Ignite Creation Date:
2024-05-05 @ 4:50 PM
Last Modification Date:
2024-10-26 @ 9:24 AM
Study NCT ID:
NCT00320723
Status:
COMPLETED
Last Update Posted:
2009-05-19
First Post:
2006-04-28
Brief Title:
Nicotine Replacement Therapy for Smoking Cessation in Schizophrenia
Sponsor:
North Suffolk Mental Health Association
Organization:
North Suffolk Mental Health Association
Study Overview
Official Title:
Nicotine Replacement Therapy Added to Cognitive Behavioral Therapy for Smoking Cessation in Patients With Major Mental Illness
Status:
COMPLETED
Status Verified Date:
2009-05
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
This proposal seeks to evaluate a pilot smoking cessation treatment program that will combine nicotine replacement therapy with or without bupropion sustained-release SR with cognitive behavioral therapy for smoking cessation in patients with major mental illness
Detailed Description:
Background
Seventy-four to 92 of patients with schizophrenia smoke cigarettes compared to 24 of the adult US population and 18 of adults in Massachusetts 1-3 Patients with schizophrenia also smoke more cigarettes on average per day 4 and attain higher serum levels of cotinine the primary metabolite of nicotine a finding attributed to deeper smoke inhalation 5 Cigarette smoking has been identified as the single most important source of preventable morbidity and premature mortality in the general US population for the last 29 years 6 7 Compounded by the problem that patients with schizophrenia live a less healthy lifestyle 8 and may be less likely to receive adequate routine and preventative medical care 9-12 heavy smoking represents a significant and neglected public health problem for people with schizophrenia Patients with schizophrenia clearly have greater morbidity and early mortality from natural causes than people without schizophrenia 13-22 and are more likely to die prematurely from cardiovascular or pulmonary disease 14 19 23-26 Women with schizophrenia have been shown to have increased risk of premature death from cancer 24 and previous studies showing lower mortality from cancer in patients with schizophrenia compared to the general population have not been confirmed 14 27 28 Successful smoking cessation programs for patients with schizophrenia could reduce this increased medical morbidity and mortality A recent report of patterns of nicotine use in a cohort of 50 patients with schizophrenia or schizoaffective disorder underscores this point the cohort had a mean age of 47 years and mean age at onset of daily smoking of 20 years 458 reported they currently have a smoking related health problem 958 had tried unsuccessfully to cut down on their smoking 70 had made a serious attempt to quit smoking 29 Smoking cessation programs for patients with schizophrenia have reported compliance rates as high as 80 30
Nicotinic receptors have been shown to be reduced in number in patients with schizophrenia 31 32 and heavy smoking in schizophrenia may be attributable to attempts to overcome this deficit Benefits of nicotine to patients with schizophrenia include reversal of some of the specific cognitive deficits associated with schizophrenia and antipsychotic treatment 33-37 Nicotine has been shown to improve learning visual and spatial working memory attention auditory sensory gating smooth pursuit eye movements and reaction time 38 39 The positive effects of chronic nicotine treatment appear to persist over time and in some studies improvements in cognition with chronic nicotine treatment become more robust over time 40 Smoking cessation in patients with schizophrenia is associated with increase in positive symptoms 30 Treatment with atypical antipsychotics may enhance the effectiveness of smoking cessation treatment 41-43 The mechanism of this effect is not known but may be due to decreased extrapyramidal side effects improved efficacy for negative symptoms or effects on glutamatergic systems Combination of NRT and antidepressant medication has been shown to increase cessation rates over monotherapy with NRT 44 but not over antidepressant medication alone 45
Nicotine replacement therapy NRT is a powerful aid to smoking cessation with well established efficacy 46-49 in non-psychiatric patients and has been proposed as a potential tool in increasing smoking harm reduction in persons unable to achieve smoking abstinence 50 Smoking cessation outcomes in patients with schizophrenia using NRT have been extremely variable Ziedonis and colleagues used a range of doses of NRT administered by patch gum or combination in addition to CBT for up to 10 weeks in 24 patients with schizophrenia 51 Twelve subjects completed the trial The cessation rate was 13 at 6 months 51 In one study atypical antipsychotic agents in combination with the nicotine transdermal patch have been shown to significantly enhance the rate of smoking cessation 556 in the atypical agent group versus 222 in the typical group 41 In this study the overall end of treatment point prevalence smoking cessation rate in 45 patients with schizophrenia was 35 In another study of the acute effects of transdermal nicotine patch in psychiatric patients however no patients quit smoking acutely and only heavy smokers reduced their cigarette consumption 52
