Quick question--DEA Schedules

[wellbutrin.girlfriend]

Hi y'all, med student here! Quick question--school recently started back and we covered DEA schedules in my pharm class. I had always assumed that benzos generally would be schedule II drugs alongside amphetamine and opioids. I was really surprised that benzos are schedule IV as this does not match my perception of the extent and consequences of their misuse. I did a quick Google search and there doesn't seem to be much transparency regarding DEA scheduling. I'd be interested to hear your perspectives or any recommended resources to help me understand DEA scheduling with a bit more nuance.

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[splik]

There isn't any nuance to it. This is based on law (moreso than science), which is made by politicians and thus influenced by politics. For example Marinol which has very little abuse potention is Schedule III because the federal government has hated cannabis since the hippies. That said, opioids and amphetamines are more commonly abused than benzos. There is not the same market for benzos as there is for opiates and stimulants. Most dependence is iatrogenic though of course they do have significant risk of physiological dependence. The law was also largely written in 1970. Rohypnol (once used as a date rape drug) carries schedule I penalties. There aren't many people dying of benzo ODs vs opiates etc. The answer to this question is more in the realm of sociology and anthropology.

 

[clausewitz2]

There isn't any nuance to it. This is based on law (moreso than science), which is made by politicians and thus influenced by politics. For example Marinol which has very little abuse potention is Schedule III because the federal government has hated cannabis since the hippies. That said, opioids and amphetamines are more commonly abused than benzos. There is not the same market for benzos as there is for opiates and stimulants. Most dependence is iatrogenic though of course they do have significant risk of physiological dependence. The law was also largely written in 1970. Rohypnol (once used as a date rape drug) carries schedule I penalties. There aren't many people dying of benzo ODs vs opiates etc. The answer to this question is more in the realm of sociology and anthropology.

In 1973 20% of American women and 8% of American men reported taking Valium the prior year. They were never going to make it schedule II in that era.

EDIT: Also the feds started going after cannabis well before the hippies in the 30's. This was mostly due to the strong associations with Black and Mexican people so no surprise that the government of a country with genuine racial apartheid at the time was going to be suspicious of it.

 

[birchswing]

In 1973 20% of American women and 8% of American men reported taking Valium the prior year. They were never going to make it schedule II in that era.

<Not a doctor or medical student>

It wasn't even scheduled then at all. I think it wasn't scheduled until sometime in the 80s.

I have heard chatter from pharmacists who want to schedule Xanax in particular. Apparently that has more of a following of recreational users. I wrote out a whole long thing a whiel ago I never posted about how Xanax is the last one still actively promoting their drug --they have a Xanax app even with a virtual savings card and make a big deal about their special bars on their web-site being the way to avoid fakes. It has the look of big tobacco.

I agree with Splik. There are racial biases in the scheduling. Cultural changes. This was partly a backlash to the culture of the 1960s. And this came about in the era when Nixon met Elvis. Elvis even got a non-official DEA badge directly from Nixon. A lot of hypocrisy.

 

[Stagg737]

Here's a link to the DEA's website with their (vague) criteria for each schedule: Drug Scheduling

DEA resource guide with more information and specifics on certain scheduled meds: https://www.dea.gov/sites/default/files/2020-04/Drugs of Abuse 2020-Web Version-508 compliant-4-24-20_0.pdf

If you really want to dig, here's the full legislation: https://uscode.house.gov/view.xhtml?path=/prelim@title21/chapter13&edition=prelim

You'll notice that none of these resources provide definitions for the terms "abuse", "psychological dependence", or "physical dependence" despite these terms essentially being the criteria for how they classify substances. Also, notice that they've done a poor job of staying up to date with their classifications as certain substances clearly do not meet the criteria for the schedule they're in. The most obvious example is marijuana/cannabis as a schedule 1 when schedule 1 substances "are defined as drugs with no currently accepted medical use and a high potential for abuse".

