Journal of Neural Transmission

, Volume 122, Issue 2, pp 301–306 | Cite as

Influence of comorbid alcohol use disorder on treatment response of depressive patients

  • Eri Hashimoto
  • Masaya Tayama
  • Hiromi Ishikawa
  • Megumi Yamamoto
  • Toshikazu Saito
Psychiatry and Preclinical Psychiatric Studies - Original Article


Patients with major depressive disorder (MDD) frequently also have alcohol use disorder (AUD) and they are more likely to experience symptomatic recurrence and resist treatment. How the two disorders interrelate has not yet been fully examined in Japanese subjects. The treatment response of 47 MDD patients was followed for 12 weeks. Depressive symptoms were rated by the 17-item Hamilton Rating Scale for Depression (HAM-D) and those whose HAM-D score was less than 16 were excluded. The MDD patients were divided into a non-alcohol use disorder (NAUD) and an alcohol use disorder (AUD) group according to the Alcohol Use Disorder Identification Test (AUDIT). We applied a cutoff score of 12 in the AUDIT scale. After 8 weeks, HAM-D NAUD group scores were significantly lower compared with AUD patients. The NAUD group, 23 individuals, prescribed therapeutic doses of antidepressant (equivalent to more than 150 mg of imipramine per day) significantly improved their HAM-D scores but no improvement occurred in the AUD subjects. Correlation analysis in all subjects revealed a significant negative correlation between AUDIT score and improved HAM-D score at endpoint. Moreover, a significant negative correlation was found between total alcohol consumption during the study period and improvement of HAM-D score at endpoint in AUD patients. These results suggest that co-occurrence of MDD and AUD is associated with a lower response to antidepressant treatment and it may reflect an inhibitory effect of ethanol on antidepressants action in the brain.


Alcohol use disorder Depression Comorbidity Antidepressant 



We thank Dr. Tomonobu Sirasaka (Ishibashi Hospital Otaru, Japan), Dr. Kenji Yanbe (Asahiyama Hospital, Sapporo, Japan), Dr. Kimihiro Nakajima (Goryokai Hospital, Sapporo, Japan), Dr. Jiro Miyazawa (Tokiwa Hospital, Sapporo, Japan), and Dr. Tomonari Irie (Nakae Hospital, Sapporo, Japan).


