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  1. I've done a lot of reading on how to transition problematic chronic pain non-OUD patients and I think I've got a good one. There's not a lot written about outpatient transitions for community pain patients so I've borrowed from a lot of case series like the links below. Using a single Butrans patch for 5 days, tapering down full agonist opioids over 3 and starting sublingual buprenorphine on day 3 and increasing should do it! The varying fractions of flims for bernese-style protocols just confused my patients but slapping a butrans patch on seems like an elegant solution to slow microtransitions. What do you think? See attached pdf. I've already had success with this other case series using Butrans: https://doi.org/10.7812/TPP/19.124 and https://jamanetwork.com/journals/jamainternalmedicine/article-abstract/2720129?utm_campaign=articlePDF&utm_medium=articlePDFlink&utm_source=articlePDF&utm_content=jamainternmed.2018.6749 Buprenorphine Microdosing with Patch protocol Perez.pdf
  2. Could I get advice for transitioning a problematic legacy methadone pain patient to buprenorphine? he’s on 20mg TID methadone and the traditional approach will take months. I’ve never done bupe microdosing. Any advice or protocols? I was reading there are 3 week ones. Thanks!
  3. There is a recently updated PCSS guidance on diversion and adherence of buprenorphine: http://pcssmat.org/wp-content/uploads/2014/02/PCSS-MATGuidanceAdherence-diversion-bup.Martin.pdf David Fiellin
  4. How are programs around the country doing MAT during pregnancy? My local hospital is having terrible problems with neonatal abstinence syndrome. There is some evidence that bup is associated with less severe NAS. Should we be trying to get more of these mothers on bup instead of methadone? Why is bup preferred over bup/naloxone in pregnancy. Naloxone is not absorbed SL; how could it harm the fetus? J. Cockey Dr James Cockey PCSS-MAT has a module and a separate guidance on this issue: http://pcssmat.org/new-pcssmat-online-module-posted-opioid-dependence-in-pregnancy-clinical-challenges/ http://pcssmat.org/wp-content/uploads/2014/06/PCSS-MATGuidancePregnancy-and-Buprenorphine.Martin.pdf David Fiellin Two archived webinars on this topic as well: http://www.psychiatry.org/pcssbwebinars Special Populations · Inducting and Stabilizing Opioid-Dependent Pregnant Women on Methadone or Buprenorphine: Current Research and Future Treatment Implications · Buprenorphine Treatment During Pregnancy David Fiellin Hello Dr. Cockey, Please note PCSS-MAT provides mentors that have extensive experience working with pregnant patients: Drs. Martin, Meyer, Michaels, Starer, and Wright. More information regarding these mentors can be found here: http://pcssmat.org/mentoring/mentor-directory Kind regards, Justina Andonian, MBA On behalf of Dr. John Brooklyn: You may want to review the MOTHER study published in NEJM ( link here) for evidence based info on NAS. The use of either drugs is associated with better outcomes than no treatment at all. Getting compliance is the most important thing rather than the medication, per se. http://www.nejm.org/doi/full/10.1056/NEJMoa1005359 Also is a link to our program at UVM for care of the NAS (link here) http://www.uvm.edu/medicine/vchip/?Page=ICON.html There are a number of factors involved, however often inadequate dosing during pregnancy is associated with NAS. Further complicating it is not using proper assessment tools for NAS. I hope the above links help you get started in approaching this problem. While there are many women who are taking bup/nal and become pregnant and don’t know it for a few months and inadvertently expose their fetuses to it without complication or adverse outcomes, the recommendation is for bup mono. Some of this is due to fear of inducting a pregnant heroin user on bup/nal and potentially inducing withdrawal. Since some naloxone can be absorbed systemically, albeit very little, the theoretical concern is what trumps common experience. We have a community based treatment team for all our opioid dependent pregnancies that meets monthly at our hospital with the OB, neonatal, addiction services meeting along with VNA, public health nursing and Dept of Children and Families for comprehensive medical and case management. It is called CHARM and there are links to this at the UVM site listed above. I hope this helps, Info@PCSS-O.org My apologies if this has been sent more than once...Having difficulty responding to the group/ckh: Hi, Dr. Cockey, I have been confronted by the pregnancy/MAT problem several times over the past few years. I believe the old 'Standard of Care' for the pregnant patient using Methadone has long since been passed by; literature comparing Methadone to Buprenorphine has consistently shown Bup to be the superior agent for Mom and the baby except in a few specific instances. Having said that, however, we must remember the adage, "Whatever Mom is feeling, the baby is feeling at least as bad." Hence, if the Mom is already on Methadone, it is likely the safer route to maintain the Methadone through pregnancy since induction onto Bup requires some tricky techniques, and initial withdrawal (remember the baby) is required and can be unpredictable. I did have one patient on Methadone call with the request for Bup induction, and I gave her the advice to stay on it...Her reply was that she was going to move to Bup with or without my help. So I did a VERY careful low/slow induction with her High-Risk OB/GYN following the fetal distress situation with monitoring. It turned out well and I was a hero. If an induction to Bup is necessary, current recommendations are to do it carefully during the 2nd trimester...safest for the baby. As for the tendency to use monotherapy instead of the combo Bup/Naloxone, you're absolutely correct. Little Naloxone is absorbed and probably less is delivered to the fetus. It is simply the usual common wisdom to use fewer drugs in any situation, resulting in fewer potential surprises. I have personally seen no difference in babies with Moms on Mono or Combo Therapy...Many others have echoed the same experience. As for NAS on Bup, unless a large dose is being used (G.T. 16mg), the babies seem do well with calm, quiet environments, CoolCaps, etc. The biggest problem is to calm down the Neonatologists when they try to bolt for the NICU if the baby even grimaces. And to answer the question you didn't ask, current recommendations suggest no problem with breast feeding while on Bup. (See the ACOG position paper on-line). Thanks for the opportunity to 'Expose my experiences.' CK Hebdon MD, MS, D/ABAM
  5. Hello all - so glad for this resource, and hope that it will gain momentum. Great idea. I am a pediatrician/adolescent medicine doc, just started as a doc in an outpatient and residential drug treatment program. I have clients asking for naltrexone as well as buprenorphine. I have been prescribing buprenorphine for one year, at the university health center. Hope to learn a lot here. Deborah Stewart
  6. I am new to the list serv. have been working on plans for perioperative pain management for suboxone patients. I realize there are a variety of strategies. I would prefer to continue suboxone and treat with short acting opiates which seems to be an emerging strategy from my research. What experience to other prescribers have with this issue? Thank you, lindasuehermans@gmail.com How can a partial agonist/ antagonist (Suboxone) facilitate pain relief when added an agonist is blocked from activation? I would appreciate what your lit search reveals. I have a different approach using partial agonist parenterally while maintained on SL dose. Scott McNairy MD Please continue this discussion. This is such a treatment challenge especially when surgery is unplanned. And those of us without access to addiction specialists are just winging it as best we can. I so appreciate the insight of those of you with more experience. Diana For more options: https://urldefense.proofpoint.com/v2/url?u=https-3A__groups.google.com_d_optout&d=AwIFaQ&c=ND-Z_FnoJTOCBd6ZraMT0-wJD0GDS_U0VV_Zq7yxAI4&r=nn-Dxwnb7v6A-MWmvsGjok_tBZ3YHZe5eIO50ac9ZjU&m=DXuF18_BYWGzqK1qkdQS67a__FcaOxAatQmrl1KvZOc&s=v9gLEN42YNZ4EvpvsHJRsbzlLsIaVoyg_zw_YDnEmmE&e= DianaRae@fhshealth.org On behalf of Dr. David A. Fiellin (david.fiellin@yale.edu), PCSS-O Listserv Moderator: Welcome to the listserv! There is a PCSS guidance on this topic that was updated less than a year ago. Here is the link: http://pcssmat.org/wp-content/uploads/2014/03/PCSS-MATGuidanceTreatmentOfAcutePainInPatientsReceivingBup.Fiellin.pdf Info@PCSS-O.org I also did a webinar on this subject for PCSS-MAT in August 2014. It is archived at http://pcssmat.org/education-training/archived-webinars/ Dan Alford I have attached a guidance my nurse uses, and sometimes gives to patients and other physicians on treating pain in buprenorphine patients. I have been using something similar for 8 or so years, mostly with good success. I have rarely had a patient relapse, solely due to this sort of thing. I have had two patients on narcotics for disastrous trauma and surgeries for as long as 4 months, and then transitioned back on the buprenorphine at some point successfully. This is the "fun" part of medicine, where experience and judgment come into play, when really good evidence is hard to come by. * Attachment 1 William Yarborough MD, FACP Dr. Yarborough, I looked at your attachment concerning Guidance for Pain Management in Patients on Buprenorphine , I am a general dentist practicing in a small rural community population 8000, I have had two cases where after consulting with the prescribing Physician, had the patient stop the Buprenorphine, had the procedure, (extractions) and prescribe opioids, and unfortunately the patient did not return to Buprenorphine. I have had better success having the patient increase their dosages of Buprenorphine and use a combination APAP and Ibuprofen on a 24-48 hour dosage. Actually much better success, it did involve lengthy discussions with the patients physician. I was interested in your # 3 in Dental Procedures concerning Percocet 10. Would this precipitate any acute withdrawal issues? Also, a concern of mine would be if the patients opioid of choice was Oxycodone, would we be on the “slippery slope” again? I would greatly appreciate your comments on this. Thank you very much. William T. Kane, DDS, MBA Your experience is certainly my experience. I much prefer keeping them on the Bup, when at all possible. I have not had anyone really “relapse”, when I kept them on their Bup at increased dosages, and even when using higher dosage of acute pain meds, for a very short time. It seems that when I stopped the Bup, and give them pain meds, they often seem to want to stay on the pain meds longer. A lot of this from the treatment end is motivation of the patient. As far as the Percocet thing, I just use that as an example. I am not for sure the is more of a slippery slope than hydrocodone, but I do think about that sometimes. I just hadn’t had any problems with that technique to date. One of the other doctors, in our practice, sometimes adds tramadol, due to it supposed dual action effect for pain, but I haven’t found much use for tramadol, other than little old ladies with arthritis, and detoxing opiate addicts. William Yarborough MD, FACP I had to write this for another group, so am posting to this one. I would very much appreciate comments. Thanks! All medications are shot guns, not rifles. They hit a lot of different things, some of which are targets and some of which are not. For example, while aspirin decreases inflammation and decreases pain, it also decreases platelet adherence and irritates the stomach. Opiates are shotguns as well. They decrease pain, spike dopamine in the forebrain, slow the gut (constipation), induce hyperalgesia, etc. etc, etc. Buprenorphine also does a lot of different things. It is a VERY GOOD pain med with estimates of its morphine equivalency as high as 30:1. However, this particular target (pain relief) is only hit if buprenorphine is dosed intermittently. Buprenorphine is also unique in that, in most patients, it maintains dopamine tone as opposed to spiking it, and thus avoids inciting and maintaining the disease of addiction. So, its target in Addiction is reduction of cravings to a level where the patient can engage in counseling. For this particular target- controlling cravings- it is dosed once per day or less. Because Buprenorphine is a mixed agonist/antagonist, it also blocks the analgesic properties of other opiates. There are antidotal reports of buprenorphine being “overridden” by intravenous Fentanyl in acute pain situations such as child birth and acute trauma. There is also increasing evidence that buprenorphine can be used for pain relief in and of itself. Personally, I have been able to provide good acute pain control for patients on buprenorphine maintenance by using intermittent dosing. I recently got a patient through a ruptured appendix comfortably by using this approach, and I also have a patient who is in palliative care due to end stage diabetes with good pain control using intermittent dosing. Due to the ineffectiveness for pain control of other opiates when buprenorphine is in the system, and the tendency of other opiates to spike dopamine and incite cravings, the risks of giving patients with the Disease of Addiction pain meds such as hydrocodone, oxycodone, etc, outweigh the benefits. The overwhelming affinity for the mu receptors by buprenorphine is unlikely allow other pain meds to bind, thus making them useless for pain control. However, the induction of dopamine spikes in the forebrain can lead to cravings and relapse. Relapse, which is too often lethal, should be avoided at all costs. The risks of ALL psychoactive medications, including benzodiazepine and stimulants, to induce dopamine spikes in the forebrain, thus leading to cravings and relapse, must always be weighed against the benefits. Prescribers have an obligation to weigh risks and benefits, and to always give greatest weight to the condition which will kiss the patient first. Since Addiction is highly lethal, it general comes first in these considerations. Please note that buprenorphine is different from methadone which is a full agonist. Patients on MMT can receive some pain control from other opioids. However, as above, the prescriber always has to weigh the risks and benefits. Mary G. McMasters, MD, FASAM I should have used another term. "Intermittent" means the daily dose divided into parts. The smaller the part, the better the pain control. For instance, taking 1/4 four times a day give better pain control than 1/2 twice per day. Mary G. McMasters, MD, FASAM So, if we want to use Buprenorphine for perioperative pain, can the surgeon prescribe it without being certified as an office that provides addiction treatment? T. Madden My preference is to manage perioperative buprenorphine prescribing in my patients. The attached addresses your question (4th clinical vignette addressed by the DEA). While off-label prescribing of sublingual buprenorphine products that are FDA approved for the treat of opioid use disorder is not prohibited, there are issues to be considered. These issues are outlined in a PCSS-MAT guidance: http://pcssmat.org/wp-content/uploads/2014/02/PCSS-MATGuidanceOff-label-bup-for-pain.Gordon.pdf * Attachment 2 David Fiellin If the indication for the Rx is pain, a waiver to prescribe is not required. Anyone who can prescribe a schedule 3 is allowed to prescribe buprenorphine off-label for pain. AKolodny@maimonidesmed.org For perioperative pain management, does one use buprenorphine or Suboxone? Do you use IM, sublingual, transdermal administration? If Dr. McMasters recommends dividing the usual daily dose by four, what is the actual dose per day? T. Madden I’m hoping to get some clarification about Dr. McMasters’ last point regarding buprenorphine versus methadone. Why would the fact that one is a partial agonist and the other a pure agonist have any impact on whether additional opioids produce additional analgesic effects? Shouldn’t it be based purely on the affinity for the opioid receptor? Also, I’m wondering if Dr. McMasters can clarify the dopamine stimulation in the forebrain. With its high affinity for the mu receptor, shouldn’t buprenorphine also block the dopaminergic effects of other opioids? Or are these dopamine spikes mediated through other receptors? Thanks for clarifying! Joshua Blum MD Attachment 1-GUIDANCE FOR PAIN MANAGEMENT IN PATIENTS ON BUPRENORPHINE THERAPY (1).docx Attachment 2-DearDEA2004.pdf