 

[Merovinge]

There aren't many people dying of benzo ODs vs opiates etc.

Trends in Nonfatal and Fatal Overdoses Involving...

This report describes trends in overdoses involving benzodiazepines during 2019–2020.

www.cdc.gov

"Benzodiazepines were involved in 6,982 (16.8%) of 41,496 overdose deaths during January 2019–June 2020 reported by 23 states, with opioids involved in 6,384 (91.4%) benzodiazepine deaths"

Drug Overdose Death Rates | National Institute on Drug Abuse

The Centers for Disease Control and Prevention collects information on deaths involving many commonly used drugs

nida.nih.gov

This shows BZD's involved in almost as many overdose deaths as heroin.

I certainly wouldn't say benzos are benign from an OD standpoint. Sure they pale in comparison to Fentanyl, but everything does.

 

[ObsequiousAplomb]

Trends in Nonfatal and Fatal Overdoses Involving...

This report describes trends in overdoses involving benzodiazepines during 2019–2020.

www.cdc.gov

"Benzodiazepines were involved in 6,982 (16.8%) of 41,496 overdose deaths during January 2019–June 2020 reported by 23 states, with opioids involved in 6,384 (91.4%) benzodiazepine deaths"

Drug Overdose Death Rates | National Institute on Drug Abuse

The Centers for Disease Control and Prevention collects information on deaths involving many commonly used drugs

nida.nih.gov

This shows BZD's involved in almost as many overdose deaths as heroin.

I certainly wouldn't say benzos are benign from an OD standpoint. Sure they pale in comparison to Fentanyl, but everything does.

While 16.8% may have had benzodiazepines tested positive, it was not the most likely cause of the death. Take a benzo a week before you shoot an 8-ball and the benzo ends up in that figure. Benzodiazepines being so available makes them a common codrug. Almost nobody dies of an overdose on only benzodiazepines. They might as well look at whether the person had pizza in the past month when looking at heart attack deaths.

 

[birchswing]

Trends in Nonfatal and Fatal Overdoses Involving...

This report describes trends in overdoses involving benzodiazepines during 2019–2020.

www.cdc.gov

"Benzodiazepines were involved in 6,982 (16.8%) of 41,496 overdose deaths during January 2019–June 2020 reported by 23 states, with opioids involved in 6,384 (91.4%) benzodiazepine deaths"

Drug Overdose Death Rates | National Institute on Drug Abuse

The Centers for Disease Control and Prevention collects information on deaths involving many commonly used drugs

nida.nih.gov

This shows BZD's involved in almost as many overdose deaths as heroin.

I certainly wouldn't say benzos are benign from an OD standpoint. Sure they pale in comparison to Fentanyl, but everything does.

<Not a doctor or medical student>

From my understanding, it's very difficult to OD on benzodiazepines in isolation, as is evidenced with the botched execution attempts where they try to use benzodiazepines for that purpose. But they easily help tilt the scales when combined with other depressants. I remember just instinctively thinking I shouldn't ever drink on my medications, and no one ever told me that. I was terrified of all sorts of interactions. I'm the one who my only year I survived at college was known as the person who asked the marijuana smokers to go smoke in the woods behind the dorm because I was terrified the marijuana second-hand would interact with my meds. So I think there probably are a lot of people who dutifully take benzos, misguidedly but "safely."

Your statistic showed that benzos were implicated in only 16% of ODs, and when they were involved you virtually had to have an opioid on board to cause death—if I am understanding that correclty.

In my state, gabapentin became scheduled, so I did some research as to why. It was often being taken by people who OD'd on opioids, which seems to be why it became scheduled. But then I looked into it more and found it's the 10th most prescribed medication in the US, and it's used to treat pain. Pain patients probably take it and opioids because both treat pain, and maybe the overdose had nothing to do with the gabapentin, but it was just present and guilty by association. I really don't know. I just know they used the logic of seeing it in people who overdose.