  1. Agartz I, Momenan R, Rawlings RR et al (1999) Hippocampal volume in patients with alcohol dependence. Arch Gen Psychiat 56:356–363PubMedCrossRefGoogle Scholar
  2. Badawy AA, Doughrty DM, Marsh-Richard DM et al (2009) Activation of liver tryptophan pyrrolase mediates the decrease in tryptophan availability to the brain after acute alcohol consumption by normal subjects. Alcohol Alcohol 44:267–271PubMedCentralPubMedCrossRefGoogle Scholar
  3. Bertolote JM, Fleischmann A (2002) Suicide and psychiatric diagnosis: a worldwide perspective. World Psychiat Off J World Psychiatric Assoc (WPA) 1:181–185Google Scholar
  4. Bremner JD (2002) Structural changes in the brain in depression and relationship to symptom recurrence. CNS Spectr 7(129–130):135–139Google Scholar
  5. Conner KR, McCloskey MS, Duberstein PR (2008) Psychiatric risk factors for suicide in the alcohol-dependent patient. Psychiatr Ann 38:742–748CrossRefGoogle Scholar
  6. Cornelius JR, Salloum IM, Day NL et al (1996) Patterns of suicidality and alcohol use in alcoholics with major depression. Alcohol Clin Exp Res 20:1451–1455PubMedCrossRefGoogle Scholar
  7. Crews FT, Nixon K, Wilkie ME (2004) Exercise reverses ethanol inhibition of neural stem cell proliferation. Alcohol 33:63–71PubMedCrossRefGoogle Scholar
  8. Davis LL, Rush JA, Wisniewski SR et al (2005) Substance use disorder comorbidity in major depressive disorder: an exploratory analysis of the Sequenced Treatment Alternatives to Relieve Depression cohort. Compr Psychiatry 46:81–89PubMedCrossRefGoogle Scholar
  9. Davis LL, Frazier E, Husain MM et al (2006) Substance use disorder comorbidity in major depressive disorder: a confirmatory analysis of the STAR*D cohort. Am J Addict 15:278–285PubMedCrossRefGoogle Scholar
  10. Davis LL, Wisniewski SR, Howland RH et al (2010) Does comorbid subsutance use disorder impair recovery from major depression with SSRI treatment? an analysis of the STAR*D level one treatment outcomes. Drug Alcohol Depend 107:161–170PubMedCrossRefGoogle Scholar
  11. Donovan DM, Kivlahan DR, Doyle SR et al (2006) Concurrent validity of the Alcohol Use Disorders Identification Test (AUDIT) and AUDIT zones in defining levels of severity among out-patients with alcohol dependence in the COMBINE study. Addiction 101:1696–1704PubMedCrossRefGoogle Scholar
  12. Fortney JC, Booth BM, Curran GM (1999) Do patients with alcohol dependence use more services? a comparative analysis with other chronic disorders. Alcohol Clin Exp Res 23:127–133PubMedCrossRefGoogle Scholar
  13. Gilman SE, Abraham HD (2001) A longitudinal study of the order of onset of alcohol dependence and major depression. Drug Alcohol Depend 63:277–286PubMedCrossRefGoogle Scholar
  14. Grant BF, Dawson DA (1998) Age of onset of drug use and its association with DSM-IV drug abuse and dependence: results from the National Longitudinal Alcohol Epidemiologic Survey. J Subst Abuse 10:163–173PubMedCrossRefGoogle Scholar
  15. Grant BF, Hartford TC (1995) Comorbidity between DSM-IV alcohol use disorders and major depression: results of a national survey. Drug Alcohol Depend 39:197–206PubMedCrossRefGoogle Scholar
  16. Hamilton M (1960) A rating scale for depression. J Neurol Neurosurg 23:56–62CrossRefGoogle Scholar
  17. Hasin DS, Grant BF (2002) Major depression in 6050 former drinkers: association with past alcohol dependence. Arch Gen Psychiat 59:794–800PubMedCrossRefGoogle Scholar
  18. Hasin DS, Liu X, Nunes E et al (2002) Effects of major depression on remission and relapse of substance dependence. Arch Gen Psychiat 59:375–380PubMedCrossRefGoogle Scholar
  19. Hiro H, Shima S (1996) Availability of the Alochol Use Disorders Identification Test (AUDIT) for a complete health examination in Japan. Jpn J Alcohol Drug Depend 31:437–450 (in Japanese)Google Scholar
  20. Hiro H, Shima S (1997) The effectiveness of CAGE and AUDIT in the detection of problem drinkers. Jpn J Clin Med 55:589–593 (in Japanese)Google Scholar
