Comparative efficacy and acceptability of 12 new-generation antidepressants: A multiple treatments meta-analysis

Department of Medicine and Public Health, Section of Psychiatry and Clinical Psychology, University of Verona, Italy
The Lancet (Impact Factor: 45.22). 02/2009; 373(9665):746-58. DOI: 10.1016/S0140-6736(09)60046-5
Source: PubMed


Conventional meta-analyses have shown inconsistent results for efficacy of second-generation antidepressants. We therefore did a multiple-treatments meta-analysis, which accounts for both direct and indirect comparisons, to assess the effects of 12 new-generation antidepressants on major depression.
We systematically reviewed 117 randomised controlled trials (25 928 participants) from 1991 up to Nov 30, 2007, which compared any of the following antidepressants at therapeutic dose range for the acute treatment of unipolar major depression in adults: bupropion, citalopram, duloxetine, escitalopram, fluoxetine, fluvoxamine, milnacipran, mirtazapine, paroxetine, reboxetine, sertraline, and venlafaxine. The main outcomes were the proportion of patients who responded to or dropped out of the allocated treatment. Analysis was done on an intention-to-treat basis.
Mirtazapine, escitalopram, venlafaxine, and sertraline were significantly more efficacious than duloxetine (odds ratios [OR] 1.39, 1.33, 1.30 and 1.27, respectively), fluoxetine (1.37, 1.32, 1.28, and 1.25, respectively), fluvoxamine (1.41, 1.35, 1.30, and 1.27, respectively), paroxetine (1.35, 1.30, 1.27, and 1.22, respectively), and reboxetine (2.03, 1.95, 1.89, and 1.85, respectively). Reboxetine was significantly less efficacious than all the other antidepressants tested. Escitalopram and sertraline showed the best profile of acceptability, leading to significantly fewer discontinuations than did duloxetine, fluvoxamine, paroxetine, reboxetine, and venlafaxine.
Clinically important differences exist between commonly prescribed antidepressants for both efficacy and acceptability in favour of escitalopram and sertraline. Sertraline might be the best choice when starting treatment for moderate to severe major depression in adults because it has the most favourable balance between benefits, acceptability, and acquisition cost.

Download full-text


Available from: Andrea Cipriani
  • Source
    • "For adults, there is a large and diverse group of effective medications available for the treatment of depression (Gartlehner et al. 2011;Hirschfeld 2012), although the selective serotonin reuptake inhibitors (SSRIs) have become predominate over the last few decades (Pratt et al. 2011). The popularity of SSRIs stems from their safety and side-effect profiles, as well as their effectiveness at reducing symptoms of depression and anxiety (Cipriani et al. 2009). In contrast to the multiple pharmacotherapies available for adult populations, only fluoxetine, an SSRI, has proven effective at treating depression in children and adolescents (Mann et al. 2006;Lovrin 2009;Masi et al. 2010;Hetrick et al. 2012). "
    [Show abstract] [Hide abstract]
    ABSTRACT: The SSRI antidepressant fluoxetine is one of the few drugs that is effective at treating depression in adolescent humans. In contrast, the SSRI paroxetine has limited efficacy and is more at risk for inducing suicidal behavior. The purpose of the present study was to more fully characterize the differential actions of paroxetine and fluoxetine. In experiment 1, male and female rats were injected with paroxetine (2.5 or 10 mg/kg), fluoxetine (10 mg/kg), or vehicle for 10 days starting on postnatal day (PD) 35, and affective behaviors were assessed using sucrose preference and elevated plus maze tasks. A separate set of rats were used to examine monoamine levels. In experiment 2, rats were injected with paroxetine (2.5, 5, or 10 mg/kg), fluoxetine (5, 10, or 20 mg/kg), or vehicle during the same time frame as experiment 1, and anxiety-like behaviors were measured using elevated plus maze, light/dark box, and acoustic startle. Repeated SSRI treatment failed to alter sucrose preference, although both paroxetine and fluoxetine reduced time spent in the open arms of the elevated plus maze and light compartment of the light/dark box. Paroxetine, but not fluoxetine, enhanced acoustic startle and interfered with habituation. Serotonin turnover was decreased by both acute and repeated fluoxetine treatment but unaltered by paroxetine administration. These results show that repeated treatment with paroxetine and fluoxetine has dissociable actions in adolescent rats. In particular, paroxetine, but not fluoxetine, increases acoustic startle at low doses and may increase sensitivity to environmental stressors.
    Preview · Article · Jul 2015 · Psychopharmacology
    • "A planar representation by definition is only possible for graph-theoretically planar graphs, such as stars. It is, for example, not possible for the Cipriani antidepressants data in Figure 1 (Cipriani et al., 2009), but it is possible more often than the frequent use of circular representations might suggest. In chemistry, a planar representation, for G. RÜCKER AND G. SCHWARZER example, of the molecule in Figure 2, a hydrocarbon called cubane, is called a Schlegel diagram (Pisanski et al., 1995; Babic & Trinajstic, 2001). "
    [Show abstract] [Hide abstract]
    ABSTRACT: In systematic reviews based on network meta-analysis, the network structure should be visualized. Network plots often have been drawn by hand using generic graphical software. A typical way of drawing networks, also implemented in statistical software for network meta-analysis, is a circular representation, often with many crossing lines. We use methods from graph theory in order to generate network plots in an automated way. We give a number of requirements for graph drawing and present an algorithm that fits prespecified ideal distances between the nodes representing the treatments. The method was implemented in the function netgraph of the R package netmeta and applied to a number of networks from the literature. We show that graph representations with a small number of crossing lines are often preferable to circular representations. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.
    No preview · Article · Jun 2015 · Research Synthesis Methods
  • Source
    • "As outlined in previous studies, acceptability may encompass efficacy and tolerability outcomes (Cipriani et al., 2009, 2011). In our analysis, under the reviewed atypical antipsychotics only quetiapine (mean dosage: 250–350 mg daily) had significantly more all-cause discontinuations than placebo. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Previous meta-analyses of atypical antipsychotics for depression were limited by few trials with direct comparisons between two treatments. We performed a network meta-analysis, which integrates direct and indirect evidence from randomized controlled trials (RCTs), to investigate the comparative efficacy and tolerability of adjunctive atypical antipsychotics for treatment-resistant depression (TRD). Systematic searches resulted in 18 RCTs (total N=4422) of seven different types and different dosages of atypical antipsychotics and placebo that were included in the review. All standard-dose atypical antipsychotics were significantly more efficacious than placebo in the efficacy (SMDs ranged from -0.27 to -0.43). There were no significant differences between these drugs. Low-dose atypical antipsychotics were not significantly more efficacious than placebo. In terms of tolerability, all standard-dose atypical antipsychotics, apart from risperidone, had significantly more side-effect discontinuations than placebo (ORs ranged from 2.72 to 6.40). In terms of acceptability, only quetiapine (mean 250-350 mg daily) had a significantly more all-cause discontinuation than placebo (OR = 1.89). In terms of quality of life/functioning, standard-dose risperidone and standard-dose aripiprazole were more beneficial than placebo (SMD = -0.38; SMD = -0.26, respectively), and standard-dose risperidone was superior to quetiapine (mean 250-350 mg daily). All standard-dose atypical antipsychotics for the adjunctive treatment of TRD are efficacious in reducing depressive symptoms. Risperidone and aripiprazole also showed benefits in improving the quality of life of patients. Atypical antipsychotics should be prescribed with caution due to abundant evidence of side effects. © The Author 2015. Published by Oxford University Press on behalf of CINP.
    Full-text · Article · May 2015 · The International Journal of Neuropsychopharmacology
Show more