Edit: None of what I wrote is to imply I don't think they should be scheduled differently. If scheduling benzos higher required a treatment plan and more informed consent, I'd be all for it. Just wasn't as sure about the overdose--I feel like you have to be into other stuff for that to happen. I see huge harms with benzos, OD is just not on my radar personally as the major harms they have caused to either me or the community of people I've interacted with.

 

[Merovinge]

While 16.8% may have had benzodiazepines tested positive, it was not the most likely cause of the death. Take a benzo a week before you shoot an 8-ball and the benzo ends up in that figure. Benzodiazepines being so available makes them a common codrug. Almost nobody dies of an overdose on only benzodiazepines. They might as well look at whether the person had pizza in the past month when looking at heart attack deaths.

True, they are rarely lethal in isolation, although certainly the potential is there (unlike say THC or LSD). But it's completely disingenuous to compare them to people eating pizza prior to a heart attack. It's very well known how BZDs add to the respiratory depression of opioids and certainly makes it so that less opioid is needed to die.

 

[ObsequiousAplomb]

True, they are rarely lethal in isolation, although certainly the potential is there (unlike say THC or LSD). But it's completely disingenuous to compare them to people eating pizza prior to a heart attack. It's very well known how BZDs add to the respiratory depression of opioids and certainly makes it so that less opioid is needed to die.

I'm not denying the fact that benzodiazepines can be dangerous when coingested with opioids or barbiturates. I don't think that SSRIs or St John's Wort need to be scheduled because they can be fatal when taken with an MAOi. People abuse any drug they can get their hands on. If we tested for Benadryl, Miralax, docusate, and clonidine with the ability to detect recent use the way we can with benzodiazepines we would also see just how commonly those are congested with opioids.

I also think (but don't have evidence on hand) that the benzodiazepines in people who have fatal opioid overdoses are often ingested unknowingly. Street opioids are cut with benzodiazepines and street benzodiazepines are cut with opioids. Fentanyl/heroin and a benzodiazepine that come in the US not in the form of an Rx should ideally not effect the legality of the Rx.

I don't coprescribe them as a general rule outside of an inpatient taper. It's not a good combo. If there were a combo pill I would advocate that it be removed from the market. I avoid long-term benzodiazepines. I don't think they need to be any more than schedule IV though. Honestly, some of the stimulants would probably benefit from being dropped from II to IV.

 

[Stagg737]

I'm not denying the fact that benzodiazepines can be dangerous when coingested with opioids or barbiturates. I don't think that SSRIs or St John's Wort need to be scheduled because they can be fatal when taken with an MAOi. People abuse any drug they can get their hands on. If we tested for Benadryl, Miralax, docusate, and clonidine with the ability to detect recent use the way we can with benzodiazepines we would also see just how commonly those are congested with opioids.

How many people do you think are actually abusing SSRIs or St. John's Wort? Is this even remotely comparable to the number of people abusing benzos? Do you think the combination of SSRIs or St. John's Wort with an MAOI is as dangerous as a benzo + an opiate/alcohol/other significant CNS/respiratory depressant? You also typically need a lot fewer pills with benzos to do real damage than antidepressants. They just have a lot higher risk potential, and all the data supports that.

Even with the poor definitions, abuse/dependence potential + accessibility + much narrower therapeutic index when taken with other substances warrants that it be scheduled at some level, imo.

 

[FlowRate]

Along the lines of what seems like semi-arbitrary scheduling--why is pregabalin scheduled but gabapentin isn't? Are they really sufficiently different to make one come with all of the hassles of being on a schedule? (There may actually be a semi-legit justification around pregabalin having overall linear dose-response effects but gabapentin having diminishing returns.)

 

[Stagg737]

Along the lines of what seems like semi-arbitrary scheduling--why is pregabalin scheduled but gabapentin isn't? Are they really sufficiently different to make one come with all of the hassles of being on a schedule? (There may actually be a semi-legit justification around pregabalin having overall linear dose-response effects but gabapentin having diminishing returns.)

