Cymbalta (duloxetine delayed-release capsules) - 6 indications

Scroll down for more information on each indication:

• for the treatment of depression; approved August 2004
• for diabetic peripheral neuropathic pain; approved September of 2004
• for generalized anxiety disorder; approved February of 2007
• for major depressive disorder; approved November of 2007
• for the management of fibromyalgia; approved June of 2008
• for chronic musculoskeletal pain; approved November of 2010

General Information

Cymbalta (duloxetine hydrochloride) is a oral dual reuptake inhibitor that enhances the levels of the neurotransmitters, serotonin and norepinephrine.

Cymbalta is supplied as a capsule for oral administration. Scroll down for recommended dosing/administration for each indication.

Mechanism of Action

Cymbalta (duloxetine hydrochloride) is a oral dual reuptake inhibitor that enhances the levels of the neurotransmitters, serotonin and norepinephrine. Although the exact mechanisms of the antidepressant, central pain inhibitory and anxiolytic actions of duloxetine in humans are unknown, these actions are believed to be related to its potentiation of serotonergic and noradrenergic activity in the CNS.

Side Effects

Adverse events associated with the use of Cymbalta may include (but are not limited to) the following:

• Nausea
• Dry mouth
• Constipation
• Decreased appetite
• Fatigue
• Somnolence
• Increased sweating

Indication 1 - for the treatment of depression/Major Depressive Disorder

approved August 2004 and November of 2007

Dosing/Administration

The recommended starting dosage in adults with depression/MDD is 40 mg/day (given as 20 mg twice daily) to 60 mg/day (given either once daily or as 30 mg twice daily). For some patients, it may be desirable to start at 30 mg once daily for 1 week, to allow patients to adjust to Cymbalta before increasing to 60 mg once daily. While a 120 mg/day dose was shown to be effective, there is no evidence that doses greater than 60 mg/day confer any additional benefits. Periodically reassess to determine the need for maintenance treatment and the appropriate dosage for such treatment.

Clinical Trial Results

The efficacy of Cymbalta as a treatment for depression was established in 4 randomized, double-blind, placebo-controlled, fixed-dose studies in adult outpatients (18 to 83 years) meeting DSM-IV criteria for major depression. In 2 studies, patients were randomized to Cymbalta 60 mg once daily (N=123 and N=128, respectively) or placebo (N=122 and N=139, respectively) for 9 weeks; in the third study, patients were randomized to Cymbalta 20 or 40 mg twice daily (N=86 and N=91, respectively) or placebo (N=89) for 8 weeks; in the fourth study, patients were randomized to Cymbalta 40 or 60 mg twice daily (N=95 and N=93, respectively) or placebo (N=93) for 8 weeks. There is no evidence that doses greater than 60 mg/day confer any additional  benefit. In all 4 studies, Cymbalta demonstrated superiority over placebo as measured by improvement in the 17-item Hamilton Depression Rating Scale (HAMD-17) total score.

Indication 2 - for diabetic peripheral neuropathic pain

approved September of 2004

Dosing/Administration

Administer 60 mg once daily in adults with diabetic peripheral neuropathic pain. There is no evidence that doses higher than 60 mg once daily confer additional significant benefit and the higher dosage is clearly less well tolerated. For patients for whom tolerability is a concern, a lower starting dose may be considered.

Since diabetes is frequently complicated by renal disease, consider a lower starting dosage and gradual increase in dosage for patients with renal impairment.

Clinical Trial Results

The safety and effectiveness of Cymbalta were established in two randomized, controlled studies of approximately 1,074 patients. Although the mechanism of action is unknown, patients treated with Cymbalta reported a greater decrease in pain compared to placebo. In these trials, 51 percent of patients treated with Cymbalta reported at least a 30 percent sustained reduction in pain. In comparison, 31 percent of patients treated with placebo reported this magnitude of sustained pain reduction. 

Indication 3 - for generalized anxiety disorder

approved February of 2007

Dosing/Administration

Recommended Dosage in Adults Less than 65 Years of Age

For most adults less than 65 years of age with GAD, initiate Cymbalta 60 mg once daily. For some patients, it may be desirable to start at 30 mg once daily for 1 week, to allow patients to adjust to Cymbalta before increasing to 60 mg once daily. While a 120 mg once daily dosage was shown to be effective, there is no evidence that doses greater than 60 mg/day confer additional benefit. Nevertheless, if a decision is made to increase the dosage beyond 60 mg once daily, increase dosage in increments of 30 mg once daily. Periodically reassess to determine the continued need for maintenance treatment and the appropriate dosage for such treatment.

