Role of gabapentin and pregabalin for the treatment of chronic pain
Although originally developed as an add-on therapy for the treatment of epilepsy, gabapentin quickly became used off-label for the management of chronic pain. From an analgesic viewpoint, it is FDA approved only for postherpetic neuralgia. It is nevertheless widely prescribed off-label for many other chronic pain states, including diabetic neuropathy, complex regional pain syndrome, fibromyalgia, and various headache types. From an analgesic viewpoint, pregabalin is FDA approved for the treatment of postherpetic neuralgia, neuropathic pain associated with diabetic neuropathy, pain associated with spinal cord injury, and fibromyalgia. Gabapentin and pregabalin are believed to act as a neuronal calcium channel α2-δ ligand, dampening hyperexcitablity in excited neurons. Side effects for each are similar, including sedation, dizziness, peripheral edema, and weight gain. Unlike pregabalin, gabapentin demonstrates nonlinear pharmacokinetics, so as doses of gabapentin are increased, the bioavailability of the medication actually decreases. Pregabalin, on the other hand, demonstrates linear bioavailablity. There are currently two forms of gabapentin that have been approved, in addition to the original form, that were designed in part of improve upon the bioavailability and to reduce the incidence of the side effects of gabapentin. These include a gastroretentive form of gabapentin taken once daily with dinner, as well as gabapentin enacarbil, a prodrug of gabapentin with more favorable bioavailability and adverse effects. Each of the forms of gabapentin as well as pregabalin have a low potential for pharmacokinetic drug interactions.
