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The Cochrane Database of Systematic... Dec 2011Mirtazapine has a unique mechanism of antidepressive action and is one of the commonly used antidepressants in clinical practice. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Mirtazapine has a unique mechanism of antidepressive action and is one of the commonly used antidepressants in clinical practice.
OBJECTIVES
The aim of the present review was to assess the evidence on the efficacy and acceptability of mirtazapine compared with other antidepressive agents in the acute-phase treatment of major depression in adults.
SEARCH METHODS
We searched the Cochrane Collaboration Depression, Anxiety and Neurosis review group's specialised register (CCDANCTR), which includes relevant randomised controlled trials from the following bibliographic databases: The Cochrane Library (all years to April 2011), EMBASE, (1980 to July 2011) MEDLINE (1950 to July 2011) and PsycINFO (1974 to July 2011). Reference lists of the reports of relevant studies were checked and experts in the field contacted. The review was not limited to English-language articles.
SELECTION CRITERIA
Randomised controlled trials (RCTs) allocating participants with major depression to mirtazapine versus any other antidepressive agent.
DATA COLLECTION AND ANALYSIS
Two authors independently checked eligibility and extracted data on an intention-to-treat basis. The primary outcome was response to treatment. The secondary outcomes included dropouts and individual adverse events.Meta-analyses were conducted using the random-effects model.
MAIN RESULTS
A total of 29 RCTs (n = 4974), mostly following up the participants for six weeks in outpatient clinics and inadequately reporting the risk of bias, were included. In comparison with tricyclic antidepressants (10 trials, n = 1553) there was no robust evidence to detect a difference between mirtazapine and tricyclics in terms of response at two weeks (odds ratio (OR) 0.85, 95% confidence interval (CI) 0.64 to 1.13) or at the end of acute-phase treatment (at 6 to 12 weeks) (OR 0.89, 95% CI 0.72 to 1.10). In comparison with selective serotonin reuptake inhibitors (SSRIs) (12 trials, n = 2626) mirtazapine was significantly more effective at two weeks (OR 1.57, 95% CI 1.30 to 1.88) and at the end of acute-phase treatment (OR 1.19, 95% CI 1.01 to 1.39). Mirtazapine was significantly more effective than a serotonin-noradrenaline reuptake inhibitor (venlafaxine only, two trials, n = 415) at two weeks (OR 2.29, 95% CI 1.45 to 3.59) and at the end of acute-phase treatment (OR 1.53, 95% CI 1.03 to 2.25).In terms of dropouts, there was no robust evidence to detect a difference between mirtazapine and other antidepressants. Mirtazapine was more likely to cause weight gain or increased appetite and somnolence than SSRIs but less likely to cause nausea or vomiting and sexual dysfunction.
AUTHORS' CONCLUSIONS
Some statistically significant and possibly clinically meaningful differences between mirtazapine and other antidepressive agents were found for the acute-phase treatment of major depression. Mirtazapine is likely to have a faster onset of action than SSRIs during the acute-phase treatment. Dropouts occur similarly in participants treated with mirtazapine and those treated with other antidepressants, although the adverse event profile of mirtazapine is unique.