Not sure, but I believe it's due to the contribution to increased risk of fatal OD with pregabalin over gabapentin: Pregabalin and gabapentin in non-opioid poisoning deaths

As an aside, gabapentin is considered a schedule V substance by some states, and others require refills to be included in their state PDMP reports.
https://www.goodrx.com/gabapentin/is-gabapentin-a-controlled-substance

 

[ObsequiousAplomb]

How many people do you think are actually abusing SSRIs or St. John's Wort? Is this even remotely comparable to the number of people abusing benzos? Do you think the combination of SSRIs or St. John's Wort with an MAOI is as dangerous as a benzo + an opiate/alcohol/other significant CNS/respiratory depressant? You also typically need a lot fewer pills with benzos to do real damage than antidepressants. They just have a lot higher risk potential, and all the data supports that.

Even with the poor definitions, abuse/dependence potential + accessibility + much narrower therapeutic index when taken with other substances warrants that it be scheduled at some level, imo.

In terms of potential lethality, I assume that 30 days of:
1. full dose tranylcypromine + one of (A. Prozac 80 mg, B. clomipramine 200 mg C. Elavil 150 mg D. Cymbalta 60 mg) is probably more fatal than 30 days of:
2. 80 MME + Ativan 6 mg / day in divided doses. If you have evidence that this statement is inaccurate, please share it. I would never, ever recommend someone take either 1 or 2, but I have a suspicion that 1 would be more fatal. I also don't imagine anyone would really tolerate 1 enough to take it for a month. I have to admit though, I've never seen 1 but I've seen 2 too many times to count. The only people I knew taking 2 who died were in hospice or died from an overdose of IV street opioids.

A far greater a proportion of people abuse prescribed benzodiazepines than SSRIs or St John's Wort. I never implied a greater ratio of antidepressant prescriptions are abused than not. I think benzodiazepines make plenty of sense to be schedule IV. I also never implied otherwise. Considering all causes of death, more people probably die taking SSRIs in the past several weeks than benzodiazepines in the past several weeks, but that's because of the huge difference in prescription of the two classes. I do think St John's Wort should probably be made prescription-only.

Fewer pills of TCAs cause lethality than benzodiazepines, generally. Just 7 of the Doxepin 150 mg tabs could be fatal to a drug-naive person. It would take a lot more than 7 of the 2 mg Xanax bars to be fatal in isolation to a drug-naive person. I don't think TCAs should be schedule IV. I do think benzodiazepine should be.

Dextromethorphan is highly abused. I don't think it needs to even stop being OTC, even though I counsel almost all of my patients to avoid it. There's no great evidence that it works well for cough suppression. I guess the people who got the DXM/Bupropion combo pill must have found some evidence that it works for at least one condition, but really only when coprescribe with another antidepressant that also makes the DXM last longer than NyQuil.

Seroquel is highly abused. I usually don't prescribe it. Lots of health systems (correctional, mostly) outright don't allow it. I don't think it needs to be scheduled.

Cannabis is highly abused. I'm not sure it even needs to be schedule I, II, IV, or even a prescription medication.

Ketamine is highly abused and has some good medical uses. I think it it scheduled appropriately. I also wouldn't really recommend people take it with an opioid or a benzodiazepine without an anesthesiologist nearby. Actually, I wouldn't recommend anyone take ketamine at all without an anesthesiologist nearby.

Gabapentin / pregabalin are very often abused. Im not entirely of the opinion they should be schedule IV. They do increase the risk of fatal overdose with opioids. I imagine slightly less than benzodiazepines, but I honestly don't know. I don't prescribe them often, though I do see them being used as benzodiazepine alternatives, which doesn't make much sense to me. I do agree with their prescriptions being present in prescription drug monitoring databases.

