Navigating controversies and complexity in concurrent alcohol use, and mood and anxiety disorders management

Disclaimer: This article will not address Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs) or Norepinephrine Reuptake Inhibitors (NRIs) as there is insufficient evidence to offer guidance at the time of writing.

Authors

Vivian Tsang MD (biography, no disclosures), Julius Elefante MD (biography and disclosures) and Paxton Bach MD, MSc, ABIM, FRCPC, FASAM (biography and disclosures)

Dr. Julius Elefante’s disclosures: I have received funding from the US National Institute on Drug Abuse (NIDA) Grant: R25-DA037756 as part of the NIDA-funded research training fellowship offered in partnership with the BC Centre on Substance Use, St. Paul’s Hospital, and the University of British Columbia. I have received educational funds for the development of lectures for UBC, Vancouver Coastal Health, Fraser Health, and the Provincial Health Services Authority. Mitigating potential bias: None of these organizations has influenced the content of my work at any stage.

Dr. Paxton Bach’s disclosures: Received honoraria from UBC CPD: member of the UBC CPD Scientific Planning Committee for an online module on the clinical management of high-risk drinking and alcohol use disorder for primary care providers. Received honoraria for speaking engagements from BCCSU ECHO Program, Moms Stop the Harm, Kentucky Overdose Prevention Education Network, Prince Albert Addiction Medicine Network, American College of Academic Addiction Medicine, American Society of Addiction Medicine (no ongoing relationships and no funding received from for-profit organizations). Received funding from CIHR, Michael Smith Health Research BC, for research grants not related to this content. Mitigating potential bias: Recommendations are consistent with published guidelines: CCSA and BC AUD Guidelines.

What care gaps or frequently asked questions we have noticed

About 80% of Canadians consume alcohol and approximately one in five Canadians will meet criteria for alcohol use disorder at some point in their lives.¹ Of all Canadians who endorsed a history of alcohol use in the last year, 21% experienced at least one alcohol-related harm.² Patients with alcohol use disorders (AUD) commonly present with concurrent mood and anxiety disorders. According to data from the US National Comorbidity Survey, the lifetime prevalence of major depression is estimated to be approximately 24.3% among men with alcohol dependence, and 48.5% among women with alcohol dependence.³

The Canadian Research Initiative in Substance Matters (CRISM) recently published the Canadian clinical guidelines for the clinical management of high-risk drinking and alcohol use disorder,⁴ providing evidence-based recommendations on the management of AUD. Its thirteenth recommendation has proven to be controversial as it strongly recommended against the prescription of selective serotonin reuptake inhibitor (SSRI) antidepressants for adults and youth with AUD, even when there is a concurrent depressive or anxiety disorder. The guideline authors justify their recommendations by citing data that suggests a link between SSRIs and worse outcomes in select populations with a concurrent AUD diagnosis.^5-11

The recommendation generated a variety of responses, including a number of calls for nuance in its interpretation.^12,13 The studies cited have significant limitations to consider when navigating the diversity and complexity of patients with concurrent disorders. Moreover, the standard for treatment for moderate and severe depression, as recommended by the Canadian Network for Mood and Anxiety Treatments (CanMAT) Task Force, is to offer the full range of pharmacological and psychological treatment.¹⁴ Nonetheless, the caution expressed by the AUD guideline is not novel. Although the language and strength of the recommendation are new, the principles are consistent with previous guidance from Psychiatry Choosing Wisely.¹⁵ This leaves several critical questions in how recommendation #13 of CRISM can be reconciled with the breadth of individuals presenting with concurrent depression and/or anxiety and AUD in routine clinical practice, including:

• • In what scenarios might prescribing SSRIs among patients with AUD still be considered?

  • What are the exceptions to recommendation #13 of the CRISM AUD guidelines, if any?

  • What are additional considerations in the interpretation of this nuanced recommendation?

  • Do the CRISM AUD guidelines address deprescribing of SSRIs?

Data that answers these questions or gaps

In reviewing the citations supporting this recommendation, limited conclusions can be drawn regarding how to best support patients with concurrent AUD and depressive or anxiety disorders. Two of the cited randomized controlled trials (RCTs) evaluated the use of SSRIs for the treatment of AUD rather than the use of SSRIs for the treatment of depressive or anxiety disorders in patients with AUD, and also actively excluded patients with a primary psychiatric illness.^6,7 One of these RCTs, which cited poor drinking outcomes after citalopram treatment, used the medication in the treatment of AUD instead of a known depressive or anxiety disorder.⁶ This study, which included both patients with and without depression, excluded patients who were already using any psychiatric medications and also had a high rate of attrition in trial completion and follow-up. Similarly, a second RCT cited, which tested the use of sertraline for alcohol dependence, explored its use for treatment of AUD, not for a primary depressive or anxiety disorder and excluded patients with a concurrent diagnosis of major depressive disorder.⁷ What is clear from these two studies, however, is that SSRIs have no demonstrated efficacy in the treatment of AUD. A third primary study cited an RCT that demonstrated poor drinking outcomes with the serotonergic agent trazodone. However, it appears that the increase in drinking occurred after cessation of this medication.⁸

