Trial Information

Randomized Trial of a Smoking Cessation Program for Persons With SMI

Smoking is the leading cause of preventable death in the United States. Smoking contributes
to increased rates of diseases such as lung cancer and heart disease, and adds dangerous
complications to health problems such as diabetes and obesity. Despite widespread
recognition of the devastating health effects of smoking, over 70% of people with
schizophrenia and other serious and persistent mental illnesses (SPMI) smoke cigarettes, a
rate that is at least double that of the general population and remains high despite
decreases in rates of smoking in the general population. These extraordinary smoking rates
contribute to elevated morbidity and mortality, have other life-threatening health-related
consequences, and increase health care costs for treating smoking related illnesses in this
population. Treating smoking is critical in improving the health of people with SPMI.

The newly revised VA/Department of Defense Clinical Practice Guideline for the Management of
Tobacco Use 1 outlines the VHA's comprehensive program for smoking cessation. Beginning in
1997, the VA central office directed that the AHCPR smoking cessation guideline (the 5 A's -
Ask, Advise, Assess, Assist, Arrange) be implemented in all its health care facilities.
Reinforcing their commitment to increasing veterans' access to evidence-based smoking
cessation interventions, the VHA recently released a new policy mandating that smoking
cessation treatment be made available without restriction at all VA sites2. Our previous
study implementing the 5A's in community mental health clinics has found reduced smoking and
increased use of smoking cessation aids such as nicotine replacement therapy (NRT), but no
only modest increases in abstinence. Implementation of the 5 A's was limited by inability to
adequately assist patients to stop smoking.

Consideration of how best to supplement the "Assist" and "Arrange" phases reveals the
troubling observation that existing "best practice" treatments for smoking cessation have
limited effectiveness for persons with SPMI. The most widely tested treatments consist
generally of adaptations of American Lung Association (ALA) or comparable 10-14 session
weekly groups supplemented by either nicotine replacement therapy (NRT) or Bupropion. Such
programs produce low abstinence rates (0-25%) at end of intervention. Sustained abstinence
is virtually non-existent. Abstinence at 6-month or 1-year follow-up points ranges from
0-10%.

These findings have led us to consider alternative approaches that have shown greater
promise in overcoming the specific barriers that persons with SPMI face in achieving
abstinence from other addictive substances. We have developed an intervention the treatment
of cocaine and heroin use disorders among persons with SPMI, called Behavioral Treatment for
Substance Abuse in Serious and Persistent Mental Illness (BTSAS). BTSAS was developed with a
series of NIDA-funded treatment development grants as a treatment program for substance
abuse that accommodated the cognitive and motivational impairments that characterize SPMI.
The goal was to incorporate strategies that have been found to be effective in reducing drug
use more generally, but to tailor them to meet the needs of people with SPMI. BTSAS provides
a model for this application's test of an innovative smoking cessation treatment. Our basic
premise is that we must first acknowledge nicotine dependence as an addiction with
characteristics common to other substance addictions, and then specify the additional
biological, social, cognitive, psychological and environmental barriers to quitting smoking
for people with SPMI. We must then fully optimize available technologies for addiction in
general and smoking cessation in particular to address these deficits. Existing approaches
to smoking cessation for persons with SPMI do not use the full range of biological,
contingency management, social modeling and behavioral tools that have been shown to work in
treating other addictions in this population. Further, research on treatment of substance
use disorders in persons with SPMI has suggested that, for best outcomes, interventions may
need to be more intensive that what is provided for other groups of substance abusers.
Applied to smoking, this suggests that for people with SPMI, smoking cessation may need to
be more intensive than the 9 weekly sessions typical of conventional smoking cessation
programs.

Based on our work developing BTSAS, and the above features of smoking in SPMI, we have
developed an intervention called Behavioral Treatment of Smoking Cessation in SPMI (BTSCS),
an innovative intervention that supplements pharmacotherapy and education with contingency
management and a multifaceted behavioral group treatment program that lasts for three months
(24 sessions). BTSCS is designed to address the cognitive, motivational, and social support
problems characteristic of people with SPMI. We propose to conduct a randomized clinical
trial comparing BTSCS to a standard smoking cessation treatment.