Topics: Adult; Antidepressive Agents; Antidepressive Agents, Tricyclic; Cyclohexanols; Depression; Humans; Mianserin; Mirtazapine; Randomized Controlled Trials as Topic; Venlafaxine Hydrochloride
PubMed: 22161405
DOI: 10.1002/14651858.CD006528.pub2 -
Journal of Clinical Psychopharmacology Apr 2011This systematic review evaluated Chinese trials examining the efficacy of venlafaxine in the treatment of depression. Chinese databases CNKI and VIP and western... (Comparative Study)
Comparative Study Meta-Analysis Review
This systematic review evaluated Chinese trials examining the efficacy of venlafaxine in the treatment of depression. Chinese databases CNKI and VIP and western databases were searched for blinded randomized controlled trial publications comparing venlafaxine to other antidepressants or placebo (in English or Chinese). Trials had to establish diagnosis of depression according to the Chinese Classification of Mental Disorders, Diagnostic and Statistical Manual of Mental Disorders, or International Classification of Diseases. Studies were excluded if more than 20% of participants had a primary diagnosis of dysthymia or if more than 15% had a primary diagnosis of bipolar disorder. Effect sizes were calculated as Hedges' g for rating scale scores and Mantel-Haenszel risk ratios (MH RR) for response and remission data. Effect sizes were combined in a fixed-effects model. A total of 25 studies were included. Nine trials compared venlafaxine to selective serotonin reuptake inhibitor; placebo-controlled trials were lacking. Quality was at best modest, and all trials were underpowered. There were more responders (MH RR, 1.08; 95% confidence interval [CI], 1.02-1.15) and remitters (MH RR, 1.12; 95% CI, 1.02-1.24) in venlafaxine groups compared with those in tricyclic antidepressant group. Hamilton Depression Rating Scale end point scores in the venlafaxine groups were lower (Hedges' g = 0.16; 95% CI, 0.04-0.27), and venlafaxine was better tolerated than tricyclic antidepressant (Hedges' g = 0.56; 95% CI, 0.37-0.74). There were no significant differences between venlafaxine and selective serotonin reuptake inhibitor on any of these parameters. Analyses of publication bias were inconclusive. Chinese researchers have published a number of randomized controlled trials comparing venlafaxine to active comparators, but study quality was found to be low. To make optimal use of their research potential Chinese, researchers will have to improve trial reporting and the peer-review process.
Topics: Asian People; Cyclohexanols; Depressive Disorder; Humans; Randomized Controlled Trials as Topic; Venlafaxine Hydrochloride
PubMed: 21346611
DOI: 10.1097/JCP.0b013e31820f932a -
Acta Psychiatrica Scandinavica Apr 2011To determine the short-term antidepressant efficacy and tolerability of duloxetine and venlafaxine vs. each other, placebo, selective serotonin reuptake inhibitors... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To determine the short-term antidepressant efficacy and tolerability of duloxetine and venlafaxine vs. each other, placebo, selective serotonin reuptake inhibitors (SSRIs), and tri- and tetracyclic antidepressants (TCAs) in adults with major depression.
METHOD
Meta-analysis of randomised controlled trials identified through bibliographical databases and other sources, including unpublished manufacturer reports.
RESULTS
Fifty-four studies including venlafaxine arms (n = 12,816), 14 including duloxetine arms (n = 4,528), and two direct comparisons (n = 836) were analysed. Twenty-three studies were previously unpublished. In the meta-analysis, both duloxetine and venlafaxine showed superior efficacy (higher remission and response rates) and inferior tolerability (higher discontinuation rates due to adverse events) to placebo. Venlafaxine had superior efficacy in response rates but inferior tolerability to SSRIs (OR = 1.20, 95% CI 1.07-1.35 and 1.38, 95% CI 1.15-1.66, respectively), and no differences in efficacy and tolerability to TCAs. Duloxetine did not show any advantages over other antidepressants and was less well tolerated than SSRIs and venlafaxine (OR = 1.53, 95% CI 1.10-2.13 and OR 1.79, 95% CI 1.16-2.78, respectively).
CONCLUSION
Rather than being a first-line option, venlafaxine appears to be a valid alternative in patients who do not tolerate or respond to SSRIs or TCAs. Duloxetine does not seem to be indicated as a first-line treatment.
Topics: Adult; Antidepressive Agents, Second-Generation; Antidepressive Agents, Tricyclic; Cyclohexanols; Depressive Disorder, Major; Dose-Response Relationship, Drug; Drug Resistance; Duloxetine Hydrochloride; Humans; Pharmacological Phenomena; Randomized Controlled Trials as Topic; Remission Induction; Therapeutic Equivalency; Thiophenes; Treatment Outcome; Venlafaxine Hydrochloride
PubMed: 20831742
DOI: 10.1111/j.1600-0447.2010.01599.x -
Current Medical Research and Opinion May 2009The 505(b)(2) route of a New Drug Application (NDA) allows published literature or previous FDA findings of safety and effectiveness to be used for approval. Such drugs... (Review)
Review
INTRODUCTION
The 505(b)(2) route of a New Drug Application (NDA) allows published literature or previous FDA findings of safety and effectiveness to be used for approval. Such drugs are not therapeutic equivalents (i.e., generics); instead, the FDA calls them pharmaceutical alternatives. A recent example is the approval of venlafaxine extended-release (ER) tablets, developed as an alternative to the widely used ER venlafaxine capsules. The smaller size of the tablets makes them available in a 225-mg strength, which is the approved maximum dose in major depressive disorder after up-titration but currently unavailable in the capsule formulation, requiring patients on this dose to take two or three capsules; in addition, the tablets are priced at a discount compared to the capsules.
