Swapnil Gupta, author of Deprescribing in Psychiatry, shares tips on how to help patients taper off benzodiazepines and psychostimulants in this podcast. She adds a special therapeutic ingredient, but it’s not a medication. Then we digress into one of the oldest medications known to humankind: Opium.
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Chris Aiken, MD- Kellie Newsome, PMH-NP
You are seeing this patient for the first time, but already things are getting dicey. They’ve been prescribed a steady dose of Adderall 80 mg a day and Klonopin 3 mg a day for over 10 years, but they don’t have ADHD, panic disorder, or any other clear reason for taking these. What do you do?
CHRIS AIKEN: Many People Taking Antidepressants Discover They Cannot Quit was the headline in the New York Time’s Health Section on April 7, 2018. The article caught the attention of a lot of patients – you could say it went viral – which is not surprising, considering that 15.5 million Americans have been on antidepressants for over 5 years, or 1 in 12 adults. And the most popular antidepressants – the serotonergic class – are the most difficult to come off.
Coincident or not, we’ve seen a sharp increase in research on this understudied issue since that article came out, including a textbook on Deprescribing in Psychiatry. This month we interviewed one of the authors of that textbook, Swapnil Gupta, on how she tapers antidepressants, stimulants, and benzodiazepines.
KELLIE NEWSOME: All three of those medications can cause withdrawal problems, and while it would be nice if we could substitute another medication to treat the withdrawal, there’s really no evidence that doing so works. We have some evidence though that the speed of the taper can be optimized to reduce withdrawal symptoms, using something called a hyperbolic taper – where you go faster in the beginning and slow down as you get into the lower dose range. The problem is that this often requires microdosing in smaller and smaller increments as you reach the bottom of the barrel, and you can only cut up a medication in half so many times before it pulverizes into a heap of crumbs. So Dr. Swapnil discussed three strategies to get around this. Liquid formulations and compounding pharmacies can create microdoses, or savy patients can compound the medication on their own using a commercial compounding solution that essentially liquefies the pill. In our online edition we have a step-by-step guide to home compounding, but a word of caution: We only recommend this for capable and motivated patients. Professional compounding at a mom-and-pop style independent pharmacy is the preferred method.
CHRIS AIKEN: And while we don’t have medications to treat these withdrawal syndromes – other than the same med that is causing the withdrawal or a medication from the same class – Dr. Swapnil does substitute something else with biological effects: The therapeutic relationship.
KELLIE NEWSOME: Coming off a medication is anxiety provoking in itself, and that’s on top of any anxiety caused by the physiologic withdrawal. But when you’ve established a trusting relationship, and take the time to make sure your patient understands the rationale for the taper and that you have their best interest in mind, that anxiety goes down. The therapeutic alliance is one of the best predictors of outcomes when starting a medication, so it’s all the more important when you are taking a medication away. You could say – it’s just about all you got when the med is tapering off. Here Dr. Swapnil shares some tips on enhancing that alliance during benzo withdrawal.
[Dr. Swapnil]
Antidotes for Benzo Withdrawal
KELLIE NEWSOME: I gotta say I was surprised to learn that nothing outside of benzos treats benzodiazepine withdrawal. I mean, you’d think that something like gabapentin would help.
CHRIS AIKEN: You’d think so, as gabapentin (Neurontin) does boast some controlled trial evidence in various anxiety disorders, but the only randomized controlled trial we could find of gabapentin (average dose 2666 mg/day) for benzo withdrawal was negative.
KELLIE NEWSOME: OK I’m looking at the abstract of that gabapentin study right now and – Dr. Aiken I just got to say this is it ok if I go on a little conspiratorial digression?
CHRIS AIKEN: Be my guest.
KELLIE NEWSOME: So the abstract in pubmed claims that “gabapentin DID significantly decrease benzodiazepine use relative to placebo.” But the full text version of the article has a different abstract that states the opposite: “Gabapentin was not found to differ from placebo.” So which one is right?
CHRIS AIKEN: That is strange – but reading the actual data there was no difference from placebo on any measure so the full text is correct. We’ll have to write the editor on that one.
KELLIE NEWSOME: Ok So gabapentin is out, but what about other meds?