Flexeril is reported where I live. I think that's a little silly. I can see why they report it, but imo it's not worth the waste of time / effort. It feels to me like reporting Benadryl or Seroquel or Elavil prescriptions.


All I was saying is that benzodiazepine tests are far more sensitive over an extended time period than other medications that can also contribute to fatal overdose. The fact that a medication CAN be abused, to me, doesn't really say enough about it's risk and need to be scheduled.

Thinking that 6 mg / day of Ativan is as dangerous as 80 mg a day of morphine is rather silly. I've had residents freak out that someone has a single pill of Ativan 0.5 mg in an inpatient setting thinking that it will both be potentially fatal and make them addicted. I certainly wouldn't recommend anyone take them both at once, and I really wouldn't recommend most people take either in isolation at the 6/80 doses. If the two could theoretically treat the same condition with equal benefit, I would rather people take the Ativan. If there were a non- IV or II option that could help just as much, I would most likely recommend that.

But since Tylenol is OTC and is probably the highest risk of any of the drugs in this post, maybe the scheduling system doesn't really care about the risk of fatal overdose? No matter what medications you prescribe someone, if they want to kill themselves via overdose, they'll be most successful if they buy a bottle of Tylenol and take it all. Despite all the medications I prescribe, the only medications that my patients have ended up in emergency rooms for intentional overdose with are Tylenol and Benadryl (that I know of).

 

[birchswing]

<Not a doctor or medical student>

Both are scheduled in my state. IIRC, gabapentin was actually scheduled before pregabalin. It's unfortunate. I think some practitioners aren't familiar with the medications. I think some think gabapentin is GABAergic and don't realize that olanzapine which they are happy to prescribe actually is GABAergic along with metabolically and cardiovascularly disastrous. The scheduling just reinforces preconceptions. Gabapentin to me seems like a uniquely versatile medication with fewer downsides than a lot of other psychiatric/neurological/pain medications.

 

[birchswing]

though I do see them being used as benzodiazepine alternatives

Do you mean when a doctor would otherwise use benzos or as as benzo reduction agent? There are some good research articles on using gabapentin for more rapid and more successful taper of benzos.

 

[clausewitz2]

In terms of potential lethality, I assume that 30 days of:
1. full dose tranylcypromine + one of (A. Prozac 80 mg, B. clomipramine 200 mg C. Elavil 150 mg D. Cymbalta 60 mg) is probably more fatal than 30 days of:
2. 80 MME + Ativan 6 mg / day in divided doses.

While A, B, and D are a terrible idea and very dangerous, 40+ mg of TCP and 150 mg Elavil is perfectly safe. I have prescribed it to people before on more than one occasion.

 

[ObsequiousAplomb]

While A, B, and D are a terrible idea and very dangerous, 40+ mg of TCP and 150 mg Elavil is perfectly safe. I have prescribed it to people before on more than one occasion.

I believe that. I've never tried it, though I have heard of people using that combination. It was not a great combo to list there, my bad. Do you usually cross-titrate, or what? What I have read was up to 20 of tranylcypromine, but I believe you that 40 mg can be safe, too.

 

[Merovinge]

In terms of potential lethality, I assume that 30 days of:
1. full dose tranylcypromine + one of (A. Prozac 80 mg, B. clomipramine 200 mg C. Elavil 150 mg D. Cymbalta 60 mg) is probably more fatal than 30 days of:
2. 80 MME + Ativan 6 mg / day in divided doses.

Just to be clear, you're suggesting that 180mg of Ativan + 2400mg of morphine you've seen "too many times to count" and has almost never proven to be fatal?

Edit: I see, you mean when taken as prescribed, not when taken to OD or abused.

 

[FlowRate]

While A, B, and D are a terrible idea and very dangerous, 40+ mg of TCP and 150 mg Elavil is perfectly safe. I have prescribed it to people before on more than one occasion.

Adding on this, I found this paper really helpful/reassuring regarding coprescriptioin of amitriptyline and nortriptyline with other (serotonergic) meds especially at the lower doses used for pain/migraines.

