Major Depressive Disorder
Duloxetine hydrochloride is used for the acute and maintenance treatment of major depressive disorder in adults.
Efficacy of duloxetine for the acute treatment of major depression has principally been established by 4 double-blind, placebo-controlled studies of 8-9 weeks' duration in outpatient settings in adults. In these studies, patients receiving duloxetine (40-120 mg daily) had greater improvements in the 17-item Hamilton depression rating scale (HAMD-17) total score than did patients receiving placebo. No age-, race-, or gender-related differences in efficacy were noted in these studies.
Efficacy of duloxetine for the maintenance treatment of major depressive disorder has been established in a randomized, placebo-controlled relapse prevention study in which 533 adult outpatients who met DSM-IV criteria for major depressive disorder initially received duloxetine 60 mg once daily in a 12-week, open-label acute phase. Patients who responded to treatment during the acute phase were then randomized to continue receiving duloxetine at the same dosage or to receive placebo for 26 weeks in the continuation phase. The duloxetine-treated patients experienced a longer time to relapse of depression compared with the placebo recipients. In addition, more placebo recipients relapsed compared with patients receiving duloxetine (approximately 29% and 17%, respectively).
The manufacturer states that if duloxetine is used for extended periods, the need for continued therapy should be reassessed periodically.
Antidepressant efficacy of duloxetine in hospital settings has not been adequately studied to date.
For further information on treatment of major depressive disorder and considerations in choosing the most appropriate antidepressant for a particular patient, including considerations related to patient tolerance, patient age, and cardiovascular, sedative, and suicidal risk, .
Generalized Anxiety Disorder
Duloxetine hydrochloride is used for the acute management of generalized anxiety disorder in adults. Efficacy of duloxetine for this indication has been established by 3 placebo-controlled trials of 9-10 weeks' duration in outpatient settings in adults who met DSM-IV criteria for generalized anxiety disorder. In these studies, patients receiving duloxetine (60-120 mg daily) had greater improvements in the Hamilton anxiety scale (HAM-A) total score and the Sheehan Disability Scale (SDS) global functional impairment score than did patients receiving placebo. No age- or gender-related differences in efficacy were noted in these studies.
The manufacturer states that the anxiolytic efficacy of duloxetine for long-term use (i.e., exceeding 10 weeks) has not been established by controlled studies to date. If duloxetine is used for extended periods, the need for continued therapy should be reassessed periodically.
Duloxetine hydrochloride is used for the management of neuropathic pain associated with diabetic peripheral neuropathy in adults. Efficacy of duloxetine for this indication has been established by 2 controlled studies of 12 weeks' duration in adults with type 1 or 2 diabetes mellitus and a diagnosis of painful distal symmetrical sensorimotor polyneuropathy for at least 6 months. Patients were excluded from the studies if they met DSM-IV-TR criteria for major depressive disorder and dysthymia. In these studies, 51% of patients receiving duloxetine (60-120 mg daily) and up to 4 g of acetaminophen daily (as needed) reported at least a 30% sustained reduction in pain compared with 31% of those receiving placebo plus acetaminophen (as needed). Some patients in the study experienced a decrease in pain as early as week 1, which persisted throughout the study.
Duloxetine hydrochloride is used for the management of fibromyalgia in adults. Efficacy of duloxetine for this indication has been established by 2 randomized, double-blind, placebo-controlled, fixed-dose studies in adults with a diagnosis of fibromyalgia based on the American College of Rheumatology (ACR) criteria (i.e., history of widespread pain for 3 months and pain present in 11 or more of the 18 specific tender point sites). The first study was of 3 months' duration and enrolled female patients only while the second study was of 6 months' duration and enrolled both male and female patients. Approximately 25% of the patients had concurrent major depressive disorder. Both of these studies compared duloxetine 60 mg once daily or 120 mg daily (given in divided doses in study 1 and as a single daily dose in study 2) with placebo. In addition, Study 2 compared duloxetine 20 mg daily with placebo during the initial 3 months of the 6-month study; after 3 months, the duloxetine dosage was titrated up to 60 mg once daily for the remainder of the study. In these studies, duloxetine therapy in dosages of 60 or 120 mg daily significantly improved the endpoint mean pain scores from baseline and increased the number of patients who had at least a 50% reduction in pain score compared with baseline. Although pain reduction was observed in patients both with and without major depressive disorder, the degree of pain reduction may be greater in patients with major depressive disorder. Some patients experienced a reduction in pain as early as week 1, which persisted throughout the study. Improvement also was noted on measures of function as well as on the Patient Global Impression of Improvement (PGI) scale. Neither study demonstrated an additional therapeutic benefit of 120 mg daily compared with 60 mg daily, and the higher dosage was associated with more frequent adverse effects and early discontinuance of therapy.
The manufacturer states that the efficacy of duloxetine for long-term use (i.e., exceeding 3 months) has not been established by controlled studies to date. However, longer-term efficacy of the drug has been demonstrated for up to 6 months in extension phases of 2 controlled studies to date. The manufacturer recommends that the decision to continue therapy with the drug be based on individual patient response.
Stress Urinary Incontinence
Duloxetine has been used for the management of moderate to severe stress urinary incontinence (SUI) in women. In a number of placebo-controlled clinical trials involving women with predominantly SUI receiving duloxetine or placebo for up to 12 weeks, duloxetine was significantly better than placebo in reducing the frequency of incontinence episodes (which were reduced by approximately 50% in patients receiving duloxetine) and improving patients' quality of life (as assessed by Incontinence Quality of Life questionnaire scores). Therapy with the drug generally was well tolerated in these studies, with nausea being the most commonly reported adverse effect.
Data from one subsequent analysis suggest that the beneficial effects of duloxetine in women with SUI are maintained for up to 30 months. In addition, some data suggest that combining duloxetine and pelvic floor muscle training exercises may be more effective than either treatment alone. The potential role of duloxetine therapy relative to other forms of treatment (including pelvic floor muscle training, management of fluid intake and voiding, weight loss, devices, and surgery) remains to be established and requires additional study.