see attachments below1 page summary of these articles.

4/22/2018 Buprenorphine maintenance versus placebo or methadone maintenance for opioid dependence

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Send e ma il fo r u pdate s

yo ur. e m ail@ addre ss

Ab ou t u pdate s

R evie w analy sis

Th is e n tr y is o u r a n aly sis o f a r e vie w o r s y n th esis o f r e se a rc h fin din gs c o n sid ere d p artic u la rly

r e le va n t t o imp ro vin g o u tc o me s fr o m dru g o r a lc o h ol in te rv e n tio n s in t h e U K. T h e o rig in al

re vie w w as n ot p u blis h ed b y F in din gs; c lic k T it le t o o rd er a c o p y. L in ks t o o th er d ocu me nts .

H ove r o ve r fo r n ote s. C lic k t o h ig h lig h t p assa g e r e fe rre d t o . U nfo ld e xtr a t e xt T h e

Su mma ry c o n ve ys t h e fin din gs a n d v ie w s e xp re sse d in t h e r e vie w . B elo w is a c o m men ta ry

fr o m Dru g a n d Al co h ol F in din gs.

T it le a n d lin k fo r c o p yin g C omme nt/ q u ery t o e d it o r

Tweet

B upre n orp h in e m ain te n an ce v ers u s p lace b o o r m eth ad on e m ain te n an ce

fo r o pio id dep en den ce .

M attic k R .P ., B re en C ., K im ber J . e t a l.

Coch ra n e Dat ab ase o f S yste m atic R evie ws: 2 014, 2 , a rt. n o.: C D0 02207.

Auth orit a tiv e a n aly sis o f c lin ic a lly r e le va n t t r ia ls o f b u pre n orp h in e v e rs u s m eth ad on e m ain te n an ce

fo r h ero in d ep en den ce c o n fir m s t h at b u pre n orp h in e h as le ss ‘h old in g p ow er’, a n d t h at a m on g

patie n ts w ho a re r e ta in ed , t h ere a re e q u iv a le n t r e d u ctio n s in ille g al d ru g u se . B ut is m eth ad on e’s

‘s tic k in ess’ an a d va n ta g e o r a lia b ilit y ?

S U M MAR Y O ra l m eth ad on e a n d s u blin gu al ( a b so rb ed u nder t h e t o n gu e) b u pre n orp h in e a re t h e

m ain m ed ic a tio n s p re scrib ed lo n g-te rm ( o n a ‘m ain te n an ce ’ b asis ) t o p atie n ts t o s u bstit u te fo r

h ero in a n d o th er o p ia te -ty p e d ru gs o n w hic h t h ey h ave b eco m e d ep en den t. Su bstit u tin g le g al

o p io id s in k n ow n d ose s a n d p u rit y p ro vid es a n o p portu nit y t o s ta b ilis e t h e p atie n t b y e lim in atin g

w it h dra w al, c ra vin g, p artic ip atio n in o b ta in in g ille g al o p io id s, a n d in je ctin g.

Th is u pdate d r e vie w fo r t h e C och ra n e C olla b ora tio n , o n e o f t h e w orld ’s m ost t r u ste d s o u rc e s fo r

re se a rc h a n aly se s, in clu ded 3 1 t r ia ls t o ta llin g 5 430 p artic ip an ts c o m pare d t o t h e 2 4 a n d 4 497 o f t h e

2 008 v e rs io n . I t fo cu se d o n s tu die s w hic h a llo w ed c lin ic ia n s t o a d ju st t h e d ose d ep en din g o n h ow

th e p atie n t h as r e a cte d ; t h ese m ore c lo se ly r e fle ct a ctu al a n d re co m men ded c lin ic a l p ra ctic e t h an

fix e d -d ose s tu die s.

