Choosing Opiate Agonist Treatment

Choosing opioid agonist treatment

Dr. Meldon Kahan

Dr. Maya Nader

Dr. Anita Srivastava

Excellent presentation by three clinicians at the Canadian Society of Addiction Medicine annual meeting in Vancouver, 2013

These are my rough notes which hopefully give an idea of what was a very well presented, researched and clinically useful talk

Learning objections

initiation of opioid agonist treatment

 recent evidence regarding efficacy and side effects of buprenophine versus methadone

Opioid Agonist Treatment - OAT

-bruprenorphine USA 1980

-approved in Canada 2008

History of methadone

synthesized in germany in 1941

first methadone maitenance program in the world founded in Vancouver in 1967

Potential considerations

efficacy, safety, weight gain, mental clouding, sedation, sexual function, pain, withdrawal

Methadone more likely to retain patients than buprenorphine

With fixed medium dosing - buprenorphine less likely to suppress heroin desire

questions raised by cochrane review

-retention - was induction to buprenorphine too slow, etc

Stepped care approach

-Kakko 2007

Only 46% who started buprenorphine stayed and rest switched to MMT 

-treatment retention and urine screens and problems good with this group

Safety concerns

 buprenorphine considered safe

Bell 2009 , australia

QT intervals - evidence for prolonged QT - at higher dosages 200 to 300

Safety - Benzos

risk of overdose increased with any opiates

when benzo used with methadone or buprenorphine - methadone did poorer on benzo - Lintzeris et al 2007

Age

Opioids are a risk factor for fractures in the elderly and it’s dose related

Diversion - patients who use methadone nonmedically have higher hospitalizations rates, greater icu, poorer outcomes

Patient preference

-Summit Trial , Pinto et al 2010

patients preferred methadone 2:1

-subset wouldn’t go on methadone

main reason for choosing buprenorphine

-ease of detoxification

• more clear headed

Withdrawal severity may be less intense with buprenorphine - gowling et al, cochrane review 2009

At end of day similar relapse rates during withdrawal whether patient was on buprenorphine or methadone

PAIN

-Neuman, 2013 - equally reduced in methadone and buprenorphine

-suggested alot of pain related to addiction

Adolescent Heroin Users

-better treatment retention with methadone than buprenorphine

-better treatment retention with long term buprenorphine treatemnt versus detox or abstinence (bell, 2006;woody208,)

Weight Gain

-perception of greater weight gain with MMT

-non dose related increase in first 2 years - but when compared to general populations methadone patients less

-no different in weight gain between methadone and buprenorphine

review of patient blogs - mixed response

Mental Alertness/sedation

-both methadone and buprenorphine appear to affect mental alertness and sedation 

-up to 100 mg no difference - but greater than 100 mg more with methadone-winstock 2009

Driving

Increased risk of traffic accidents in both patients on MMT and BMT

Bup pts performed somewhat better on psychomotor tasks than methadone

No on road testing done 

Mood

-double blind controlled trial (n=150)  - showed improvement in mood on beck in all with no improvement of one over the other drug

Quality of Life

Beneficial effects for both

Early onset of benefits with Methadone versus Buprenorphine but both good

Sexual Function

MMT patients have more erectile dysfunction and lower testosterone levels than buprenorphine

Side Effects

-Summit Trial

greater proportion of MMT complained of sweating, seadation and constipation than buprenorphine

Programmatic differences

-contigency management differences

-patient randomized to buprenorphine in one post jail study - more flexible environment for buprenorphine versus MMT - resulted in better retention and follow up

Soft Factors

-factors other than intrinsic pharmacological 

-family/work obligations -strict MMT requirements associated with treatment to protect against overdose 

-lack of mobility 

-comorbities - tying care to family doctor - a diabetic have buprenorphine in office versus going to clinic

-patient receiving high oral opioid doses from one doctor only

-socially unstable, doesn’t follow up with appointments - methadone might have better retention rate

In states and france - buprenorphine can be prescribed by a family doctor in office versus the clinic based methadone

