{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T04:06:13Z","timestamp":1793419573243,"version":"4.5.0"},"reference-count":48,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,1,4]],"date-time":"2022-01-04T00:00:00Z","timestamp":1641254400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Psychiatry"],"abstract":"<jats:p><jats:bold>Objective:<\/jats:bold> Depression and post-traumatic stress disorder (PTSD) highly co-occur with alcohol use disorder (AUD). The comparative effects of noradrenergic vs. serotonergic antidepressants on drinking and depressive outcomes for those with AUD and co-occurring depression and\/or PTSD are not well known.<\/jats:p><jats:p><jats:bold>Methods:<\/jats:bold> This study was an analysis of a randomized control trial of 128 patients with AUD who had co-occurring depression and\/or PTSD. They were randomized to treatment with paroxetine vs. desipramine and naltrexone vs. placebo leading to four groups: paroxetine plus naltrexone, paroxetine plus placebo, desipramine plus naltrexone, and desipramine plus placebo. Outcomes were percent of drinking days, percent heavy drinking days, drinks per drinking day (Time Line Follow-back Method), and depressive symptoms (Hamilton Depression Scale). Groups compared were (1) depression without PTSD (depression group; <jats:italic>n<\/jats:italic> = 35), (2) PTSD without depression (PTSD group; <jats:italic>n<\/jats:italic> = 33), and (3) both depression and PTSD (comorbid group; <jats:italic>n<\/jats:italic> = 60).<\/jats:p><jats:p><jats:bold>Results:<\/jats:bold> There were no overall significant differences in drinking outcomes by medication in the entire sample, and no significant interaction when diagnostic groups were not considered. However, when diagnostic groups were included in the model, the interactions between time, diagnostic group, and medication (desipramine vs. paroxetine) were significant for percent drinking days (<jats:italic>p<\/jats:italic> = 0.042), and percent heavy drinking days (<jats:italic>p<\/jats:italic> = 0.036); paroxetine showed better drinking outcomes within the depression group, whereas desipramine showed better drinking outcomes in the PTSD and comorbid groups. Regarding depressive symptoms, paroxetine was statistically superior to desipramine in the total sample (<jats:italic>p<\/jats:italic> = 0.007), but there was no significant interaction of diagnostic group and medication. Naltrexone led to a decrease in craving but no change in drinking outcomes.<\/jats:p><jats:p><jats:bold>Conclusions:<\/jats:bold> The results of this study suggest that drinking outcomes may respond differently to desipramine and paroxetine depending on comorbid MDD and\/or PTSD.<\/jats:p>","DOI":"10.3389\/fpsyt.2021.768318","type":"journal-article","created":{"date-parts":[[2022,1,4]],"date-time":"2022-01-04T15:45:34Z","timestamp":1641311134000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":6,"title":["Depression and\/or PTSD Comorbidity Affects Response to Antidepressants in Those With Alcohol Use Disorder"],"prefix":"10.3389","volume":"12","author":[{"given":"Peter J.","family":"Na","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth","family":"Ralevski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oluwole","family":"Jegede","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aaron","family":"Wolfgang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ismene L.","family":"Petrakis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,1,4]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"757","DOI":"10.1001\/jamapsychiatry.2015.0584","article-title":"Epidemiology of DSM-5 alcohol use disorder: results from the National Epidemiologic Survey on Alcohol and related conditions III","volume":"72","author":"Grant","year":"2015","journal-title":"JAMA Psychiatry."},{"key":"B2","doi-asserted-by":"publisher","first-page":"1786","DOI":"10.1111\/add.13423","article-title":"The burden of alcohol use disorders in US military veterans: results from the National Health and Resilience in Veterans Study","volume":"111","author":"Fuehrlein","year":"2016","journal-title":"Addiction."},{"key":"B3","doi-asserted-by":"publisher","first-page":"25","DOI":"10.2147\/SAR.S37399","article-title":"PTSD and comorbid AUD: a review of pharmacological and alternative treatment options","volume":"5","author":"Ralevski","year":"2014","journal-title":"Subst Abuse Rehabil."