Tricyclic antidepressant pharmacology and therapeutic drug interactions updated

New data on the pharmacology of tricyclic antidepressants (TCAs), their affinities for human cloned CNS receptors and their cytochrome P450 enzyme inhibition profiles, allow improved deductions concerning their effects and interactions and indicate which ...

www.ncbi.nlm.nih.gov

 

[ObsequiousAplomb]

Do you mean when a doctor would otherwise use benzos or as as benzo reduction agent? There are some good research articles on using gabapentin for more rapid and more successful taper of benzos.

I mean things like this:
- prescribing gabapentin as a PRN
- taking someone's 0.25 mg Klonopin qhs that was 80% effective and making it gabapentin 100 qhs instead of 0.5 mg Klonopin, claiming treatment failure after one dose of 0.25
- gabapentin 600 for acute akathisia

Gabapentin can be very helpful in medically assisted withdrawal protocols, yeah. It potentiates opioids and benzodiazepines. One of the exact reasons it can be abused is why it helps in that setting. Just like Phenergan, Vistaril, etc.

 

[ObsequiousAplomb]

Just to be clear, you're suggesting that 180mg of Ativan + 2400mg of morphine you've seen "too many times to count" and has almost never proven to be fatal?

As a monthly prescription. I don't at all mean someone taking that amount all at once. Nothing in what I was saying implied I see people taking 180 mg of Ativan and 2400 mg of morphine all at once. There are plenty of patients going to pain management and getting 80 MME while also seeing a psychiatrist or PCP that prescribes the equivalent of Ativan 2 TID. Usually it's Xanax though. I've seen way more than 80 MME for these patients, too.

I've never seen someone taking tranylcypromine 40+ and clomipramine 250+ every day.

 

[Stagg737]

I think benzodiazepines make plenty of sense to be schedule IV. I also never implied otherwise. Considering all causes of death, more people probably die taking SSRIs in the past several weeks than benzodiazepines in the past several weeks, but that's because of the huge difference in prescription of the two classes. I do think St John's Wort should probably be made prescription-only.

It sounded like you were implying that, but that's my mistake with misreading. Are you arguing that more people die BECAUSE OF taking SSRIs than benzos or just that more people who die from ODs have antidepressants in their system? Because that's where I really have a hard time with the former statement and ime is incorrect. Some data from NIDA: Overdose Death Rates | National Institute on Drug Abuse

Fewer pills of TCAs cause lethality than benzodiazepines, generally. Just 7 of the Doxepin 150 mg tabs could be fatal to a drug-naive person. It would take a lot more than 7 of the 2 mg Xanax bars to be fatal in isolation to a drug-naive person. I don't think TCAs should be schedule IV. I do think benzodiazepine should be.

Sure, high doses of TCAs to a med naive person can be fatal, same goes for benzos though despite what some people argue. I've had a patient end up in the ICU for several days with only substance in their system being a benzodiazepine which turned out to be 12-15mg of Xanax, which shockingly occurred at our VA. I would not expect that, but I have seen a couple patients go into full-blown respiratory failure from only benzodiazepine use.

 

[Stagg737]

All I was saying is that benzodiazepine tests are far more sensitive over an extended time period than other medications that can also contribute to fatal overdose. The fact that a medication CAN be abused, to me, doesn't really say enough about it's risk and need to be scheduled.

We'll just have to disagree on the bolded. The fact that a potentially lethal medication has abuse/dependence potential drastically increases the risk of an accidental overdose, which IMO is worth considering in terms of drug scheduling/prescribing.

 

[ObsequiousAplomb]

We'll just have to disagree on the bolded. The fact that a potentially lethal medication has abuse/dependence potential drastically increases the risk of an accidental overdose, which IMO is worth considering in terms of drug scheduling/prescribing.

