1. By: Nellie Dennis
“EXTENDED VS. SHORT-TERM
BUPRENORPHINE-NALOXONE
FOR TREATMENT OF OPIOID-
ADDICTED YOUTH”
-A RANDOMIZED TRIAL-
2. Opioid dependence—physical addiction to prescription painkillers
and heroin—affects many people in the US.” ("Understanding
opioid dependence", 2015)
“If you or someone you know may be dependent on opioids, you
are not alone. In 2013, there were nearly 2.4 million reports of
people† that had abused or were dependent on opioids—such as
heroin—or prescription painkillers.” ("Understanding opioid
dependence", 2015)
“Know your opioids: Opioids can be prescription painkillers. For
example, Oxycodone, hydrocodone, and fentanyl—better known by
the brand names as OxyContin®, Vicodin®, Percocet®, and
Actiq®—are opioids. The street drug heroin is also an opioid.”
("Understanding opioid dependence", 2015)
JAMA: Journal of the American Medical Association,
Vol 300(17), Nov, 2008. pp. 2003-2011..
UNDERSTANDING OPIOID DEPENDENCE
3. Treats an addiction to or dependence on narcotic
medicine.
Brand name: Suboxone
Side Effects:
Side effects of buprenorphine are similar to those of other
opioids and include nausea, vomiting, and constipation.
Buprenorphine/naloxone can precipitate the opioid
withdrawal syndrome. Combination of: Naloxone,
Buprenorphine ("Understanding opioid dependence", 2015)
Legal status: Schedule III controlled substance
Other drugs in same class: Buprenorphine, Naloxone,
Naltrexone
WHAT IS BUPRENORPHINE-NALOXONE?
JAMA: Journal of the American Medical Association,
Vol 300(17), Nov, 2008. pp. 2003-2011..
4. Buprenorphine/naloxone may cause drowsiness or dizziness.
These effects may be worse if you take it with alcohol or
certain medicines. Use buprenorphine/naloxone with caution.
Do not drink alcohol while you are using
buprenorphine/naloxone.
Buprenorphine/naloxone may cause dizziness, light-
headedness, or fainting; alcohol, hot weather, exercise, or
fever may increase these effects. Do NOT change your dose,
use more often than prescribed, or suddenly stop taking
buprenorphine/naloxone without checking with your doctor.
Do not switch to another dose form of
buprenorphine/naloxone without talking to your doctor.
SAFETY INFORMATION
JAMA: Journal of the American Medical Association,
Vol 300(17), Nov, 2008. pp. 2003-2011..
5. Many of you work/intern in the Chemical Dependency
focus, just like myself; What are your views on the
effectiveness of Suboxone and/or detox?
QUESTION
JAMA: Journal of the American Medical Association,
Vol 300(17), Nov, 2008. pp. 2003-2011..
6. “To evaluate the efficacy of continuing
buprenorphine-naloxone for 12 weeks vs.
detoxification for opioid-addicted youth.” (JAMA: Journal
of the American Medical Association, Vol 300(17), Nov, 2008. pp.
2003-2011.)
“The usual treatment for opioid-addicted youth is
short-term detoxification and individual or group
therapy in residential or outpatient settings over
weeks or months.” (JAMA: Journal of the American Medical
Association, Vol 300(17), Nov, 2008. pp. 2003-2011.)
OBJECTIVE
JAMA: Journal of the American Medical Association,
Vol 300(17), Nov, 2008. pp. 2003-2011..
7. Clinical trial at 6 community programs in the
National Institute on Drug Abuse from July 2003 to
December 2006.
152 patients aged 14 to 21 years
CASE STUDY DESIGN
JAMA: Journal of the American Medical Association,
Vol 300(17), Nov, 2008. pp. 2003-2011..
8. All patients were randomized to 12 weeks of buprenorphine-
naloxone (Suboxone) or a 14-day taper (Detox) between July,
2003 and December, 2005
“A biased-coin randomization protected against severe
imbalance of sex, ethnicity, route of administration, and age
across the treatment groups.” (JAMA: Journal of the American
Medical Association, Vol 300(17), Nov, 2008. pp. 2003-2011.)
