KCQ 2&3 ALL:
Sep 24/10
Oct 19 (Rev). June 30 10 July 19/10 (Arjun). Aug 2 CH. Aug 16/10 CH. Sep 13/10 AK. Sep 20CH
8 studies need a 2nd reviewer
http://www.gacguidelines.ca/index.cfm?pagepath=Contact_Us&id=21076
Summary A: Daily vs. Non-daily (CH needs to reorganize this)
UDS: Retention:
Favors daily 1 No difference 6 Favors non-daily 0 Favors non-daily 1 (cohort) No difference 5 No difference 3
Subjective/withdrawal/pt preference:
Favors daily (w/d) 3
Favors non-daily (agonist) 3
Adherence:
Abstinence/Illicit use: No difference 4
Favors daily 1 Favors non-daily 2 (incl cohort)
Favors non-daily 0
No difference 4
Summary B: Dosing Issues
Detox vs BMT: Favors BMT: 1. Also one uncontrolled study (Kornor 2006) favours longer term treatment
More rapid initiation: Favors more rapid: 2 (Leonardi, Compton 1996) (but no stat data presented)
Higher vs. Lower dose: Favors higher dose: 7 ( but all studies are basically fixed dose and 3/6 involve not clinically meaningful interventions (Comer & Walker 2005, Greenwald 2002 and Correia 2006) .
Observed dosing vs unobserved: See Bell x 2 and Barau 2001
Summary C: Contingency Management
7 of 9 studies deemed “not relevant” by Mini-Team
2 remaining studies:
Money improves retention: 2 no
Money improves abstinence: 1 yes (for 12 weeks, not 24 weeks), 1 no
Withholding doses improves abstinence: 1 yes
Summary D: Patient/Clinic Characteristics
Primary care clinic vs addiction clinic: Two studies: PCC superior in one (O’Connor) and no difference in the other (Gibson)
Patient: major depression may favour bupe (Gerra 2004) to meth
Homeless men and housed men respond equally to bupe (Alford 2007)
Bupe may be better than meth for decreasing opioid use in those with hx of BZ abuse (Schottenfeld 1998)
Bupe and meth equal wrt depression (Dean 2004)
Bupe may be better for depression than other concurrent D/O grps (Gerra 2006)
Summary E: Therapy
Extended couselling same as regular counseling (Fiellin 2006)
Network Therapy (involving family) superior to medical mgmt wrt abstinence (Galanter 2004)
Psychothrapay decreased cocaine use (Monotoya 2005)
Non significant improvement in opioid use with specific drug counseling (Pantalon 2004)
1
KCQ 2&3 ALL: Oct 19 (Rev)
DATA TABLES
A. Daily vs Non-daily Dispensing (N=15) /Study
Reference / # pts / Study Design / Intervention / Primary Outcome Measures / Primary Outcome Results / Secondary Outcome
Measures / Secondary Outcome Results / Comments / Yes/No /
261. Amass 2001
CH/MC / 46 opioid dependent / · Randomized trial
· 11 week outpatient. Mostly injection users. 41 had been on meth previously. / · Day 1 induction 2mg bupe/naloxone
· Day 2 induction 8mg bupe/naloxone
· Day 17 were given either:
o A Daily dosing: daily observed
o B 3 day at clinic: double dose M/W and triple dose on Fri
o C 3 day with take home: observed single dose M/W/F with daily take-homes in between
· Designed so each subject experienced each of the three dosing schedules. “Randomly” assigned.
· With counselling / · Completion / · 13 completed the study
· 22 dropped out before day 17
· 11 more dropped out after day 17 (5 in daily group, 3 in each of the 3-day groups).
· Ie…only 13/46 completed the study as designed / · Subject rated measures (VAS) / · Higher for both 3-day schedules (p=0.002).
· 85% of the 13 pts who completed the study rated the 3 day with take home as “best”. / Large dropout rate
Unsatisfactory description as to how did each group experience each treatment condition
No reported outcomes between the 3d/wk observed to 3d/wk with take-homes.
Tracers/tab recall was not used to determine whether ingestion had in fact occurred. Ie study could not speak to diversion issue. / Yes /
· Medication compliance / · More doses taken in both 3-day groups (p=0.007) /
· UDS / · No difference between groups /
276. Petry 1999
CH/MC / 26 outpatients opioid dependent / · Randomized trial
· Approx 60 days / · After 18 days at a single daily maintenance dose, buprenorphine solution given daily, q 2, q 3 or q 4 days with placebo on the non-bupe taking days
· Each dose given 5 times.
