michaelrack

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why do we still use methadone for opioid replacement therapy?? I can understand its past use, given its half-life. The only rationale I can see for using it compared to other modern long-acting opiates is that it supposedly blocks the euphoric effects of heroin. I haven't been able to find the mechanism of action for this in any of the articles I have looked at. Do other opiates (besides suboxone) do this??
 
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HarryMTieboutMD

This is begging the question, but we still use it because people are on it and it works. It's binding affinity to the MOR is higher than most other opioids (explaining blocking euphoric effects of other opioids for the same reason buprenorphine does), and in the 1960s people noticed that it would quell cravings without producing changes in consciousness or levels of functioning (people could still work, appropriately interact, etc).

Compare with Buprenorphine methadone has better treatment retention rates but access remains a problem (meaning, you need a licensed clinic). Additionally dosing and prescribing methadone takes more training and understanding of pharmacology (given it's variable but long half life, it's storage in peripheral tissues with delayed release in blood stream, significant interactions with other drugs, potential for cardiotoxicity etc).

A lot of older OBGYNs prefer to prescribe it during pregnancy due to familiarity and the bulk of literature advocating for its use during pregnancy because this is what they used during the heroin epidemic in the 1970s. However this too is changing given that Buprenorphine is safe, easy to use, as effective (though again greater retention in treatment), and more straightforward in pregnant patients. Additionally it produces a less severe neonatal abstinence syndrome.

One of the reasons I like Buprenorphine a little better is because, as one of my attendings says, the two things that are guaranteed with opioid addiction are constipation and depression. Work from Gold and Kleber in the 1980s shows that chronic MTD (and by extension other opioid agonist) treatment suppresses release of endogenous opioids, and emerging optogenetics work is elucidating the link between the opioid system and dysphoric/anehdonic states. The KOR antagonism of Buprenorphine can really help patients with this, but again, pharmacotherapy is only a piece of the puzzle.
 
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michaelrack

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thank you, HarryMTieboutMD, for the explanation. I didn't know about the higher binding affinity for the MOR. I have been working part-time at a methadone clinic for the last 6 months- I have read extensively about methadone drug interactions, side effects, and dosing; but this is the first I have heard about the MOR high binding affinity. thank you.
 
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NickNaylor

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Other cases for methadone use include comorbid opiate use disorder/chronic pain which is poorly controlled with buprenorphine and inadequate control of withdrawal symptoms with buprenorphine even at high doses (e.g., 32 mg daily). Given buprenorphine's MOA you will only get some much opioid activity even at high doses, which is less of an issue with methadone. Methadone also tends to be cheaper.
 
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HarryMTieboutMD

Other cases for methadone use include comorbid opiate use disorder/chronic pain which is poorly controlled with buprenorphine and inadequate control of withdrawal symptoms with buprenorphine even at high doses (e.g., 32 mg daily). Given buprenorphine's MOA you will only get some much opioid activity even at high doses, which is less of an issue with methadone. Methadone also tends to be cheaper.
This is not really standard of care or necessarily good practice since most opioid withdrawal symptoms peak at 72 hours and are over within a week. I have yet to see a case of withdrawal from abrupt cessation where the patient's symptoms would not significantly lessen with Bup- they might still feel sick and might even vomit, but it's transient and non life threatening. The exception is precipitated withdrawal (I saw 2 cases of heroin addicts deciding it was a good idea to take PO naltrexone) in which case I would go straight to IM methadone bc you probably can;t even get them still enough to give PO meds.
 
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