T h e r e vie w s o u gh t t r ia ls w hic h h ad ra n dom ly a llo ca te d p atie n ts d ep en den t o n h ero in o r a llie d d ru gs

to b u pre n orp h in e m ain te n an ce , v e rs u s e it h er a p la ce b o o r m ain te n an ce o n m eth ad on e. Wh ere

p ossib le , r e su lt s o f s im ila r s tu die s w ere s ta tis tic a lly p oole d . O f t h e 3 1 t r ia ls , 1 5 w ere fr o m N orth

Am eric a a n d n in e E u ro p e. M ost ( 2 2) w ere r e p orte d ly ‘d ou ble -b lin d’, m ea n in g n eit h er p atie n ts n or

clin ic ia n s w ere t o ld w hic h p re p ara tio n t h e p atie n t w as t a kin g. Wh en m eth ad on e w as c o m pare d w it h

b u pre n orp h in e, c o n ce a lm en t e n ta ile d r e q u ir in g a ll p atie n ts t o t a ke t w o p re p ara tio n s, o n e t h e a ctiv e

m ed ic a tio n , t h e o th er a p la ce b o v e rs io n o f t h e s e co n d m ed ic a tio n . U rin e t e sts r e su lt s w ere b ase d o n

th e n um ber o f t e sts in dic a tiv e o f c o n tin uin g ille g al h ero in u se . [ E dit o r’s n ote : Al l e ls e b ein g e q u al,

t h e m eth od u se d in t h e r e vie w fa vo u re d p re p ara tio n s w hic h d o le ss w ell a t r e ta in in g p atie n ts in

t r e a tm en t a n d w hic h t h ere fo re o ffe r le ss s co p e fo r p atie n ts t o a ccu m ula te t e sts in dic a tiv e o f

co n tin uin g ille g al d ru g u se . An oth er c o m m on m eth od is t o a ssu m e m is s e d t e sts w ou ld h ave

in dic a te d a r e tu rn t o d ru g u se , fa vo u rin g m ed ic a tio n s w hic h b est r e ta in p atie n ts .]

Main findings

D osin g le ve ls w ere fle xib le in 1 1 s tu die s w hic h c o m pare d t h e t w o m ed ic a tio n s. Ac ro ss t h ese , t h e

ch an ce s o f a p atie n t le avin g t r e a tm en t d u rin g stu dy p erio d s r a n gin g fr o m s ix w eeks t o a y e a r w as

1 7% lo w er o n m eth ad on e. T h is m ea n s fo r e xa m ple t h at if 6 0 o u t o f 1 00 p atie n ts a re r e ta in ed o n

b u pre n orp h in e, h ad t h ey in ste a d b een p re scrib ed m eth ad on e, t y p ic a lly a n oth er 1 2 w ou ld h ave

sta ye d in t r e a tm en t. R esu lt s w ere s im ila r a n d m ore c o n sis te n t a cro ss t h e fiv e d ou ble -b lin d s tu die s

in w hic h n eit h er p atie n ts n or c lin ic ia n s w ere t o ld w hic h m ed ic a tio n t h e p atie n t w as t a kin g. Am on g

th e r e m ain in g s ix n on -b lin ded s tu die s, m eth ad on e’s r e te n tio n a d va n ta g e w as n ot q u it e s ta tis tic a lly

s ig n if ic a n t a n d v a rie d c o n sid era b ly b etw ee n s tu die s.

S EN D

Hom e Mailin g lis t S ea rc h B ro w se H ot t o p ic s M atr ic e s A bou t H elp C on ta ct 4/22/2018 Buprenorphine maintenance versus placebo or methadone maintenance for opioid dependence

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Acro ss t h e e ig h t fle xib le -d ose s tu die s w hic h p ro vid ed t h is d ata , n um bers o f u rin e t e sts in dic a tiv e o f

co n tin uin g h ero in u se o n ly s lig h tly a n d n on -s ig n if ic a n tly fa vo u re d b u pre n orp h in e. T h e s a m e w as

tr u e fo r t h e p atie n ts ’ ow n a cco u nts o f t h eir h ero in u se . T h ere w ere a ls o n o s ig n if ic a n t d if fe re n ce s in

u se o f c o ca in e o r b en zo d ia ze p in es, t h ou gh in b oth c a se s t h ere w as a s lig h t a d va n ta g e fo r

m eth ad on e. J u st t w o s tu die s c o n tr ib u te d t o t h e a n aly sis o f c rim in al a ctiv it y , c u m ula tin g t o n o

sig n if ic a n t d if fe re n ce b etw een t h e m ed ic a tio n s.

