Cymbalta Helped Patients with Depression Stay Better Longer, New Data Show

Main Category: Depression
Article Date: 04 May 2004 - 0:00 PDT


Patients treated successfully with 60 mg per day of the investigational antidepressant Cymbalta® (duloxetine hydrochloride), were less likely to have their emotional and physical symptoms of depression return than those who stopped taking medication after beginning to feel better, according to results of a 38-week study presented today at the American Psychiatric Association meeting.

At the conclusion of the trial, roughly 80 percent of Cymbalta-treated patients remained free of the emotional and physical symptoms of depression. Increasing the dose of Cymbalta from 60 mg once a day to 120 mg (60 mg twice daily) was a benefit for the majority of the smaller group of patients whose symptoms did return (n=29), and did not produce additional side effects.

Increasing daily doses of medication is a common clinical practice when patients experience a re-emergence of symptoms.

In clinical practice for the treatment of major depressive disorder, the prevention of relapse and the ability to "rescue" relapsed patients with a previously well-tolerated and efficacious antidepressant is a significant advantage. In this study, the time to relapse was longer in Cymbalta-treated patients than in those who received sugar pills.

"Patients have the best chance of sustaining symptom control when they continue treatment for at least six months after their symptoms resolve," said Michael Detke, M.D., Ph.D., Cymbalta medical director, Eli Lilly and Company. "This study demonstrates that in these patients Cymbalta was effective at keeping depression at bay. These data can also give healthcare practitioners insight into a compound's safety when increasing the dose in instances when relapse does occur."

Complete elimination of symptoms, or remission, is the primary goal of depression treatment. Treating the full spectrum of emotional and physical symptoms to remission puts patients at a decreased risk of relapse.1,2 Among the 19 million Americans with depression annually, an estimated 50 percent will suffer a relapse within two years.3

Cymbalta is a potent serotonin and norepinephrine reuptake inhibitor. The U.S. Food and Drug Administration is reviewing it as a potential treatment for Major Depressive Disorder.

Additional Study Highlights

-- By 12 weeks, 68 percent of patients treated with 60 mg of Cymbalta once daily responded to treatment, defined as 50 percent reduction in symptoms, and 53 percent were virtually symptom free, which is the definition of achieving remission.

-- By 38 weeks, patients treated with Cymbalta had overall greater symptom control (HAMD17) compared with patients taking sugar pills.

-- Cymbalta-treated patients had greater relief of physical symptoms, including headaches, back pain, shoulder pain, and pain while awake and reported increased quality of life (QLDS), by the end of the study.

-- Among patients who relapsed while taking 60 mg of Cymbalta once a day, 62 percent responded to an increased dose, with 38 percent becoming virtually symptom free.

-- Among patients whose symptoms returned while taking a sugar pill, 77 percent responded once they resumed taking 60 mg Cymbalta once a day with 57 percent becoming virtually symptom free.

-- Cymbalta 60 mg, at both once and twice daily, was well tolerated.

Methods

Data were gathered from 533 adult outpatients who participated in a randomized, double-blind, multi-site, placebo-controlled study in Europe and the United States. Participants met the criteria for major depressive disorder and had Hamilton Depression Rating Scale (HAMD17) scores of > 18 at the first and second visits and a Clinical Global Impression-Severity (CGI-Severity) score of > 4 at the first and second visits.

During the first 12 weeks of the study, all patients (n=533) received 60 mg of Cymbalta in an open-label setting. At the beginning of the continuation phase (weeks 13-38), patients who no longer met the criteria for major depressive disorder were randomized to either continue on 60 mg of Cymbalta (n=136) or receive placebo (n=142).

Patients who relapsed during this period had the option of entering the rescue phase for up to 12 weeks. During this phase, placebo-treated patients received 60 mg of Cymbalta (n=56) and Cymbalta-treated patients had their dose doubled to 120 mg/day (n=29).

All patients (n=200) entered a one-week follow-up phase after either completing the study or following early discontinuation during either the continuation or rescue phases. At that time, Cymbalta-treated patients had their dose reduced by 50 percent for three days and safety and efficacy data was collected.

The primary efficacy measure was analysis of time to relapse. Secondary efficacy measures analyzed were HAMD17 subscores, the CGI Severity scale, the Patient Global Impression of Improvement (PGI-I) scale, the Symptom Questionnaire-Somatic subscale (SQ-SS), Visual analog scales (VAS), the Quality of Life in Depression Scale (QLDS) and the Sheehan Disability Scale (SDS).

About Cymbalta

In placebo-controlled clinical trials for major depressive disorder, the most commonly observed adverse events (>/= 5 percent and at least twice placebo) for Cymbalta vs. placebo (n = 1,139 vs. 777) were: nausea (20 percent vs. 7 percent), dry mouth (15 percent vs. 6 percent), constipation (11 percent vs. 4 percent), decreased appetite (8 percent vs. 2 percent), fatigue (8 percent vs. 4 percent), sleepiness (7 percent vs. 3 percent) and increased sweating (6 percent vs. 2 percent). The overall discontinuation rate due to adverse events for Cymbalta vs. placebo was 10 percent vs. 4 percent. Nausea was the only common adverse event reported as a reason for discontinuation and considered to be drug related (1.4 percent vs. 0.1 percent).

The US Food and Drug Administration issued an approvable letter for Cymbalta (duloxetine for depression) in September 2003 based upon eight- and nine-week trials. Duloxetine hydrochloride also is being studied by Lilly for the treatment of stress urinary incontinence and diabetic neuropathic pain, conditions mediated by serotonin and norepinephrine.

About Lilly

Lilly, a leading innovation-driven corporation, is developing a growing portfolio of first-in-class and best-in-class pharmaceutical products by applying the latest research from its own worldwide laboratories and from collaborations with eminent scientific organizations. Headquartered in Indianapolis, Ind., Lilly provides answers - through medicines and information - for some of the world's most urgent medical needs. Additional information about Lilly is available at www.lilly.com.

This press release contains forward-looking statements about the potential of an investigational compound, duloxetine, for the treatment of depression and reflects Lilly's current beliefs. However, as with any pharmaceutical product under development, there are substantial risks and uncertainties in the process of development and regulatory review. There is no guarantee that the product will receive regulatory approvals, or that the regulatory approval will be for the indications(s) anticipated by the company. There is also no guarantee that the product will prove to be commercially successful. For further discussion of these and other risks and uncertainties, see Lilly's filing with the United States Securities and Exchange Commission. Lilly undertakes no update to forward-looking statements.

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References

1. Nierenberg, A. Long-Term Management of Chronic Depression. J Clin Psychiatry 2001; 62 (Suppl 6): 17-20

2. Delgado, P. Approaches to the Enhancement of Patient Adherence to Antidepressant Medication Treatment. J Clin Psychiatry 2000; 61 (Suppl 6): 6-9

3. Hirschfeld RMA, Keller MB, Panico S, et. al. The National Depressive and Manic Depressive Association Consensus Statement on the Undertreatment of Depression. JAMA, 1997; 277; 333-340

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