Safety of NRT in patients with schizophrenia has only been evaluated on a very small scale One important trial examined the effects of a 21 mg nicotine patch on smoking behavior nicotine levels in blood and signs of toxicity in patients with schizophrenia 53 In this crossover trial 10 male veterans were monitored while wearing nicotine vs placebo patches The nicotine patch condition was associated with increased nicotine levels without signs of toxicity and decreased CO levels in 80 of patients No trials have reported worsening of psychiatric symptoms with NRT Larger studies in which NRT is combined with behavioral support are needed to evaluate the efficacy and safety of NRT in schizophrenia
Treatment Component
Subjects will be outpatients who are clinically stable and currently in treatment for schizophrenia or schizoaffective disorder Subjects will be recruited through referral from case managers residential treatment settings and outpatient treaters Subjects must smoke 12 pack per day of cigarettes and wish to quit smoking
Subjects will be randomly assigned to receive cognitive behavioral smoking cessation therapy CBT with nicotine patch NRT plus placebo or nicotine patch combined with bupropion SR Subjects who are unable to tolerate or who have a contraindication to treatment with zyban may be enrolled to receive CBT and open label NRT alone All subjects will receive a 12 session group cognitive behavioral therapy CBT program designed for smoking cessation treatment in patients with schizophrenia in addition to pharmacologic treatment
Evaluation Component
The evaluation component of this protocol involves monitoring patients for stability of psychiatric symptoms serum levels of psychiatric medications and medication side effects at baseline and weeks 4 8 12 and 14 and degree of smoking reduction or cessation weekly during the treatment intervention and at 6 12 and 24 months
At baseline subjects will complete a demographic questionnaire Prior to beginning treatment subjects will be evaluated for symptoms of psychosis depression anxiety and medication side effects with standard clinical rating scales that include the schedule for assessment of negative symptoms SANS positive and negative symptom scale PANSS Hamilton depression scale HamD Hamilton anxiety scale HamA abnormal involuntary movement scale AIMS Simpson Angus Scale and SAFTEE A brief cognitive battery will include tests of response inhibition the single trial Stroop vigilance continuous performance test verbal fluency FAS verbal memory California Verbal Learning Test working memory letter number span non-verbal memory Benton visual retention test psychomotor ability grooved peg board task and executive functioning trail making or tower of London Baseline carbon monoxide CO measurements will be used with self report to verify number of cigarettes smoked per day Serum will be drawn for cotinine and antipsychotic levels at baseline Weight will be checked at baseline 12 and 24 weeks
Subjects will set a quit date between weeks 3 and 4 The evaluation battery will be repeated at week 4 just following the quit date It will also be repeated at week 12 when patients discontinue the group and medication treatment An evaluation that includes the clinical battery and CO measurement will be performed at week 14 two weeks following termination of smoking cessation treatment and at week 24 Subjects will also be contacted at 1 and 2 years for follow up self report of tobacco use and CO measurement
Specific Aims Treatment
1 Increase availability of nicotine replacement therapy which is not currently available by prescription to patients with major mental illness
2 Train staff members with expertise in treating patients with major mental illness to be Tobacco Treatment Specialists using the training protocol developed by University of Massachusetts Medical School in collaboration with the Massachusetts Department of Public Health
3 Establish a network of centers able to deliver tobacco treatment to patients with major mental illness
Specific Aims Evaluation
1 Evaluate smoking cessation rates smoking reduction rates and stability of psychiatric symptoms in patients with schizophrenia and schizoaffective disorder during a smoking cessation attempt using cognitive behavioral therapy combined with NRT plus placebo and NRT bupropion SR
2 Evaluate safety of nicotine replacement therapy in patients with schizophrenia and schizoaffective disorder when combined with antipsychotic medications
3 Evaluate safety of nicotine replacement therapy in patients with schizophrenia and schizoaffective disorder when combined with bupropion SR and antipsychotic medications
Hypotheses
1 Nicotine replacement therapy combined with bupropion SR and cognitive behavioral therapy will be associated with improvement in smoking cessation and smoking reduction rates when compared to NRT alone added to CBT in patients with schizophrenia and schizoaffective disorder
2 Nicotine replacement therapy combined with bupropion SR will be associated with improvement in negative symptoms depression and impulsivity when compared to NRT alone in patients with schizophrenia and schizoaffective disorder who quit smoking
