Duloxetine (Cymbalta)

  • Generic name: Duloxetine hcl
  • Brand names: Cymbalta, Yentreve
  • Therapeutic class: Antidepressant, Serotonin and norepinephrine reuptake inhibitor (SNRIs)

What is Cymbalta used for?

  • Depression, anxiety
  • Fibromyalgia
  • Diabetic peripheral neuropathic pain and other types of nerve pain
  • Chronic pain (e.g. osteoarthritis, back pain)
  • Chronic fatigue syndrome
  • Stress urinary incontinence

Strict contraindications

  • Uncontrolled narrow-angle glaucoma
  • Severe kidney function impairment
  • Liver function impairment
  • Concomitant use or within 2 weeks of MAO inhibitors.

Serious drug interactions

  • Serotonergic agents (e.g. triptans, sibutramine, SSRIs, SNRIs, tryptophan): possible serotonin syndrome.
  • MAO inhibitors: potentially fatal serotonin syndrome. Concomitant use is contraindicated.
  • Thioridazine: increased plasma thioridazine concentrations which can result in serious ventricular arrhythmias. Concomitant use should be avoided.
  • Quinolones (e.g., ciprofloxacin, enoxacin): possible decreased duloxetine clearance and increased plasma concentrations. Concomitant use not recommended (contraindicated in Canadian labeling).

How long does it take for Cymbalta to start working?

Depression: It takes 2–3 weeks before you start to notice improvement in depressed mood 2. Duloxetine may take up to 6 weeks before it is fully effective.

Pain relief, fibromyalgia: Improvement is usually noted within the first week 1.

Medications Comparable to Cymbalta

SNRI Antidepressants:

  • Venlafaxine (Effexor) is the most similar medication to Cymbalta (duloxetine), which is also a dual acting SNRI. However, dual effect of duloxetine begins right away while venlafaxine has only the serotonin benefit until the dose is raised high enough for the norepinephrine effect to kick in.
  • Desvenlafaxine (Pristiq) - approved for the treatment of major depressive disorder; some evidence suggests lower response rates compared to duloxetine.
  • Milnacipran (Savella) - approved for treatment of fibromyalgia only, but is very effective for depression as well.

Other Alternatives to Cymbalta:

  • Amitriptyline (Elavil) - provides similar efficacy in painful diabetic neuropathy4.
  • Pregabalin (Lyrica) - provides similar efficacy in neuropathic pain4.


  • 1. Wernicke JF, Pritchett YL, D'Souza DN, Waninger A, Tran P, Iyengar S, Raskin J. A randomized controlled trial of duloxetine in diabetic peripheral neuropathic pain. Neurology. 2006 Oct 24;67(8):1411-20.
  • 2. Brannan SK, Mallinckrodt CH, Detke MJ, Watkin JG, Tollefson GD. Onset of action for duloxetine 60 mg once daily: double-blind, placebo-controlled studies. J Psychiatr Res. 2005 Mar;39(2):161-72.
  • 3. Duloxetine Monograph by American Society of Health-System Pharmacists.
  • 4. Boyle J, Eriksson ME, Gribble L, Gouni R, Johnsen S, Coppini DV, Kerr D. Randomized, placebo-controlled comparison of amitriptyline, duloxetine, and pregabalin in patients with chronic diabetic peripheral neuropathic pain. Diabetes Care. 2012 Dec;35(12):2451-8. doi: 10.2337/dc12-0656. PubMed
  • 5. Hoog SL, Cheng Y, Elpers J, Dowsett SA. Duloxetine and pregnancy outcomes: safety surveillance findings. Int J Med Sci. 2013;10(4):413-9. PubMed
  • 6. Briggs GG, Ambrose PJ, Ilett KF, Hackett LP, Nageotte MP, Padilla G. Use of duloxetine in pregnancy and lactation. Ann Pharmacother. 2009 Nov;43(11):1898-902 PubMed

Last updated: May 24, 2015

Advanced Consumer Info

  • Pregnancy Category: C. Human data suggests risk in 3rd trimester. The present reports suggest that duloxetine is not associated with major malformations5.
  • Breastfeeding: Breastfeeding is not recommended by the manufacturer. Duloxetine is excreted into breastmilk in small amounts. There are no reports of any serious side effects in infants whilst the mother was taking duloxetine6.
  • Elimination half-life: 8 to 17 hours
  • Mechanism of action: Inhibits serotonin and norepinephrine reuptake at CNS neuronal presynaptic membranes.
  • Smoking decreases the bioavailability of duloxetine by about a third.
  • Cymbalta may be more effective when taken in the morning than in the evening.