Association between adherence to free nicotine replacement therapy and successful quitting.

INTRODUCTION: Providing free nicotine replacement therapy (NRT) can be a cost-effective strategy for increasing quit attempts and cessation rates at a population level. However, the optimal amount of NRT to provide is unknown. Associations between duration of NRT use and abstinence may be overestimated as a result of reverse causality due to discontinuation following relapse. We examined the association between adherence to 10weeks of cost-free NRT and quit success at 6-month follow-up, after controlling for reverse causation by excluding participants who reported nonadherence due to relapse. METHODS: Individuals 18years or older who smoked at least 10 cigarettes daily and intended to quit within 30days received 10weeks of NRT at a smoking cessation workshop. There were 3922 participants who attended one of 114 workshops in 70 different localities in Ontario, Canada from 2007 to 2008. RESULTS: At end of treatment participants were asked whether they had used "all" of the NRT (20%), "most" of it (28%), "some" of it (47%), or whether they "did not use any" of it (5%). After controlling for reverse causation and adjusting for potential confounding variables, poorer quit success was reported by those who used either some (AOR=0.43, 95% CI=0.26-0.69, p=0.001) or none (AOR=0.30, 95% CI=0.09-0.95, p=0.041) of the NRT versus all 10weeks. Post-estimation contrasts revealed using some versus most of the NRT was also associated with poorer quit success (p=0.026). CONCLUSIONS: After controlling for reverse causation, adherence to 10weeks of cost-free NRT was associated with successful abstinence at six months post-treatment.

Individualized Treatment for Tobacco Dependence in Addictions Treatment Settings: The Role of Current Depressive Symptoms on Outcomes at 3 and 6 Months.

INTRODUCTION: Individuals with concurrent tobacco dependence and other addictions often report symptoms of low mood and depression and as such may have more difficulty quitting smoking. We hypothesized that current symptoms of depression would be a significant predictor of quit success among a group of smokers receiving individualized treatment for tobacco dependence within addiction treatment settings. METHODS: Individuals in treatment for other addictions were enrolled in a smoking cessation program involving brief behavioral counseling and individualized dosing of nicotine replacement therapy. The baseline assessment included the Patient Health Questionnaire (PHQ9) for depression. Smoking cessation outcomes were measured at 3 and 6 months post-enrollment. Bivariate associations between cessation outcomes and PHQ9 score were analyzed. RESULTS: Of the 1,196 subjects enrolled to date, 1,171 (98%) completed the PHQ9. Moderate to severe depression (score >9) was reported by 28% of the sample, and another 29% reported mild depression (score between 5 and 9). Contrary to the extant literature and other findings by our own group, there was no association between current depression and cessation outcome at either 3 months (n = 1,171) (17.0% in those with PHQ9 > 9 vs. 19.8% in those with PHQ9 < 5, p = .32) or 6 months (n = 834) (17.8% vs. 18.9%, p = .74). CONCLUSIONS: Contrary to our hypothesis, depression severity as measured by the PHQ9 did not predict cessation outcome in this clinical population. A possible explanation may be the individualized treatment and supportive environment of an addictions treatment setting. These data indicate that patients in an addictions treatment setting can successfully quit smoking regardless of current depressive symptoms.

Effects of stress and alcohol cues in men with and without problem gambling and alcohol use disorder.