Specific Aims: To determine if BTSCS is more effective in producing abstinence from smoking
than a manualized smoking cessation program that reflects current best practices (StSST).

Hypothesis 1: BTSCS will result in greater rates of abstinence than StSST as shown by:

1. A higher percentage of negative expired carbon monoxide levels at biweekly treatment
sessions

2. Increased days of abstinence reported at biweekly treatment sessions

3. A higher percentage of negative expired carbon monoxide levels immediately
post-treatment.

4. A higher percentage of participants reporting abstinence in the 7-day interval
preceding the post-treatment assessment.

Secondary Aims: We will assess the effectiveness of BTSCS on a set of intermediate outcomes
including a reduction in smoking severity and improvement in readiness to quit smoking among
smokers who have not been able to quit. We will also assess if increased treatment
attendance and use of NRT's and bupropion moderate the hypothesized increases in abstinence.

To determine if BTSCS is more effective at the 6- and 12-month assessments in producing
abstinence from smoking than a manualized smoking cessation program (StSST) that reflects
current best practices.

Exploratory analyses will examines costs and identify moderators of abstinence, and examine
whether BTSCS is more or less useful with participants from different diagnostic categories.

D.1. Overview. This application proposes a randomized trial for persons with SPMI that
compares (1) BTSCS: a 6-month manualized smoking cessation program adapted from an effective
substance abuse treatment program for this population to (2) StSST: a standard ALA-based
manualized smoking cessation program which reflects current best practices.

D.2. Description of Treatment Conditions D.2.1. General procedures. Treatment groups will be
matched for time and location. Both conditions will offer 2 treatment groups per week for 3
months (24 sessions total). Groups will take place at the Baltimore and Perry Point VAMCs.
There are several procedures that represent good clinical practice in SPMI and will be used
in both conditions.

Outreach. All participants will receive a brief period of outreach to ensure that they
engage in whichever intervention they are assigned. This is important in terms of testing
our study hypotheses - we must avoid a situation in which a lack of treatment engagement in
one group or the other precludes our ability to test the effectiveness of the interventions.
Engagement-oriented outreach will begin when the participant has completed baseline
assessments, last for no more than 2 weeks, be done by the group therapist, and focus on
getting the participant to attend the first group, following which the outreach will end.
This brief, engagement-focused outreach will include: (1) The group therapist will meet the
participant at the end of the baseline assessment and provide contact information in case
there are any group-related questions; (2) The group therapist will provide a reminder call
to the participant the day before the first group; (3) The group therapist will inform the
participant's treatment team that he/she will be attending the study group and the date of
the first group; (4) If the participant misses the first group, the group therapist will
call the participant and inform him/her of the date and time of the next group, and then
provide a reminder call the day before this group; (5) Step 4 will be repeated if the
participant misses the second scheduled group time permitting (i.e. if there is still time
within the 2-week window).

Medications for smoking cessation. Participants in both conditions will receive general
educational material about the usefulness of FDA approved medications, specifically
bupropion and some form of nicotine replacement therapy (NRT), to aid in smoking cessation.
Group leaders will refer interested participants to the study physician's assistant (SPA)
who will arrange a meeting before or after group. The SPA, with consultation, as needed from
Dr. Fischer, will conduct a pre-medication evaluation and provide information about
available aids, education about the risks and benefits of the chosen aid, prescription
writing, and follow-up regarding side-effects as part of an ongoing clinical assessment. The
SPA will also communicate with the participant's psychiatrist and ensure that there is no
additional relevant information or contra-indication to the use of NRT or bupropion. With
regard to the prescription of bupropion, the SPA will exclude participants with a history of
seizures or disorders that put them at increased risk of having a seizure, including a
current eating disorder and alcohol dependence. Additionally, participants with a history
of polydipsia will be given a spot sodium test to rule out hyponatremia that could put them
at increased risk of seizures. Those participants with hyponatremia will be required to show
two normal consecutive sodium levels before they can be prescribed bupropion. The SPA will
assume responsibility for monitoring the use of bupropion for participants who are already
prescribed the drug. During the initial assessment period, the SPA will review the available
NRT products and teach the participant how to use the form of NRT chosen. NRT will be
dispensed by the SPA who will counsel the participant to begin to use the NRT on their quit
date. Bupropion prescriptions will be written by the SPA, and participants will be counseled
to start the medication at least 2 weeks prior to the targeted quit date. Dosing will be
initiated at 150mg in the morning for seven days with an increase to 150mg twice daily, if
the participant tolerates the initial dose. For participants who experience the common
side-effects of agitation, anxiety or insomnia, the dose will be decreased to100mg in the
morning with attempts to increase the dose at weekly intervals until the target dose of
150mg twice daily is reached. Participants who agree to use either NRT or bupropion will be
seen by the SPA weekly until two weeks after the target dose is reached, and then they will
be seen monthly for the remainder of the study. At either the participant's or group
leader's request, the SPA will be available to provide clinical assessment at anytime during
the course of the study, with consultation provided by Dr. Dixon.