· Max dose 8mg/70kg
· With weekly counselling / · Subjective withdrawal and VAS scores / · Withdrawal scores increased P<0.05 for end of 72 hour and 96 hour dosing intervals compared to daily dosing
· No significant increases in self-reported agonist effects 24 hrs after 4x dose compared to daily dose. / · Observer ratings / · No observer reported increase in agonist effects when 4x dose given under observation
· Pupil size 24hrs after dose decreased as dose increased (p<0.001)
· No significant difference in observer reported withdrawal scores / Subjects removed from study after 2 pos UDSs (5/26) / Yes /
· % pos UDS / · For opioids:
Q daily 11%
Q2d 9%
Q3d 4%
Q4d 6%
· Statistical data not given /
262. Amass 2000
CH/DG / 47 opioid dependence / · Randomized trial / · 11 week Bupe/naloxone tablets
· Initial maintenance after induction was 8mg/2mg for 14 days. Then:
o A 8mg/24 hrs
o B 8mg/48hrs
o C 16mg/48hrs
· “randomly assigned” / · Completion Rate / · 21/47 dropped out during the baseline
· 26/47 entered the study
· 14/26 completed.
· 5 drop outs 8mg/24hr gp
· 5 drop outs 8mg/48hr gp
· 2 dropouts 16mg/48hr gp
· Statistical data not presented / · Subjective / · No difference / Yes /
· Med compliance / · No difference / · Pupil diameter / · Larger 8mg/48 than in 16mg/48hrs /
· Illicit drug use / · No difference /
265.
de los Cobos 2000
CH/DG / 60 IV heroin dependent / · Randomized trial / · 12 weeks
· Daily 8mg vs 16mg M and W and 24mg Fri. Placebo on non-bupe days
· All doses observed / · Days of retention in treatment / · No difference (p=0.60) / Yes /
· Opioid positive urines / · Higher in three times per week group (p=0.001) /
· >4 weeks abstinent / · Higher in daily group (p=0.036) /
272. Marsch Bickel 2005
CH/DG / 134 opioid dependent / · Randomized trial / · Bupe maintenance
· Doses 4, 8, 10 or 12mg/d depending on pt response.
· Then dispensed daily, 3x per week (M W and F) or 2x per week (M and F).
· Also one hour of behavioural therapy per week
· 24 weeks of maintenance then taper over 8 weeks / · Opioid abstinence / · No difference / Underwent a 3 hour “laboratory safety assessment x 3hrs to ensure they could tolerate largest dose to which they would be exposed. No failures
Retrospective analysis: 3 predictors of abstinence:
1. Employment
2. 3x weekly dosing for those who had longer opioid use histories
3. Females better than males in twice weekly regimen / Yes /
· Cocaine abstinence / · No difference /
· Combined abstinence / · No difference /
· Treatment retention / · No difference (p=0.70) /
· HIV risk behaviour / · No difference /
· Addiction Severity Index (ASI) / · No difference /
260 Amass 1994
ML/CH / 13 opioid dependent (12 IVDU) / · Double Blind Crossover / · Initial 2mg, 4mg or 8mg/70kg maintenance dose for 13 days.
· 21 d of daily sl bupr vs alt. day dosing. Placebo used on interposed days
· After 21d each subject received the alternative option for 21 days / · Opioid agonist effects measured / · Pre-dose subject rated opioid agonist effect less with alternate day dosing.
· No difference found on objective measures. / · Withdrawal symptoms documented / · No significant differences in W/D symptoms between regimes
· More symptoms of withdrawal reported when placebo administered than when maintenance drug administered
· Statistical data not presented / Yes /
275 Petry 2001
ML/CH / 33 opioid dependent / · Double blind / · Buprenorphine solution dosing every day, q3d, or q5days. / · Subjective/Objective measurements of W/D / · Significant w/d reported at 96 and 120 hrs in q5d dosing regime (p<0.05), not with daily or q3d regimes / · UDS testing / · Did not vary systematically across conditions
· No statistical data presented / Authors comment that Bupr dosing q 3 or 4 days appears to be the upper practical dosing limit. / Yes /
268 Gross
2001
EJ/SS / 14 / · RCT / · 2 weeks of daily maintenance dosing (daily doses BUP 4-8mg/70kg), then:
· Subjects given 5x daily dose Q5D or 6x daily dose Q5D / · Subjective withdrawal and opiate agonist effects at 120h / · Significant increase in subjective withdrawal symptoms after 96 hrs in both groups.
· Symptoms appearing after 96 hrs are same in both groups
· Significant increase in subjective agonist effects 24 hrs after dose in both groups / · UDS / · No systematic difference between groups / 93% IV opioid users / Yes /
271 Leonardi 2008
CH/MC / 979 with opioid addiction / · Cohort
· 2001-2003 / · Bupe SL tablet either administered:
o A 2mg and then a further 2mg for as long as withdrawal was evident. No daily max
o B Same as above but 8mg max first day, 16mg max 2nd day and 24mg 3rd day max
o C 4mg doses given followed by further 4mg dose increaes
· After 3 day induction doses remained stable.
