Methadone is quickly becoming an outdated treatment protocol with risks outweighing benefits. Buprenorphine, IMHO of over 6,000 patient visits, is far superior, a C-3, and has a blocking and ceiling effect, as well as being 20x stronger for comorbid pain situations. Methadone, with a 72 hour half life and the " drool effect", watch patients in recovery and pick out the ones on methadone, make it obsolete. All this being said, the focus should be on psychotherapy , NOT more drugs. The answer is neuro-cognitive restructuring. and re-birth of the frontal cortex of the brain, which in addictions, is not communicating effectively with the mid-brain. I see nearly 100 opioid addicted patients a week, between group and individual case management , the difficulty encountered with weaning, and the horror stories of sub standard care I hear from methadone maintenance programs is problematic.. ( 2 week withdrawal periods are not uncommon). For pain, small doses of multiple agents can be used, but the effects are diminished by hyperalgesia so fast at higher doses , that there is NO longitudinal evidence of continued efficacy on non-cancer pain. Buprenorphine remains one of the most understudied, and most mis-understood medicines out there, this is across all disciplines. Long answer short. Don't do it. The concurrent depression of the neuro-hormonal axis as well as hyperalgesia, and increasing dependence are deal breakers.

I agree with Dr. Dillon that methadone is quickly becoming obsolete for patients with Opioid Use Disorder (DSM Dx 304.xx), but for different reasons.  Methadone, WHEN ADMINISTERED PROPERLY, remains the "gold standard" for maintenance treatment.  The problem is, it's very expensive to administer it properly - you need drugs-of-misuse screening tests, complementary therapy - in other words, a very well-run methadone clinic - these are few and far between.  I have not observed the "drool effect" Dr. Dillon references in PROPERLY DOSED PATIENTS in top-decile clinics, which I have visited.  On the other hand, patients with too high a dose of a strong opioid will always drool, nod, etcetera.  

Buprenorphine is safer and more convenient for the patient, and far less mis-usable amongst pts with even mild opioid tolerance.  Speaking of safety, and to answer the original question: no!  Not only do you risk hyperalgesia but also you risk RESPIRATORY DEPRESSION AND MORTALITY if you COMBINE MORPHINE AND METHADONE.  This is a VERY VERY RISKY MAINTENANCE STRATEGY (mixing long-acting and short-acting opioids) and even assuming it's all done inpatient, the risks of something going wrong, in my option, outweigh any possible benefits.  

Best option: switch to buprenorphine.  Worst option, if you feel you MUST augment morphine (again, not suggesting you do this): use something a little less RD (respiratory depressive) than morphine, such as hydrocodone (fast acting, high bioavailability through oral administration).  

Also, with all due respect, maintenance medications are supposed to be "quiet BORING drugs" and patients should get used to it.  The meds (bupe and methadone) are supposed to eliminate the craving for opioids, and NOT act as a euphorigenic.   

I agree with the use of buprenorphine rather than a combination of morphine and methadone mainly for the reasons stated above. However, two caveats:

1. If the patient is given the buprenorphine to take away to self medicate then provide it as a combined formulation with nalorphine or naltrexone. This combination makes buprenorphine ineffective if injected. The opiate antagonist is brojen down by first passmetabolism leaving the buprenorphine to get on with the job.

2. There is not a drug which will solve all the situations in addiction. While you might not like the use of methadone, don't turn your back on it completely.  It is still an option for when others have failed.

Please forgive the spelling errors above. (Arthritic fingers and a slippy tablet screen!) 

Dear colleagues,

please apologize ma bad english! thank you very much for engaged answers and advices! I think, I have to be more precise to make you understand my problem:

As you may know: in Germany there is still officialy no “Addiction Medicine” and an actual study says, that young docs are able to handle diabetes or high blood pressure, but they never heard about addiction…. (Strobel, L; Schneider, NK; Krampe, H; et al: German medical students lack knowledge of how to treat smoking and problem drinking. Addiction Vol.10,1878–1882, October 2012)

I work as a GP after some years in Abstinence-REHAB (for adults, then for children…) since 1997 in OST together with 2 psychiatrists and 7 GPs, 30 nurses and 27 psychologists and drug counsellors. We run 3 outpatient treatment centres in Berlin and actually see 850 OST-patients/day (www. aid-berlin.org ). Actually 5000 Berliners are in OST.

In 1993 my colleague and former chef Dr. C. Jacoboski wrote a little bilance on „5 Jahre Berliner Linie in der Substitution“ At that time in Berlin 100 GPs (and no Psychiatrist…) gave Methadone to 1200 patients, psychosocial treatment („PSB“) had been made by drug counsellors. 300 MMT-patients were identified by „Kassenärztliche Vereinigung Berlin“ (i.e.: Chamber of Physicians allowed to bill insurances) as „Not-able-to-sit-in-a-GP´s-waiting-room-Patients“.

