Although pharmacological and psychological interventions are both effective for major depression, in primary and secondary care settings antidepressant drugs remain the mainstay of treatment. Amongst antidepressants many different agents are available. Duloxetine hydrochloride is a dual reuptake inhibitor of serotonin and norepinephrine and has been licensed by the Food and Drug Administration in the US for major depressive disorder (MDD), generalised anxiety disorder, diabetic peripheral neuropathic pain, fibromyalgia and chronic musculoskeletal pain.
To assess the evidence for the efficacy, acceptability and tolerability of duloxetine in comparison with all other antidepressant agents in the acute-phase treatment of major depression.
MEDLINE (1966 to 2012), EMBASE (1974 to 2012), the Cochrane Collaboration Depression, Anxiety and Neurosis Controlled Trials Register and the Cochrane Central Register of Controlled Trials up to March 2012. No language restriction was applied. Reference lists of relevant papers and previous systematic reviews were hand-searched. Pharmaceutical company marketing duloxetine and experts in this field were contacted for supplemental data.
Randomised controlled trials allocating patients with major depression to duloxetine versus any other antidepressive agent.
Two review authors independently extracted data and a double-entry procedure was employed. Information extracted included study characteristics, participant characteristics, intervention details and outcome measures in terms of efficacy, acceptability and tolerability.
A total of 16 randomised controlled trials (overall 5735 participants) were included in this systematic review. Of these, three trials were unpublished. We found 11 studies (overall 3304 participants) comparing duloxetine with one selective serotonin reuptake inhibitor (SSRI) (six studies versus paroxetine, three studies versus escitalopram and two versus fluoxetine), four studies (overall 1978 participants) comparing duloxetine with a newer antidepressants (three with venlafaxine and one with desvenlafaxine, respectively) and one study (overall 453 participants) comparing duloxetine with an antipsychotic drug which is also used as an antidepressive agent, quetiapine. No studies were found comparing duloxetine with tricyclic antidepressants. The pooled confidence intervals were rather wide and there were no statistically significant differences in efficacy when comparing duloxetine with other antidepressants. However, when compared with escitalopram or venlafaxine, there was a higher rate of drop out due to any cause in the patients randomised to duloxetine (odds ratio (OR) 1.62; 95% confidence interval (CI) 1.01 to 2.62 and OR 1.56; 95% CI 1.14 to 2.15, respectively). There was also some weak evidence suggesting that patients taking duloxetine experienced more adverse events than paroxetine (OR 1.24; 95% CI 0.99 to 1.55).
Duloxetine did not seem to provide a significant advantage in efficacy over other antidepressive agents for the acute-phase treatment of major depression. No differences in terms of efficacy were found, even though duloxetine was worse than some SSRIs (most of all, escitalopram) and newer antidepressants (like venlafaxine) in terms of acceptability and tolerability. Unfortunately, we only found evidence comparing duloxetine with a handful of other active antidepressive agents and only a few trials per comparison were found (in some cases we retrieved just one trial). This limited the power of the review to detect moderate, but clinically meaningful differences between the drugs. As many statistical tests have been used in the review, the findings from this review are better thought of as hypothesis forming rather than hypothesis testing and it would be very comforting to see the conclusions replicated in future trials. Most of included studies were sponsored by the drug industry manufacturing duloxetine. As for all other new investigational compounds, the potential for overestimation of treatment effect due to sponsorship bias should be borne in mind. In the present review no trials reported economic outcomes. Given that several SSRIs and the great majority of antidepressants are now available as generic formulation (only escitalopram, desvenlafaxine and duloxetine are still on patent), more comprehensive economic estimates of antidepressant treatment effect should be considered to better inform healthcare policy.
"In the literature from other parts of the world, SSRIs have been compared among each other in terms of efficacy and acceptability, and one meta-analysis has reported advantage of escitalopram and sertraline over others. Also, meta-analysis has been conducted using newer medications like venlafaxine and duloxetine. However, in the present meta-analysis, we did not calculate the effect sizes for individual comparisons between the drugs due to the lower number of studies. "
[Show abstract][Hide abstract] ABSTRACT: Antidepressants hold the center stage in the treatment of depression in current clinical practice. However, it is also well-known that the treatment response and dosage requirement are influenced by ethnic variations. Although many efficacy studies have evaluated the efficacy of antidepressants, there is lack of systematic reviews and meta-analysis of the existing literature from India.
To systematically review the efficacy of treatment of depression in the Indian context.
We searched PubMed, Psychinfo, Medknow and Google scholar to identify studies published in peer-reviewed English language journals. All controlled trials from India evaluating the clinical efficacy of antidepressants, electroconvulsive therapy (ECT), and repetitive transcranial magnetic stimulation (rTMS) for management of depression were evaluated. Data were extracted using standard procedures and risk of bias was evaluated. Effect sizes were computed for the individual studies.
Effect sizes were computed from 35 clinical trials. Overall, medications were superior to placebo for treatment of depression (mean effect size (ES) of 0.87, confidence intervals (CI of 0.71-1.02). The effect was greatest for tricyclic antidepressants (ES of 1.00, CI of 0.80-1.21) followed by monoamine oxidase inhibitors (ES 0.54, CI of 0.40-0.67). ECT was superior to antidepressants (ES 0.32, CI of - 0.21 to 0.86) and active rTMS was found to be superior to sham rTMS with mean effect size of 0.74 (CI 0.39-1.08). Risk of bias was found to be considerable. However, the review literature suggests that most of the studies have not been powered adequately and have been limited to small sample sizes.
Although there is some data from India with respect to efficacy of antidepressants, most of the trials have been of shorter duration have been inadequately powered. The available data support the superiority of antidepressants over placebo and that of ECT over antidepressants.
Indian Journal of Psychiatry 03/2014; 56(1):29-38. DOI:10.4103/0019-5545.124711
[Show abstract][Hide abstract] ABSTRACT: Significant progress has been made in assessing and managing neuropathic pain. Newer, more effective treatments with minimal side effects are available. Despite advances in treatments, neuropathic pain remains a multifaceted phenomenon that can be difficult to alleviate. Diagnosis, mechanisms of injury, and treatment recommendations are critical components of life care plans for patients with neuropathic pain. A clear understanding of the underlying issues and careful coordination with neurologists and other treatment providers are key to providing optimal life care plans. Understanding that pain treatments vary over time and by individual patient is integral to comprehensive life care planning.
Physical Medicine and Rehabilitation Clinics of North America 08/2013; 24(3):507-20. DOI:10.1016/j.pmr.2013.03.001 · 0.93 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Depressive disorders are among the most common ailments affecting humankind and some of the world's leading causes of medical disability. Despite being common, disabling and a major public health problem, the etiology of depression is unknown. Indeed, investigators have suggested that the causes of depression are multiple and multi-factorial. With these considerations in mind, in this article we examine the hypothesis that our inability to identify the causes of depressive disorders is because depression is a nonspecific epiphenomenon of brain injury or insult arising through multiple pathways.
Current Psychiatry Reports 09/2013; 15(9):386. DOI:10.1007/s11920-013-0386-z · 3.24 Impact Factor
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