Is the Effect of Anhedonia on Smoking Cessation Greater for Women Versus Men?

INTRODUCTION: Anhedonia has been recognized as a major risk factor for smoking persistence. Potential gender differences in the effect of anhedonia on smoking cessation have not been studied. Using data from a completed clinical trial of maintenance nicotine patch therapy, we hypothesized that gender would moderate the effect of anhedonia on short-term abstinence, such that anhedonic women would be less likely to achieve abstinence. METHODS: Participants (N = 525; 50% female, 48.2% Black/African American, average age: 46 years) received 21mg/day nicotine patch and four brief behavior counseling sessions over 8 weeks. Participants were classified at baseline using the Snaith-Hamilton Pleasure Scale as anhedonic (scores > 2) or hedonic (scores ≤ 2). Bioverified 7-day point prevalence abstinence was measured at week 8. Using logistic regression analysis, we tested the interaction of anhedonia by gender predicting abstinence, adjusting for age, race, nicotine dependence, and baseline depressive symptomatology. RESULTS: Seventy participants (13%) were classified as anhedonic. Men were more likely to be anhedonic than women (16.6% vs. 10.2%, p = .03). Contrary to our hypothesis, the interaction of anhedonic status (hedonic vs. anhedonic) by gender was nonsignificant (p = .18). There was a main effect of hedonic capacity, such that anhedonia predicted abstinence, odds ratio = 3.24, 95% confidence interval = 1.39-7.51, p = .006. CONCLUSION: Both male and female anhedonic smokers were more likely to be abstinent, which contrasts with prior research indicating that anhedonia is a risk factor for difficulty quitting. This unexpected finding may be explained by a possible selective benefit of nicotine patch therapy, which has been observed in some studies to have antidepressant effects. IMPLICATIONS: This is the first study to examine whether the association between pretreatment anhedonia and smoking cessation differs by gender. For both women and men, anhedonia was associated with a greater likelihood of abstinence after 8 weeks of treatment with 21mg/day nicotine patch and behavior counseling. Our findings indicate that the association between anhedonia and smoking cessation is not as clear as has been assumed and may depend in part on the type of treatment delivered.

A placebo-controlled randomized clinical trial of naltrexone in the context of different levels of psychosocial intervention.

BACKGROUND: Naltrexone is approved for the treatment of alcohol dependence when used in conjunction with a psychosocial intervention. This study was undertaken to examine the impact of 3 types of psychosocial treatment combined with either naltrexone or placebo treatment on alcohol dependency over 24 weeks of treatment: (1) Cognitive-Behavioral Therapy (CBT) + medication clinic, (2) BRENDA (an intervention promoting pharmacotherapy) + medication clinic, and (3) a medication clinic model with limited therapeutic content. METHODS: Two hundred and forty alcohol-dependent subjects were enrolled in a 24-week double-blind placebo-controlled study of naltrexone (100 mg/d). Subjects were also randomly assigned to 1 of 3 psychosocial interventions. All patients were assessed for alcohol use, medication adherence, and adverse events at regularly scheduled research visits. RESULTS: There was a modest main treatment effect for the psychosocial condition favoring those subjects randomized to CBT. Intent-to-treat analyses suggested that there was no overall efficacy of naltrexone and no medication by psychosocial intervention interaction. There was a relatively low level of medication adherence (50% adhered) across conditions, and this was associated with poor outcome. CONCLUSIONS: Results from this 24-week treatment study demonstrate the importance of the psychosocial component in the treatment of alcohol dependence. Moreover, results demonstrate a substantial association between medication adherence and treatment outcomes. The findings suggest that further research is needed to determine the appropriate use of pharmacotherapy in maximizing treatment response.

A placebo-controlled trial of modafinil for nicotine dependence.

