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4/22/2018 Treatment Retention among Patients Randomized to Buprenorphine/Naloxone Compared to Methadone in A Multi-site T rial
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3947022/ 1/15
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Addic tio n . A uth or m anuscrip t; a va ila ble in P M C 2 015 J a n 1 .
P ublis h ed in fin al e dit e d fo rm a s:
A ddic tio n. 2 014 J a n; 1 09(1 ): 7 9–87.
P ublis h ed o nlin e 2 013 O ct 9 . d oi: 1 0.1 111 /a dd.1 2333
P M CID : P M C3947022
N IH M SID : N IH M S519619
P M ID : 2 3961726
T re atm ent R ete ntio n a m ong P atie n ts R an dom iz e d to
B upre norp hin e/N alo xo ne C om pare d to M eth adone in A M ult i- s it e T ria l
Yih -In g H se r , P h.D ., A ndre w J . S axo n , M .D ., D avid H uang , P h.D ., A l H asso n , M .S .W ., C hris tie T hom as ,
M .P .H ., M aure en H illh ouse , P h.D ., P etr a J a co bs , M .D ., C hery l T e ru ya , P h.D ., P aul M cL aughlin , M .A .,
K ath arin a W ie st , P h.D ., A lla n C ohen , M .A ., a nd W alt e r L in g , M .D .
Univ e rs it y o f C alif o rn ia , L os A ngele s
V ete ra ns A ff a ir s P uget S ound H ealt h C are S yste m
N atio nal In stit u te o n D ru g A buse
H artfo rd D is p ensa ry , C T
CO DA, In c., O R
Bay A re a A ddic tio n R ese arc h a nd T re atm ent, C A
Corre sp ondin g A uth or: Y ih -In g H se r, P h.D ., U CLA In te gra te d S ub sta nce A bu se P ro gra m s, 1 1 075 S an ta M onic a B lv d ., S uit e 2 00, L os
A ngele s, C A 9 0025, 3 10-2 67-5 388; F A X: 3 10-3 12-0 55 2; y h se r@ ucla .e du
C opyrig ht n otic e
T he p ublis h er's fin al e dit e d v e rs io n o f th is a rtic le is a va ila ble a t A ddic tio n
S ee o th er a rtic le s in P M C th at c it e th e p ublis h ed a rtic le .
T his a rtic le h as b een cit e d b y s yste m atic r e vie w s in P ubM ed.
A bstr a ct
A im s
To e x am in e p atie n t a n d m ed ic atio n c h ara cte ris tic s a sso cia te d w ith r e te n tio n a n d c o ntin ued i llic it o pio id
u se i n m eth ad one ( M ET) v ers u s b upre n orp hin e/n alo xone ( B U P) t r e atm en t f o r o pio id d ep en den ce.
D esig n/S ettin gs/P artic ip ants
T his s e co ndary a n aly sis i n clu ded 1 ,2 67 o pio id -d ep en den t i n div id uals p artic ip atin g i n 9 o pio id
t r e atm en t p ro gra m s b etw een 2 006 a n d 2 0 09 a n d r a n dom iz ed t o r e ceiv e o pen -la b el B U P o r M ET f o r 2 4
w eek s.
M easu re m ents
T he a n aly se s i n clu ded m easu re s o f p atie n t c h ara cte ris tic s a t b ase lin e ( d em ogra p hic s; u se o f a lc o hol,
c ig are tte s, a n d i llic it d ru gs; s e lf -ra te d m en ta l a n d p hysic al h ealth ), m ed ic atio n d ose a n d u rin e d ru g
sc re en s d urin g t r e atm en t, a n d t r e atm en t c o m ple tio n a n d d ay s i n t r e atm en t d urin g t h e 2 4 w eek t r ia l.
F in din gs
T he t r e atm en t c o m ple tio n r a te w as 7 4% f o r M ET v s. 4 6% f o r B U P ( p < .0 1); t h e r a te a m ong M ET
partic ip an ts i n cre ase d t o 8 0% w hen t h e m ax im um M ET d ose r e ach ed o r e x ceed ed 6 0m g/d ay. W ith
B U P, t h e c o m ple tio n r a te i n cre ase d l in ea rly w ith h ig her d ose s, r e ach in g 6 0% w ith d ose s o f 3 0–
1 2 1 1
1 1 3 1 4
5 6 1
1
2
3
4
5
6 4/22/2018 Treatment Retention among Patients Randomized to Buprenorphine/Naloxone Compared to Methadone in A Multi-site T rial
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3 2m g/d ay. O f t h ose r e m ain in g i n t r e atm en t, p ositiv e o pio id u rin e r e su lts w ere s ig nif ic an tly l o w er
(O R=0.6 3, 9 5% CI= 0.5 2–0.7 6, p < .0 1) a m ong B U P r e la tiv e t o M ET p artic ip an ts d urin g t h e f ir s t 9 w eek s
of t r e atm en t. H ig her m ed ic atio n d ose w as r e la te d t o l o w er o pia te u se , m ore s o a m ong B U P p atie n ts . A
C ox p ro portio nal h azard s m odel r e v eale d f a cto rs a sso cia te d w ith d ro pout: ( 1 ) B U P ( v s. M ET,
H R=1.6 1, C I:1 .2 0–2.1 5), ( 2 ) l o w er m ed ic atio n d ose ( < 16m g f o r B U P, < 60m g f o r M ET; H R=3.0 9,
C I:2 .1 9–4.3 7), ( 3 ) t h e i n te ra ctio n o f d ose a n d t r e atm en t c o nditio n ( th ose w ith h ig her B U P d ose w ere
1 .0 4 t im es m ore l ik ely t o d ro p o ut t h an t h ose w ith l o w er M ET d ose , a n d ( 4 ) b ein g y ounger, H is p an ic ,
a n d u sin g h ero in o r o th er s u bsta n ces d urin g t r e atm en t.
C onclu sio ns
Pro vis io n o f m eth ad one a p pears t o b e a sso cia te d w ith b ette r r e te n tio n i n t r e atm en t f o r o pio id
d ep en den ce t h an b upre n orp hin e, a s d oes u se o f p ro vis io n o f h ig her d ose s o f b oth m ed ic atio ns.
P ro vis io n o f b upre n orp hin e i s a sso cia te d w ith l o w er c o ntin ued u se o f i llic it o pio id s.
T he e arly y ears o f t h e 2 1st c en tu ry h av e w itn esse d a s tr ik in g i n cre ase i n r a te s o f o pio id m is u se a n d
ad dic tio n w ith c o nco m ita n t i n cre ase s i n o pio id o verd ose d eath s. T his s itu atio n c alls f o r i m pro ved
tr e atm en ts f o r t h is p ote n tia lly l e th al d is o rd er. B oth m eth ad one ( M ET) a n d b upre n orp hin e ( B U P) a re
e ff e ctiv e t r e atm en ts f o r o pio id a d dic tio n. M ET i s t h e m ost w id ely u se d o pio id a g onis t t h era p y i n t h e
w orld , a n d B U P i s w id ely a v aila b le i n s e le cte d E uro pean c o untr ie s, t h e U nite d S ta te s ( U .S .) , C an ad a,
a n d A ustr a lia . S ev era l s tu die s h av e r e p orte d l o w er t r e atm en t r e te n tio n a sso cia te d w ith B U P r e la tiv e t o
M ET. A r e cen t C och ra n e r e v ie w o f r a n dom iz ed c lin ic al t r ia ls h as i n dic ate d t h at r e te n tio n w ith M ET
is b ette r t h an B U P, a lth ough t h e t w o m ed ic atio ns w ere e q uiv ale n t i n s u ppre ssin g i llic it o pia te u se .
