Alcoholism, clinical and experimental res
`v. 2S, no. 5, suppl. (May 2002'
`DUP - GenN.al Collection
`W1 ·' l 30&R
`2002-05-21 0? · :~ ·~ :00
`
`PROPERTY O F THE
`NATIONAL
`LIBRARY OF
`MEDICINE
`
`AMN1035
`IPR of Patent No. 7,919,499
`
`

`

`RSA ABSTRACTS
`
`752-767
`
`750
`
`COMBINING NALTREXONE AND MEMANTINE TO BLOCK THE
`REWARDING EFFECTS OF ALCOHOL AN EXPERIMENTAL PILOT
`STUDY IN HUMAN SUBJECTS
`cG SchOlz, C Mayer, G Koller, M Werntcke, R Gueorgweva, JH Krystal
`Bonn Untverstty, Stgmund-Freund Str 25. Bonn Germany Yale
`Untversrty, 34 Park Str New Haven CT
`
`The htgh pnonty for developmg new pharmacotherapy approaches to
`the treatment of alcoholism has not decreased With recent data
`tndtcating the lack of efftcacy of naltrexone treatment m alcohol
`dependent veterans (Krystal et at 2001) Supported by results from
`precltntcal work (HOlter et al 1990), we have been collectmg data on the
`capacity of naltrexone (unspectftc op101d antagontst). memantme (an
`uncompett\Jve NMOA receptor antagont~t), and the combtnatton to bloc.k
`the rewardtng effects of ethanol mtox1cattonm healthy human subjects
`Our expert mental study Is betng conducted m a double blmd, placebo
`controlled, cross-over fashion Subjects recetve 37 5 mg naltrexone or
`placebo before admtmstratton of 30 mgf70kg memantme or placebo
`Two hours later a total of 49gf70kg of alcoholts admJntstered tn a
`wtthtn-sesston cumula1Jve-dos1ng procedure Stunulatmg subjective
`effects are assessed tn several measurements, mcludmg the BAES
`(Btphastc Alcohol Effect Scale) Further assessments mclude
`cogn1t1vron (CPT, word recall) and coordmatton (one leg stand) Results
`are analyzed usmg generalized l1near m1xed models (SAS PROC
`MIXED, SAS PROC GENMOD). Our ptlot data m 8 healthy human
`subJects tndicate that memantine and naltrexone, by themselves.
`Influence the basal level of sttmulalton (naltrexone 1s mtldly sedatmg,
`memantine is mtldly sttmulating) Of greatest mterest. our data suggest
`that the combmat1on of memantme and naltrexone (but not etther drug
`alone) blocks the dose-related Stimulatory effects of ethanol Suntlarly,
`naltrexone blocks the memantme-poten!Jatton of dtscr1mmattve stm1Uius
`effects of ethanol (i e , blocks the abrltty of 1ncreastng doses of ethanol
`to be perceived as '"more ethanol like"") Together. these data suggest
`that naltrexone might be a cnttcal therapeuttc adjuvant 1f memant1ne or
`other related drugs are developed as pharmacotherapres for alcohol
`dependence Krystal JH et al NEJM 2001.345 1734-1739 Holter SM et
`al Eur J Pharamcol1996. 31 314-315
`
`751
`
`NALTREXONE AND ACAMPROSATE META-ANALYSIS OF TWO
`MEDICAL TREATMENTS FOR ALCOHOLISM
`J S Hopktns. J C Garbutt, C L. Poole. S L West, T S Carey
`Center for Alcohol Studies, Departments of Psychiatry and
`Eprdemtology, Unlverstty of North Carolma, Chapel Hrll, NC 27599
`
`A meta-analysrs was performed to assess the relattve effecttveness of
