Randomised Study to Compare the Efficacy and Tolerability of Duloxetine and Escitalopram in subjects with Major Depressive Disorder

Management of depression presents a significant medical challenge. Drugs with improved efficacy and better tolerability are valuable additions to the present therapy of this disorder. Evidence suggests that therapy with a combined serotonin and noradrenaline reuptake inhibitor may be a more effective therapy of major depressive disorder (MDD) than a single neurotransmitter inhibitor. The present study assessed the efficacy and tolerability between duloxetine (dual neurotransmitter reuptake inhibitor) 40-60 mg/day and escitalopram (single neurotransmitter reuptake inhibitor) 10-20mg/day in 24 patients as an open labeled randomized study over a duration of 12 weeks. The primary efficacy measure was the mean total change in 17 items Hamilton rating scale for depression (HAMD₁₇) from baseline to end point using the last observation carrying forward. Tolerability was evaluated by assessing discontinuation rates, adverse event rates, vital signs, and laboratory tests. In the present study, the primary analysis detected a statistically significant difference at p=.025 using Fischer’s test between duloxetine and escitalopram in both response and remission rates. There was no significant difference detected in efficacy of onset between the two study groups. Response rate, remission rate and efficacy of onset were highly significant at p<0.05 using Wilcoxon signed rank test within each group. There were a few adverse effects that were mild and self limiting with both molecules. Duloxetine is superior to escitalopram in response and remission of treatment of MDD in similar clinical setting. Both duloxetine and escitalopram are well tolerated molecules at comparable doses.

Hamilton rating scale for depression (HAMD17), Major depressive disorder (MDD).

Project on the Decade of the Brain. www.loc.gov/loc/brain/ [accessed 2014 Nov 20].

Canadian Psychiatric Association and the Canadian Network for Mood and Anxiety Treatment (CANMAT). Clinical guidelines for the treatment of depressive disorders. Can J Psychiatry 2001; 46 Suppl1: 1S-92S.

Sullivan PW, Valuck R, Saseen J, MacFall HM. A comparison of the direct costs and cost effectiveness of serotonin reuptake inhibitors and associated adverse drug reactions. CNS Drugs 2004; 18 (13): 911-32.

Goodwin GM. How do antidepressants affect serotonin receptors? The role of serotonin receptors in the therapeutic and side effect profile of the SSRIs. J Clin Psychiatry 1996; 57(S4):9–13.

Waugh J, Goa KL. Escitalopram: a review of its use in the management of major depressive and anxiety disorders. CNS Drugs 2003; 17 (5): 343-62.

Forest Laboratories Inc. Lexapro™ (escitalopram oxalate) US prescribing information [online]. Available from URL: http://www.fda.gov [Accessed 2014 Nov19]

H.Lundbeck AS. Cipralex: European summary of product characteristics [online]. Available from URL: http://www.cipralex.com/images/Cipralex/smpc.pdf [Accessed 2014 Nov 21]

Lundbeck Canada Inc. Annotated prescribing information: escitalopram. Canada: Lundbeck Canada Inc., 2005.

Chen F, Larsen MB, Sanchez C. The S-enantiomer of R, S-citalopram, increases inhibitor binding to the human serotonin transporter by an allosteric mechanism. Comparison with other serotonin transporter inhibitors. Eur Neuropsychopharmacol 2005 Mar; 15 (2): 193-8.

Baldessarini RJ. Drugs and the treatment of psychiatric disorders, depression, and anxiety disorders. In: Hardman JG, Limbird LE, editors. Goodman and Gillman’s the pharmacological basis of therapeutics. 11th ed. New York: McGraw-Hill; 2001:437.

Thase ME, Entsuah AR, Rudolph RL. Remisssion rates during treatment with venlafaxine or selective serotonin reuptake inhibitors. Br J Psychiatry 2001;178:234-241.

Tran PV, Bymaster FP, McNamara RK, Potter WZ. Dual monoamine modulation for improved treatment of major depressive disorder. J Clin Psychopharmacol 2003; 23(1):78-86.

Nelson JC. Synergistic benefits of serotonin and noradrenaline reuptake inhibition. Depress Anxiety 1998; 7(suppl 1):5-6.

American Psychiatric Association. Practice guidelines for the treatment of patients with major depressive disorder (revision). Am J Psychiatry 2000; 157(suppl 4):1-45.

Goldstein DJ, Mallinckrodt C, Lu Y, Detke MJ, Wiltse C, Demitrack MA. Duloxetine in the treatment of major depressive disorder: a double-blind clinical trial. J Clin Psychiatry 2002; 63:225–31.

Detke MJ, Lu Y, Goldstein DJ, Hayes JR, Demitrack MA. Duloxetine 60 mg once daily, for major depressive disorder: a randomized double-blind placebo-controlled trial. J Clin Psychiatry 2002; 63:308–15.

Detke MJ, Lu Y, Goldstein DJ, McNamara RK, Demitrack MA. Duloxetine 60 mg once daily dosing versus placebo in the acute treatment of major depression. J Psychiatric Res 2002; 36:383–90.

Moore N, Verdoux H, Fantino B. Prospective, multicentre, randomized, double-blind study of the efficacy of escitalopram versus citalopram in outpatient treatment of major depressive disorder. Int Clin Psychopharmacol 2005 May; 20 (3): 131-7.

Alexopoulos GS, Gordon J, Zhang D. A placebo-controlled trial of escitalopram and sertraline in the treatment of major depressive disorder [abstract no. 54]. Neuropsychopharmacology 2004; 29 Suppl. 1: 87.

Baldwin D, Hindmarch I, Huusom AKT. Escitalopram and paroxetine in the short and long-term treatment of major depressive disorder (MDD) [abstract no. P01.135]. Int J Neuropsychopharmacol 2004 Jun 22; 7 Suppl. 1: S168.

Wightman D, Horrigan JP, Modell JG. The tolerability and safety of bupropion XL versus escitalopram in the treatment of major depressive disorder [poster]. 13th Congress of the Association of European Psychiatrists (AEP); 2005 Apr 2-6; Munich.

Bielski RJ, Ventura D, Chang CC. A double-blind comparison of escitalopram and venlafaxine extended release in the treatment of major depressive disorder. J Clin Psychiatry 2004 Sep; 65 (9): 1190-6.