San Diego, California, 23 May 2007 - The antidepressant duloxetinehydrochloride was equally effective in reducing painful symptoms indepressed patients who did not respond, or responded only partially, totreatment with a selective serotonin reuptake inhibitor (SSRI),regardless of whether those patients were switched from an SSRIabruptly or gradually. ¹ This new data was presented today at the American Psychiatric Association’s 160 ^th Annual Meeting in San Diego, Calif.

Between 30-50 percent of individuals treated with a given antidepressant do not respond to that treatment. ^2,3As a result, physicians often need to switch patients from oneantidepressant to another. Although this is a common clinical scenario,there are relatively few published studies to guide physicians on howto switch patients from one antidepressant to another.

“Recent data suggests the more antidepressants an individual has tried,the less likely they are to benefit from a new antidepressant. ⁴Therefore it is important to maximise the chance of remission earlierin the treatment pathway,” said Prof. Angel L. Montejo, PsychiatryResearch Coordinator, University Hospital of Salamanca, Spain. “Theseresults demonstrate that a switch to duloxetine results in asignificant decrease in the painful symptoms in patients withdepression and was well tolerated regardless of the switch method used.”

The new results are based on several secondary endpoints from a studycomparing the efficacy, safety and tolerability of two switch methodsin 368 patients who remained depressed despite taking an SSRI for atleast six weeks. ⁵Participants were randomized to either abrupt discontinuation of theirSSRI (the Direct Switch, or DS group) or to a gradual/tapereddiscontinuation of their SSRI (the Start-Taper Switch, or STS group).Both groups began taking duloxetine 60 mg/day at the beginning of thestudy. The dosage could be increased to a maximum of 120 mg/day basedon the investigator’s discretion. ¹

The primary data disclosure took place at a major medical conference in December 2006. ⁵The primary objective of the overall study was to demonstrate thenon-inferiority of Direct Switch (DS) compared with Start-taper Switch(STS) based on changes in HAMD17 total scores. Overall, that initialdata disclosure showed that switch to duloxetine was associated withsignificant improvements in the emotional symptoms of depression, andwas well tolerated and safe, regardless of which SSRI the patient wastaking at study entry.

This new analysis focused on the prevalence and severity of painfulsymptoms following the switch to duloxetine and in relation to switchmethod. The study participants, as a group, had average pain scoresindicating clinically significant physical pain. Ten weeks afterswitching to duloxetine, patients made significant improvements on allpain measures evaluated, regardless of which switch method was used. ¹

Efficacy, safety, and tolerability outcomes following Direct Switch(DS) from SSRI to duloxetine were similar to those observed forStart-taper Switch (STS). The most commonly reported adverse events inthe study were headache (13.1 percent for DS vs. 9.7 percent STS), drymouth (10.4 percent DS vs. 11.9 percent STS), and nausea (8.2 percentDS vs. 8.1 percent STS). No adverse event was reported by significantlymore patients in one group compared with the other. An excess ofadverse events was not evident following switch from any particularSSRI. ¹

“This study provides some much-needed clinical evidence to helpphysicians successfully switch patients from one antidepressant toanother when they remain depressed,” Montejo said. “It also highlightsthe continued prevalence and severity of painful symptoms amongpatients who are not adequately responding to SSRI therapy,” he said.

Duloxetine, a member of a class of drugs commonly referred to as serotonin and norepinephrine reuptake inhibitors (SNRI) ⁵, is approved in more than 70 countries for the treatment of major depression.

There is a possibility of an increased risk of suicidal thoughts orbehaviour in children and young adults treated with antidepressants.Patients should call their doctor right away if they experienceworsening depression symptoms, unusual changes in behaviour or thoughtsof suicide, especially at the beginning of treatment or after a changein dose.

Notes to Editors:

About the Study ¹
Methodology
Subjects were outpatients who met criteria for MDD despite having takenan SSRI antidepressant for at least 6 weeks, and who had a HamiltonDepression Rating Scale (HAMD17) total score of ≥15 and a ClinicalGlobal Impression of Severity (CGI-S) score of ≥3. Eligible patientswere randomized to either abrupt discontinuation of their SSRIimmediately followed by initiation of duloxetine (Direct Switch) or totapered discontinuation of their SSRI over 2 weeks and simultaneousadministration of duloxetine (Start-taper Switch). Painful physicalsymptoms were assessed at baseline and at the 10-week study endpointvia a variety of measures including 6 Visual Analogue Scales (VAS) forpain, and the Symptom Questionnaire-Somatic Subscale (SQ-SS).

Results included: ¹

• Clinically significant levels of pain (mean baseline VAS scores>30 mm) were seen across all VAS pain measures prior to switching.
• Switch to duloxetine resulted in significant improvements on all pain measures in both treatment groups.
• Mean improvements in each of the VAS pain scores, expressed as apercentage of baseline VAS scores for the Direct-Switch andStart-Taper-Switch groups respectively, were:
  • Overall Pain 20.3 percent, 17.9 percent;
  • Headache 25.6 percent, 15.6 percent;
  • Back Pain 18.2 percent, 20.2 percent;
  • Shoulder Pain 17.9 percent, 16.2 percent;
  • Interference with Daily Activities 29.5 percent, 23.2 percent;
  • Time in Pain While Awake 28.8 percent, 26.3 percent.