BACKGROUND: Nicotine deprivation symptoms, including fatigue and attentional deficits, predict relapse following smoking cessation. Modafinil (Provigil), a wakefulness medication shown to have efficacy for the treatment of cocaine addiction, was tested as a novel therapy for nicotine dependence in a double-blind placebo-controlled trial. METHODS: One hundred and fifty-seven treatment-seeking smokers received brief smoking cessation counseling and were randomized to: (1) 8 weeks of modafinil (200mg/day), or (2) 8 weeks of placebo. The primary outcome was biochemically verified 7-day point prevalence abstinence at the end of treatment (EOT). Secondary outcomes included cigarette smoking rate and post-quit nicotine deprivation symptoms (e.g., negative affect, withdrawal). RESULTS: In this interim study analysis, EOT quit rates did not differ between treatment arms (42% for placebo vs. 34% for modafinil; OR=0.67 [0.34-1.31], p=0.24). Further, from the target quit date to EOT, the daily smoking rate was 44% higher among non-abstainers in the modafinil arm, compared to non-abstainers in the placebo arm (IRR=1.44, CI95=1.09-1.89, p<0.01). Modafinil-treated participants also reported greater increases in negative affect and withdrawal symptoms, vs. participants randomized to placebo (ps<0.05). CONCLUSIONS: These data do not support the use of modafinil for the treatment of nicotine dependence and, as a consequence, this trial was discontinued. Cigarette smoking should be considered when modafinil is prescribed, particularly among those with psychiatric conditions that have high comorbidity with nicotine dependence.

Why do those who request smoking treatment fail to attend the first appointment?

As part of a larger trial of pharmacological and counseling interventions for light smokers, we performed a telephone-screening interview followed by a scheduled time for an in-person eligibility appointment. Of the 407 who screened positive and expressed interest in participation, 202 failed to attend the first scheduled appointment. This article examines person, study, and study-site characteristics that differentiated those who did follow through from those who did not. The study also examined the self-reported quit rates of both groups 12 weeks later, the time of the study termination. Analyses suggested that nonattendees were more likely to be younger, unemployed, and African American. The most frequently cited reasons for missing the eligibility appointment were work/family obligations, inconvenient appointment times, and personal schedule problems. Those who kept the initial appointment were more likely to report smoking abstinence at 12 weeks. The study has implications for increasing the utilization of potentially effective treatments for smokers.

Concurrent varenicline and prolonged exposure for patients with nicotine dependence and PTSD: A randomized controlled trial.

BACKGROUND: Prevalence of smoking among individuals with posttraumatic stress disorder (PTSD) is disproportionately high, and PTSD is associated with especially poor response to smoking cessation treatment. OBJECTIVE: The current study examined whether integrating treatments for smoking cessation (varenicline plus smoking cessation counseling; VARCC) and PTSD (prolonged exposure therapy; PE) enhances smoking outcomes among smokers diagnosed with PTSD. METHOD: 142 adults with nicotine dependence (ND) and PTSD were randomized to a treatment program consisting of varenicline, smoking cessation counseling, and PE (VARCC + PE) or to VARCC only. Seven-day point prevalence abstinence (PPA) at posttreatment (3-months postquit day) and follow-up (6-months postquit day), verified by serum cotinine levels and exhaled carbon monoxide, was the primary smoking outcome. Psychological outcomes were PTSD and depression severity. Mixed effects models included baseline PTSD severity as a moderator of treatment condition effects. RESULTS: Overall, VARCC + PE participants did not show greater PPA than VARCC participants. However, treatment effects were moderated by baseline PTSD severity. For participants with moderate and high PTSD severity, VARCC + PE led to significantly higher PPA than VARCC alone (ps<.05). No differences between treatment conditions emerged for participants with low baseline PTSD severity. Participants who received PE showed significantly greater reduction of PTSD and depression symptoms than those who did not receive PE. CONCLUSIONS: Integrating psychological treatment for PTSD and smoking cessation treatment enhances smoking cessation for participants with moderate or severe PTSD symptom severity, but does not enhance smoking cessation for participants with low baseline PTSD severity. (PsycINFO Database Record

A double-blind, placebo-controlled trial of amantadine, propranolol, and their combination for the treatment of cocaine dependence in patients with severe cocaine withdrawal symptoms.

BACKGROUND: This trial evaluated the efficacy of amantadine, propranolol and their combination in cocaine dependent patients with severe cocaine withdrawal symptoms. METHODS: Cocaine withdrawal symptom severity was measured by the cocaine selective severity assessment (CSSA). One hundred and ninety-nine patients with high scores on the CSSA participated in a 10-week double-blind trial. Patients were randomly assigned to receive amantadine (300 mg/day), propranolol (100mg/day), a combination of amantadine (300 mg/day) and propranolol (100mg/day) or matching placebo capsules. The primary outcome measure was cocaine abstinence. RESULTS: In the intent-to-treat sample, there were no significant differences between the four medication groups in treatment retention. The odds of cocaine abstinence showed a marginally significant increase over time in the propranolol group (p=0.06) but not in the other three groups. In highly medication-adherent patients, treatment retention was significantly better in the propranolol group compared to the placebo group (p=0.01) and the odds of cocaine abstinence increased significantly over time in the propranolol group but not in the other three groups. CONCLUSION: In the intent-to-treat sample, none of the three active treatments (propranolol, amantadine or their combination) was significantly more effective than placebo in promoting abstinence from cocaine among patients who entered treatment with more severe cocaine withdrawal symptoms. Among patients highly adherent to study medication, propranolol treatment was associated with better treatment retention and higher rates of cocaine abstinence compared to placebo.

