Subject: A retrospective, cross-sectional, observational survey study to analyse the role of fixed dose combination (FDC) of Pregabalin + Duloxetine in the treatment of neuropathic pain in adults

Neuropathic pain is a chronic condition which represents a significant burden for patients, society and healthcare systems.¹ The prevalence of neuropathic pain in the general population has been estimated at 6.9–10.0%.²

It is very difficult to estimate true-prevalence of neuropathic pain (NeP) because of underreporting. The fact sheet of the International Association for the Study of Pain IASP for 2014–2015 reported 7%–10`% prevalence of NeP in adults.³ In epidemiological studies from various regions of India reported the overall prevalence of peripheral neuropathy (PN) varying from 5 to 2400 per 10,000 population.⁴ The economic burden of NeP is a significant concern in developing countries like India.

Neuropathic pain is witnessed in varied clinical conditions, such as radiculopathy, sciatica, diabetes, spinal cord injury, post-surgery, herpes infection, stroke, fibromyalgia, etc. It may be classified as peripheral neuropathic pain, central neuropathic pain and mixed neuropathic pain depending upon the affected area of the neurons.⁵ Neuropathic pain is different from nociceptive pain and requires a different therapeutic approach, the management of neuropathic pain is complicated and continues to be a challenge.⁶

Neuropathic pain is a common and disabling consequence of DN, affecting between 25% and 50% of patients. The symptoms and signs in DN reflect sensory loss, with reduced sensitivity to touch, pinprick, hot and cold temperatures, and pain hypersensitivity with hyperalgesia or allodynia as well as ongoing (i.e., stimulus-independent) pain.⁷
Several classes of pharmacologic agents have been demonstrated to reduce pain in patients with neuropathy. However, complete resolution of symptoms is often not achieved. Patients expect a high degree of pain relief, and many expect complete pain resolution.⁸

Clinical management of neuropathic pain is challenging, and response to existing treatments is often inadequate. While tricyclic antidepressants, duloxetine, venlafaxine, pregabalin, and gabapentin have been recommended for first-line use in painful diabetic neuropathy, there is only limited evidence of efficacy for certain other anticonvulsants such as lamotrigine, carbamazepine, oxcarbazepine, valproate, topiramate, and lacosamide.¹¹

Duloxetine, is a selective serotonin and norepinephrine re-uptake inhibitor, and pregabalin, an anticonvulsant that modulates the a2-d-calcium channel subunits.¹¹

In patients showing partial response to standard therapy with either drug, combination treatment of duloxetine and pregabalin at standard doses may provide better pain relief and tolerability than the administration of maximum doses of each drug, which may be limited by adverse effects . Due to the different but potentially complementary mechanisms of action of duloxetine and pregabalin , their combination may have a clinically additive effect in the treatment of painful diabetic neuropathy, resulting in an enhanced pain relief compared to the use of either drug alone.⁹

Fixed dose combination (FDC) of Pregabalin + Duloxetine is marketed by Sun Pharmaceutical Industries Ltd. Although every product is marketed only after regulatory approval, it is important to know how it performs in day-to-day practice of individual medical practitioners. For this purpose, we have planned to conduct a retrospective, cross-sectional, observational survey to assess the role of FDC of Pregabalin + Duloxetine in patients with neuropathy.