  7. My understanding is that there is no “optimum” time for maintenance. The high rate of relapse after stopping buprenorphine is a sobering factor and the consequences of relapse can be severe/deadly. Having said that, it is a reasonable goal with perhaps early on, more focus on the journey then the goal. By journey, I mean a steady focus on establishing a robust, steady, solid, dependable, tried & true, storm proof recovery program is a must. The approach is of course individualized and there may be exceptions but they are rare in my experience. Many people want to get off fast after feeling “normal” for the first time in years. That may be related to circumstances, flight into health or perhaps more often, shame. I try to use an MI approach in managing this. I hear the patient’s perspective and reflect it, and then (if appropriate), with permission, offer a concern about the risk of relapse. Hope this helps. Mike Newberry, MD That is the $100,000 question! The data from R-B suggested that less than 10% of the patients can be weaned off at the same time that they stayed sober. There was recent "small group discussion" where the Physician had been able to wean off 80%. In my limited experience, less than 1% are able to wean off and remain sober. Pedro Ballester, M.D. There was a great webinar yesterday by Drs. Fiellin and Renner, discussing this very issue. http://pcss-o.org/wp-content/uploads/2015/09/FiellinRenner-Live-Webinar-9.15.15-FINAL.pdf This presentation detailed the argument for a long-term maintenance (without the specified duration upfront) for most cases. However for patients with high motivation to stop medication but engaged in other treatment and recovery-oriented activities and with positive prognostic factors a taper can be attempted. Seems that longer tapers are more likely to be successful and there is a possibility that some patients may benefit from a period of naltrexone maintenance post buprenorphine detoxification to minimize the risk of relapse, which usually occurs early post-detoxification. However, there is no clear empirical evidence to support these approaches only the accumulated clinical experience. Adam Bisaga M.D. Yes I was on yesterday’s webinar and use the strategies for taper. But my question is how long to keep a person on bup before the taper? Elizabeth Lottes At Minneapolis VA we are just now looking at the data on outcomes of 299 patients treated with bupe/nx since inception in spring 2004 to spring 2015 (11 years). About 120 remain in various stages of active treatment with med while the rest are off med. From our clinical experience a year of MAT is certainly not too long and most were on MAT well beyond that. Hope to have the preliminary report at AAAP in December and a more extended report at ASAM in April. The excellent Webinar presented by Fiellin and Renner on Tuesday was most helpful in noting the lack of substantial outcomes data. Stay tuned. Scott McNairy MD Great topic, a question I ask myself (and other people) all the time. Any published guideline references on this topic would be appreciated! Sincerely, Frederick Michael Elliott, MD http://www.psychiatry.org/psychiatrists/practice/professional-interests/addiction-psychiatry/pcss-mat-archive Click on PCSS-MAT Archive. I did a webinar on March 10, 2015 reviewing the evidence on maintenance vs. taper with both methadone and buprenorphine. The evidence for indefinite maintenance is overwhelming. On April 14, Drs. Timothy Wong, John Renner, and myself, discussed clinical cases involving tapering, in another webinar. These 2 webinars tie in nicely with Drs. Fiellin and Renner’s webinar yesterday. Edwin A. Salsitz, M.D., FASAM As it was noted, we have minimal data to determine what is the optimal duration of buprenorphine treatment to maximize long-term outcome (I presume this is most often “full recovery" - remission of symptoms+changed life). We only have observational and clinical anecdotes to guide us in this regard, and there is no controlled studies on the horizon. So every clinician develops their own approach (algorithm) to guide them. Here is mine: - For patients with a history of pain I tend to recommend long-term (no pre-defined length) maintenance while trying gradually to decrease dose to 2-4 mg and keep it there. Those patients like to be on some kind of "pain-management” regimen and tend to stay on. -For patients with a primary addiction problem you may recommend the same approach but many will get “tired of it” and will stop buprenorphine on their own anyway, without your help. There is some evidence that is the default mode of buprenorphine maintenance, multiple short episodes of treatment - but this is not the optimal outcome as there are additional risks involved in relapse. So avoiding the issue of "wanting to be off meds" is probably not very good for the patient, better to partner with them in setting the goal of controlled discontinuation early on. Once they meet their treatment targets I recommend discontinuation attempt with transition onto Vivitrol. They may realize along the way that they prefer to stay on the buprenorphine for longer, so at least they get a better sense of what works for them. People who do not do well on buprenorphine (continue using despite increase in dose and treatment intensity) I recommend methadone or detoxification and transition onto Vivitrol. Some of them will do well on Vivitrol some will not, but I have not seen many who suddenly get better on buprenorphine after failing it initially. Actually probably you will see if someone will respond to buprenorphine in the first month of treatment and it may make sense to switch treatment plan early on. I would be interested to learn what strategies others have adopted. Adam Bisaga Is there data on efficacy of prolonged antagonist use? Paul C. Coelho, MD The longest is 18 months, a 12 month extension to the pivotal 6 months trial http://www.ncbi.nlm.nih.gov/pubmed/23701526 Conclusion: During a 1-year open-label extension phase of injectable XR-NTX for the prevention of relapse in opioid dependence, 62.3% of patients completed the phase and 50.9% were abstinent from opioids. No new safety concerns were evident. Adam Bisaga This is basically what I do and people who have been on buprenorphine a long time seem to do better switching over to Vivitrol. Not sure if no more daily dosing removes a trigger or if Naltrexone is just a better medicine. Currently we are involved in NIDA-CTN 0051 which is evaluating Suboxone vs Vivitrol . Trial is still going but participants are only on either medication for 6 months. I like your thought process for pain patients being on 2-4mg. Elizabeth Lottes
  8. Likely a topic talked about before. But if a patient is already on buprenorphine for history of opioid dependence how do you manage the pain when they get admitted to the hospital with an acute condition like appendicitis or cellulitis etc.?
  9. Question from Dr. Paul Coelho: Question for the group - I have observed a significant increase in spasticity in tetraparetics who are in withdrawal awaiting induction. Can anyone explain the mechanism here? Is it a failure of descending suppression akin to nocturnal myoclonus? info@pcss-o.org Question for the group: I have created a brief guide for the management of opioid withdrawal that will be used in a large upcoming clinical trial on opioid-induced hyperalgesia. Would anybody be interested in reviewing it to make sure I didn’t miss anything? Nat Katz Thank you both – for anyone interested/available to review the guideline to managing opioid withdrawal for that clinical trial please provide your full name and email address – all I seem to get is the listserv address. Thanks and apologies for the broad email. Nat Katz We have recently revised the detoxification protocol at our center and will be happy to review yours Adam Bisaga Yes, I would be very interested. I had a patient like this recently that was very challenging, and had unusual symptoms. William H. Yarborough Sure. Send it my way along with your time-line for feed-back. Dr. Lynda Williamson I would like to see the planned protocol. I have been slowly withdrawing people from buprenorphine for the last 10 years and have come to appreciate how variable the process is. Attention to anxiety about it is important. Gary Horwitz, MD
  10. Question below from a Listserv member: Please assist: What detox would be best in patients addicted to both Benzos and opioids? info@pcss-o.org In my opinion, the best strategy is a sequential detoxification; patients are first detoxified off benzodiazepine while remaining on a stable dose of an opioid agonist (buprenorphine). Once the benzo detox is completed, one can then discuss with the patient maintenance on buprenorphine (which should be a preferred treatment for most patients) or detoxification off buprenorphine and transition onto XR-naltrexone (if the patient is unable/unwilling to be maintained on an agonist). Clearly, detoxification of both benzos and opioids and referral to a medication-free treatment would be the least preferred plan, as the risk for relapse and overdose in such patients is very (unacceptably) high. Adam Bisaga Benzo's #1. Check out SAMSHA tip 54: http://store.samhsa.gov/product/TIP-54-Managing-Chronic-Pain-in-Adults-With-or-in-Recovery-From-Substance-Use-Disorders/SMA13-4671 #2. I've extended it for my referring PCPs: http://www.slideshare.net/101N/alternatives-to-benzodiazepines-60240127 I'm open to constructive criticism on #2. Paul C. Coelho, MD I think Adam's right on. For me the most important principles in play here are as follows: Detox is really not a safe or appropriate model here, unless "detox" is defined as a very slow taper, with goal of eventual discontinuation of benzodiazepine. Certainly the benzodiazepine habit should be defined/quantified as clearly as possible, then controlled (if appropriate, with substitution using long-acting benzodiazepine), then slowly tapered and ideally, eventually discontinued. For opioid habit, maintenance therapy is the model. Crucial first step: begin sublingual buprenorphine and get to stable dose -- and away from illicit opioid -- asap. Then as soon as stable (or at least relatively stable) on MAT, initiate (again, very slow) benzodiazepine taper. An excellent guide for benzodiazepine dependence treatment is here: http://www.benzo.org.uk/manual/index.htm Hope this helps. Jim Recht Paul, I have found outstanding results with clonidine 0.1 for anxiety and panic disorder. The rebound hypertension is not a problem unless it is used regularly, so that is my first line. The other I will use is hydroxyzine - either for panic or (more usually) for sleep. David Gunn Jim, are you sure Heather Ashton’s work should be the model with benzos? I’m familiar with it, and I’ve spoken to a couple of British addictionologists (not a scientific sample, of course), who described Ashton’s reputation in the UK as very controversial up until about 4-5 years ago. Then I read the British Association of Psychopharm’s 2012 Expert Consensus Guideline which not only described benzodiazepine tapering procedures totally inconsistent with Ashton’s theory, I was rather surprised to find no citation of any of her work in the Guideline. Very conspicuous by its absence, I thought. Not saying I’m an expert in British addiction treatment standards of care, but the Guideline sent the message to me that Ashton’s work is discredited, at least in some circles in the UK. I haven’t seen any other citations of her work in any NICE guidelines or other British sources. David Streem Thanks Paul, I forwarded to my colleagues David Gunn I agree that Ashton’s work is not accepted into the mainstream, though it is certainly popular among people who search internet. I believe one of the reasons is that there is no controlled evidence to support this approach but it is presented as such. It is more of a common sense approach to experienced clinicians, slower the better, but you have to take into account patient’s unique circumstances and the treatment response to adjust the protocol. It also diverts attention from the need for a behavioral treatment, as if a carefully executed taper is all that is needed. Adam Bisaga I'm not certain, Dave! I really appreciate your input here. I'm sorry to say I had not thought to check NICE for citations of her work. On the other hand, it's difficult for me to understand how this work could be "discredited." Perhaps the author herself? (I don't know much about her). The manual itself is could hardly be more straightforward. I can't quite picture what "discrediting" it would even look like. If you've reviewed it and see problems with it, I would love to hear about those. For better or worse, I'm always learning something new in this field! Jim Recht Would it then be safe to combine buprenorphine and some BZD in a detox regime, where methadone is clearly not accepted? info@pcss-o.org Buprenorphine and a benzodiazepine can be used together safely, for motivated patients who have a solid support network and consistent behavioral and supportive therapy, as long as dosing is cautious and closely monitored. Jim Rech Here are some resources I've been using with patients on benzos who are either also on opioids, or who also have substance use disorders. Below is a summary that I either send to outside benzo-prescribing doctors or give to patients. Attached is a very helpful handout for patients with panic attacks that gives them hope and confidence that their symptoms can be treated (with therapy) while they are tapering off of benzos. BENZODIAZEPINES WITH SUBSTANCE USE DISORDERS, OR IN PATIENTS TAKING OPIOIDS: “Prescription of benzodiazepines in conjunction with methadone is no longer regarded as good clinical practice.” Benzodiazepines: Risks and Benefits. A Reconsideration. Baldwin DS et al, Journal Psychopharmacology 27(11) 967–971 ************************************** “Patients with a history of … psychoactive substance abuse or dependence should generally be excluded from treatment [with benzodiazepines] …” Bandelow B, et al. World Federation of Societies of Biological Psychiatry (WFSBP) guidelines for the pharmacological treatment of anxiety’ World J Biol Psychiatry 9: 248–312. ************************************** “Benzodiazepines pose significant risk for addiction relapse and functional impairment. . . The consensus panel recommends that clinicians treat comorbid anxiety and insomnia with antidepressants or anticonvulsants.” Substance Abuse and Mental Health Services Administration, 2012 www.ncbi.nlm.nih.gov/books/NBK92048 ************************************** “For the vast majority of patients treated with methadone or Suboxone, the risks of taking benzodiazepines will likely outweigh the benefits.” . . . The combination can present significant individual and public health risks of morbidity and mortality.” From: ‘Clinical Guidelines for the Use of Benzodiazepines Among Patients Receiving Medication-Assisted Treatment for Opioid Dependence’ - Behavioral Health System Baltimore, May, 2013. [‘Research and Reports’ - ‘Data Reports and Publications’ - ‘Link to additional Publications and Reports’] ************************************** “In treating panic symptoms in patients with co-occurring substance use disorder, benzodiazepines should be avoided whenever possible in favor of CBT and/or antidepressants.”2010 American Psychiatric Association Practice Guideline for the Treatment of Patients With Panic Disorder *************************************** Joseph A. Adams, M.D. I guess I was always troubled by Dr. Ashton’s theories because there seemed to be little appreciation of the psychological dynamics at work in the addicted individual. I agree that the manual is very straightforward, but to me it offers little guidance to help those for whom benzodiazepine dependence is connected to difficulty coping with fear, shame, trauma