M an y o f t h e t r ia ls i n clu ded i n t h e C och ra n e r e v ie w u se d r e la tiv ely l o w d ose s o f B U P a n d s lo w ,
in fle x ib le i n ductio n, w ith a m ax im um d ose o f 1 6m g p er d ay. N ev erth ele ss, e v en w hen p atie n t
pre fe re n ce w as t a k en i n to c o nsid era tio n, a s tu dy w ith f le x ib le d osin g ( a m ax im um B U P d ose o f 2 0m g)
sh ow ed t h at t h ose p re sc rib ed M ET w ere m ore t h an t w ic e a s l ik ely t o b e r e ta in ed r e la tiv e t o t h ose s e lf -
s e le ctin g B U P.
T re atm en t r e te n tio n i s a n i m porta n t p re d ic to r o f f a v ora b le t r e atm en t o utc o m es, s o i m pro vin g B U P
tr e atm en t o utc o m es n ecessita te s e n han cin g r e te n tio n r a te s. P ote n tia lly n eg ativ e a sp ects o f B U P
tr e atm en t r e p orte d b y p atie n ts i n clu de t h e p ote n tia l t o p re cip ita te w ith dra w al s y m pto m s a t i n ductio n,
th e u nple asa n t t a ste o f t h e s u blin gual f o rm ula tio n, a n d s lo w d is so lu tio n o f t h e s u blin gual t a b le t.
F acto rs t h at f a cilita te r e te n tio n h av e n ot b een w id ely s tu die d , b ut a r e cen t m eta -a n aly sis b ase d o n 2 1
ra n dom iz ed c lin ic al t r ia ls i n dic ate s t h at a h ig her B U P d ose ( 1 6–32m g p er d ay ) p re d ic te d b ette r
re te n tio n i n t r e atm en t c o m pare d w ith a l o w er d ose ( le ss t h an 1 6m g p er d ay ), a n d t h at p ositiv e u rin e
dru g s c re en s f o r o pia te s p re d ic te d t r e atm en t d ro pout. F urth erm ore , r e te n tio n i n t r e atm en t p re d ic te d l e ss
illic it o pia te u se , a n d p ositiv e u rin e d ru g s c re en s f o r c o cain e p re d ic te d m ore i llic it o pia te u se .
T he p re se n t s tu dy t a k es a d van ta g e o f a l a rg e r a n dom iz ed t r ia l r e cen tly c o nducte d i n t h e U .S . i n w hic h
o pio id -d ep en den t p artic ip an ts w ere r a n dom iz ed t o M ET v s. B U P f o r 2 4 w eek s t o c o m pare l iv er h ealth
o utc o m es. T his s tu dy c o m pare s t r e atm en t c o m ple ti o n a n d r e te n tio n r a te s f o r B U P a n d M ET g ro ups,
a n d i d en tif ie s p artic ip an t a n d m ed ic atio n f a cto rs t h at i n flu en ced r e te n tio n.
M ETH O DS
Partic ip ants
A s d esc rib ed e ls e w here , t h e r e cen tly c o m ple te d o rig in al s tu dy w as a m ultis ite , o pen -la b el, p hase I V
s tu dy t o a sse ss l iv er f u nctio n i n p artic ip an ts r a n dom iz ed t o m ed ic atio n c o nditio n ( B U P [ g iv en i n t h e
fo rm o f b upre n orp hin e/n alo xone], M ET). A t o ta l o f 1 ,2 69 e lig ib le p atie n ts f ro m 9 f e d era lly l ic en se d
1,2 3
4,5 6
7
8
9
10 11
1 2
13
13 4/22/2018 Treatment Retention among Patients Randomized to Buprenorphine/Naloxone Compared to Methadone in A Multi-site T rial
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3947022/ 3/15
Partic ip ant C hara cte ris tic s
U rin e D ru g S cre ens ( U DS)
M edic a tio n D ose
o pio id t r e atm en t p ro gra m s a cro ss t h e U .S . w ere r a n dom iz ed ( w ith in s ite ) a n d i n ducte d o n s tu dy
m ed ic atio n ( B U P = 7 40, M ET = 5 29) f ro m 2 006 t o 2 009. T he u neq ual s a m ple s iz es i n t h e t w o
co nditio ns o ccu rre d b ecau se t h e s tu dy n eed ed t o a ch ie v e t a rg et s a m ple s iz es f o r e ach m ed ic atio n ( 3 00
each w ho c o m ple te d 2 4 w eek s o f m ed ic a tio n a n d p ro vid ed t h e r e q uir e d l iv er t e sts ), s o t h e i n itia l
ra n dom iz atio n s c h em e o f 1 :1 ( B U P:M ET) w as c h an ged t o 2 :1 i n D ecem ber 2 007 ( 1 8 m onth s a fte r
in itia tio n) d ue t o t h e h ig her d ro pout i n t h e B U P c o nditio n. B ecau se t h e p re se n t s tu dy i s f o cu se d o n
eff e cts o f p artic ip an t a n d m ed ic atio n c h ara cte ris tic s o n t r e atm en t r e te n tio n, e x clu ded w ere 2 w om en
w ho b ecam e p re g nan t a n d w ere r e assig ned f ro m B U P t o M ET, r e su ltin g i n t h e u se o f d ata f ro m 1 ,2 67
partic ip an ts ( B U P= 738, M ET=529) i n t h e p re se n t a n aly sis .
P ro ce dure /In te rv e ntio n
Partic ip an ts w ere i n ducte d o n m ed ic atio n a fte r b ein g i n str u cte d t o a b sta in f ro m o pio id s f o r 1 2–24 h ours
to p re se n t i n m ild t o m odera te o pio id w ith dra w al ( C lin ic al O pio id W ith dra w al S cale s c o re ≥ 8) o r a s
d eem ed a p pro pria te b y t h e s tu dy p hysic ia n . P artic ip an ts c am e t o t h e c lin ic d aily f o r o bse rv ed
m ed ic atio n a d m in is tr a tio n e x cep t S unday s a n d h olid ay s o r w hen t a k e-h om e m ed ic atio ns w ere
p erm itte d b y F ed era l/S ta te r e g ula tio ns. P artic ip an ts w ere t itr a te d t o a n a p pro pria te m ed ic atio n d ose a s
d ete rm in ed b y t h e l o cal s tu dy p hysic ia n , r e m ain ed o n s tu dy m ed ic atio n f o r 2 4 w eek s, a n d w ere t h en
ta p ere d o ff m ed ic atio n o ver ≤ 8 w eek s o r r e fe rre d f o r o ngoin g c lin ic al t r e atm en t, w ith s tu dy c o m ple tio n
by W eek 3 2. M ean m ax im um d aily d ose s t h ro ughout t h e t r ia l w ere 2 2.1 m g ( ra n ge = 2 –32m g) o f B U P
an d 9 3.1 m g ( ra n ge = 5 –397m g) o f M ET.
