More Comparisons

Duloxetine (Cymbalta) versus Other

Duloxetine (Cymbalta) vs. Escitalopram (Lexapro)

Escitalopram may be superior to duloxetine in acute treatment and at least as efficacious and better tolerated in long-term treatment of major depressive disorder.

  • Efficacy:
    Major depressive disorder:
    Duloxetine (Cymbalta) and escitalopram (Lexapro) were compared in an 8-month, randomized, double-blind, placebo-controlled trial in major depressive disorder. Both drugs demonstrated similar remission rates over the course of the study, with the probability of remission reaching 70% for duloxetine and 75% for escitalopram. Similar improvement was observed for both duloxetine and escitalopram on efficacy measures 5.
    Escitalopram appears to have a significant advantage over duloxetine in improving sleep 5.
    In recent comparative study of the efficacy of treatment with escitalopram versus duloxetine at week 8, the proportion of responders was 69% with escitalopram and 58% with duloxetine. Remission rates were 56% with escitalopram and 48% with duloxetine 6.
  • Side effects and tolerability:
    The rate of treatment discontinuation due to side effects is lower for escitalopram (9%) compared to duloxetine (17%). Nausea, dry mouth, vomiting, yawning, insomnia and constipation occur significantly more frequently with duloxetine than with escitalopram5,6.
    Duloxetine side effects tend to emerge early in treatment (e.g., nausea, dry mouth), whereas escitalopram adverse effects tend to emerge later in treatment (e.g., diarrhea, weight increase).
    In clinical tial statistically significant drug differences were identified in the mean changes from baseline to study endpoint for pulse (+3.05 beats per minute (bpm), duloxetine; 0.89 bpm, escitalopram) and systolic blood pressure (+3.73 mmHg, duloxetine; +0.31 mmHg, escitalopram). At 8 months, mean change in weight was significantly higher for escitalopram compared with duloxetine (+0.61 kg, duloxetine; +1.83 kg, escitalopram). However, the incidence of treatment-emergent abnormal weight gain (>/= 7% increase in weight from baseline) was similar between drugs 5.

Duloxetine (Cymbalta) vs. Paroxetine (Paxil)
  • Efficacy:
    Major depressive disorder: In clinical study duloxetine treated patients (80 and 120 mg/day) showed significantly greater improvement in the HAMD(17) total score at week 8 compared with placebo. Paroxetine was not significantly different from placebo on mean change on the HAMD(17). Duloxetine 120 mg/day also showed significant improvement on most secondary efficacy measures (six of nine) compared with placebo while duloxetine 80 mg/day (three of nine) and paroxetine (three of nine) were significantly superior to placebo on fewer secondary measures. Both duloxetine doses met statistical criteria for non-inferiority to paroxetine 3.
  • Side effects: Nausea occurs more frequently with duloxetine. The incidence of sexual dysfunction is significantly higher with paroxetine 2. Insomnia occurs significantly more frequently with duloxetine than with paroxetine (19.8% vs. 8.0% for paroxetine respectively) 4.

Duloxetine (Cymbalta) vs. Venlafaxine (Effexor)

Duloxetine more potently blocks serotonin and norephinepherine transporters in vitro and in vivo than venlafaxine 8.

  • Efficacy:
    Major depressive disorder:
    Venlafaxine-XR tends to have a favorable trend in remission and response rates compared with duloxetine1.
    Generalised anxiety disorder (GAD)
    Duloxetine has similar efficacy to venlafaxine in the treatment of generalised anxiety disorder (GAD)9.
  • Side effects: Nausea is the most common treatment-emergent side effect for both drugs, and is significantly higher with duloxetine 60mg/day compared to venlafaxine 150mg/day. Sustained elevations of systolic blood pressure occur significantly more frequently with venlafaxine than with duloxetine 7.
  • Withdrawal symptoms: Venlafaxine is associated with significantly more discontinuation symptoms than duloxetine 7.

Further reading
  • 1. Vis PM, van Baardewijk M, Einarson TR. Duloxetine and venlafaxine-XR in the treatment of major depressive disorder: a meta-analysis of randomized clinical trials. Ann Pharmacother. 2005 Nov;39(11):1798-807. Epub 2005 Sep 27. PubMed
  • 2. Delgado PL, Brannan SK, Mallinckrodt CH, Tran PV, McNamara RK, Wang F, Watkin JG, Detke MJ. Sexual functioning assessed in 4 double-blind placebo- and paroxetine-controlled trials of duloxetine for major depressive disorder. J Clin Psychiatry. 2005 Jun;66(6):686-92. PubMed
  • 3. Perahia DG, Wang F, Mallinckrodt CH, Walker DJ, Detke MJ. Duloxetine in the treatment of major depressive disorder: a placebo- and paroxetine-controlled trial. Eur Psychiatry. 2006 Sep;21(6):367-78. Epub 2006 May 11. PubMed
  • 4. Goldstein DJ, Lu Y, Detke MJ, Wiltse C, Mallinckrodt C, Demitrack MA. Duloxetine in the treatment of depression: a double-blind placebo-controlled comparison with paroxetine. J Clin Psychopharmacol. 2004 Aug;24(4):389-99. PubMed
  • 5. Pigott TA, Prakash A, Arnold LM, Aaronson ST, Mallinckrodt CH, Wohlreich MM. Duloxetine versus escitalopram and placebo: an 8-month, double-blind trial in patients with major depressive disorder. Curr Med Res Opin. 2007 Apr 27. PubMed
  • 6. Wade A, Gembert K, Florea I. A comparative study of the efficacy of acute and continuation treatment with escitalopram versus duloxetine in patients with major depressive disorder. Curr Med Res Opin. 2007 Jul;23(7):1605-14. PubMed
  • 7. Perahia DG, Pritchett YL, Kajdasz DK, Bauer M, Jain R, Russell JM, Walker DJ, Spencer KA, Froud DM, Raskin J, Thase ME. A randomized, double-blind comparison of duloxetine and venlafaxine in the treatment of patients with major depressive disorder. J Psychiatr Res. 2007 Apr 17. PubMed
  • 8. Bymaster FP, Dreshfield-Ahmad LJ, Threlkeld PG, Shaw JL, Thompson L, Nelson DL, Hemrick-Luecke SK, Wong DT. Comparative affinity of duloxetine and venlafaxine for serotonin and norepinephrine transporters in vitro and in vivo, human serotonin receptor subtypes, and other neuronal receptors. Neuropsychopharmacology. 2001 Dec;25(6):871-80. PubMed
  • 9. Allgulander C, Nutt D, Detke M, et al. A non-inferiority comparison of duloxetine and venlafaxine in the treatment of adult patients with generalized anxiety disorder. J Psychopharmacol. 2008;22:417–25 PubMed

Published: March 31, 2008
Last updated: March 24, 2014