},{"key":"B4","doi-asserted-by":"publisher","first-page":"173","DOI":"10.1016\/S0272-7358(99)00026-4","article-title":"The comorbidity of depression and substance use disorders","volume":"20","author":"Swendsen","year":"2000","journal-title":"Clin Psychol Rev."},{"key":"B5","doi-asserted-by":"publisher","first-page":"207","DOI":"10.1001\/archpsyc.1991.01810270019002","article-title":"Lifetime and current prevalence of specific psychiatric disorders among Vietnam veterans and controls","volume":"48","author":"Jordan","year":"1991","journal-title":"Arch Gen Psychiatry."},{"key":"B6","first-page":"161","article-title":"Co-occurring post-traumatic stress disorder and alcohol use disorder in U","volume-title":"Alcohol Res.","author":"Dworkin","year":"2018"},{"key":"B7","doi-asserted-by":"publisher","first-page":"224","DOI":"10.1037\/adb0000348","article-title":"The burden of co-occurring alcohol use disorder and PTSD in U","volume":"32","author":"Norman","year":"2018","journal-title":"Psychol Addict Behav."},{"key":"B8","doi-asserted-by":"publisher","first-page":"S97","DOI":"10.1080\/09540120412301315259","article-title":"Understanding the interface of HIV, trauma, post-traumatic stress disorder, and substance use and its implications for health outcomes","volume":"16","author":"Brief","year":"2004","journal-title":"AIDS Care."},{"key":"B9","doi-asserted-by":"publisher","first-page":"242","DOI":"10.1097\/YCO.0b013e3282fc9889","article-title":"Substance use, post-traumatic stress disorder and violence","volume":"21","author":"Johnson","year":"2008","journal-title":"Curr Opin Psychiatry."},{"key":"B10","doi-asserted-by":"publisher","first-page":"e0126870","DOI":"10.1371\/journal.pone.0126870","article-title":"Alcohol-related risk of suicidal ideation, suicide attempt, and completed suicide: a meta-analysis","volume":"10","author":"Darvishi","year":"2015","journal-title":"PLoS ONE."},{"key":"B11","doi-asserted-by":"publisher","first-page":"112","DOI":"10.1176\/appi.ps.201700194","article-title":"A change in perspective: from dual diagnosis to multimorbidity","volume":"69","author":"Bhalla","year":"2017","journal-title":"Psychiatr Serv."},{"key":"B12","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1080\/15622970701227829","article-title":"World Federation of Societies of Biological Psychiatry (WFSBP) guidelines for biological treatment of unipolar depressive disorders in primary care","volume":"8","author":"Bauer","year":"2007","journal-title":"World J Biol Psychiatry."},{"key":"B13","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1097\/HRP.0000000000000186","article-title":"Evidence-based treatment of posttraumatic stress disorder: an updated review of validated psychotherapeutic and pharmacological approaches","volume":"26","author":"Charney","year":"2018","journal-title":"Harv Rev Psychiatry."},{"key":"B14","doi-asserted-by":"publisher","first-page":"996","DOI":"10.1038\/npp.2011.283","article-title":"Noradrenergic vs serotonergic antidepressant with or withour naltrexone for veterans with PTSD and comorbid alcohol dependence","volume":"37","author":"Petrakis","year":"2012","journal-title":"Neuropsychopharmacology."},{"key":"B15","doi-asserted-by":"publisher","first-page":"359","DOI":"10.1037\/a0038719","article-title":"Combining seeking safety with sertraline for PTSD and alcohol use disorders: a randomized controlled trial","volume":"83","author":"Hien","year":"2015","journal-title":"J Consult Clin Psychol."},{"key":"B16","doi-asserted-by":"publisher","first-page":"700","DOI":"10.1001\/archpsyc.1997.01830200024004","article-title":"Fluoxetine in depressed alcoholics. A double-blind, placebo-controlled trial","volume":"54","author":"Cornelius","year":"1997","journal-title":"Arch Gen Psychiatry."},{"key":"B17","doi-asserted-by":"publisher","first-page":"arcr","DOI":"10.35946\/arcr.v40.1.01","article-title":"Alcohol use disorders and depressive disorders","volume":"40","author":"McHugh","year":"2019","journal-title":"Alcohol Res."},{"key":"B18","doi-asserted-by":"publisher","first-page":"761","DOI":"10.1001\/jama.275.10.761","article-title":"A double-blind, placebo-controlled trial of desipramine for primary alcohol dependence stratified on the presence or absence of major depression","volume":"275","author":"Mason","year":"1996","journal-title":"JAMA."