BACKGROUND: Relapse is a serious challenge in problem gambling (PG), as it is in substance addiction. Stress and cues are implicated in relapse in both conditions. However, experimental research on motivational effects of stress in PG subjects is scant. This study examined subjective-motivational, cognitive and physiological effects of stress and alcohol cues in subjects with PG, alcohol use disorder (AD), co-occurring PG and AD (CO), and healthy controls (HC). METHODS: Fifty-two (12/clinical group; 16 HC) physically healthy men received stress in the form of 10-min uncontrollable noise (U-Noise vs. controllable noise; C-Noise) and cues (355 ml non-alcoholic 'placebo' beer; P-Beer vs. soft drink) under Separate or Combined conditions on two test sessions. Visual analogue scales assessed subjective effects. Emotional Stroop and Go/No-Go 'Shift' tasks assessed inhibitory control. Systolic blood pressure (SBP) indexed physiological reactivity. RESULTS: U-Noise and C-Noise increased desire for alcohol in all groups. U-Noise selectively inhibited desire to gamble in PG subjects. Both U-Noise and C-Noise inhibited desire to gamble in CO subjects. Neither manipulation reliably altered cognitive performance. Compared to Neutral words, Alcohol words impaired Stroop color-naming in all groups except PG, which displayed relatively faster color-naming of Alcohol words (facilitation). U-Noise increased SBP relative to C-Noise in AD and HC groups. U-Noise plus P-Beer and U-Noise per se decreased SBP in PG and CO groups, respectively. CONCLUSIONS: Noise stress has opposite motivational and physiological effects in men with problem gambling vs. alcohol use disorder. A homeostatic process may explain the impact of stress in problem gamblers.

Stress and alcohol cues exert conjoint effects on go and stop signal responding in male problem drinkers.

Stress, cues, and pharmacological priming are linked with relapse to addictive behavior. Increased salience and decreased inhibitory control are thought to mediate the effects of relapse-related stimuli. However, the functional relationship between these two processes is unclear. To address this issue, a modified Stop Signal Task was employed, which used Alcohol, Neutral, and Non-Words as Go stimuli, and lexical decision as the Go response. Subjects were 38 male problem drinkers (mean Alcohol Dependence Scale (ADS) score: 18.0). Uncontrollable noise (∼ 10 min at 110 dB) was the stressor; nonalcoholic placebo beer (P-Beer) was the cue manipulation, and alcohol (0.7 g/kg), the pharmacological prime. Half the sample received alcohol, and half P-Beer. Stress and beverage (test drink vs soft drink) were manipulated within subjects on two sessions, with half the sample receiving active manipulations together and half receiving them separately. Go response time (RT) and Stop Signal RT (SSRT) were slower to Alcohol than Neutral words. Stress augmented this bias. Alcohol and P-Beer impaired overall SSRT. Stress impaired neither overall SSRT nor Go RT. SSRT to Neutral words and Non-Words correlated inversely with Go RT to Alcohol and Neutral words, and Non-Words. ADS correlated directly with SSRT to Alcohol words. A resource allocation account was proposed, whereby diversion of limited resources to salient cues effectively yoked otherwise independent Go and Stop processes. Disturbances of prefrontal norepinephrine and dopamine were cited as possibly accounting for these effects. Treatments that optimize prefrontal catecholamine transmission may deter relapse by reducing disinhibitory effects of salient eliciting stimuli.

Individualized smoking cessation treatment in an outpatient setting: Predictors of outcome in a sample with psychiatric and addictions co-morbidity.

OBJECTIVE: Patients with psychiatric disorders have higher rates of smoking and greater difficulty quitting smoking. However, few studies have compared patients with schizophrenia or schizoaffective disorders to patients with other psychiatric diagnoses without psychosis, addressing ability to quit and differences in treatment characteristics. METHOD: A retrospective chart review was conducted on a sample of 165 cigarette smokers admitted to an outpatient smoking cessation clinic located in a large inner-city psychiatric hospital. Patients with schizophrenia and schizoaffective disorder (n=55) were matched for age and sex at a ratio of 1:2 with a comparison group without psychosis (n=110) from the same clinic. Primary outcomes of interest were quit status (7-day point prevalence) and significant reduction in cigarettes per day (>or=50% but not quit) at final treatment session. RESULTS: There were no significant differences between groups for end-of-treatment quit rate or significant reduction (>or=50%) in cigarettes per day. Patients with schizophrenia made significantly more visits to the clinic and were in treatment for a longer period of time. A greater number of individual treatment sessions and being male were the most significant predictors of cessation. CONCLUSION: Patients with schizophrenia were as likely to quit smoking as a comparison group of patients with a high rate of other psychiatric comorbidities without psychosis. Findings suggest treatment success in this population requires an extended number of clinic visits, group therapy, and possibly higher doses of nicotine replacement.

