title: Varenicline Treatment of Concurrent Alcohol and Nicotine Dependence in Schizophrenia: A Randomized, Placebo-Controlled Pilot Trial Neuropsychiatric safety and efficacy of varenicline, bupropion, and nicotine patch in smokers with and without psychiatric disorders (EAGLES): a double-blind, randomised, placebo-controlled clinical trial Smoking history and motivation to quit in smokers with schizophrenia in a smoking cessation program A placebo controlled trial of bupropion for smoking cessation in schizophrenia Nicotine transdermal patch and atypical antipsychotic medications for smoking cessation in schizophrenia. A pilot trial of bupropion added to cognitive behavioral therapy for smoking cessation in schizophrenia. Impact of an Electronic Cigarette on Smoking Reduction and Cessation in Schizophrenic Smokers: A Prospective 12-Month Pilot Study Nicotine–Haloperidol Interactions and Cognitive Performance in Schizophrenics A randomized, double-blind, placebo-controlled study evaluating the safety and efficacy of varenicline for smoking cessation in patients with schizophrenia or schizoaffective disorder. Effects of contingency management and bupropion on cigarette smoking in smokers with schizophrenia A Double-blind Placebo-Controlled Trial of Bupropion Sustained-Release for Smoking Cessation in Schizophrenia A 12-Week Double-Blind, Placebo-Controlled Study of Bupropion SR Added to High-Dose Dual Nicotine Replacement Therapy for Smoking Cessation or Reduction in Schizophrenia The effectiveness of nicotine-patch therapy for smoking cessation in patients with schizophrenia. A double-blind randomized clinical trial of different doses of transdermal nicotine patch for smoking reduction and cessation in long-term hospitalized schizophrenic patients Varenicline plus healthy lifestyle intervention for smoking cessation in psychotic disorders. Neuropsychological deficits are associated with smoking cessation treatment failure in patients with schizophrenia Does reducing withdrawal severity mediate nicotine patch efficacy? A randomized clinical trial. Maintenance treatment with varenicline for smoking cessation in patients with schizophrenia and bipolar disorder: a randomized clinical trial.
abstract: Abstract Alcohol and nicotine dependence are common in schizophrenia .  Varenicline is effective in smoking cessation and has also been shown to decrease alcohol consumption in smokers . The present pilot study assessed the safety and effectiveness of varenicline for treatment of concurrent nicotine and alcohol dependence in schizophrenia . Out patients with schizophrenia or schizoaffective disorder and concurrent alcohol and nicotine dependence were enrolled in this 8-week , double-blind , r and omized , placebo-controlled trial . Alcohol use and smoking were assessed using self-report ( Timeline Follow-Back ) and biological measures . Adverse events were recorded . Changes in the number of st and ard drinks per week and cigarettes per week were compared in the 2 groups . Because of safety concerns or loss to follow-up , of 55 patients enrolled , only 10 started study medication , 5 each on varenicline and placebo .  Gastrointestinal adverse effects , such as severe abdominal pain , limited study completion to only 4 subjects . Number of st and ard alcoholic drinks consumed per week decreased by [ mean ( SD ) ] 16.6 ( 20.1 ) in the varenicline group and by 2.4 ( 27.4 ) in the placebo group . Mean ( SD ) number of cigarettes smoked per week decreased by 66 ( 65 ) in the varenicline group and by 47 ( 77 ) in the placebo group . Varenicline treatment of concurrent alcohol and nicotine dependence in schizophrenia may be problematic because of safety concerns limiting recruitment and poor tolerability ( gastrointestinal adverse effects ) limiting retention . There was no increased number of serious neuropsychiatric adverse events in the varenicline group . Based on this small sample , concurrent alcohol and nicotine dependence in schizophrenia may present special obstacles to successful treatment with varenicline BACKGROUND Substantial concerns have been raised about the neuropsychiatric safety of the smoking cessation medications varenicline and bupropion . Their efficacy relative to nicotine patch largely relies on indirect comparisons , and there is limited information on safety and efficacy in smokers with psychiatric disorders . We compared the relative neuropsychiatric safety risk and efficacy of varenicline and bupropion with nicotine patch and placebo in smokers with and without psychiatric disorders . METHODS We did a r and omised , double-blind , triple-dummy , placebo-controlled and active-controlled ( nicotine patch ; 21 mg per day with taper ) trial of varenicline ( 1 mg twice a day ) and bupropion ( 150 mg twice a day ) for 12 weeks with 12-week non-treatment follow-up done at 140 centres ( clinical trial centres , academic centres , and outpatient clinics ) in 16 countries between Nov 30 , 2011 , and Jan 13 , 2015 . Participants were motivated-to-quit smokers with and without psychiatric disorders who received brief cessation counselling at each visit . R and omisation was computer generated ( 1:1:1:1 ratio ) . Participants , investigators , and research personnel were masked to treatment assignments . The primary endpoint was the incidence of a composite measure of moderate and severe neuropsychiatric adverse events . The main efficacy endpoint was biochemically confirmed continuous abstinence for weeks 9 - 12 . All participants r and omly assigned were included in the efficacy analysis and those who received treatment were included in the safety analysis . The trial is registered at Clinical Trials.gov ( number NCT01456936 ) and is now closed . FINDINGS 8144 participants were r and omly assigned , 4116 to the psychiatric cohort ( 4074 included in the safety analysis ) and 4028 to the non-psychiatric cohort ( 3984 included in the safety analysis ) . In the non-psychiatric cohort , 13 ( 1·3 % ) of 990 participants reported moderate and severe neuropsychiatric adverse events in the varenicline group , 22 ( 2·2 % ) of 989 in the bupropion group , 25 ( 2·5 % ) of 1006 in the nicotine patch group , and 24 ( 2·4 % ) of 999 in the placebo group . The varenicline-placebo and  bupropion-placebo risk differences ( RDs ) for moderate and severe neuropsychiatric adverse events were -1·28 ( 95 % CI -2·40 to -0·15 ) and -0·08 ( -1·37 to 1·21 ) , respectively ; the RDs for comparisons with nicotine patch were -1·07 ( -2·21 to 0·08 ) and 0·13 ( -1·19 to 1·45 ) , respectively . In the psychiatric cohort , moderate and severe neuropsychiatric adverse events were reported in 67 ( 6·5 % ) of 1026 participants in the varenicline group , 68 ( 6·7 % ) of 1017 in the bupropion group , 53 ( 5·2 % ) of 1016 in the nicotine patch group , and 50 ( 4·9 % ) of 1015 in the placebo group . The varenicline-placebo  and bupropion-placebo RDs were 1·59 ( 95 % CI -0·42 to 3·59 ) and 1·78 ( -0·24 to 3·81 ) , respectively ; the RDs versus nicotine patch were 1·22 ( -0·81 to 3·25 ) and 1·42 ( -0·63 to 3·46 ) , respectively  . Varenicline-treated participants achieved higher abstinence rates than those on placebo ( odds ratio [ OR ] 3·61 , 95 % CI 3·07 to 4·24 ) , nicotine patch ( 1·68 , 1·46 to 1·93 ) , and bupropion ( 1·75 , 1·52 to 2·01 ) . Those on bupropion and nicotine patch achieved higher abstinence rates than those on placebo ( OR 2·07 [ 1·75 to 2·45 ] and 2·15 [ 1·82 to 2·54 ] , respectively ) . Across cohorts , the most frequent adverse events by treatment group were nausea  ( varenicline , 25 % [ 511 of 2016 participants ] ) , insomnia  ( bupropion , 12 % [ 245 of 2006 participants ] ) , abnormal dreams  ( nicotine patch , 12 % [ 251 of 2022 participants ] ) , and headache ( placebo , 10 % [ 199 of 2014 participants ] ) . Efficacy treatment comparison did not differ by cohort . INTERPRETATION The study did not show a significant increase in neuropsychiatric adverse events  attributable to varenicline or bupropion relative to nicotine patch or placebo . Varenicline was more effective than placebo , nicotine patch , and bupropion in helping smokers achieve abstinence , whereas bupropion and nicotine patch were more effective than placebo . FUNDING Pfizer and GlaxoSmithKline OBJECTIVE The present study sought to better underst and the relationships among smoking history , motivation to change , and smoking cessation outcomes in people with schizophrenia who smoke . METHOD We examined smoking and quit history , negative consequences due to smoking , readiness to change , smoking temptation , and confidence to quit in a sample of people diagnosed with schizophrenia or schizoaffective disorder according to DSM-IV criteria who were participating in a larger r and omized trial of bupropion SR and a psychoeducational intervention for smoking cessation .  