Recommended Dosage in Geriatric Patients

In geriatric patients with GAD, initiate Cymbalta at a dosage of 30 mg once daily for 2 weeks before considering an increase to the target dose of 60 mg/day. Thereafter, patients may benefit from doses above 60 mg once daily. If a decision is made to increase the dose beyond 60 mg once daily, increase dose in increments of 30 mg once daily. The maximum dose studied was 120 mg per day.

Recommended Dosage in Pediatric Patients 7 to 17 Years of Age

Initiate Cymbalta in pediatric patients 7 to 17 years of age with GAD at a dosage of 30 mg once daily for 2 weeks before considering an increase to 60 mg once daily. The recommended dosage range is 30 to 60 mg once daily. Some patients may benefit from dosages above 60 mg once daily. If a decision is made to increase the dose beyond 60 mg once daily, increase dosage in increments of 30 mg once daily. The maximum dose studied was 120 mg per day.

Clinical Trial Results

The safety and efficacy of Cymbalta in the treatment of GAD was established in three randomized, double-blind, placebo-controlled studies in more than 800 non-depressed adults with GAD. In all studies, Cymbalta significantly improved core anxiety symptoms as measured by the Hamilton Anxiety Scale (HAMA), compared with placebo. In addition, Cymbalta patients reported greater improvement in functional impairment associated with the illness, including improved ability to perform everyday activities at work, home, and in social situations.

Indication 4 - for the management of fibromyalgia

approved June of 2008

Dosing/Administration

Recommended Dosage in Adults

The recommended Cymbalta dosage is 60 mg once daily in adults with fibromyalgia. Begin treatment at 30 mg once daily for 1 week, to allow patients to adjust to Cymbalta before increasing to 60 mg once daily. Some patients may respond to the starting dosage. There is no evidence that dosages greater than 60 mg/day confer additional benefit, even in patients who do not respond to a 60 mg/day dosage, and higher dosages were associated with a higher rate of adverse reactions. 

Recommended Dosage in Pediatric Patients 13 to 17 Years of Age

The recommended starting Cymbalta dosage in pediatric patients 13-17 years of age with fibromyalgia is 30 mg once daily. The dosage may be increased to 60 mg once daily based on response and tolerability.

Clinical Trial Results

The efficacy of Cymbalta was assessed in two pivotal three-month clinical trials involving 874 patients with fibromyalgia. In both studies, Cymbalta reduced pain at study endpoint compared with placebo as measured by the Brief Pain Inventory (BPI) 24-hour average pain scale. The BPI is a scale that measures the severity of pain.

Significant improvement in pain for Cymbalta vs. placebo was observed in the first week of each study. Fifty-one percent and 55 percent of patients on Cymbalta had a 30 percent improvement on the BPI at endpoint (clinically meaningful relief is considered at least 30 percent pain reduction.

In addition, 65 percent and 66 percent of patients taking Cymbalta 60 mg daily reported feeling better at endpoint as measured by the Patient Global Impression of Improvement (PGI-I). The PGI-I is a patient-rated scale that evaluates how much improvement has occurred since beginning treatment.

Cymbalta 60 mg was superior to placebo on the Fibromyalgia Impact Questionnaire (FIQ) Total Score. The FIQ is a scale that is used to assess and evaluate the impact of fibromyalgia on aspects of health and functioning believed to be most affected by the disorder.

Indication 5 - for chronic musculoskeletal pain

approved November of 2010

Dosing/Administration

The recommended Cymbalta dosage is 60 mg once daily in adults with chronic musculoskeletal pain. Begin treatment at 30 mg once daily for one week, to allow patients to adjust to Cymbalta before increasing to 60 mg once daily. There is no evidence that higher dosages confer additional benefit, even in patients who do not respond to a 60 mg once daily dosage, and higher dosages are associated with a higher rate of adverse reactions.

Clinical Trial Results

Cymbalta was assessed in two 12- to 13-week trials in adult patients with chronic low back pain (CLBP) (Studies CLBP-1 and CLBP-3) and one 13-week trial in adult patients with chronic pain due to osteoarthritis (OA) (Study OA-1). In patients with CLBP, patients with radicular symptoms experienced an average 32% reduction in pain after 4 weeks of treatment with duloxetine. In Study OA-1, two hundred fifty-six patients enrolled and 204 completed the trial. Patients had a mean baseline pain rating of 6 on a numerical rating scale ranging from 0 (no pain) to 10 (worst possible pain). After 13 weeks of treatment, patients taking Cymbalta had significantly greater pain reduction than patients taking placebo. Subgroup analyses did not indicate that there were differences in treatment outcomes as a function of NSAIDs use.