Cymbalta (Duloxetine HCl) was safe and well tolerated in a 52-week open-label study of 1,279 patients with major depressive disorder, according to data published in the current issue of the Journal of Clinical Psychiatry.
There were no significant tolerability issues attributable to chronic vs. acute use of the investigational agent Cymbalta; patients who tolerated Cymbalta during the early period of the trial were likely to tolerate long-term dosing. Of the patients in the study, 520 remained on Cymbalta for at least 360 days, yielding approximately 808 patient-years of total exposure.
In addition, patients in the study who responded to treatment with Cymbalta had a high probability of achieving remission. Remission rates at 52 weeks in this study were close to response rates (81.8 per cent and 89.1 per cent, respectively), implying that patients who responded had a high probability of achieving complete resolution of their depressive symptoms.
"Long-term tolerability is important for antidepressant effectiveness in the complete treatment of depression. The higher-than-expected completion rate in this open-label study implies that Cymbalta was well-tolerated in these patients and was effective in helping them relieve their depressive illness," said Joel Raskin, MD, Lilly senior clinical research physician and lead author of the study.
Cymbalta was safely administered and well-tolerated in long-term chronic dosing, despite higher dosages than those used in most other Cymbalta studies.
Most treatment-emergent adverse events were either mild or moderate in severity and occurred early in the study.
Efficacy was demonstrated on all assessed measures, both clinician- and patient-rated. Furthermore, discontinuation due to adverse events over the entire 52-week study was 17 per cent - a favorable rate given the long duration of the study.
Data were gathered from a 52-week, open-label, multinational study of 1,279 adult outpatients who met the criteria for major depressive disorder. Patients were administered duloxetine 80 to 120 mg/day as two equal doses of 40 mg or 60 mg.
Efficacy was assessed using the Clinical Global Impression-Severity (CGI-Severity) scale, the Hamilton Depression Rating Scale (HAMD17), the Beck Depression Inventory-II and the Patient Global Impression-Improvement (PGI-Improvement) scale. Patient-rated quality was evaluated with the Sheehan Disability Scale. Response was defined as a 50 percent decrease from baseline on the HAMD17 total score and remission was defined as a HAMD17 total score of < 7.
Mean changes from baseline to last observation in laboratory analyses, vital signs and electrocardiograms intervals were assessed using an analysis of variance with models that included the investigator. Longitudinal mean changes and categorical changes were assessed using likelihood-based, mixed-models repeated measures and last observation carried forward.
Discontinuation due to adverse events over the entire 52-week study was 17 percent - a favorable rate given the long duration of the study. The most common reasons for discontinuation included adverse event (17 per cent), personal conflict/other reasons (10.2 per cent), and lost to follow-up (9.3 per cent).
The most common treatment-emergent adverse events in the study included nausea (34 per cent), somnolence (29.8 per cent), insomnia (31.3 per cent), headache (30.4 per cent), dry mouth (23.5 per cent), constipation (21.3 per cent) and dizziness (23.3 per cent). Most side effects occurred early in the study and generally dissipated over time. Only one side effect (headache) occurred in more than 10 percent of patients in weeks nine through 52 of the study.
The rate of serious adverse events per patient-year-exposure was low - roughly one event per 13 years of exposure. A total of 64 patients experienced serious adverse events, but investigators considered most unrelated to the study medication.
Efficacy was demonstrated on all assessed measures, both clinician-and patient-rated. The high rates of improvement at week one and two, while difficult to define and assess, were consistent with results from double blind, placebo-controlled studies.
Accumulating evidence suggests complete resolution of disease symptoms, or remission, rather than simple treatment response, should be the primary goal of depression treatment. Current medical literature suggests that depressed patients frequently experience lingering symptoms, such as persistent unexplained pain, putting them at a higher risk for relapse or recurrence.
Although interpreting results in an open-label study can be problematic, the remission rates in this 52-week study were high, implying Cymbalta was effective in relieving the symptoms of major depression in these patients.
"By treating a broad spectrum of depressive symptoms - emotional and physical - Cymbalta, once approved by the FDA, may help more patients achieve remission," Raskin said. "These data show that these patients were able to easily tolerate Cymbalta over the long-term, enabling them to achieve even higher rates of response and remission the longer they remain on therapy."
The U.S. Food and Drug Administration (FDA) 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 treatment of stress urinary incontinence, a condition mediated by serotonin and norepinephrine.