  21. Inagaki A, Inada T (2006) Dose equivalence of psychotropic drugs. Part X VIII: dose equivalence of psychotropic drugs: 2006-Version. Jpn J Clin Psychopharmacol 9:1443–1447 (in Japanese)Google Scholar
  22. Iovieno N, Tedeschini E, Bentley KH et al (2011) Antidepressants for major depressive disorder and dysthymic disorder in patients with comorbid alcohol use disoreders: a meta-analysis of placebo-controlled randomized trials. J Clin Psychiatry 72:1144–1151PubMedCrossRefGoogle Scholar
  23. Kessler RC, Crum RM, Warner LA et al (1997) Lifetime co-occurrence of DSM-III-R alcohol abuse and dependence with other psychiatric disorders in the National Comorbidity Survey. Arch Gen Psychiatry 53:232–240Google Scholar
  24. Mueller TI, Lavori PW, Keller MB et al (1994) Prognostic effect of the variable course of alcoholism on the 10-year course of depression. Am J Psychiat 151:701–706PubMedCrossRefGoogle Scholar
  25. Nandi A, Beard JR, Galea S (2009) Epidemiologic heterogeneity of common mood and anxiety disorders over the lifecourse in the general population: a systematic review. BMC Psychiatry 9(1):31PubMedCentralPubMedCrossRefGoogle Scholar
  26. Nixon K, Crews FT (2004) Temporally specific burst in cell proliferation increases hippocampal neurogenesis in protracted abstinence from alcohol. J Neurosci 24:9714–9722PubMedCrossRefGoogle Scholar
  27. Nunes E, Levin F (2004) Treatment of depression in patients with alcohol or other drug dependence. A meta-analysis. JAMA 291:1887–1896PubMedCrossRefGoogle Scholar
  28. Otsubo T, Tanaka K, Koda R et al (2005) Reliability and validity of Japanese version of the Mini-International Neuropsychiatric Interview. Psychiatry Clin Neurosci 59:517–526PubMedCrossRefGoogle Scholar
  29. Ozawa H, Gsell W, Frölich L et al (1993) Imbalance of the Gs and Gi/o function in post-mortem human brain of depressed patients. J Neural Transm Gen Sect 94:63–69PubMedCrossRefGoogle Scholar
  30. Pandey SC, Saito T, Yoshimura M et al (2001) cAmp signaling cascade: a promising role in ethanol tolerance and dependence. Alcohol Clin Exp Res 25(Suppl):46S–48SPubMedCrossRefGoogle Scholar
  31. Pettinati HM (2004) Antidepressant treatment of co-occurring depression and alcohol dependence. Biol Psychiatry 56:785–792PubMedCrossRefGoogle Scholar
  32. Pettinati HM, O’Brien CP, Dundon WD (2013) Current status of co-occurring mood and substance use disorders: a new therapeutic target. Am J Psychiatry 170:23–30PubMedCentralPubMedCrossRefGoogle Scholar
  33. Saunders JB, Aasland OG, Babor TF et al (1993) Development of the Alcohol Use Disorders Identification Test (AUDIT): WHO Collaborative Project on Early Detection of Persons with Harmful Alcohol Consumption-II. Addiciton (Abingdon, England) 88:791–804Google Scholar
  34. Sher L, Stanley BH, Harkavy-Friedman JM et al (2008) Depressed patients with co-occurring alcohol use disorders: a unique patient population. J Clin Psychiatry 69:907–915PubMedCrossRefGoogle Scholar
  35. Sullivan LE, Fiellin DA, O’Conner PG (2005) The prevalence and impact of alcohol problems in major depression: a systematic review. Am J Med 118:330–341PubMedCrossRefGoogle Scholar
  36. Tabuse H, Kalali A, Azuma H et al (2007) The new GRID Hamilton Rating Scale for Depression demonstrates excellent inter-rater reliability for inexperienced and experienced raters before and after training. Psychiat Res 153:61–67CrossRefGoogle Scholar
  37. Ukai W, Ishii T, Hashimoto E et al (2009) The common aspects of pathophysiology of alcoholism and depression. Jap J Alcohol Drug Dependence 44:704–711Google Scholar
  38. World Health Organization (1992) The ICD-10 Classification of Mental and Behavioural Disorders: Clinical descriptions and diagnostic guidelines, GenevaGoogle Scholar

Copyright information

© Springer-Verlag Wien 2014

Authors and Affiliations

  • Eri Hashimoto
    • 1
  • Masaya Tayama
    • 1
  • Hiromi Ishikawa
    • 1
  • Megumi Yamamoto
    • 1
  • Toshikazu Saito
    • 1
  1. 1.Department of Neuropsychiatry, School of MedicineSapporo Medical UniversitySapporoJapan

Personalised recommendations