Early 1950s

Tuberculosis researchers discover that a drug that treats infections, called iproniazid, also boosts patients' mood. They learn that iproniazid slows the breakdown of three chemicals in the brain— serotonin, norepinephrine and dopamine. These molecules take center stage in the next two decades, as scientists search for antidepressants.


Eli Lilly researchers develop fluoxetine (Prozac), the first selective serotonin reuptake inhibitor. Fluoxetine thwarts the absorption, or “reuptake,” of serotonin. This boosts levels of the chemical in the pockets of space between neurons. Prozac does not hit drugstore shelves until 1988.


Scientists start tinkering with the reuptake of norepinephrine and dopamine, which, in addition to elevating mood, can relieve muscle and joint pain. They dub this new class of antidepressants serotonin-norepinephrine reuptake inhibitors (SNRIs).

At Eli Lilly, scientists begin developing an SNRI with a special focus on norepinephrine. One of their molecules becomes known as duloxetine, later branded Cymbalta.


Eli Lilly applies for a patent for duloxetine.


The company receives the patent.


Eli Lilly runs the large, multinational clinical trials—conducted in phases I, II and III—that the Food and Drug Administration requires before approving a new drug.


Eli Lilly wraps up phase I, which tests a drug's safety, and phase II, which looks at its efficacy. In a 2002 study, for example, 267 depressed adults took either duloxetine or a placebo for nine weeks. Those taking duloxetine had fewer symptoms of depression and less physical pain.


Eli Lilly completes phase III trials at 21 sites in Europe and Russia. In this step, scientists compare duloxetine to drugs on the market and attempt to identify the correct dosage. In a 2004 study of 367 depressed patients, for instance, they found that daily duloxetine doses of 40 and 80 milligrams offered more relief than a 20-mg daily dose of paroxetine (Paxil).


Eli Lilly makes its first attempt at FDA approval of duloxetine. The FDA asks the company to do more clinical trials.


The FDA recommends against approval of duloxetine because of violations at Eli Lilly's Indianapolis plant, where the drug would be manufactured. The agency also cites potential liver toxicity.


The FDA reviews more liver health data and approves duloxetine for depression and diabetic neuropathy (pain), based on another set of clinical trials. Serotonin and norepinephrine can stifle pain signals traveling from the brain to the rest of the body.


Cymbalta continues to be studied as a treatment for various mood and pain disorders.


Cymbalta goes off patent at the end of the year. In July, Eli Lilly is expected to lay off up to 1,000 sales workers in anticipation of the revenue loss. Cymbalta and osteoporosis drug Evista together bring in $5 billion annually for Eli Lilly; Evista goes off patent in early 2014.