METHODS
The objective of this review was to investigate how the change in formulation of ER venlafaxine from capsules to tablets, as an example of such a change in formulation, can potentially offer value to patients and society, with a specific focus on pill burden, drug cost, and adherence. Based on a MEDLINE literature search, the pertinent literature was reviewed in a qualitative manner.
REVIEW OF THE LITERATURE
Simplifying treatment regimens, reducing pill burden, and reducing drug costs are recognized strategies for improving adherence. This can be of particular benefit in psychiatric illness because of high rates of nonadherence to treatment. Lack of adherence may negatively impact treatment outcomes and increase disease cost. As such, the ER venlafaxine tablets have the potential to reduce pill burden, improve adherence and outcomes, and reduce cost to patients and society. These preliminary findings need to be corroborated with more primary research and a systematic review of formulation changes.
CONCLUSION
A change in formulation of established therapies such as ER venlafaxine has the potential to offer clinical and pharmacoeconomic benefits to patients and society.
Topics: Cyclohexanols; Delayed-Action Preparations; Dose-Response Relationship, Drug; Drug Compounding; Drug Therapy; Humans; Models, Biological; United States; United States Food and Drug Administration; Venlafaxine Hydrochloride
PubMed: 19301988
DOI: 10.1185/03007990902858303 -
Journal of Psychopharmacology (Oxford,... Aug 2009With respect to the pharmacological characteristic, venlafaxine is comparable with tricyclic antidepressants (TCAs), and venlafaxine might be comparable in efficacy. We... (Comparative Study)
Comparative Study Meta-Analysis Review
With respect to the pharmacological characteristic, venlafaxine is comparable with tricyclic antidepressants (TCAs), and venlafaxine might be comparable in efficacy. We performed a systematic review investigating the relative efficacy and tolerability of venlafaxine compared with TCAs (imipramine, clomipramine, amitriptyline, nortriptyline and desipramine). Relevant double-blind randomised trials were identified from systematic searches of electronic databases. An exact analysis of the estimated odds ratios of response of the TCA relative to venlafaxine showed no overall significance of treatment effect (P = 0.38). The odds ratios were not homogenous across studies (P = 0.0213). The average dose of venlafaxine was 103.5 mg/day and for the TCA 106.1 mg/day. An exact analysis of the estimated odds ratios of the withdrawals and side effects in the trials with a TCA relative to venlafaxine showed no overall significance of withdrawal. From our review, no significant difference in treatment effect between low dose of both venlafaxine and the TCAs could be found. In our opinion, because of the heterogeneity of the odds ratios, one cannot conclude that they are of equal efficacy.
Topics: Antidepressive Agents, Second-Generation; Antidepressive Agents, Tricyclic; Cyclohexanols; Depressive Disorder; Humans; Odds Ratio; Randomized Controlled Trials as Topic; Research Design; Treatment Outcome; Venlafaxine Hydrochloride
PubMed: 18562424
DOI: 10.1177/0269881108089821 -
BMC Psychiatry Jul 2006Data comparing duloxetine with existing antidepressant treatments is limited. A comparison of duloxetine with fluoxetine has been performed but no comparison with... (Comparative Study)
Comparative Study Meta-Analysis Review
BACKGROUND
Data comparing duloxetine with existing antidepressant treatments is limited. A comparison of duloxetine with fluoxetine has been performed but no comparison with venlafaxine, the other antidepressant in the same therapeutic class with a significant market share, has been undertaken. In the absence of relevant data to assess the place that duloxetine should occupy in the therapeutic arsenal, indirect comparisons are the most rigorous way to go. We conducted a systematic review of the efficacy of duloxetine, fluoxetine and venlafaxine versus placebo in the treatment of Major Depressive Disorder (MDD), and performed indirect comparisons through meta-regressions.