Buprenorphine has been used in patients who were iatrogenically addicted to opiates for pain management and they are more willing to take buprenorphine

Pregnancy

Methadone approved in pregnancy

buprenorphine/naloxone is not

-consider methadone for women at high-risk or planning a pregnancy

Funding 

-cost - buprenorphine more expensive than methadone

Q&A

Opiates can reduce testosterone and testosterone replacement and viagra can help

Paitents who are on heroin usually have poor sexual function and the majority have improvement with methadone maintenance

A Call for Evidence Based Treatment (in Addiction)

A Call for Evidence Based Treatment

Dr. Bohdan Nosyk  bnosyk@sfu.ca

-health economist with a research focus on substance abuse and infectious disease

Presented at the Canadian Society of Addiction Medicine Annual Meeting, Vancouver, BC 2013. These are my rough notes which only give a jist of the wealth of information presented. Dr. Nosyk has contributed to many papers and his slides were excellent often taking graphs from the research he’d published elsewhere. I hope that these notes though will direct someone to where they might find information they are looking for as well as give some idea of the depth and breadth and controversies in this area.

key recommendations

eliminate financial barriers

increase acces to office based

reduce reliance on detox treatment

evaluate integrate new technologies

increase surveillance, evaluation of quality of care

Background Epidemiology

US 2.3 million with opioid dependence 

75-125,000 injection drugs users; 200,000 people with prescription opioid dependence

Opioid overdose second leading cause of accidental death in US - surpassed only by MVA

In ontario deaths related to PO doubled

Treatment Options

Methadone

Buprenorphine

Methadone still more effective and less costly than buprenorphine

Nosyk et al, Am J of Epidemiology 2009

Primary finding was that patients with multiple treatment tended over time to stay in treatment and morbidity and mortality

Tends to be a pattern of increasing length of time in treatment

Abstinence durations were longer folllowing sustatined treatemn versu incarceration.  Paitents with multiple abstience episodes tend to go onto abstinence

OST has been deemed highly cost effective if not cost saving

often the cost of tratemnt are more than offset by recuction in acquisitive crime and use of health resourcs realted to transmission of HIV or Hep C

Diacetylmorphine - NAOMI  - trial 

Nosyk et al, CMAJ 2012 

all the benefits were derived from the longer retentions and 85% , when they relapsed the crime went up and health went down

DAM cohorts - NAOMI cost-effectiveness

Nosyk et al CMAJ 2012

If you have ‘retention benefit’ to treatment you will be cost effective

Eliminating financial barriers to treatment

Canada - universal health care - medications covered to varying degrees - relaxing constraints on the availability, length of take-home doses could reduce costs to clients who pay for their own pharmacy services

Other benefits - increase access to clients in rural areas, allow patients who have demonstrated stability greater freedom to participate in family life and employment

Regulations in place to prevent diversion is the primary argument - ‘the argument is moot if it is only provided under direct observation in a pharmacy or clinic”

-given pharmacological properties, methadone is less subject to abuse and less desirable to other readily available opiates

Mortality due to methadone overdoses cited as another barrier - increases in overdose are largely from methadone prescriptions for pain,

Undue restrictions on prescribind medications counter production

Weekend training and methadone certification programs for GPs

Lower mainland, greater toronto - vast increases in access, indications of satisfied demand

but elsewhere - waiting lists from 2 weeks to 12 months , St. John 12 month, Montreal, 6 to 12 months, Manitoba 6-12 months, BC waitlists problems outside lower mainland

Availability of buprenorphine BP-NX and their inclusion in drug formularies - several provinces have allowed coverage under special authority

-good idea to allow as secondary option to Methadone

Opioid Detoxification

• most people relapse after detoxification
• alot of tapering and desire to taper
• longer tapers have higher odds of success - 12 to 52 weeks versus 12 weeks)
• 4x more likely to succeed
• tapers taking more than a year 7x more likely

5% for week for tapering is clinical guideline

Best to decrease by stepped every 2 to 4 weeks

Extended vers Short term Buprenorphine - Naloxone for treatment of Opioid Addicted Youth

