Tranquillisers and Buspirone Other Pharmacotherapies

after฀7฀days฀of฀treatment,฀as฀well฀as฀anxiety฀symptoms,฀restlessness฀and฀excitability฀ [133] .฀ These฀and฀other฀studies฀are฀not฀conclusive,฀and฀a฀larger฀study฀over฀a฀more฀extended฀period฀ is฀required฀in฀order฀for฀eficacy฀to฀be฀demonstrated฀unequivocally฀ [16] .฀Buspirone฀is฀not฀ approved฀anywhere฀for฀use฀in฀smoking฀cessation.

11.3.7 Rimonabant

Rimonabant฀hydrochloride฀represents฀the฀irst฀drug฀in฀a฀new฀class฀of฀selective฀cannabinoid฀ type฀1฀CB1฀receptor฀antagonists.฀This฀compound฀is฀showing฀promise฀in฀clinical฀trials฀for฀the฀ treatment฀of฀obesity฀and฀related฀metabolic฀risk฀factors.฀Also,฀it฀may฀be฀of฀help฀in฀smoking฀ cessation฀therapy.฀The฀drug฀may฀assist฀with฀smoking฀cessation฀by฀restoring฀the฀balance฀of฀the฀ endocannabinoid฀system,฀which฀can฀be฀disrupted฀by฀prolonged฀use฀of฀nicotine.฀Rimonabant฀ also฀seeks฀to฀address฀many฀smokers’฀reluctance฀to฀persist฀with฀a฀quit฀attempt฀because฀of฀ concerns฀ about฀ weight฀ gain.฀ Cahill฀ and฀ Ussher฀ performed฀ a฀ meta-analysis฀ to฀ determine฀ whether฀selective฀CB1฀receptor฀antagonists฀increase฀the฀numbers฀of฀people฀stopping฀smoking฀ [134] .฀ Three฀ trials฀ that฀ met฀ the฀ inclusion฀ criteria,฀ covering฀ 1,567฀ smokers฀ cessation:฀ STRATUS-EU฀and฀STRATUS-US฀and฀1,661฀quitters฀relapse฀prevention:฀STRATUS-WW฀ were฀included฀in฀the฀analysis.฀At฀1฀year,฀the฀pooled฀OR฀for฀quitting฀with฀rimonabant฀20฀mg฀ was฀1.61฀95฀CI฀1.12–2.30.฀No฀signiicant฀beneit฀was฀demonstrated฀for฀rimonabant฀at฀5฀mg฀ dosage.฀The฀AEs฀included฀nausea฀and฀upper฀respiratory฀tract฀infections.฀In฀the฀one฀relapse฀ prevention฀trial,฀smokers฀who฀had฀quit฀on฀the฀20฀mg฀regimen฀were฀112฀times฀more฀likely฀ to฀remain฀abstinent฀on฀either฀active฀regimen฀than฀on฀placebo;฀the฀OR฀for฀the฀20฀mg฀mainte- nance฀group฀was฀1.49฀95฀CI฀1.09–2.04,฀and฀for฀the฀5฀mg฀maintenance฀group฀1.51฀95฀CI฀ 1.11–2.07฀8,131.฀There฀appeared฀to฀be฀no฀signiicant฀beneit฀of฀maintenance฀treatment฀for฀ the฀5฀mg฀quitters.฀Weight฀gain฀was฀reported฀to฀be฀signiicantly฀lower฀among฀the฀20฀mg฀quit- ters฀than฀in฀the฀5฀mg฀or฀placebo฀quitters.฀During฀the฀treatment,฀overweight฀or฀obese฀smokers฀ tended฀to฀lose฀weight,฀while฀normal฀weight฀smokers฀did฀not.฀Cahill฀and฀Ussher฀concluded฀ from฀the฀preliminary฀trial฀reports฀available฀that฀rimonabant฀20฀mg฀may฀increase฀the฀odds฀of฀ quitting฀approximately฀112-fold.฀Whereas฀the฀risk฀of฀serious฀AEs฀was฀reported฀to฀be฀low,฀ concerns฀were฀raised฀over฀rates฀of฀depression฀and฀suicidal฀thoughts฀in฀people฀taking฀rimona- bant฀for฀weight฀control฀ [134] .฀In฀summary,฀the฀present฀evidence฀for฀rimonabant฀in฀concerning฀ tobacco฀abstinence฀and฀its฀adverse฀effects฀is฀inconclusive฀and฀further฀research฀is฀needed.

11.3.8 Various Antidepressants

The฀antidepressants฀imipramine,฀doxepin,฀luoxetine,฀venlafaxine฀and฀moclobemide฀have฀ also฀been฀investigated฀as฀aids฀to฀smoking฀cessation.฀Overall,฀while฀these฀compounds฀may฀ support฀efforts฀to฀achieve฀smoking฀cessation,฀no฀deinitive฀cessation฀effect฀has฀been฀dem- onstrated฀ [16] . Doxepin฀has฀been฀investigated฀only฀in฀one฀small฀3-week฀study,฀and฀the฀participants฀were฀ additionally฀promised฀a฀inancial฀bonus฀on฀stopping฀smoking.฀The฀initially฀good฀effect฀had฀ 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] .