Duloxetine Antidepressant Action Begins in One Week

Laurie Barclay, MD

November 12, 2002

Nov. 12, 2002 — Two studies presented at the recent 15th Annual U.S. Psychiatric and Mental Health Congress in Las Vegas, Nevada, showed that duloxetine (Cymbalta), a new serotonin/norepinephrine inhibitor similar to venlafaxine, is safe and effective for long-term use. More importantly, its efficacy begins in one week, faster than the usual two- to four-week time to onset for most other antidepressants.

"Rapid response to treatment helps doctors recognize that a therapy may be the right one for the patient, but even more importantly if the patient is able to feel improvement quickly, the more likely that patient will stick with treatment and ultimately get well," presenter Stephen K. Brannan, MD, from Eli Lilly and Company in Indianapolis, Indiana, says in a news release.

The investigators analyzed pooled data from two nine-week, double-blind, randomized studies in 512 patients who met criteria for major depressive disorder (MDD). After one week of therapy, depressed patients taking duloxetine, 60 mg once daily, had significantly greater improvement in mood and anxiety measures than did patients treated with placebo. These improvements were sustained throughout treatment.

By week one, duloxetine-treated patients had a significant improvement in score on Item 1 (depressed mood) of the Hamilton Depression Rating Scale, HAMD-17. Overall depressive symptoms on this scale significantly improved by week two. By the first week, significantly more patients treated with duloxetine than with placebo had improvement of depressive symptoms on the Clinical Global Impression Scale of Severity (CGI-S Scale) and on the Patient Global Impression of Improvement Scale (PGI-I Scale).

Compared with the placebo group, more patients in the duloxetine group improved by week one on Item 10 (psychic anxiety) of the HAMD-17, which measures anxiety associated with depression. By week two, duloxetine-treated patients had a significantly greater improvement in anxiety associated with depression, as reflected in the HAMD-17 Anxiety Sub-Scale.

In an open-label, multinational trial, 79% of 1,279 patients with MDD achieved response and 69% achieved symptom remission after one year of treatment with duloxetine, 80 mg or 120 mg daily. The drug was relatively well tolerated and safe over the one-year treatment period.

Most adverse events occurred early in the study period and were mild to moderate. Discontinuation due to adverse events occurred in 17% of subjects. Adverse events occurring in more than 1% of subjects and resulting in discontinuation were nausea in 1.5% of patients and somnolence in 1.4%. Sexual adverse events leading to discontinuation included erectile dysfunction in 0.2% and abnormal orgasm in 0.2%. After one year of treatment, mean change in weight from baseline was a gain of 1.1 kg. When treatment was abruptly discontinued at study termination, dizziness occurred in 8.3%, anxiety in 4.3%, and nausea in 4.2%.

Rapid, sustained improvement in depressive symptoms could allow earlier restoration of functional well-being and greater cost savings, the investigators conclude.

Eli Lilly and Company received conditional U.S. Food and Drug Administration approval for Cymbalta in September, with final approval contingent on labeling discussions and resolution of outstanding manufacturing issues. Lilly is also studying duloxetine in stress urinary incontinence, which is also mediated by serotonin and norepinephrine.

U.S. Psychiatric and Mental Health 15th Annual Congress. October 28-31, 2002.

Reviewed by Gary D. Vogin, MD