and other problems. Mostly I’ve found her all too willing to dodge the issue of benzodiazepine addiction entirely and focus on the problem as one of simple tapering pharmacology. Still, I remember reading an addiction text about ten years ago—maybe an old edition of Principles of Addiction Medicine—in which her work was cited respectfully in the chapter on benzodiazepines. I think at least three of her papers were in the references, which was at least three more references than I had in the book. So I tried to learn what I could from it. Maybe the word “discredited” applies more to her personally than her work? Maybe. If you’ve perused her website benzo.org.uk, you’ve seen some of the feisty letters she’s fired off (then posted for all to see) to various Health Ministers, MPs, Royal College of General Practitioners, etc. Those probably didn’t make her any allies, and if that’s a taste of her usual interactions, I can imagine what happened in the BAP and other organizations after she retired. The letters are fun to read though. Maybe the word “discredited” is harsh, but I can’t think of a better descriptor if the British professionals that followed her thought so little of her work that they thought it no longer deserved to influence their guidelines and standards of care, or even a mention in the references. I think if the NICE has moved away from Ashton’s philosophy as well, that’s confirmation that this was more than just a personality thing. David Streem, MD Thanks for these great resources. We have also seen a very high morbidity with co-prescribed opiates and benzos. Although the standards all say to use with caution on a limited basis, in practice, it is common to see co-prescribing in as many as 55-85% of opioid patients in several studies. We have also collected a range of quotes from the industry: o ASAM § The use of benzodiazepines and other sedative hypnotics may be a reason to suspend agonist treatment because of safety concerns related to respiratory depression. (ASAM, 2015, p. 13) § OBOT may not be suitable for patients with active alcohol use disorder or sedative, hypnotic, or anxiolytic use disorder (or who are in the treatment of addiction involving the use of alcohol or other sedative drugs, including benzodiazepines or benzodiazepine receptor agonists). It may also be unsuitable for persons who are regularly using alcohol or other sedatives but do not have addiction or a specific substance use disorder related to that class of drugs. The prescribing of benzodiazepines or other sedative-hypnotics should be used with extreme caution in patients who are prescribed methadone or buprenorphine for the treatment of an opioid use disorder. (ASAM, 2015, p. 15) o IRETA § “CNS (central nervous system) depressant use is not an absolute contraindication for the use of either methadone or buprenorphine in MAT, but it is a reason for caution because of potential respiratory depression” (IRETA, 2013, p. 1) § “Avoid prescribing alprazolam to individuals receiving methadone” (IRETA, 2013, p. 19). o SAMHSA § “Benzodiazepines are highly associated with overdose fatalities when combined with opioids” (SAMHSA, 2015, p. 38). § “Benzodiazepines have been associated with toxic drug interaction with opioids, including methadone and buprenorphine (SAMSHA, 2012, p. 4).” § “Benzodiazepines are also one of the most frequently mentioned classes of drugs found to be present in deaths associate with methadone and buprenorphine (SAMHSA 2012, p. 4).” o CDC § “ Methadone should not be prescribed to opioid-naive patients, and, whenever possible should not be prescribed to patients taking benzodiazepine antianxiety agents because of risk of an increased risk for severe respiratory depression.” (Paulozzi et al., 2012, p. 4) § “A few states have been able to change prescribing patterns by increasing prescriber use of their PDMP’s…States can take other actions that will affect prescribers. Developing or adopting existing guidelines for prescribing Opioid pain relievers and other controlled substances can establish local standards of care that might help bring prescribing rates more in line with the current best practices. State Medicaid programs can manage pharmacy benefits so as to promote cautious, consistent use of opioid pain relievers and benzodiazepines. In addition, a number of states have passed laws designed to address the most egregious prescribing practices.” (Paulozzi et al., 2014, p. 129) o Minkoff article on dual diagnosis § For patients with known substance dependence (active or remitted), the continuation of prescriptions for of benzodiazepines, addictive pain medications, or non- specific sedative/hypnotics is not recommended, with or without comorbid psychiatric disorder. On the other hand, medications with addiction potential should not be withheld for carefully selected patients with well-established abstinence who demonstrates specific beneficial responses to them without signs of misuse, merely because of a history of addiction. However, consideration of continuing prescription of potentially addictive medications for consumers with diagnosed substance dependence, is an indication for both (a) careful discussion of risks and benefits with the patient (and, where indicated, the family) and (b) documentation of expert consultation or peer review. o McCance-Katz: § “Sound clinical approach to psychiatric complaints in this population is to monitor for a period of time rather than prescribing immediately; select nonbenzodiazepine interventions whenever possible (e.g., cognitive-behavioral therapy); and, if necessary, utilize certain of the selective serotonin reuptake inhibitors (below) for anxiety and depressive symptoms; address other co-occurring drug and alcohol abuse that may be contributing to the symptoms presented; and provide education on sleep hygiene. (Maxwell & McCance-Katz, 2009, p. 84)” o American Pain Society Methadone Safety Guidelines § “The panel suggests that clinicians generally avoid benzodiazepines in patients prescribed methadone because of the possible association with increased overdose risk.” o Mijatovic et al., (2013) § “It would be advisable to perform both pretreatment and regular ECG checkup after 1 month of MMT, especially in case of concomitant use of benzodiazepines.” o Perles et al., (2008) § The tricyclic antidepressant amitriptyline as suspected to be abused by methadone maintenance treatment (MMT) patients in Israel. Given its potentially dangerous interaction with methadone, and even more so with benzodiazepines, which is highly abused among MMT patients, we did a crossectional study of all 303 patients.” References American Society of Addiction Medicine (ASAM), (2015). ASAM National Practice Guidelines on the Use of Medications in the Treatment of Addiction Involving Opioid Use. Ballesteros, M. P., Budnitz, D. M., Sandford, C. M., Gilchrist, J. M., Agyekum, G. M., & and Butts, J. M. (2003). Increase in Deaths Due to Methadone in North Carolina. JAMA, 290. Bernard, J., Havnes, I., Slørdal, L., Waal, H., Mørland, J., & Khiabani, H. Z. (2013). Methadone-related deaths in Norway. Forensic Science International (Online), 224(1), 111-116. doi:http://dx.doi.org/10.1016/j.forsciint.2012.11.010 Bleich, A., Gelkopf, M., Weizman, T., & Adelson, M. (2002). Benzodiazepine abuse in a methodone maintenance treatment clinic in Israel: Characteristics and a pharmacotherapeutic approach. The Israel Journal of Psychiatry and Related Sciences, 39(2), 104-12. Retrieved fromhttp://search.proquest.com/docview/236974880?accountid=34899 CDC. (2013, July). Center for Disease Control and Prevention . Retrieved May 1, 2015, from Center for Disease Control and Prevention:http://www.cdc.gove/VitalSigns/PrescriptionPainkillerOverdoses Dr. Ken Martz We have looked at the evidence on treating sedative-hypnotic use disorder not too long ago and summarized it for the Galanter/Kleber Textbook for Substance Abuse Treatment, which I am attaching. This was 2-3 years ago but I do not believe much have changed since, perhaps there is more emphasis on the recognition of abuse/misuse potential of benzodiazepines, which may be related to the Rx opioid misuse epidemic (either having a directional effect: opioids to benzos or the shared etiology: e.g., self-medication of economic problems). In any case, it is very difficult, if not impossible, to successfully treat sedative-hypnotic use disorder by using medication taper alone. This is a place where evidence based behavioral treatment should be at a center of the treatment plan. Adam Bisaga These are super helpful insights, David! I ought to have been more cautious (or at least more specific) in my recommendation for the Ashton Manual. In fact, I generally use it as a sort of technical reference, pretty much exclusively for its detailed taper examples, and never as a stand-alone guide for treatment planning or education. Behavioral therapy and psychoeducation are virtually always central and essential. Jim Recht Just to let you know, if you have not seen these, that the VA/DoD Guidelines for Substance Use Disorders was recently revised (2015). The link is here and also addresses this issue to an extent. http://www.healthquality.va.gov/guidelines/MH/sud/ Adam J Gordon Of course, I don’t think we’ll ever hurt any patient by following Ashton’s tapering schedules. I totally agree that may be the most useful part of her manual. And by applying more of an appreciation of the intersection between addiction and pharmacology, we can do a lot of good J David Streem
  11. Have been prescribing suboxone for about 10 years- no clinically significant drug interactions have come to light in that time. aronow2@comcast.net The only clinically significant interaction I have seen in 9 years is St. John's Wort. Twice. Nancy C. Blake, M.D. Emergency Room question: I recently gave an interdisciplinary seminar on curbing opioid misuse. There was a Emergency Room Physician Assistant in the audience. He illustrated a problem in his department that makes it hard to change clinician prescribing practices. Seems that patient evaluations carry a lot of weight but most of the negative patient evaluations come from patients who do not get opioid prescriptions when presenting with inappropriate requests for them. Does any one on the list serve have knowledge of ways to get around this problem? Maybe patient evaluation tools that allow the hospital administrator to reward staff who curb opioid prescriptions despite complaints coming from such patients? Thank you in advance for any advice. Theresa E. Madden, DDS, PhD, MS, FACD Dr. Madden - did the person have any evidence to support this claim? I have been involved with ED physician groups looking at this issue and so far the data does not correspond to the fears and assumptions. Not only do many people with pain not return their surveys, but also we have looked at amount opioid prescribed and patient satisfaction by provider and found no relationship. It seems at this point to be an assumption driving provider's practice that may not be based in fact. I have seen excellent success with ED's who use pain education and scripting to help providers keep patients satisfied - even though they may not receive an opioid prescription. The Studor group has some resources, or I can connect you to some physicians innovating pain practice in the ED if you would like to know more. Marian Wilson, PhD, MPH, RN-BC Attached is an editorial which deals with the issue you have raised. *Attachment 1 Edwin A. Salsitz, M.D., FASAM I recently gave an interdisciplinary seminar on curbing opioid misuse. There was a Emergency Room Physician Assistant in the audience. He illustrated a problem in his department that makes it hard to change clinician prescribing practices. Seems that patient evaluations carry a lot of weight but most of the negative patient evaluations come from patients who do not get opioid prescriptions when presenting with inappropriate requests for them pcss-o@googlegroups.com That is the main reason we are in such a mess. We, the physician community, need to rise up in force against this lunacy that is driving the premature deaths of so many and has addicted a generation. In our hospital there is a policy that ER patients get no more than 3 days of opioids, and that can help Josiah D. "Jody" Rich, MD, MPH In Minneapolis the ERs have more or less banded together to prescribe not more than a few doses of medications; and direction to go to primary care clinic for follow up. Physicians have tried to be diligent in informing administration if the difficulties of er or doc shopping in the face of opioid overuse, seems to be helping largely, although individual patient’s end up disappointed or very very disappointed. Dan Riley MD Do you find primary care docs willing to prescribe for these patients? That is our primary problem. Roberta Goff MSN Ed, RN-BC, ACNS-BC, ONC While I agree with the sentiments of the last two posts, the underlying problem is much, much bigger than addiction. SAMSHA estimates that there are about 2M people addicted to opioids in the US. In contrast the IOM estimates that there are 100M with chronic non-cancer pain. The CNP problem is 50 fold larger than the addiction problem and yet most of the national dialog continues to focus on addiction. I understand the deadly nature of the disease but it is a symptom of something going on - suffering - that is much, much bigger. Until all prescribers begin to envision most all chronic non-cancer pain in working-aged adults as a largely central, rather than nociceptive, process I don't think we will move the needle. A new way of envisioning CNP - a brain condition akin to addiction -in working-aged adults is emerging from fMRI data. We all need to codify that and start talking about it - destigmatizing the concept of 'brain pain' or 'central sensitization - as soon as we can. 1. http://www.ncbi.nlm.nih.gov/pubmed/23574118 2. http://www.ncbi.nlm.nih.gov/pubmed/23574124 3. http://www.ncbi.nlm.nih.gov/pubmed/23983029 4. http://www.ncbi.nlm.nih.gov/pubmed/26266995 5. http://www.amazon.com/Brain-Adapting-Pain-Contribution-Neuroimaging-ebook/dp/B00YFOSVAI/ref=sr_1_1?ie=UTF8&qid=1454424421&sr=8-1&keywords=brain+and+pain+and+apkarian Paul C. Coelho, MD At one of the large hospitals in Ohio, they give monetary bonuses based on a % of good evaluations. If there are too many unfavorable evaluations the physician does not get the bonus and the rest of the physicians on staff do not get one either. So if the patient does not get opioids, antibiotics, lab tests or whatever their request, the person's physician and the entire group of physicians suffer. Try to practice good medicine with those rules! 