• treatment was far better than taper

Mortality among regular or dependent users of heroin and other opioidsL a systematic review 

• people are more likely to die outside of treatment by 2.8 factor
• Degenhard - Drug Alcohol Dependence 2009- 
• Mortality among clients of a state wide opioid pharmacotherapy program over 20 years  and lives saved

Analysis of OST outcomes in publicly funded clinicisn in Calirofornia 1991 to 2011

-total unique individuals 200,000 plus

-every time they reentered detox - likelihood of success decreased

-every contact with methadone maintenance program - tended to stay longer

Current emphasis on detoxification needs to be addressed

-clients desire unlikely to change

-practitioners should obtain and sign release showing they ahve been advised of risk

New developments

 Injectable morphine

injectable heroin

Buprenorphine Implants for Treatment of Opiod dependence

• Rosenthal et AL, ADDICTION, 2013
• - promising 

Naltrexone - was done in russia where methadone illegal

-high proportion of confirmed abstinence

-long acting antagonist - what do you do if your client in car accident with legitimate need for opiate

Need for data collection to improve quality of care

BC Pharmanet, Popdata BC - gold standard

6 patterns of dosing noted in research

Q&A

-difficulty of giving buprenorphine and methadone in aboriginal communities

Pregnancy and Addiction - Dr. Stacy Seikel

Dr. Stacy Seikel ( http://stacyseikelmd.com/biography/) presented at the IDAA 2012 Medical Conference in Orlando Florida on the topic of Addiction and Pregnancy.  Her slides were remarkable and her presentation one of the most informative and engaging presentations I've been priviledged to hear.  Given the importance of her message regarding the future generation and the unborn child, universal screening is the very least that can be considered.  The hundreds present were equally impressed given the level of applause. Dr. Seikel's work is not only cutting edge technologically but she had done amazing networking to ensure that women and families can access the treatments that are needed for the betterment of individuals and society.  It was clear that she was motivated by a deep spiritual and ethical moral system of concern for pregnant women suffering from addiction.  She demonstrated the compassion and empathy for these women who are so commonly ashamed and carry such stigma with their addiction when they simply can't say 'no' without the help of doctors and society when pregnant they want to change.  Dr. Seikel is clearly there for her patients.
The following are the rough notes I took during the presentation with just a few highlights taken from many slides in which she simply wanted to point to one aspect of the problem or the solution. I was unable to get all the information but know that her slides and notes are available through the www.idaa.org.  International Doctors in Alcoholics Anonymous was very fortunate indeed to have someone of Dr. Seikel's training, experience and high level of functioning in the system where it counts, most to come to the conference to present in the Continuing Medical Education in Addiction Medicine portion of the conference. I would strongly recommend her as one of the finest lecturers I've heard on a terribly important topic in our present day.

Pregnancy and Addiction

• Dr. Stacy Seikel 

IDAA - Orlando - 2012

Prevalence

12 to 24% women use drug and alcohol during pregnancy

1 of every 3-4 women expose fetus to alcohol

Risk Factors

Family history of addiction

Experienced violence in childhood

Clues in medical history

No prenatal care

-fear of discovery of addiction

-secondary to general chaos in her life

Tattoos or self scarring

-seconary to IVDU or skin popping

Burns on hands and clothing

Positive hepatitis

Nicotine abuse

Screening

All pregnant women should be screened for drug and alcohol use

-T-Ace

-TWEAK

A positive test indicates need for a further evaluation

Elements of the history and physical may indicate need for drug screen

Immunoassay Drug Screens (not test)

• POC UDS = immunoassay
• semi quantitative immunoassay - not confirmation test
• lab screen UDS = immunoassay
• GCMS= Confirmation test
• LCMSMS = Confirmation test
• It’s important to know that a second immunoassay isn’t a ‘confirmation test’, must order a ‘confirmation test’ to know.