In t h e fix e d -d ose s tu die s w hic h c o m pare d b u pre n orp h in e w it h m eth ad on e, r e te n tio n w as o n ly

s ig n if ic a n tly d if fe re n t ( p atie n ts s ta ye d lo n ger o n m eth ad on e) in t h e lo w -d ose c o m paris o n s o f le ss

th an 1 6m g o f b u pre n orp h in e v e rs u s le ss t h an 4 0m g o f m eth ad on e. I n n o d ose r a n ge d id o n e

m ed ic a tio n v e rs u s t h e o th er r e su lt in s ig n if ic a n tly fe w er u rin e t e sts o r s e lf - re p orts fr o m t h e p atie n ts

in dic a tiv e o f h ero in u se .

Ac ro ss t h e 1 1 s tu die s w hic h c o m pare d b u pre n orp h in e t o a p la ce b o , b u pre n orp h in e in w hate ve r d ose

ra n ge r e ta in ed p atie n ts b ette r in t r e a tm en t. H ow eve r, o n ly h ig h -d ose ( a t le a st 1 6m g p er d ay)

b u pre n orp h in e le d t o fe w er u rin e t e sts in dic a tiv e o f c o n tin uin g ille g al h ero in u se .

Am on g a ll 3 1 s tu die s, t h e fe w t o c o m pare r a te s o f u nw elc o m e p ossib le s id e e ffe cts fo u nd n o

dif fe re n ce s b etw een b u pre n orp h in e a n d p la ce b o o r m eth ad on e, w it h t h e e xce p tio n o f o n e s tu dy

w hic h fo u nd m ore m eth ad on e t h an b u pre n orp h in e p atie n ts e xp erie n ce d s e d atio n .

The authors’ conclusions

B ro ad p ra ctic e im plic a tio n s r e m ain u nch an ged f r o m 2 008. B upre n orp h in e is a n e ffe ctiv e m ed ic a tio n ,

bette rin g a p la ce b o o n r e te n tio n , a n d in h ig h d ose s a ls o in u rin e t e st r e su lt s in dic a tiv e o f c o n tin ued

h ero in u se . P re scrib ed a t fle xib le d ose s, s u perio r r e te n tio n m ea n s m eth ad on e s h ou ld b e t h e d efa u lt

m ain te n an ce m ed ic a tio n , w it h b u pre n orp h in e r e se rv e d f o r s it u atio n s w here h ig h er d ose m eth ad on e

is n ot p ossib le , fo r p atie n ts w ho d o n ot r e a ct w ell t o m eth ad on e, o r t o p ro vid e p atie n t a n d c lin ic ia n

ch oic e . T h ou gh b oth m ed ic a tio n s s u ppre ss ille g al h ero in u se , o n t h is c rit e rio n t h ey d id n ot

sig n if ic a n tly d if fe r. D esp it e t h ese fin din gs, b u pre n orp h in e m ay h ave a d va n ta g es in s o m e s e ttin gs

an d u nder s o m e p olic ie s w here it s r e la tiv e s a fe ty a n d a b ilit y t o b e t a ke n e ve ry o th er d ay a re

p artic u la rly u se fu l.

F in din gs in r e sp ect o f c o n se q u en ce s w hic h t a ke t im e t o b eco m e n otic e a b ly d if fe re n t, in clu din g m orta lit y , a d ve rs e s id e e ffe cts

a n d c rime , ma y h ave s u ffe re d fr o m th e t y p ic a lly s h ort d u ra tio n o f r a n dom is e d t r ia ls .

C O M MEN TA R Y T h e a n aly sts ’ ve rd ic t w as t h at g iv e n a d eq u ate d ose s, m eth ad on e w as

th e m ore e ffe ctiv e t r e a tm en t, b u t n ot b y s u ch a m arg in t h at b u pre n orp h in e c o u ld p osit iv e ly b e

ad vis e d a g ain st. G re a te r r e te n tio n w as t h e k e y a d va n ta g e – im porta n t, b eca u se o ve r t h e p erio d s

re p re se n te d in t h e s tu die s, w hen p atie n ts le ave , r e la p se t o d ep en den t illic it o p ia te u se is t h e n orm .