2muellers@att.net I can't say I have ever seen data on this topic. It seems rather prejudicial and inflammatory. No reference was cited in the article.I am wondering if anyone has a reference or background for this statement in the attached JAMA editorial: "In many instances, doctors are fully aware that their patients are abusing these medications or diverting them to others for non-medical use, but they prescribe them anyway. " Michelle Witkop DNP, FNP-BC There is a way to refuse a patient's treatment recommendations without upsetting them. It's as simple as slowing down and looking the patient in the eye , even holding their hand , and tell them the reason for not getting antibiotics or a particular test. and that you feel that a different medication or test would be better. I often lower a patient's chronic pain medicine or refuse to prescribe antibiotics, and with a little explanation there's little difficulty. Gregory Denzel I am having a little trouble picking up on the thread of this conversation, in the middle-and might be responding out of context. I think Dr. Rich included me in the thread. Let me take this opportunity however to remind folks on this mailing that we are offering outpatient opioid detox/Buprenorphine inductions at Butler hospital, and can often assist the community when struggling with patients that are difficult to manage in relation to opioids. Alan Gordon MD Another editorial on the topic. *Attachment 2 Paul C. Coelho, MD There have been several great responses to this question. All have elements of good ways of responding to the patients who are seeking opioids for whatever reason. However, in my opinion, the use of patient feed-back tools and surveys should be put in an appropriate context. Unhappy, disgruntled, offended patients or patients whose needs were not met at a medical visit will be the most-likely to respond to such surveys. Their negative responses must be understood in context. Administrators need to be wise-enough to handle these responses appropriately and not base so much of their appraisal of a clinician's value or abilities on these surveys. The survey process has many limitations and flaws while at the same time, it can provide some useful feed-back. Patients who present to ED's in pain can be evaluated and the source of pain must be identified. This is essential. Once a diagnosis has been made, the choices of management should be multiple. This provides the clinician and patient an opportunity for some discussion. The clinician's experience, fatigue-level at the moment, resources available in the community and to that particular patient will further refine the realistic treatment options. If the diagnosis truly is "opioid deficit" and addiction/abuse vs physiologic dependency in a chronic pain patient is determined, then careful short-term management to prevent overdose and/or life-threatening complications of withdrawal will be important until admission to substance-abuse treatment can be arranged/agreed upon. Acute pain should take the clinician's diagnostic work-up in a different direction. Patients with physiologic-dependency to opioids will have the co-morbid condition of anxiety and episodic panic-disorder which will complicate any rational discussion in the ED. This too needs to be factored into the management of these patients. The issue of patient evaluations is an issue of educating administrators and the people who interpret such evaluations into aggregate for any individual clinician. I also see this as an opportunity for involving another clinician, or a social-worker for a second-opinion. It makes it less likely the patient's evaluation will single-out a clinician for a derogatory evaluation if there are two professionals who support a similar treatment plan and can make this a thoughtful, respectful discussion with the patient. I appreciate that all of the above gives me as well as other clinicians who are pressed for time and productivity palpitations, as this is not a quick solution. Dr. Lynda Williamson - A magazine article on NY Times posted by Paul C. Coelho, MD - Thank you, Dr. Coelho! We are passing along these articles to the Providence Hospital ER in question. I am also preparing an email concerning the negative impact of lack of dental services in ERs. Theresa E. Madden DDS MS PhD FACD Attachment 1-Why_Prescribers_Prescribe_Nejm_2012.pdf Attachment 2-PatientSatisfaction,PrescriptionDurgAbuse.pdf
  12. In training for my Suboxone certification I was told verbally that drug drug interactions were mostly clinically nonsignificant. It makes sense to me but I cannot find any data to support this. What is your opinion? Gregory Denzel Here you can find our guidance that discusses buprenorphine's interactions http://pcssmat.org/wp-content/uploads/2014/03/PCSSMAT-Clinically-Relevant-Drug-Interactions-Buprenorphine-or-Methadone-with-Other-Frequently-Prescribed-Drugs-9-24-101.pdf Adam Bisaga There is a nice PCSS guidance on this topic: http://pcssmat.org/wp-content/uploads/2014/03/PCSSMAT-Clinically-Relevant-D rug-Interactions-Buprenorphine-or-Methadone-with-Other-Frequently-Prescribed-Drugs-9-24-101.pdf There is some information regarding interactions between buprenorphine and psychiatric medications in another guidance: http://pcssmat.org/wp-content/uploads/2014/02/PCSS-MATGuidanceManagement-of-psychiatric-medications.Renner.pdf I have attached both guidances. In addition there are some PCSS webinars and modules that address these issues: http://pcssmat.org/event/methadone-and-buprenorphine-clinical-impact-of-drug-interactions/ http://pcssmat.org/benzodiazepines-and-buprenorphine-whats-the-problem/ *Attachment 1, Attachment 2 David Fiellin Yes I read that link before asking the question. I was hoping to get a little more personalized answer from a doctor familiar with the use of Suboxone. The presenters at the certification training specifically said it was not clinically significant. Gregory Denzel Agreed, there are few clinically significant interactions. We will work to get you connected to a mentoring physician familiar with buprenorphine through the PCSS-MAT. David Fiellin Given the frequency of co-occurring disorders, is anyone else concerned about all the "not studied in human pharmacokinectics studies" for psych meds? Thomas.Grinley@dhhs.state.nh.us A word of caution for new prescribers treating dual diagnosis addiction/pain patients. I'm a pain guy and I can't tell you how many patient intake questionnaires that I screen with allergies claimed to : Tramadol, NSAIDS, ASA, Butrans, Nycynta, Morphine, ... Claiming an 'allergy' buprenorphine can be perceived as an easy way to opt out of treatment with it in exchange for something with more euphoric effects. I've never seen a true allergy to it, or even a clear side-effect that I could unequivocally attribute to it. Paul C. Coelho, MD Attachment 1-PCSS-MATGuidanceManagement-of-psychiatric-medications.Renner.pdf Attachment 2-PCSSMAT-Clinically-Relevant-Drug-Interactions-Buprenorphine-or-Methadone-with-Other-Frequently-Prescribed-Drugs-9-24-101.pdf
  13. I am a DATA waivered physician and one of my patients was hospitalized for an unrelated medical reason by one of my colleagues last week. The patient was to be put started on buprenorphine while in the hospital, the medication was ordered and the inpatient teaching hospital pharmacist refused to dispense the medication to the patient, citing CFR 21 1306.07 (pasted below), and claiming that the hospital did not have authority to treat her opioid dependence. The patient became upset, understandably, and left the hospital, against medical advice. I believe that DATA waivered physicians are able to initiate buprenorphine at any time, and especially while the patients are in the hospital, and, furthermore, that they are able to initiate methadone maintenance during unrelated medical hospitalization, as long as arrangements are made for a certified methadone maintenance program to continue treatment after release from the hospital. Have any of you run into these issues and how would you suggest proceeding with my hospital pharmacist? I am thinking that if she is under this (presumably false) impression then perhaps many others are as well. Thanks a lot Josiah D. Rich, MD, MPH SAMHSA/CSAT is clear on this issue: http://buprenorphine.samhsa.gov/faq.html#A14 <10>Can physicians and other authorized hospital staff administer buprenorphine to a patient who is addicted to opioids but who is admitted to a hospital for a condition other than opioid addiction? Neither the Controlled Substances Act (as amended by the Drug Addiction Treatment Act of 2000) nor DEA implementing regulations (21 CFR 1306.07(c)) impose any limitations on a physician or other authorized hospital staff to maintain or detoxify a person with an opioid treatment drug like buprenorphine as an incidental adjunct to medical or surgical conditions other than opioid addiction. Thus, a patient with opioid addiction who is admitted to a hospital for a primary medical problem other than opioid addiction, e.g., myocardial infarction, may be administered opioid agonist medications (e.g., methadone, buprenorphine) to prevent opioid withdrawal that would complicate the primary medical problem. A DATA 2000 waiver is not required for practitioners in order to administer or dispense buprenorphine (or methadone) in this circumstance. It is good practice for the admitting physician to consult with the patient's addiction treatment provider, when possible, to obtain treatment history. David Fiellin Good morning, It has been my understanding that if the primary reason for admission is a medical or psychiatric reason and the secondary problem is dependence on opioids, the patient may be treated with methadone or buprenorphine to prevent withdrawal. We at UVM have many non waivered MDs who start buprenorphine and the hospital dispenses it. It is even more surprising that you as a DATA waived physician were unable to treat as you have prescribing authority for bup. The citation refers to NTPs which is not applicable in your case. Some hospitals have special waivers for dispensing methadone from the DEA which would allow it to be prescribed and dispensed in these circumstances. I have had my patients under identical situations admitted by non waivered MDs and they have been started or continued on buprenorphine Hope this helps Best, John Brooklyn, MD I had the same situation. The patient ended up having his own medication, prescribed by me, brought in and self administered. Nancy Blake This sounds like a lack of information at your particular facilities. I am a hospital pharmacist and have always dispensed buprenorphine or methadone for opioid-dependent patients when needed. Per SAMHSA’s buprenorphine FAQs (link below): <10>Can physicians and other authorized hospital staff administer buprenorphine to a patient who is addicted to opioids but who is admitted to a hospital for a condition other than opioid addiction? Neither the Controlled Substances Act (as amended by the Drug Addiction Treatment Act of 2000) nor DEA implementing regulations (21 CFR 1306.07(c)) impose any limitations on a physician or other authorized hospital staff to maintain or detoxify a person with an opioid treatment drug like buprenorphine as an incidental adjunct to medical or surgical conditions other than opioid addiction. Thus, a patient with opioid addiction who is admitted to a hospital for a primary medical problem other than opioid addiction, e.g., myocardial infarction, may be administered opioid agonist medications (e.g., methadone, buprenorphine) to prevent opioid withdrawal that would complicate the primary medical problem. A DATA 2000 waiver is not required for practitioners in order to administer or dispense buprenorphine (or methadone) in this circumstance. It is good practice for the admitting physician to consult with the patient's addiction treatment provider, when possible, to obtain treatment history. http://buprenorphine.samhsa.gov/faq.html#A8 I hope this helps! Traci M. Dutton, PharmD, BCPP, BCPS I have wondered who decides the reason for admission. At our hospital Emergency medicine admits to internal medicine. Often a patient will be admitted to the general medical hospital for ‘opioid addiction/intoxication/withdrawal’ with unstable vital signs. The admission H&P and daily notes by the primary service (medicine) have “opioid addiction/withdrawal” as the primary reason for hospitalization. Regards, Curtis McKnight, MD
  14. My health department's methadone program is negotiating with our local detention center about continuing methadone and buprenorphine treatment to our MAT clients who are incarcerated. We already perform that service for pregnant MAT clients who are incarcerated. The warden has expressed a concern about liability issue for the detention center on clients who are on work release, whose work duties involve driving or operating heavy machinery. While we routinely encourage clients on MAT to live normal lives, including driving and work, how can I address his liability concerns? A position statement from some authoritative organization would be helpful. Is there data on auto accidents for people taking methadone or buprenorphine? J. A. Cockey, MD, FACP Thanks for raising this question. Of course, it is extremely important to help dispel the terrible myths and stigma that our patients suffer from. Nothing combats stigma like proactively informing methadone patients that they can work as a commercial driver, or get a nursing or other professional license, while on methadone. I used to be unclear about how to counsel patients about this. (And I’m still a little unclear). We all need an authoritative answer; I’m very interested in hearing from others on this. I live in Maryland also; the Maryland CDL Manual (Commercial Drivers License) is at: http://www.mva.maryland.gov/_resources/docs/DL-151.pdf After looking through the whole thing; the only pertinent section, on page 2-40, is Section 2.22.2 – “Other Drugs:” “Laws . . . prohibit being under the influence of any “controlled substance,” . . . narcotics, or any other substance, which can make the driver unsafe. [which] could include a variety of prescription and cold medicines. . . . However, possession and use of a drug given to a driver by a doctor is permitted if the doctor informs the driver that it will not affect safe driving ability.” Apparently: not a problem. Also reassuring is the following, from the Handbook of Methadone Prescribing and Buprenorphine Therapy, Ricardo A. Cruciani, Helena Knotkova, editors, 2014, published by Springer. page 61: “Numerous studies have reported no differences between methadone-maintained individuals when compared to control subjects on psychomotor and cognitive performance tasks, while others employing a broader range of tests have found some performance decrements in methadone-maintained patients in comparison to former heroin abusers [11] and nondrug using controls [12]. However, as these impairments are frequently described relative to incompletely matched control groups (e.g. nondrug using controls), the observed effects cannot be directly attributed to methadone alone . . . [13]” [11] Gritz ER, et al. Physiological and psychological effects of methadone in man. Arch Gen Psychiatry. 1975; 32:237-42. [12] Mintzer MZ et al. Cognitive impairment in methadone maintenance patients. Drug Alcohol Depend. 2002; 67(1):41-51. [13] Darke S, et al. Cognitive imparment amount methadone maintenance patients Addiction. 2000;95(5):687-95. Joe Adams, M.D. SAMHSA covers some of this on page 5 of their document: http://www.samhsa.gov/sites/default/files/partnersforrecovery/docs/Know_Your_Rights_Brochure_0110.pdf Additional resources at: http://lac.org/wp-content/uploads/2014/12/mmt-memo_on_driving_and_psychomotor_studies.pdf Recent reviews at: http://www.ncbi.nlm.nih.gov/pubmed/24222013 http://www.ncbi.nlm.nih.gov/pubmed/23259516 David Fiellin In my state of NH, law enforcement are generally not concerned about persons driving while using buprenorphine or methadone therapeutically as dispensed or prescribed. They do raise concerns, however, about persons in MMT or on bup/nx driving when then are also identifies (on UDT) as using marijuana, alcohol, illicitly obtained sedatives etc. They have dozens of accident reports and results of roadside drug evaluations identifying impairment under such circumstances (their drug use by drug class recognition skills based on physical exam is more sophisticated than most physicians) that support their concerns… They have asked the State to consider a requirement that persons identified as using other (illicit or non-prescribed) drugs along with MMT or bup/nx be required to use public transportation or bring a driver. This is something we continue to discuss and I think it is not unreasonable, though of course it is can serve as a barrier to care especially in a rural state like ours.. At some point, however, I think the positive impact of MAT using a harm reduction model (i.e. Continuing medications when persons are using other substances) is overridden by the potential public health hazards of intoxication by additive substances (including a contribution of our treatment medications) I haven’t heard this discussed much in the addiction community as we work to retain patients in treatment. Interested in others thoughts. Thanks! Seddon R. Savage One could argue that a regulation preventing driving by people using illicit substances *who are in treatment* would increase the stigma of treatment, discourage people from seeking treatment (and making it impossible for some people to get treatment, as you pointed out), since it would not apply to people using illicit substances who are not in treatment. IMO, it should not be a broad prohibition that applies to anyone with any kind of positive drug screen. Joe Adams, M.D.
