What is Duloxetine (Cymbalta)?

From the Guidelines

Duloxetine is a selective serotonin and norepinephrine reuptake inhibitor (SSNRI) primarily used to treat major depressive disorder, generalized anxiety disorder, and certain types of chronic pain, including diabetic peripheral neuropathy (DPN) and fibromyalgia, with a typical starting dose of 30 mg once daily and a usual dose of 60 mg once daily for chronic pain conditions. According to the most recent and highest quality study 1, duloxetine has shown efficacy in the treatment of pain associated with DPN in multicenter randomized trials, with doses of 60 and 120 mg/day, and also appeared to improve neuropathy-related quality of life. The medication works by increasing the levels of serotonin and norepinephrine in the brain, which helps improve mood, reduce anxiety, and alleviate pain. Some key points to consider when prescribing duloxetine include:

• Common side effects, such as nausea, dry mouth, constipation, and decreased appetite
• Potential interactions with other medications, including NSAIDs and blood thinners
• The importance of taking the medication as prescribed and not stopping abruptly to avoid withdrawal symptoms
• Regular follow-ups with a healthcare provider to monitor progress and adjust treatment as necessary
• A small increase in A1C was reported in people with diabetes treated with duloxetine compared with placebo, and adverse events may be more severe in older people but may be attenuated with lower doses and slower titration of duloxetine. It is essential to weigh the benefits and risks of duloxetine, particularly in patients with diabetes, and to consider alternative treatment options, such as gabapentin or pregabalin, which may have a more favorable safety profile. However, based on the current evidence, duloxetine remains a viable treatment option for patients with DPN and other chronic pain conditions, and its use should be guided by careful consideration of the individual patient's needs and medical history.

From the FDA Drug Label

Duloxetine delayed-release capsules are selective serotonin and norepinephrine reuptake inhibitor (SNRI) for oral administration. Its chemical designation is (+)-( S)- N-methyl-γ-(1-naphthyloxy)-2-thiophenepropylamine hydrochloride. Duloxetine (Cymbalta) is a selective serotonin and norepinephrine reuptake inhibitor (SNRI), which means it works by increasing the levels of serotonin and norepinephrine in the brain to help improve mood, sleep, and appetite.

• It is used to treat major depressive disorder, generalized anxiety disorder, fibromyalgia, and neuropathic pain.
• The exact mechanisms of its actions are unknown, but it is believed to be related to its potentiation of serotonergic and noradrenergic activity in the central nervous system 2.

From the Research

Definition and Mechanism of Duloxetine

• Duloxetine is a selective dual neuronal serotonin (5-Hydroxytryptamine, 5-HT) and norepinephrine reuptake inhibitor (SSNRI) 3, 4.
• It is indicated in the United States for treatment of major depressive disorder (MDD), generalized anxiety disorder (GAD), and several chronic pain conditions, including management of diabetic peripheral neuropathic pain, fibromyalgia, and chronic musculoskeletal pain due to chronic osteoarthritis (OA) pain and chronic low back pain (LBP) 3, 4, 5, 6.

Indications and Efficacy

• Duloxetine is effective for the management of diabetic peripheral neuropathic pain, fibromyalgia, and chronic musculoskeletal pain due to chronic OA pain and chronic LBP 3, 4.
• It may be an effective treatment for mood spectrum disorders, panic disorder, several symptom clusters of borderline personality, and as add-on drug in schizophrenia 6.
• Duloxetine did not seem to provide a significant advantage in efficacy over other antidepressive agents for the acute-phase treatment of major depression 7.

Safety and Tolerability

• The most common treatment-emergent adverse events (TEAEs) were in the System Organ Class of gastrointestinal, nervous system, and psychiatric 5.
• Increases of systolic blood pressure and pulse rate at endpoint were reported 5.
• Duloxetine was worse than some SSRIs (most of all, escitalopram) and newer antidepressants (like venlafaxine) in terms of acceptability and tolerability 7.