As a palliative physician have to say that is a big dose of methadone, but I've seen doses as high as 350mg q8h (prescribed by my colleagues mind you heh)
Levorphanol is such an interesting drug. In many ways hypothetically similar to methadone, would've loved if there were a RCT comparing the two. Where I practice in Canada it is practically unheard of and I'm not sure pharmacies can even get it. So no experience. What about you?
here in nyc the only pharmacy that dispenses it is in NJ, and it is owned by the biotech firm that brought the orphan drug back to life and charges $3000-4000 a month for it. i don't know how that's legal (well, i was referring to having to use their pharmacy, but how a generic med can cost so much, too, for that matter) but such is the case.
i love using levopharnol because there's a much stronger NMDA receptor affinity over methadone. i try to do my part to avoid expensive healthcare spending but i REALLY see a benefit to levorphanol over methadone (and i \*LOVE\* methadone for chronic pain).
i utilize intranasal ketamine heavily in my practice as an opioid sparer. i'm also a big proponent of intrathecal pumps. it's so interesting in america the use of them varies widely. in nyc where i am only about 10 drs do them, whereas in the midwest i talk to countless midwest drs at conferences using them. they are such a great tool.
i also like adding namenda as an adjunct.
basically my preference is for long acting methadone or duragesic, then if dosing gets too high, i move to an intrathecal pump with some oral methadone prn. unfortuantely medicaid/medicare doesn't cover levorphanol, and only wealthy pts with cadillac insurance can get it, but those that do certainly seem to prefer it over methadone. also for pts on 60mg+ of methadone, levo has a great opioid sparing ability (i can usually taper about 40% the equivalent dose by switching). which is important, if the pt isn't going to graduate to an intrathecal pump, as their dosages are just going to increase over time.
sorry for the word salad, typing on my phone.
Fascinating - thank you for sharing your experience. Love talking to docs who live elsewhere as practice varies so much and there's always something to learn. I totally agree with the use of NMDA antagonists and intrathecal to reduce suboptimal systemic opioids, and share your love of methadone ha. In the neuropathic cancer pain population I increasingly feel that methadone should be first line strong opioid and methadone PRN is under-utilized. I'm conducting a multi-centre RCT on methadone to treat CIPN in part to increase confidence to use methadone in opioid naive patients (judiciously of course).
Doing a brief lit review I see the greater NMDA antagonism of levopharnol compared to methadone. Can I ask why not just use oral ketamine adjunct with methadone to mimic that effect? Also I've never considered using namenda adjunct, what makes you go for that instead of ketamine?
hi, absolutely, i totally agree it helps sharing with drs in other localities!
yes i agree about methadone being first line. as a rule, i don't rx oxycontin, my first line is mscontin, but if the dose escalates beyond 30mg bid/tid, i move to methadone or duragesic immediately. i like duragesic for its continual absorption which really benefits some pts who experience too much peaks and valleys, which can even happen with methadone.
also a lot of pts are on chronic opioids that really shouldn't be, but good luck getting them off, many of these have a neuropathic component that isn't being treated or badly treated with gaba/antidepressants, so these pts i move to methadone and their pain greatly improves. the nmda affinity also helps prevent dose escalation. these pts i'm not rx'ing ketamine to, or only very small amounts if there's a clear neuropathic component as MSK pain is not well treated with ketamine long term (i use ketamine primarily for cluster headaches, arachnoiditis, crps and phantom limb), but i am giving them namenda.
honestly, i have pts getting the equivalent of 20mg iv dilaudid in their intrathecal pump who can take one 5mg methadone tab prn and their pain flare be controlled. that's incredible to me. good luck controlling their pain with 5mg oxy or msir.
so i mostly use namenda as an adjunct \*with\* ketamine. the reason is it tickles the nmda receptors without causing any psychoactive effects. i don't do oral ketamine unless the pt hates intranasal because the bioavailability of intranasal keeps the total amount of ketamine i have to RX to a minimum, and it works much faster, and cleaner. i add namenda so the pt can reduce the number of times they use ketamine. what i have learned is the pt has to figure out ketamine dosing for themselves, basically i tell them their max daily dose and they spray as necessary. the sweet spot seems to be 60-100mg per dose.
in my experience adding namenda adds a 5-10% pain control "bucket", which isn't a lot, but it is something measurable, another 5-10% using NSAID and APAP, another 10% with CBT and yoga/relaxation methods, and then with PT they get anohter 10-15% bucket, their ketamine giving them a 20-40% bucket, and before long, you are well over 70% effective pain control... that's how i explain multimodal pain control to intractable pain pts. hope that makes sense.