ENROLLMENT AND RANDOMIZATION
JAMA: Journal of the American Medical Association,
Vol 300(17), Nov, 2008. pp. 2003-2011..
9. Reckitt Benckiser Pharmaceuticals Inc. provided medication,
and the NIDA coordinated its distribution.
Day 1:
First Dose: 2-mg. of Suboxone with 0.5-mg of naloxone.
Second Dose: 2-6-mg was administered if appropriate.
Day 2:
Received dose from day 1 unless considered over-medicated or
under-medicated.
Dose adjusted by 2-6-mg as needed.
Day 3:
Received dose from day 2 unless needed adjustment
MEDICATION AND DOSAGE
JAMA: Journal of the American Medical Association,
Vol 300(17), Nov, 2008. pp. 2003-2011..
10. Suboxone Group:
Received a maximum amount of 24-mg per day and began
tapering at week 9 that would end by week 12!
Detox Group:
Patients in the detox group received up to a maximum amount
of 14-mg buprenorphine per day and ended their taper by day
14.
MEDICATION AND DOSAGE
JAMA: Journal of the American Medical Association,
Vol 300(17), Nov, 2008. pp. 2003-2011..
11. All patients were scheduled for 1 individual and 1 group
session per week with more frequent sessions if needed!
Counseling Process:
Making positive relationships
Stopping the drug use
Coping mechanisms throughout treatment
Prescribed Medications
Triggering situations
Education on addiction
Feedback on achieving personal goals
Encouraging self-help meetings
DRUG COUNSELING
JAMA: Journal of the American Medical Association,
Vol 300(17), Nov, 2008. pp. 2003-2011..
12. The primary outcome was opioid-positive urine test results at
weeks 4, 8, 12. Urine samples were tested for adulteration
(color, specific gravity, temperature)
Two tests were used:
The Sure Step (Inverness Medical Innovations, Bedford,
England) that identifies amphetamine, barbiturate,
benzodiazepines, cocaine, methadone, methamphetamine,
morphine, hydrocodone, hydromorphone, oxycodone,
phencyclidine, and tetrahydrocannabinol.
The second was the Rapid One OXY (American Bio Medica Corp,
Kinderhook, New York), which is more sensitive to oxycodone.
PRIMARY OUTCOMES
JAMA: Journal of the American Medical Association,
Vol 300(17), Nov, 2008. pp. 2003-2011..
13. Secondary outcomes were dropout from the assigned
condition, self-reported use, injecting, enrollment in addiction
treatment outside the assigned condition, other drug use, and
adverse events.
Patients were considered drop outs if they missed medication
for 3 consecutive days in the detox group or 7 consecutive
days if in the 12 week suboxone group
Follow up visits as months 6, 9, and 23 included assessing
self-reported use of opioids, alcohol, marijuana, and cocaine
and injecting in the past month and determining whether
patients were receiving other addiction treatment.
SECONDARY OUTCOMES
JAMA: Journal of the American Medical Association,
Vol 300(17), Nov, 2008. pp. 2003-2011..
15. Among 78 Detox patients, 16 (20.5%) completed
Among 74 in the D12-week buprenorphine-naloxone
group, 52 (70%) completed.
The most common reason for non completion was
missing 2 weeks of counseling.
RESULTS
JAMA: Journal of the American Medical Association,
Vol 300(17), Nov, 2008. pp. 2003-2011..
16. Months 6, 9, and 12
Patients in the detox group provided higher proportions of positive
urine test results than patients in the 12-week suboxone group.
Although high rates were seen in both groups:
Suboxone: 48%
Detox: 72%
There was a trend for fewer detox patients to be in other addiction
treatment and for detox patients to have higher rates of marijuana
use
The 2 groups did not differ in rates of self-reported use of alcohol.