Data were collected from June 2003 to May 2005 . RESULTS At baseline , participants reported high levels of nicotine dependence and daily smoking , as well as multiple recent and lifetime quit attempts that were generally brief in nature . Participants were most concerned about the health effects of smoking and endorsed reasons for smoking related to coping with negative affect and boredom . Most participants reported wanting to quit smoking , but the sample generally reported low levels of confidence in their ability to quit . During the course of participation in the intervention , self-efficacy to quit increased while temptation to smoke decreased ; however readiness to quit remained unchanged . CONCLUSION Smoking cessation programs for people with schizophrenia should focus on teaching coping skills for negative affect , boredom , and specific " high risk situations " for smoking in addition to education , medication , or nicotine replacement therapy . Further , cessation efforts may benefit from directly addressing low self-efficacy for quitting , rather than readiness for change alone , among people with schizophrenia BACKGROUND Schizophrenic patients have high rates of cigarette smoking compared with the general population . We compared sustained-release ( SR ) bupropion with placebo for smoking cessation in patients with schizophrenic disorders . We also examined how antipsychotic class predicts smoking cessation outcomes with bupropion . METHODS Thirty-two subjects meeting DSM-IV criteria for schizophrenia or schizoaffective disorder and nicotine dependence were r and omized to bupropion SR ( BUP , 300 mg/day ) or placebo ( PLA ) . Outcomes included treatment retention , smoking abstinence rates , expired breath carbon monoxide ( CO ) levels , psychotic symptoms , and medication side effects . RESULTS Bupropion significantly increased trial endpoint 7-day point prevalence smoking abstinence rates compared with placebo [ BUP , 8/16 ( 50.0 % ) , PLA , 2/16 ( 12.5 % ) ; chi(2 ) = 5.24 , df = 1 , p < .05 ] , and reduced CO levels during the trial [ Medication x Time interaction ; Z = 3.09 , p < .01 ] . Positive schizophrenia symptoms were not altered by BUP , but negative symptoms were significantly reduced . Atypical antipsychotic drug treatment enhanced smoking cessation responses to BUP . Major side effects were dry mouth , gastrointestinal symptoms , headache , and insomnia . CONCLUSIONS Our results suggest that 1 ) BUP enhances smoking abstinence rates compared with PLA in nicotine-dependent schizophrenic smokers ; 2 ) BUP is well-tolerated and safe for use in these patients ; and 3 ) atypical antipsychotics may enhance smoking cessation outcomes with BUP OBJECTIVE Schizophrenic patients have high rates of cigarette smoking .  The authors compared the outcomes of two group psychotherapy programs for smoking cessation in patients with schizophrenia or schizoaffective disorder who were also treated with the nicotine transdermal patch and with either atypical or typical antipsychotic medications . METHOD Forty-five subjects were r and omly assigned to 1 ) the group therapy program of the American Lung Association ( N=17 ) or 2 )  a specialized group therapy program for smokers with schizophrenia ( N=28 ) that emphasized motivational enhancement , relapse prevention , social skills training , and psychoeducation . All subjects participated in 10 weeks of treatment with the nicotine transdermal patch ( 21 mg/day ) and 10 weekly group therapy sessions and continued to receive their pre study atypical ( N=18 ) or typical ( N=27 ) antipsychotic medications . Outcome variables included treatment retention , rate of smoking abstinence , and expired-breath carbon monoxide level . RESULTS Smoking abstinence rates did not differ in the two group therapy programs . However , atypical antipsychotic agents , in combination with the nicotine transdermal patch , significantly enhanced the rate of smoking cessation ( 55.6 % in the atypical agent group versus 22.2 % in the typical group ) , which was reflected by a significant effect of atypical versus typical agents on carbon monoxide levels . Risperidone and olanzapine were associated with the highest quit rates . CONCLUSIONS The results suggest that 1 ) smoking cessation rates with the nicotine transdermal patch are modest in schizophrenia , 2 ) specialized group therapy for schizophrenic patients is not significantly different from American Lung Association group therapy in its effect on smoking cessation , and 3 ) atypical agents may be superior to typical agents in combination with the nicotine transdermal patch for smoking cessation in schizophrenia The purpose of this study was to investigate the effect of adding sustained-release ( SR ) bupropion to cognitive behavioral therapy ( CBT ) on smoking behavior and stability of psychiatric symptoms in patients with schizophrenia . We conducted a 3-month , double-blind , placebo-controlled trial of bupropion SR , 150 mg/day , added to a concurrent CBT program with 3-month follow-up in 19 stable out patients with schizophrenia who wanted to quit smoking . Eighteen subjects completed the trial .  