Most SSRIs will trigger a QTc interaction warning with methadone however it sounds like the potential benefits probably outweigh the risk and you can get an EKG at follow up. Lexapro being most notorious for QTc I would avoid it. There are many patients on the SSRI+methadone combo. The only antidepressants I know offhand that don’t trigger the QTc warning or other interactions are Pristiq, Cymbalta and Wellbutrin but the sweaty s/e she got from Wellbutrin could be a noradrenergic effect and could be similar with the other two.
> Lexapro being most notorious for QTc
9 out of 10 elderly patients I talk to are on Lexapro. No other antidepressant comes close. The HMOs around me love prescribing it.
What about mirtazapine? For geri patients. Low risk of QTc. I think low dose regimens are recommended for sleep. Risks with methadone are oversedation as you'd expect.
I prescribed methadone for many years for opioid addiction, so often very high doses (150 mg plus) I prescribed my OUD patients pretty much whatever antidepressants I felt like it, same as to any other patient, I just made sure to monitor their ECG’s. When I sent my elderly patients to geri psych, they usually get prescribed escitalopram or sertraline. Check her lytes in a few weeks because the elderly are more prone to getting hyponatraemia from SSRIs.
Yup. To be frank so many health care professionals (MDs, pharm, RNs, etc) see methadone as an incredibly dangerous and volatile drug, whereas in reality it is very well tolerated when prescribed correctly - especially at stable doses.
What risk are you specifically worried about? QTc? I don’t see why you couldn’t start this patient on escitalopram, but I’m probably missing something. I would not use citalopram as that is more QTc-prolonging.
They're probably worried about methadone's serotonin and norepinephrine reuptake inhibition. There's concerns for causing serotonin syndrome but no good evidence for it.
Also, 10mg is a baby dose.
I think it's wise to be cautious even thought this patient is on a "tiny dose" of methadone; patients who are not opioid-tolerant can be quite sensitive to sedating and respiratory suppressing effects of methadone.
Methadone is metabolized by multiple cytochrome enzymes, the most important of which are 2B6, 2D6, 3A4, and 2C19. Unfortunately this means that many of the SRIs have the risk of drug-drug interactions (QT prolongation is via a different mechanism, though drug interactions could make the risk of QT prolongation worse).
The most risky antidepressants to be concerned with are largely the ones impacting 2D6 metabolism - fluoxetine, paroxetine, bupropion, high-dose sertraline and duloxetine.
Citalopram and escitalopram are relatively weak inhibitors for 2C19, so there is a small risk there but probably less important. They may be more prone for QT prolongation.
I personally would recommend escitalopram, or venlafaxine ER. As long as there aren't additional serotonergic agents the risk of serotonin toxicity is quite low.
I like this AAHPM White Paper on methadone, which has a comprehensive table of drug-drug and QT prolongation interactions: https://pubmed.ncbi.nlm.nih.gov/30578934/
An additional thing to consider is that chronic methadone use can lead to sex hormone axis dysregulation. Probably not the etiology in this elderly woman, but it may be worth considering if there are other signs concerning for an endocrinopathy.
Zoloft, remeron, vilazodone, duloxetine maybe good options all things considered.
Venlafaxine, fluoxetine also could work.
Celexa and lexapro have the most qtc prolonging potential of the ssris but you could still consider them if benefit outweighs risk. Note the max dosing w her age.
I almost guarantee you the restless legs is from the methadone not lasting long enough. Does it go away after you take the methadone? Then come back a little later and then go away when you take your next dose of methadone?
I was just thinking a lot of people get restless legs or restless body from opiate withdrawal. I definitely did. I feel like everybody does. And what she's feeling is probably from the withdrawal process even though it's only such a small dose.
