***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: 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 Varenicline is approved as an aid to smoking cessation in adults aged > or = 18 years . OBJECTIVE The goal of this study was to characterize the multiple-dose pharmacokinetics , safety , and tolerability of varenicline in adolescent smokers . METHODS This multicenter , r and omized , double-blind , placebo-controlled , parallel-group study enrolled healthy 12- to 16-year-old smokers ( > or =3 cigarettes daily ) into high-body-weight ( > 55 kg ) and low-body-weight ( < or = 55 kg ) groups . Subjects were r and omized to receive 14 days of treatment with a high dose of varenicline , a low dose of varenicline , or placebo . The varenicline doses in the high-body-weight group were 1 mg BID and 0.5 mg BID ; the varenicline doses in the low-body-weight group were 0.5 mg BID and 0.5 mg once daily . The apparent renal clearance ( CL/F ) and volume of distribution ( V/F ) of varenicline and the effect of body weight on these parameters were estimated using nonlinear mixed-effects modeling . RESULTS The high-body-weight group consisted of 35 subjects ( 65.7 % male ; 77.1 % white ; mean age , 15.2 years ) . The low-body-weight group consisted of 37 subjects ( 37.8 % male ; 48.6 % white ; mean age , 14.3 years ) . The pharmacokinetic parameters of varenicline were dose proportional over the dose range from 0.5 to 2 mg/d . The CL/F for a 70-kg adolescent was 10.4 L/h , comparable to that in a 70-kg adult . The estimated varenicline V/F was decreased in individuals of small body size , thus predicting a varenicline C(max ) approximately 30 % greater in low-body-weight subjects than in high-body-weight subjects . In high-body-weight subjects , steady-state varenicline exposure , as represented by the AUC(0 - 24 ) , was 197.0 ng . h/mL for varenicline 1 mg BID and 95.7 ng . h/mL for varenicline 0.5 mg BID , consistent with values reported previously in adult smokers at the equivalent doses . In low-body-weight subjects , varenicline exposure was 126.3 ng . h/mL for varenicline 0.5 mg BID and 60.1 ng . h/mL for varenicline 0.5 mg once daily , values at the lower end of the range observed previously in adults at doses of 1 mg BID and 0.5 mg BID , respectively . Among high-body-weight subjects , adverse events ( AEs ) were reported by 57.1 % of subjects in both the high- and low-dose varenicline groups and by 14.3 % of subjects in the placebo group ; among low-body-weight subjects , AEs were reported by 64.3 % , 73.3 % , and 12.5 % of subjects in the high-dose varenicline , low-dose varenicline , and placebo groups , respectively . The most common AEs were nausea , headache , vomiting , and dizziness . Psychiatric AEs that were considered treatment related included abnormal dreams in 2 subjects and mild , transient anger in 1 subject . Of the AEs reported by > or = 1 subject in any treatment group , > or = 92 % were mild in intensity . No subject discontinued the study because of an AE . CONCLUSIONS Varenicline steady-state exposure in study subjects weighing > 55 kg was similar to that observed previously in adults . The body-weight effect on varenicline pharmacokinetics , which result ed in higher exposure in individuals of smaller body size ( < or = 55 kg ) , was adequately offset by administration of half the varenicline dose recommended in adults . Varenicline was generally well tolerated during the 14-day treatment period . Clinical Trials Identification Number : NCT00463918 Background — Smoking cessation is a key component of secondary cardiovascular disease prevention . Varenicline , a partial & agr;4&bgr;2 nicotinic acetylcholine receptor agonist , is effective for smoking cessation in healthy smokers , but its efficacy and safety in smokers with cardiovascular disease are unknown . Methods and Results — A multicenter , r and omized , double-blind , placebo-controlled trial compared the efficacy and safety of varenicline with placebo for smoking cessation in 714 smokers with stable cardiovascular disease . Participants received varenicline ( 1 mg twice daily ) or placebo , along with smoking-cessation counseling , for 12 weeks . Follow-up lasted 52 weeks . The primary end point was carbon monoxide – confirmed continuous abstinence rate for weeks 9 through 12 ( last 4 weeks of treatment ) . The continuous abstinence rate was higher for varenicline than placebo during weeks 9 through 12 ( 47.0 % versus 13.9 % ; odds ratio , 6.11 ; 95 % confidence interval [ CI ] , 4.18 to 8.93 ) and weeks 9 through 52 ( 19.2 % versus 7.2 % ; odds ratio , 3.14 ; 95 % CI , 1.93 to 5.11 ) . The varenicline and placebo groups did not differ significantly in cardiovascular mortality ( 0.3 % versus 0.6 % ; difference , −0.3 % ; 95 % CI , −1.3 to 0.7 ) , all-cause mortality ( 0.6 % versus 1.4 % ; difference , −0.8 % ; 95 % CI , −2.3 to 0.6 ) , cardiovascular events ( 7.1 % versus 5.7 % ; difference , 1.4 % ; 95 % CI , −2.3 to 5.0 ) , or serious adverse events ( 6.5 % and 6.0 % ; difference , 0.5 % ; 95 % CI , −3.1 to 4.1 ) . As a result of adverse events , 9.6 % of varenicline and 4.3 % of placebo participants discontinued study drug . Conclusions — Varenicline is effective for smoking cessation in smokers with cardiovascular disease . It was well tolerated and did not increase cardiovascular events or mortality ; however , trial size and duration limit definitive conclusions about safety . Clinical Trial Registration Information— URL : http://www . clinical trials.gov/ct2/show/NCT00282984 . Unique identifier : NCT00282984 BACKGROUND Currently available smoking cessation therapies have limited success rates . Varenicline tartrate is a novel , selective nicotinic receptor partial agonist developed specifically for smoking cessation . This study evaluated the efficacy , tolerability , and safety of 3 varenicline doses for smoking cessation . Bupropion hydrochloride was included as an active control . METHODS A phase 2 , multicenter , r and omized , double-blind , placebo-controlled study of healthy smokers ( 18 - 65 years old ) . Subjects were r and omized to varenicline tartrate , 0.3 mg once daily ( n = 128 ) , 1.0 mg once daily ( n = 128 ) , or 1.0 mg twice daily ( n = 127 ) , for 6 weeks plus placebo for 1 week ; to 150-mg sustained-release bupropion hydrochloride twice daily ( n = 128 ) for 7 weeks ; or to placebo ( n = 127 ) for 7 weeks . RESULTS During the treatment phase , the continuous quit rates for any 4 weeks were significantly higher for varenicline tartrate , 1.0 mg twice daily ( 48.0 % ; P<.001 ) and 1.0 mg once daily ( 37.3 % ; P<.001 ) , than for placebo ( 17.1 % ) . The  bupropion  rate was 33.3 % ( P = .002 vs placebo ) . The carbon monoxide-confirmed continuous quit rates from week 4 to week 52 were significantly higher in the varenicline tartrate , 1.0 mg twice daily , group compared with the placebo group ( 14.4 % vs 4.9 % ; P = .002 ) . The  bupropion rate was 6.3 % ( P = .60 vs placebo ) . Discontinuation owing to treatment-emergent adverse events was 15.9 % for bupropion , 11.2 % to 14.3 % for varenicline , and 9.8 % for placebo . No dose-related increases occurred in adverse events for varenicline . CONCLUSIONS Varenicline tartrate demonstrated both short-term ( 1 mg twice daily and 1 mg once daily ) and long-term efficacy ( 1 mg twice daily ) vs placebo . Varenicline was well tolerated and may provide a novel therapy to aid smoking cessation Objective : The objective of this double-blind , placebo-controlled , r and omized study was to evaluate the efficacy of varenicline ( Chantix ) , a partial agonist at α4β2 neuronal nicotinic acetylcholine receptors used for smoking cessation , in patients with spinocerebellar ataxia ( SCA ) 3 . Methods : Patients with genetically confirmed SCA3 were r and omly assigned to receive either varenicline ( 4 weeks for titration and 4 weeks at a dose of 1 mg twice daily ) or placebo . Outcome measures included changes in the Scale for the Rating and Assessment of Ataxia ( SARA ) scores at endpoint ( 8 weeks ) compared with baseline , a timed 25-foot walk and 9-hole peg test , measurements of mood and anxiety , and adverse events . Results : Twenty patients with SCA3 ( mean age = 51 ± 10.98 years ; mean disease duration = 14 ± 9.82 years ; mean SARA score = 16.13 ± 4.67 ) were enrolled in the study , and data on 18 patients were analyzed in period I. The most common side effect associated with varenicline was nausea . Improvements were noted in the SARA subsections for gait ( p = 0.04 ) , stance ( p = 0.03 ) , rapid alternating movements ( p = 0.003 ) , and timed 25-foot walk ( p = 0.05 ) and Beck Depression Inventory scores ( p = 0.03 ) in patients taking varenicline compared with those taking placebo at endpoint , with a trend toward improvement in the SARA total score ( p = 0.06 ) in the varenicline group . Conclusions : In this controlled study , varenicline significantly improved axial symptoms and rapid alternating movements in patients with SCA3 as measured by SARA subscores and was fairly well tolerated . Classification of evidence : This study provides Class II evidence that varenicline improved the axial functions of gait , stance , and timed 25-foot walk but did not improve appendicular function , except for rapid alternating movements , in adult patients with genetically confirmed SCA3 BACKGROUND The selective nicotinic acetylcholine receptor partial agonist , varenicline tartrate , represents a novel type of therapy for smoking cessation . This study evaluated the efficacy , safety , and tolerability of 4 varenicline dose regimens , 2 with progressive dos 
    Output:
    
This meta- analysis found no evidence of an increased risk of suicide or attempted suicide , suicidal ideation , depression , or death with varenicline .
These findings provide some reassurance for users and prescribers regarding the neuropsychiatric safety of varenicline .
There was evidence that varenicline was associated with a higher risk of sleep problems such as insomnia and abnormal dreams .