A double-blind, randomized, placebo-controlled, active-reference study of Lu AA21004 in patients with major depressive disorder (MDD)

Servei de Psiquiatría, Hospital de Sant Pau, Universidat Autonoma de Barcelona, Barcelona, Spain.
The International Journal of Neuropsychopharmacology (Impact Factor: 4.01). 07/2011; 15(5):589-600. DOI: 10.1017/S1461145711001027
Source: PubMed


The efficacy, safety, and tolerability of Lu AA21004 vs. placebo using venlafaxine XR as active reference in patients with DSM-IV-TR major depressive disorder (MDD) were evaluated. Lu AA21004 is a novel antidepressant that is a 5-HT3 and 5-HT7 receptor antagonist, 5-HT1A receptor agonist, 5-HT1B receptor partial agonist and inhibitor of the 5-HT transporter in recombinant cell lines. In this 6-wk, multi-site study, 429 patients were randomly assigned (1:1:1:1) to 5 or 10 mg Lu AA21004, placebo or 225 mg venlafaxine XR. All patients had a baseline Montgomery-Åsberg Depression Rating Scale (MADRS) total score ≥ 30. The primary efficacy analysis was based on the MADRS total score adjusting for multiplicity using a hierarchical testing procedure starting with the highest dose vs. placebo. Lu AA21004 was statistically significantly superior to placebo (n=105) in mean change from baseline in MADRS total score at week 6 (p<0.0001, last observation carried forward), with a mean treatment difference vs. placebo of 5.9 (5 mg, n=108), and 5.7 (10 mg, n=100) points. Venlafaxine XR (n=112) was also significantly superior to placebo at week 6 (p<0.0001). In total, 30 patients withdrew due to adverse events (AEs)--placebo: four (4%); 5 mg Lu AA21004: three (3%); 10 mg Lu AA21004: seven (7%); and venlafaxine: 16 (14%). The most common AEs were nausea, headache, hyperhidrosis, and dry mouth. No clinically relevant changes over time were seen in the clinical laboratory results, vital signs, weight, or ECG parameters. In this study, treatment with 5 mg and 10 mg Lu AA21004 for 6 wk was efficacious and well tolerated in patients with MDD.

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Available from: Perez Victor, Apr 25, 2014
    • "Currently, there are seven positive placebo-controlled 6–8- week studies (e.g. Alvarez et al., 2012; Baldwin et al., 2012; Jain et al., 2013), including one study of elderly subjects (Katona et al., 2012) and one positive maintenance study of adults (Baldwin et al., 2012) which have demonstrated the efficacy of vortioxetine in MDD in a dose range from 5 to 20 mg/day. Two low-dose studies (2.5 mg/day and 5 mg/day of vortioxetine) did not yield differences to placebo. "
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    • "Major depressive disorder (MDD) is a serious public health problem affecting the lives of millions in the worldwide and leading causes of disability and disease [1]. This disease causes disorder in social, mental and physical functions of patients [2]. "
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    Journal of Behavioral and Brain Science 10/2015; 5(10):430-439. DOI:10.4236/jbbs.2015.510041
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    • "In vitro studies, using cell lines expressing cloned human receptors and the 5-HT transporter, show that vortioxetine is a 5-HT 3A (Ki = 3.7 nM), 5-HT 7 (Ki = 19 nM) and 5-HT 1D (Ki = 54 nM) receptor antagonist, 5-HT 1B receptor partial agonist (Ki = 33 nM; IA 55%), 5-HT 1A receptor agonist (Ki = 15 nM) and inhibitor of the 5-HT transporter (SERT; Ki = 1.6 nM) (Bang-Andersen et al., 2011; Westrich et al., 2012). Interestingly, in both preclinical and clinical studies of MDD, vortioxetine has shown positive effects against cognitive dysfunction (Adell, 2010; Alvarez et al., 2012; du Jardin et al., 2014; Katona et al., 2012; Mørk et al., 2012, 2013). "
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