  15. Question: Is the method for determining the effective Suboxone dose, through induction, always reliable, including for patients with subjective symptoms of withdrawal (assuming they are telling the truth about their symptoms)? And does it matter how much withdrawal they are in during induction? This assumes they are taking the medicine correctly, and that adequate time has elapsed before evaluating each dose during induction (such as one hour between doses; can it be less than an hour?). At times I have carefully determined the correct dose through induction, but the patient returns one or more weeks later reporting that the dose doesn’t hold. In other words, is it possible that a careful induction process with a patient in withdrawal may determine an incorrect dose? I realize that other possibilities are that patients aren’t telling the truth, or aren’t taking / absorbing the medicine optimally. (I may not have instructed the patients carefully enough on how to use the strips). I’d like to be confident about this process in order to cut down on diversion which is rampant in my area. (I’m not talking about the phenomenon in which patients may be overly worried about normal body sensations, and misinterpret them as withdrawal symptoms). Thank You!!! Joseph Adams, M.D. In my experience and in a number of trials, optimal dosing to achieve abstinence can take weeks. There are two phenomenon that opioid agonist maintenance is designed to address: Cross-tolerance – the dose that prevents withdrawal and decreases craving. Narcotic blockade – the dose that blocks the effect of exogenous (non-MAT) opioids. It can take a while (not one or two days) to determine the optimal dose to address each of these independent phenomenon. Dose escalation in the first weeks to months of treatment is not unusual in most medical conditions, including opioid use disorder. The following reference may be useful: Buprenorphine maintenance and mu-opioid receptor availability in the treatment of opioid use disorder: implications for clinical use and policy. Greenwald MK, Comer SD, Fiellin DA. Drug Alcohol Depend. 2014 Nov 1;144:1-11. doi: 10.1016/j.drugalcdep.2014.07.035. Epub 2014 Aug 19. PMID: 25179217 David Fiellin One thing that is absent from DEA reports of diversion is tracking back the barcoded film packages to the pharmacy and patient with Suboxone strips. In addition to child safety this was to be a real help to determine if diverted film was “out the back door” of pharmacies and not yet prescribed. If diverted by RX recipients that is grounds for immediate d/c of bupe. We then offer them option of depot naltrexone in 2 weeks as the last alternative. Most have already rejected methadone maint. because of the daily admin. Interesting that I talked with a regional DEA Diversion manager and he was not aware of the barcoded tracking option! But they dislike the med because it is found so often with the dealers they bust. We use less strips overall because of the more economical generic SL tabs which vary in potency. Also is takes a while to reach steady state with bupe and 2-3 days observation is the just first stopping point. Whereas after a month of stabilization it can look different ; there are rapid and slow metabolizers and of course competitive induction/inhibition rates when combined with other meds. I cannot imagine how some practitioners just “phone it in” with inductions out in the community (as has been reported by pts. who failed and then came to the VA where we follow the TIPS 43 protocol.) We added a weekly peer support group in 2004 where newbies can be schooled by persons on the med much longer and can attest to the variable phases in the first 1-3 months (esp. with comorbid pain). It reduces their anxiety and increases their motivation to succeed as others have by example (as well as cut themselves off from their still using peers). The group started when the mandatory recovery activity participation could not be met by traditional step groups with an anti-MAT bias. However that rejection appears to be changing. I tell the patients that “MAT stabilizes your brain so you CAN do the work of recovery.” Otherwise the drop-out rate in the first month is substantial. Scott McNairy MD Our counselors do an excellent job of counting used and unused Suboxone wrappers at patient visits and actually note the LOT numbers on individual wrappers. We have actually called local pharmacies to determine what the average variance of lot numbers in an individual prescription is. Pharmacies generally tell us no more than 2-3 different lots are aggregated in a typical one month prescription. When we have patients bring in films with more than 3 lots (sometimes as much as 10 different lot numbers), this raises our suspicion of diversion. Frederick Michael Elliott, MD Since bup may take several days to reach steady state, what do you tell new patients about the duration of action? I believe this means that the duration may be less than 24 hours in the first several days. Is this true? And if so, is it a good idea to inform new patients about this? Usually I just reassure them that the medicine lasts at least 24 hours. Joe Adams, M.D. You raise some interesting points. In our MAT we require patients to bring in used wrappers and occasionally will get bar codes that have never been in our inventory. We do random recalls so they bring in used and unused strips . Get some various bar codes then because patients want to have the right number of wrappers. Odd that the DEA is not aware of this. We also d/c for diverted bup. We did use tabs but because of diversion only use strips for take homes. I concur about the “phone it in” and also the Sub Mills that have sprung up, have led to poor care and even worse outcomes. It would be a shame if buprenorphine would become restricted like methadone. Even less people could have access for substance use disorder treatment. Elizabeth Lottes Due to buprenorphine’s high affinity at the mu opioid receptor, plasma concentrations and receptor occupancy do not always correlate. Buprenrophine and its active metabolite norbuprenorphine can be active at receptors in the absence of a steady state. I find it helpful to inform patients that the duration of action is at least 24 hours. I try to do this in a way that mitigates against them taking the medication more frequently (not necessary). I believe taking the medication daily helps patients get away from the mindset that they were used to when using illicit opioids – needing to use “something” every 4-6 hours. Sublinqual buprenorphine when used for the treatment of opioid use disorder is a daily medication that patients can learn to trust to prevent opioid withdrawal. David Fiellin
  16. I would like to hear from providers on their preferred routine and dosing decisions for initiating Buprenorphine and follow up to maintenance dosing. Also, are providers offering weekly group sessions as a requirement for new patients until stabilization on maintenance? Are providers doing weekly UDS in office or outside labs for new patients? Please share your creative practice and monitoring of patients. Dr. Daggett We see them once a week for the first month. If they are compliant with counseling and have had no dirty UDS’s then go to q2 weeks for 1 month then to q1 month visits thereafter. If they show aberrancy, (ie dirty urine or fail to go to counseling, missed appointment etc) they get bumped back to q1week and have to earn their way back to q month. We do point of care UDS at each visit, which is much cheaper, and send out any unexpected results for confirmation. As far as dosing, most patients seem to end up at 16 mg a day, although there is some variation and we have folks on 2-16. Beth Freedman MD We give them a prescription for 2 days which they fill on the first day of induction. If they attend group the next day, they get a 6 day prescription. (Which is handy because the doctor, me, is in once a week). If they become fully compliant with groups, they start getting prescriptions once a week; eventually more if doing well. If they miss groups, they're demoted back to getting a prescription twice a week. ($1 copays with Medicaid). Joe Adams, M.D. I would like to add 2 comments to this email thread: OBOT with Buprenorphine allows physicians to individualize treatment and to have the ability to be flexible. There is no one way to treat all patients. The frequent prescriptions mentioned in the emails is only feasible with Medicaid, since commercial insurance co-pays and prior authorizations would not allow such a paradigm. Some patients are more stable than others, some patients have significant others who can help secure, and in some cases dispense medication. In those patients who are employed, we don’t want to jeopardize their employment with overly restrictive “rules” and “regulations.” This has always been the problem in MMTPS/OTPs dispensing methadone. Some patients do remarkably well with the medication, and brief physician medical visits, and with either limited or no formal counseling, outside of the medical management. We should use accurate medical terminology and vocabulary, and avoid slang and pejorative terms. Urines are best described as positive for or negative for x, y, or z. We should encourage patients, significant others, counselors, and other providers to avoid terms such as “clean,” or “dirty” urines, junkies, pothead, etc. Edwin A. Salsitz, M.D., FASAM I totally agree with the idea that patients should be individualized, as far as how often they are seen, how often they may see counselors, or have groups, etc. In Oklahoma, even with Medicaid, it is not feasible to do what is described. Our building pharmacy will do this when necessary, but as far as Medicaid is concerned, if I write one week, and they fill it, that is all they get paid for, during the month. My experience with commercial insurance is the same. Having been a buprenorphine provider from the outset, I do have somewhat of a system, but different patient treatment plans may look different than others. I do occasionally see people weekly or even more often, but not everyone. I do use positive and negative urines, to guide some of my follow ups, as well as other factors. It is my opinion, as Dr. Salsitz suggests, that we have to be careful with over restricting folks who are trying to get their life back, but have good clinical reasoning, for when we do use a more restrictive approach. This, to me, is the joy of buprenorphine treatment. Yarborough, William H Dr. Salsitz, Thank you for your call for appropriate language! To all, please see the editorial in Substance Abuse journal on person-centered language. http://www.tandfonline.com/doi/abs/10.1080/08897077.2014.930372 Please share this with others. The words we use matter. Deborah S. Finnell, DNS, PMHNP-BC, CARN-AP, FAAN GREAT points. For both UDS and Prescription Monitoring Program reports, I like to avoid pejorative language. I use the term "unexpected results". Mary G. McMasters, MD, FASAM Does anyone have experience using buprenorphine for pain in individuals without substance use disorders? If so, when, at what doses? What has been your experience with it? Lora Jasman, MD I have used Butrans quite a bit. The dosing is significantly less than what we use for addiction treatment. The largest patch is 20 mcg. Each patch lasts 7 days. Basically if your patient requires 80 mg Morphine Equiv or less this is a viable treatment. For individuals without substance abuse disorders, I would be cautious about using Buep before trying other substances mostly because of the high potency of the medication. Hope this helps, Eugene Wang, D.O. There is a PCSS-O guidance on this topic: The Off-Label Use of Sublingual Buprenorphine and Buprenorphine/Naloxone for Pain http://pcssmat.org/wp-content/uploads/2014/02/PCSS-MATGuidanceOff-label-bup-for-pain.Gordon.pdf David Fiellin The last time I worked with buprenorphine was 2012 and I recall on the day of induction we would dose with 2/0.5, assess for 2 hours and then bump up to 4/1 on the same day if still experiencing withdrawal symptoms. We would then bring them back the next day for further adjustment which was most often necessary. I recall that within the 1st 24 hours we would bring them up to the dose that controls the withdrawal symptoms and then reassess weekly after that. I realize that some providers are more conservative and some more aggressive but would like to hear feedback on this. Dr. Daggett It is best to use Butrans patch if you wish to use buprenorphine for pain. Most insurance companies when I call for PA (prior authorization) consider that off label prescribing and will not cover. Suspect most physicians if the are getting it covered are using Opioid Dependency codes and not a pain or other ICD-9 codes. I work in Texas. Kim Henderson, M.D. Having done this several different ways, it seems to me that giving them just enough to stop withdrawal as an outpatient, and seeing them weekly, might put some folks at increased risk. I have done the lowest effective dose thing, while patients are in supervised residential treatment, but have not had good experiences with it, as an outpatient through my office. I guess I don't understand the physiology of the low dose approach, and why one would adopt that. I would be interested in feedback. Overall in my panel my dosages are not high, with stable patients, even though I may have started out some of them with "higher" dosages. I have, in the last few years, h adopted the philosophy of treating a predictably fatal disease, with whatever tools I might legally have available, and then bridge them to lower dose maintenance and perhaps abstinence over a period of months to years. This is a chronic disease, and should be treated as such. Interesting to know the philosophy and rationalization of other providers. William Yarborough MD, FACP I have curiously had several patient with RA referred to me, on buprenorphine for pain in their joints, not responsive to other opioids. Not for sure if there is some specific issue with RA, but seemed interesting to me. I have also had a patient with "interstitial cystitis" that only responded to buprenorphine. Not had any real problems getting insurance to cover the patch. I have been able to get PAs for subutex for occasional breakthrough on a couple of these RA patients, and a couple that use subutex, only for pain. It was a bit of a hassle, and had to document failure of other drugs, or intolerance of other drugs. William Yarborough MD, FACP "Although buprenorphine does have a favorable safety effect profile and a ceiling on its agonist effects." IMO there is a role for SL buprenorphine in the treatment of high-dose, 'lost generation', CNP patients with no history of addiction or aberrant behavior. Some - many - of these patients struggle with a protracted taper and conversion to buprenorphine for 'pain' is middle ground harm reduction tactic that I sometimes use. Pain Med. 2014 Dec;15(12):2087-94. doi: 10.1111/pme.12520. Epub 2014 Sep 12. Conversion from high-dose full-opioid agonists to sublingual buprenorphine reduces pain scores and improves quality of life for chronic pain patients. Daitch D1, Daitch J, Novinson D, Frey M, Mitnick C, Pergolizzi J Jr. Author information Abstract oBJECTIVE: This study aims to determine the effectiveness of converting patients from high doses of full-opioid agonists to sublingual (SL) buprenorphine. DESIGN: An observational report of outcomes assessment. SETTING: An interventional pain management practice setting in the United States. SUBJECTS: Thirty-five chronic pain patients (age 24-66) were previously treated with high-dose opioid-agonist drugs and converted to SL buprenorphine. Patients' daily morphine equivalents ranged from 200 mg to 1,370 mg preconversion, with a mean daily dose of 550 mg. METHODS: A retrospective chart analysis examined numerical pain levels and quality of life scores before and 2 months after conversion to SL buprenorphine. RESULTS: After continuation of SL buprenorphine therapy for 2 months, the mean pain score decreased from 7.2 to 3.5 (P < 0.001), with 34 of the 35 patients examined reporting a decrease in pain. This pain score decrease was robust with regard to initial pain score and preconversion morphine equivalent dosage. Quality of life scores improved from 6.1 to 7.1 (P = 0.005). CONCLUSION: Average pain scores decreased from 7.2 to 3.5, and quality of life scores increased from 6.1 to 7.1 for 35 patients converted from high-dose full-opioid agonists to SL buprenorphine therapy for more than 60 days. Clinicians should consider buprenorphine SL conversion for all patients on high-dose opioids, particularly patients with severe pain (7-10) unrelieved by their current opioid regimen or patients for whom the clinician does not feel comfortable prescribing high-dose opioids. Paul C. Coelho, MD Re: your discussion of “off label use” SL product related to treatment of CP patients. DSM5 Opioid Use Disorder, mild-mod. could be applied to pts with chronic pain who manifest drug craving, tolerance and withdrawal, taken in larger amts. or over a longer period “than was intended”, persistent desire or unsuccessful efforts to cut down or control opioid use. Scott McNairy Yes, a VERY gray area. IME fear of withdrawal perpetuates use in CNP, not continued pain. But, regardless of what you call it - dual dx vs pain - Buprenorphine is a safer choice. 1. Arch Intern Med. 2012 Sep 24;172(17):1342-3. doi: 10.1001/archinternmed.2012.3212. Opioid Dependence vs Addiction: A Distinction Without a Difference? Ballantyne JC, Sullivan MD, Kolodny A. 2. J Subst Abuse Treat. 2014 Aug;47(2):140-5. doi: 10.1016/j.jsat.2014.03.004. Epub 2014 Apr 4. Reasons for opioid use among patients with dependence on prescription opioids: the role of chronic pain. Weiss RD1, Potter JS2, Griffin ML3, McHugh RK3, Haller D4, Jacobs P5, Gardin J 2nd6, Fischer D7, Rosen KD8. Author information Abstract The number of individuals seeking treatment for prescription opioid dependence has increased dramatically, fostering a need for research on this population. The aim of this study was to examine reasons for prescription opioid use among 653 participants with and without chronic pain, enrolled in the Prescription Opioid Addiction Treatment Study, a randomized controlled trial of treatment for prescription opioid dependence. Participants identified initial and current reasons for opioid use. Participants with chronic pain were more likely to report pain as their primary initial reason for use; avoiding withdrawal was rated as the most important reason for current use in both groups. Participants with chronic pain rated using opioids to cope with physical pain as more important, and using opioids in response to social interactions and craving as less important, than those without chronic pain. Results highlight the importance of physical pain as a reason for opioid use among patients with chronic pain. Paul C. Coelho, MD This letter clarifies the legality of using buprenorphine for chronic pain. You would use your regular DEA number rather than the X number. *Attachment 1 Joshua Bloom Don’t we have enough experience with opioids and chronic pain? Why create another mess by using buprenorphine for pain? Someday, we all are going to be “weed the people” any way! Why add another substance which won’t work in the long run. Benzos don’t work for anxiety and alcohol does not work for sleep. Dr. Chittaranjan Shukla I couldn't agree more. But, my comments were specific to patients with CNP who have been managed on high dose opioids for years without aberrant behavior. I did not start the opioids for any of these people but what we now know about dose and risk means something must change. Tapers are possible, I have to do them and support the – typically unwilling- patients through them. Trust me they aren't fun. In this very, very limited circumstance conversion to buprenophine can sometimes make everyone's life safer and simpler. Paul C. Coelho, MD Thank you for responding. And, Suboxone will be easier to taper due to long half-life and after pt had some “Rx” in him! Dr. Chittaranjan Shukla Attachment 1-DEA_Bup_for_pain_letter.pdf
