The abuse of prescription medications is reaching epidemic proportions worldwide. Some judge prescription drug abuse to be as prevalent and as deadly as an epidemic caused by an infectious agent. Consider recent news reports about an HIV outbreak in a rural Indiana town that resulted from widespread addiction to a prescription painkiller.
The tragedy of Austin, Indiana is the tip of the iceberg. Prescription drug abuse is responsible for 16,000 deaths annually in the United States, a number that's rising steadily. Meanwhile, 52 million people over age 12 in the US - nearly 1 in 6 - have misused prescription drugs, 6 million of them in the past month alone.
There's the teenager who takes her mother's migraine medicine because she likes the euphoria she experiences, the weary husband of a cancer patient who begins using her pain medication, the athlete who injects anabolic steroids in order to gain a competitive edge.
Regulatory bodies responsible for licensing new medicines, including the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA), have responded with concern and tough new regulations. Now, if research establishes that a potential treatment reaches the brain, the developer must assess the treatment's potential for abuse and tell regulators before the drug can be licensed.
"In the US, information about the potential for abuse is part of a drug's safety profile and must be included in the new drug application (NDA)," said Beatriz Rocha, Covance's Executive Director and Head of Regulatory Affairs Clinical Strategy.
The requirement for testing affects every new drug that impacts the brain, not just the opioids, stimulants and depressants that are most often associated with abuse. From antipsychotics and drugs for obesity to treatments for Alzheimer's disease and even diabetes, the universe of drugs that impact the brain is huge. So are the potential headaches for sponsors: Drugs with demonstrated abuse potential will be classified as scheduled, subjecting them to government controls on use and distribution.
One might say that the earliest efforts to prevent prescription drug abuse begin with Beatriz and her team. They counsel sponsors about when and how to assess treatments that are in development for potential abuse, as well as how to address the issue with regulatory authorities. Every case presents a unique set of challenges.
"There is no recipe and one plan doesn't fit all," Beatriz said. "We have to have case-by-case discussions with sponsors about testing."
Abuse liability testing, as it's known, involves the use of animal and human studies to find out whether a new treatment is likely to be used for non-medical reasons - that is, to get high or to enhance performance. While animal testing may be sufficient to establish a drug's abuse profile, further testing in humans is necessary if there are signs that a drug is vulnerable to misuse.
"The hurdles are very high, mostly for compounds with new mechanisms of action," abuse Beatriz explained. "The first step is to understand the new drug: Does it enter the brain and once there, what is its function? Does it behave like something we already know or not?"
Based on the answer, Beatriz and her team make strategic recommendations about testing to sponsors. Although they advise sponsors to start testing before human studies begin, optimistic sponsors who believe abuse is unlikely prefer to wait. Then, something unexpected may happen - subjects in a Phase III trial begin experiencing hallucinations, for example - and optimism gives way to immediate testing.
"It's very important for sponsors to be open to discussions about the potential for abuse even if they don't think abuse will be an issue," Beatriz noted. "You can never know until you complete the studies."
No one understands that better than she. In addition to extensive experience in regulatory affairs, psychopharmacology and preclinical research, Beatriz is an anesthesiologist by training. She has worked in the area of pain management and treated patients who were addicted to prescription analgesics.
"Understanding the potential for abuse of a new treatment can help us prevent future prescription drug abuse," she related. "An Alzheimer's patient is unlikely to misuse a drug, but we know from our experience with opioid abuse that the medicine cabinet is often the source of drugs that are abused."
"It's important to remember that that Alzheimer's drug is in the medicine cabinet, where anyone can take it," Beatriz added.