`naltrexone and acamprosate in the treatment of alcoholism Studies
`tdenttfted from the medical literature were collected and revtewed
`Databases searched for relevant studtes Included Medlin e. PSYCinfo,
`EM BASE, IPA, and CINAHL Outcomes common to the maJorrty of
`studtes were chosen for quantttattve analysts For the naltrexone
`stud1es, outcomes tncluded relapse to heavy dnnk1ng, relapse to any
`drmkmg, and percentage of dnnkmg days dur1ng the treatment penod
`For the acamprosate studtes, only relapse to any dnnkmg was
`assessed m all of the tnals summary rtsk differences for dtchotomous
`outcomes were calculated wtthm each group of stud1es Metol-
`regresston was performed to compare the two drugs dtrectly and to
`assess the influence of study charactensttcs on treatment effect
`B naltrewne studies (N = 1 ,462) and 15 acamprosate stUdieS (N =
`3,979) were included m thts analysts Random effects e~ttmates were
`reported, due to the high between-study varrance for all outcomes tn
`both treatment groups For naltrexone, the nsk dtfference for relapse to
`heavy drmkmg In treatment versus placebo groups was 16 (95% Cl
`07, 25. NNT = 6 28) The rtsk difference for relapse to any drmktng
`was 08 (95% Cl -02, .17; NNT = 12 95) In the acamprosate studies,
`the overall nsk difference for relapse to any dnnktng was .12 (95% Cl
`08. 17, NNT = 8 15) Meta-regression mdtcated that prescrtbmg
`acamprosate versus naltrexone (p < 1) and gtvmg some form of
`requued psychotherapy (p < .05) were both predtctors of treatment
`effect on absttnence. The evidence of effecttveness of these two
`medtcattons ts considered m the context of thts cumulattve body of
`published studtes Wh1le more research Will be necessary to understand
`fully the effectiveness of these drugs and the populations m whtch one
`or the other may be Indicated, these results suggest that acamprosate
`1s more effecttve than nallrexone at helprng weaned alcoholiC pattents
`ma1nta1n abstmence
`
`B. Early intervention
`752
`
`CONSIDERATIONS FOR SCREENING INSTRUMENTS IN A
`HOSPITAL TRAUMA SETTING
`T R. Apodaca, C R Schermer; D 0 Squtres
`Untverstty of New Mexico, Albuquerque, NM 87131
`
`Evtdence has accumulated over the past ten years that brtef
`mterventtons can be as effective as more mtenstve treatments wtlh at-
`nsk or problem dnnkers, and there is a growing consensus that
`screening and brtef interventions should be promoted m health care
`settmgs Trauma and emergency department settings in particular are
`tdeal for thts type of mtervenliOn, when pattents m the mtdst of
`expertencmg physical distress related to their alcohol use may be ready
`to change thetr drtnktng Because ltme ts extremely ltmtted In these
`settmgs, the current study examined var1ous ways of gathermg
`mformatton for use tn the feedback component used in many bnef
`mterventtons The Alcohol Use Disorders ldenltftcatton Test (AUDIT).