CHRIS AIKEN: The Cochrane review looked at 38 trials of antidotes for benzo withdrawal, and concluded there was no good evidence supporting any of them. But getting a thumbs up from the Cochrane group is pretty hard, so let’s look at the individual studies. Buspar, no, melatonin, no, antidepressants possibly – but then again, just treating the underlying anxiety disorder is going to help here and most patients on benzos have already tried or are already on antidepressants so that’s not going to do us much good. Actually some of the more promising data comes from anticonvulsants, and these meds make sense because they might prevent the worst outcome of benzo withdrawal – seizures. Anticonvulsants like valproate, gabapentin, and carbamazepine are used successfully to treat alcohol withdrawal for this same reason.
Despite the fact that gabapentin is a structural GABA analogue, and in spite of its name, it does not bind to the GABA receptors, does not convert into GABA or another GABA receptor agonist in vivo, and does not modulate GABA transport or metabolism. Instead, it binds to the alpha-2-delta subunit of voltage-gated calcium channels, increasing the release of excitatory neurotransmitters, such as glutamate, thereby decreasing neuronal excitability.
What’s less well known is that valproate (Depakote) also has gaba-ergic properties, and it treated anxiety due to bipolar, generalized anxiety disorder, and non-specific stress in controlled trials. So here’s a study of 78 patients where valproate doubled the chance of being off a benzo compared to placebo at 5 weeks, but unfortunately it did not succeed in other measures or at other time points so could have been just a random flux.
KELLIE NEWSOME: What dose of Depakote did they use?
CHRIS AIKEN: Similar to what we use in bipolar disorder, with an average serum level of 90. Carbamazepine also has a suggestive study in benzo withdrawal, but it was not placebo controlled. And gabapentin’s cousin pregabalin (Lyrica) was tested for benzo withdrawal in a controlled trial of 106 patients. The dose was 300-600mg a day. It didn’t help patients get off benzos – there was only a non-significant trend there – but it did reduce anxiety. However, this study was done in patients with generalized anxiety disorder, and we know that pregabalin treats generalized anxiety very well – it has a bigger effect size than SSRIs for generalized anxiety – so again what this is telling us is that treating the underlying anxiety disorder will help in getting off benzos.
Therapy for Benzo Withdrawal
KELLIE NEWSOME: But when pharmacologic antidotes don’t help for benzodiazepine withdrawal, cognitive behavioral therapy can come to the rescue. This year a meta-analysis found an impressive number needed to treat of 3 for cognitive behavioral therapy (CBT) in benzodiazepine, which means that you’d need to try it on 3 patients to successfully help 1 patient get off the benzo. By comparison, the number needed to treat for most psychiatric medications in around 4-5. The CBT they used is similar to what therapists do for panic disorder, with a lot of relaxation techniques like deep breathing, and cognitive work around fears of physical withdrawal symptoms. Michael Otto and Mark Pollack have written a brief book on it called Stopping Anxiety Medication, with an edition for therapists and one for patients.
CHRIS AIKEN: And that brings us back where we started – the therapeutic relationship. One thing Dr. Gupta emphasized is to mind your counter transference and avoid power struggles and unnecessary conflicts with patients. Our goal here is to create a trusting relationship where the patient feels safe coming off the medication, not an adversarial one.
KELLIE NEWSOME: Maybe that’s easier said than done. I mean – when a patient shows up for their first visit on 80 mg a day of Adderall and a high dose of Klonopin, it can feel like your license is on the line.
CHRIS AIKEN: Especially in this era where most states have a centralized controlled substance database where they can monitor doctors who are outliers. These databases are a necessary response to the opioid crisis, but they can also have unintended consequences. They’ve changed medical culture – and the pharmacists who dispense the controlled substances are under the same pressures we are, but they don’t even know the patient or the rationale. So it’s more and more common to get a call from a pharmacist when your patient is on multiple controlled substances or high doses of them, and it’s our job to have a clear rationale for using them that we can explain to the pharmacist. Because if you can’t defend what you’re doing, the pharmacist might refuse to fill it or even report you to the boards. So, there are risks here, yes, but if we don’t take care of these patients they are going to be out on the streets managing their benzos through the black market. And that is not what the governing bodies want. When I’ve been to talks by the regulators who run these databases, they warn against an overly rigid reliance on the database. Our job is to treat the patient, not our license, and there are risks of malpractice and board complaints in everything we do, but we go about the work anyway, because steering away from those risks would be abandoning the patients who have the highest severity.