W eek ly a sse ssm en ts i n clu ded u rin e d ru g s c re en s a n d a d vers e e v en t a sse ssm en ts , a n d s e lf -re p orte d d ru g
use d ata w ere c o lle cte d e v ery f o ur w eek s. P artic ip an ts w ho m is se d 3 o r m ore c o nse cu tiv e d ay s o f
m ed ic atio n, r e tu rn ed t o t h e c lin ic w ith in 1 4 d ay s o f t h e l a st d ose , a n d w is h ed t o c o ntin ue m ed ic atio n,
w ere r e -in ducte d i f d eem ed a p pro pria te . P artic ip an ts w ho m is se d 1 4 o r m ore c o nse cu tiv e d ay s o f s tu dy
m ed ic atio n w ere t e rm in ate d f ro m t h e s tu d y. C om pen sa tio n w as p ro vid ed i n a cco rd an ce w ith l o cal s ite
p olic ie s, b ut t y pic ally i n clu ded c o m pen sa tio n f o r e ach r e se arc h a sse ssm en t. N o d if f e re n ces w ere f o und
betw een t h e t w o c o nditio ns i n t h e n um ber o f s e rio us a d vers e e v en ts .
O utc o m es
T re atm en t c o m ple tio n i s d efin ed a s t h e p artic ip an t c o ntin uin g i n t h e a ssig ned m ed ic atio n g ro up f o r 2 4
w eek s w ith out b ein g w ith dra w n. T re atm en t r e te n tio n i s c alc u la te d a s d ay s i n t r e atm en t s in ce
ra n dom iz atio n u ntil t h e l a st d ay o f m ed ic atio n d urin g t h e 2 4 w eek s o f t r e atm en t.
M easu re m ents
M easu re m en ts w ere c o nducte d a t b ase lin e f o r p artic ip an t c h ara cte ris tic s a n d d urin g t h e t r ia l f o r d ose
a n d u rin e d ru g s c re en s.
B ase lin e a sse ssm en ts i n clu ded d em ogra p hic s ( p artic ip an ts ’ a g e, g en der, r a ce
a n d e th nic ity ), n um ber o f c ig are tte s s m oked p er d ay, a lc o hol u se , d ru g i n je ctio n i n t h e p ast 3 0 d ay s, a n d
Short F orm 3 6-ite m H ea lth S urv ey (S F -3 6 , a s e lf -re p ort i n str u m en t t o a sse ss h ealth s ta tu s o ver a 4 -
w eek -p erio d p ro vid in g s u m mary s c o re s o f p hysic al a n d m en ta l h ealth c o m ponen ts ).
U rin e s p ecim en s w ere c o lle cte d u sin g a d ru g t e st c u p w ith t e m pera tu re
c o ntr o lle d m onito rin g a n d t e st s tr ip s f o r o pia te s, m eth ad one, o xyco done, c o cain e m eta b olite ,
a m pheta m in es, m eth am pheta m in es, c an nab in oid s a n d b en zo dia zep in es. U DS w ere c o lle cte d d urin g
base lin e a n d w eek ly t h ro ugh W eek 2 4.
D ate , m ed ic atio n, d ose , a n d a d m in is tr a tio n l o catio n d ata w ere c ap tu re d i n t h e D ose
L og. M ax im um d ose s i n m g d urin g t h e 2 4 w eek s w ere c ate g oriz ed i n to 0 –10, 1 2–14, 1 6–20, 2 2–28,
13
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14 4/22/2018 Treatment Retention among Patients Randomized to Buprenorphine/Naloxone Compared to Methadone in A Multi-site T rial
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3 0–32 f o r B U P a n d 0 –40, 4 1–60, 6 1–80, 8 1–120, a n d 1 21 o r h ig her f o r M ET. W eek ly a v era g e d ose
w as t h e d ose a v era g ed o ver a w eek , i n clu din g d ose = 0 f o r n o s h ow . D ose s o n t h e l a st d ay o f t r e atm en t
w ere c ate g oriz ed a s h ig her ( > =16m g f o r B U P, o r > =60m g f o r M ET) v ers u s l o w er i n t h e C ox m odel.
S ta tis tic a l A naly se s
G ro up d if f e re n ces b etw een B U P v s. M ET w ere t e ste d u sin g c h i- s q uare ( fo r c ate g oric al v aria b le s) o r t -
t e sts ( fo r c o ntin uous m easu re s). T he u nad ju ste d s u rv iv al f u nctio n w as a sse sse d u sin g t h e K ap la n -M eie r
m eth od, w ith a l o g r a n k t e st o f g ro up d if f e re n ces. C ox p ro portio nal h azard m odels w ere c o nducte d
to e x am in e c o m para tiv e s u rv iv al r a te s b etw een t h e t w o c o nditio ns a s w ell a s t o i d en tif y p re d ic to rs o f
re te n tio n i n clu din g p atie n t a n d m ed ic atio n c h ara cte ris tic s. T he g en era liz ed e stim atin g e q uatio ns ( G EE)
ap pro ach , a r e g re ssio n t e ch niq ue, w as a p plie d t o a sse ss t h e r e la tio nsh ip s b etw een d ose a n d o pia te u se
(e v id en ced b y p ositiv e u rin e r e su lts ) o ver t im e. T he G EE i s p artic u la rly a p pro pria te f o r a n aly zin g
lo ngitu din al d ata b ecau se i t t a k es t im e a n d t im e-in varia n t a n d t im e-v ary in g c o varia te s i n to a cco unt a n d
allo w s a d ju stm en t f o r w ith in -s u bje ct c o rr e la tio n. T he l o git l in k f u nctio n w ith b in ary d is tr ib utio n a n d
th e u nstr u ctu re d c o rre la tio n s tr u ctu re w ere a p plie d i n t h e G EE a n aly se s. A ll s ta tis tic al a n aly se s w ere
c o nducte d w ith p ro ced ure s F R EQ f o r t a b le s a n d c h i- s q uare t e sts , T TEST f o r t - te sts , L IF E TEST f o r t h e
lo g r a n k t e st, P H REG f o r C ox m odels , a n d G EN M OD f o r G EE a p pro ach o f S A S v ers io n 9 .2 .
R ESU LT S
Base lin e c h ara cte ris tic s o f t h e t o ta l s a m ple a s w ell a s f o r e ach g ro up s e p ara te ly b y t r e atm en t c o nditio n
(B U P v s. M ET) a re p ro vid ed i n T ab le 1 . W ith t h e e x cep tio n o f c ig are tte s m okin g a n d c o cain e p ositiv e
U DS, t h ere w ere n o s ig nif ic an t d if f e re n ce s b etw een t h e t w o c o nditio ns i n a ll o f t h e v aria b le s e x am in ed .
B asic ally , t h ese p artic ip an ts w ere e arly m id dle -a g ed ( M =37, S D =11 ), t w o-th ir d s m ale , w ith t h e h ig hest
p erc en ta g e o f w hite p artic ip an ts ( 7 1% , b ut a ls o i n clu ded 1 2% H is p an ic s a n d 9 % A fric an A m eric an s).
A lm ost 9 0% s m oked c ig are tte s ( m ore a m ong p artic ip an ts o n M ET, p < .0 5), 2 7% u se d a lc o hol, a n d 6 9%
in je cte d d ru gs i n t h e p ast 3 0 d ay s. M an y a ls o t e ste d p ositiv e f o r d ru gs o th er t h an o pio id s; 3 7% p ositiv e
fo r c o cain e ( 4 2% f o r M ET v s. 3 4% f o r B U P, p < .0 1), 9 % f o r a m pheta m in e, a n d 2 4% f o r m ariju an a.