3 Concurrent treatment with atypical antipsychotic medications will further enhance the effectiveness of NRT combined with bupropion SR and NRT plus placebo for smoking cessation and reduction in patients with schizophrenia and schizoaffective disorder compared to concurrent treatment with conventional antipsychotics
4 Patients with low baseline cotinine 250 ngml will have higher cessation rates than patients with high baseline cotinine 250 ngml
Seventy-four to 92 of patients with schizophrenia smoke cigarettes compared to 24 of the adult US population and 18 of adults in Massachusetts 1-3 Patients with schizophrenia also smoke more cigarettes on average per day 4 and attain higher serum levels of cotinine the primary metabolite of nicotine a finding attributed to deeper smoke inhalation 5 Cigarette smoking has been identified as the single most important source of preventable morbidity and premature mortality in the general US population for the last 29 years 6 7 Compounded by the problem that patients with schizophrenia live a less healthy lifestyle 8 and may be less likely to receive adequate routine and preventative medical care 9-12 heavy smoking represents a significant and neglected public health problem for people with schizophrenia Patients with schizophrenia clearly have greater morbidity and early mortality from natural causes than people without schizophrenia 13-22 and are more likely to die prematurely from cardiovascular or pulmonary disease 14 19 23-26 Women with schizophrenia have been shown to have increased risk of premature death from cancer 24 and previous studies showing lower mortality from cancer in patients with schizophrenia compared to the general population have not been confirmed 14 27 28 Successful smoking cessation programs for patients with schizophrenia could reduce this increased medical morbidity and mortality A recent report of patterns of nicotine use in a cohort of 50 patients with schizophrenia or schizoaffective disorder underscores this point the cohort had a mean age of 47 years and mean age at onset of daily smoking of 20 years 458 reported they currently have a smoking related health problem 958 had tried unsuccessfully to cut down on their smoking 70 had made a serious attempt to quit smoking 29 Smoking cessation programs for patients with schizophrenia have reported compliance rates as high as 80 30
Nicotinic receptors have been shown to be reduced in number in patients with schizophrenia 31 32 and heavy smoking in schizophrenia may be attributable to attempts to overcome this deficit Benefits of nicotine to patients with schizophrenia include reversal of some of the specific cognitive deficits associated with schizophrenia and antipsychotic treatment 33-37 Nicotine has been shown to improve learning visual and spatial working memory attention auditory sensory gating smooth pursuit eye movements and reaction time 38 39 The positive effects of chronic nicotine treatment appear to persist over time and in some studies improvements in cognition with chronic nicotine treatment become more robust over time 40 Smoking cessation in patients with schizophrenia is associated with increase in positive symptoms 30 Treatment with atypical antipsychotics may enhance the effectiveness of smoking cessation treatment 41-43 The mechanism of this effect is not known but may be due to decreased extrapyramidal side effects improved efficacy for negative symptoms or effects on glutamatergic systems Combination of NRT and antidepressant medication has been shown to increase cessation rates over monotherapy with NRT 44 but not over antidepressant medication alone 45
Nicotine replacement therapy NRT is a powerful aid to smoking cessation with well established efficacy 46-49 in non-psychiatric patients and has been proposed as a potential tool in increasing smoking harm reduction in persons unable to achieve smoking abstinence 50 Smoking cessation outcomes in patients with schizophrenia using NRT have been extremely variable Ziedonis and colleagues used a range of doses of NRT administered by patch gum or combination in addition to CBT for up to 10 weeks in 24 patients with schizophrenia 51 Twelve subjects completed the trial The cessation rate was 13 at 6 months 51 In one study atypical antipsychotic agents in combination with the nicotine transdermal patch have been shown to significantly enhance the rate of smoking cessation 556 in the atypical agent group versus 222 in the typical group 41 In this study the overall end of treatment point prevalence smoking cessation rate in 45 patients with schizophrenia was 35 In another study of the acute effects of transdermal nicotine patch in psychiatric patients however no patients quit smoking acutely and only heavy smokers reduced their cigarette consumption 52
Safety of NRT in patients with schizophrenia has only been evaluated on a very small scale One important trial examined the effects of a 21 mg nicotine patch on smoking behavior nicotine levels in blood and signs of toxicity in patients with schizophrenia 53 In this crossover trial 10 male veterans were monitored while wearing nicotine vs placebo patches The nicotine patch condition was associated with increased nicotine levels without signs of toxicity and decreased CO levels in 80 of patients No trials have reported worsening of psychiatric symptoms with NRT Larger studies in which NRT is combined with behavioral support are needed to evaluate the efficacy and safety of NRT in schizophrenia