There is some evidence that women may respond differently to NRT than men. Some research
suggests that outcomes may be poorer for women than for men treated with NRT, possibly
because women experience more severe withdrawal symptoms and report poorer compliance with
NRT80-81.

In the present study, NRT is not a required component of participation. For those who select
to use it, use of NRT will be supported: participants will be taught how to use it properly
and problems will be addressed immediately. These strategies may reduce poor compliance in
women. As reviewed above, bupropion is also an option that participants will be educated
about, and there is data suggest that nonnicotine pharmacotherapies such as bupropion have
equivalent efficacy for women and men80.

In addition to bupropion and NRT, the FDA has approved varenicline (Chantix) for smoking
cessation in the general population. There have been three studies of varenicline in healthy
normal controls (two double-blind, placebo-controlled studies comparing varenicline to both
bupropion and placebo82-83, and one study reporting long-term follow-up data84) which have
found that varenicline promotes smoking abstinence and is associated with higher continuous
abstinence rates. To date, there has been one study varenicline in smokers with mental
illness85. Results showed no extraordinary adverse reactions to varenicline in the sample.
Participants with mental illness showed equivalent quit rates as those without mental
illness. Because the safety and efficacy of varenicline in SPMI is not fully established, we
are not including varenicline in the medication education component of this application. The
goal is to support use of any medications for smoking cessation that participants are using;
participants who are taking varenicline as prescribed by their physician are eligible to
participate, and we would assist the client with varenicline use as we would other
medications.

To monitor participant adherence to bupropion and NRT, the SPA will meet with each
participant before or after group to record the start date and dose of bupropion and/or NRT
and/or the number of unused pills, patches, and/or pieces of gum. If participants forget to
bring their medication bottle, packet, etc, the research assistant will remind the
participant to bring it to the next session. We have used this procedure in previous trials
and have found it to be a reliable procedure to monitor medication adherence. Participants
receiving 75% of the assigned medication will be considered adherent. The 75% criterion
ensures that participants will receive adequate treatment to evaluate the efficacy of
medication.

Treatment engagement and retention. Procedures to enhance engagement and retention will
include: (1) All participants will receive $3.00 as an incentive for group attendance; (2)
We will not require a commitment to abstinence for participation (see below for rationale);
(3) When possible, we will enlist the help of a significant other to encourage attendance,
remind participants of appointments, and serve as a contact person if the client is not
compliant; and (4) We will provide frequent telephone and mail contacts, and clinicians will
immediately contact participants following missed groups.

Rolling admission. To minimize delay in entering participants into groups, we will employ
open enrollment and begin a new group whenever enrollment exceeds 6 participants.
Participants can enter a group at any point during the 3 months; participants within a group
will differ in terms of their length of time in the group. Open enrollment allows us to
recruit on an ongoing basis (in contrast to recruiting only when we are planning to begin a
new cohort) and enter participants more quickly, reducing attrition of consenting
participants. While rolling admission does not allow us to examine the effect of group
make-up on outcome, in the proposed study we are interested in the acceptability of the
treatment overall, not the acceptability of the particular group a participant might be
assigned to one point in time. Our experience with open enrollment in NIAAA and NIDA
treatment trials suggests that the process will be seamless. Both BTSCS and StSST are
designed to be tailored to individual needs (see below for a more in-depth description), and
length of time in group is one such factor.