Rate of nicotine metabolism and smoking cessation outcomes in a community-based sample of treatment-seeking smokers.

BACKGROUND: In samples from controlled randomized clinical trials, a smoker's rate of nicotine metabolism, measured by the 3-hydroxycotinine to cotinine ratio (NMR), predicts response to transdermal nicotine. Replication of this relationship in community-based samples of treatment-seeking smokers may help guide the implementation of the NMR for personalized treatment for nicotine dependence. METHODS: Data from a community-based sample of treatment seeking smokers (N=499) who received 8weeks of transdermal nicotine and 4 behavioral counseling sessions were used to evaluate associations between the NMR and smoking cessation. Secondary outcomes included withdrawal and craving, depression and anxiety, side effects, and treatment adherence. RESULTS: The NMR was a significant predictor of abstinence (OR=.56, 95% CI: 0.33-0.95, p=.03), with faster metabolizers showing lower quit rates than slower metabolizers (24% vs. 33%). Faster nicotine metabolizers exhibited significantly higher levels of anxiety symptoms over time during treatment, vs. slower metabolizers (NMR x Time interaction: F[3,357]=3.29, p=.02). NMR was not associated with changes in withdrawal, craving, depression, side effects, and treatment adherence (p's>.05). CONCLUSIONS: In a community-based sample of treatment-seeking smokers, faster nicotine metabolizers were significantly less likely to quit smoking and showed higher rates of anxiety symptoms during a smoking cessation treatment program, vs. slower nicotine metabolizers. These results provide further evidence that transdermal nicotine is less effective for faster nicotine metabolizers and suggest the need to address cessation-induced anxiety symptoms among these smokers to increase the chances for successful smoking cessation.

Long-term nicotine replacement therapy: a randomized clinical trial.

IMPORTANCE: The US Food and Drug Administration adopted labeling for nicotine patches to allow use beyond the standard 8 weeks. This decision was based in part on data showing increased efficacy for 24 weeks of treatment. Few studies have examined whether the use of nicotine patches beyond 24 weeks provides additional therapeutic benefit. OBJECTIVE: To compare 8 (standard), 24 (extended), and 52 (maintenance) weeks of nicotine patch treatment for promoting tobacco abstinence. DESIGN, SETTING, AND PARTICIPANTS: We recruited 525 treatment-seeking smokers for a randomized clinical trial conducted from June 22, 2009, through April 15, 2014, through 2 universities. INTERVENTIONS: Smokers received 12 smoking cessation behavioral counseling sessions and were randomized to 8, 24, or 52 weeks of nicotine patch treatment. MAIN OUTCOMES AND MEASURES: The primary outcome was 7-day point prevalence abstinence, confirmed with breath levels of carbon monoxide at 6 and 12 months (intention to treat). RESULTS: At 24 weeks, 21.7% of participants in the standard treatment arm were abstinent, compared with 27.2% of participants in the extended and maintenance treatment arms (χ(2)(1) = 1.98; P = .17). In a multivariate model controlled for covariates, participants in the extended and maintenance treatment arms reported significantly greater abstinence rates at 24 weeks compared with participants in the standard treatment arm (odds ratio [OR], 1.70 [95% CI, 1.03-2.81]; P = .04), had a longer duration of abstinence until relapse (ß = 21.30 [95% CI, 10.30-32.25]; P < .001), reported smoking fewer cigarettes per day if not abstinent (mean [SD], 5.8 [5.3] vs 6.4 [5.1] cigarettes per day; ß = 0.43 [95% CI, 0.06-0.82]; P = .02), and reported more abstinent days (mean [SD], 80.5 [38.1] vs 68.2 [43.7] days; OR, 1.55 [95% CI, 1.06-2.26]; P = .02). At 52 weeks, participants in the maintenance treatment arm did not report significantly greater abstinence rates compared with participants in the standard and extended treatment arms (20.3% vs 23.8%; OR, 1.17 [95% CI, 0.69-1.98]; P = .57). Similarly, we found no difference in week 52 abstinence rates between participants in the extended and standard treatment arms (26.0% vs 21.7%; OR, 1.33 [95% CI, 0.72-2.45]; P = .36). Treatment duration was not associated with any adverse effects or adherence to the counseling regimen, but participants in the maintenance treatment arm reported lower adherence to the nicotine patch regimen compared with those in the standard and extended treatment arms (mean [SD], 3.94 [2.5], 4.61 [2.0], and 4.7 [2.4] patches/wk, respectively; F2,522 = 6.03; P = .003). CONCLUSIONS AND RELEVANCE: The findings support the safety of long-term use of nicotine patch treatment, although they do not support efficacy beyond 24 weeks of treatment in a broad group of smokers. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01047527.

Validating a dipstick method for detecting recent smoking.

This report evaluates the validity of a new method for verifying self-reported smoking status in patients presenting for pulmonary medicine treatment. A prospective comparison was made between self-reports of smoking status and a new semiquantitative, enzyme-linked, immunosorbent assay-based method testing for the presence of a prime nicotine metabolite, cotinine. Results were validated by gas chromatography/mass spectrometry. Data were collected in an urban, academic, tertiary health care setting. The study included 76 consecutive new patients presenting to participating clinical practices at the Pulmonology or Thoracic Surgery Services. Before taking a smoking history, patients were informed that their urine would be tested onsite for the presence of nicotine using a new method, the NicoMeter, for determining tobacco product exposure, followed by more standard laboratory testing. The level of agreement between the biochemical measurement types was excellent, kappa = 0.777. The new biochemical measurement type used was easy to use. Self-reported smoking status corresponded closely to biochemical testing. However, there was a 5.3-9.5% misclassification of smoking status among the group studied, depending upon the measurement type used. Among 32 lung cancer patients, 15.6%, most likely misrepresented their current smoking status. The NicoMeter appears to be a valid and useful method for confirming self-reported smoking status. Lung cancer patients had a higher rate of inaccurate nonsmoking compared with patients with nonmalignant pulmonary disease. The findings have implications for investigators who accept self-reported smoking status without biochemical verification.

Detecting smoking following smoking cessation treatment.

Our study compared the results of self-report (SR) plus breath carbon monoxide (CO) monitoring to SR plus urine cotinine (COT) analysis of recent tobacco use for a recently completed smoking cessation study that compared the efficacy of different intensities of psychosocial treatments coupled with 8 weeks of patch treatment. Treatment outcomes were assessed 9, 26, and 52 weeks from treatment initiation in 200+ patients using both measurement types. COT was able to detect self-reported smoking in over 97% of the cases at all time points, while CO detected self-reported smoking 62, 84, and 89% of the time for the three follow-up assessments. Under 2% of those reporting nonsmoking were found to be smoking via CO, whereas COT found smoking to have occurred for 23, 15, and 7% of the 'nonsmoking' SRs at the three time points. Abstinence rates using SR plus CO were 49, 29, and 26%, contrasted with abstinence rates of 38, 26, and 25% for SR plus COT. These findings suggest that use of urine analysis for COT may lead to more accurate but lowered measured abstinence rates.

Adding a nicotine blocking agent to cigarette tapering.

A non-pharmacologic nicotine-blocking agent (Accu Drop; AD) was preliminarily tested in combination with cigarette tapering and brief counseling (C) in a random assignment, double-blind, placebo controlled, 6-week smoking cessation study (n = 60). It was hypothesized that the AD&C group would have higher rates of treatment completion and smoking abstinence than the placebo drop group plus counseling (PD&C). The participants were 37 women and 23 men averaging 24 cigarettes per day along with high Fagerstrom nicotine dependence scores (FTQ approximately 7) and high plasma cotinine levels (> 250ng/ml). There were no significant differences between groups for withdrawal scores, treatment completion (55%), or average number of sessions attended. Point prevalence followup evaluations were obtained 1 week, 1 month, and 6 months post projected treatment completion. Biochemically confirmed abstinence rates at followups did not differ between treatment groups (AD&C = 10%, 13%, 10% vs. PD&C = 3%, 10%, 13%). There is not enough evidence to suggest a Stage II trial.

Varying results for immunoassay screening kits for cotinine level.