Wh en ( a s in n orm al p ra ctic e in B rit a in ) p atie n ts a n d c lin ic ia n s c h oose e it h er m ed ic a tio n , t h e

re te n tio n a d va n ta g e o f m eth ad on e h as b een m uch g re a te r t h an in t r ia ls w here p atie n ts a cce p t

bein g r a n dom ly a llo ca te d . P e rh ap s p artly b eca u se p atie n ts w ho w an t t h is c h oo se b u pre n orp h in e,

a n d p artly d u e t o it s o p ia te -b lo ck in g p ro p ertie s, w hile in t r e a tm en t p atie n ts w ho o p t fo r t h e d ru g

als o u se ille g al o p ia te s le ss o ft e n ( 1 2) , a c o n tr a st t o t h e e q u iv a le n ce fo u nd a cro ss r a n dom is e d

tr ia ls .

T h e a n aly sts ’ rid er t h at b u pre n orp h in e m ig h t b e o ff e re d s im ply t o c re a te c h oic e is m ore im porta n t

th an t h e m in or m en tio n w arra n te d in a r e vie w o f s tu die s in w hic h p atie n ts d id n ot h ave a c h oic e .

C hoic e is lik e ly t o h elp e n gag e a n d r e ta in p atie n ts in t r e a tm en t w ho w an t o r e xp ect d if fe re n t t h in gs

fr o m t h eir m ed ic a tio n s. I n on e E n glis h s tu dy , t h e c o n se q u en ce s o f a m is m atc h b etw een u se r

p re fe re n ce s a n d s e rv ic e p olic ie s w as v is ib le in t h e e a rly d ro p -o u t o f w ou ld -b e p atie n ts d en ie d

b u pre n orp h in e, w hic h m an y v a lu ed fo r w hat t h ey s a w a s it s s u perio r o p ia te -b lo ck in g p ro p ertie s.

B upre n orp h in e’s b ette r s a fe ty p ro file a n d it s a ttr a ctio n fo r a le ss s e ve re ly a ffe cte d c a se lo ad

co m men d it p artic u la rly t o p rim ary c a re s e ttin gs; in B ir m in gh am fo r e xa m ple , it w as t w ic e a s lik e ly

t o b e p re scrib ed a s a m ain te n an ce d ru g b y G Ps a s b y s p ecia lis t a d dic tio n s e rv ic e s.

Randomised but still not a level playing field

L im it a tio n s in t h e fe a tu re d a n aly sis a n d in t h e fle xib le -d osin g s tu die s it r e lie d o n in tr o d u ce

co n sid era b le u nce rta in ty o ve r t h e m ea n in g o f t h e fin din gs. Som e o f t h ese lim it a tio n s p ro b ab ly

m ea n t m eth ad on e’s a d va n ta g e w ou ld h ave b ee n g re a te r in e ve ry d ay p ra ctic e . E ve n w hen in m an y

stu die s t h ey c o u ld h ave g ot m eth ad on e e ls e w here , p atie n ts w ere p re p are d t o a cce p t a llo ca tio n t o

a n u nfa m ilia r m ed ic a tio n . P o ssib ly t h ey w ere k e en o n t r y in g a n ew m ed ic a tio n w it h le ss s tr o n g 4/22/2018 Buprenorphine maintenance versus placebo or methadone maintenance for opioid dependence

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op ia te -ty p e e ffe cts . I n m ost o f t h e s tu die s t h ey w ere ( c o m pare d t o U K c a se lo ad s) e it h er e a rly in

t h eir a d dic tio n o r t r e a tm en t c a re ers , r e la tiv e ly y o u ng, o r r e la tiv e ly s o cia lly in clu ded . O ne o f t h e

qu estio n s m ark s o ve r b u pre n orp h in e is it s s u it a b ilit y f o r m ore d ep en den t, h ig h -d ose h ero in u se rs .

Al so p erh ap s d is d ava n ta g in g m eth ad on e w as t h e w ay t h e u rin e t e st c o m paris o n w as c a lc u la te d .