Efficacy, safety, and tolerability outcomes following direct switchfrom SSRI to duloxetine were similar to those observed for start-taperswitch. Few patients experienced a serious adverse event (5 patientsduring the 10 weeks of treatment and 1 during the taper period), andthere was a low rate of discontinuations due to adverse events (6.6percent DS vs. 3.8 percent STS).

This was an open-label study, so biases inherent in open-label studiescould have been a factor in the observed outcomes. Due to the largenumber of possible SSRI/dose possibilities for patients entering thestudy, it was necessary for study investigators to use their clinicaljudgment to devise an appropriate 2-week down-titration regimen forpatients in the STS group. Although general guidance was provided toinvestigators within the study protocol, the taper was nevertheless notrigidly standardized.

About Duloxetine
While duloxetine’s mechanism of action in humans is not fully known, itis believed to affect both serotonin and norepinephrine/noradrenalinemediated nerve signalling in the brain and the spinal cord. Based onpre-clinical studies, duloxetine is a balanced and potent reuptakeinhibitor of serotonin and norepinephrine/noradrenaline. Scientistsbelieve its effect on pain perception is due to increasing the activityof serotonin and norepinephrine in the central nervous system.

Duloxetine is approved for the treatment of depression and diabeticperipheral neuropathic pain in many countries and is approved in somecountries for the treatment of stress urinary incontinence. Duloxetineis approved only for adults 18 and over. There is a possibility of anincreased risk of suicidal thoughts or behaviour in children and youngadults treated with antidepressants. Patients should call their doctorright away if they experience worsening depression symptoms, unusualchanges in behaviour or thoughts of suicide, especially at thebeginning of treatment or after a change in dose.

Patients taking Cymbalta may experience dizziness or fainting upon standing. The most common side effects of Cymbalta include:

• For depression: Nausea, dry mouth, headache, insomnia, diarrhea
• For diabetic peripheral neuropathic pain: Nausea, somnolence (sleepiness), fatigue, headache, dizziness
• For stress urinary incontinence: Nausea, dry mouth, fatigue

This is not a complete list of side effects.

Duloxetine is contraindicated in patients who are allergic to it, whohave liver disease resulting in hepatic impairment, who are taking amonoamine oxidase inhibitor (MAOI), fluvoxamine, ciprofloxacin orenoxacine or who have severe kidney disease. The initiation oftreatment with duloxetine also is contraindicated in patients withuncontrolled hypertension that could expose patients to a potentialrisk of hypertensive crisis.

About Depression
Major Depressive Disorder (MDD) affects approximately 121 million people worldwide. ⁷The World Health Organization estimates depression will be among thehighest-ranking causes of disability in developed countries by 2020,second only to ischemic heart disease worldwide. ⁸ It canhappen to anyone of any age, race or ethnicity; however, women arenearly twice as likely to experience depression as men. ⁹ Although it is one of the most frequently seen psychiatric disorders in the primary care setting, ^10,11 it often goes undiagnosed or is under-treated. ^7,12This might be because depressed people often present with physicalsymptoms rather than emotional complaints; in one large study, 69percent of patients with MDD reported only physical symptoms as thereason for visiting their physician. ¹³

Complete elimination of symptoms, or remission, is the primary goal ofdepression treatment. Treating the full spectrum of emotional andphysical symptoms to remission significantly decreases a patient’s riskof relapse. ¹⁴

Eli Lilly and Company and Boehringer Ingelheim
In November 2002, Eli Lilly and Company and Boehringer Ingelheim signeda long-term agreement to jointly develop and commercialize duloxetinehydrochloride. This partnership covers neuroscience indications in mostcountries outside of the United States and Japan, with few exceptions.

About Eli Lilly and Company
Lilly, a leading innovation-driven corporation, is developing a growingportfolio of best-in-class pharmaceutical products by applying thelatest research from its own worldwide laboratories and fromcollaborations with eminent scientific organizations. Headquartered inIndianapolis, Ind., Lilly provides answers – through medicines andinformation – for some of the world`s most urgent medical needs.

About Boehringer Ingelheim
The Boehringer Ingelheim group is one of the world’s 20 leadingpharmaceutical companies. Headquartered in Ingelheim, Germany, itoperates globally with 137 affiliates in 47 countries and

38,400 employees. Since it was founded in 1885, the family-ownedcompany has been committed to researching, developing, manufacturingand marketing novel products of high therapeutic value for human andveterinary medicine.

In 2006, Boehringer Ingelheim posted net sales of 10.6 billion eurowhile spending one fifth of net sales in its largest business segmentPrescription Medicines on research and development.

Please be advised
This release is from the Corporate Headquarters of Boehringer Ingelheimand is intended for all international markets. This being the case,please be aware that there may be some differences between countriesregarding specific medical information including licensed uses. Pleasetake account of this when referring to the material.

Duloxetine for depression and diabetic peripheral neuropathic painis marketed by Lilly and Boehringer Ingelheim in all countries includedin the partnership under the brand name Cymbalta, except for Greece,Italy and Spain. In Greece, Italy and Spain Lilly markets the productas Cymbalta and Boehringer Ingelheim markets the product as Xeristar ^®.In the United States, Cymbalta is marketed by Lilly and Quintiles. InJapan, duloxetine will be co-developed and co-marketed by Lilly andShionogi & Co., Ltd.

Duloxetine for stress urinary incontinence is marketed by Lilly under the brand name Yentreve ^®.