Saturday, November 7, 2015

To Determine Abuse Potential Of A Drug Bring Two Turtles To The Temple Of The FDA

The FDA is wacky. Around every corner there seems to be another head scratching approval, denial, process or event. Answering a simple question took me down a new enlightening, and hilarious path. Now, this may sound Seinfeld-ish but ‘what’s the deal with controlled substances?’

Lacosamide is a newer antiepileptic drug that you have likely seen on a medication reconciliation profile of a patient to two in your emergency department by now. With this newer drug, there isn’t a whole lot of interesting pharmacokinetics or horrifying toxicities with normal therapeutic use. On the surface it’s pretty bland. However, I’m sure it has caused problems in terms of either stocking the drug or delivering it to nurses who are waiting on it to discharge the patient from the ED. The reason being, it’s a schedule C-V drug.

Why would this drug be any different from other newer antiepileptic drugs that are not controlled (levetiracetam, vigabatrin…)? I can’t say there are any frequent flyers coming in with allergies to phenytoin, keppra, carbamazepine and valproate that need that one that starts with a Vin-something, “yea, Vimpat… I need 50 of Benadryl with that too.” Or why is pregablin controlled and gabapentin not? How about Fioricet vs Fiorinal? Maybe the bigger question is who and how is abuse potential tested in drugs?
There is no easy way to say this so here it goes. Drugs are given to “experienced” drug users who rate the drug in question for any pleasurable effects. Literally asking “do you like the drug.”
One thing that I have learned in my brief experience is that the more I learn, the more I realize how little I know. Assuming a process or medical dogma is logically based on decent evidence, then after some investigation discovering poor quality or no evidence at all is becoming the rule rather than the exception. I have no idea why this abuse potential screening seems so strange to me, but it does. I hadn’t ever thought of how drugs were assigned to a controlled schedule, and this may very well be this is the best way to do it. Or perhaps it’s just another quirk with the FDA. (Reminds me of Nick Offerman talking about the book Leviticus of the Bible).
In the FDA’s draft guidance document for the process by which abuse potential is determined is outlined. Before drugs reach the human phase, these compounds are assessed in numerous ways to identify if they share structural or other qualities with existing controlled substances. These phases include: preclinical screening, chemistry and manufacturing, animal models and PK/PD studies. When in the human phase, as outlined above, the drug is administered to experienced, and sometimes naive individuals to determine if any euphoric or abuse potential effects exist.
With lacosamide, its abuse potential study was outlined in its prescribing information. Briefely, single doses of 200 mg and 800 mg lacosamide produced euphoria-type subjective responses that differentiated statistically from placebo. Interestingly, at 800 mg the drug displayed similar effects as alprazolam, but did not last nearly as long.
So like a CIV but not as long of a duration... ummm… CV!
This is concerning when we start to think about initiatives to increase the schedule of drugs like ketamine, or to think of how propofol is the most abused drug among anesthetists but is not controlled. How the FDA/DEA will act is unknown, but it will likely be a hair-brained process similar to this.