Various Antidepressants Other Pharmacotherapies

disappeared฀within฀one฀further฀week฀ [135] .฀Fluoxetine฀has฀been฀compared฀with฀dexfenlu- ramine฀and฀placebo฀in฀97฀subjects,฀but฀eficacy฀was฀poorer฀than฀with฀placebo฀ [136] .฀Eficacy฀ was฀poor฀with฀imipramine฀when฀compared฀with฀lobeline฀and฀dextroamphetamine฀ [137] ฀and฀ with฀venlafaxine฀ [138] ฀when฀compared฀with฀placebo.฀Similarly,฀moclobemide฀was฀shown฀ to฀possess฀a฀slight฀degree฀of฀eficacy฀in฀one฀study฀ [139] ฀25฀vs.฀16,฀active฀treatment฀vs.฀ placebo,฀but฀the฀effect฀was฀no฀longer฀signiicant฀after฀12฀months. The฀latest฀Cochrane฀metaanalsis฀screended฀six฀trials฀of฀selective฀serotonin฀reuptake฀ inhibitors;฀ four฀ of฀ luoxetine,฀ one฀ of฀ sertraline฀ and฀ one฀ of฀ paroxetine.฀ None฀ of฀ these฀ detected฀signiicant฀long-term฀effects,฀and฀there฀was฀no฀evidence฀of฀a฀signiicant฀beneit฀ when฀results฀were฀pooled.฀There฀was฀one฀trial฀of฀the฀monoamine฀oxidase฀inhibitor฀moclo- bemide,฀and฀one฀of฀the฀atypical฀antidepressant฀venlafaxine.฀Neither฀of฀these฀detected฀a฀ signiicant฀long-term฀beneit฀ [114] .

11.3.9 Opioid Antagonists

Opioid฀antagonists฀are฀used฀for฀the฀treatment฀of฀various฀forms฀of฀dependence฀alcohol,฀cocaine,฀ opioids,฀and฀initial฀studies฀have฀also฀been฀published฀concerning฀the฀eficacy฀of฀naloxone฀and฀ naltrexone฀in฀smoking฀cessation.฀A฀reduction฀in฀the฀number฀of฀cigarettes฀smoked฀daily฀was฀ shown฀in฀two฀placebo-controlled฀studies฀with฀naloxone฀ [140,฀141] ,฀but฀this฀was฀not฀conirmed฀ in฀a฀further฀study฀ [142] .฀Because฀of฀its฀longer฀half-life,฀naltrexone฀might฀be฀beneicial,฀but฀here฀ too฀the฀results฀have฀not฀been฀convincing฀OR฀=฀1.34;฀CI:฀0.49–3.63฀ [143,฀144] .฀Combination฀ of฀naltrexone฀with฀nicotine฀patches฀has฀yielded฀a฀slightly฀higher฀success฀rate฀ [145] .฀On฀the฀ basis฀of฀the฀results฀available฀at฀present,฀no฀deinitive฀assessment฀is฀possible฀ [146] ,฀and฀the฀ effectiveness฀of฀both฀opioid฀antagonists฀needs฀to฀be฀veriied฀in฀a฀larger฀patient฀sample. David฀et฀al.฀performed฀a฀meta-analysis฀on฀opiod฀antagonists฀for฀smoking฀cessation฀and฀ found฀out฀that฀four฀trials฀of฀naltrexone฀met฀Cochrane฀inclusion฀criteria฀for฀meta-analyses฀for฀ long-term฀cessation฀ [147] .฀All฀the฀four฀trials฀failed฀to฀detect฀a฀signiicant฀difference฀in฀quit฀ rates฀between฀naltrexone฀and฀placebo.฀In฀a฀pooled฀analysis,฀there฀was฀no฀signiicant฀effect฀of฀ naltrexone฀on฀long-term฀abstinence,฀and฀CIs฀were฀wide฀OR฀1.26,฀95฀CI฀0.80–2.01.฀No฀ trials฀of฀naloxone฀or฀buprenorphine฀reported฀long-term฀follow-up.฀It฀can฀therefore฀be฀con- cluded฀that฀on฀the฀basis฀of฀limited฀data฀from฀four฀trials฀it฀is฀not฀possible฀to฀conirm฀or฀refute฀ whether฀naltrexone฀helps฀smokers฀quit.฀The฀CIs฀are฀compatible฀with฀both฀clinically฀signiicant฀ beneit฀and฀possible฀negative฀effects฀of฀naltrexone฀in฀promoting฀abstinence.฀Data฀from฀larger฀ trials฀of฀naltrexone฀are฀needed฀to฀settle฀the฀question฀of฀eficacy฀for฀smoking฀cessation฀ [147] .