As doctors we have a special permission by KV to treat 100 patients, as long, as we take these patients and no normal GP-populations – and that is what we do.

So we are financed by the Insurance and controlled by KV Berlin and the still very harsh German Opioid-law. Our Task: addiction medicine, HCV, HIV, Internal medical problems, Psychiatric problems. We cooperate with the patient and all institutions involved in his/her life: social welfare, drug counselling and abstinence oriented REHAB, justice, other medical services….

Only in Berlin the psychosocial treatment is financed by the district-government by hourly wage rate:

“PSB” is controlled by public health services:

„PSB“ in Berlin gives a 6-month estimate to communal psychiatric services for each patient about

1. Daily self-treatment in major life activities: housing, finances, nutrition, personal hygiene, …,

2. Daytime activities: maintain a structured day, recreation, important dates, …,

3. Personal and social relations,

4. Professional education, engagement and work,

5. Addiction and consume of other psychoactive drugs: legal restrictions, experience in drug addiction treatment, … personal treatment goals,…,

(6. Automatic information of the youth welfare office, if there are underage persons living in the same household.)

After permisson by „SPD“ communal financial authorities pay treatment-hours/patient from hours every day to 1 hour all 2 weeks. That depends on the treatment plan of the PSB and the doctor`s vote.

In my clinic in Berlin Neukölln we see these patients (N = 239, Sept. 2013):

Age: 17 – 68; with non-german origin: 28% (Russia, Afghanistan, Chechnia, Poland, Baltic States, Turkey, Libanon, Syria, Irak, Iran, other europ. Countries, USA)

82% male (42y): 6,8 years in prison, badly educated, jobless, homeless

18% femal (39y): 3,2 years in prison, 1.5 children, badly educated, jobless

„OST“:

=> d/l-Methadone: 79 (33%, 42y.)

=> l-Methadone: 104 (44%, 42y.)

=> Buprenorphine: 38 (16%, 30y.)

=> Bup/Nalox: 17 (7%, 29y.)

(=> DHC: 1 (0,4%))

Not only because of the law, but also because we think that “controle” (i.e. objectify reality…) is one of the basic demands in addiction-medicine, we know quiet a lot about the daily concomitant use of other drugs:

(N = 1974 in 2013, all patients aid-berlin)

18.1% use amphetamines (2,3% methamphetamine)

23.8% use opiats/opioids (12,1% 6.MAM-positive!)

19% use benzodiazepines

The tests were made with Oral Fluid, no Immunoassays were used: all test were done chromatographically! A max. of 4% of our patients are monovalent dependend on opioids, most of them depend on more then 3 types of drugs.

ALCOHOL: The BIG FAT SOUL-ALLAYER for everybody in OST:

literature: 51% ICD 10, F10.1 - 38% ICD 10,F10.2

(Dampz, M., 2010, 2009; Körkel, J., 2009, 2008)

aid-neukölln, N=244: act. 29% in daily alcohol-test-routine (70);

medic. history of ICD 10, F10.2: 41.4% (101)

act. alcohol-dependent: 14.0% (35)

22 out of 44 HCV-pat: no treatment possible! The combination of alcohol and benzodiazepines seems to be our biggest drug-induced problem!

Psychiatric comorbidity is higher, then in literature, we know that nearly 100% of our patients have been loaded with a lot of psychiatric problems from PTDS (>30% of the males) to depression, anxiety, “psychosis” or “personality disorders” and we know, that most of these problems started before they began to use drugs.

In our experience, methadone is still the gold standart BUT buprenorphine is not for everybody and there are a lot of “double-diagnosis”-patients suffering from emotional flattening (“I can`t laugh anymore….”) with methadone. Even slowly reducing methadone is a risky undertaking often wrongly responded by fresh demands on other drugs and alcohol. We learned to be very careful and we learned that abstinence always has to be paid by the patients with a lot of - mostly very old - trouble. We still miss psychotherapy and psychotherapists who are willing to work with our patients on that kind of problems.

And some of the patients in MMT can`t stop using opioids intraveneously. Since last year we have an outpatient treatment centre working with diacethylmorphine. The law says that this medication has to be injected. But a lot of patients in OST stopped successfully to use drugs intraveneously. They do not want to inject AND they are not able to stop taking methadone or switching on buprenorphine and at the same time hate the feeling of being emotionally dead. Also these patients do not want to drink alcohole or use benzodiazepines

What do you recommend for these patients?

Best regards!