D ay s o f o pio id u se i n t h e p ast 3 0 d ay s d id n ot d if f e r b etw een t h e t w o g ro ups. P hysic al C om ponen t
S um mary s c o re s o n t h e S F-3 6 w ere c o m para b le t o t h e a v era g e a m ong t h e g en era l p opula tio n o f s im ila r
a g e a n d g en der, b ut M en ta l C om ponen t S um mary s c o re s w ere a t a b out 3 9, 2 s ta n dard d ev ia tio ns b elo w
th e a v era g e f o r t h e g en era l p opula tio n.
Ta ble 1
C lin ic al P ro file s a t B ase lin e
B upre n orp hin e/N alo xon e M eth ad on e T ota l
(n = 738) (n = 529) (n = 1,2 67)
A ge, %
18–24 14.9 1 4.6 1 4.8
25–34 32.0 3 4.0 3 2.8
35–44 22.2 2 3.4 2 2.7
45–54 23.6 2 2.7 2 3.2
55+ 7.3 5 .3 6 .5
A ge, M ean ( S D ) 37.5 ( 1 1 .2 ) 37.3 ( 1 0.9 ) 37.4 ( 1 1 .1 )
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Open i n a s e p ara te w in dow
p< 0.0 5;
p< 0.0 1
U DS= urin e d ru g s c re en
T re atm ent C om ple tio n a nd R ete ntio n
A s s h ow n i n T ab le 2 , s ig nif ic an tly f e w er B U P p artic ip an ts ( 4 6% ) t h an M ET p artic ip an ts ( 7 4% )
co m ple te d t r e atm en t ( p < .0 1) a t 2 4 w eek s. T he m ean n um ber o f d ay s i n t r e atm en t w as 1 03.8 ( 6 6.9 ) f o r
B U P a n d 1 41.3 ( 5 0.8 ) f o r M ET. S ig nif ic an tly m ore B U P p artic ip an ts t h an M ET p artic ip an ts ( 2 4.8 % v s.
8 .3 % , p < .0 01) d ro pped o ut w ith in t h e f ir s t 3 0 d ay s o f t r e atm en t; a m ong t h ose w ho s ta y ed m ore t h an 3 0
day s, B U P p artic ip an ts s till s h ow ed a s ig n if ic an tly l o w er c o m ple tio n r a te t h an M ET p artic ip an ts
( 6 1.3 % v s. 8 0.3 % , p < .0 01). S urv iv al c u rv es t o 2 4 w eek s f o r t h e t w o g ro ups a re d is p la y ed i n F ig ure 1 .
A l o g-ra n k t e st c o m parin g M ET t o B U P i n dic ate d s ig nif ic an tly d if f e re n t s u rv iv al f u nctio ns ( p < .0 01).
M ore t h an 6 0% o f t h e d ro pouts i n b oth M ET a n d B U P w ere d ue t o h av in g m is se d 1 4 o r m ore d ay s, b ut
m ore B U P p artic ip an ts t h an M ET p artic ip an ts d ro pped o ut b ecau se t h ey n o l o nger w is h ed t o p artic ip ate
i n t h eir a ssig ned t r e atm en t ( 2 5.6 % v s. 1 2.4 % , p < .0 01).
B upre n orp hin e/N alo xon e M eth ad on e T ota l
(n = 738) (n = 529) (n = 1,2 67)
F em ale G en der, % 3 2.0 3 2.1 3 2.0
R ace/E th nic ity , %
White 6 9.4 7 4.1 7 1.4
Afric an A m eric an 8 .5 8 .9 8 .7
His p an ic 1 3.4 1 0.0 1 2.0
Oth er 8 .7 7 .0 8 .0
C lin ic s ite l o catio n, %
West c o ast 7 0.3 6 7.3 6 9.1
East c o ast 2 9.8 3 2.7 3 0.9
# c ig are tte s s m oked p er d ay, %
0 12.2 9 .5 1 1 .1
<10 28.6 2 6.8 2 7.9
11 –20 44.9 4 6.1 4 5.4
21–30 11 .9 1 2.1 1 2.0
31+ 2.4 5 .5 3 .7
D ay s u sin g o pio id s i n p ast 3 0 d ay s 26.8 ( 6 .5 ) 26.7 ( 6 .6 ) 26.8 ( 6 .5 )
A lc o hol u se , % 2 6.3 2 7.5 2 6.8
C ocain e p ositiv e U DS, % 3 4.0 4 2.0 3 7.3
A m pheta m in e p ositiv e U DS, % 8 .7 9 .5 9 .0
C an nab in oid s p ositiv e U DS, % 2 5.3 2 1.4 2 3.7
D ru g i n je ctio n i n p ast 3 0 d ay s, % 6 8.3 6 9.3 6 8.7
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Fig ure 1
S urv iv al C urv es f o r B upre n orp hin e V ers u s M eth ad one
T a ble 2
T re atm en t C om ple tio n a n d D ro pout R ea so ns ( % )
Bupre n orp hin e/N alo xon e M eth ad on e T ota l
(n = 738) (n = 529) (n = 1,2 67)
D ro pout d urin g t h e f ir s t 3 0 d ay s o f t r e atm en t, % 2 4.8 8 .3 1 7.9
C om ple te d t h e 2 4-w eek t r ia l, % 4 6.1 7 4.1 5 7.8
R ete n tio n ( d ay s i n t r e atm en t) , M ean ( S D ) 103.8 ( 6 6.9 ) 141.3
( 5 0.8 )
11 9.4 ( 6 3.5 )
D ro pout r e aso ns, % n = 398 n= 137 n= 535
Mis se d 1 4 o r m ore d ay s 63.1 6 8.6 6 4.5
No l o nger w is h t o p artic ip ate 2 5.6 1 2.4 2 2.2
Adm in is tr a tiv e d is c h arg ed 3 .5 4 .4 3 .7
Not m ed ic ally a p pro pria te 3 .8 3 .7 3 .7
Oth er r e aso ns ( in carc era tio n, m oved ) 4.0 1 1 .0 5 .8
P artic ip an ts w ho s ta y ed i n t r e atm en t m ore t h an 3 0
day s
n= 555 n= 529 n= 1,0 40
Com ple te d t h e 2 4-w eek t r ia l, % 61.3 8 0.8 7 0.4
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Bupre n orp hin e/N alo xon e M eth ad on e T ota l
(n = 738) (n = 529) (n = 1,2 67)
Rete n tio n ( d ay s i n t r e atm en t) , M ean ( S D ) 1 33.3 ( 4 9.2 ) 152.8
( 3 4.8 )
142.4
( 4 4.1 )
O pen i n a s e p ara te w in dow
P< 0.0 1
M axim um D ose o f M edic a tio n a nd R ete ntio n
To e x plic ate t h e d ose a n d r e te n tio n r e la tio nsh ip a n d f o r e ase o f u nders ta n din g, w e c la ssif ie d t h e
m ax im um d ose b y d is c re te c ate g orie s a n d p lo tte d t h e d ose c ate g orie s a n d r e te n tio n r a te s i n F ig ure 2 .
