Phase IIb Trial of an α7 Nicotinic Receptor Partial Agonist With and Without Nicotine Patch for Withdrawal-Associated Cognitive Deficits and Tobacco Abstinence.

PURPOSE/BACKGROUND: The objective of this study was to determine whether a novel α7 nicotinic acetylcholine receptor partial agonist improves cognition during nicotine withdrawal and improves abstinence rates. To do so, the effect of the α7 nicotinic acetylcholine receptor partial agonist, encenicline, on cognition and abstinence was evaluated when given as monotherapy and when combined with transdermal nicotine patch (nicotine replacement therapy [NRT]). METHODS: Adult daily smokers, n = 160, who were motivated to quit smoking completed cognitive testing at satiated baseline and after overnight abstinence and then were randomized to receive a 12-week trial of encenicline 1 mg twice daily or identical placebo the day of the overnight abstinent cognitive testing. In the first 6 weeks of the 12-week encenicline administration, participants were also randomized to 6 weeks of NRT patch or placebo patch. Primary outcomes were cognition during abstinence and 7-day point-prevalence abstinence at week 12. RESULTS: No beneficial effects of encenicline were observed on cognition or abstinence when compared with placebo or when combined with NRT compared with placebo capsule + NRT. Of the 4 conditions, abstinence rates were lowest among those assigned to encenicline alone. CONCLUSIONS: Beneficial effects of NRT were observed on cognitive and abstinence outcomes when combined with encenicline compared with encenicline plus placebo patch. Addition of NRT to encenicline improved odds of abstinence approximately 3-fold compared with encenicline plus placebo patch. We conclude that encenicline, 1 mg/d, did not improve abstinence-associated cognitive impairment or abstinence rates as monotherapy or adjunctive therapy to NRT patch.

Prospective association between major depressive disorder and leukocyte telomere length over two years.

BACKGROUND: Reduced leukocyte telomere length (LTL) has been found to be associated with multiple common age-related diseases, including heart disease, diabetes, and cancer. A link has also been suggested between shortened LTL and major depressive disorder (MDD), suggesting that MDD may be a disease of accelerated aging. This prospective, longitudinal study examined the association between depression diagnosis at baseline and change in LTL over two years in a well-characterized sample of N = 117 adults with or without MDD at baseline, using rigorous entry criteria. METHODS: Participants aged 18-70 were assessed with validated instruments by trained, doctoral-level clinician raters at baseline and at two-year follow-up, and blood samples were obtained at both visits. LTL was assayed under identical methods using quantitative polymerase chain reaction (qPCR). The effect of an MDD diagnosis at baseline on change in LTL over two years was examined via hierarchical mixed models, which included potential confounders. RESULTS: Individuals with MDD at baseline had greater LTL shortening over two years than individuals without MDD (p = 0.03), even after controlling for differences in age, sex, and body mass index (BMI). In the sub-sample of individuals with MDD diagnoses at baseline, no significant associations between LTL change and symptom severity or duration were found. CONCLUSION: A baseline diagnosis of MDD prospectively predicted LTL shortening over two years. Our results provide further support for MDD as a disease associated with accelerated aging in a well-characterized sample using validated, clinician-rated measures.