).

Conclusions: Patients with better antidepressant adherence and adherence/persistence demonstrated better HbA1c control, with lower all-cause total and medical costs. Adherence, persistence, or adherence/persistence to antidepressants was associated with improved adherence to oral diabetes medications.     

Treatment adherence and persistence with duloxetine,venlafaxine XR,and escitalopram among patients with major depressive disorder and chronic pain-related diseases

Abstract

Objective:

Chronic pain is prevalent in patients with major depressive disorder (MDD). This study compared adherence and persistence rates among MDD patients with comorbid chronic pain-related diseases (CPD, including fibromyalgia, diabetes with neurological manifestations, osteoarthritis, low back pain, and headache) for three antidepressants: duloxetine, venlafaxine XR, and escitalopram.     

Efficacy and safety of rofecoxib 12.5 mg and celecoxib 200 mg in two similarly designed osteoarthritis studies

ABSTRACT

Objective:?To compare the lower osteoarthritis (OA) dose of rofecoxib to the recommended dose of celecoxib in two identically designed studies.

Methods:?Patients with knee OA were randomized (2:2:1 ratio: rofecoxib 12.5?mg once daily (qd), celecoxib 200?mg qd, or placebo, respectively). The primary endpoint was patient global assessment of response to therapy (PGART) averaged over 6 weeks on a five-point scale. Rofecoxib would be declared at least as effective as celecoxib if the lower bound of the 95% confidence interval (95% CI) for difference in means was no lower than –0.5. Additional endpoints included Pain and Physical Function subscales of the Western Ontario and McMaster (WOMAC) OA Index. Adverse experiences (AEs) were recorded and combined from the two studies for analysis.

Results:?Study 1 enrolled 395 patients (rofecoxib, n = 160; celecoxib, n = 157; placebo, n = 78). Study 2 enrolled 413 patients (rofecoxib, n = 159; celecoxib, n = 169; placebo, n = 85). Rofecoxib 12.5?mg was at least as effective as celecoxib 200?mg by PGART (Study 1 difference –0.09 [95% CI: –0.32, 0.14] and Study 2 difference 0.02 [95% CI: –0.20, 0.24]), and both were significantly (?p < 0.001) more effective than placebo. Comparable efficacy was also seen for WOMAC Pain and Physical Function subscales with the active treatments. There was a significantly higher (?p < 0.05) incidence of serious AEs with celecoxib than rofecoxib or placebo, none of which was drug-related. There were no significant differences in the pre-specified measurements of safety including drug-related AEs or discontinuations due to AEs, and the medications demonstrated similar safety as assessed by spontaneous reporting.

Conclusions:?Rofecoxib 12.5?mg and celecoxib 200?mg provided comparable efficacy over 6 weeks, and both were significantly more efficacious than placebo. The medications demonstrated similar safety compared to one another and placebo. The primary limitations of these studies were that they were only 6 weeks long and were powered for efficacy. Therefore, conclusions about long-term safety cannot be inferred.     

Vortioxetine (Lu AA21004) 5 mg in generalized anxiety disorder: Results of an 8-week randomized,double-blind,placebo-controlled clinical trial in the United States

The goal of the current clinical study, conducted in the United States (US), was to evaluate the efficacy and tolerability of vortioxetine 5 mg vs placebo in adults with a primary diagnosis of generalized anxiety disorder (GAD; HAM-A total score ≥20 and MADRS score ≤16). Subjects were randomized (1:1) to receive vortioxetine 5 mg (n=152) or placebo (n=152) for 8 weeks. Efficacy was assessed using change from baseline in HAM-A total scores after 8 weeks of treatment compared with placebo, using mixed-model repeated measures (MMRM) analyses. Adverse events (AEs) were assessed throughout the study. A total of 304 subjects were randomized (mean age, 41.2 years). After 8 weeks of treatment, there was no statistically significant difference in the reduction in HAM-A total score from baseline between the Vortioxetine (n=145) and placebo (n=145) groups. There were no statistically significant differences in any key secondary efficacy outcome between vortioxetine and placebo. Factors potentially contributing to the differences between the results of this study and those of one of identical design conducted outside the US are discussed. The most common treatment-emergent AEs were nausea, headache, dizziness, and dry mouth. Nausea was more frequently reported in the vortioxetine group (25% vs 4.6% for the placebo group). Most AEs were mild to moderate in severity. In conclusion, in this trial, vortioxetine did not improve symptoms of GAD (compared with placebo) over 8 weeks of treatment. Vortioxetine was well tolerated in this study.