Nicotine Replacement Therapy for Smoking Cessation in Schizophrenia
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|ClinicalTrials.gov Identifier: NCT00320723|
Recruitment Status : Completed
First Posted : May 3, 2006
Last Update Posted : May 19, 2009
|First Submitted Date ICMJE||April 28, 2006|
|First Posted Date ICMJE||May 3, 2006|
|Last Update Posted Date||May 19, 2009|
|Study Start Date ICMJE||July 2001|
|Primary Completion Date||Not Provided|
|Current Primary Outcome Measures ICMJE
||improvement in smoking cessation and smoking reduction rates when compared to NRT alone added to CBT in patients with schizophrenia and schizoaffective disorder|
|Original Primary Outcome Measures ICMJE
||improvement in smoking cessation and smoking reduction rates when compared to NRT alone added to CBT in patients with schizophrenia and schizoaffective disorder.|
|Current Secondary Outcome Measures ICMJE
||improvement in negative symptoms, depression and impulsivity when compared to NRT alone in patients with schizophrenia and schizoaffective disorder who quit smoking|
|Original Secondary Outcome Measures ICMJE
||improvement in negative symptoms, depression and impulsivity when compared to NRT alone in patients with schizophrenia and schizoaffective disorder who quit smoking.|
|Current Other Pre-specified Outcome Measures||Not Provided|
|Original Other Pre-specified Outcome Measures||Not Provided|
|Brief Title ICMJE||Nicotine Replacement Therapy for Smoking Cessation in Schizophrenia|
|Official Title ICMJE||Nicotine Replacement Therapy Added to Cognitive Behavioral Therapy for Smoking Cessation in Patients With Major Mental Illness|
|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.|
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 U.S. 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; 45.8% reported they currently have a smoking related health problem; 95.8% 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 (55.6% in the atypical agent group versus 22.2% 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.
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 =1/2 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.
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
Specific Aims: Evaluation
|Study Type ICMJE||Interventional|
|Study Phase ICMJE||Phase 4|
|Study Design ICMJE||Allocation: Randomized
Intervention Model: Parallel Assignment
Primary Purpose: Treatment
|Intervention ICMJE||Drug: bupropion, transdermal nicotine patch|
|Study Arms ICMJE||Not Provided|
|Publications *||Not Provided|
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
|Recruitment Status ICMJE||Completed|
|Original Enrollment ICMJE||Same as current|
|Study Completion Date ICMJE||December 2005|
|Primary Completion Date||Not Provided|
|Eligibility Criteria ICMJE||
|Ages ICMJE||18 Years to 70 Years (Adult, Older Adult)|
|Accepts Healthy Volunteers ICMJE||No|
|Contacts ICMJE||Contact information is only displayed when the study is recruiting subjects|
|Listed Location Countries ICMJE||United States|
|Removed Location Countries|
|NCT Number ICMJE||NCT00320723|
|Other Study ID Numbers ICMJE||DMH CORRC 20-01|
|Has Data Monitoring Committee||Not Provided|
|U.S. FDA-regulated Product||Not Provided|
|IPD Sharing Statement ICMJE||Not Provided|
|Responsible Party||A Eden Evins, MD, MPH, Massachusetts General Hospital|
|Study Sponsor ICMJE||North Suffolk Mental Health Association|
|Collaborators ICMJE||Not Provided|
|PRS Account||North Suffolk Mental Health Association|
|Verification Date||May 2009|
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP