Randomized Placebo-Controlled Trial of Memantine for Smoking Cessation (CCCWFU 99311)

IntroductionQuitting smoking is challenging even with existing pharmacotherapy. Thus, discovery of new cessation medications is imperative. Memantine, a well-tolerated Alzheimer's disease drug, partially antagonizes glutamate at the N-methyl-D-Aspartate receptor (NMDAR), modulating dopamine release in addiction pathways. Memantine may interrupt nicotine reward and promote smoking cessation.Materials and MethodsAt 23 community oncology practices nationwide, we recruited 130 breast, prostate, lung, or colorectal cancer survivors ≥ six months beyond definitive treatment who currently smoked at least 10 cigarettes daily and wanted to quit. In a double-blind fashion, participants were randomized to take either memantine (10 mg) or a matching placebo twice daily for 12 weeks (65 per arm). Toxicity, nicotine dependence, and past-week abstinence were recorded at 2, 4-, 6-, 9-, and 12-weeks post-randomization. The primary endpoint was feasibility and preliminary estimation of 12-week self-reported past-week smoking abstinence.ResultsThere were no significant differences in abstinence rates or nicotine dependence between the two groups at 12 weeks. Twelve-week completion of therapy was low, but lower in memantine than control participants (42% vs 63%, respectively; <i>P</i> = .01). Memantine participants reported trends of less anxiety, craving, and hunger. No significant differences in toxicity were observed between groups. Serious adverse events (3 in memantine arm, 1 in control arm) occurred; none considered possibly or probably related to study medication.ConclusionMemantine did not improve 12-week smoking abstinence rates in cancer survivors. While other NMDAR antagonists might deserve evaluation, this study suggests memantine is not efficacious for smoking cessation in a cancer survivor subpopulation.Trial registration numberNCT01535040 - February 17, 2012.