},{"key":"B19","first-page":"26","article-title":"The use of selective serotonin reuptake inhibitors in treating alcoholic subtypes","volume":"62","author":"Pettinati","year":"2001","journal-title":"J Clin Psychiatry."},{"key":"B20","doi-asserted-by":"publisher","first-page":"785","DOI":"10.1016\/j.biopsych.2004.07.016","article-title":"Antidepressant treatment of co-occurring depression and alcohol dependence","volume":"56","author":"Pettinati","year":"2004","journal-title":"Biol Psychiatry."},{"key":"B21","doi-asserted-by":"publisher","first-page":"395","DOI":"10.1097\/01.ALC.0000156129.98265.57","article-title":"Sertraline in the treatment of co-occurring alcohol dependence and posttraumatic stress disorder","volume":"29","author":"Brady","year":"2005","journal-title":"Alcohol Clin Exp Res."},{"key":"B22","doi-asserted-by":"publisher","first-page":"226","DOI":"10.1111\/acer.13297","article-title":"Posttraumatic stress disorder and alcohol use disorder: a critical review of pharmacologic treatments","volume":"41","author":"Petrakis","year":"2017","journal-title":"Alcohol Clin Exp Res."},{"key":"B23","doi-asserted-by":"publisher","first-page":"1144","DOI":"10.4088\/JCP.10m06217","article-title":"Antidepressants for major depressive disorder and dysthymic disorder in patients with comorbid alcohol use disorders: a meta-analysis of placebo-controlled randomized trials","volume":"72","author":"Iovieno","year":"2011","journal-title":"J Clin Psychiatry."},{"key":"B24","doi-asserted-by":"publisher","first-page":"453","DOI":"10.1146\/annurev.med.50.1.453","article-title":"Natural history and preventative treatment of recurrent mood disorders","volume":"50","author":"Frank","year":"1999","journal-title":"Ann Rev Med."},{"key":"B25","unstructured":"2021"},{"key":"B26","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1016\/j.brainres.2009.03.044","article-title":"Noradrenergic and serotonergic mechanisms in the neurobiology of posttraumatic stress disorder and resilience","volume":"1293","author":"Krystal","year":"2009","journal-title":"Brain Res."},{"key":"B27","doi-asserted-by":"publisher","first-page":"9","DOI":"10.2147\/NDT.S19619","article-title":"The importance of norepinephrine in depression","volume":"7","author":"Moret","year":"2011","journal-title":"Neuropsychiatr Dis Treat."},{"key":"B28","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1037\/a0038550","article-title":"A brief history of the development of antidepressant drugs: from monoamines to glutamate","volume":"23","author":"Hillhouse","year":"2015","journal-title":"Exp Clin Psychopharmacol."},{"key":"B29","doi-asserted-by":"publisher","first-page":"259","DOI":"10.1097\/01.jcp.0000222514.71390.c1","article-title":"Venlafaxine extended release in posttraumatic stress disorder: a sertraline- and placebo-controlled study","volume":"26","author":"Davidson","year":"2006","journal-title":"J Clin Psychopharmacol."},{"key":"B30","doi-asserted-by":"publisher","first-page":"713","DOI":"10.1046\/j.1360-0443.1998.9357137.x","article-title":"Treatment of cocaine and alcohol dependence with psychotherapy and disulfiram","volume":"93","author":"Carroll","year":"1998","journal-title":"Addiction."},{"key":"B31","volume-title":"Alcohol Dependence Scale (ADS): User's Guide","author":"Skinner","year":"1984"},{"key":"B32","volume-title":"Alcohol Timeline Followback Users' Manual","author":"Sobell","year":"1995"},{"key":"B33","article-title":"The obsessive compulsive drinking scale: a new method of assessing outcome in alcoholism treatment studies Arch Gen Psychiatry","author":"Anton","year":"1996"},{"key":"B34","volume-title":"The Structured Clinical Interview for DSM-IV Axis I Disorders (SCID-I) and the Structured Clinical Interview for DSM-IV Axis II Disorders (SCID-II)","author":"First","year":"2004"},{"key":"B35","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1136\/jnnp.23.1.56","article-title":"A rating scale for depression","volume":"23","author":"Hamilton","year":"1960","journal-title":"J Neurol Neurosurg Psychiatry."