Harm reduction approach. Abstinence is generally viewed as the most appropriate goal for
primary substance abusers, and it has been suggested that it is the most appropriate goal
for SPMI clients56. Nevertheless, abstinence is not a viable goal for all clients who enter
treatment177-178. We will adopt a harm reduction approach48, 179 and promote abstinence but
not demand it as a precondition for participation. This approach is well-suited to this
population. The impairments associated with SPMI make behavior change difficult. Overall
change is best conceptualized as a long-term process with many components, some of which
have little to do with smoking per se. For example, many participants need time to feel
comfortable interacting with new people. Reductions in smoking made at any point in this
process are significant, and may bring a client closer to abstinence. For those who are
working towards abstinence, we attempt to build self-efficacy, reinforce reductions in the
frequency and intensity of smoking, and teach skills that will support efforts at
abstinence.

D.2.2. Description of BTSCS components. BTSCS is an innovative treatment that supplements
pharmacotherapy and education with contingency management and a multifaceted behavioral
group intervention. BTSCS aims to help SPMI smokers increase motivation to quit, reinforce
behaviors that bring one closer to change, and provide direct and active assistance in
attending study groups and other clinic appointments. The focus of training is on behavior -
teaching effective skills to reduce smoking and cigarette consumption - rather than
psychological processes (will power). BTSCS emphasizes positive reinforcement (social,
financial), and avoids overt or implied censure or criticism. The medium for change is
skills training and behavioral rehearsal, rather than discussion or isolated support. In
each segment of the intervention, participants are taught new skills for reducing smoking
and managing mood states or situations that accompany smoking, and provided an opportunity
to practice these skills in a warm and positive atmosphere. Feedback is provided in a
positive way, participants are not criticized or blamed for lack of progress, any progress
(reduction or cessation) is reinforced, and goals are tailored for individuals at different
motivational levels. BTSCS lasts 3 months, includes two 60-minute group sessions per week
(24 sessions total), and is delivered in small groups of 4-8 participants run by a trained
therapist (see below). The intervention is manualized and closely supervised to enhance
consistency across therapists and within therapists over time. BTSCS is designed
specifically to address the cognitive, motivational, and social support problems that are
characteristic of people with SPMI and serve as barriers to effective smoking cessation
treatment. Efforts are made to minimize the demand on cognitive abilities (e.g., attention
and memory); and there is active planning to foster generalization to the community. The
small group format allows for individual tailoring of training procedures and behavioral
rehearsal.

Individualized approach. BTSCS is tailored to the individual needs and motivational levels
of participants. Given that level of motivation to quit smoking, as well as actual smoking
status, will vary among participants, BTSCS will serve a heterogeneous population of smokers
with SPMI and so must have the flexibility to be relevant to their differing treatment
needs. While each session has a specific topic to be discussed, the content within the
session is adjusted to meet the needs of each participant. Content during the Stop Smoking
Strategies component will differ depending on whether the participant has quit smoking, is
attempting to quit, or is ambivalent about quitting smoking. Additionally, BTSCS includes
individualized goal-setting at the start of each session. Reinforcement for all participants
is based on their individual accomplishments and goals, rather than reinforcing only smoking
cessation (i.e. some may be reinforced for quitting, others for attending BTSCS groups,
others for reducing the number of cigarettes smoked between sessions). Overall, BTSCS
sessions and topics follow a pre-determined order, but the intervention is flexible such
that topics can be reviewed when any participant requires it.

