A review of the clinical utility of duloxetine in the treatment of diabetic peripheral neuropathic pain

Abstract

Diabetes mellitus is a world-wide epidemic with many long-term complications, with neuropathy being the most common. In particular, diabetic peripheral neuropathic pain (DPNP), can be one of the most distressing complications associated with diabetes, leading to decreases in physical and mental quality of life. Despite the availability of many efficient medications, DPNP remains a challenge to treat, and the optimal sequencing of pharmacotherapy remains unknown. Currently, there are only three medications approved by the US Food and Drug Administration specifically for the management of DPNP. Duloxetine (DUL), a selective serotonin-norepinephrine reuptake inhibitor, is one of these. With the goal of optimizing pharmacotherapy use in DPNP population, a review of current literature was conducted, and the clinical utility of DUL described. Along with early clinical trials, recently published observational studies and pharmacoeconomic models may be useful in guiding decision making by clinicians and managed care organizations. In real-world practice settings, DUL is associated with decreased or similar opioid utilization, increased medication adherence, and similar health care costs compared with current standard of care. DUL has consistently been found to be a cost-effective option over short time-horizons. Currently, the long-term cost-effectiveness of DUL is unknown. Evidence derived from randomized clinical trials, real-world observations, and economic models support the use of DUL as a first-line treatment option from the perspective of the patient, clinician, and managed care payer.

Monoamines as Drug Targets in Chronic Pain: Focusing on Neuropathic Pain

“…However, optimum analgesia is usually achieved at lower doses than those required for their antidepressant activity and thus, such side effects occur less frequently. Non-tricyclic antidepressants are thought to be safer than TCAs, and duloxetine is the first antidepressant approved by the FDA to treat neuropathic pain, considered the best election for peripheral diabetic neuropathic pain (Kaur et al, 2011;King et al, 2015). Less convincing results have been obtained in terms of the selective action on 5-HT receptors, yet preclinical studies indicate that the coadministration of antidepressants with certain 5-HT receptor antagonists (e.g., those of the 5-HT1A receptor) potentiates the analgesic effect of these drugs (Ardid et al, 2001;Singh et al, 2001;Anjaneyulu and Chopra, 2004).…”

“…Animal studies have helped us to elucidate some possible mechanisms responsible for the ineffectiveness of SSRIs in chronic pain, such as the facilitatory role of serotonin on 5-HT3 receptors and the alterations to 5-HT2A receptors in this condition. However, other drugs with dual action on NA and 5-HT reuptake inhibitors have proved to be efficacious in treating several forms of chronic pain, such as venlafaxine and duloxetine for fibromyalgia, migraine and diabetic neuropathy (Kaur et al, 2011;King et al, 2015;Burch, 2019). Hence, further studies should be carried out to assess how to achieve effective analgesia through the 5-HT system.…”

Pharmacotherapy for Neuropathic Pain: A Review

“…Duloxetine has shown consistent efficacy in painful diabetic neuropathy and low back pain [ 11 , 12 ]. Dosing of duloxetine is simple with 60 mg once or twice daily appearing to be equally effective.…”

An observational study of duloxetine versus SSRI monotherapy in Japanese patients with major depressive disorder: subgroup analyses of treatment effectiveness for pain, depressive symptoms, and quality of life

“…Duloxetine is a unique serotonin norepinephrine reuptake inhibitor which has been shown to be effective in the treatment of pain in patients with fibromyalgia, 16 chronic low back pain, 17 or diabetic peripheral neuropathic pain. 18 While duloxetine was associated with significantly greater benefit on measures of pain and functioning compared with selective serotonin reuptake inhibitors (SSRIs) in a randomized clinical trial in patients with MDD, 19 systematic analysis did not reveal an advantage of duloxetine over SSRIs in the treatment of patients with depression. 20 The question remains how the use of antidepressants can be optimized for patients with MDD and associated PPS and which patient subgroup might benefit most from a given treatment approach.…”