},{"key":"B36","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1002\/jts.2490080106","article-title":"The development of a clinician-administered PTSD scale","volume":"8","author":"Blake","year":"1995","journal-title":"J Trauma Stress."},{"key":"B37","volume-title":"Nonparametric Analysis of Longitudinal Data in Factorial Experiments","author":"Brunner","year":"2002"},{"key":"B38","doi-asserted-by":"publisher","first-page":"310","DOI":"10.1001\/archpsyc.61.3.310","article-title":"Move over ANOVA: progress in analyzing repeated-measures data and its reflection in papers published in the Archives of General Psychiatry","volume":"61","author":"Gueorguieva","year":"2004","journal-title":"Arch Gen Psychiatry."},{"key":"B39","doi-asserted-by":"publisher","first-page":"255","DOI":"10.1111\/j.1530-0277.2008.00807.x","article-title":"A pilot trial of the alpha-1 adrenergic antagonist, prazosin, for alcohol dependence","volume":"33","author":"Simpson","year":"2009","journal-title":"Alcohol Clin Exp Res."},{"key":"B40","doi-asserted-by":"publisher","first-page":"1216","DOI":"10.1176\/appi.ajp.2018.17080913","article-title":"Double-blind randomized clinical trail of prazosin for alcohol use disorder","volume":"175","author":"Simpson","year":"2018","journal-title":"Am J Psychiatry."},{"key":"B41","doi-asserted-by":"publisher","first-page":"904","DOI":"10.1111\/adb.12275","article-title":"Role of the \u03b11 blocker doxazosin in alcoholism: a proof-of-concept randomized controlled trial","volume":"21","author":"Kenna","year":"2016","journal-title":"Addict Biol."},{"key":"B42","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1016\/j.drugalcdep.2017.03.016","article-title":"Higher pretreatment blood pressure is associated with greater alcohol drinking reduction in alcohol-dependent individuals treated with doxazosin","volume":"177","author":"Haass-Koffler","year":"2017","journal-title":"Drug Alcohol Depend."},{"key":"B43","doi-asserted-by":"publisher","first-page":"808","DOI":"10.1111\/acer.12703","article-title":"A pilot trail of prazosin, an alpha-1 adrenergic antagonist, for comorbid alcohol dependence and posttraumatic stress disorder","volume":"39","author":"Simpson","year":"2015","journal-title":"Alcohol Clin Exp Res."},{"key":"B44","doi-asserted-by":"crossref","DOI":"10.1007\/978-94-007-0753-5_1059","article-title":"Floor effect. In: Michalos AC, editor","volume-title":"Encyclopedia of Quality of Life and Well-Being Research","author":"Garin","year":"2014"},{"key":"B45","doi-asserted-by":"publisher","first-page":"963","DOI":"10.1001\/jama.284.8.963","article-title":"Ondansetron for reduction of drinking among biologically predisposed alcoholic patients: a randomized controlled trial","volume":"284","author":"Johnson","year":"2000","journal-title":"JAMA."},{"key":"B46","doi-asserted-by":"publisher","first-page":"1150","DOI":"10.1097\/01.ALC.0000075547.77464.76","article-title":"Effects of ondansetron in early- versus late-onset alcoholics: a prospective, open-label study","volume":"27","author":"Kranzler","year":"2003","journal-title":"Alcohol Clin Exp Res."},{"key":"B47","doi-asserted-by":"publisher","first-page":"177","DOI":"10.1111\/j.1365-2710.2009.01050.x","article-title":"Comparison of SSRIs and SNRIs in major depressive disorder: a meta-analysis of head-to-head randomized clinical trials","volume":"35","author":"Machado","year":"2010","journal-title":"J Clin Pharm Ther."},{"key":"B48","doi-asserted-by":"publisher","first-page":"1185","DOI":"10.1111\/cns.13437","article-title":"Efficacy of pharmacotherapeutics for patients comorbid with alcohol use disorders and depressive symptoms\u2014a Bayesian network meta-analysis","volume":"26","author":"Li","year":"2020","journal-title":"CNS Neurosci Ther."}],"container-title":["Frontiers in Psychiatry"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fpsyt.2021.768318\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,1,4]],"date-time":"2022-01-04T15:45:46Z","timestamp":1641311146000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fpsyt.2021.768318\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,1,4]]},"references-count":48,"alternative-id":["10.3389\/fpsyt.2021.768318"],"URL":"https:\/\/doi.org\/10.3389\/fpsyt.2021.768318","relation":{},"ISSN":["1664-0640"],"issn-type":[{"value":"1664-0640","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,1,4]]},"article-number":"768318"}}