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 at the American Psychiatric Association meeting.

At the conclusion of the trial, roughly 80 per cent 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. Among the 19 million Americans with depression annually, an estimated 50 per cent will suffer a relapse within two years.

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.

By 12 weeks, 68 per cent of patients treated with 60 mg of Cymbalta once daily responded to treatment, defined as 50 per cent reduction in symptoms, and 53 per cent 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 per cent responded to an increased dose, with 38 per cent becoming virtually symptom free.

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

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

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 per cent 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).

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

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.