Bupropion treatment was associated with significantly greater reduction in smoking , as measured by self-report verified by expired-air carbon monoxide ( 6/9 subjects , 66 % ) , than placebo ( 1/9 subjects , 11 % ) during the 3-month active treatment period and the 3-month follow-up period . One subject in the bupropion group ( 11 % ) and no subjects in the placebo group achieved sustained tobacco abstinence for the 6-month trial . Bupropion treatment was associated with improvement in negative symptoms and greater stability of psychotic and depressive symptoms , compared with placebo , during the quit attempt . Subjects in the bupropion group experienced significant weight loss , compared with those on placebo during the smoking cessation attempt . These data suggest that bupropion SR , 150 mg/day , combined with CBT , may facilitate smoking reduction in patients with schizophrenia while stabilizing psychiatric symptoms during a quit attempt Background : Cigarette smoking is a tough addiction to break . This dependence is the most common dual diagnosis for individuals with schizophrenia . Currently three effective drugs are approved for smoking cessation : nicotine replacement therapy ( NRT ) , varenicline and bupropion . However , some serious side effects of varenicline have been reported , including depression , suicidal thoughts , and suicide . The use of bupropion also has side effects . It should not be used by people who have epilepsy or any condition that lowers the seizure threshold , nor by people who take a specific class of drugs called monoamine oxidase inhibitors . Hence , there are pharmacodynamic reason to believe they could precipitate or exacerbate psychosis . For its capacity to deliver nicotine and provide a coping mechanism for conditioned smoking cues by replacing some of the rituals associated with smoking gestures , electronic-cigarettes may reduce nicotine withdrawal symptoms without serious side effects . Our recent work with ECs in healthy smokers not intending to quit consistently show surprisingly high success rates . We hypothesised that these positive findings could be replicated in difficult patients with schizophrenia This tool may help smokers with schizophrenia remain abstinent during their quitting attempts or to reduce cigarette consumption . Efficacy and safety of these devices in long-term smoking cessation and /or smoking reduction studies have never been investigated for this special population . Methods : In this study we monitored possible modifications in smoking habits of 14 smokers ( not intending to quit ) with schizophrenia experimenting with the “ Categoria ” e-Cigarette  with a focus on smoking reduction and smoking abstinence . Study participants were invited to attend six study visits : at baseline , week-4 , week-8 , week-12 week-24 and week 52 . Product use , number of cigarettes smoked , carbon monoxide in exhaled breath ( eCO ) and positive and negative symptoms of schizophrenia levels were measured at each visit . Smoking reduction and abstinence rates were calculated . Adverse events were also review ed . Results : Sustained 50 % reduction in the number of cig/day at week-52 was shown in 7/14 ( 50 % ) participants ; their median of 30 cig/day decreasing significantly to 15 cig/day ( p = 0.018 ) . Sustained smoking abstinence at week-52 was observed in 2/14 ( 14.3 % ) participants . Combined sustained 50 % reduction and smoking abstinence was shown in 9/14 ( 64.3 % ) participants . Nausea was observed in 2/14 ( 14.4 % ) of participants , throat irritation in 2/14 ( 14.4 % ) of participants , headache in 2/14 ( 14.4 % ) of participants , and dry cough in 4/14 ( 28.6 % ) of participants . However , these adverse events diminished substantially by week-24 . Overall , one to two cartridges/day were used throughout the study . Positive and negative symptoms of schizophrenia are not increased after smoking reduction/cessation in patients using e-cigarettes . Conclusions : We have shown for the first time that the use of e-cigarette substantially decreased cigarette consumption without causing significant side effects in chronic schizophrenic patients who smoke not intending to quit . This was achieved without negative impacts on the symptoms of schizophrenia as assessed by SAPS and SANS symptoms scales Nearly 90 % of schizophrenics smoke cigarettes , considerably higher than the general population 's rate of 25 % . There is some indication that schizophrenics may smoke as a form of self-medication . Nicotine has a variety of pharmacologic effects that may both counteract some of the cognitive deficits of schizophrenia and counteract some of the adverse side effects of antipsychotic drugs . In the current study , we assessed the interactions of haloperidol and nicotine on cognitive performance of a group of schizophrenics . These patients were in a double-blind study , r and omly assigning them to low , moderate , and high dose levels of haloperidol .  