11.3.10 Lobeline

Lobeline฀ is฀ an฀ alkaloid฀ possessing฀ nicotine-like฀ activity฀ with฀ attenuated฀ central฀ and฀ peripheral฀effects.฀Lobeline฀used฀to฀be฀employed฀to฀promote฀smoking฀cessation.฀However,฀ there฀are฀no฀controlled฀studies฀available฀[148].฀Therefore,฀its฀use฀cannot฀be฀recommended฀ according฀to฀a฀Cochrane฀analysis฀ [14] .

11.3.11 Silver Acetate

Silver฀acetate฀in฀the฀form฀of฀chewing฀gum฀or฀mouth฀spray฀has฀been฀compared฀with฀placebo฀ in฀four฀aversive฀smoking฀studies฀ [149] ,฀but฀no฀signiicant฀results฀were฀reported.฀In฀one฀ triple-arm฀study,฀silver฀acetate฀and฀the฀2-mg฀nicotine฀chewing฀gum฀formulation฀were฀com- pared฀with฀placebo฀OR฀=฀1.05;฀CI:฀0.63–1.73฀ [150] .฀An฀additional฀4฀gain฀after฀2฀months฀ is฀too฀small฀to฀be฀deemed฀a฀success฀ [17] .

11.3.12 Nicotine-Vaccination

There฀are฀three฀different฀companies฀presently฀that฀have฀completed฀Phase฀II฀clinical฀studies฀ of฀their฀anti-nicotine฀vaccines.฀They฀are฀all฀rushing฀to฀obtain฀regulatory฀approval฀and฀to฀ bring฀their฀vaccine฀candidates฀to฀the฀market฀ [151] . In฀general,฀nicotine฀vaccines฀are฀composed฀of฀a฀linkage฀between฀the฀nicotine฀molecule฀ and฀an฀adjuvant฀with฀a฀carrier฀protein.฀Preliminary฀results฀of฀the฀three฀Phase฀II฀clinical฀ studies฀are฀encouraging.฀In฀this฀respect,฀subjects฀who฀have฀a฀high฀anti-nicotine฀antibody฀ level฀also฀present฀high฀quit฀rates฀ [152] .฀However,฀the฀data฀available฀are฀by฀far฀too฀prelimi- nary฀to฀extrapolate฀for฀long-term฀quit฀rates.฀It฀can฀be฀expected฀that฀vaccines฀may฀appear฀on฀ the฀market฀in฀2011.

11.4 Therapeutic Monitoring in Smoking Cessation

Most฀physicians฀use฀the฀self-report฀SR฀conirmed฀by฀carbon฀monoxide฀CO฀readings฀as฀the฀ method฀usually฀employed฀in฀clinical฀practice฀to฀determine฀whether฀“ex-smokers”฀are฀smok- ing฀tobacco฀during฀and฀following฀treatment.฀The฀combination฀of฀SR฀and฀CO฀was฀evaluated฀ in฀some฀studies,฀and฀a฀close฀relationship฀between฀CO฀readings฀and฀SR฀was฀found฀in฀ex- smokers฀who฀had฀been฀informed฀beforehand฀that฀CO฀reading฀would฀be฀taken฀ [153,฀154] .฀A฀ relatively฀low฀average฀false-negative฀rate฀of฀6฀was฀reported฀in฀an฀analysis฀of฀12฀additional฀ intervention฀studies฀using฀CO฀conirmation฀ [107] .฀Data฀such฀as฀these฀have฀been฀taken฀as฀ evidence฀that฀CO฀evaluation฀can฀detect฀under-representation฀of฀smoking฀in฀self-reports.฀If฀the฀ patient฀has฀been฀informed฀that฀CO฀reading฀will฀be฀taken,฀then฀the฀inconsistent฀smoking฀patient฀ may฀stop฀smoking฀for฀several฀hours฀before฀CO฀reading.฀On฀the฀other฀hand,฀the฀measurement฀ of฀CO฀in฀expired฀air฀may฀be฀problematic฀because฀increased฀values฀10฀ppm฀have฀been฀ recorded฀in฀ex-smokers฀or฀in฀smokers฀who฀quit฀smoking฀several฀days฀prior฀to฀measurement. A฀second฀possibility฀to฀control฀smoking฀cessation฀is฀the฀analysis฀of฀cotinine฀in฀plasma,฀ urine,฀or฀saliva.฀In฀a฀sample฀of฀hospital฀outpatients฀self-report,฀CO฀and฀cotinine฀analyses฀ were฀used฀to฀validate฀the฀eficacy฀of฀smoking฀cessation฀ [155] .฀Up฀to฀20฀of฀claimed฀ex- smokers฀were฀classiied฀as฀smokers฀by฀each฀test.฀The฀cotinine฀analyses฀were฀superior฀to฀CO฀ readings,฀although฀CO฀also฀worked฀relatively฀well฀ [155] .฀Because฀of฀cost฀considerations,฀ the฀cotinine฀analysis฀should฀not฀be฀used฀routinely฀ [155] .฀In฀only฀one฀1-year฀study,฀the฀CO฀