Th is a p pea rs t o h ave ig n ore d m is se d t e sts r a th er t h an t r e a tin g t h em a s p osit iv e ( s h orte r r e te n tio n

m ea n s b u pre n orp h in e p atie n ts p ro b ab ly m is s e d m ore ) a n d t o h ave c re d it e d t o b u pre n orp h in e

re su lt s fr o m p atie n ts w ho a vo id ed p osit iv e t e sts b y s w it c h in g t o m eth ad on e.

O n t h e o th er h an d, b u pre n orp h in e p atie n ts t o o m ig h t h ave b ee n d is a d va n ta g ed . T h e d ru g p erm it s

n on -d aily d osin g a n d p erh ap s a n e a rlie r s h if t t o u nsu perv is e d c o n su m ptio n . F o r m an y p atie n ts , t h is

o ffe rs a m ore a ttr a ctiv e r e g im en t h an d aily s u perv is e d m eth ad on e. T h e k e y s tu die s s a crif ic e d t h ese

a d va n ta g es t o ‘b lin d’ p atie n ts a n d s ta ff t o w hic h d ru g w as b ein g t a ke n .

NICE verdict

Si nce it d re w o n t h is d ata , t h ese s o u rc e s o f u nce rta in ty w ere a ls o in co rp ora te d in a n asse ssm en t fo r

th e U K’s N atio n al I n stit u te fo r H ea lt h a n d C lin ic a l E xce lle n ce ( N IC E), w hic h it s e lf a d ded fu rth er

la ye rs o f u nce rta in ty . I t fo u nd t h at m eth ad on e’s r e te n tio n a d va n ta g e in fle xib le -d ose s tu die s

tr a n sla te d in t o s lig h tly g re a te r im pro ve m en ts in ( la rg ely h ea lt h -re la te d ) q u alit y o f lif e . Si nce

m eth ad on e a ls o r e su lt e d in lo w er h ea lt h c a re c o sts , it w as ju dged m ore c o st- e ffe ctiv e t h an

b u pre n orp h in e.

Fo r t h e fe a tu re d r e vie w ers , s im ila r fin din gs m ea n t m eth ad on e s h ou ld b e t h e d efa u lt c h oic e , b u t

exp erts a n d a d vis e rs c o n ve n ed b y N IC E p u t a d if fe re n t s p in o n la rg ely t h e s a m e e vid en ce . T h eir

a d vic e w as t h at t h e c h oic e b etw een t h e m ed ic a tio n s s h ou ld b e m ad e “ c a se b y c a se ”, b ase d o n

is su es lik e w heth er b u pre n orp h in e’s s a fe ty w as a p rio rit y in t h at in div id u al c a se , w heth er t h e p atie n t

w as a im in g t o w it h dra w fr o m o p ia te -ty p e d ru gs a lt o g eth er ( e a sie r w it h b u pre n orp h in e), a n d p atie n t

pre fe re n ce . Wh en fo r a n in div id u al t h e m ed ic a tio n s w ere e q u ally a p pro p ria te , m eth ad on e m ig h t

ta ke p re ce d en ce b eca u se it c o st le ss a n d o n a ve ra g e e xte n ded t h e b en efit s o f b ein g in t r e a tm en t.

U K p re scrib in g g u id elin es t a ke a s im ila r lin e.

N eit h er t h e C och ra n e n or t h e N IC E a ss e ssm en t fu lly a cco u nte d f o r t h e c o st- s a vin gs a n d

co n ve n ie n ce p ossib le d u e t o b u pre n orp h in e’s e xte n ded a ctio n a n d r e la tiv e s a fe ty , s u ch a s b ein g a b le

t o a llo w m ore u nsu perv is e d d osin g. T h ese a re n ot ju st t h eo re tic a l, b u t h ave b een t a ke n a d va n ta g e

of in B rit a in . Al so n ot fu lly a cco u nte d fo r w ere t h e w ays in w hic h b u pre n orp h in e m ig h t fu rth er

en han ce q u alit y o f lif e . H ow eve r, n eit h er d id t h e a sse ssm en ts fu lly a cco u nt fo r t h e b en efit s o f

g re a te r r e te n tio n o n m eth ad on e.

How to choose?