E-Forcse

Florida’s Prescription Drug Monitoring Program 

PMP - shows every controlled substance prescribed and where from - helps get around the denial, 

Patient advisory reports - used by the methadone maintenance program

We know that relapse is harmful to the fetus hence methadone is better.

Taper isn’t as good but will work with those who want a as a plan b.

Treatment Barriers

Fear, shame and guilt about use

-will she lose children if in treatment

-does she have family support

-attitudes of medical providers

Lack of comprehensive clinical care for all the problems of pregnancy and addiction

• can she get treatment?  Transportation problems?
• Care is fragment
• lack of childcare in treatment
• basic needs must be met for her to engage in treatment

Co morbid diagnois impacting ability to access services

• multiple problems associated with co morbidity, ex psychiatric symptons

Alcohol

-known teratogen

-no safe level of drinking in pregnancy

New Alcohol Biomarker in cord blood

=3-4 week retrospective of alcohol use

Medical Complications of Drug Abuse in Pregnancy

Same as in regualar patients

Obstetrical complications of opiate abuse

-Polysubstance abuse is the norm

-increase in spontaneous abortion, esp first trimester

-amnionitis

-intrauterine growth retardation

-placental insufficiency

-postpartum hemorrhage

-preeclampsia, eclampsia

-premature labor/membrane ruptures

-septic thrombo

Opioid Dependence (DSM IV) Aka Addiction

Opioid Addiction

-chronic progressive, relapsing

-neurobiolgic changes

 -pharmacologica treatments are effective in normalizing neurobiology

There is a big difference between short acting and long acting opiates.

• animal studies show long acting opiates can cause healing of the mu receptors which can go back to normal state
• brain makes new endorphins - so when I ‘m tapering off buprenorphines I encourage my patients to ‘go make endorphins’ - walk the dog, eat chocolate, take a bubble bath etc.

90 meetings in 90 days, is said in AA but it’s no coincidence because the first 90 days has so much healing that is going on.  

Medication assisted treament is one option for people to engage in a treatment program to develop psychosocial skills to be able to tolerate a taper when they have some relapse prevention skills

Drug addiction is a brain disease

• prefrontal cortex mri studies show ‘disruption of brain circuits involved in reward and punishment’
• prefrontal cortex is the executive function

Morphine has a jack hammer on and off mu effect

• altered gene expression - you no longer are the person you were before you used drugs
• limbic system in overdrive
• prefrontal cortex not working
• “You have to use to survive”

-this is why a pregnant woman will use and she is so ashamed, because there’s nothing worse in her eyes and in the eyes of others than a woman who uses drugs

Because relapse is high in this population we have found maintaining women on methadone 

Various Discipline see the Maternal Fetal Dyad differently

-obstetricians

-therapists

-addiction specialists

-psychaitrists

-pediatricians

-corrections officers

“Those in recovery who have themselves experienced loss of control will hopefully have some compassion for these women who get very little compassion from anyone else”

In Florida Orange County have developed an interdisciplinary program involving methadone treatment, hospital, high risk obstetric unit, outpatients and jail

Methadone and Pregnancy

-Methadone is only agonist therapy recognised for use in pregnancy,  Supported by 30 years of research

Federal Laws Governing Addiction Treatment

-requires special federal license

-rules and rules and rules

Opiod agonist maintenance in pregnancy

• maintenance with methadone during pregnancy produces the same benefits as treatment in non pregnant 
• The studies  (Jones H, 2008) are really poor by evidence based medicine for taper because of the high risk of relapse.  But if patient individually demands this despite the evidence against it, taper in second trimester - make sure though that there is no significant abstinence syndrome (Luty,J, Nilodeau V, Bearn J 2004) 

Pregnancy patients receive all the same results methadone treatment programs for non pregnant

Clinical Study last year showed buprenorphine may have less abstinence but can have complications for c section 

 Methadone Induction

-start low - go slow

5 days until steady state obtained

• peaks 2-3 hour after dosing
• Consider dosing in office and observing patient for 3 hours

