Authors:
Kalpajit Dutta and Rakesh Garg*
Affiliation(s):
Department of Onco-Anaesthesiology, Pain and Palliative Care, Dr BRAIRCH, AIIMS, New Delhi, India
Dates:
Received: 20 June, 2016; Accepted: 27 June, 2016; Published: 29 June, 2016
*Corresponding author:
Dr. Rakesh Garg, MD, DNB, Assistant Professor, Room No. 139, Ist floor, Department of Anaesthesiology, Pain and Palliative Care, Dr. Brairch, All India Institute of Medical Sciences, Ansari Nagar, New Delhi-110029, India, Tel: +91 9810394950; +91 9868398335; E-mail: @
Citation:
Dutta K, Garg R (2016) Role of Duloxetine as Adjuvant in Chemotherapy Induced Peripheral Neuropathic Pain-An Update. J Addict Med Ther Sci 2(1): 010-012. DOI: 10.17352/2455-3484.000014
Copyright:
© 2016 Dutta K, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Introduction

Chemotherapy-induced peripheral neuropathy (CIPN) is a common side effect of many anticancer drugs such as platinum compounds, antitubulins (taxanes and vinca alkaloids), bortezomib and thalidomide [1]. CIPN may manifest as sensory symptoms in hands and feet, typically in a “glove and stocking” pattern; pain, numbness, tingling etc; or motor symptoms such as weakness, deficits in the cranial nerve or autonomic neuropathy [2]. Various pharmacological agents have been evaluated for management of CIPN and have been reported to have variable effects. These agents include amitriptyline, nortriptyline, venlafaxine, gabapentin, pregabaline, lamotrigine, gel mixture of baclofen, amitriptyline and ketamine. These agents have shown variable effects for management of CIPN. The studies have observed to have limited success because of insignificant relief in pain and paresthesia or no difference in pain scores with these drugs [3-7] (Table 1).

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    Table 1:

    Pharmacological agents for CIPN.

Need of newer drug for CIPN

Due to the potential harm, limited data available regarding efficacy and increase cost, new drugs are always introduced into clinical research. Duloxetine is mainly prescribed for generalized anxiety disorder and major depression. Duloxetine has recently been reported for its role in management of CIPN.

Mechanism of action: Duloxetine is a serotonin norepinephrine reuptake inhibitor (SNRI). Reuptake of serotonin and norepinephrine (NE) is inhibited by duloxetine in the central nervous system. Duloxetine increases dopamine level specifically in the prefrontal cortex, via the inhibition of NE reuptake pumps (NET) which is believed to mediate reuptake of DA and NE [7]. Inhibition of serotonin metabolism causes a decrease in pro-inflammatory cytokine activity and an increase in anti-inflammatory cytokines; duloxetine may act through this mechanism in its effect on depression [8]. The analgesic properties of duloxetine in the treatment of and central pain syndromes and diabetic neuropathy are believed to be due to sodium ion channel blockade [9].

Adverse effects: Duloxetine has been reported to be a safer drug without any major adverse effect. However, 10% to 20% of patients do report some minor side effects [10]. The published studies report various side effects with the nausea, somnolence, insomnia, dry mouth, headache and dizziness. Sexual dysfunction is often a side effect [11].

Contraindications: Duloxetine should be avoided in patients with hypersensitivity, concomitant use in patients taking MAOIs, triptans etc, and patients with uncontrolled narrow-angle glaucoma (Table 2).

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    Table 2:

    Overview of clinical studies for role of Duloxetine in CIPN.

Discussion

Duloxetine has been approved for the pain associated with diabetic peripheral neuropathy (DPN), based on the positive results of clinical trials [12-14]. However two recent studies Yang et al. (2011), and Smith et al. (2013), used duloxetine in CIPN and they found significant reduction in pain scores in duloxetine group than the placebo [15,16]. In both the studies they used duloxetine 30 mg per day increasing up to 60mg per day for 4-12 weeks. The side effects documented were very minimal fatigue (7%) insomnia (5%) and nausea (5%). In addition to a decrease in pain, data from the trial also supported that duloxetine decreased numbness and tingling symptoms [15]. Based on the results of this study, the ASCO clinical practice guidelines categorized this drug for use in patients with cancer experiencing CIPN under moderate recommendation, moderate benefit, intermediate strength of evidence and low harm [17,18].

Conclusion

There is great interest in interventions to treat CIPN, as well as to characterize this treatment-related adverse effect. Although treatment and prevention options for CIPN are limited at present, the use of duloxetine for painful CIPN has been recommended at a dose of 30-60 mg per day for 4-12 weeks. However further studies are required to prove its efficacy in clinical practice.

Clinical application of this knowledge for routine clinical practice

Chemotherapy-induced peripheral neuropathy (CIPN) remains a major issue affecting quality of life in cancer patients receiving chemotherapy. The drug armamentarium for CIPN management have limited outcome. The newer role of Duloxetine for CIPN is emerging and would prove useful for better neuropathic pain management. Its dose needs to be titrated as per response and the suggested dose is 30-60 mg/day. This needs to be continued for 4-12 weeks for optimal response.

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