The subjects , all smokers , came to the laboratory on four different mornings after overnight deprivation from cigarettes . In a double-blind fashion , they were administered placebo , low ( 7 mg/day ) , medium ( 14 mg/day ) , or high ( 21 mg/day ) dose nicotine skin patches . Three hours after administration of the skin patch , the subjects were given a computerized cognitive test battery including : simple reaction time , complex reaction time ( spatial rotation ) , delayed matching to sample , the Sternberg memory test , and the Conners continuous performance test ( CPT ) . With the placebo nicotine patch , there was a haloperidol dose-related impairment in delayed matching to sample choice accuracy and an increase in response time on the complex reaction time task . Nicotine caused a dose-related reversal of the haloperidol-induced impairments in memory performance and complex reaction time . In the CPT , nicotine reduced the variability in response that is associated with attentional deficit . These results demonstrate the effects of nicotine in reversing some of the adverse side effects of haloperidol and improving cognitive performance in schizophrenia . © 1996 American College of OBJECTIVE Effective smoking cessation treatments are needed for patients with schizophrenia , who , compared with the general population , have high rates of cigarette smoking and more difficulty quitting . We evaluated the safety and efficacy of varenicline for smoking cessation in out patients with stable schizophrenia or schizoaffective disorder . METHOD In this 12-week , r and omized , double-blind , multicenter trial ( May 8 , 2008 , to April 1 , 2010 ) , 127 smokers ( ≥ 15 cigarettes/d ) with DSM-IV-confirmed schizophrenia or schizoaffective disorder received varenicline or placebo ( 2:1 ratio ) . The primary outcome was safety and tolerability of varenicline  assessed by adverse events frequency and changes in ratings on the Positive and Negative Syndrome Scale and other psychiatric scales from baseline to 24 weeks . Abstinence was defined as no smoking 7 days prior to weeks 12 and 24 , verified by carbon monoxide level . RESULTS Eighty-four participants received varenicline ; 43 , placebo . At 12 weeks ( end of treatment ) , 16/84 varenicline-treated patients ( 19.0 % ) met smoking cessation criteria versus 2/43 ( 4.7 % ) for placebo ( P = .046 ) . At 24 weeks , 10/84 ( 11.9 % ) varenicline-treated and 1/43 ( 2.3 % ) placebo-treated patients , respectively , met abstinence criteria ( P = .090 ) . Total adverse event rates were similar between groups , with no significant changes in symptoms of schizophrenia or in mood and anxiety ratings . Rates of suicidal ideation adverse events were 6.0 % ( varenicline ) and 7.0 % ( placebo ) ( P = 1.0 ) . There was 1 suicide attempt by a varenicline patient with a lifetime history of similar attempts and no completed suicides . CONCLUSIONS Varenicline was well tolerated , with no evidence of exacerbation of symptoms , and was associated with significantly higher smoking cessation rates versus placebo at 12 weeks . Our findings suggest varenicline is a suitable smoking cessation therapy for patients with schizophrenia or schizoaffective disorder . TRIAL REGISTRATION Clinical Trials.gov identifier : NCT00644969 Rationale Individuals with schizophrenia have high smoking-related morbidity and mortality rates and need powerful and innovative smoking cessation interventions . Objectives This proof-of-concept study investigated the feasibility and initial efficacy of combining a contingency management intervention with bupropion to reduce smoking in people with schizophrenia . Methods Using a double-blind , placebo-controlled , between-groups design , 57 non-treatment-seeking participants were r and omized to receive 300 mg/day bupropion or placebo . One week later , participants were r and omized to a contingency management ( CM ) intervention in which reductions in urinary cotinine levels were reinforced , or a non-contingent reinforcement ( NR ) condition in which session attendance was reinforced , regardless of cotinine level . Over the 