KELLIE NEWSOME: Yes in my state the boards specifically state that you should not use the controlled substance database to screen out patients. They know that there are unintended consequences to these monitoring systems – and the medical or nursing boards are just as likely to go after providers who abandon or refuse to see patients because of a high risk in the controlled substance database as they are to go after those who are overly generous with their controlled scripts.
CHRIS AIKEN: So with that in mind we asked Dr. Gupta how she would handle a patient that strikes fear in the hearts of many providers – one who presents to us on a high dose of Adderall and Klonopin without any medical justification for their use.
[Dr. Gupta]
KELLIE NEWSOME: Dr. Swapnil Gupta is a coauthor of the Deprescribing in Psychiatry and an Associate professor at the Icahn School of Medicine at Mount Sinai. You can read our full interview online in our March issue, where she gives more details on how to taper off benzos, stimulants, antidepressants and – in our February issue – tapering off antipsychotics.
Our cohost Kellie Newsome must not have read this sign when she lived in Tazmania
Opium
And now for the word of the day…. Opium
KELLIE NEWSOME: The brilliant red poppy flower Papaver somniferum is the source of the poppy seed, and from those seed pods exudes a milky white sap called latex that is contains one of the oldest medications known to humankind: Opium. We think that people have been using opium as a sedative and analgesic since about 3 and a half thousand years (3,400) before Christ. Opium is no longer used in medicine because we now know what its active ingredient is: Morphine. Merk pharmaceuticals began producing morphine in 1827, and 25 years later the use of this opioid really took off with the invention of the the hypodermic syringe. In America, the Civil War escalated that use further, and by the turn of there was an epidemic of morphine and other synthetic opioids in part because so many injured soldiers had been placed on the drugs long term. Heroin, hydrocodone, and oxycodone can all be synthesized from the raw materials of the poppy plant.
Poppy seeds also come from this plant – and opium can be found within those seeds along with 4 other opioids – enough to score a false positive on a urine drug screen if you get it done within a few hours of eating a poppy seed bagel. And here’s a tip: If you or your patient ever find yourselves caught in this quandary, a hair follicle test is much more accurate and will not yield a false-positive result even if you are a regular consumer of poppy seed products.
Opium is found in the poppy sap
I spent my childhood in the shadow of this towering red flower, in a little island off the coast of Australia called Tazmania, which is one of the world’s top producers of poppy and opioids.
CHRIS AIKEN: And I spent my college years in another version of that theme at the University of Virginia.
KELLIE NEWSOME: Yea go on and tell that story Dr. Aiken, it’s about time that Charlottesville became known for something other than Unite the Right.
CHRIS AIKEN: Thomas Jefferson built the University of Virginia, and his Monticello home sits perched on a mountain overlooking the campus. It’s also on the back of the nickel. Jefferson cultivated the opium poppy, and the people that run Monticello went to great lengths to restore all the native plants in Jefferson’s garden. It’s a big deal – like when I graduated we were all given a seedling from one of Jefferson’s oak trees to plant. Unfortunately they might have gone a little too far. In 1987 the DEA raided Jefferson’s museum-home with a demanded that they remove all the poppy plants and stop selling seedlings from Jefferson’s poppy in the gift shop.
KELLIE NEWSOME: Well, that must have really changed things on campus.
CHRIS AIKEN: Not exactly. I think the student body was more concerned with the prohibitions on alcohol. A lot of states raised the drinking age to 21 around that same time. Before that, they actually served beer in the student dining hall, but not after, which inspired a lyric in REM’s song The End of the World as We Know It about the Cavalier’s – our school mascot – having no beer.
KELLIE NEWSOME: The past year has seemed more and more like the end of the world as we know it, and I hope you’ll join us next week where we’ll interview psychiatrists Ashwin Paktar and Richard Weisler about opioid use during the pandemic.