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Erin Knox, PharmD, BCPP, Director of Experiental Education
UCI School of Pharmacy & Pharmaceutical Sciences, Irvine, CA

“The relationship between depression and alcohol use is complex. Treatment of dual diagnosis patients is challenging.”

Dr. Dana Chiulli, Pharm.D., BCPP, began her informative presentation at CPNP’s 2021 Annual Meeting with this sobering introduction, preparing the audience for a review on this often difficult to treat patient population. She described her goal of helping participants develop a framework for treating the patient with depression and alcohol use disorder (AUD).

Prevalence of Major Depressive Disorder (MDD) with AUD is estimated to be 14.1% 1, emphasizing the high likelihood that psychiatric pharmacists will encounter patients requiring treatment for these co-occurring conditions. Dr. Chiulli described the complicated relationship between these disorders that share common risk factors and similar pathophysiology: AUD increases the risk for depressive disorders, and depressive disorders increase the risk of AUD. Compared to the general population, people with AUD are 2.3 times as likely to have alcohol dependence; people with alcohol dependence are 3.7 times as likely to have MDD in the previous year 2.

Various treatment modalities may be employed, though the best response is often seen with the integrated treatment approach, entailing one unified treatment team responsible for the management of AUD and depression in a single setting. This approach has demonstrated evidence for increased retention and decreased hospitalization rates, although access to this treatment type is limited for many patients3.

Pharmacological interventions have been studied with mixed results. Dr. Chiulli presented a meta-analysis demonstrating no significant reduction in alcohol use for patients with AUD and without MDD who were treated with antidepressants4. For patients with co-occurring AUD and MDD, studies have demonstrated differing results. In one study, early initiation of antidepressants decreased risk of relapse with alcohol 5, however other trials found no difference in alcohol use for patients treated with SSRIs 4,6.

Dr. Chiulli reviewed trials evaluating medication assisted treatment (MAT) for alcohol use disorder in patients with MDD. This pharmacological intervention led to decreased depression severity and fewer drinking days with more consecutive days of absence. This trial also found that patients with depression were 7.58 times more likely to become non-depressed if they were continuously abstinent from alcohol 7.

A trial evaluating sertraline and naltrexone with cognitive behavioral therapy (CBT) found the fewest reported adverse effects with sertraline combination with naltrexone. Compared to either pharmacological intervention alone, combination therapy led to the longest time to any alcohol use and longest time to first heavy drinking.8 Dr. Chiulli pointed out that patients treated for AUD and MDD may want to pursue non-pharmacological treatment; several of these interventions were reviewed, including CBT and relapse prevention therapy.

No specific treatment guidelines are published for these co-occurring disorders; antidepressants combined with MAT are generally accepted as the best option. Additional medication pearls were reviewed by Dr. Chiulli:

  • Due to relative safety and tolerability, SSRIs are preferred over TCAs, despite mixed results on which provides better efficacy; sertraline is the most widely studied SSRI.
  • No significant drug-drug interactions exist between MAT and antidepressants.
  • Severe renal impairment may preclude the use of acamprosate or duloxetine.
  • Naltrexone, vortioxetine, MAOIs, or duloxetine should not be used in patients with hepatic impairment.
  • Patients with poor adherence are not ideal candidates for disulfiram but may be considered for naltrexone long-acting injectable.

An important consideration is the risk for alcohol-medication-related interactions, including the lowered seizure threshold with bupropion and TCAs, as well as the potential for enhanced psychomotor impairment. Although worsened depression has been reported with naltrexone and acamprosate, Dr. Chiulli emphasized that this is not a precaution nor contraindication for use, rather use of these medications has demonstrated improvement in depression symptomatology.

To highlight considerations in treatment selection, Dr. Chiulli presented a patient case, employing audience polling and reviewing multiple touchpoints over time to describe the consideration that went into each treatment decision.

Take home points:

  • AUD and MDD share symptoms and pathophysiology, each having the potential to worsen the other.
  • Treating patients with co-occurring AUD and MDD is challenging, complicated by a lack of treatment guidelines.
  • Integrated treatment, utilizing the same treatment team in one setting, leads to the best patient outcomes.
  • Combination of antidepressants + MAT is considered first-line pharmacotherapy, with SSRIs generally preferred over other classes of antidepressants.


  1. Hasin DS, Goodwin RD, Stinson FS, et al. Epidemiology of major depressive disorder: results from the National Epidemiologic Survey on Alcoholism and Related Conditions. Archives of general psychiatry. 2005 Oct 1;62(10):1097-106.
  2. Grant BF, Stinson FS, Dawson DA, et al. Prevalence and co-occurrence of substance use disorders and independent tmood and anxiety disorders: Results from the national epidemiologic survey on alcohol and related conditions. Archives of general psychiatry. 2004 Aug 1;61(8):807-16.
  3. Drake RE, Mueser KT, Clark RE, et al. The course, treatment, and outcome of substance disorder in persons with severe mental illness. American Journal of Orthopsychiatry. 1996 Jan;66(1):42-51.
  4. Torrens M, Fonseca F, Mateu G, et al. Efficacy of antidepressants in substance use disorders with and without comorbid depression: a systematic review and meta-analysis. Drug and alcohol dependence. 2005 Apr 4;78(1):1-22.
  5. Greenfield SF, Weiss RD, Muenz LR, et al. The effect of depression on return to drinking: a prospective study. Archives of general psychiatry. 1998 Mar 1;55(3):259-65.
  6. Iovieno N, Tedeschini E, Bentley KH, et al. Antidepressants for major depressive disorder and dysthymic disorder in patients with comorbid alcohol use disorders: a meta-analysis of placebo-controlled randomized trials. J Clin Psychiatry. 2011 Aug;72(8):1144-51.
  7. Lejoyeux M, Lehert P. Alcohol-use disorders and depression: results from individual patient data meta-analysis of the acamprosate-controlled studies. Alcohol and Alcoholism. 2011 Jan 1;46(1):61-7.
  8. Pettinati HM, Oslin DW, Kampman KM, et al. A double-blind, placebo-controlled trial combining sertraline and naltrexone for treating co-occurring depression and alcohol dependence. American Journal of Psychiatry. 2010 Jun 1;167(6):668-75.
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