22-day study period , participants visited the laboratory approximately three times per week to provide urine sample s for analysis of cotinine levels , to give breath sample s for analysis of carbon monoxide ( CO ) levels , and to report number of cigarettes smoked per day , nicotine withdrawal symptoms , cigarette craving , and psychiatric symptoms . Results Cotinine and CO levels significantly decreased during the study period in participants r and omized to the CM condition , but not the NR condition . Bupropion did not reduce cotinine levels or increase the efficacy of CM . Cigarette craving and psychiatric symptom levels significantly decreased during the study in all groups . Conclusions The results of this study indicate the efficacy and feasibility of this CM intervention for reducing smoking in individuals with schizophrenia Abstract : The objective of this study was to examine the efficacy of bupropion for smoking cessation in patients with schizophrenia . Adults with schizophrenia who smoked more than 10 cigarettes per day and wished to try to quit smoking were recruited from community mental health centers , enrolled in a 12-week group cognitive behavioral therapy intervention , and r and omly assigned to receive either bupropion sustained-release 300 mg/d or identical placebo .  Fifty-three adults , 25 on bupropion and 28 on placebo  , were r and omized , completed at least 1 postbaseline assessment and were included in the analysis . The primary outcome measures were 7-day point prevalence abstinence in the week after the quit date ( week 4 ) and at the end of the intervention ( week 12 ) . Subjects in the bupropion group were significantly more likely to be abstinent for the week after the quit date ( 36 % [ 9/25 ] vs. 7 % [ 2/28 ] , P = 0.016 ) and at end of the intervention ( 16 % [ 4/25 ] vs. 0 % , P = 0.043 ) . Subjects in the bupropion group also had a higher rate of 4-week continuous abstinence ( weeks 8 - 12 ) ( 16 % [ 4/25 ] vs. 0 % , P = 0.043 ) and a longer duration of abstinence ( 4.2 [ 3.2 ] weeks vs. 1.8 [ 0.96 ] weeks , t = 2.30 , P = 0.037 ) . The effect of bupropion did not persist after discontinuation of treatment . Subjects in the bupropion group had no worsening of clinical symptoms and had a trend toward improvement in depressive and negative symptoms . We conclude that bupropion does not worsen clinical symptoms of schizophrenia and is modestly effective for smoking cessation  in patients with schizophrenia . The relapse rate is high after treatment discontinuation The objective of this study was to examine whether there is a benefit of adding bupropion SR to high-dose combination nicotine replacement therapy ( NRT ) and weekly group cognitive behavioral therapy ( CBT ) for smoking reduction or cessation in schizophrenia . Fifty-one adult smokers with schizophrenia were r and omly assigned to a 12-week trial of bupropion SR 300 mg/d or placebo added to transdermal nicotine patch , nicotine polacrilex gum , and CBT . The treatment goal was smoking cessation . The primary outcome measure was biochemically confirmed 7-day point-prevalence of 50 % to 100 % smoking reduction at week 12 . Secondary outcomes were biochemically confirmed tobacco abstinence and change from baseline in expired air carbon monoxide ( CO ) and psychiatric symptoms . Subjects on bupropion + NRT had a greater rate of 50 % to 100 % smoking reduction at weeks 12 ( 60 % vs. 31 % ; P = 0.036 ) and 24 , a lower expired air CO in the treatment and follow-up periods , ( F = 13.8 ; P < 0.001 ) and a greater continuous abstinence rate at week 8 , before NRT taper , ( 52 % vs. 19 % ; P = 0.014 ) . However , relapse rates in subjects on bupropion + dual NRT were 31 % during NRT taper ( weeks 8 - 12 ) and 77 % at the 12-month follow-up . Abstinence rates did not differ by treatment group at weeks 12 ( 36 % vs. 19 % ) , 24 ( 20 % vs. 8 % ) , or 52 ( 12 % vs. 8 % ) . Because abstinence rates were high during treatment with combination pharmacotherapy and relapse rates were very high during taper and after discontinuation of treatment , study of longer term treatment with combination pharmacotherapy and CBT for sustained abstinence is warranted in those who attain initial abstinence with this intervention The purpose of this study was to determine the effectiveness of nicotine-patch therapy for smoking cessation in patients with schizophrenia . This was a longitudinal study and sixty-eight schizophrenic patients were assigned to 8 weeks of a nicotine-patch therapy program or a control group . The generalized estimating equation analysis revealed that there were significant