Cocaine and amphetamine regulated transcript (CART) gene in the comorbidity of schizophrenia with alcohol use disorders and nicotine dependence.

Studies have shown a genetic susceptibility to develop schizophrenia, alcohol use disorders and nicotine dependence. Brain areas related to reward and reinforcement show high expression of the cocaine and amphetamine regulated transcript (CART). Nicotine and alcohol are also able to modulate CART expression in the hypothalamic areas. In this study, we evaluated whether CART variants would influence the predisposition of schizophrenia subjects to alcohol use disorders and nicotine dependence. Clinical and genetic data were obtained from 190 unrelated Caucasian schizophrenia subjects collected at the Centre for Addiction and Mental Health. We found no association of CART variants with alcohol use disorders or nicotine dependence. We found a trend for allelic association of rs11575893 with the heaviness of smoking behaviour (p=0.057). Our results indicate that genetic variants in the CART gene may not play a major role in the vulnerability of schizophrenia subjects to concurrent alcohol use disorders and nicotine dependence. Additional association studies in independent samples can evaluate whether CART gene is playing a role in the schizophrenia comorbidity with alcohol use disorders and nicotine dependence.

Comorbidity between bipolar disorder and alcohol use disorder: association of dopamine and serotonin gene polymorphisms.

Bipolar disorder is a chronic mental illness with high prevalence of co-occurring alcohol use disorder. Linkage studies have revealed several candidate genes in the dopaminergic and serotonergic pathways which may be associated with both bipolar and alcohol use disorders. We investigated the relationship between polymorphisms in candidate genes and alcohol use disorder comorbidity in bipolar patients. We performed a retrospective study of a genomic database consisting of 278 bipolar disorder patients. Diagnosis of bipolar disorder was according to the Structured Clinical Interview for DSM-IV Axis I disorders (SCID-I). RFLP analysis of single nucleotide polymorphisms were performed in dopamine (DRD1, DRD2 and DRD3) and serotonin receptor and transporter genes (5HTTLPR, 5HT1B, 5HT2A, 5HT2C). There were 179 (64%) females in the database. Seventy-one (25.5%) of the bipolar patients were diagnosed as comorbid alcohol use disorder. Chi-square analysis indicated that in female bipolar patients, there was a significant difference in genotype frequency between the bipolar patients with comorbid alcohol use disorder and non-comorbid bipolar patients for the Ser23Cys (rs6318) polymorphism of the 5HT2C gene. Overall, the results indicate a possible association between 5HT2C and alcohol use disorder comorbidity.

Effect of metabolic blockade on the psychoactive effects of dextromethorphan.

OBJECTIVE: Variation in the activity of cytochrome P450 2D6 (CYP2D6) affects the pharmacokinetics and effectiveness of dextromethorphan (DM), because it controls the production of dextrorphan, an active metabolite, with higher affinity for the NMDA receptor than the parent compound. This study examined whether pharmacological inhibition of CYP2D6 activity with quinidine would mimic the genetic mutation and thus also alter the psychoactive effects of DM. METHODS: In a single-blind, within-subjects study, eight healthy volunteers (all homozygous for the wild type allele for CYP2D6) received placebo and varying doses of DM, both with and without quinidine pre-treatment. Pharmacokinetic and pharmacodynamic measures were assessed at baseline and every hour post-drug for 6 h. RESULTS: Compared to the no quinidine condition, quinidine pre-treatment decreased the area under the dose-response curve on subjective measures of positively reinforcing effects (e.g., euphoria, p < 0.04; drug liking, p < 0.05), and was significantly greater for measures of dysphoria (e.g., unpleasantness, p < 0.02). These changes corresponded to increased DM and decreased dextrorphan plasma concentrations. CONCLUSIONS: Compared to DM alone, quinidine pre-treatment inhibited DM metabolism and changed its subjective effects, demonstrating that the psychoactive properties of DM are a function of drug metabolism. These results demonstrate the relationship between CYP2D6 activity, plasma drug levels, and psychoactive drug effects, and have implications for both the abuse liability and therapeutic utility of DM.