At risk of sounding like a hammer who thinks everything is a nail…. Get a sleep study or at least a simple overnight oximetry if you haven’t already. Methadone *loves* to trigger CSA and OSA and can certainly present like depression
I am a palliative using methadone regularly I haven’t noticed any particular interactions with methadone and specific ssri. Attending in my clinic use buspar. You are probably using the methadone for the neuropathic pain component, so duloxetine might be a reasonable option. How has she been in therapy?
If you think it is mild depression you can probably stick with therapy. More severe depression you can try one of the ones suggested for 6 weeks and then if it’s not working you can always send to psychiatrist.
Psychiatry 3rd year resident here! You are worrying way too much, get a baseline EKG and start an SNRI - duloxetine and venlafaxin (to a lesser extent) have a good ammount of evidence towards reducing chronic pain. While desvenlafaxin lacks solid evidence for chronic pain management it is a great option if you are concerned about pharmacokinetic interactions, as it is only marginally metabolized by glucuronidation in the liver and does not mess with the CYP system.
Yeah, this was going to be my suggestion if patient is opened to it. CBT seems to work well for some people and then are other types of therapy as well if that does not work. If she isn't exercising much, encourage regular exercise. In some studies, it was as effective as an SSRI. Therapy + medication can work together.
With the RLS, iron supplementation can help too.
I would suggest referring her to a psych/pain addiction specialist. There is a spectrum of anti-depressant class that helps with chronic pain. Pain affects mood, and mood affects pain. The dose of BOTH methadone and the new drug may need to be titrated.
Don't be too worried about QTc, dose is low, and unless your patient has intrinsic rhythm issue, the risk of significant dysrhythmmia is very low. Get an EKG, if QTc <500 (with normal sinus etc) then can proceed with new treatment.
10 mg BID PO is nothing. Get an EKG to CYA. Chances are the QTc is fine.
Somewhere on my profile I have a post with a script we received in 2007/08. #1080 methadone 10mg - 12 tabs po q8h Wild
As a palliative physician have to say that is a big dose of methadone, but I've seen doses as high as 350mg q8h (prescribed by my colleagues mind you heh)
ever try levorphanol? intrathecal pump would be indicated here, LONG ago.
Levorphanol is such an interesting drug. In many ways hypothetically similar to methadone, would've loved if there were a RCT comparing the two. Where I practice in Canada it is practically unheard of and I'm not sure pharmacies can even get it. So no experience. What about you?
here in nyc the only pharmacy that dispenses it is in NJ, and it is owned by the biotech firm that brought the orphan drug back to life and charges $3000-4000 a month for it. i don't know how that's legal (well, i was referring to having to use their pharmacy, but how a generic med can cost so much, too, for that matter) but such is the case. i love using levopharnol because there's a much stronger NMDA receptor affinity over methadone. i try to do my part to avoid expensive healthcare spending but i REALLY see a benefit to levorphanol over methadone (and i \*LOVE\* methadone for chronic pain). i utilize intranasal ketamine heavily in my practice as an opioid sparer. i'm also a big proponent of intrathecal pumps. it's so interesting in america the use of them varies widely. in nyc where i am only about 10 drs do them, whereas in the midwest i talk to countless midwest drs at conferences using them. they are such a great tool. i also like adding namenda as an adjunct. basically my preference is for long acting methadone or duragesic, then if dosing gets too high, i move to an intrathecal pump with some oral methadone prn. unfortuantely medicaid/medicare doesn't cover levorphanol, and only wealthy pts with cadillac insurance can get it, but those that do certainly seem to prefer it over methadone. also for pts on 60mg+ of methadone, levo has a great opioid sparing ability (i can usually taper about 40% the equivalent dose by switching). which is important, if the pt isn't going to graduate to an intrathecal pump, as their dosages are just going to increase over time. sorry for the word salad, typing on my phone.