· Either daily or every other day. Observed. / · Treatment relapse
· (UDS pos during induction or voluntarily stopped treatment) / · 33% relapsed during induction phase. Lower induction doses=higher induction relapse rates.
o 51.2% inducted with 2mg
o 39.2% on 4mg
o 31.5% on 8mg
o 20.6% on 10mg
· No statistical data given. / No precipitated withdrawal observed
Higher doses “well tolerated” but no data given / Yes /
· Treatment retention / · 51% completed after 2 years
· Alternate day dosing showed better compliance and retention (Approx 80% vs 20% after 12 mos) (statistical data not shown).
· Data do not appear available comparing A,B,C groups for this outcome /
· Reduction in UDS positive for cannabis and cocaine / · More reduction for >16mg group than <8mg group. No statistical data presented /
Fiellin 2006
SS/EJCH / 166
opioid dependence from 2000-2004 / · RTC of three groups
· Randomized after a 2 week induction and stabilization
· 24 week study / · Standard Medical Management
o Brief manual-guided, medically focused counselling with either:
o Once weekly or thrice weekly (M/W/F) buprenorphine tablet.
o Take-home doses provided for all non-observed doses
· Enhanced Medical Management
o Each session was enhanced
o 24wks duration and bupe dispensed thrice weekly (M/W/F) / · Self-reported illicit opioid use, / · Self-reported illicit opioid use: All decreased but no difference between the three groups (p=0.73) / · Adherence (nurses notes and computerized medication bottles) / · Similar (p=0.87)
· Overall 71% adherence
· Increased adherence=improved treatment outcomes / Brief wkly counselling & once wkly med dispensing did not significantly differ from extended wkly counselling & 3 x wkly dispensing
Dose 17.5+- 2.5mg;
Brief counselling=
20min;
Extended=
45min and more in-depth coverage of the same issues as brief counselling
All done by primary care nurse. Only saw physician for 20 mins per month
50% lost to follow up / Yes /
· Retention / · No diff (p=0.64) /
· % negative UDS / · % negative UDS: Similar for all three groups (p=0.82) / · % cocaine –ve UDS / · No diff (p=0.73) /
· Use of social services / · No diff (no data) /
· Max # of consecutive wks of abstinence / · Max # consecutive weeks abstinent: Same p=0.54 / · Client satisfaction / · Preferred enhanced group (p=0.049)
· Within standard management preferred wkly dispensing vs thrice weekly (p=0.04) /
259 Amass 1998
SC/CH / 18 opioid dependent / · Crossover / · Maintenance dose determined during first week either 2mg, 4mg or 8mg/70kg/d (ie. Fixed doses)
· 4 x 14-day dosing conditions:
o Blind daily versus alternate day
o Open daily versus alternate day
· All participants spent time in each condition
· Daily clinic visits. Alternate day dosing got placebo on non-drug days
· Bupe solution used
· Opioid abstinence required / · Subjective and objective rating scales of opioid effect and withdrawal / · Similar between all groups / · Retention / · No difference in retention / Alternate day buprenorphine dosing is preferred to daily dosing by opioid dependent humans / Yes /
· Non-opioid drug use / · No difference /
· Preference for alternate day dosing / · In the choice phase of the study all 7 who completed this phase chose alternate daily dosing /
278 Schottenfeld 2000
EJ/SS / 92 / · Randomized, double blind, 12 weeks / · Buprenorphine SL Solution – dosed by weight (112mg/70kg/week)
· Daily dose vs 3x/wk
· All doses observed / · Treatment retention / · No difference (p=0.64) / · Medication compliance / · No difference / Yes /
· Number of positive urines for opioids or cocaine / · No difference between groups for various measures / · Attendance at counseling sessions / · No difference /
318 Bickel 1999
CH. Needs 2nd / 16 opioid dependent / · Crossover / · Bupe SL solution
· Dose stabilized during 1st week
· Maintenance then given for 13 days (this was baseline).
· Each pt then received each condition for 21-22 days (double or triple dose) / · Self reported agonist and withdrawal effects at 24hrs / · More withdrawal “sick” at 72 hrs of q 72 hr group than at 24 hrs of q 24hr group.
· Increased agonist effect in double and triple-dosed pts. / Yes /
· Observer ratings / · No ratings of intoxication /
· Pupil diameter / · Increased /
328 Johnson 1995
CH. Needs 2nd / 99 / · RCT / · All received 8mg SL bupe solution daily and then one group had 2nd day dose tapered to zero and got 8mg q 2d