Our earlier study found that although enzyme-linked immunosorbent analysis (ELISA) screening assays for urine cotinine indicated use in former smoking treatment patients who reported abstinence, this finding was sometimes incorrect when validated against gas chromatography/mass spectrometry (GC/ MS; P. Gariti, A. I. Alterman, R. Ehrmann, F. D. Mulvaney, & C. P. O'Brien, 2002). In the current validation study, separate urine samples of 71 of these same patients were reanalyzed by an independent laboratory in blinded fashion using a screening enzyme immunoassay (EIA) analysis and GC/MS confirmation. EIA results showed almost total agreement with confirmatory testing. The findings indicate that use of screening ELISA/EIA for urine cotinine can detect unreported cases of smoking in former patients, but that care is needed in selecting a laboratory for conducting these tests.

Scheduled appointments and patient-staff compliance.

Studies of medication compliance have focused primarily on patient resistance to treatment, medication side effects, or the complexity of the medication regimen. This study of patient visits in a large psychiatric clinic found that, because of failure to schedule appointments or to notify receptionists of rescheduled appointments, physician noncompliance was as important as patient failure.

Comparing smoking treatment programs for lighter smokers with and without a history of heavier smoking.

The study examined the impact of counseling intensity (high vs. low) combined with either bupropion or the nicotine patch. Two hundred sixty participants smoking 6 to 15 cigarettes per day (cpd) were enrolled in a year-long study to examine the effects of treatment. Four groups of smokers under medication-blinded conditions were compared for treatment completion and abstinence at three follow-up points from the initiation of treatment (Weeks 12, 26, and 52). Both counseling groups had similar treatment completion rates (i.e., defined by a combination of counseling attendance and medication adherence levels). There was a main treatment effect for abstinence favoring the high counseling condition in early follow-up (Week 12) and for continuous abstinence. Participants with a history of heavier smoking (> or =20 cpd) and African American smokers were least likely to be smoke free at the end of the study. The study has implications for identifying the treatment needs of lighter smokers.

Determining the need for gender-specific chemical dependence treatment: assessment of treatment variables.

The effects of gender on selected treatment variables of substance-abusing persons were investigated with the long-term goal of designing gender-appropriate programs for the treatment of addiction. A population of 120 male and female substance abusers was drawn from two urban outpatient drug treatment centers and one HIV outpatient counseling center. Participants were given questionnaires to measure the following variables: trait anxiety, depression, coping style, and level of differentiation of self. Results demonstrated significant gender differences in differentiation of self (p < .005) and coping styles (p < .02) but no significant differences in anxiety or depression.

Retrospective study: influence of menstrual cycle on cue-induced cigarette craving.

Cigarettes acquire reinforcing properties from nicotine and from cues associated with their intake. However, smoking in males and females may be reinforced differentially. Smoking in females is posited to be influenced more by cues whereas male smoking is influenced predominantly by the direct pharmacological actions of nicotine in the brain. Menstrual cycle phase may contribute to some of the sex differences observed in smokers. We hypothesized that females may report more intense craving to smoking cue exposure than males and, further, that female craving scores may be influenced by menstrual cycle phase. Thus, we reexamined previously collected cue exposure data with respect to sex and cycle phase. Self-report measures were collected from subjects prior to and immediately following exposure to visual smoking stimuli. The study included 69 male and 41 female treatment-seeking subjects who smoked more than 15 cigarettes per day for more than 10 years. Females were grouped according to cycle phase. Of the female subjects, 17 were classified as follicular phase females (FFemales) and 24 were classified as luteal phase females (LFemales). Change scores were calculated from the subjective data collected before and after stimulus presentation. Contrary to our hypothesis, overall, males and all females did not differ in their level of cue-induced craving; however, when females were separated into groups by cycle phase, FFemales reported significantly less craving than either males or LFemales (p<.05). The suppressed craving response in FFemales suggests an influence of cycle phase on cue-induced craving.

Nicotine intervention during detoxification and treatment for other substance use.

This preliminary study evaluated the efficacy of a brief smoking cessation intervention (30 controls, 34 intervention groups) on a smoke-free inpatient unit for substance use detoxification. Controls received usual care, including the transdermal nicotine patch and referral to an outpatient smoking program. The intervention group additionally received a structured motivational enhancement program. Biochemically confirmed smoking cessation rate and abstinence/reduction of alcohol or other drug use were the main outcome measures taken 6 months after treatment initiation. The smoking cessation intervention did not result in greater participation in formal outpatient smoking cessation treatment and was not associated with either enhanced smoking cessation (6 vs. 0%) or greater smoking reduction at follow-up. Both groups significantly reduced the number of cigarettes smoked per day (cpd) from about 24 at baseline to 10cpd. The groups did not differ on abstinence from nonnicotine addictive substances. Smoking cessation treatment in substance users undergoing detoxification resulted in little or no smoking cessation advantage.