`and several Ukert-scaled questtons regardmg alcohol use were
`admmistered to 61 pattents admttled wtth a posittve blood alcohol
`concentration to a Level 1 trauma center Results indtcate that paltents
`were more likely to attribute thetr InJUry to thetr alcohol use when usmg
`a Ltkert-scaled questiOn (75%) than a stmtlar questton on the AUDIT
`(38%). In order to tmplement effecttve bnef mterventtons wtth pattents
`hospttalized followmg an alcohol-related InJury, 1t may be helpful to
`supplement the AUDIT wtth add1t1onal questtons when conductmg
`screentng
`
`This mat€ ria I was copiEd
`atth.a NLM and may be
`Su !J.je<t US OJ·pyright Laws
`
`130A
`
`7 4 7
`LCOHOLISM TREATMENT·
`SEROTONERGIC AGENT~~:t BY COMPUTER SIMULATION
`TESTING THE JOHNSON
`sF Stoltenberg
`d 1 Research Center, Ann Arbor, Ml 48108
`University of Michigan Ad IC ion
`
`1 may respond better to treatment w1th
`Those With early onset alcoho ISm tagonlst) than With selective serotonin
`ondansetron.(a 5-HT3 receptor fnthose w1th late onset alcoholism may
`reuptake Inhibitors (SSRis). w~l ~ m subtyping may be useful1n makmg
`respond bette~ to SSRis. Alec 0 '\ent's genotype at loci that mfluence
`treatment de.clslons, although ~ pa ore so Johnson {ACER 24 1597-
`the dysfunctional syst~~ ~~~ro~:nm (S-HT) funct1on that focuses on a
`1601) proposed a mo e
`1 5 HT transporter regulatory reg1on (5-
`- allzes and extends Johnson's
`common genetiC variant In t 18
`HDLPR) The present study fo;m based stmulatton that uses ftntte
`descnpttve model mto ~ com~u e:~nables used m the ~odel were
`dtfference equ~ttons Value~ ~~ human and animal literature Data
`based on empmcal findmgs tn
`e by 100 stmulatlon runs Results of
`were generated for each condttton ctattons that the LL genotype would
`the model are conststent wtth ex~~ 5 HT than the S genotype
`have lower mean levels of synap 1 ctl;n due to chrontc alcoholism
`Reducttons m 5-H~ tral~~~~srt;~/~;e LL genotype by B2?o and for the S_
`tncreased meaon SFHT h se with alcoholtsm, bmge drmkmg episodes
`or 1 0
`genotype by 2 Vo
`%and 54% for LL's and S_s,
`ratsed mean 5-HT levels by 111 d mean 5-HT levels by 75% for LL's
`respecttvely. SSRI treatme~t :at~~esults suggest that SSRI treatment
`and 57% for S_s. Th~ st:n~.~i~~als wtlh the LL genotype because bmge
`may ~ot be effecttve or ~~u~ctton to a greater degree Durmg bmge
`tment decreased 5-HT3 receptor medtated
`dnnkmQ enhances 5-H;
`drtnklnQ, ondansetrono~~~ LLs and by 33% m S_s Ondansetron
`dopamtne ftnng by ~1 ~ttve at reducmg alcohol's rewardtng effects tn
`treatment ts more e e
`Th
`esults generally supportthe Johnson
`e~pes may become useful for treatment
`those wtth the Ll genotype
`model, na.,nd1~~~tl~~t:J..8g~~5)
`·
`
`deCISIO "
`
`7 48
`E TO NALTREXONE IN THE
`PREDICTORS OF RESPH06LSDEPENDENCE IN MEN
`TREATMENT OF ALJC~ Ol a sergto Orttz, M A Jtmenez-Arrtero. J
`G Ponce, G Rubto,
`.
`IV
`'
`Manzanares. T. PalomoH
`t 112 de Octubre, Avda Cordoba s/n,
`Servtcto de Pstqutalna, ospt a
`28041 Madnd, Spatn
`
`be effecttve in the treatment of alcohol
`Naltrexone has shown t~
`ffecttveness vanes from patten! to patten!