Opiate intolerant (or someone you’re not sure) Day 1 10-15 mg max

Opiate tolerant day 1 25 to 40 mg max

Increase every 5 days

The right dose throughout pregnancy is the dose that stops withdrawal

Buprenorphine

not fda approved, methadone gold standard in pregnancy but can be used and is widely used in Europe

NEJM Dec 2011 study

Suboxone can be changed directly to Subutex

Induction is very tricky because you are supposed to give suboxone when people are in withdrawn but this is contraindicated so while it can be done it’s 

I don’t go from methadone to buprenorphine because of the withdrawal problems

Ongoing illicit or polysubstance use

Perioperative pain management for patients on buprenorphine

anesthetists need to know last dose, 

-continue dose tid or qid (don’t stop because we must avoid withdrawal for fetus in pregnancy

-use non narcotic pain medications

-Fentanyl with it’s high affinity may over ride antagonist effect

With methadone in pregnancy dose once a day and realize post op may need 10 to 20% more narcotic because of pain

Discharge Pain Meds should be a fixed amount - tend to give ‘excess’ medications especially the post op patients who give too much - teen agers are dying from pills in medicine cabinet

Breast Feeding on Methadone

• it’s okay to breast feed - came from American Academy of Pediatrics

Suboxone and Dr. Patrick Fay

Even the offer of a splendid dinner in one of Vancouver's finest restaurants, the Market, in the Shangri la Hotel, isn't likely to get me out for an evening of learning after a normal grueling 10 hour work day so common to Canadian physicians.  As an addiction psychiatrist having family physician, specialist, subspecialist and more subspecialist certification, and an even unhealthier proclivity for extensive self learning,  I am usually finding in my own practice that the rate limitting steps in health care management are the stupidity and hostility of overpaid, under educated,  beaurocratic thugs with position authority and purse strings.  My rich patients can get the health care they need here or overseas but increasingly those most in need are targetted alongside their care givers for chronic abuse.
That said, Dr. Patrick Fay of Orchard Treatment Centre is not only a leading authority in addiction medicine but one of the most respected clinicians I personally know. Having had the honour of treating patients who have known him I've had the privilege to hear of his empathy and compassion as a human from those patients  as well as see the genius in his medical management with patients who frankly were most unlikely to make it. Dr. Gary Horvath another leader in the treatment of opiate dependent patients encouraged me to come out if only to have the pleasure of bantering with my addiction medicine specialist colleagues,  Dr. David Tsung and Dr. Leszek Kalinowski.  In addition to these two racanteurs I was delighted to finally meet  Dr. (George) Djordges Kljacic, a most highly regarded clinician and the author of The Art and Wisdom of Healthy Living. http://www.amazon.ca/Art-Wisdom-Healthy-Living/dp/1467033138. Across the table I saw Allison, Olive and Sean, the administrative and counselling staff of Doc Side Medical Clinic,  also present.
Sarah Hardy, the representative of Reckitt Benckiser Pharmaceuticals was a surprise.  I thought she was a Vogue model and shocked to have her speak to me till my mind overrode my eyes and accepted that this must truly be one of those unfortunate women of brains whose beauty confuses the average male, not that I was such a human.  She welcomed me and immediately began talking science, mu receptors, k receptors and partial agonists till my mind  was spinning. When the waitress offered me a glass of wine I gladly took a cup of coffee instead.