U nce rta in ty a b ou t o ve ra ll a d va n ta g e, a llie d w it h d if fe re n ce s in t h e s a fe ty a n d e ffe cts o f t h e d ru gs

an d fe a sib le d is p en sin g a rra n gem en ts , s u ggest t h at s o m e p atie n ts w ill b e b est s u it e d t o m eth ad on e,

o th ers t o b u pre n orp h in e. U nfo rtu nate ly , t h ere is lit tle in t h e r e se a rc h t o in dic a te w ho w ill b e in

w hic h c a m p. B upre n orp h in e p ossib ly h elp s d ep re sse d p atie n ts m ore t h an t h ose n ot s u ffe rin g

dep re ssio n , w hile p atie n ts d ep en den t o n la rg e d ose s o f o p ia te s m ay f in d it in ad eq u ate b eca u se

th ere is a c e ilin g b eyo n d w hic h h ig h er d ose s d o n ot a u gm en t o p ia te -ty p e e ffe cts . P a tie n ts w ho v a lu e

th e ‘w ra p ped in c o tto n w ool’ fe elin g t y p ic a l o f h ero in a re lik e ly t o p re fe r m eth ad on e ; t h ose w ho

va lu e a c le a re r h ea d m ig h t p re fe r b u pre n orp h in e. P a tie n ts a im in g f o r a r e la tiv e ly r a p id b re a k fr o m

all o p ia te -ty p e d ru gs m ig h t d o b est t o o p t fo r b u pre n orp h in e in it ia lly , o r t o s w it c h t o it a ft e r

sta b ilis in g o n m eth ad on e, b u t h ave t o a cc e p t t h e r is k t h at in ste a d t h ey w ill d ro p o u t a n d r e tu rn t o

d ep en den ce o n ille g al d ru gs.

M eth ad on e is lik e ly t o r e m ain t h e m ain sta y o f m ain te n an ce p re scrib in g d u e t o it s w id er a p pea l t o

p atie n ts a n d lo w er c o st, b u t t h e c a se fo r c o n sid erin g b u pre n orp h in e is s tr o n g a n d m ay g et s tr o n ger

if p ote n tia l c o st s a vin gs a re fu rth er r e a lis e d , a n d a s m eth ad on e’s m ajo r a d va n ta g e – g re a te r

re te n tio n – c o m es t o b e s e en a s a n im ped im en t t o le avin g t r e a tm en t. U ntil r e ce n tly , in B rit a in

r e te n tio n fo r 1 2 w eeks w as t h e p rim e b en ch m ark o f e ffe ctiv e t r e a tm en t a n d p artly d ete rm in ed lo ca l

fu ndin g. N ow t h e e m ph asis ( 1 2) is o n m ovin g p atie n ts t h ro u gh a n d o u t o f t r e a tm en t t o ( it is

h op ed ) s e cu re r e co ve ry v ia s o cia l r e in te g ra tio n . I n lin e w it h p olic y, ‘s ucce ssfu l’ tr e a tm en t e xit

f e a tu re s s tr o n gly a s a g oal in ‘p aym en t b y r e su lt s ’ co m m is s io n in g c rit e ria in E n gla n d. Ag ain st t h is

b ack d ro p , b u pre n orp h in e’s a b ilit y t o h elp p atie n ts t a ke a h alf - s te p a w ay f r o m r e lia n ce o n o p ia te -

ty p e e ffe cts a n d it s g re a te r ‘l e ava b ilit y ’ co u ld b eco m e v a lu ed m ore , w hile m eth ad on e’s ‘s tic k a b ilit y ’

is b ein g s e en n ot ( o r n ot o n ly ) a s a s tr e n gth , b u t a lia b ilit y . H ow eve r, b u pre n orp h in e’s le ava b ilit y is 4/22/2018 Buprenorphine maintenance versus placebo or methadone maintenance for opioid dependence

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it s e lf a lia b ilit y if it m ea n s ( a s in t h is B rit is h s tu dy ) t h at m an y m ore p atie n ts d ro p o u t a n d s till o n ly a

s m all m in orit y le ave a ft e r s u cce ssfu l d eto xif ic a tio n .