  17. Does anyone have experience with every other day Suboxone dosing? Are there problems with withdrawal symptoms between doses? Is the initiation process different? Overall gestalt about potential benefits vs. difficulties in dosing this way? Are there any good resources about this you could point me to? John Muench This can be useful in a variety of situations, including the use of a buprenorphine mono product and/or concerns regarding diversion. This is addressed in TIP #40 (page 56-57) http://www.ncbi.nlm.nih.gov/books/NBK64245/ Typically no real issues with withdrawal in between. Initiation process is similar and then convert over to QOD once stabilized. Benefits: Can decrease risk of diversion, useful in directly observed therapy. Difficulties: Patients can forget to take their meds, perhaps more opioid positive urines, may be problematic to double up on dosing days in patients who require high doses (e.g. 24 mg of bup). References below: Counseling and directly observed medication for primary care buprenorphine maintenance: a pilot study. Moore BA, Barry DT, Sullivan LE, O?connor PG, Cutter CJ, Schottenfeld RS, Fiellin DA. J Addict Med. 2012 Sep;6(3):205-11. doi: 10.1097/ADM.0b013e3182596492. PMID: 22614936 Thrice-weekly supervised dosing with the combination buprenorphine-naloxone tablet is preferred to daily supervised dosing by opioid-dependent humans. Amass L, Kamien JB, Mikulich SK. Drug Alcohol Depend. 2001 Jan 1;61(2):173-81. PMID: 11137282 Efficacy of daily and alternate-day dosing regimens with the combination buprenorphine-naloxone tablet. Amass L, Kamien JB, Mikulich SK. Drug Alcohol Depend. 2000 Feb 1;58(1-2):143-52. PMID: 10669065 Alternate-day buprenorphine dosing is preferred to daily dosing by opioid-dependent humans. Amass L, Bickel WK, Crean JP, Blake J, Higgins ST. Psychopharmacology (Berl). 1998 Apr;136(3):217-25. PMID: 9566806 Alternate-day dosing during buprenorphine treatment of opioid dependence. Amass L, Bickel WK, Higgins ST, Badger GJ. Life Sci. 1994;54(17):1215-28. PMID: 8164503 David Fiellin I would be interested if there are any resources or studies out there. I have several patients who take their buprenorphine like this. They are usually folks that are doing well, and have been on the med for a while, and want to eventually get off. I also use the QOD thing if I am doing a slow taper, usually at the patients request. It has a long half life, and I have noted that usually patients can be off for a day or two, before they have much withdrawal. The other question might be, what if any advantage there might be in using bupe this way. William Yarborough MD, FACP Thanks to Dr Fiellin for referencing the articles of studies that were done at the University of Vermont. We have a long history of using buprenorphine in this way of alternate day double dosing and triple dosing. The OTP clinics in Vermont all prescribe buprenorphine and we regularly use this method to reduce daily travel to the clinic early in treatment and to reduce diversion risk. Our protocol starts people on buprenorphine daily until they reach a stable dose that lasts 24 hours. We then start with double dosing on Monday and Wednesday and triple dosing on Fridays. We have people who are on doses over 16 mg and we dose them accordingly. We have administered doses of 40 mg at a time for double dosers. If it appears that someone on double dosing feels that the dose does not last 48 hours we assess them on the following day with a COWS/CINA and occasionally adjust upward by a small amount and rechallenge them at the higher dose. We have found wide acceptance for this except for those individuals who feel odd not taking something daily and we work with them on this area with supportive means. The advantages are also seen in an outpatient setting were a person may need to go to a pharmacy or come to the office for directly observed therapy in reducing travel. Urine drug test results are not different in the daily vs less than daily groups and counseling compliance is about equal. We do not use it in pregnancy as there are no studies that we are aware of for this. In addition to the studies cited are these which discuss longer durations of dosing: Addiction. 2000 Jul;95(7):1069-77. A comparison of four buprenorphine dosing regimens using open-dosing procedures: is twice-weekly dosing possible? Petry NM1, Bickel WK, Badger GJ. Addiction. 2001 Jun;96(6):823-34. Examining the limits of the buprenorphine interdosing interval: daily, every-third-day and every-fifth-day dosing regimens. Petry NM1, Bickel WK, Badger GJ. John Brooklyn, MD
  18. I have a few patients who have been very stable in their sobriety and are motivated to wean off completely but just can't come off due to sx of extreme fatigue or abdominal cramps. Any advice out there beyond just going very slowly? lindasuehermans@gmail.com This is a great convo to get going. My understanding is whether the pt is taking 1 mg or 16mg and tapers, that final termination is equally uncomfortable as they detox. Jan Kline I'm fascinated by Ockert approach-but haven't tried it Ockert et al performed an open-label outpatient opioid detoxification study in 223 heroin dependent patients. That protocol included a titration of clonidine, lorazepam, trazodone and methylphenidate. In general patients were opioid abstinent for seven days and free of significant withdrawal symptoms when beginning oral naltrexone. Approximately 77% of patients completed outpatient detoxification with 61% successfully completing induction to oral naltrexone. The addition of stimulants reportedly improved patient sedation and reduced the incidence of hypotension. Patient selection criteria that were associated with the best success included social support, employee assistance programs referral, private insurance or self a funding source, and full-time employment. This study appears to be the most relevant in terms of offering outpatient treatment which is more available and cost-effective. Ockert also starts to explore predictors of successful outcome and alternative ancillary medications targeting other symptoms such as sedation and hypotension with short-term use of stimulants. AGordon@butler.org My experience with this is variable, much like detox from other substances. It does seem, though, that last milligram can be the toughest for many. I haven't seen much abdominal cramping and extreme fatigue, just patients complaining of anxiety and a craving like feeling. On the other hand, I have seen some folks hop off at 2mg without much of an issue, after a slow taper. In general tapering down to 6-8mg seems pretty easy for most, and then it gets harder, so I tend to slow down. I have on occasion, given people a little clonidine, and even something to sleep for a couple of days, only. Not for sure how much it helped, though. I had one guy that went down to a half a milligram, and had trouble, and wanted to go back on. He has now decided to take 2 mg a day indefinitely. He is a very successful individual that didn't want to take chances. Sometimes this variability amongst patients is what makes being a doctor interesting. William-Yarborough@ouhsc.edu Most patients starting treatment with buprenorphine expect to stop taking it at some point. Noticing benefits of treatment, some decide to remain on it long term but many would like to stop it and initiate gradual taper.The majority of patients will find the last stage of discontinuation most difficult. This is often confusing to them, and to clinicians, as they found gradual decrease from the initial 16-24 mg dose to 2-4 mg dose relatively easy (if done over extended period of time). There is also a perception that over time the taper should become easier, in line with the extended duration of abstinence. However, the physiological response that occurs when dose is changed from 2mg to 0mg is probably greater than at any other time during the taper, even with more substantial dose reductions (in mg/time). Also, with the extended abstinence, it has been a long time since patients had to deal with physical discomfort associated with opioid withdrawal, so their tolerance for distress has diminished. Psychoeducation plays an essential role in this final stage of taper. I find it better to conceptualize the last stage of treatment as ³detoxification² rather than ³continuing taper² as the physiology underlying both phenomena are so different. Patients, and physicians, need to prepare for ³detoxification² off buprenorphine as being distinctly different from what they experienced so far during treatment and requiring different approach. This include adjunctive medications targeting emerging symptoms (anxiety, restlessness, insomnia, low energy, GI distress), behavioral strategies to deal with symptoms, and time away from usual demands of life. This process is even more difficult in patients with co-occurring psychiatric disorders. At times even brief inpatient stay may be needed to expedite and successfully complete the process. However, the risk of relapse to illicit opioids is the greatest on treatment discontinuation therefore a worthwhile strategy is to transition from buprenorphine onto naltrexone and continue on naltrexone for several months before stopping it. This will not only protect against relapse/overdose but may also accelerate the transition and shorten the duration of post-acute withdrawal and he final taper off naltrexone is not associated with any physical changes. Finally, some patients will not be able to tolerate transition off buprenorphine and will prefer to remain on a low (2 mg) dose indefinitely, minimizing adverse effects but preserving benefits of this treatment. Adam Bisaga The Ockert detox may work for weaning patients who are simply physically dependent, but I wouldn't want to use it in patients who are also Addicted. Addiction= loss of control. Handing a patient with Addiction MORE psychoactive medications, methylphenidate and lorazepam, is dangerous because addiction is not substance specific (they'll abuse any psychoactive med) and giving them BNZs, when combined with their substance of choice, opiates, is synergistic for respiratory depression. Sounds dangerous to me. Mary G. McMasters, MD, FASAM I get patients down to 0.5 mg/day, for 2-3 weeks, then tell them to take 0.5 mg a day IF AND ONLY IF symptoms kick in more than they can tolerate. They end up doing that about every other day for a week and then every 3 days, then it's over. I found this last stage of PRN works very well and patients feel like they are not left with nothing. Nancy Blake Low dose Baclofen for the muscle soreness and cramps. coffee and Folbee (B complex Vitamins) to combat the fatigue. Clonidine 0.1-0.2 mg hs helps with withdrawal associated insomnia. Wayne Sampson, MD. Regarding "jumping off" 1-2 mg: in a forum I cannot recall, I recently noted that 1 mg filled 40% of mu opi receptors. If true, this perfectly explains the difficulty. In a 2000 study in Neuropsychopharmacology, liquid BUP 2 mg occupied 40-50% roughly, whereas 16 mg occupied 85-95 % roughly. So very low dose tapers are probably needed for comfort/function. Regarding detox, the non-opioid protocol from Swedish Addiction Recovery Services in Seattle is available as a PDF file; was presented in ASAM poster session ?2013?? It uses tizanidine, hydroxyzine and gabapentin and had quite reasonable patient satisfaction scores. Especially useful for folks with CJ involvement or transitioning to naltrexone. David Battista MD former ASAM 1994-2014 batt590@hotmail.com Lethargy, dysphoria, and various mild withdrawal symptoms are common with the reductions below 2 and especially below 1mg daily. I have slowed reductions by using 25% to 50% reductions in dose at 1 month interval. Examples are 1/4 strip of Suboxone 2/.5, then 1/4 and 1/8 on alternate days, then 1/8 daily and so on. For those cases very sensitive to these reductions, slow it even more. I have a couple people now on 1/16 strip every other day. Think about the known structure and neural pathway changes that occur with addiction and that these changes of receptors and neuronal connections are epigenetic changes as adaptations to overactive neuronal activity. The genes that were turned on and the proteins that up or down regulated need enough time in the new environment to revert to the natural state as best possible. Motivation to come off the med and a collaborative relationship are essential. Much preparation is needed to get through anticipatory anxiety from the repeated trauma of past withdrawals. The can also be true conditioned responses by which a symptoms or just the change in routine acts like Pavlov's bell and triggers actual physiologic withdrawal symptoms. Gary Horwitz I agree that in principle, prescribing controlled substances to know "substance abusers” is problematic and should be minimized. On the other hand, controlled substances are among most effective medications we have to treat addictions (e.g., methadone). Benzodiazepines are gold standard to minimize severity of alcohol withdrawal and similarly can be useful in opioid withdrawal. Medications given briefly under close monitoring, like proposed by Ockert or others (Sigmon et al., 2012,http://www.ncbi.nlm.nih.gov/pubmed/22404717) can be very useful and rarely become problematic. Adam Bisaga MD
  19. Had a patient that developed respiratory depression after switching from buprenorphine to methadone. 8 mg TID buprenorphine, to methadone 10 mg TID. I am interested in how to factor the conversion of buprenorphine to methadone-the fact that buprenorphine has a much shorter half-life, but is much more potent seems that it could lead to sudden sedation when the last buprenorphine dose wears off and methadone then becomes more potent. I would appreciate any thoughts Alan Gordon Consider underlying sleep apnea. 2muellers@att.net Alan: fwiw, no direct conversion I know of. I wonder, though, if pt took all 3 every day, or if had sleep apnea/severe obesity, or baclofen or Soma use. That said, I think bup half life may be the longer of the 2, since Q48 hr directly observed dosing has been found effective, and MTDN is daily ( LAAM was Q48 hr ). Certainly, soon after last bup it wouls be blocking MTDN, with blocking decaying as time went on. Inter-patient variability of MTDN metabolism is legendary, but 10 mg TID doesn't sound excessive, and is of course the max first dose in OTP +/- 10 mg more later. In hindsight, 5 TID may've been better. Steady-state accumulation has been reported to usually occur in 5-10 days, with 12 days as outlier in at least 1 report. Hope that helps, Dave Battista MD, med director OTP in Las Cruces, NM, expired ASAM after 1994-2014 certification... batt590@hotmail.com I assume you were dosing this way for pain. Do you get push back from payors? Paul C. Coelho, MD Yes-dual diagnosis, opioid dependence, chronic pain-methadone focused on pain, naturally buprenorphine covers both to some extent. No pushback from payors. This patient was young, using high doses of narcotics prior to admission, so not naïve, healthy and thin, note sleep apnea suspected Alan Gordon My first thought when I hear about respiratory depression is what else was in the patient's system at the time? Benzos? ETOH??? Mary G. McMasters, MD, FASAM I'd to know the group's thoughts on buprenorphine and respiratory suppression. I'm in the 'pain' rather than 'addiction' world and a number of states are adopting a dose ceiling of 120MED for chronic non-cancer pain. Generally speaking I think this is a good thing. However, since the biggest risk with increasing dose with full mu agonists is respiratory suppression I'm wondering if this guideline should apply to Buprenorphine with a standard conversion of 30:1. Is it fair to say that an 8/2 Suboxone film (240MED) has the equivalent effect on suppressing respiration as 240MED of a full mu agonist or is the analgesic conversion uncoupled from the respiratory suppression curve for Buprenorphine. I have a handful of complex pain patients that I managed off label with Suboxone. Most of these exceed the 120MED recommendations and yet I feel this is still a safer option with respect to respiratory suppression. Paul C. Coelho, MD Those conversions are based upon parenteral dosing with buprenorphine I suspect not the sublingual doses. This same problem of ratios between methadone and MEQ depend upon which reference textbook you read. Our VA pharmD use 8:1 which is a max dose of only 15mg in conversion from 120mg MS or 5mg tid. While that may be “safe” not clear it is effective for pain mgmt. as tolerance develops. However Qtc problems have shifted the focus of safety. Likewise bupe to methadone is about 24mg = 60mg or 2 to 5 and is far safer as far as Qtc. Most PCP are not comfortable with greater than methadone 10mg tid for pain. Which again = 240 MEQ similar to buprenorphine and exceeds the safety guidelines. Scott McNairy, MD (Attachment) I believe dose equivalencies for buprenorphine to MEQs are problematic AND you are correct, the risk of respiratory suppression is significantly lower with the partial agonist buprenorphine. In fact, w/o adding alcohol, benzo’s etc. even in overdose respiratory rate is said not to drop below 10/min with bup alone. In contrast, a limit of 8/2 bup/nal would below the usual effective dose for this medication (in my experience about 16 mg bup). Kevin Sevarino
