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The nicotine metabolite ratio (NMR) represents variation in the rate of nicotine metabolism and has been associated with smoking behaviors and response to tobacco treatments. We compared NMR between smokers with current or past MDD (MDD+) vs smokers without MDD (MDD\u2212). We also assessed correlates of NMR and compared withdrawal and craving between MDD+ and MDD\u2212 smokers.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Using baseline data from two clinical trials and propensity score weighting based on sex, race, body mass index, and smoking rate, we compared NMR between MDD+ (<jats:italic>N<\/jats:italic>\u2009=\u2009279) and MDD\u2212 (<jats:italic>N<\/jats:italic>\u2009=\u20091575) smokers. We also compared groups on and nicotine withdrawal and craving.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Mean NMR (<jats:italic>\u03b2<\/jats:italic>\u2009=\u2009\u2212.02, 95% confidence interval [CI]: \u22120.05 to 0.01, <jats:italic>P<\/jats:italic>\u2009=\u2009.13) and the distribution of smokers across NMR quartiles (odds ratio [OR]\u2009=\u20090.76, 95% CI: 0.50 to 1.16, <jats:italic>P<\/jats:italic>\u2009=\u2009.21) were similar between MDD+ and MDD\u2212 samples. This relationship was not affected by antidepressant medication. In the MDD+ sample, African Americans had significantly lower mean NMR, while older smokers and smokers with lower education had higher mean NMR (<jats:italic>P<\/jats:italic>s\u2009&lt;\u2009.05). MDD+ smokers had significantly higher withdrawal and craving than MDD\u2212 smokers (<jats:italic>P<\/jats:italic>s\u2009&lt;\u2009.05).<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion and Conclusions<\/jats:title><jats:p>While variability in NMR may not explain differences in smoking rates between MDD+ and MDD\u2212 smokers, MDD+ smokers report increased withdrawal and craving.<\/jats:p><\/jats:sec><jats:sec><jats:title>Scientific Significance<\/jats:title><jats:p>In this first study to assess NMR among MDD+ smokers, the findings underscore the need to address withdrawal and craving within smoking cessation treatments for those with MDD. (Am J Addict 2021;00:00\u201300)<\/jats:p><\/jats:sec>","DOI":"10.1111\/ajad.13155","type":"journal-article","created":{"date-parts":[[2021,3,27]],"date-time":"2021-03-27T03:53:48Z","timestamp":1616817228000},"page":"382-388","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Comparing the Rate of Nicotine Metabolism Among Smokers With Current or Past Major Depressive Disorder"],"prefix":"10.1111","volume":"30","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4089-856X","authenticated-orcid":false,"given":"Robert","family":"Schnoll","sequence":"first","affiliation":[{"name":"Department of Psychiatry, Abramson Cancer Center University of Pennsylvania  Philadelphia Pennsylvania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"E.","family":"Paul Wileyto","sequence":"additional","affiliation":[{"name":"Center for Clinical Epidemiology and Biostatistics University of Pennsylvania  Philadelphia Pennsylvania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna\u2010Marika","family":"Bauer","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Perelman School of Medicine University of Pennsylvania  Philadelphia Pennsylvania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Erica","family":"Fox","sequence":"additional","affiliation":[{"name":"Department of Preventive Medicine, Feinberg School of Medicine Northwestern University  Evanston Illinois"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Frank","family":"Leone","sequence":"additional","affiliation":[{"name":"Pulmonary, Allergy, &amp; Critical Care Division University of Pennsylvania  Philadelphia Pennsylvania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Caryn","family":"Lerman","sequence":"additional","affiliation":[{"name":"Keck School of Medicine, USC Norris Comprehensive Cancer Center University of Southern California  Los Angeles California"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rachel F.","family":"Tyndale","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Department of Pharmacology and Toxicology, Division of Brain and Therapeutics, Centre for Addiction and Mental Health, Campbell Family Mental Health Research Institute University of Toronto  Toronto Ontario Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tony P.","family":"George","sequence":"additional","affiliation":[{"name":"Addictions Division, Centre for Addiction and Mental Health, Department of Psychiatry University of Toronto  Toronto Ontario Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"suffix":"Jr.","given":"Larry","family":"Hawk","sequence":"additional","affiliation":[{"name":"Department of Psychology State University of New York Buffalo  Buffalo New York"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paul","family":"Cinciripini","sequence":"additional","affiliation":[{"name":"Department of Behavioral Science The University of Texas MD Anderson Cancer Center  Houston Texas"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mackenzie","family":"Quinn","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Perelman School of Medicine University of Pennsylvania  Philadelphia Pennsylvania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Janelle","family":"Purnell","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Perelman School of Medicine University of Pennsylvania  Philadelphia Pennsylvania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jane","family":"Hatzell","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Perelman School of Medicine University of Pennsylvania  Philadelphia Pennsylvania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brian","family":"Hitsman","sequence":"additional","affiliation":[{"name":"Department of Preventive Medicine, Feinberg School of Medicine Northwestern University  Evanston Illinois"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2021,3,26]]},"reference":[{"key":"e_1_2_8_2_1","unstructured":"PrattLA. 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