Motivational enhancement (ME). Motivational Interviewing is widely employed as a technique
for increasing motivation to reduce substance use53, and a variation (Motivational
Enhancement Therapy) was one of the primary interventions in Project Match54. Our approach
is connected with Miller and Rollnick's (1991)55 innovative work. However, there are a
number of differences between our approach to ME and Motivational Interviewing. The more
exclusively open-ended, reflective approach to self-exploration central to Miller and
Rollnick's approach can be problematic for many people with SPMI, given their problems with
abstraction, introspection, and other higher level cognitive processes. We have adapted our
ME to include a more directive approach to helping patients toward recognition of one or a
few key factors that can serve as motivators for smoking cessation. For the most part, these
focal issues involve concrete, negative circumstances, such as health problems that are due
to or worsened by smoking, and the ongoing and increasing monetary costs of smoking. The
therapist is respectful but active in reminding the participant of problems identified
during pre-treatment assessments, rather than being more reactive and waiting for the
participant to come to her own realization of how smoking has harmed her. ME is incorporated
into the intervention in several ways. First, we will conduct an individual ME session
during the first week of treatment, in order to help participants think about individual
reasons for smoking cessation. This ME session concludes with a written contract for a
concrete, short term cessation-related goal and specific steps required to achieve the goal.
Second, we use an ME approach, including using feedback and supporting self efficacy and
responsibility for change, throughout the intervention. The difficulty in quitting will be
openly discussed, and therapists will work with participants to develop a plan for coping
with low motivation. Therapists routinely will check in with participants concerning
progress with their smoking, reward any behaviors that move the participant towards
cessation, and assist participants when motivation wanes. Participants are accepted and
welcomed into the intervention group and their attendance is rewarded regardless of smoking
status, and the group is designed to help break the process of smoking cessation down into
smaller and more achievable steps that are rewarded when accomplished. Third, we add a
number of additional techniques and strategies, such as contingency management and saving
money not spent on cigarettes for other purchases (both described below), designed to boost
motivation in very concrete ways. Fourth, we incorporate an active, concerned, empathic
outreach approach that includes frequent reminder calls, calls following missed sessions,
linking with the participant's treatment team to ensure attendance at clinic appointments,
problem-solving practical issues such as transportation and other barriers that block
treatment attendance, and active helping with other problems that impact smoking.

Contingency management procedures and goal-setting. The contingency management and
goal-setting components of BTSCS are designed to reward any reductions in smoking and to
help participants establish and achieve concrete, short-term abstinence or reduction goals.
Contingency management procedures (CM) have been used to address poor treatment attendance
(common among individuals with low motivation to change) by reinforcing attendance and
short-term behavior change in high-risk samples56. CM procedures and voucher-based
incentives have been shown to be beneficial in reducing substance use in samples of primary
substance abusers56-59, and those with dual disorders60, as well as in non-SPMI smokers61,
62. CM procedures will be implemented at the beginning of each session. The CM portion of
our intervention is designed to reward any reductions in smoking. We have used a similar CM
procedure very effectively in our drug abuse treatment studies. Participants will be tested
on site with EC50 Micro III Smokerlyzer Breath CO Monitor63, and the results will be told to
the participant immediately. Participants who test less than 10 ppm indicating no smoking
during the last six hours receive social and financial reinforcement. We do not expect this
modest reinforcer to be sufficient to drive behavior change on its own, but the combination
of money coupled with social reinforcement and public attention to smoking is intended to:
a) provide a tangible reward for success, b) increase the salience of goals for reduced use,
and c) secure a valid report of recent smoking for guiding targeted coping skills training
(e.g., participants cannot simply say they are doing well and not smoking). The financial
reinforcer will begin at $1.50 and is increased by $0.25 (to a maximum of $3.50) each time
the participant achieves negative tests in 2 successive scheduled sessions, and is reset to
$1.50 after a positive result. In addition, the way that the CM procedures are conducted
includes providing both financial and social reinforcement, including applause, praise, and
support for negative breath tests. Our drug treatment studies suggest that these displays of
support and encouragement from the group are experienced as positive and reinforcing for
participants and encourage the development of peer support.

Goal-setting will follow the contingency at the start of each group session. Participants
will collaborate with the therapist to create a concrete goal to work on between sessions.
Often these goals will involve attempting smoking cessation from one group to the next.
Other times participants who are not yet ready or able to commit to smoking cessation will
develop goals such as reducing smoking, saving money rather than spending it on cigarettes,
or simply attending the next treatment session. Goals will always be written down in a
formal "contract" that is signed by both parties and the participant is given a copy to
keep. Goals will be reviewed at the start of each group session, success will be reinforced,
and failures will be responded to with problem solving and encouragement.