I was not saying that SSRIs are causing the fatality. I was pointing out that presence in the tissue of deceased persons are plenty of substances that didn't cause their death. That was why I was previously making an absurdist argument about junk food in the tissues of people who die of heart attacks.

I don't think it's entirely clear that a prescription benzodiazepine is THE drug to blame when someone shoots 4 grams of street fentanyl that has more carfentanyl than could kill an elephant that also has been cut with a benzodiazepine that wasn't obtained through an Rx. I'm saying that 16% of the fatal overdoses having had benzodiazepines detectable may be partially artifact, speculating that if someone is taking a benzodiazepine they are probably at risk for untimely death due to the factors that had them taking a benzodiazepine. For the majority of those deaths I do believe that the benzodiazepine exacerbated the risks of fatal overdose. If someone is prescribed a benzodiazepine they're also hopefully prescribed an antidepressant as well. And most people prescribed SSRIs aren't prescribed benzodiazepines. Due to the higher rates of SSRIs in Americans' tissues then the raw number of deaths in the US with SSRIs on board is higher than the raw number of deaths with benzodiazepines on board.

Instead of SSRIs, we can look at other controlled substances. Because benzodiazepines are safer than barbiturates or opioids they are more available to be abused. If someone took the equivalent dose of phenobarbital as Ativan, they would be much higher risk. since they're scheduled the same, it's not the scheduling that makes phenobarbital less prescribed. Benzos and barbiturates arestill safer in overdose than Tylenol.

Since plenty of non-schedule II or IV drugs are abused, I'm saying that abusability is not the best metric for whether a drug is schedule IV or below. If it were, then DXM, Benadryl, Phenergan, caffeine, taurine, nicotine, alcohol, etc would all need to be &lt; schedule IV.

 

[clausewitz2]

I believe that. I've never tried it, though I have heard of people using that combination. It was not a great combo to list there, my bad. Do you usually cross-titrate, or what? What I have read was up to 20 of tranylcypromine, but I believe you that 40 mg can be safe, too.

Generally it happens when someone is already getting some partial benefit out of Elavil (though I tend to prefer Pamelor for most folks) but can't tolerate side effects of dose increases. Then I start the TCP. I know the old school folks will tell you 90-100 mg of Parnate is perfectly fine as a dose, and mechanistically should be about as safe as 40 mg with Elavil, but I will confess I haven't quite had the brass ones to try much higher than 50 in combination.

 

[aim-agm]

Along the lines of what seems like semi-arbitrary scheduling--why is pregabalin scheduled but gabapentin isn't? Are they really sufficiently different to make one come with all of the hassles of being on a schedule? (There may actually be a semi-legit justification around pregabalin having overall linear dose-response effects but gabapentin having diminishing returns.)

It's a little bit arbitrary but to my understanding there is a good rationale for pregabalin being much more abuseable than gabapentin. Generally speaking, the ability to get high off something is in part a function of how quickly you can raise CSF concentrations of it, and also in part how high you can get that concentration.
Pregabalin absorbs 3-4x faster than gabapentin. Also, gabapentin absorption is saturateable so increasing doses have diminishing returns (e.g. 80% PO bioavailability of 100 mg q8h, but only 27% at 1600 mg q8h) which probably limits how high a CSF concentration you can achieve with it, while pregabalins does not have such constraints.

 

[Merovinge]

It's a little bit arbitrary but to my understanding there is a good rationale for pregabalin being much more abuseable than gabapentin. Generally speaking, the ability to get high off something is in part a function of how quickly you can raise CSF concentrations of it, and also in part how high you can get that concentration.
Pregabalin absorbs 3-4x faster than gabapentin. Also, gabapentin absorption is saturateable so increasing doses have diminishing returns (e.g. 80% PO bioavailability of 100 mg q8h, but only 27% at 1600 mg q8h) which probably limits how high a CSF concentration you can achieve with it, while pregabalins does not have such constraints.

That doesn't seem arbitrary at all and makes total sense. Best explanation I have heard about it before!