Organic Depression Organic Depression and Schizophrenia

Considering฀the฀effects฀of฀mental฀illnesses฀on฀the฀type฀of฀withdrawal฀symptoms,฀anx- ious฀and฀depressive฀patients,฀as฀well฀as฀patients฀with฀eating฀disorders,฀tend฀to฀experience฀ withdrawal฀symptoms฀within฀the฀clinical฀framework฀of฀their฀illness,฀whereas฀patients฀with฀ stronger฀nicotine฀dependence฀frequently฀show฀craving,฀sleep฀disturbances฀and฀cognitive- affective฀disturbances฀ [192] .

11.5.5.2 Schizophrenic Patients

Smoking฀cessation฀in฀schizophrenic฀patients฀is฀rendered฀dificult฀by฀a฀variety฀of฀affective,฀ cognitive฀and฀social฀problems฀ [193] ,฀but฀it฀can฀be฀achieved฀using฀specially฀designed฀smok- ing฀cessation฀programmes฀ [194] ฀involving฀a฀combination฀of฀group฀therapy฀with฀nicotine฀ patches฀and฀neuroleptics฀preferably฀olanzapine฀and฀risperidone.฀These฀two฀substances฀ have฀ proved฀ superior฀ to฀ the฀ classic฀ neuroleptics฀ success฀ rates฀ of฀ 56฀ vs.฀ 22฀ [195] .฀ According฀to฀other฀studies,฀clozapine฀was฀more฀effective฀in฀promoting฀smoking฀cessation฀ in฀schizophrenics฀than฀other฀typical฀as฀well฀as฀atypical฀neuroleptics฀ [196,฀197] ,฀besides฀ which฀the฀antipsychotic฀effect฀of฀clozapine฀was฀more฀pronounced฀in฀smokers฀ [198] .฀The฀ reasons฀for฀these฀effects฀of฀clozapine฀ [199] ฀may฀involve฀inhibition฀of฀nicotine฀metabolism,฀ especially฀in฀view฀of฀the฀fact฀that฀raised฀plasma฀nicotine฀levels฀are฀measured฀in฀smoking฀ schizophrenics฀ [199] . The฀spectrum฀of฀adverse฀effects฀of฀neuroleptics฀remains฀essentially฀unchanged฀in฀smok- ers.฀With฀increasing฀age,฀smokers฀require฀higher฀doses฀of฀neuroleptics,฀while฀non-smokers฀ require฀lower฀doses฀to฀achieve฀a฀suficient฀level฀of฀eficacy฀ [200] ,฀although฀smoking฀does฀ not฀alter฀plasma฀levels฀signiicantly.฀The฀incidence฀of฀neuroleptic-induced฀parkinsonism฀ and฀tardive฀dyskinesias฀was฀not฀higher฀among฀smokers฀despite฀considerably฀higher฀aver- age฀dosage฀levels฀ [201,฀202] .฀Smoking฀was฀reported฀to฀have฀a฀protective฀effect฀against฀ incipient฀dementia฀in฀smokers฀ [203] ;฀cases฀of฀akathisia฀were฀observed฀frequently฀in฀women฀ smokers.฀Neuroleptic-induced฀parkinsonism฀was฀observed฀less฀frequently฀in฀smokers฀than฀ in฀non-smokers฀ [203] .฀Another฀study฀found฀an฀association฀between฀high฀neuroleptic฀dos- age฀ and฀ smoking฀ in฀ non-schizophrenics฀ only฀ [204] .฀ Smoking฀ reportedly฀ does฀ not฀ alter฀ plasma฀clozapine฀levels,฀in฀spite฀of฀which฀the฀individual฀plasma฀levels฀vary฀under฀constant฀ dosage.฀Antipsychotic฀eficacy฀correlates฀with฀the฀dosage฀level฀ [205] .฀Haloperidol฀treat- ment฀was฀initiated฀in฀ten฀smoking฀patients฀with฀acute฀schizophrenia.฀An฀increased฀desire฀ to฀smoke฀was฀observed฀in฀a฀2-h฀ad฀libitum฀smoking฀phase฀ [197] .