Stop smoking strategies. Skills for reducing smoking will include planning for a quit date;
ways to cope with cravings, weight gain, and other potential side effects from quitting; and
identifying triggers to smoking and ways to cope with these triggers. Participants will be
encouraged to keep savings accrued from fewer purchases of cigarettes in either a bank
account or some other place and to use these savings periodically to purchase other desired
goods. Opportunity is built into the structure of the group to check in about symptoms, to
assess whether the stress of smoking reduction is causing exacerbations, and to monitor for
the emergence of new side-effects related to changes in drug blood levels. In addition,
participants will learn coping skills to address the dysphoria, depression, anxiety, and
boredom that play a significant role in smoking SPMI patients. Coping skills training will
be used to teach patients strategies for coping with negative affective states (depression,
stress, medication symptoms and side effects) without smoking. We will also teach a muscle
relaxation strategy based on guidelines for self-control relaxation provided by Lichstein
(1988)64. We will use modeling and rehearsal to teach a few elemental cognitive and
interpersonal techniques: Defining and identifying habits, cravings, and triggers for
smoking, (2) Defining and identifying high-risk smoking situations, (3) Defining and using
avoidance and escape to cope with high-risk smoking situations, (4) Coping with depression
without smoking, (5) Coping with anxiety and stress without smoking, (6) Coping with other
forms of negative affect without smoking, (7) Coping with low motivation to quit, (8) Coping
with boredom without smoking, (9) Coping with symptoms of mental illness without smoking;
(10) Coping with medication side effects without smoking, (11) Coping with other high-risk
smoking situations (being around others who are smoking, while drinking coffee, first waking
up in the morning); (12) Coping with cravings for cigarettes; (13) Coping with side effects
of smoking cessation including irritability, weight gain, and no longer being a smoker. Each
training session will involve a discussion of the specific negative affective state, how to
recognize this affective state, and creating a plan to cope with the particular form of
negative affect when it occurs. In addition, most participants have a number of "high risk"
situations in which they have much more difficulty coping without smoking. Each participant
will be helped to identify the 3-4 most risky situations for him/her through group
discussion. We will then use problem solving to teach participants how to anticipate these
situations and help them identify specific ways to cope with them. They will be given note
cards to help them remember their high-risk situations and the behavioral alternatives, and
they will be prompted about the items in subsequent sessions. The goal will be to identify
specific risks and solutions, rather than teach a generic strategy. Once again, our premise
is that people with SPMI are not likely to initiate or effectively implement a multi-step
problem solving routine in the face of real life pressures, but they can benefit from a
circumscribed strategy that involves few choices and makes modest demands on executive
functions. The aim is to teach about the persistence of high-risk situations, to help the
identify situations that will be risky, and to devise coping strategies.

Social skills training. SST is designed to help participants engaged in social interactions
that do not involve smoking, as well as reduce interpersonal conflict that might lead to
stress and other negative affect that leads to smoking. We include units on basic
conversational skills, including beginning and ending conversations, asking open-ended
questions, giving personal information, and making "I" statements. We believe that a
primary reason why traditional assertion skills do not generalize to the community is
because patients often experience assertion as anxiety provoking and find it safer to escape
from or avoid situations that involve even minor confrontations. However, avoidance and
escape may, themselves, result in increased conflict and stress. Consequently, we focus on
skills that serve to decrease conflict and arousal, including compromise, giving reasons,
and making requests. We also teach participants how to make "graceful" exits from stressful
or unpleasant situations. Two points should be noted about the SST component. As noted
earlier, the SST component of BTSCS, like the rest of the intervention, is tailored to the
needs and abilities of each participant. Hence, the specific content will vary across
participants, according to what each participant needs to learn or practice. Second,
treatment is consistently focused on smoking cessation. The SST component is not designed to
resolve all social skill deficits. Rather, it addresses social skills specifically relevant
to smoking cessation. In that regard, the literature on behavior change and our experience
with BTSAS indicates that public declarations of intentions to change (i.e., reduce smoking)
can be an important factor. Therefore, a major aspect of SST will be on rehearsal of public
declarations about smoking goals. Further, an important aspect of the role play is increased
self-efficacy for both making public declarations and in refusing/avoiding cigarettes.