METHODS
The bibliography of the Agency for Health Care Policy and Research and the CENTRAL, Medline, and Embase databases were interrogated using advanced search strategies based on a combination of text and index terms. The search focused on randomized placebo-controlled clinical trials involving adult patients treated for acute phase Major Depressive Disorder. All outcomes were derived to take account for varying placebo responses throughout studies. Primary outcome was treatment efficacy as measured by Hedge's g effect size. Secondary outcomes were response and dropout rates as measured by log odds ratios. Meta-regressions were run to indirectly compare the drugs. Sensitivity analysis, assessing the influence of individual studies over the results, and the influence of patients' characteristics were run.
RESULTS
22 studies involving fluoxetine, 9 involving duloxetine and 8 involving venlafaxine were selected. Using indirect comparison methodology, estimated effect sizes for efficacy compared with duloxetine were 0.11 [-0.14;0.36] for fluoxetine and 0.22 [0.06;0.38] for venlafaxine. Response log odds ratios were -0.21 [-0.44;0.03], 0.70 [0.26;1.14]. Dropout log odds ratios were -0.02 [-0.33;0.29], 0.21 [-0.13;0.55]. Sensitivity analyses showed that results were consistent.
CONCLUSION
Fluoxetine was not statistically different in either tolerability or efficacy when compared with duloxetine. Venlafaxine was significantly superior to duloxetine in all analyses except dropout rate. In the absence of relevant data from head-to-head comparison trials, results suggest that venlafaxine is superior compared with duloxetine and that duloxetine does not differentiate from fluoxetine.
Topics: Antidepressive Agents; Antidepressive Agents, Second-Generation; Cyclohexanols; Depressive Disorder, Major; Duloxetine Hydrochloride; Fluoxetine; Humans; Randomized Controlled Trials as Topic; Regression Analysis; Thiophenes; Treatment Outcome; Venlafaxine Hydrochloride
PubMed: 16867188
DOI: 10.1186/1471-244X-6-30 -
Actas Espanolas de Psiquiatria 2006To compare the efficiency of the treatment of major depressive disorder (MDD) and generalized anxiety disorder (GAD) with venlafaxine in comparison with tricyclic... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To compare the efficiency of the treatment of major depressive disorder (MDD) and generalized anxiety disorder (GAD) with venlafaxine in comparison with tricyclic antidepressants (TCA) and selective serotonin reuptake inhibitors (SSRI).
METHODS
A bibliographic systematic review of the published pharmacoeconomic studies in which one of the treatments was venlafaxine (immediate or extended-release) was conducted for MDD or GAD indications.
RESULTS
Nine studies for immediate-release venlafaxine and seven with extended-release in MDD were published, two with Spanish data. In the more extended Spanish model (1 year treatment), in depressive disorder, 106, 97 and 99 depression symptom free days (SFD) were achieved by venlafaxine, TCA and SSRI respectively, with annual costs of 6,791, 7,116 and 7,029 euros. Similar results were obtained in the second Spanish 6 month study. Regarding GAD, after the treatment of elderly patients during 8 weeks, 17 and 5 SFD were obtained with venlafaxine and placebo, with a cost per SFD of 22.94 and 65.40 euros, respectively.
CONCLUSIONS
According to the available studies, venlafaxine generates lower total costs (due to the reduction of treatment failure costs) than SSRI and TCA for the treatment of MDD. Venlafaxine is cost-effective in comparison with no treatment for GAD.
Topics: Anxiety Disorders; Cost-Benefit Analysis; Cyclohexanols; Depressive Disorder; Humans; Selective Serotonin Reuptake Inhibitors; Venlafaxine Hydrochloride
PubMed: 16736393
DOI: No ID Found -
Revista Brasileira de Psiquiatria (Sao... Mar 2005To investigate the efficacy and acceptability of antidepressants in the treatment of generalized anxiety disorder. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To investigate the efficacy and acceptability of antidepressants in the treatment of generalized anxiety disorder.
METHODS
All randomized controlled trials assessing the use of antidepressants in generalized anxiety disorder up to may 2002 were included. Non randomized trials and those that included patients with both generalized anxiety disorder and another Axis I co-morbidity were excluded. Relative risks, weighted mean difference and number needed to treat were estimated. People who died or dropped out were regarded as having had no improvement.
RESULTS
Antidepressants (imipramine, venlafaxine and paroxetine) were found to be superior to placebo in treating generalized anxiety disorder. The calculated number needed to treat for antidepressants in generalized anxiety disorder was 5.15. Dropout rates did not differ between antidepressants and placebo.