reductions in the subjects ' nicotine dependence ( Fagerstrom Tolerance Question naire ) , the number of cigarettes per day , and CO levels over an 8-week period of nicotine-patch therapy and 3-month follow-up . The point-prevalence rates of abstinence from smoking were an abstinence of 26.9 % at 8 weeks and 26.9 % at a 3-month follow-up . At the 3-month follow-up , the rate of continuous smoking abstinence in the nicotine-patch group was 23.1 % There have been many studies of smoking cessation using nicotine replacement therapy ( NRT ) with schizophrenic patients , but none exploring the smoking-reduction effects of varying doses of NRT in long-stay patients with schizophrenia . This study aim ed to examine the effect of different doses of the nicotine transdermal patch on smoking-reduction and cessation outcomes in long-term hospitalized schizophrenic patients . A total of 184 subjects participated in a r and omized , controlled , double-blind 8-week clinical trial . Participants were r and omized into two groups using two different doses of NRT : a high-dose NRT group ( 31.2 mg for the first 4 weeks , then 20.8 mg for 4 weeks , n = 92 ) or a low-dose NRT group ( 20.8 mg for 8 weeks , n = 92 ) . The 7-day point prevalence of abstinence was 2.7 % ( 5/184 ) . Participants in the low-dose NRT group reduced smoking by 3.1 more cigarettes on average than those in the high-dose group ( p = 0.005 ) . However , a repeated measures analysis of variance revealed that the main effect of changes in the number of cigarettes smoked , comparing the two types of treatment across periods , was not significant ( p = 0.35 , partial eta square = 0.018 ) . In summary , among a cohort of chronic institutionalized schizophrenic patients , smoking cessation and reduction outcomes were not correlated with NRT dose , and the cessation rate was much lower than rates in similar studies . It indicates that long-term hospitalized schizophrenic patients have more difficulties with quitting smoking . More effective integrative smoking cessation programs should be addressed for these patients BACKGROUND We were interested in exploring the efficacy and safety of varenicline as an adjunct to a healthy lifestyle intervention for smoking cessation among individuals with a severe mental illness . METHODS We used varenicline as an adjunct to a healthy lifestyle intervention in 14 smokers with a psychotic illness . RESULTS Overall , smoking cessation rates were 36 % at 3 months and 42 % at 6 months . The most commonly reported side effects were sleep disturbance and nausea . These tended to occur early in treatment , and patients responded to general measures of support and reassurance . Of the 14 participants , 1 dropped out because of psychiatric problems and 2 because of other side effects . CONCLUSIONS Varenicline appears to be an effective adjunct to a healthy lifestyle intervention for smokers with a psychotic illness . Although the results of this open study are encouraging , replication in an adequately powered , r and omized controlled trial is required before definitive conclusions can be drawn Schizophrenics have deficits in neuropsychological performance , some of which are modified by cigarette smoking . These patients also have high rates of smoking and resistance to smoking cessation interventions . We examined whether the presence of neuropsychological deficits prior to smoking cessation treatment was associated with smoking cessation treatment failure in schizophrenic as compared to non-psychiatric control smokers . Neuropsychological assessment s were performed prior to treatment with pharmacological agents during the course of placebo-controlled trials in schizophrenic and non-psychiatric control smokers , and included the  Wisconsin Card Sorting Test ( WCST ) , a Visuospatial Working Memory ( VSWM ) task , the Stroop Color Word Test ( SCWT ) and the Continuous Performance Test ( CPT ) .  