D ose s o f M ET g re ate r t h an 6 0m g d em onstr a te d 8 0% o r b ette r r e te n tio n w ith 1 20m g o r h ig her s h ow in g
a 9 1% c o m ple tio n r a te . I n c o ntr a st, B U P d ose s a n d r e te n tio n r a te s s h ow ed a l in ear r e la tio nsh ip , w ith
i n cre asin g d ose y ie ld in g i m pro ved r e te n tio n, w ith t h e h ig hest d ose c ate g ory o f 3 0–32m g B U P r e su ltin g
in a c o m ple tio n r a te o f a b out 6 0% .
Fig ure 2
C om parin g R ete n tio n a t 2 4 W eek s b y M ax im um D ose o f M ed ic atio n P re sc rib ed
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Urin e R esu lt s d urin g th e T ria l
T he u nderly in g m ech an is m f o r i n cre ase d r e te n tio n w ith h ig her d ose s c o uld b e t h at h ig her d ose s r e d uce
c ra v in g a n d o pia te u se , t h ere b y r e ta in in g p artic ip an ts i n t r e atm en t. T o t e st t h is h ypoth esis , w e f u rth er
e x am in ed i f a l o w er d ose p re d ic ts o pia te u se ( a s i n dic ate d b y a p ositiv e o pia te u rin e t e st) o ver t im e
durin g t h e t r ia l. F ig ure 3 p re se n ts t h e t r a je cto rie s o f t h e w eek ly a v era g e d ose a n d p ositiv e o pia te t e st
re su lts o ver t h e 2 4 w eek s o f t h e t r ia l f o r M ET a n d B U P s e p ara te ly . G EE w ere a p plie d , d em onstr a tin g a
s ig nif ic an t m ain e ff e ct o f d ose a n d a s ig nif ic an t i n te ra ctio n e ff e ct o f d ose a n d t r e atm en t c o nditio n.
S pecif ic ally , i n cre ase d d ose w as n eg ativ ely r e la te d t o c o ntin ued o pia te u se ( O R=0.9 9, 9 5% CI= 0 .9 8–
0.9 9, p < .0 01), w ith B U P p artic ip an ts r e la tiv e t o M ET p artic ip an ts s h ow in g a l o w er l ik elih ood o f
positiv e o pia te t e st r e su lts f o r e v ery m g d ose i n cre ase ( O R=0.9 8, 9 5% CI= 0.9 7–0 .9 9, p < .0 01).
F urth erm ore , o pia te u se w as s ig nif ic an tl y l o w er a m ong B U P t h an M ET p artic ip an ts d urin g t h e f ir s t 9
w eek s o f t h e t r e atm en t ( O R=0.6 3, 9 5% CI= 0.5 2–0.7 6, p < .0 1).
F ig ure 3
A vera g ed D ose a n d P ositiv e O pia te U rin e T est A cro ss W eek s b y T re atm en t G ro up ( n = 1,2 67)
C ox M odel P re dic tin g R ete ntio n 4/22/2018 Treatment Retention among Patients Randomized to Buprenorphine/Naloxone Compared to Methadone in A Multi-site T rial
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The u nad ju ste d h azard r a tio f o r r e te n tio n o n M ET c o m pare d w ith B U P o ver t h e 2 4 w eek s o f t h e t r ia l
w as 2 .6 5 ( 9 5% C I= 2 .1 8–3.2 2, p < .0 1). A dju ste d h azard r a tio w as 1 .6 1 ( 9 5% C I= 1.2 0–2.1 5, p < .0 1)
co ntr o llin g f o r c o varia te s a t b ase lin e i n t h e C ox m odel ( T ab le 3 ) .
T a ble 3
C ox M odel P re d ic tin g T re atm en t R ete n ti o n
B upre n orp hin e/N alo xon e M eth ad on e T ota l
(n = 738) (n = 529) (n = 1,2 67)
H aza rd R atio s
(9 5% C I)
H aza rd
R atio s
(9 5% C I)
H aza rd
R atio s
(9 5% C I)
E xperim en ta l g ro up, B upre n orp hin e ( v s. M eth ad one) – –
1 .6 1
(1 .2 0 –
2 .1 5)
A ge
0.9 9
(0 .9 8 – 1 .0 0)
0.9 8
(0 .9 6 –
1 .0 0)
0.9 9
(0 .9 8 –
0 .9 9)
G en der, M ale s ( v s. F em ale s)
0 .7 1
(0 .5 7 – 0 .8 8)
2.0 8
(1 .3 5 –
3 .2 1)
0.9 2
(0 .7 6 –
1 .1 2)
R ace/E th nic ity
Afric an A m eric an ( v s. W hite )
1 .1 0
(0 .7 3 – 1 .6 7)
0.7 2
(0 .2 9 –
1 .7 6)
1.0 5
(0 .7 3 –
1 .5 3)
His p an ic ( v s. W hite )
1 .2 6
(0 .9 3 – 1 .6 9)
1.6 4
(0 .9 6 –
2 .8 0)
1.4 0
(1 .0 8 –
1 .8 1)
Oth er ( v s. W hite )
1 .0 8
(0 .7 5 – 1 .5 4)
1.8 9
(1 .0 4 –
3 .4 5)
1.2 2
(0 .9 0 –
1 .6 6)
S ite
West c o ast ( v s. E ast c o ast) 0 .5 4
(0 .4 3 – 0 .6 8)
0.5 9
(0 .3 8 –
0 .9 0)
0.5 7
(0 .4 7 –
0 .7 0)
B ase lin e c h ara cte ris tic s
A lc o hol u se
1 .0 9
(0 .8 6 – 1 .3 7)
0.8 8
(0 .5 7 –
1 .3 6)
0.9 8
(0 .8 0 –
1 .2 0)
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Go to :
O pen i n a s e p ara te w in dow
p< 0.0 5,
P < 0.0 1
R esu lts o f t h e C ox m odel i d en tif ie d a d ditio nal m easu re s p re d ic tin g r e te n tio n. F or t h e t o ta l s a m ple ,
y ounger a g e, H is p an ic ( re la tiv e t o w hite ), a n d u se o f o pio id s, a m pheta m in e, c an nab in oid s o r c o cain e
w ere a sso cia te d w ith d ro pout f ro m t h e t r ia l r e su ltin g i n s h orte r r e te n tio n. H ow ev er, s ite ( i.e ., p ro gra m s
on W est C oast; H R=0.5 7, 9 5% C I= 0.4 7–0.7 0, p < .0 1) a n d h ig her m ed ic atio n d ose ( a t l e ast 1 6m g f o r
B U P a n d 6 0m g f o r M ET H R=0.3 2, 9 5% C I= 0.2 3–0.4 6, p < .0 1) w ere a sso cia te d w ith l o w er r is k f o r
dro pout. I n o th er w ord s, p artic ip an ts r e ceiv in g a n l o w er m ed ic atio n d ose w ere 3 .0 9 t im es ( C I= 2.1 9–
4.3 7) m ore l ik ely t h an t h ose r e ceiv in g a n h ig her d ose t o d ro p o ut o f t r e atm en t. F urth erm ore , t h e
in te ra ctio n t e rm o f e x perim en ta l c o nditio n a n d d ose l e v el ( o n t h e l a st d ay o f t r e atm en t) w as a ls o
sig nif ic an t. T ak in g m eth ad one-w ith -lo w er- d ose ( H R=1) a s t h e r e fe re n ce g ro up, t h e H R o f B U P w as
1 .6 1 ( p < .0 1) i n dic atin g t h at B U P-w ith -lo w er- d ose w as 1 .6 1 t im es m ore l ik ely t o d ro p o ut t h an t h e
re fe re n ce g ro up. O n t h e o th er h an d, m eth ad one-w ith -h ig her- d ose w as 0 .3 2 l e ss l ik ely t o d ro p o ut t h an
th e r e fe re n ce g ro up, w here as t h e s ig nif ic an t i n te ra ctio n o f 2 .0 0 ( p < .0 1) i n dic ate d t h at B U P-w ith -h ig her-
d ose w as m ore l ik ely t o d ro p o ut ( a lth ou gh o nly a b out 1 .0 4 t im es) t h an t h e r e fe re n ce g ro up. S ep ara te
a n aly se s f o r t h e t w o g ro ups s h ow ed t h at s ite ( i.e ., p ro gra m s i n W est C oast, r e la tiv e t o t h ose i n t h e E ast
C oast) a n d u se o f o pio id s, a m pheta m in e, c an nab in oid s, o r c o cain e d urin g t r e atm en t w ere s ig nif ic an t f o r
both t h e B U P a n d M ET g ro ups. T he i n flu en ce o f g en der w as i n a n o pposite d ir e ctio n f o r t h e t w o
gro ups. M ale s i n t h e B U P g ro up w ere l e ss l ik ely t o d ro p o ut, a n d i n c o ntr a st, m ale s i n t h e M ET g ro up
w ere m ore l ik ely t o d ro p o ut.
