Abstract
Antiepileptic drugs (AEDs) are extensively used worldwide to treat a wide range of disorders other than epilepsy, such as neuropathic pain, migraine, and bipolar disorder. Due to this situation more than 20 new third-generation AEDs have been introduced in the market recently. The future design of new AEDs must also have potential to help in the non-epileptic disorders. The wide acceptance of second generation AEDs for the management of various non-epileptic disorders has caused the emergence of generics in the market. The wide use of approved AEDs outside epilepsy is based on both economic and scientific reasons. Bipolar disorders, migraine prophylaxis, fibromyalgia, and neuropathic pain represent the most attractive indication expansion opportunities for anticonvulsant developers, providing blockbuster revenues. Strong growth in non-epilepsy conditions will see Pfizer’s Lyrica become the market leading brand by 2018. In this review, we mainly focus on the current status of new AEDs in the treatment of chronic pain and migraine prophylaxis. AEDs have a strong analgesic potential and this is demonstrated by the wide use of carbamazepine in trigeminal neuralgia and sodium valproate in migraine prophylaxis. At present, data on the new AEDs for non-epileptic conditions are inconclusive. Not all AEDs are effective in the management of neuropathic pain and migraine. Only those AEDs whose mechanisms of action are match with pathophysiology of the disease, have potential to show efficacy in non-epileptic disorder. For this better understanding of the pathophysiology of the disease and mechanisms of action of new AEDs are essential requirement before initiating pre-clinical and clinical trials. Many new AEDs show good results in the animal model and open-label studies but fail to provide strong evidence at randomized, placebo-controlled trials. The final decision regarding the clinical efficacy of the particular AEDs in a specific non-epileptic disorder should be withdrawal from randomized placebo trials rather than open-label studies; otherwise this may lead to off-label uses of drug. The purpose of the present review is to relate the various mechanisms of action of new AEDs to pathophysiological mechanisms and clinical efficacy in neuropathic pain and migraine.
Highlights
Neuropathic pain is chronic pain caused by injury to, or disease of, the central and peripheral nervous systems, occurring as a result of a cascade of neurobiological processes, which lead to hyperexcitability in conducting pathways of somatosensory neurons
Carbamazepine (CBZ), gabapentin (GBP), and pregabalin (PGB) are currently the only three antiepileptic drugs (AEDs) approved by the U.S Food and Drug Administration (FDA) and European Medicines Agency (EMA) for the treatment of neuropathic pain
Results for painful diabetic neuropathy showed that compared to the baseline the proportion of participants who reported a 50% reduction of pain scores after 16 weeks of treatment was significantly higher in the OXC group than the placebo group, with RR 1.91 and number of people needed to treat for an additional beneficial outcome (NNTB) 6.0
Summary
Neuropathic pain is chronic pain caused by injury to, or disease of, the central and peripheral nervous systems, occurring as a result of a cascade of neurobiological processes, which lead to hyperexcitability in conducting pathways of somatosensory neurons. Many of the AEDs have been Food and Drug Administration (FDA)-approved for neuropathic pain but many others are commonly used in an off-label manner. The most commonly studied neuropathic pain subtypes include diabetic neuropathic pain (DNP), postherpetic neuralgia (PHN), and HIV-related neuropathic pain. These three conditions were estimated to affect over six million people across the seven major pharmaceutical markets (USA, UK, Japan, France, Germany, Spain, and Italy) in 2010 (Nightingale, 2012) the total affected population is considerably larger owing to the number of additional off-label uses, such as neuropathic lower back pain, cancer-related neuropathic pain, complex regional pain syndrome and postoperative neuropathic pain
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.