Pregabalin and Gabapentin for Neuropathic Pain and CRPS/RSD
By Brett R. Stacey, MD, and Pamela Campbell, MDRecently, pregabalin (Lyrica®) was approved by the Food and Drug Administration (FDA) for the treatment of post herpetic neuralgia (PHN) and painful diabetic peripheral neuropathy (DPN). Pregabalin has a chemical structure similar to gabapentin (Neurontin®), a medication originally developed to treat seizures that is now widely used to treat many varieties of neuropathic pain including CRPS/RSD. Both medications reduce pain by normalizing overactive pain pathways. Pregabalin is the first drug ever approved in the United States for two different neuropathic pain conditions. We believe it will be an important treatment option for many patients with CRPS. Gabapentin has been a great advance in treating CRPS/RSD and neuropathic pain. In addition to its effectiveness, it is very safe, with no reports of fatal overdose or organ failure. However, it does not work for everyone and sometimes the side effects are very bothersome. Does pregabalin offer an improvement? There are currently at least six large studies with pregabalin for the treatment of PHN and DPN. In these studies pregabalin shows up to a 50 percent decrease in pain scores. This is better than the roughly 30 to 40 percent reduction in pain scores observed in the trials of gabapentin for the same indications. In addition to pain relief, patients treated with pregabalin report improvements in sleep, mood, and day-to-day function. Because of its longer half-life, pregabalin can be dosed on a twice a day schedule. (Gabapentin is dosed three times a day.) At high doses, much of the gabapentin is never absorbed from the bowel, whereas pregabalin is easily absorbed at all doses, making for more predictable dosing. Data suggest that pregabalin can begin reducing pain as quickly as one day after it has been started. This is quicker than ever reported with gabapentin. Finally, preliminary results from a study of patients with neuropathic pain who had not responded to gabapentin and two other medicines shows that even in those patients, pregabalin can provide significant relief. The majority of patients in this study (who had PHN and DPN) strongly preferred pregabalin to gabapentin. In addition to neuropathic pain, pregabalin has been shown to be effective in fibromyalgia pain, the pain after spinal cord injury, and anxiety. Pregabalin comes in 8 dosage strengths from 25mg up to 300mg. All capsule sizes are the same price Roughly 1,800 mg of pregabalin is approximately $90, while pregabalin twice a day for all doses is around $118.
Gabapentin and pregabalin have similar side effects. The most common are dizziness and sedation. Patients placed on gabapentin usually experience side effects as they titrate slowly up to an effective dose, which is roughly 1,200 to 3,600 mg per day. Conversely, for patients taking pregabalin the typical starting dose of 150 mg per day can be helpful.. The range of effective doses is 150 to 600mg per day. For both medications, side effects tend to decrease over time. Less common side effects include peripheral edema and weight gain especially when taken in combination with oral hypoglycemics.
Pregabalin is categorized by the FDA as a schedule V drug, the lowest level of surveillance from the FDA. This means it is a controlled substance. The earliest reports of gabapentin’s use in treating pain were case reports of a few patients with CRPS/RSD who improved with gabapentin. Unfortunately, there have never been larger, controlled studies that definitively prove the benefits of gabapentin. As of yet, there are no studies in CRPS/RSD for pregabalin. CRPS and all other nerve pathology other than PHN and DPN are considered off label since studies in nerve pain have only been done in these specific conditions.
Our clinical experience
Here at Oregon Health & Science University, we have 8 years of research experience with pregabalin and since September of 2005 many of our patients have received it. Almost every patient converted to pregabalin from gabapentin prefers pregabalin either because of improved pain control or fewer side effects. Some patients have pain relief immediately. As everyone reading this knows, treating neuropathic pain is challenging, so pregabalin certainly doesn’t work for everyone. Our experience coupled with the extensive research supporting its use in other painful conditions makes us optimistic that pregabalin will prove to be a valuable tool in treating CRPS.
Brett R. Stacey, MD, Pamela Campbell, MD
Comprehensive Pain Center, Oregon Health & Science University, Portland, Oregon