D IS C USSIO N
This i s t h e f ir s t l a rg e s c ale r a n dom iz ed t r ia l t h at p ro vid es t h e o pportu nity t o c o m pare t h e t r e atm en t
re te n tio n o f p artic ip an ts o n b upre n orp hin e a n d m eth ad one i n c o m munity t r e atm en t p ro gra m s i n t h e
U .S . T he r e su lts d em onstr a te t h at t h ose t r e ate d w ith B U P w ere m ore t h an 5 0% l e ss l ik ely t o r e m ain i n
t r e atm en t f o r 2 4 w eek s t h an t h ose r e ceiv in g M ET. T his f in din g i s c o nsis te n t w ith o th er c o ntr o lle d t r ia ls
o r o bse rv atio nal ( n onra n dom iz ed ) s tu die s, e v en i n clu din g s tu die s t h at f o cu se d o n s p ecia l p opula tio ns
su ch a s p re g nan t p atie n ts . O th er f in din gs o f t h e s tu dy a re a ls o c o nsis te n t w ith p rio r l ite ra tu re ,
in clu din g h ig her d ose r e la te d t o l o nger r e te n tio n, u se o f o th er d ru gs ( e .g ., c o cain e, a m pheta m in e)
a sso cia te d w ith l o w er r e te n tio n, a n d o pia te u se d urin g t r e atm en t n eg ativ ely r e la te d t o d ose f o r b oth
g ro ups. T he u niq ue c o ntr ib utio n o f t h e p re se n t s tu dy i s t h at t h ese f in din gs w ere c o nfir m ed w ith t h is
r a n dom iz ed t r ia l c o nducte d i n c o m munity t r e atm en t p ro gra m s i n t h e U .S .
T he s tu dy a ls o r e v eale d a d ditio nal f in din gs r e g ard in g B U P d ose a n d t r e atm en t r e te n tio n. F ir s t,
a p pro xim ate ly 2 5% o f t h e B U P p artic ip an ts d ro pped o ut w ith in f ir s t 3 0 d ay s o f t r e atm en t, s u ggestin g a
c ritic al p erio d c allin g f o r s p ecia l e ff o rts i n r e ta in in g t h ese p artic ip an ts . S eco nd, o f t h ose w ho r e m ain ed
in t r e atm en t, p ositiv e o pia te u rin e r e su lts w ere s ig nif ic an tly l o w er a m ong B U P r e la tiv e t o M ET
partic ip an ts d urin g t h e f ir s t 9 w eek s o f t r e atm en t. T his f in din g c o nfir m s t h e a d van ta g e o f B U P
re q uir in g a m uch s h orte r t im e f o r i n ductio n t h an M ET. T hir d , t h ere w as a l in ear p ositiv e r e la tio nsh ip
b etw een B U P d ose a n d t h e t r e atm en t c o m ple tio n r a te , s u ggestin g t h e b en efit o f d osin g g re ate r t h an t h e
co m mon p ra ctic e o f a m ax im um d ose o f 1 6m g. H ow ev er, e v en w ith t h e h ig hest B U P d ose l e v el o f 3 0–
32m g a llo w ed i n t h is t r ia l, t h e r e te n tio n r a te w as l e ss t h an t h e r a te i n t h e M ET g ro up ( e .g ., 6 0% v s
74% ), a n d a p pro xim ate ly 3 0% o f t h e p artic ip an ts c o ntin ued o pio id u se . B esid es a d ditio nal s tr a te g ie s
fo cu sin g o n r e ta in in g B U P p artic ip an ts b ey ond 3 0 d ay s o f t r e atm en t, t h ese f in din gs s u ggest t h at
p artic ip an ts m ay y et f a re b ette r w ith B U P d ose s h ig her t h an t h e 3 2m g u se d i n t h is s tu dy. G iv en t h e
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g en era lly h ig h s a fe ty p ro file o f B U P a n d t h e l a ck o f a n y s ig nif ic an t s id e e ff e cts a n d o th er a d vers e
e ff e cts a t t h e h ig h d ose r a n ge o bse rv ed i n t h is s tu dy, w e b elie v e w ith p ro per m on ito rin g s a fe ty w ill n ot
be a c lin ic al c o ncern i n s u ch a n e ff o rt.
F in ally , t h e s tu dy h as i d en tif ie d a d ditio nal p artic ip an t c h ara cte ris tic s p re d ic tin g d ro pout, i n clu din g
bein g y oung, H is p an ic , a n d c o nco m ita n t u se o f h ero in o r o th er d ru gs s u ch a s c an nab in oid s, c o cain e o r
am pheta m in e d urin g t r e atm en t. T re atm en t p ro gra m s m ay c o nsid er p ay in g s p ecia l a tte n tio n t o p atie n ts
w ith t h ese c h ara cte ris tic s t o p re v en t d ro po ut. I t s h ould b e n ote d t h at o ur f in din g o n c an nab in oid s i s i n
c o ntr a st t o m ost p rio r s tu die s t h at h av e f o und n o e ff e ct o f t h e u se o f c an nab is o n m eth ad one t r e atm en t
outc o m es i n clu din g t r e atm en t r e te n tio n. A p ote n tia l e x pla n atio n f o r t h is d is c re p an cy m ay b e t h at
str a in s o f m ariju an a a v aila b le m ore r e cen tly , w hen t h e c u rre n t s tu dy w as c o nducte d , h av e b een
d elib era te ly b re d t o h av e h ig h c o ncen tr a tio ns o f d elta -9 -te tr a h ydro can nab in ol m ak in g t h em m uch m ore
p ote n t a n d p ote n tia lly m ore d esta b iliz in g f o r p atie n ts o n o pio id m ain te n an ce t h era p y.