Th e p re vio u s v e rs io n o f t h e r e vie w w as a n aly se d b y F in din g o n t h e b asis o f a n exte n ded a n aly sis o f t h e e ig h t fle xib le d ose

stu die s t h en a va ila b le . T h is s till s e ems a v a lid b asis fo r a sse ss in g t h e r e vie w ’s im plic a tio n s. N on e o f t h e t h re e n ew t o t h e

cu rre n t v e rs io n w ere a mo ng t h e d ou ble -b lin d s tu die s w hic h c o n stit u te t h e m ost s tr in gen t c o m paris o n o f t h e t w o m ed ic a tio n s

pre scrib ed fle xib ly . I n on e r e te n tio n a ctu ally me an t c o mp le tin g t r e a tme nt w hile in p ris o n , a n oth er w as a sma ll G erma n s tu dy

w hic h fo u nd r e te n tio n a b ou t e q u al, a n d t h e la st w as a N orw eg ia n t r ia l w hic h w as a rg u ab ly a n in va lid c o mp aris o n b eca u se

me th ad on e d ose s c o u ld v a ry w hile b u pre n orp h in e w as fix e d a t 1 6m g.

Fo r c lin ic a l g u id an ce o n h ow t o u se b u pre n orp h in e s e e U K p re scrib in g gu id elin es a n d a re vie w fr o m th re e le a d in g U S

re se a rc h ers .

T h an ks fo r t h eir c o m men ts o n t h e o rig in al e n tr y t o T om C arn w ath , t h en c o n su lt a n t p sy ch ia tr is t a t t h e T ee s, E sk & W ea r

V alle ys N H S Tru st in E n gla n d. C om men ta to rs b ea r n o r e sp on sib ilit y fo r t h e t e xt in clu din g t h e in te rp re ta tio n s a n d a n y

re m ain in g e rro rs .

L a st r e vis e d 1 1 M arc h 2 014. F ir s t u plo ad ed 1 1 J a n uary 2 008

C omme nt/ q u ery t o e d it o r

G iv e u s y o u r fe ed back o n t h e s it e ( o n e-mi nute s u rv e y)

O pen E ffe ctiv e n ess B an k h ome p ag e

Ad d y o u r n ame t o t h e ma ilin g lis t t o b e a le rte d t o n ew s tu die s a n d o th er s it e u pdate s

T o p 1 0 m ost c lo se ly rela te d d ocu m en ts o n t his site. F or m ore t ry a su bje ct o r fr e e t ex t

se a rc h

REVI EW 2017 Su perv is e d d osin g w it h a lo n g-a ctin g o p io id me dic a tio n in t h e m an ag em en t o f o p io id d ep en den ce

D O CU M EN T 2 017 D ru g mi su se a n d d ep en den ce : U K g u id elin es o n c lin ic a l m an ag em en t

ST UD Y 2 010 Th e SU MMIT T ria l: a fie ld c o mp aris o n o f b u pre n orp h in e v e rs u s m eth ad on e m ain te n an ce t r e a tm en t

R EVI EW 2012 Th e e ffe ctiv e n ess o f o p io id ma in te n an ce t r e a tme nt in p ris o n s e tt in gs: a s y ste m atic r e vie w

D O CU M EN T 2 013 C ommu nit y lo se s fr o m fa ilu re t o o ffe r ma in te n an ce p re scrib in g in p ris o n s

ST UD Y 2 015 R is k o f mo rta lit y o n a n d o ff me th ad on e s u bstit u tio n t r e a tm en t in p rim ary c a re : a n atio n al c o h ort s tu dy

ST UD Y 2 012 R an domi ze d t r ia l o f s ta n dard me th ad on e t r e a tme nt c o m pare d t o in it ia tin g m eth ad on e w it h ou t c o u nse lin g: 1 2-

mo nth fin din gs

R EVI EW 2011 H ero in ma in te n an ce fo r c h ro n ic h ero in -d ep en den t in div id u als

R EVI EW 2008 In te rn atio n al r e vie w a n d U K g u id an ce w eig h me rit s o f b u pre n orp h in e v e rs u s m eth ad on e m ain te n an ce

R EVI EW 2014 A re vie w o f b u pre n orp h in e d iv e rs io n a n d mi su se : t h e c u rre n t e vid en ce b ase a n d e xp erie n ce s fr o m a ro u nd t h e

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