POST-TREATMENT RESULTS
JAMA: Journal of the American Medical Association,
Vol 300(17), Nov, 2008. pp. 2003-2011..
17. No serious adverse events attributable to suboxone were
removed for adverse events
Headaches were the most common events reported by 16% to
21% of patients in both groups
Other symptoms of nausea, insomnia, stomachache, vomiting,
anxiety were reported by less than 10%
One death occurred in a 19 year old patient in the suboxone
group who dropped out.
JAMA: Journal of the American Medical Association,
Vol 300(17), Nov, 2008. pp. 2003-2011..
COMMENTS
18. Short term vs long term addiction
Young adult vs Adult
Suboxone patients are much more engaged in longer term
treatment = better success?
JAMA: Journal of the American Medical Association,
Vol 300(17), Nov, 2008. pp. 2003-2011..
COMMENTS
19. Small proportion of patients younger than 18 years
Almost total absence of young African American individuals
Frequent observed tox
Good or Bad?
Low follow-up rate
Did not access adverse effects beyond 12 months
JAMA: Journal of the American Medical Association,
Vol 300(17), Nov, 2008. pp. 2003-2011..
LIMITATIONS
20. Do you feel that this study is valid regardless of the
limitations I have found?
Do you feel that Suboxone is an effective method after
looking at this study?
How could this study improve, in your opinion?
JAMA: Journal of the American Medical Association,
Vol 300(17), Nov, 2008. pp. 2003-2011..
QUESTIONS
21. Woody, G. (2003). “Extended vs. Short-term Buprenorphine-
Naloxone for Treatment of Opioid-Addicted Youth”-A
Randomized Trial-. 300(17), 2003-2011. Retrieved January 1,
2011, from PsycINFO.
Understanding opioid dependence. (2014, January 1).
Retrieved April 7, 2015, from
http://www.suboxone.com/understanding-opioid-dependence
REFERENCES
Editor's Notes
Just to give a bit of a background on opioid dependence and addictions in this area, I figured I would research some data about how large of a concern opioids are becoming for young adults and adults all around the world, especially in New York.
Opioid dependence—physical addiction to prescription painkillers and heroin—affects many people in the US.” ("Understanding opioid dependence", 2015)
“If you or someone you know may be dependent on opioids, you are not alone. In 2013, there were nearly 2.4 million reports of people† that had abused or were dependent on opioids—such as heroin—or prescription painkillers.” ("Understanding opioid dependence", 2015)
“Know your opioids: Opioids can be prescription painkillers. For example, Oxycodone, hydrocodone, and fentanyl—better known by the brand names as OxyContin®, Vicodin®, Percocet®, and Actiq®—are opioids. The street drug heroin is also an opioid.” ("Understanding opioid dependence", 2015)
What is suboxone?
Treats an addiction to or dependence on narcotic medicine.
Brand name: Suboxone
Side Effects:
Side effects of buprenorphine are similar to those of other opioids and include nausea, vomiting, and constipation. Buprenorphine/naloxone can precipitate the opioid withdrawal syndrome. Combination of: Naloxone, Buprenorphine
Legal status: Schedule III controlled substance
Other drugs in same class: Buprenorphine, Naloxone, Naltrexone
It is used in many facilities such as Horizon- Health Services where I have been completing my internship for the past year as many of you know! There are generally suboxone doctor’s and/or doctor’s that enter the facility to complete all of the prescribing, regardless of what the drug is! Please remember that this substance should be prescribed to only fully functioning addicts otherwise this can cause abuse concerns etc. Which I will get into a little bit further later.
SUBOXONE Film is a prescription medicine that contains the active ingredients buprenorphine and naloxone. It is used to treat adults who are dependent on (addicted to) opioids (either prescription or illegal).
SUBOXONE Film is indicated for treatment of opioid dependence and should be used as part of a complete treatment plan to include counseling and psychosocial support.
Treatment should be initiated under the direction of physicians qualified under the Drug Addiction Treatment Act.
Treatment should begin under the supervision of a doctor. In appropriate patients, treatment may continue at home with follow-up visits to a doctor at reasonable intervals.
