A fuller awareness of the risks, costs, and consequences of opioid medication use in clinical pain management is growing, and the search for safe, effective, and affordable alternatives to them has taken on new urgency. The quest for opioid alternatives that offer a measure of effective analgesia (without craving, tolerance, and addiction) is taking on an increased priority in discovery laboratories and across the ranks of practicing clinicians and other health care professionals. Beyond new discovery, another potential source of such alternatives is in reevaluating existing medications approved for pain as well as those approved for other uses that may also hold promise for use as analgesics. A good example of this is anticonvulsant medications, which first came forward on applications for Food and Drug Administration (FDA) approval based on studies that described their effectiveness and safety in seizure disorders. The known pharmacologic activity of anticonvulsants suggested a “calming” or “damping” effect on nerve transmission activity that might also be useful in reducing the sensation of pain. This formed a rational basis for studies that followed to validate their use in certain pain conditions. Lyrica® pregabalin, for example, is FDA labeled both for partial onset seizures in adult patients and for several neuropathic pain conditions such as diabetic peripheral neuropathy, herpetic neuralgia, fibromyalgia, and nerve pain related to spinal injury. Medications in other therapeutic categories also share this “crossover” effectiveness from one targeted condition to another, namely certain antidepressant medications (nortriptyline, duloxetine, venlafaxine, et.al.) and nonsteroidal anti-inflammatory drugs (NSAIDs) that have been studied and demonstrated to be effective in pain conditions. So, if you’ve wondered why a medication assigned to a certain therapeutic category, (e.g., anticonvulsants), is commonly used to treat pain, it is often because the assigned category is based on the first approved indication for its use and not the full appreciation of how it is actually used in clinical practice. When a medication is prescribed for a use that is not in the FDA approved label, it is called “off-label” prescribing and happens when physicians expect that a drug may be useful for a condition that isn’t listed. Off-label prescribing is a common practice. When off-label use is not supported by an expert guideline, such as the Official Disability Guidelines (ODG) or American College of Occupational and Environmental Medicine (ACOEM), or other credible evidence in the scientific literature, First Script’s Smart Prior Authorization system will alert adjusters to this situation.