Treatment Component
Subjects will be outpatients who are clinically stable and currently in treatment for schizophrenia or schizoaffective disorder Subjects will be recruited through referral from case managers residential treatment settings and outpatient treaters Subjects must smoke 12 pack per day of cigarettes and wish to quit smoking
Subjects will be randomly assigned to receive cognitive behavioral smoking cessation therapy CBT with nicotine patch NRT plus placebo or nicotine patch combined with bupropion SR Subjects who are unable to tolerate or who have a contraindication to treatment with zyban may be enrolled to receive CBT and open label NRT alone All subjects will receive a 12 session group cognitive behavioral therapy CBT program designed for smoking cessation treatment in patients with schizophrenia in addition to pharmacologic treatment
Evaluation Component
The evaluation component of this protocol involves monitoring patients for stability of psychiatric symptoms serum levels of psychiatric medications and medication side effects at baseline and weeks 4 8 12 and 14 and degree of smoking reduction or cessation weekly during the treatment intervention and at 6 12 and 24 months
At baseline subjects will complete a demographic questionnaire Prior to beginning treatment subjects will be evaluated for symptoms of psychosis depression anxiety and medication side effects with standard clinical rating scales that include the schedule for assessment of negative symptoms SANS positive and negative symptom scale PANSS Hamilton depression scale HamD Hamilton anxiety scale HamA abnormal involuntary movement scale AIMS Simpson Angus Scale and SAFTEE A brief cognitive battery will include tests of response inhibition the single trial Stroop vigilance continuous performance test verbal fluency FAS verbal memory California Verbal Learning Test working memory letter number span non-verbal memory Benton visual retention test psychomotor ability grooved peg board task and executive functioning trail making or tower of London Baseline carbon monoxide CO measurements will be used with self report to verify number of cigarettes smoked per day Serum will be drawn for cotinine and antipsychotic levels at baseline Weight will be checked at baseline 12 and 24 weeks
Subjects will set a quit date between weeks 3 and 4 The evaluation battery will be repeated at week 4 just following the quit date It will also be repeated at week 12 when patients discontinue the group and medication treatment An evaluation that includes the clinical battery and CO measurement will be performed at week 14 two weeks following termination of smoking cessation treatment and at week 24 Subjects will also be contacted at 1 and 2 years for follow up self report of tobacco use and CO measurement
Specific Aims Treatment
1 Increase availability of nicotine replacement therapy which is not currently available by prescription to patients with major mental illness
2 Train staff members with expertise in treating patients with major mental illness to be Tobacco Treatment Specialists using the training protocol developed by University of Massachusetts Medical School in collaboration with the Massachusetts Department of Public Health
3 Establish a network of centers able to deliver tobacco treatment to patients with major mental illness
Specific Aims Evaluation
1 Evaluate smoking cessation rates smoking reduction rates and stability of psychiatric symptoms in patients with schizophrenia and schizoaffective disorder during a smoking cessation attempt using cognitive behavioral therapy combined with NRT plus placebo and NRT bupropion SR
2 Evaluate safety of nicotine replacement therapy in patients with schizophrenia and schizoaffective disorder when combined with antipsychotic medications
3 Evaluate safety of nicotine replacement therapy in patients with schizophrenia and schizoaffective disorder when combined with bupropion SR and antipsychotic medications
Hypotheses
1 Nicotine replacement therapy combined with bupropion SR and cognitive behavioral therapy will be associated with improvement in smoking cessation and smoking reduction rates when compared to NRT alone added to CBT in patients with schizophrenia and schizoaffective disorder
2 Nicotine replacement therapy combined with bupropion SR will be associated with improvement in negative symptoms depression and impulsivity when compared to NRT alone in patients with schizophrenia and schizoaffective disorder who quit smoking
3 Concurrent treatment with atypical antipsychotic medications will further enhance the effectiveness of NRT combined with bupropion SR and NRT plus placebo for smoking cessation and reduction in patients with schizophrenia and schizoaffective disorder compared to concurrent treatment with conventional antipsychotics
4 Patients with low baseline cotinine 250 ngml will have higher cessation rates than patients with high baseline cotinine 250 ngml
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None