In schizophrenics ( n=32 ) , subjects who had greater deficits in VSWM and WCST performance were significantly less likely to quit smoking , but this association was not observed in controls ( n=40 ) . Differences between quitters and non-quitters were not likely related to atypical antipsychotic treatment or differences in depressive symptoms . No associations between baseline performance on CPT or SCWT and quit status were found in either group . These preliminary data suggest that in schizophrenics , neuropsychological deficits are associated with smoking cessation treatment failure Nicotine replacement therapy ( NRT ) repeatedly has been shown to improve smoking treatment outcome . The major mechanism posited for this improvement in outcome is that NRT reduces nicotine craving and withdrawal . The authors tested this hypothesized mechanism of action using real-time data on craving and withdrawal , collected by ecological momentary assessment s administered on a palm-top computer . Smokers ( N = 324 ) were r and omized to receive either active high-dose ( 35 mg ) 24-hr patches or placebo . Increases in positive affect and decreases in craving , negative affect , and attention disturbance severity were related to lower risk of lapsing . Although NRT treatment did significantly decrease withdrawal and craving severity , these reductions only partially accounted for NRT 's impact on time to first lapse : The results from a mediation analysis showed that the hazard ratio for NRT , when controlling for withdrawal and craving severity , was only a third to a half lower than the uncontrolled hazard ratio for NRT alone . This suggests that other mechanisms for the effectiveness of NRT need to be examined IMPORTANCE It is estimated that more than half of those with serious mental illness smoke tobacco regularly . St and ard courses of pharmacotherapeutic cessation aids improve short-term abstinence , but most who attain abstinence relapse rapidly after discontinuation of pharmacotherapy . OBJECTIVE To determine whether smokers diagnosed with schizophrenia and bipolar disease have higher rates of prolonged tobacco abstinence with maintenance pharmacotherapy than with st and ard treatment . DESIGN , SETTING , AND PARTICIPANTS R and omized , double-blind , placebo-controlled , parallel-group , relapse-prevention clinical trial conducted in 10 community mental-health centers . Of 247 smokers with schizophrenia or bipolar disease recruited from March 2008-April 2012 , 203 received 12-weeks ' open-label varenicline and cognitive behavioral therapy and 87 met abstinence criteria to enter the relapse prevention intervention .  INTERVENTIONS Participants who had 2 weeks or more of continuous abstinence at week 12 of open treatment were r and omly assigned to receive cognitive behavioral therapy and double-blind varenicline ( 1 mg , 2 per day ) or placebo from weeks 12 to 52 . Participants then discontinued study treatment and were followed up to week 76 . MAIN OUTCOMES AND MEASURES Seven-day rate of continuous abstinence at study week 52 , the end of the relapse-prevention phase , confirmed by exhaled carbon monoxide . Secondary outcomes were continuous abstinence rates for weeks 12 through 64 based on biochemically verified abstinence and weeks 12 through 76 , based on self-reported smoking behavior . RESULTS Sixty-one participants completed the relapse-prevention phase ; 26 discontinued participation ( 7 varenicline , 19 placebo ) and were considered to have relapsed for the analyses ; 18 of these had relapsed prior to dropout . At week 52 , point-prevalence abstinence rates were 60 % in the varenicline group ( 24 of 40 ) vs 19 % ( 9 of 47 ) in the placebo group ( odds ratio [ OR ] , 6.2 ; 95 % CI , 2.2 - 19.2 ; P < .001 ) . From weeks 12 through 64 , 45 % ( 18 of 40 ) among those in the varenicline group vs 15 % ( 7 of 47 ) in the placebo group were continuously abstinent ( OR , 4.6 ; 95 % CI , 1.5 - 15.7 ; P = .004 ) , and from weeks 12 through 76 , 30 % ( 12 of 40 ) in the varenicline group vs 11 % ( 5 of 47 ) in the placebo group were continuously abstinent ( OR , 3.4 ; 95 % CI , 1.02 - 13.6 ; P = .03 ) . There were no significant treatment effects on psychiatric symptom ratings or psychiatric adverse events . CONCLUSIONS AND RELEVANCE Among smokers with serious mental illness who attained initial abstinence with st and ard treatment , maintenance pharmacotherapy with varenicline and cognitive behavioral therapy improved prolonged tobacco abstinence rates compared with cognitive behavioral therapy alone after 1 year of treatment and at 6 months after treatment discontinuation . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00621777
target: Overall , nicotine replacement therapy , bupropion , and varenicline have all proven their effectiveness at either promoting smoking abstinence or a significant reduction in cigarette use
background: Smoking cessation is a chronic issue surrounding individuals with schizophrenia .
  It is estimated that up to 90 % of patients diagnosed with schizophrenia smoke cigarettes .
  The purpose of this article is to provide a non systematic review of the efficacy of  smoking cessation interventions as well as to explore the potential neuropsychiatric adverse effects of these agents in patients with schizophrenia .