Dopaminergic activity in depressed smokers: a positron emission tomography study.

Tobacco dependence is highly prevalent in depressed patients. We assessed changes in [(11)C]-raclopride binding potential (BP) using positron emission tomography (PET) before and after the oral administration of d-amphetamine in healthy controls and unmedicated patients with current depression with and without current tobacco dependence. Over a single study day 2 [(11)C]-raclopride positron emission tomography scans were taken in 38 subjects: at baseline and 2 h following oral d-amphetamine 30 mg. Twenty controls (9 smokers, 11 nonsmokers) and 18 subjects with current major depressive episode (8 smokers, 10 non-smokers). Striatal [(11)C]-raclopride binding potential was measured before and after d-amphetamine administration. Depressed smokers had a lower baseline [(11)C]-raclopride binding potential compared with both control non-smokers (P < 0.007) and depressed non-smokers (P < 0.001). There was a main effect of smoking status on amphetamine-induced change in [(11)C]-raclopride binding potential (P < 0.02), but no main effect of depression. This may be due to a floor effect because of the low BP at baseline. Depressed subjects reported significant increase of positive mood after d-amphetamine administration compared with controls (depressed smokers vs. control smokers: P < 0.05; depressed non-smokers vs. controls: P < 0.055). Tobacco dependence appears to decrease d-amphetamine-induced changes in [(11)C]-raclopride binding potential as measured by positron emission tomography. Comorbid major depression and tobacco dependence exacerbates this effect, suggesting an altered dopamine system in comorbid patients.

Comparative abuse liability and pharmacological effects of meprobamate, triazolam, and butabarbital.

Implementation of regulations to control the prescribing of benzodiazepines in New York State in 1989 resulted in a 55% decrease in benzodiazepine prescribing, with a concomitant increase in the rates of prescribing older sedative-hypnotic compounds such as butabarbital (30% increase) and meprobamate (125% increase). In a double-blind, crossover, placebo-controlled study, we compared the behavioral and pharmacological effects of triazolam, meprobamate, and butabarbital in 14 recreational drug users. Placebo and three doses each of triazolam, meprobamate, and butabarbital were administered to each subject in a random order. Objective tests (motor performance, concentration) and subjective response questionnaires measured drug effects. Triazolam, meprobamate, and butabarbital showed comparable negative dose-response slopes on the objective measures. On the basis of these objective data, equivalent doses for the three compounds were determined to be as follows: 0.5 mg triazolam = 2,400 mg meprobamate = 400 mg butabarbital. Subjective effects data on equivalent doses show that butabarbital produced the highest peak score on Cole/ARCI Abuse Potential, ARCI Pentobarbital Chlorpromazine Alcohol Group (PCAG), and "drug strength" scales. Triazolam and butabarbital produced equivalent results on ARCI Morphine Benzedrine Group (MBG), Cole/ARCI Euphoria, and "drug liking" scales. Meprobamate was indistinguishable from placebo on euphoria and abuse potential scales. Behavioral economics analysis indicated a price crossover point two times higher for butabarbital (400 mg) than for any other drug condition. These data indicate a comparative abuse liability of butabarbital > triazolam > or = meprobamate, suggesting that the prescribing restrictions on benzodiazepines had little net benefit on abuse risk in the population and may have increased the risk of overdose morbidity and mortality.