SUBOXONE Film is intended for administration under the tongue and is available in four dosage strengths.
Some of you may have heard of Zubsolv as another option for example: Zubsolv sublingual tablet is indicated for the maintenance treatment of opioid dependence and should be used as part of a complete treatment plan to include counseling and psychosocial support.
Buprenorphine/naloxone may cause drowsiness or dizziness. These effects may be worse if you take it with alcohol or certain medicines. Use buprenorphine/naloxone with caution. Do not drink alcohol while you are using buprenorphine/naloxone.
Buprenorphine/naloxone may cause dizziness, light-headedness, or fainting; alcohol, hot weather, exercise, or fever may increase these effects. Do NOT change your dose, use more often than prescribed, or suddenly stop taking buprenorphine/naloxone without checking with your doctor.
Do not switch to another dose form of buprenorphine/naloxone without talking to your doctor.
This has become a large concern at Horizons due to many clients taking advantage of being placed on the suboxone to assist with their opioid addiction. Many people, unfortunately, have been selling the suboxone that they receive for themselves, abusing it by taking more than prescribed, and even switching the doses as described here without their doctor’s consent. This can effect a client drastically. As we know, medicine’s will have different impacts on everyone. At Horizons for example, they have set a structure up to have each client on suboxone have to come in and have their Primary Counselor count their medication periodically to ensure they are taking it as prescribed, meeting frequently with the prescriber and primary counselor and even continuously discussing the educational piece behind what the drug is used for and creating that close relationship between all that are involved to avoid any abuse.
So, to start out, I know many of you are working and/or interning with the Chemical Dependency focus, just like myself at Horizons? If so, I wanted to know what some of your views are on the effectiveness of Suboxone and/or detox and how successful you feel it is for clients?
What are some things we could change or improve when suboxone is prescribed to clients, based on your experiences in the field so far?
The overall objective of this study is to evaluate the efficacy of continuing suboxone treatment for 12 weeks vs. detoxification for opioid addicted youth.
The usual treatment for opioid-addicted youth is detoxification and counseling within a weekly sessions of both individual and group setting.
The study states that relapse is high, yet many programs remain strongly committed to this approach and, except for treating withdrawal, do not use agonist medication.
There tends to be more family focus and involvement for youth still living at home and/or those that have a closer relationship with family/parental role.
Extended medication-assisted therapy may be more helpful.
The study initiated a randomized trial of more extended treatment vs. the usual short term detox among youth. The study was conducted at 6 different sites in the National Institute on Drug Abuse (NIDA) Clinical Trials Network.
Four of these programs were methadone programs and two were adolescent programs that started using Suboxone for the study.
The study was open to individuals aged 14- 21 years whom met the DSM-IV criteria for opioid dependence with physiologic features and who sought out treatment.
Participants 18-21 years old had to provide written consent and correctly answer 9 out of 10 questions testing their understanding of the study.
Participants 14-17 had to provide written assent and written parental consent and both the client and the parents had to pass the exam about the study.
There were many criteria for participating in the study and I thought it would be interesting to share with you all.
You were excluded from the study if you had medical or psychiatric conditions, those that were abusing alcohol or sedatives or using benzodiazepines for more than 15 days in the last 28 days, having had a sedative overdose in the past 6 months, being able to provide a negative urine test for benzos and methadone, receiving other addiction treatment, being likely to be incarcerated or to leave the area, breastfeeding or being pregnant, unable or un willing to use effective birth control, or receiving psychotropic medication other than a selective serotonin reuptake inhibitor.
All patients were enrolled between July, 2003 and December, 2005 and randomized to a 14-day outpatient detoxification or 12 weeks of treatment with Suboxone.
Randomization occurred through an automated 24 hour service at the Veterans Affairs Cooperative Studies Program in Maryland, that was programmed to randomize patients separately by site. A biased-coin randomization protected against severe imbalance of sex, ethnicity, route of administration, and age across treatment groups. Age was dichotomized as 14-18 years or 18-21 years.