  20. "Is it possible for patients to be rapid metabolizers of buprenorphine similar to rapid methadone metabolizer and how could this be documented. P&T levels?? Also how do others evaluate possible diversion with buprenorphine?" Holy Johnson Off the top of my head: It is possible to be a rapid metabolizer, but this appears to be relevant to the pain relieving qualities of buprenorphine, not the anti-craving properties. 96% of brain receptors are occupied at 16mg per day, so for addiction tx, it isn't useful to go above that dose. Genetic typing would probably be more useful than checking a peak and trough. (IntegralLabs does them.) The new Bup REMS doesn't advise going above 16mg per day in any case and feels that doses above 16mg per day are diversion. However, I'll ask around. Hope all is well with you! Mary Mc There is a fair amount of inter-indvidual variation in plasma buprenorphine levels that does not reflect activity at the mu opioid receptor. Buprenorphine has a high binding affinity at the opioid receptor such that plasma levels to not always accurately effect what is going on in the brain. Peak and trough levels are not currently recommended. Suggested references: The clinical pharmacology of buprenorphine: extrapolating from the laboratory to the clinic. . 2003 May 21;70(2 Suppl):S13-27. Review.Drug Alcohol DependWalsh SL, Eissenberg T. PMID: 12738347 Buprenorphine maintenance and mu-opioid receptor availability in the treatment of opioid use disorder: implications for clinical use and policy. Greenwald MK, Comer SD, Fiellin DA. Drug Alcohol Depend. 2014 Nov 1;144:1-11. doi: 10.1016/j.drugalcdep.2014.07.035. Epub 2014 Aug 19. 25179217 PMID: Pharmacokinetics of the combination tablet of buprenorphine and naloxone. Chiang. 2003 May 21;70(2 Suppl):S39-47. Review.Drug Alcohol Depend CN, Hawks RL. 12738349 PMID: Buprenorphine: clinical pharmacokinetics in the treatment of opioid dependence. Elkader A, Sproule B. Clin Pharmacokinet;44(7):661-80. Review.2005. PMID: 15966752 David Fiellin In my experience patients with alarming 'low levels' are usually taking much less of the drug than what's prescribed. The typical patient will vehemently deny this but more than likely one day you are going to find that patient without the metabolite Norbuprenorphine, and low or high levels of Buprenorphine, suggestive of spiking the urine sample. Diversion is nearly impossible to preventl. There is no fool proof way to prevent this. At best you are aiming to reduce the incidence of this. Wayne Sampson, M.D. Dr Sampson – how do you usually handle those cases? If the patient is denying it ….can turn into quite an argument – I see this with opiates prescribed for pain where it’s in high amount in the urine but no metabolites… Gayle Newshan, PhD, NP What lab provides levels of buprenorphine? Our lab only tests for presence of bup and norbup after a certain cutoff in GC. Elizabeth Lottes I agree with Wayne however there are instances where unusual ratios of Buprenorphine and norbuprenorphine May be attributed to either rapid or poor metabolism CYP 3A4. cherndon12@gmail.com I usually hold firm to the urine confirmation test results. Basically, I say; "I know what you are saying but I have to be guided by the results of the urine test." 75 % of the patients will stick with their story line, the rest will break down and tell you what really happened. Dr. Wayne A. Sampson That would be demonstrated by consistently similar findings with every UDS (unusual rations related to metabolism). Jan Kline, MA, BSN
  21. New question for PCSS-O Listserv: How do you handle alcohol treatment at the same time as giving Buprenorphine? Info@PCSS-O.org There are 3 FDA approved pharmacotherapies for alcohol use disorder – Disulfiram, acamprosate, and naltrexone (oral and injectable). The only one(s) that would be contraindicated in patients receiving buprenorphine would be the naltrexone formulations. A variety of counseling strategies are efficacious for patients with alcohol use disorder. None of those would be contraindicated in patients receiving buprenorphine. Some potentially useful resources: http://pubs.niaaa.nih.gov/publications/Treatment/treatment.htm http://www.ncbi.nlm.nih.gov/books/NBK64041/ David Fiellin
  22. 1.) Has anyone seen a nor-buprenorphine conc. of > 2,500 ng/ml? 2.) What interpretation would you give to a patient with opioid use disorder who has intermittently used illicitly obtained buprenorphine (Suboxone), and gives an unwitnessed urine specimen that come back with quantitative confirmation of > 2,500 ng/ml buprenorphine and > 2,500 ng/ml nor-buprenorphine? The lab pathologist seems to think this is not very uncommon. I would appreciate others’ opinions. Thank you. Dave Simon, M.D., J.D. Be sure you are speaking with toxicologist fully familiar with the lab and tests and equipment being used and that the confirmation was done with gas or liquid mass-spectrometry. Are there any adulterants? Sp.gr appropriate? Creatinine appropropriate? Dr. Lynda Williamson It is consistent with Buprenorphine ingestion (and metabolism to nor-bup). I wouldn't put too much stake in the concentration because there are many variables that impact it and currently we aren't able to correlate it to dose. Joanna Starre Joanna, what about IV administration of bup4:nx1 ? Dave Simon Classification: UNCLASSIFIED Caveats: NONE Should be GCMSMS or LCMSMS as tandem mass spectrometry is the standard. Anthony Dekker David and others— I reached out to Ted Shuts about this, the toxicologist who writes the Medical Review Officer Handbook and knows a lot about urine drug testing. Below is his response. “Hi Joanna You have a tough question to track down in the literature. However, in 2010 a paper was published on urine levels of drugs in pain patients. The paper is titled: Urine drug testing of chronic pain patients. III. Normetabolites as biomarkers of synthetic opioid use. J Anal Toxicol. 2010 Oct;34(8):444-9. In that paper the authors report that after looking at 11,000 urine specimens they found about 600 positive for buprenorphine. They reported the average concentration as 381.2 ± 208.9 ng/mL. The median was 48.8 ng/mL and the range was from 1.0–116,990 ng/ml. The nor-buprenorphine results were similar in terms of mean and narrower in terms of range. The mean was 277.6 ± 13.9. The average was 156.3 and the range for the nor metabolite was 2.6–3026. Your results are clearly on the high end of the bell curve. This is a free article on the Journal of Analytical Toxicology web site. I would recommend getting a pdf copy of the paper. There is more information on oral fluid tests and buprenorphine levels and I tend to recommend oral fluid tests for many of these drugs. You may also want to look at panel of benzos for this patient. I have recently been told that the benzos remove the agonist ceiling for bup. Hope this is helpful. Ted Shults” Joanna Starre Thank you so much, Joanna. That was great investigative work. I also did a cursory literature review that supports Joanna, below. My conclusion is that if a patient has a urine tox screen of >2,500 ng/ml of both bup and norbup then something is askance. (Yes, this was typical quantitative confirmatory technology using GS or LC w MS). Dave Simon
  23. I just heard from a prison guard that two of their major drugs being sold in prison are heroin and suboxone. The 8mg suboxone film which is divided into pieces and is taken iv. I would have thought the naltrexone would have blocked the action but at $40 per hit, I doubt it. There are at least 4 hits per 8mg . Anyone else had these issues in their community? There was an article in the NY times about this problem also. Louise I. Buhrmann, MD, PA Have not heard the specifics of this problem, but it is known the naloxone in the bup/naloxone combination does not prevent IV abuse on those dependent on the combination. The naloxone would have more effect on someone dependent non full agonists but again, street addicts tell me it works just fine IV in a pinch. Unfortunately I am also hearing about this in VA. Mary G. McMasters, MD, FASAM I am gathering that the affinity for the mu receptor is much greater for buprenorphine than naloxone (as well as the retention) so the partial agonist is not displaced by the antagonist component. The inherent protective effect seems to be if taken with full agonist opioids on board; then w/d is precipitated. But MARKETING CLAIMS the IV combination produced only withdrawal effects may have been over-sold. BTW given a parenteral opioid equivalency of 10mg morphine = 0.4mg bupe. Then 2mg IV bupe (1/4 strip) would equal 50mg of morphine. Certainly enough to get a rush. How easy is it to liquefy? Still would not want to mix bupe and heroin together. Scott McNairy I have also come across a number of clients over the years who inject the combination buprenorphine/naloxone product. It seems that it does produce euphoria. So long as they are not using it on top of another opioid, they do not note any precipitated withdrawal. - Most of them only make that mistake once. Andrew Putney, MD I have heard of opiate naive people using suboxone orally, IV and snorting. They see it as a "safe" way to try opiates. It is especially prevalent in wealthier areas around me such as Charlottesville both because the 8/2mg suboxone strips are expensive and because this population is more likely to "self educate" on the internet. I have also heard of suboxone film going into the jails/prisons because it can be concealed between the pages of a book, etc. Mary Mc I don’t have much familiarity with what goes on the prison systems, around here. That to some extent is a special population and culture, and based on whatever might be available. I have spoken with several folks who have injected Suboxone, and also Subutex, and felt like there was little difference. That is likely an affinity issue, I suspect, between the Bup and the Naloxone. I have yet to see, though, a person who preferentially wants to inject buprenorphine over other available drugs, by a long shot. Just as there is a ceiling effect to the SL form, there would be a relative ceiling effect to the IV form, as well. Most of the folks that I have spoken with injected it while in withdrawal from other opiates, so getting “high” becomes a relative happening. If I was in prison and wanted to use, I would likely take what I could afford, or was available. The best I can tell, talking to people around Oklahoma is that a suboxone or subutex is worth anywhere from $5-10, on the street. Not a whole lot more than the retail costs. If you are a using addict, why buy Suboxone, when you can get a 2-3 day supply of heroin for $50? I have also heard a lot of urban legends around buprenorphine, some of which have some basis in fact, but most are anecdotal. We have had some trafficking of suboxone in our sober living and half way entities, but usually has been someone diverting their legally prescribed suboxone for cigarettes or sex. K2 is the real problem for those entities. William-Yarborough@ouhsc.edu Any idea how they dissolve it for injection? I assume water is the solvent? Does it require heating? What volumes do they use? What volume syringes? What gauge needles? Thanks, Nat Nathaniel Katz, MD, MS It really makes perfect sense. The buprenorphine has a higher affinity for the mu opioid receptor than does naloxone (AKA Narcan). So, in using the combination via IV, the naloxone is really a 'non-player,' and the naloxone is ignored. Thus, the addition of naloxone to the medication is, sadly, just, 'window dressing,' to make the combination seem less attractive... The savvy street user quickly discovers this. CK Hebdon MD, D/ABAM It is extremely soluble in water . the may filter it with cotton balls. I would think any syringe they could lay their hands on would be used . Can't see why a diabetic syringe could not be used. Louise Buhrmann, MD There is a nice table in the attached that outlines the anticipated effect of buprenorphine/naloxone depending on the host and their receptors. * Attachment 1, Attachment 2 David Fiellin This does raise the issue of making opioid agonist treatment available, as is other health care, in prisons and jails. An interesting review below: The effectiveness of opioid maintenance treatment in prison settings: a systematic review. [Review] Hedrich D. Alves P. Farrell M. Stover H. Moller L. Mayet S. Addiction. 107(3):501-17, 2012 Mar. [Journal Article. Review] UI: 21955033 Authors Full Name Hedrich, Dagmar. Alves, Paula. Farrell, Michael. Stover, Heino. Moller, Lars. Mayet, Soraya. AB AIMS: To review evidence on the effectiveness of opioid maintenance treatment (OMT) in prisonand post-release. METHODS: Systematic review of experimental and observational studies of prisoners receiving OMT regarding treatment retention, opioid use, risk behaviours, human immunodeficiency virus (HIV)/hepatitis C virus (HCV) incidence, criminality, re-incarceration and mortality. We searched electronic research databases, specialist journals and the EMCDDA library for relevant studies until January 2011. Review conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. RESULTS: Twenty-one studies were identified: six experimental and 15 observational. OMT was associated significantly with reduced heroin use, injecting and syringe-sharing in prison if doses were adequate. Pre-release OMT was associated significantly with increased treatment entry and retention after release if arrangements existed to continue treatment. For other outcomes, associations with pre-release OMT were weaker. Four of five studies found post-release reductions in heroin use. Evidence regarding crime and re-incarceration was equivocal. There was insufficient evidence concerning HIV/HCV incidence. There was limited evidence that pre-release OMT reduces post-release mortality. Disruption of OMT continuity, especially due to brief periods of imprisonment, was associated with very significant increases in HCV incidence. CONCLUSIONS: Benefits of prison OMT are similar to those in community settings. OMT presents an opportunity to recruit problem opioid users into treatment, to reduce illicit opioid use and risk behaviours in prison and potentially minimize overdose risks on release. If liaison with community-based programmes exists, prison OMT facilitates continuity of treatment and longer-term benefits can be achieved. For prisoners in OMT before imprisonment, prison OMT provides treatment continuity. 2011 The Authors, Addiction 2011 Society for the Study of Addiction. David Fiellin David, This table of effects would be the same for bup monotherapy. The second row states aversive induced WD for both bup and bup-nal. I think the point of this thread is that naloxone really doesn't do anything. There is no likely mechanism by which naloxone in 1/4 the concentration can compete effectively against bup, even when injected IV. Further, the characteristics of bup and nal that cause bup to be absorbed SL to a much greater extent than nal are the same properties that would cause bup to traverse the BBB more easily than nal. The active transporter theory of nal traversing the BBB is fantasy that is refuted by good bench research. The studies of nal that RB gave to the FDA were at lower dose than used clinically. This is probably b/c the mu receptors at low doses are not saturated by bup. At higher more clinically relevant dose, e.g. 16/4, more recent clinical studies basically show nal does nothing. Dave Simon, MD, JD, ABAM So the RB intent of the strips v. tabs was the Bar or Square coding of the package ID to a specific pt. and pharmacy to track diversion and the packaging to be child resistant. Solubility for injection is the unintended consequence of the film. Is it any easier than the tablets which are now competing products? Lastly has the DEA kept track of the sources of the strips found at dealer busts. Were the strips tracked back to individual patients or were they diverted supplies "out the back door" before they ever reached the pharmacy/patient in the delivery chain? Scott McNairy MD David, My goal was to help the listserv think about the receptor AND the host. Without a doubt, buprenorphine/naloxone is abusable and caution needs to be used in prescribing all agonists, partial or not. It appears, in the US to date, at least, that bup/nx may be less reinforcing and less likely to be abused than buprenorphine mono (or full agonist opioids) when they are all available. It is also worth noting that anytime a person takes benzodiazipines and bupenorphine/suboxone, the ceiling effect of limiting opioid binding to receptors is negated by the benzodiazipine. Many Veterans are being prescribed benzodiazipines with minimal or no consideration for their analgesic regimen. Dr. Lynda Williamson Why is the ceiling effect negated with benzos? Jane Liebschutz The ceiling effect being negated by Brenzos is something I was not aware of- very interesting. Is there anywhere I can read about this further? Thank you for your time. Dave Gunn In answer to the question about prisoners’ source of Suboxone; I assume they have people bring it in. It is so small and easy to conceal. Mostly it would be out of packaging so the source would be hard to find. As so little is needed, a person with a legal prescription could sell of a few of their strips a month and at least break even without risking withdrawal themselves. If they were taking it once a day for a few days their urine would still be positive for Suboxone at their next doctor visit. Louise I. Buhrmann, MD, PA Dear esteemed colleagues, In this pcss listserve, and in any peer-reviewed forum, I would request avoiding language such as " any syringe they could lay their hands on" -- this is offensive and not helpful. Stacy Kratz, LCSW, CAP “From Aaron Fox: In regards to Suboxone use in prison - I have been doing some research in this area, and though it's a small sample, the former prisoners in New York whom we've interviewed have not reported injection of Suboxone in prison. Participants have described that Suboxone is being taken under the tongue or sniffed. One of the issues is that people are rapidly weaned off of maintenance therapies (methadone and buprenorphine) in New York before they're transferred to state prison, and they are describing prolonged withdrawal symptoms and craving. The state prisons test for other opiates but not buprenorphine, which may make the Suboxone more attractive than other opiates. The New York Times article mentions the relative ease of smuggling the strips into prison, and there's the long half life of the medication, but our participants haven't really mentioned these factors. It seems like much of this could be remedied by offering medication assisted treatments during incarceration, but that's a separate issue... Aaron D. Fox, MD MS” Joanna Starre Attachment 1-Bup-nx and host.docx Attachment 2-PCSS_AdherenceDiversionMisuse.pdf
