Gabapentin — The Popular but Controversial Anticonvulsant Drug May Be Zeroing in on the Pathophysiology of Disease

Abstract

Originally marketed under the brand name Neurontin, the anticonvulsant drug gabapentin has become one of the most widely prescribed—and one of the most controversial—drugs in America. On the market for nearly three decades, the drug has been prescribed for everything from chronic cough to chronic pain and hot flashes to bipolar disorder; but is it the real deal, or is it just the brain-child of aggressive marketing, false advertising, and wishful thinking? This critical review will dissect gabapentin down to its molecular roots and trace its wide-ranging effects to better understand the drug and the persons who use it. It will also discuss how gabapentin (and other anticonvulsant drugs) may be doing something more profound than just treating acute symptoms. An emerging hypothesis contends that psychiatric and related function symptoms are driven by pathological hyperactivity in symptom-related circuits in the brain and that the same abnormality may, over time, be driving the development of a plethora of general medical conditions, including diabetes, high blood pressure, cardiovascular disease, autoimmune diseases, dementia, and cancer. Emerging evidence suggests that the underlying physiological abnormality—an inherent hyperexcitability of the neurological system—is very common, and clinical correlation suggests that it is inherited in a classic autosomal dominant distribution. There is also evidence that the abnormality may be reflected in one’s resting vital signs, an observation that could help carriers identify the trait themselves. Gabapentin, together with other pharmacological (and non-pharmacological) interventions that reduce neuronal excitability, may, in addition to their immediate effects, have the potential to prevent the long-term erosive effects of neuronal hyperexcitability by simply turning down the stress response. Recognition of this could usher in history’s greatest campaign in the fight against sickness and disease.