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,
    • "When the stress majorization algorithm was applied to the network of antidepressants analyzed by Cipriani et al. (2009), the graph did not gain clarity while losing aesthetic appearance (not shown). "
    [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.
    Research Synthesis Methods 06/2015; DOI:10.1002/jrsm.1143
  • 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.
    The International Journal of Neuropsychopharmacology 05/2015; DOI:10.1093/ijnp/pyv060 · 4.01 Impact Factor
  • Source
    • "re available on the safety of ADs classified as serotonin – noradrenaline reuptake inhibitors ( SNRIs or " Dual action ADs " ) , such as venlafaxine ( VEN ) , duloxetine ( DUL ) , and milnacipran ( MNL ) , in pregnancy and breastfeeding , even though these drugs have been approved for the treatment of MDD and generalized anxiety disorder ( GAD ) ( Cipriani et al . , 2009 ; Kasper and Pail , 2010 ) and , apart from MNL , are nowadays widely prescribed in women affected by mood and / or anxiety disorders . The aim of this paper is to review the results of the studies focusing on the safety of SNRIs in newborns exposed to such drugs during early and late pregnancy and in breastfeeding . METHODS We searched"
    [Show abstract] [Hide abstract]
    ABSTRACT: OBJECTIVE: The present study provides a comprehensive review of the existing literature on the safety of serotonin-noradrenaline reuptake inhibitors (SNRIs) in pregnancy and lactation. METHODS: Studies published in English, reporting the use of SNRIs in pregnant and/or breastfeeding women, were identified by searching MEDLINE/Pubmed, PsycINFO, and EMBASE. RESULTS: Twenty-nine studies were included in the review. Altogether, the initial evidence coming from the reviewed studies suggests a lack of association between SNRIs and an increased risk of major congenital malformations. Conversely, exposure to SNRIs seems to be significantly associated with an increased risk of some perinatal complications. No neonatal adverse events emerged, so far, in the few studies concerning the safety of SNRIs during breastfeeding. CONCLUSIONS: Available data suggest that venlafaxine is relatively safe during pregnancy, in particular as far as major malformations are concerned, whereas considering the small number of studies published, no definitive conclusions can be drawn on its safety during breastfeeding. Because of the few studies so far published, the safety of duloxetine during pregnancy and breastfeeding remains to be well established
    Human Psychopharmacology Clinical and Experimental 03/2015; DOI:10.1002/hup.2473. · 2.19 Impact Factor
Show more