T he s tu dy h as s e v era l l im ita tio ns. T here w ere l im ite d m easu re s o f p artic ip an t m otiv atio n a n d p ro gra m
a n d c o m munity c h ara cte ris tic s t h at a re l ik ely t o i n flu en ce t r e atm en t r e te n tio n. R easo ns f o r d ro pout
w ere c o ars e ly r e co rd ed ; a lth ough t h e d ata d id i n dic ate t h at m an y m ore B U P p artic ip an ts s im ply
d is c o ntin ued t h eir t r e atm en t. A q ualita tiv e s tu dy o f t h is s a m ple h as s u ggeste d t h at B U P p artic ip an ts
r e p orte d n eg ativ e p hysic al r e actio ns o r d id n ot l ik e B U P, b ein g p re v io usly f a m ilia r w ith M ET, a n d t h us
dro pped o ut. T he f in din gs m ust a ls o b e t a k en i n t h e c o nte x t o f a n o pen -la b el, u nblin ded c lin ic al t r ia l.
D esp ite t h ese l im ita tio ns, t h e s tu dy r e v eale d s e v era l i m porta n t f in din gs a s d is c u sse d e arlie r. G iv en t h e
lin ear t r e n d o f h ig her B U P d ose r e la te d t o i n cre ase d r e te n tio n, f u tu re s tu die s s h ould i n vestig ate i f B U P
dose s g re ate r t h an 3 2m g s h ould b e c o nsid ere d t o i n cre ase r e te n tio n, a n d p erh ap s t o f u rth er r e d uce
o pio id u se d urin g t r e atm en t. O ne s tu dy w hic h e x am in ed B U P d ose s o f 2 4–56m g/d a m ong 6 50 p atie n ts
s h ow ed a r e te n tio n r a te o ver 9 2% a t 3 0 m onth s a n d, s im ila r t o t h e p re se n t i n vestig atio n, d ecre asin g
ra te s o f i llic it s u bsta n ce u se a t t h e h ig her d ose s. I n r e se arc h o r c lin ic al p ra ctic e, B U P i s o fte n
p re sc rib ed a t a d ose o f 1 6m g o r l o w er, a s B U P i s a n o pio id p artia l a g onis t w ith a ‘ c eilin g e ff e ct’ f o r
re sp ir a to ry d ep re ssio n a n d i n p re v io us h um an l a b ora to ry s tu die s, h ig her d ose s o f B U P r e v eale d a
f la tte n in g o ut o f t h e d ose -e ff e ct c u rv e, i .e . i n cre asin g d ose s d o n ot r e su lt i n g re ate r c h an ges i n
s u bje ctiv e m easu re s o r r e sp ir a to ry r a te . A r e cen t r e v ie w a rtic le i n dic ate s t h at t h e r is k o f r e sp ir a to ry
d ep re ssio n a sso cia te d w ith B U P i s l o w er t h an w ith o th er o pio id s i n clu din g m eth ad one. I t a p pears t h at
th e c u rre n t c o m mon p ra ctic e o f p re sc rib in g a t a d ose o f 1 6m g p er d ay a n d n ot t o e x ceed 3 2m g
m ax im um i s d riv en b y t h e c eilin g e ff e ct o bse rv ed a n d a f e w P E T s c an s tu die s s h ow in g h ig h m u
re cep to r o ccu pan cy ( 7 9–95% a t 1 6m g, 8 4% a t 3 2m g ) a s w ell a s c o ncern s a b out d iv ers io n.
H ow ev er, t h ese s tu die s w ere b ase d o n s m all s a m ple s a n d d o n ot t a k e i n to a cco unt i n te r- in div id ual
v aria tio n a n d t h e o th er p ote n tia l n on-m u e ff e cts o f B U P. H is to ry h as t a u ght t h at f o r a b out 2 0 y ears i t
w as c o m mon t o h av e M ET d ose c eilin gs o f 4 0m g p er d ay, b ut i t i s n ow w ell e sta b lis h ed t h at t h is i s
i n ad eq uate t o m ain ta in t h e n ecessa ry p la sm a c o ncen tr a tio ns t o b e e ff e ctiv e; t h e e ff e ctiv e r a n ge i s
b etw een 6 0m g a n d 1 20m g o r h ig her p er d ay f o r m ost p atie n ts . T he c u rre n t s tu dy s u ggests t h e
possib ility o f B U P a t a d ose o f 3 2m g o r h ig her h av in g a p ote n tia l i m pact o n i m pro vin g t r e atm en t
re te n tio n a n d o utc o m e. T hus, f u rth er i n vestig atio ns o f t h e s a fe ty , e ff ic acy, a n d c lin ic al u tilitie s o f h ig her
d ose s o f B U P s h ould b e c o nsid ere d .
T he h ig h d ro pout r a te s a t t h e e arly p hase o f B U P t r e atm en t s u ggest t h e n eed f o r e arly i n te rv en tio ns t o
p re v en t d ro pout. I t i s p ossib le t h at m ore i n te n siv e p sy ch oso cia l s u pport c o uld h elp , a lth ough s tu die s t o
d ate i n dic ate l ittle b en efit t o i n cre ase d c o unse lin g f o r p atie n ts t r e ate d w ith b upre n orp hin e. A n
alte rn ativ e a p pro ach a s p ro pounded b y K ak ko e t a l. a n d d em onstr a te d e ff ic acio us i n a r a n dom iz ed t r ia l
is p ro m pt, e arly t r a n sfe r t o M ET o f p atie n ts w ho d o n ot q uic k ly s ta b iliz e o n B U P. A m ore
w id esp re ad i n tr o ductio n o f c o ntin gen cy m an ag em en t i n to o pio id t r e atm en t p ro gra m s c o uld a ls o h elp t o
o ptim iz e r e te n tio n a n d o utc o m es f o r b oth B U P a n d M ET. F in ally , h ero in -a ssis te d t r e atm en t i s u se d i n
1 3
20
21
22
23
24
25
26 ,27
26 27 28 ,29
30
31 ,32 ,33
34
35 4/22/2018 Treatment Retention among Patients Randomized to Buprenorphine/Naloxone Compared to Methadone in A Multi-site T rial
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3947022/ 12/15
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G o to :
se v era l E uro pean c o untr ie s w ith s u ccess , p artic u la rly f o r p eo ple w ith o pio id d ep en den ce w ho c o ntin ue
in tr a v en ous h ero in w hile o n m eth ad one m ain te n an ce o r w ho a re n ot e n ro lle d i n t r e atm en t.
B U P r e te n tio n m ay a ls o b e i m pro ved w ith t a k e-h om e d ose s a s p erm itte d b y r e g ula tio n a n d a s s ta n dard
in o ff ic e-b ase d p ra ctic e s u perv is e d b y p hysic ia n s, w hic h o bvia te s t h e n eed f o r d aily a tte n dan ce i n c lin ic
f o r d osin g. A s d esc rib ed e arlie r, t h e t r ia l w as c o nducte d a m ong c o m munity m eth ad one m ain te n an ce
p ro gra m s a n d t h us m ay n ot b e o ptim al f o r d eliv erin g B U P t r e atm en t. T he n in e c lin ic s w ere a ll f e d era lly
l ic en se d o pio id t r e atm en t p ro gra m s t h at h av e p ro vid ed t r e atm en t w ith m eth ad one f o r m an y y ears . A ll
s ta ff a n d m ost p artic ip an ts h ad p re v io us e x perie n ce w ith M ET, a n d p artic ip an ts c am e t o t h ese p ro gra m s
fo r m eth ad one t r e atm en t. B ecau se B U P w as d eliv ere d w ith in t h ese m eth ad one m ain te n an ce p ro gra m s,
a ll p ro gra m s d eliv ere d B U P f o llo w in g t h e s a m e r u le s a n d r e g ula tio ns f o r m eth ad one p re sc rip tio n ( e .g .,
d aily d ose i n c lin ic ), p re clu din g t h e f le x ib ility a n d i n div id ualiz atio n p ossib le i n o ff ic e-b ase d t r e atm en t
th at m ay h elp t o r e ta in s o m e p atie n ts .