C. Jellinek

NB - This post does not constitute medical advice; this is merely my personal non-medical opinion about policies at your clinic

I agree with you that comorbidity between substance use disorders (SUDs) and other psychiatric diagnosis is very high, probably close to 100% as you state.  That does make treating patients more difficult, and it also probably explains why there is no optimal treatment strategy that works for EVERY PATIENT.  Addiction treatment must be INDIVIDUALIZED to the patient; some respond better to different OST meds, some can achieve remission without OST.

Here in the US, the general view (I think) is that a patient on OST should not be using any other substances, including alcohol.  The better outpatient clinics (methadone & buprenorphine are the only legal medications for OST here) insist that patients are tested regularly for other substance use, and they have policies that suspend the OST if the patient tests positive.  In fact, by law in the US, methadone clinics are not supposed to give the pt methadone if they test positive, period.  This seems a little harsh to me, as it often has the consequence of forcing the patient to resume using illicit opioids ONLY.  

So, when you say "some of the patients in MMT can't stop using opioids intravenously" I would suggest you consider the possibility that MMT is NOT WORKING for those patients, or develop some system whereby if they CONTINUE to use opioids intravenously (on top of the MMT, this is obviously increases overdose risk, as many patients are not good at calculating their precise tolerance levels when "overloading" OST) - if they are injecting opioids, I think most clinicians here would do everything possible to discourage it.  Here in the US, clinicians would hesitate to continue MMT for patients who are continuing to misuse other substances.

I see that you are using diacetylmorphine (Heroin, right?) as OST, such as they do in the Netherlands.  This is a pretty controversial practice, as diacetylmorphine is in many ways not an optimal maintenance med (short half-life, hard to maintain stable blood levels, etc).  Worse still, if patients don't want to inject it, it is suboptimal for them.  However, you seem to be saying that they don't feel "emotionally dead" when on short-half-life (heroin, etc) OST but do feel that way on long-half-life (methadone, buprenorphine) OST.  I would say that this is, unfortunately, a very hard problem that remains unsolved.  But, I think that being "emotionally dead" is better than being ACTUALLY DEAD, which is what might happen if they weren't on MMT.  

This all goes back to the fact that the appropriate Tx for a patient must be individualized - there is no RIGHT ANSWER FOR ALL PATIENTS.  For those who do experience negative psychological states from MMT, here are some options I have read about:: (1) switch them to buprenorphine, which seems to have a less emotionally deadening effect in some pts (2) reduce dosage of any OST med, which increases risk of illicit misuse but would probably increase sensitivity to emotions, etc (3) consider the possibility that these patients may not be candidates for OST.  There are other medications, like long-acting naltrexone (Vivitrol; one IM dose monthly) which block the opioid receptors quite effectively.  As far as I know, there is no evidence that naltrexone causes any negative emotional effects, or any psychotropic effects, for that matter.

I am surprised that the German government does not allow you to use diacetylmorphine in a longer-acting oral formulation, but I'm not sure that would be a good idea anyway.  What are the reasons for this policy?  It seems a bit ill-conceived.  However, my personal opinion is that short-acting opioids are not the best OST meds from a policy perspective.  

As far as alcohol and benzodiazepines go, there are obvious dangers to using either with opioids.  All three are respiratory depressants, and they magnify that effect when used together.  Benzodiazepines are contraindicated with opioids, but they are sometimes co-prescribed, carefully, when a patient really needs both.  Alcohol and opioids are a recipe for mortality.  

I think that your practice is suffering from a lack of a psychiatric approach to treating addiction.  OST by itself may work for some patients, but many do better with abstinence-based treatment, or with OST in conjunction with therapy, testing, and treatment of the co-morbidities you mention.  As a policy matter, OST alone has not worked terribly well in the past for all patients. (e.g. the UK in the 1960s)

I think the US may be a bit ahead of Germany on the "learning curve".  If I were you I would imitate US policy, e.g. (1) use buprenorphine instead of methadone when possible, as it is a partial agonist/antagonist rather than a pure agonist like methadone  (2) develop a plan by which patients misusing other substances are tested for illicit substance misuse and have their OST discontinued if it is not working - that is, it is not helping with their addiction, and discontinuation would not pose even higher risks and (3) research further the risk/benefit analysis of IV diacetylmorphine as an OST medication - I think you will find the preponderance of the data suggests that this is a strategy of last resort.

Again, all of this is just my personal opinion and I am not advising you to do anything, just to consider the issues I have raised in the hope that they may help you in your quest to treat these patients.  But as you point out, you are at a significant disadvantage without the benefit of other (psychiatric) treatment modalities.  OST alone is a blunt tool that works very well for some patients, and very poorly for others.  