11.5.5.3 Interactions Between Cigarette Smoking and Administration of Psychopharmaceuticals

Tobacco฀smoking฀affects฀the฀metabolism฀of฀numerous฀neuroleptics฀and฀antidepressants฀via฀ the฀cytochrome฀P450฀system,฀complicating฀the฀therapy฀of฀smokers฀in฀psychiatric฀clinics฀ and฀out-patient฀facilities฀cf.฀Table฀ 11.8 .฀Smokers฀require฀higher฀doses฀of฀neuroleptics฀ than฀non-smokers฀ [198,฀225–227] .฀The฀neuroleptic฀dosage฀increases฀with฀age฀in฀schizo- phrenic฀smokers฀ [200] ,฀but฀decreases฀in฀schizophrenic฀non-smokers,฀apparently฀in฀associa- tion฀with฀an฀age-dependent฀reduction฀in฀D 2 ฀receptors฀in฀the฀corpus฀striatum.฀Increased฀ cigarette฀consumption฀in฀schizophrenic฀and฀non-schizophrenic฀patients฀because฀of฀admin- istration฀of฀haloperidol฀was฀measured฀on฀the฀basis฀of฀reliable฀parameters฀CO,฀nicotine฀ [200] .฀ The฀ combination฀ of฀ neuroleptics฀ and฀ smoking฀ reduces฀ the฀ frequency฀ of฀ parkin- sonism-like฀symptoms฀in฀these฀patients฀and฀can฀reduce฀the฀anticholinergic฀doses฀required฀ in฀some฀cases.฀On฀the฀other฀hand,฀the฀eficacy฀of฀haloperidol฀in฀these฀patients฀is฀reduced฀ because฀of฀raised฀elimination฀rates฀ [228–230] .฀Unfortunately,฀this฀interaction฀is฀usually฀not฀ taken฀ into฀ account฀ when฀ calculating฀ the฀ haloperidol฀ dosage.฀ Similarly,฀ smoking฀ also฀ increases฀the฀elimination฀of฀antidepressants฀amitriptyline,฀nortriptyline,฀imipramine฀and฀ desipramine฀ [220] ฀by฀inducing฀the฀hepatic฀breakdown฀of฀these฀substances฀via-CYP1A2.฀ Plasma฀protein฀binding฀by฀nortriptyline฀is฀clearly฀reduced฀as฀a฀result฀ [231] . Thus,฀smoking฀cessation฀can฀be฀expected฀to฀result฀in฀a฀paradoxical฀increase฀in฀the฀eficacy฀ of฀ neuroleptics฀ and฀ antidepressants:฀ this฀ is฀ manifested฀ most฀ particularly฀ in฀ an฀ increase฀ of฀ adverse฀effects฀e.g.฀parkinsonoid฀effects฀of฀neuroleptics,฀seizures฀caused฀by฀clozapine฀ [232] .

11.5.6 Pre-operative Smoking Cessation

Up฀to฀10฀of฀patients฀develop฀respiratory฀tract฀or฀cardiovascular฀complications฀during฀the฀ post-operative฀period.฀Men฀and฀women฀who฀smoke฀are฀especially฀at฀risk฀in฀this฀respect฀ [233] :฀they฀have฀a฀3฀to฀6-fold฀increased฀risk฀of฀intra-operative฀pulmonary฀complications฀ [234] ฀and฀there฀is฀a฀2฀to฀5-fold฀increased฀risk฀of฀perioperative฀complications฀in฀smokers฀ with฀chronic฀cardiovascular฀or฀pulmonary฀disease.฀The฀consequences฀of฀cigarette฀smoking฀ on฀the฀various฀organ฀systems฀are฀discussed฀in฀Chaps.฀5–7. Smoking฀disturbs฀post-operative฀wound฀healing฀ [235–237] ฀and฀increases฀the฀risk฀of฀ anastomotic฀leakage฀in฀colorectal฀surgery฀ [238] .฀To฀date,฀there฀exists฀only฀one฀evidence- based฀study฀conirming฀that฀pre-operative฀smoking฀cessation฀1฀or฀6–8฀weeks฀eliminates฀ Drug Interactive฀effects Benzodiazepines฀diazepam,฀ lorazepam,฀midazolam,฀ chlordiazepoxide No฀effect฀ [206–208] Bupropion No฀effect฀ [94] Chlorpromazine AUC฀ß฀−36,฀serum฀concentration฀ß฀−24;฀฀ clinical฀signiicance?฀ [209,฀210] Clorazepate AUC฀ß,฀t 0.5 ฀of฀N-desmethyldiazepam฀ß฀ [211] Clozapine Induction฀of฀CYP 1A2 ,฀clearance฀Ý,฀plasma฀concentration฀ß฀ −28฀ [205,฀212–215] Fluvoxamine Induction฀of฀CYP 1A2 ,฀metabolic฀clearance฀Ý,฀AUC฀ß฀−44,฀ plasma฀concentration฀ß฀−47฀ [216] Haloperidol Clearance฀Ý฀+44,฀serum฀concentration฀ß฀−70.฀Clinical฀ signiicance?,฀no฀observed฀differences฀in฀dose฀ [191,฀217,฀218] Imipramine Serum฀concentration฀ß,฀no฀clinical฀effect฀ [219] Nortriptyline Unclear,฀no฀clinical฀effect฀ [220,฀221] Olanzapine Induction฀of฀CYP 1A2 ,฀clearance฀Ý฀+98,฀great฀variability฀in฀ plasma฀clearance฀over฀a฀fourfold฀range฀ [222–224] Table 11.8 ฀฀฀Pharmacokinetic฀interactions฀between฀smoking฀and฀drugs฀inluencing฀the฀CNS