T he d if f e re n tia l r e te n tio n o f m ale s b y m ed ic atio n c o nditio n h as n o d efin itiv e e x pla n atio n a n d d ese rv es
fu tu re i n vestig atio n. S in ce o pio id s s u ppre ss t h e h ypoth ala m ic -p itu ita ry -g onad al a x is l e ad in g t o l o w er
te sto ste ro ne l e v els , i t m ay b e t h at B U P, a s a p artia l a g onis t, d oes s o l e ss t h an M ET, a n d t h us m ale s f in d
B U P m ore t o le ra b le i n t h at r e g ard .
In c o nclu sio n, t h e s tu dy f in din gs s u ggest t h e n eed t o ( 1 ) i n vestig ate t h e u se o f h ig her m ed ic atio n d ose s,
p artic u la rly f o r B U P, ( 2 ) a d dre ss c o ntin u ed u se o f o pia te a n d o th er d ru gs s u ch a s c o cain e,
a m pheta m in es, a n d c an nab in oid s, a n d ( 3 ) f u rth er s tu dy a n d i d en tif y f a cto rs /s tr a te g ie s i n flu en cin g B U P
re te n tio n, p artic u la rly d urin g t h e f ir s t 3 0 d ay s o f t r e atm en t i n o rd er t o h elp i n e ff o rts t o i m pro ve
en gag em en t a n d r e te n tio n i n o pio id t r e atm en t p ro gra m s.
A ckn ow le dgm ents
F undin g h as b een p ro vid ed b y t h e N atio n al I n stitu te o n D ru g A buse t h ro ugh G ra n ts U 10 U 10D A13045
an d K 05D A017648.
F ootn ote s
Decla ra tio n o f In te re st: A uth ors d is clo sin g r e le va nt fin a ncia l in te re sts , a ctiv it ie s, r e la tio n sh ip s, a nd a ff ilia tio ns a re :
Y ih -In g H se r: R ece iv e d a s m all e duca tio nal g ra nt fr o m R eckit t B en ckis e r P ha rm ace utic a ls to s u pport a S um m er
In stit u te o n P ro m otin g R eco ve ry w it h in th e C hangin g H ea lt h S erv ic e S yste m .
Andre w S axo n: C onsu lt a nt to R eckit t B enckis e r P ha rm ace utic a ls . A dvis o ry b oard m em be r fo r A lk e rm es, In c.
W alt e r L in g: C onsu lt a nt to R eckit t B enckis e r P ha rm ace utic a ls .
A ll o th er a uth ors r e port n o fin ancia l o r o th er p ossib le c o nflic ts o f in te re st.
T ria l r e g is tr a tio n: S ta rtin g T re atm ent w it h A gonis t R epla ce m en t T hera pie s ( S TA R T) o n C lin ic a lT ria ls .g ov
(N CT00315341).
T he c o rre sp ondin g a uth or, Y ih -In g H se r, h as f u ll a cce ss to a ll o f th e d ata in th e s tu dy a nd ta ke s r e sp onsib il it y fo r th e
in te grit y o f th e d ata a nd th e a ccu ra cy o f th e d ata a naly sis .
A uth or c o ntr ib utio ns to th e m anuscrip t a re a s fo llo w s:
S tu dy c o nce pt a nd d esig n: H se r, S axo n, T hom as, J a co bs, L in g
A cq uis it io n o f d ata : S axo n, T hom as, H asso n, H illh ouse , W ie st, C ohen, L in g
A naly sis a nd in te rp re ta tio n o f d ata : H se r, S axo n, H uang, T e ru ya , M cL aughlin , C oh en, L in g
D ra ftin g o f th e m anuscrip t: H se r, S axo n, H uang, L in g
C rit ic a l r e vis io n o f th e m anuscrip t fo r im porta nt in te lle ctu al c o nte nt: H se r, S axo n, H asso n, T hom as, H illh ouse ,
Ja co bs, T e ru ya , M cL aughlin , W ie st, C ohen, L in g
S ta tis tic a l a naly sis : H uang, H illh ouse
3 6 4/22/2018 Treatment Retention among Patients Randomized to Buprenorphine/Naloxone Compared to Methadone in A Multi-site T rial
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3947022/ 13/15
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O bta in in g fu ndin g: H se r, S axo n, H asso n, L in g
A dm in is tr a tiv e , te ch nic a l, o r m ate ria l s u pport: S axo n, H asso n, T hom as, H illh ouse , T e ru ya
S tu dy s u perv is io n: H se r, S axo n, T hom as, J a co bs, L in g
R efe re nce s
1. S ubsta n ce A buse a n d M en ta l H ealth S erv ic es A dm in is tr a tio n. R esu lts f ro m t h e 2 010 N atio nal
S urv ey o n D ru g U se a n d H ealth : S um mary o f N atio nal F in din gs. R ock ville , M D: 2 011 .
2. D eg en hard t L , H all W . E xte n t o f i llic it d ru g u se a n d d ep en den ce, a n d t h eir c o ntr ib utio n t o t h e g lo bal
b urd en o f d is e ase . L an cet. 2 012 J a n 7 ; 379 (9 810):5 5–70. [P ubM ed ]
3 . W arn er M , C hen L H , M ak uc D M , A nders o n R N , M in iñ o A M . D ru g p ois o nin g d eath s i n t h e U nite d
S ta te s, 1 980–2008. H yatts v ille , M D: N atio nal C en te r f o r H ealth S ta tis tic s; 2 011 .
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Roberts T , B urls A , T ay lo r R S. M eth ad one a n d b upre n orp hin e f o r t h e m an ag em en t o f o pio id
d ep en den ce: a s y ste m atic r e v ie w a n d e co nom ic e v alu atio n. H ealth T ech nol A sse ss. 2 007; 11 (9 ):1 –171.
iii– iv . [P ubM ed ]
5 . B ell J , T rin h L , B utle r B , R an dall D , R ubin G . C om parin g r e te n tio n i n t r e atm en t a n d m orta lity i n
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200. [P ubM ed ]
6 . M attic k R P, K im ber J , B re en C , D av oli M . B upre n orp hin e m ain te n an ce v ers u s p la ceb o o r m eth ad one
m ain te n an ce f o r o pio id d ep en den ce. C och ra n e D ata b ase S yst R ev. 2 008; 16 (2 ):C D 002207. [P ubM ed ]
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8 . G ers te in D R, H arw ood H J, e d ito rs . T re atin g D ru g P ro ble m s. V ol. 1 . N atio nal A cad em y P re ss;
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b upre n orp hin e a n d b upre n orp hin e/n alo xone s o lu ble -film s. C lin P harm aco l T her. 2 011 M ar; 8 9 (3 ):4 43–
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1 2. F are ed A , V ay ala p alli S , C asa re lla J , D re x le r K . E ff e ct o f b upre n orp hin e d ose o n t r e atm en t
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[P M C f re e a rtic le ] [P ubM ed ]
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