NAME THAT DRUG
BY VINNETTE BATISTE, PHD, QUEST DIAGNOSTICS An Underlying Depression A
noteworthy anticonvulsant and analgesic is featured in this edition of Name that Drug. In an
effort to treat neurological diseases, the mystery compound was discovered in the 1970s as part of a drug development and design program implemented by the companies Goedecke and Parke-Davis—subsidiaries of the pharmaceutical manufacturer Warner- Lambert. The program focused on the development of brain-penetrable amino acid derivatives of an inhibitory neurotransmitter, which may combat the overactive nerve impluses and muscular tension experienced by individuals with seizure disorders. Gerhardt Satzinger of Goedecke synthesized a series of these amino acid analogs and serendipitously discovered the mystery drug due to its potency. Further studies initiated by multiple research groups revealed that the drug was actively transported to the brain but it did not bind to its intended molecular target; rather it worked through a mechanism that influences the release of catecholamines, important signaling molecules that regulate the “flight or fight” response in the body. The drug’s effectiveness
and non-habit forming nature made it a very popular treatment for patients with neurological disorders. In 1985, clinical studies were underway
at Parke-Davis in Ann Arbor, Michigan to prove the drug’s effectiveness in the treatment of epilepsy. Initially, the efficacy of the drug was established as an add-on treatment for patients who were intolerant to standard anticonvulsants. Aſter careful deliberations, in 1993, the U.S. Food and Drug Administration (FDA) approved the drug as a monotherapy to treat partial complex seizures. Even though the mystery drug was largely sold to treat this condition, off-label uses such as a treatment of postmenopausal hot flashes, pain relief from fibromyalgia, anxiety and bipolar disorder were also promoted despite the lack of evidence from controlled research trials. In 1996, the whistleblower Dr. David Franklin initiated a lawsuit against Warner-Lambert under the Federal False Claims Act to recover losses to medical programs such as Medicaid due to this illicit marketing scheme. Te lawsuit soon spilled over to the pharmaceutical giant Pfizer, which acquired Walter Lambert in 2000. Approval for additional uses of the drug by regulatory agencies began with the treatment of postherpetic neuralgia, a nerve pain brought on by the virus responsible for producing shingles, in 2001. Franklin vs. Parke-Davis represented one of the largest recoveries against a pharmaceutical company in U.S. history. This month’s drug is typically
administered orally in the form of either a capsule, tablet, or as a solution. After oral consumption, the drug is adsorbed though the small intestine where it can reach maximum serum concentration in two to three hours. Common dosing regimens for the treatment of epilepsy or nerve pain due to shingles include
56 datia focus
titrations with an initial dose of 300 mg/day to maintenance doses of 1,800 mg/day. Due to the relatively slow adsorption and fast elimination of the drug, a higher efficacy may be achieved with dosing above 2,400 mg/ day in some patients. Utilizing gastric retention technology developed by the specialty pharmaceutical company DepoMed, the drug is also sold under the trade name Gralise® as an extended- release formulation to combat the daily repetitive dosing requirements for the treatment of nerve pain. Drowsiness, dizziness and sedation
are consistent side effects that have been reported among the numerous clinical trials and controlled studies involving the use of the mystery drug. Changes in vision, restlessness, nervousness, hostility, edema and lower back pain have also been observed. Additionally, this drug can intensify the effects of common central nervous system depressants such as alcohol, antihistamines and sedatives. However, research reveals that this drug contends as a good replacement therapy for benzodiazepines in the treatment of alcohol withdrawal due to a low addiction potential and slower metabolism by the liver. Neuropsychiatric adverse reactions, such
as hostility, hyperactivity and uncontrollable emotional displays have been observed in clinical trials involving epileptic patients utilizing the drug. Additionally, major controversy has surrounded the mystery drug and other antiepileptic medications for their roles in increased morbidity and mortality due to suicidal behaviors. Antiepileptic drug studies revealed that many of these suicides were associated with patients suffering from epilepsy rather than other conditions. Tis is thought to be due to the increased frequency of depression among this patient population, but the role of these drugs, if any, is not well
Winter 2016
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