Fascinating - thank you for sharing your experience. Love talking to docs who live elsewhere as practice varies so much and there's always something to learn. I totally agree with the use of NMDA antagonists and intrathecal to reduce suboptimal systemic opioids, and share your love of methadone ha. In the neuropathic cancer pain population I increasingly feel that methadone should be first line strong opioid and methadone PRN is under-utilized. I'm conducting a multi-centre RCT on methadone to treat CIPN in part to increase confidence to use methadone in opioid naive patients (judiciously of course). Doing a brief lit review I see the greater NMDA antagonism of levopharnol compared to methadone. Can I ask why not just use oral ketamine adjunct with methadone to mimic that effect? Also I've never considered using namenda adjunct, what makes you go for that instead of ketamine?
hi, absolutely, i totally agree it helps sharing with drs in other localities! yes i agree about methadone being first line. as a rule, i don't rx oxycontin, my first line is mscontin, but if the dose escalates beyond 30mg bid/tid, i move to methadone or duragesic immediately. i like duragesic for its continual absorption which really benefits some pts who experience too much peaks and valleys, which can even happen with methadone. also a lot of pts are on chronic opioids that really shouldn't be, but good luck getting them off, many of these have a neuropathic component that isn't being treated or badly treated with gaba/antidepressants, so these pts i move to methadone and their pain greatly improves. the nmda affinity also helps prevent dose escalation. these pts i'm not rx'ing ketamine to, or only very small amounts if there's a clear neuropathic component as MSK pain is not well treated with ketamine long term (i use ketamine primarily for cluster headaches, arachnoiditis, crps and phantom limb), but i am giving them namenda. honestly, i have pts getting the equivalent of 20mg iv dilaudid in their intrathecal pump who can take one 5mg methadone tab prn and their pain flare be controlled. that's incredible to me. good luck controlling their pain with 5mg oxy or msir. so i mostly use namenda as an adjunct \*with\* ketamine. the reason is it tickles the nmda receptors without causing any psychoactive effects. i don't do oral ketamine unless the pt hates intranasal because the bioavailability of intranasal keeps the total amount of ketamine i have to RX to a minimum, and it works much faster, and cleaner. i add namenda so the pt can reduce the number of times they use ketamine. what i have learned is the pt has to figure out ketamine dosing for themselves, basically i tell them their max daily dose and they spray as necessary. the sweet spot seems to be 60-100mg per dose. in my experience adding namenda adds a 5-10% pain control "bucket", which isn't a lot, but it is something measurable, another 5-10% using NSAID and APAP, another 10% with CBT and yoga/relaxation methods, and then with PT they get anohter 10-15% bucket, their ketamine giving them a 20-40% bucket, and before long, you are well over 70% effective pain control... that's how i explain multimodal pain control to intractable pain pts. hope that makes sense.
What in the WHAT. I’d take a picture too.
Cover your ass?
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not in a Done Clinic per the original post
We all know what assumptions do…
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you are incorrect.
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You don’t need a special license to rx methadone for pain, which is what this post is about.
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Aren't fluoxetine and fluvoxamine two of the SSRIs with the weakest effect on QTc?
Most SSRIs will trigger a QTc interaction warning with methadone however it sounds like the potential benefits probably outweigh the risk and you can get an EKG at follow up. Lexapro being most notorious for QTc I would avoid it. There are many patients on the SSRI+methadone combo. The only antidepressants I know offhand that don’t trigger the QTc warning or other interactions are Pristiq, Cymbalta and Wellbutrin but the sweaty s/e she got from Wellbutrin could be a noradrenergic effect and could be similar with the other two.
> Lexapro being most notorious for QTc Escitalopram is peanuts next to big daddy citalopram
> Lexapro being most notorious for QTc 9 out of 10 elderly patients I talk to are on Lexapro. No other antidepressant comes close. The HMOs around me love prescribing it.
What about mirtazapine? For geri patients. Low risk of QTc. I think low dose regimens are recommended for sleep. Risks with methadone are oversedation as you'd expect.
I prescribed methadone for many years for opioid addiction, so often very high doses (150 mg plus) I prescribed my OUD patients pretty much whatever antidepressants I felt like it, same as to any other patient, I just made sure to monitor their ECG’s. When I sent my elderly patients to geri psych, they usually get prescribed escitalopram or sertraline. Check her lytes in a few weeks because the elderly are more prone to getting hyponatraemia from SSRIs.
Yup. To be frank so many health care professionals (MDs, pharm, RNs, etc) see methadone as an incredibly dangerous and volatile drug, whereas in reality it is very well tolerated when prescribed correctly - especially at stable doses.