Reckitt Benckiser Pharmaceuticals Inc. provided medication, and the NIDA coordinated its distribution.
Patients receiving suboxone were instructed to not use heroin or other opioids for at least 6 hours and to be experiencing mild/moderate withdrawal prior to the first dose.
They were all told to hold the medication under the tongue until it dossolved and that it was likely to cause withdrawal if dissolved and injected by someone who was opioid dependent.
Medication was administered on site 5-7 days were week. When patients were in the facility to receive medication they were observed.
Day 1-First Dose: 2-mg. of Suboxone with 0.5-mg of naloxone. The study personnel observed the patient for 1.5 to 2 hours, and a second dose of 2-6-mg was administered if appropriate.
Day 2- Received dose from day 1 unless considered over-medicated or under-medicated. They were observed for 1.5-2 hours and the dose adjusted by 2-6 mg as needed.
Day 3- Received dose from day 2 unless needed adjustment and observed for 1.5-2 hours and given another adjustment if needed.
The suboxone group would only receive a maximum amount of 24-mg per day and began tapering at week 9 which would end by week 12.
Patients in the detox group received up to a maximum amount of 14-mg buprenorphine per day and ended their taper by day 14. If patients missed three consecutive days of doses, their medication was stopped. Medication was not restarted if this occurred. Although in the suboxone group, only if they returned within 7 days of the latest dose. They were restarted with half of the amount of the last dose received and the observations were started again.
Patients who dropped out for missing medication were encouraged to continue in counseling treatment.
Any adverse events were assessed by weekly vital signs and assessments for sedation and withdrawal, and questions about additional medications received and adverse effects in weeks 1-12. Similar assessments were completed at months 6, 9 and 12.
All patients were scheduled for 1 individual and 1 group session per week with more frequent sessions if needed!
This process encouraged…
Counseling Process:
Making positive relationships
Stopping the drug use
Coping mechanisms throughout treatment
Prescribed Medications
Triggering situations
Education on addiction
Feedback on achieving personal goals
Encouraging self-help meetings
The primary outcome was opioid-positive urine test results at weeks 4, 8, 12. Urine samples were tested for adulteration (color, specific gravity, temperature), although most patients were not observed during the collection because it was difficult to match female staff with female patients and vice-versa.
Two tests were used:
The Sure Step (Inverness Medical Innovations, Bedford, England) that identifies amphetamine, barbiturate, benzodiazepines, cocaine, methadone, methamphetamine, morphine, hydrocodone, hydromorphone, oxycodone, phencyclidine, and tetrahydrocannabinol.
The second was the Rapid One OXY (American Bio Medica Corp, Kinderhook, New York), which is more sensitive to oxycodone.
Secondary outcomes were dropout from the assigned condition, self-reported use, injecting, enrollment in addiction treatment outside the assigned condition, other drug use, and adverse events. Patients were considered drop outs if they missed medication for 3 consecutive days in the detox group or 7 consecutive days if in the 12 week suboxone group, did not have an individual group or group session lasting 30 min or more for 14 consecutive days, enrolled in other addiction treatment, asked to be withdrawn, went to jail, or died.
Follow up visits as months 6, 9, and 23 included assessing self-reported use of opioids, alcohol, marijuana, and cocaine and injecting in the past month and determining whether patients were receiving other addiction treatment.
Patients were actually paid $5 each for weekly assessments and $75 each for assessments at weeks 4, 8, and 12 and months 6, 9, and 12.
While looking at this chart given in the study, you will see that of 236 patients screened, 154 were randomized and 152 entered treatment.
The most common reasons for exclusion were use of benzodiazepines and failure to return. There were no significant group differences in sex, race, years of drug use, injecting in the past 30 days, age, hepatitis C status, work status, educational level or marital status.
Although the study was open to individuals ages 14-21 years old, there was only one 15 year old and no 14 year olds enrolled in the study.