CONCLUSION
The available evidence suggests that antidepressants would probably be a reasonable treatment for generalized anxiety disorder patients in the clinical context.
Topics: Antidepressive Agents; Anxiety Disorders; Cyclohexanols; Female; Humans; Imipramine; Male; Paroxetine; Randomized Controlled Trials as Topic; Treatment Outcome; Venlafaxine Hydrochloride
PubMed: 15867979
DOI: 10.1590/s1516-44462005000100007 -
International Clinical... Mar 2005The present study aimed to systematically compare overall loss to follow-up, discontinuation rates because of adverse events and discontinuation rates because of a lack... (Meta-Analysis)
Meta-Analysis
Discontinuation rates for selective serotonin reuptake inhibitors and other second-generation antidepressants in outpatients with major depressive disorder: a systematic review and meta-analysis.
The present study aimed to systematically compare overall loss to follow-up, discontinuation rates because of adverse events and discontinuation rates because of a lack of efficacy in published studies assessing the efficacy and tolerability of selective serotonin reuptake inhibitors (SSRIs) compared to other second-generation antidepressants in treating outpatients with major depressive disorder (MDD). We searched MEDLINE, Embase, The Cochrane Library, PsychLit and the International Pharmaceutical Abstracts from 1980 to 2004 (April). Twenty double-blinded, randomized controlled trials met our eligibility criteria and compared SSRIs to other second-generation antidepressants in adult outpatients with MDD. Pooled relative risks of discontinuation rates because of (i) any reason (overall loss to follow-up), (ii) adverse events and (iii) a lack of efficacy did not differ substantially between SSRIs as a class and other second-generation antidepressants. Taking the similar efficacy of second-generation antidepressant into account, our findings suggest that clinicians can focus on other practically or clinically relevant considerations such as costs, differences in side-effect profiles, onset of action or aspects of health-related quality of life to tailor a treatment to an individual patient's needs.
Topics: Antidepressive Agents, Second-Generation; Bupropion; Cyclohexanols; Depressive Disorder, Major; Humans; Mianserin; Mirtazapine; Outpatients; Quality of Life; Randomized Controlled Trials as Topic; Risk Assessment; Selective Serotonin Reuptake Inhibitors; Treatment Refusal; Venlafaxine Hydrochloride
PubMed: 15729080
DOI: 10.1097/00004850-200503000-00001 -
Canadian Journal of Psychiatry. Revue... Aug 2004This review critiques published randomized placebo-controlled trials pertaining to the efficacy and safety of selective serotonin reuptake inhibitors (SSRIs) and... (Review)
Review
Selective serotonin reuptake inhibitor and venlafaxine use in children and adolescents with major depressive disorder: a systematic review of published randomized controlled trials.
OBJECTIVE
This review critiques published randomized placebo-controlled trials pertaining to the efficacy and safety of selective serotonin reuptake inhibitors (SSRIs) and venlafaxine in the treatment of major depressive disorder in children and adolescents.
METHOD
Medline was searched for articles meeting defined inclusion criteria. The following key terms were used: depressive disorders, antidepressive agents, fluoxetine, paroxetine, sertraline, citalopram, fluvoxamine, venlafaxine, child, and adolescent.
RESULTS
Six articles met inclusion criteria. Only 2 studies claim efficacy by significant results in primary outcomes; both have since been contested in further analysis. Not one study adequately examines safety, particularly with respect to whether a link exists between antidepressant use and induction of suicidal ideation or attempts.
CONCLUSION
Published studies on SSRI or venlafaxine use in children and adolescents are inconclusive with respect to safety and efficacy, owing to inappropriate claims of efficacy, lack of improvement in global functioning scores, nonstandardized data collection regarding adverse effects, exclusion of suicidal subjects in the recruitment process, grouping of children and adolescents together, small sample sizes, conflict of interest posed by pharmaceutical company sponsorship, and publishing bias. Future investigators should consider these factors when developing study designs.
Topics: Adolescent; Child; Cyclohexanols; Depressive Disorder, Major; Female; Humans; Male; Randomized Controlled Trials as Topic; Selective Serotonin Reuptake Inhibitors; Venlafaxine Hydrochloride
PubMed: 15453105
DOI: 10.1177/070674370404900807