  24. Here’s an article about buprenorphine in pregnancy. It addresses the safety of buprenorphine as an acceptable treatment for opioid dependence (now opioid use disorder) in pregnancy. It indicates that in this study, neonates required less morphine, had a shorter hospital stay and had a shorter duration of treatment for the neonatal abstinence syndrome compared to methadone. I don’t see anything about breastfeeding in the article. * Attachment 1 Michael Newberry, M.D. Attachment 1-Buprenorphine and Pregnancy NEJM 2010.pdf
  25. “Dear Dr. Fiellin The Substance Abuse and Mental Health Services Administration (SAMHSA) is alerting the treatment community and the general public that since the beginning of the year a marked increase in deaths reportedly linked to the use of heroin contaminated with the drug fentanyl has been noted. Fentanyl is a form of opioid and when used in combination with heroin can rapidly cause severe injury and even death. There have been more than 17 deaths linked to the possible use of fentanyl-contaminated heroin in the Pittsburgh, Pa. area alone since January 24, 2014. In the first two weeks of January there were 22 such deaths reported in Rhode Island. It has been observed that these trends can expand quickly to include large and more distant geographic areas of the country. As yet the origin of the fentanyl is unknown but additional deaths have been reported from New Jersey and Vermont. Heroin is always an extremely dangerous drug of abuse because it subjects its users to a wide array of risks such as overdose and increased exposure to Hepatitis C and HIV/AIDS and other infectious diseases. It often contains other ingredients which render it even more potentially harmful or in some deadly. SAMHSA requests treatment providers to alert their patients and greater community stakeholders to be alert to the increased risk of fatal overdose. SAMHSA released an Opioid Overdose Toolkit late last year. It contains information on recognizing and responding appropriately to overdose. The Toolkit presents information on recognizing and responding to overdose in a manner suitable to a variety of stakeholders. It can be read or downloaded to print and share at: http://store.samhsa.gov/product/Opioid-Overdose-Prevention-Toolkit/SMA13-4742 I recognize that as treatment providers you are daily engaged in providing the most effective form of overdose prevention: medication assisted treatment. Achieving recovery remains the best method for preventing fatal overdoses and other risks. Those seeking treatment for opioid dependence a can find help through SAMHSA?s Treatment Locator at: 800-662-HELP (4357) or on line at:http://www.samhsa.gov/treatment/index.aspx. Please contact Melinda Campopiano, MD at 240-276-2701 or melinda.campopiano@samhsa.hhs.gov with questions or for further information. Sincerely, H.Westley Clark, M.D., J.D., M.P.H., CAS, FASAM Director Center for Substance Abuse Treatment” David Fiellin I have a pregnant woman on buprenorphine who very much wants to breastfeed after delivery. Does anyone have experience or knowledge about the safety of continuing buprenorphine after delivery and allowing breast feeding? This patient says she has talked with women who have done this and it allowed the baby to wean and go home from the hospital earlier, since, presumably, the baby was getting some in breast milk. Lora Jasman MD “Women should be counseled that minimal levels of methadone and buprenorphine are found in breast milk regardless of the maternal dose. Breastfeeding should be encouraged in patients without HIV who are not using additional drugs and who have no other contraindications (32). The current buprenorphine package insert advises against breastfeeding; however, a consensus panel stated that the effects on the breastfed infant are likely to be minimal and that breastfeeding is not contraindicated (33). Swaddling associated with breastfeeding may reduce neonatal abstinence syndrome symptoms, and breastfeeding contributes to bonding between mother and infant as well as providing immunity to the infant.” http://www.ncbi.nlm.nih.gov/pubmed/22525931 Tracy Harvey, PharmD, BCPS, FASCP, CPE The attached guidance addresses this question directly. Some recent citations are included below: Breastfeed Med. 2012 Aug;7:269-74. doi: 10.1089/bfm.2011.0096. Epub 2011 Oct 19. Estimated dose exposure of the neonate to buprenorphine and its metabolite norbuprenorphine via breastmilk during maternal buprenorphine substitution treatment. Ilett KF, Hackett LP, Gower S, Doherty DA, Hamilton D, Bartu AE. Author information Abstract OBJECTIVE: The aim of the present study was to estimate the dose of buprenorphine and its primary metabolite norbuprenorphine that a breastfed infant would receive during maternal maintenance treatment with buprenorphine. STUDY DESIGN: Seven pregnant opioid-dependent women taking buprenorphine (median, 7 mg/day; range, 2.4-24 mg) and who intended to breastfeed were recruited. After lactation was established, several milk samples were collected from each subject over a 24-hour dose interval, and buprenorphine and norbuprenorphine concentrations were measured by liquid chromatography-tandem mass spectrometry. The average concentration (C(avg)) across the dose interval was estimated as for bothbuprenorphine and norbuprenorphine (as buprenorphine equivalents). Absolute infant dose (AID), defined as C(avg) × daily milk intake, and relative infant dose (RID), defined as 100×AID/weight-adjusted maternal daily dose, via milk were calculated, assuming a milk intake of 0.15 L/kg/day. The infant's health and progress were assessed directly and by questionnaire on the study day. RESULTS: Mean (95% confidence interval) norbuprenorphine concentration in milk and AID values (1.94 [0.79-3.08] μg/L and 0.29 [0.12-0.46] μg/kg/day, respectively) were approximately half those for buprenorphine (3.65[1.61-5.7] μg/L and 0.55 [0.24-0.85] μg/kg/day, respectively). Similarly, the mean RID values were 0.18% (0.11-0.25%) for norbuprenorphine and 0.38% (0.23-0.53%) for buprenorphine. The breastfed infants showed no adverse effects, were all in good health, and were progressing as expected. CONCLUSION: Thus the dose of buprenorphine and norbuprenorphine received via milk is unlikely to cause any acute adverse effects in the breastfed infant. PMID: 22011128 Obstet Gynecol Surv. 2012 Dec;67(12):817-25. doi: 10.1097/OGX.0b013e3182788e8c. Opioid addiction in pregnancy. Shainker SA, Saia K, Lee-Parritz A. Author information Abstract The purpose of this review is to discuss the incidence, risks, pregnancy complications, and maintenance options for treatment of opioid addiction in pregnancy. Summary: Opioid dependence in pregnancy carries clear identifiable maternal and fetal risk. Providing care for patients with dependence is best done in a multidisciplinary care model addressing the particular needs of this population. There are limited data on maternal detoxification, with data still emerging surrounding the safety profile of this practice. Historically, methadone has been the recommended maintenance treatment; however, recent data on buprenorphineidentify this as a safe and effective option. The majority of births from women with opioid dependence result in neonatal abstinence syndrome requiring prolonged neonatal hospitalization. Intrapartum pain management should not differ from the general obstetric population. Postpartum pain is magnified in this population, and particular attention should be focused on this issue. Breast-feeding is recommended regardless of maintenance dose, unless other conditions restricting breast-feeding are present. Comprehensive postpartum care and transition of care to addiction specialists are highly recommended. J Hum Lact. 2014 Jan 7. [Epub ahead of print] The Wellbeing of Infants Exposed to Buprenorphine via Breast Milk at 4 Weeks of Age. Gower S, Bartu A, Ilett KF, Doherty D, McLaurin R, Hamilton D. Author information Abstract Background:Buprenorphine has been available in Australia since 2000 as an alternative pharmacotherapy to methadone for the treatment of opioid dependence. However, there is little information in the literature regarding the effect of buprenorphine on the wellbeing of infants exposed to buprenorphine via breast milk, following discharge from hospital.Objective:The aim of the present study was to examine the wellbeing of infants exposed to buprenorphine via breast milk up to 4 weeks postnatally.Methods:Approximately 4 weeks after birth, information on the feeding and sleeping patterns, skin color, infant elimination patterns and hydration, and Neonatal Abstinence Scores of infants (n = 7) exposed to buprenorphine via breast milk was collected via both observation and documentation.Results:Infants were progressing well, with normal sleep patterns and skin color, and 2 mothers had minor concerns regarding infant elimination patterns. Four infants were exclusively breastfed and 3 were receiving a supplement, with a range of 260 to 700 mL of formula over 24 hours. The sleep patterns following feedingranged from 1.55 to 3.33 hours, with a median of 2.12 hours.Conclusion:No adverse effects were detected in infants exposed tobuprenorphine via breast milk up to 4 weeks postnatally. Further research using larger samples to assess possible developmental effects over longer periods of time is required. David Fiellin From: Lora Jasman <jasman99@hotmail.com> Reply-To: "pcss-o@googlegroups.com" <pcss-o@googlegroups.com> Date: Saturday, February 15, 2014 8:22 PM To: "pcss-o@googlegroups.com" <pcss-o@googlegroups.com> Subject: buprenorphine while breast feeding I have a pregnant woman on buprenorphine who very much wants to breastfeed after delivery. Does anyone have experience or knowledge about the safety of continuing buprenorphine after delivery and allowing breast feeding? This patient says she has talked with women who have done this and it allowed the baby to wean and go home from the hospital earlier, since, presumably, the baby was getting some in breast milk. Lora Jasman MD From The American College of Obstetricians and Gynecologists committee opinion on “Opioid Abuse, Dependence, and Addiction in Pregnancy”: “Women should be counseled that minimal levels of methadone and buprenorphine are found in breast milk regardless of the maternal dose. Breastfeeding should be encouraged in patients without HIV who are not using additional drugs and who have no other contraindications (32). The current buprenorphine package insert advises against breastfeeding; however, a consensus panel stated that the effects on the breastfed infant are likely to be minimal and that breastfeeding is not contraindicated (33). Swaddling associated with breastfeeding may reduce neonatal abstinence syndrome symptoms, and breastfeeding contributes to bonding between mother and infant as well as providing immunity to the infant.” http://www.ncbi.nlm.nih.gov/pubmed/22525931 Tracy Harvey, PharmD, BCPS, FASCP, CPE The attached guidance addresses this question directly. Some recent citations are included below: Breastfeed Med. 2012 Aug;7:269-74. doi: 10.1089/bfm.2011.0096. Epub 2011 Oct 19. Estimated dose exposure of the neonate to buprenorphine and its metabolite norbuprenorphine via breastmilk during maternal buprenorphine substitution treatment. Ilett KF, Hackett LP, Gower S, Doherty DA, Hamilton D, Bartu AE. Author information Abstract OBJECTIVE: The aim of the present study was to estimate the dose of buprenorphine and its primary metabolite norbuprenorphine that a breastfed infant would receive during maternal maintenance treatment with buprenorphine. STUDY DESIGN: Seven pregnant opioid-dependent women taking buprenorphine (median, 7 mg/day; range, 2.4-24 mg) and who intended to breastfeed were recruited. After lactation was established, several milk samples were collected from each subject over a 24-hour dose interval, and buprenorphine and norbuprenorphine concentrations were measured by liquid chromatography-tandem mass spectrometry. The average concentration (C(avg)) across the dose interval was estimated as for bothbuprenorphine and norbuprenorphine (as buprenorphine equivalents). Absolute infant dose (AID), defined as C(avg) × daily milk intake, and relative infant dose (RID), defined as 100×AID/weight-adjusted maternal daily dose, via milk were calculated, assuming a milk intake of 0.15 L/kg/day. The infant's health and progress were assessed directly and by questionnaire on the study day. RESULTS: Mean (95% confidence interval) norbuprenorphine concentration in milk and AID values (1.94 [0.79-3.08] μg/L and 0.29 [0.12-0.46] μg/kg/day, respectively) were approximately half those for buprenorphine (3.65[1.61-5.7] μg/L and 0.55 [0.24-0.85] μg/kg/day, respectively). Similarly, the mean RID values were 0.18% (0.11-0.25%) for norbuprenorphine and 0.38% (0.23-0.53%) for buprenorphine. The breastfed infants showed no adverse effects, were all in good health, and were progressing as expected. CONCLUSION: Thus the dose of buprenorphine and norbuprenorphine received via milk is unlikely to cause any acute adverse effects in the breastfed infant. PMID: 22011128 Obstet Gynecol Surv. 2012 Dec;67(12):817-25. doi: 10.1097/OGX.0b013e3182788e8c. Opioid addiction in pregnancy. Shainker SA, Saia K, Lee-Parritz A. Author information Abstract The purpose of this review is to discuss the incidence, risks, pregnancy complications, and maintenance options for treatment of opioid addiction in pregnancy. Summary: Opioid dependence in pregnancy carries clear identifiable maternal and fetal risk. Providing care for patients with dependence is best done in a multidisciplinary care model addressing the particular needs of this population. There are limited data on maternal detoxification, with data still emerging surrounding the safety profile of this practice. Historically, methadone has been the recommended maintenance treatment; however, recent data on buprenorphineidentify this as a safe and effective option. The majority of births from women with opioid dependence result in neonatal abstinence syndrome requiring prolonged neonatal hospitalization. Intrapartum pain management should not differ from the general obstetric population. Postpartum pain is magnified in this population, and particular attention should be focused on this issue. Breast-feeding is recommended regardless of maintenance dose, unless other conditions restricting breast-feeding are present. Comprehensive postpartum care and transition of care to addiction specialists are highly recommended. J Hum Lact. 2014 Jan 7. [Epub ahead of print] The Wellbeing of Infants Exposed to Buprenorphine via Breast Milk at 4 Weeks of Age. Gower S, Bartu A, Ilett KF, Doherty D, McLaurin R, Hamilton D. Author information Abstract Background:Buprenorphine has been available in Australia since 2000 as an alternative pharmacotherapy to methadone for the treatment of opioid dependence. However, there is little information in the literature regarding the effect of buprenorphine on the wellbeing of infants exposed to buprenorphine via breast milk, following discharge from hospital.Objective:The aim of the present study was to examine the wellbeing of infants exposed to buprenorphine via breast milk up to 4 weeks postnatally.Methods:Approximately 4 weeks after birth, information on the feeding and sleeping patterns, skin color, infant elimination patterns and hydration, and Neonatal Abstinence Scores of infants (n = 7) exposed to buprenorphine via breast milk was collected via both observation and documentation.Results:Infants were progressing well, with normal sleep patterns and skin color, and 2 mothers had minor concerns regarding infant elimination patterns. Four infants were exclusively breastfed and 3 were receiving a supplement, with a range of 260 to 700 mL of formula over 24 hours. The sleep patterns following feedingranged from 1.55 to 3.33 hours, with a median of 2.12 hours.Conclusion:No adverse effects were detected in infants exposed tobuprenorphine via breast milk up to 4 weeks postnatally. Further research using larger samples to assess possible developmental effects over longer periods of time is required. * Attachment 1 David Fiellin (Attachment) Tip 40 talks about this. Short answer is that its ok. www.ncbi.nlm.nih.gov/books /NBK64230. (Chapter 5) There are many papers on this from multiple groups as well PMID: 23979084 (aap) 22525931 (acog) Dave Gunn Dave, Might you have references to any of these “many papers”? Or perhaps they are cited in TIP 40, to which, sadly , I don’t presently have access. Thank you Kerby Stewart MD http://store.samhsa.gov/product/TIP-40-Clinical-Guidelines-for-the-Use-of-Buprenorphine-in-the-Treatment-of-Opioid-Addiction/SMA07-3939 Fran Belvin, MA, LPAT http://store.samhsa.gov/product/TIP-40-Clinical-Guidelines-for-the-Use-of-Buprenorphine-in-the-Treatment-of-Opioid-Addiction/SMA07-3939 TIP 40 access Margaret E. Hanna Sorry Kerry I included the PubMed Id numbers from the acog and aap at the bottom (PMID). You can enter these numbers into pubmed.gov and they will appear. Usually these consensus statements are free. Hope this helps Dave Gunn Attachment 1-PCSS-B Pregnancy and buprenorphine treatment[1].pdf
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