`f
`dependence However, Is e
`lcohol dependence II was of tnterest
`Constdertng the heterogen~.~~ ~s ~f response to treat~ en! The purpose
`to tnvesttgate potenttal pre .1c 0 htch vartables are related wtth_ a good
`of this study was to det~rmt~et:ated Wtlh naltrexone We studted the
`outcome tn alcoholic P~ tens at the outpat1ent Untt of Problems
`outcome of 336 patten sr!~e~omized way, 168 patients recetved
`Related to Alcohol Jnv:nt and usual treament (psychotherapy, referral to
`t wtth occasional dtsulftram) and 1G8
`naltrexone as coadJ~
`self-help groups an supp~tr xone We studied the tnfluence of
`pat1ents did not recetve na r~ 1 ents present1ng vartables whtch are
`naltrexone on the outcome 0 ~: 1
`Giobally the group treated wtth
`potenttal predtctors of:~~;~~~tcome (p=ci 03) The use of naltrexone
`naltrexone show1e1~throvement 1n pattents wtth early onset of problems
`~ _0 028) those w1th postltve famtly htstory
`produced a clea
`nit~ htstory of abuse of other drugs
`related wtth alcohol p-
`(p=O 017) and those pr~se
`g dtd nottmprove the outcome of pat1ents
`(p<O 001) However, na tre~o~eln conclusion the treatment wtth
`not presenttng thesel:~~re ~ffecttve among ~lcohol dependent pattents
`naltrexone may re~u ractensttcs that Sllggest a greater vulnerabtlily to
`showmg spectftc c a
`early onset of problems related to
`h 1
`alcohol addictiOn (famtly
`ts ory, morbtdtty) Supported by Grant from
`alcohol and other drug abuse co
`FIS (0111 438 to J Manzanares)
`
`7 4 9
`C ACID VS NAL TREXONE 11'-'
`~~~'-'~~~~\~~;(cygi~6~~IBSTINENCE AN OPEN f~ANDOMIZED
`COMPA~A6IV;d~~~~;t·o~~u~:renztn1
`. M Domentcalt, A Oel Re. G
`F Caput ·
`rdt & G F Stef<lllH11
`Gd$~<Hflr1l, ~ _Bernaf
`the Study and MulttdiSCJplrnary Treatment of
`"G Fontana .centr~e 0~rtrnent of Internal MtHJrcme. CardJoarlgiOIOUY
`:~c;~~:a~~/~:;~Via ~assarentJ9, 40138, Untversrty of Bologna, Italy
`After the rem1ssron of wrth~:~~a~~~~~1~r1o:~~~da~~1~1~ntlrnega:~:~~e~~~y
`from aiLOtwlts tile ma~n g have been recently tested rn the treatment of
`pharmacologiCal a~~~ :nd GHB have proved able to ma1n!am alcohol
`nlcohfll addJct1_0 n 1120 GO% and 30-80% of treated pat1ents
`abs!JrH!n(..e Jn abo~sent there are no studieS comparmg the effect of
`respectively ~t~~~maJnt~mmg abstmence from alcohol after a short-term
`NTX "nd GH od The atm of our open randomrzed pilot-stud)' was to
`treatment pert fftcac of Gf 10 compared wrth NTX m m<~rntammg
`evaluate th~ e
`1 y hoi ilfter 3 months of treatment A total of 35
`ab~ttnence r~~e~ -~~co hoi dependence outpatrents. wer~ rculdumly
`GHB group was composed by 18 pattents
`rec.ently de to
`enrolled m two Tr~upss ~f SO mgtkg of GHB fractJonatfld tn three daily
`05~ . Nrx 'roup was composed by 17 patrents
`treated With ora
`dose~ for t~ll~r:;1~~~~~'0i 50 mggfday of NTX for t111ee months The
`dmlntstratron has been entrusted to a referred family
`treated Wit
`drugs and 11
` ~lien\!:> were abstrnent at ttme of admiSSIOn Eacl1 subject
`rnemUer AI ~eked as an outpatient every week for the duration of the
`has been ch
`d At the end of the st•Jdy a statJs!Jc<JIIy s1gnrf1cant
`treatme~t per~o 0 02) 11 the number of abstment patrents between GHB
`dtfference (p Tx
`r was found In pattents who failed to be abstment
`group and N h~~~updrtnkmg were observed in NTX group. while m
`no relapses 1~11
`,Jit~;nto; reldpsed Morf!over, a s1gmfrcant reduc;!ion m
`GHB aroup. il p d laboratOIY markers of alcohol abuse were found rn
`alcohol cravu~ a~ravmg for the drugs was observed m both groups The
`0
`. 1 study show thdl GHB IS more effrcac1ous than
`both g_roLrps
`results of Hle presen bstmence from alcoholm a short-term treatment
`~eT:o~ ~~a;~~~~t~~~r ahand. NTX confrrmed 1\s ability 1n reduc.rn:J alcohol
`relapses m htmvy drmkmg
`
`15
`
`AMN1035
`IPR of Patent No. 7,919,499
`
`