Dr. Patrick Fay's presentation on Suboxone was excellent, not just for the more academic overview of addiction and the place of buprenorphine in the treatment of opioid dependent patients but also for his extensive clinical experience.  Buprenorphone is the active opiate ingredient in Suboxone. Compared with the full agonist methadone which is also used for the treatment of opioid dependent patients, buprenophone is a partial agonist so has 'ceiling effect',  a decided limit to it's potential for abuse.  The genius of Suboxone is that it is coupled in a 4:1 ratio with Naloxone, the opioid antagonist.  Suboxone is taken sublingually which allows buprenorphine to be released without naloxone. However if it is injected the naloxone counteracts the effects, making the medication even safer from being abused IV.
Dr. Patrick Fay had excellent slides showing the 'disease' of addictiton. He distinguished addiction by the classic 3 'c's, loss of control, continuance despite negative consequence, and a compulsion to persist despite this. He briefly discussed the  MRI studies showing impairment in glucose utilization in the frontal lobes, associated with higher reasoning, and delaying gratification,  as well as discussing the impairment of the nuclear accumbens, the emotional reward centre of the brain. (http://en.wikipedia.org/wiki/Nucleus_accumbens).
Where he shone though was in detailing carefully for us clinicians how he himself began patients on suboxone.  He described the use of the COWS, Clinical Opiate Withdrawal Scale (www.naabt.org/documents/cows_induction_flow_sheet.pdf.,
Then he went on to say that though the guidelines suggest a number of 10 before starting he himself tended to prefer a number of 12. He began by giving the patient 2 mg then tended to give 8 or even more mg through that first day. He saw the patient usually three times  that first day and told the patients they needed to have that day off and a friend available to be with them.  He admitted that headache was a side effect that he'd seen but in the large numbers of patients he'd treated he'd only had one  stop because of persisting headache. He'd also had to stop one patient from going onto buprenorphine maintenance because they developed a variety of odd pains. Withdrawal syndrome was the principal concern because buprenorphine has such strong affinity to the mu opioid receptor that it displaces other opiates. When transfering a methadone maintenance patient to suboxone he reduces the methadone to roughly 30 mg a day before making the switch.
He had used suboxone extensively in young people 18 to 25 and preferred to include the parents in the care if the patients were living at home.  He found that this family approach to addiction therapy resulted in even better results. While some of his patients have been switched in the detox and treatment facilities he has at the Orchard Treatment Centre on Bowen Island the majority of his patients have been started on suboxone in the community. He himself has a clinic where he does just this on Commercial Avenue in Vancouver.  As well as young people he found those who appeared to most benefit from suboxone were those who were snorting opioids, those using opioids such as morphine or oxycontins as opposed to heroin, and those whose methadone usage was under 100 mg a day. He said that there was a belief in the community that it was easier to get off buprenorphine but that he himself had found that it was still difficult for patients to stop that last 2 mg a day.  Suboxone maintenance patients were commonly able to take their medications weekly and were seen monthly relieving them the need of daily visits to a pharmacy for witnessed injestion.  He used suboxone for detox and for maintenance of patients with very good patient report and success long term.
Overall he found that he had the best results with patients who recognised that  addiction was more than just the drug abuse but that it affected, sometimes prominently while other times subtly, their thinking and relationships as well. Addiction specialist, Rabbi Dr. Twerski has written an superb book, called "Addictive Thinking",  detailing this essentially neurological disease process.   Follow up in groups such as AA, NA, Smart Recovery,  and Cognitive Behavioural Therapy  were all associated with better long term protection from relapse. He quoted Dr. Marc Gallanter's (http://en.wikipedia.org/wiki/Marc_Galanter_(psychiatrist) research on the efficacy of 12 step programs in long term recovery.
Dr. Fay concluded his presentation with his own complex case studies of patients who really were truly extraordinary for their successful long term recovery from what was clearly a life threatening illness with near death experiences.
Dr. Fay was very optimistic about suboxone and it's benefits but certainly didn't see it as a replacement for methadone. He was clear in the need to combine the right patient with the right treatment in what has traditionally been the most successful approach to all medical treatements to date. He was insistent that addiction patients be treated fairly and with the dignity that anyone suffering a chronic disease deserves.
His presentation was excellent and well worth the time.  To prescribe suboxone now in British Columbia the physician must already have been certified as a methadone prescribing doctor and in addition complete  online educational modules at www.suboxonecme.ca.  I did this when I worked in the United States and remember the process as reasonable and relatively straight forward. Sarah told me that it usually takes about 6 hours total.  There is now also public funding for suboxone for selected patients for whom methadone is contraindicated.
sarah.hardy@reckittbenckiser.com is a great resource.  Dr. Patrick Fay's presentation was well worth the effort, even after a long day.