Maximum doses for detox patients were as follows:
24 (31%) received 2 to 8 mg and
53 (68%) received 9 to 14 mg.
For patients receiving 12 weeks of buprenorphine-naloxone, 20 (27%) received 2 to 8 mg, 43 (59%) received 9 to 16 mg, and 10 (14%) received 17 to 24 mg.
Among 78 Detox patients, 16 (20.5%) completed
Among 74 in the D12-week buprenorphine-naloxone group, 52 (70%) completed.
The most common reason for non completion was missing 2 weeks of counseling.
Detox patients were more likely to report opioid use, cocaine use, and injection. In addition, detox patients were more likely to report enrollment in other addiction treatment.
Groups did not differ in rates of self-reported alcohol use.
Patients in the 12-week suboxone treatment group attended more counseling sessions than patients in the detox group.
No serious adverse events attributable to suboxone were removed for adverse events
Headaches were the most common events reported by 16% to 21% of patients in both groups
Other symptoms of nausea, insomnia, stomachache, vomiting, anxiety were reported by less than 10%
One death occurred in a 19 year old patient in the suboxone group who dropped out after 3 doses and was not located until her obituary appeared in a newspaper 3 months later. The medical examiner report cited methadone overdose as the cause.
4 of 83 patients were tested positive for Hepatitis C at week 12. Two patients from each group.
Taken together, these data show that stopping suboxone had comparably negative effects in both groups, with effects occurring earlier and with somewhat greater severity in patients in the detox group.
Although patients were young and reported regular opioid use for 1.5 years on average, their findings resembled those after detox of opioid dependent adults with much longer periods of addiction.
12 week suboxone patients had lower proportions of opioid positive urine test results at follow up appointments, although the difference with detox patients were much less than in weeks 1 – 12 but possibly because suboxone patients are much more engaged in longer term treatment.
The data do not show much information on how long suboxone should be provided, but the potential for rapid re-addiction following medication cessation, over dose death, infection with HIV and addiction-related psychosocial impairments, they show that detox whether performed over 2 weeks to 3 months was largely ineffective for young patients with short periods of addiction when done under outpatient conditions. This shows that the medication should be continued regardless of age or length of addiction concerns.
As stated in the case study, there were a wide range of ages, and a balanced but random set of men and women of any gender. The only limitation with that is there were very few patients under the age of 18. When including a younger population, you have to take into consideration that they may not have been addicted to a substance for as long; they might have a different support system than many in the older population; their responsibilities and free time could be much more flexible and/or limited at a younger age etc. These are just a few of many thoughts that could arise when working with young adults. Just out of pure interest, I would like to know if men or women were more successful in which program. That might be something interesting to look into for counseling purposes in general!
There was a total absence of young African American individuals, let alone young adults as it is.
There were frequent observed toxes by the primary counselor and prescriber. There are many good and bad things about this part. Having observed toxes on a weekly or biweekly basis is helpful and encourages the patients to abide by the requirements of the program. On the other hand, having less supervised toxes might show the ‘true’ results on how the patients were actually doing.
There was a low follow-up rate between the counselors and the patients throughout the program. They did not mention if the patient’s were receiving counseling for their addiction their first or second or even third time? There was no real background information on the patients involved, but I know that might have made the process difficult to track that many details.
And finally, they did not access adverse effects beyond the 12 months when the case study was over. It would be beneficial for the people completing the study to reach out the patients to see if they have followed through with continued counseling or self-help meetings. The follow up would show it’s long term effect and the progression of all of the patients. Those that were not successful throughout the program might have gone back and been successful their second time around.
Clinical Implications:
1) Because much opioid addiction treatment has shifted from inpatient to outpatient where suboxone can be administered, having it available in primary care, family practice, and adolescent programs has potential to expand the treatment options available to opioid addicted youth and significantly improve outcomes. Other effective medications, or longer and more intensive psychosocial treatments, may have similarly positive results. Studies are needed to explore these possibilities and to assess the efficacy and safety of longer-term treatment with suboxone for young individuals with opioid dependence.