(2) [PDF] Teil I Empfehlungen zur ärztlichen Substitution opiatabhängiger Frauen und Männer (3) Opiate substitution treatment and HIV transmission in people who inject drugs: systematic review and meta-analysis

Hi Devine,

I agree: there is no RIGHT ANSWER FOR ALL PATIENTS and treatment has to be individualiced. Did you read what I wrote? look at the number of patients and at the number of professionals and you will understand, that we work very individualiced and never without the experience of psychaitrists.

There is a lot of evindence that concommitand use of other drugs is a fact and that there is no difference between methadone and buprenorphine when comorbidity is considered (1). The risk for fatal overdoses increases with the ending of OST (2). So ending MMT because of concommitant use means a very risky decision. Even OST without any psychosocial treatment reduces HIV-risks (3)

In our experience every addiction needs its own treatmentplan: opioid-addiction needs OST, alcohol-addiction abstinence or succesfull consum control programs (our PSB is running such a program and it works not only fpr alcohol, but also for amphetamines/kokain or thc!) and so on. we think it is not enough to end OSR because of a concommitand alcohol addiction!

regards

Chaim

(1) Ärzte Zeitung, 16.07.2009 J. Stoschek:

In der Methadon-Substitution ist der illegale Beikonsum fast die Regel

BMJ 2012; 345 doi: http://dx.doi.org/10.1136/bmj.e5945 (Published 04 October 2012) Cite this as: BMJ 2012;345:e5945

Chaim,

I meant mostly to contrast your program to the policies and procedures in most treatment centers here in the US.  You say "opioid addiction needs OST" - I agree that for some patients, that is true.  But there is also plenty of evidence that opioid use disorder can be treated successfully with (a) abstinence-based methods (b) bridging to abstinence with OST - e.g. as an intermediate term treatment and (c) even with medications like naltrexone, especially in sustained-release injections (Vivitrol, etc) which also work for alcohol.  That said, I agree that OST has a very useful role to play for many patients, and as I wrote, there are substantial risks to discontinuation of OST.

From a pure social policy standpoint, you are right - insisting that patients discontinue all substances of misuse in order to receive OST is draconian and may cause all sorts of harm -- relapse to illicit opioids, increased risk of HIV, mortality, etc.  I am just highlighting the "culture" difference between Europe and the US on OST.  Here, the prevailing view (from dozens, if not hundreds of addiction docs I speak with) is that OST should not be administered to patients who are misusing other substances.  I am not saying that is RIGHT, I am just saying that is the policy here, and indeed, by law in the US, a patient  may not continue to receive methadone if he or she tests positive for any substance of misuse - alcohol, etc - unless it is legally prescribed by a physician.  Again, I don't necessarily agree with this policy, and I know that it is ignored in some cases by treating physicians.  

While you correctly point out the risks of discontinuation of OST, your original question was how to treat the issue of a patient feeling "emotionally dead" while on either methadone or buprenorphine.  I still think there are only three options: (1) dosage adjustments - e.g. some patients are overmedicated on methadone, e.g. above 80mg a day there is little evidence of added relapse prevention (2) a path to abstinence of some kind or (3) additional medication to treat the emotional numbness - but this would be a stimulant of some kind, and that might be dangerous in a patient prone to addiction.

In my view, effective OST poses challenges in terms of patient quality of life.  YES, it saves lives, and yes, it prevents HIV, and so forth.  But the tradeoff, for some patients, is that they don't like the way "it feels".  I suppose the same can be said for cancer patients on chemotherapy; they too have a chronic illness and must suffer in some ways in order to save their lives.  On the other hand, there is evidence that many patients do very well on buprenorphine - many report antidepressant effects (long term) - in fact, there is a new antidepressant drug being developed here that is based on buprenorphine.  I can find the article about buprenorphine's antidepressant effects; I read it about a year ago...let me know if you would like it.

In any case, I wish you the very best in managing your OST patients.  You are doing noble, life-saving work.  I mostly intended to point out the differences in approach between US OST and EU/German OST. 

Very best regards,

Devin

Devin,

yes, you are right, we still have no answer to the original question!

we allready know, that slow releasing morphine is as effektiv, als methadone (1). In individualiced treatment it should be possible to combine the pharmacologig effekts of different opiats including sr-morphine and diacethylmorphine (2).

In my opinion its not a question of ideology, but of evidence. So I think we should try new ways and combine opiats for patients who do not profit from the treatments we allready established.

All the best!

Chaim

(1) Beck T. et al: Maintenenace Treatment with slow releasing oral morphine: a roandomiced cross-over, non-inveriority study versus methadone. Addiction, 2013, 109, 617-626

(2) Gschwend P: Heroingestützte Behandlung in der Schweiz, Diss. 2003