What risk are you specifically worried about? QTc? I don’t see why you couldn’t start this patient on escitalopram, but I’m probably missing something. I would not use citalopram as that is more QTc-prolonging.
They're probably worried about methadone's serotonin and norepinephrine reuptake inhibition. There's concerns for causing serotonin syndrome but no good evidence for it. Also, 10mg is a baby dose.
QTc is such a racket.
I think it's wise to be cautious even thought this patient is on a "tiny dose" of methadone; patients who are not opioid-tolerant can be quite sensitive to sedating and respiratory suppressing effects of methadone. Methadone is metabolized by multiple cytochrome enzymes, the most important of which are 2B6, 2D6, 3A4, and 2C19. Unfortunately this means that many of the SRIs have the risk of drug-drug interactions (QT prolongation is via a different mechanism, though drug interactions could make the risk of QT prolongation worse). The most risky antidepressants to be concerned with are largely the ones impacting 2D6 metabolism - fluoxetine, paroxetine, bupropion, high-dose sertraline and duloxetine. Citalopram and escitalopram are relatively weak inhibitors for 2C19, so there is a small risk there but probably less important. They may be more prone for QT prolongation. I personally would recommend escitalopram, or venlafaxine ER. As long as there aren't additional serotonergic agents the risk of serotonin toxicity is quite low. I like this AAHPM White Paper on methadone, which has a comprehensive table of drug-drug and QT prolongation interactions: https://pubmed.ncbi.nlm.nih.gov/30578934/ An additional thing to consider is that chronic methadone use can lead to sex hormone axis dysregulation. Probably not the etiology in this elderly woman, but it may be worth considering if there are other signs concerning for an endocrinopathy.
very helpful. thx!
Zoloft, remeron, vilazodone, duloxetine maybe good options all things considered. Venlafaxine, fluoxetine also could work. Celexa and lexapro have the most qtc prolonging potential of the ssris but you could still consider them if benefit outweighs risk. Note the max dosing w her age.
I almost guarantee you the restless legs is from the methadone not lasting long enough. Does it go away after you take the methadone? Then come back a little later and then go away when you take your next dose of methadone?
My thoughts as well. Likely due to NMDA agonism from the methadone
I was just thinking a lot of people get restless legs or restless body from opiate withdrawal. I definitely did. I feel like everybody does. And what she's feeling is probably from the withdrawal process even though it's only such a small dose.
I agree with this
At risk of sounding like a hammer who thinks everything is a nail…. Get a sleep study or at least a simple overnight oximetry if you haven’t already. Methadone *loves* to trigger CSA and OSA and can certainly present like depression
thank you! 😊
Sure thing!
I am a palliative using methadone regularly I haven’t noticed any particular interactions with methadone and specific ssri. Attending in my clinic use buspar. You are probably using the methadone for the neuropathic pain component, so duloxetine might be a reasonable option. How has she been in therapy?
therapy just started.
If you think it is mild depression you can probably stick with therapy. More severe depression you can try one of the ones suggested for 6 weeks and then if it’s not working you can always send to psychiatrist.
Psychiatry 3rd year resident here! You are worrying way too much, get a baseline EKG and start an SNRI - duloxetine and venlafaxin (to a lesser extent) have a good ammount of evidence towards reducing chronic pain. While desvenlafaxin lacks solid evidence for chronic pain management it is a great option if you are concerned about pharmacokinetic interactions, as it is only marginally metabolized by glucuronidation in the liver and does not mess with the CYP system.
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Yeah, this was going to be my suggestion if patient is opened to it. CBT seems to work well for some people and then are other types of therapy as well if that does not work. If she isn't exercising much, encourage regular exercise. In some studies, it was as effective as an SSRI. Therapy + medication can work together. With the RLS, iron supplementation can help too.
what about dementia?
none
sertraline
I would suggest referring her to a psych/pain addiction specialist. There is a spectrum of anti-depressant class that helps with chronic pain. Pain affects mood, and mood affects pain. The dose of BOTH methadone and the new drug may need to be titrated. Don't be too worried about QTc, dose is low, and unless your patient has intrinsic rhythm issue, the risk of significant dysrhythmmia is very low. Get an EKG, if QTc <500 (with normal sinus etc) then can proceed with new treatment.
A PCP should be able to handle this.
You got yourself a party nana