The guideline also cited three systematic reviews that examined the evidence for treatment of antidepressants in patients with co-occurring depressive or anxiety disorders and AUD. One review looking at the population of interest with both a current depressive disorder and alcohol dependence noted only modest clinical relevance. Still, the authors of this systematic review concluded that antidepressants may be useful for the treatment of depression, alcohol dependence or both.⁹ Another systematic review and meta-analysis of a similar patient population concluded that SSRIs may offer a small benefit over placebo and may result in increased remission from alcohol use, though the analysis was of low confidence and the authors also cautioned on the higher risk of adverse events with SSRI use.¹⁰ A systematic review on the use of paroxetine for the treatment of AUD and concurrent anxiety disorder concluded a very low quality of evidence on global clinical response to treatment.¹¹ These three systematic reviews and meta-analyses indicate a modest benefit of SSRIs and comment on the low quality of evidence that resulted in low confidence for any benefit conferred by treatment.

What we recommend

1. We recommend that clinicians refrain from prescribing SSRIs for the treatment of AUD, as there is evidence against the use of SSRIs solely for the treatment of AUD. Practitioners should refer to evidence-based first-line therapies for AUD treatment, such as naltrexone and acamprosate.⁴ In cases of mild mood disorders, especially when symptoms are difficult to delineate between AUD and concurrent mood disorders, treatment of AUD should be prioritized.
2. We highlight that the CRISM AUD guidelines state specifically that the thirteenth recommendation does not apply in cases of severe psychiatric illness. However, careful clinical assessment is still required for prescribing. SSRIs can be avoided as first-line therapy for patients with concurrent AUD and mild mood disorders, and non-pharmacological treatment options for mood disorders can be considered using the Canadian Network for Mood and Anxiety Treatments (CANMAT) guidelines as guidance. We recommend considering psychiatric reassessment and initiating antidepressants if mood symptoms remain after a period of documented abstinence from alcohol of two to four weeks.¹⁵ For those who are moderately to severely depressed, first-line pharmacotherapies are indicated, especially where there are safety risks.
3. It is important to consider that there will remain a number of patients whose goals regarding alcohol use may not be compatible with abstinence. Consideration of patient safety is paramount when deciding whether to initiate concurrent treatment for mood symptoms. Close follow-up and monitoring for potential harms are recommended in cases involving concurrent treatment with standard AUD approaches.
4. We recommend consideration of factors such as patient preference and engagement, chronicity of symptoms, previous experience with antidepressants and alternative treatments of mood disorders, such as non-pharmacological options in the CANMAT guidelines when making the clinical decision in applying recommendation #13.
5. We recommend clinicians consider judiciously the risk-benefit balance of deprescribing established SSRI treatment. Consider that deprescribing may bring inadvertent consequences such as the worsening of an underlying mood or anxiety disorder, or discontinuation symptoms (e.g., rebound anxiety, insomnia) that patients may try to ameliorate with increased drinking. Collaborative decision-making, close follow-up and ongoing longitudinal care are strongly recommended to navigate this common yet challenging clinical scenario.

Further reading

The Centre for Addiction and Mental Health (CAMH) has put out a detailed discussion on pharmacological considerations in the context of concurrent alcohol use and depression, along with specific recommendations. The guidelines in this article are congruent with their recommendations and we encourage readers to refer directly to their website for evidence-informed clinical recommendations. While we have not provided exhaustive guidance on all medication classes here, readers may find CAMH’s resource helpful for additional context and treatment considerations.

Resources

1. Alcohol Use: Screening, Determining Risk, and Evidence-Based Treatment (UBC CPD eLearning Course)
2. Canadian Clinical Guideline: High Risk Drinking and Alcohol Use Disorder
3. BC Guidelines: AUD Treatment Care Pathway

References

1. Canadian Centre on Substance Abuse and Addictions. Alcohol: Canadian drug summary. Accessed May 21, 2025. (View PDF)
2. Government of Canada. Dry February, you say? National Statistical Agency of Canada. . Accessed May 21, 2025. (View)
3. Conner KR, Pinquart M, Gamble SA. Meta-analysis of depression and substance use among individuals with alcohol use disorders. J Subst Abuse Treat. 2009;37(2):127-37. doi:10.1016/j.jsat.2008.11.007 (View)
4. Wood E, Bright J, Hsu K, et al; Canadian Alcohol Use Disorder Guideline Committee. Canadian guideline for the clinical management of high-risk drinking and alcohol use disorder. CMAJ. 2023;195(40):E1364–E1379. doi:10.1503/cmaj.230715 (View)
5. Brookwell L, Hogan C, Healy D, Mangin D. Ninety-three cases of alcohol dependence following SSRI treatment. Int J Risk Saf Med. 2014;26(2):99-107. doi:10.3233/JRS-140616 (View with UBC)
6. Charney DA, Heath LM, Zikos E, Palacios-Boix J, Gill KJ. Poorer drinking outcomes with citalopram treatment for alcohol dependence: a randomized, double-blind, placebo-controlled trial. Alcohol Clin Exp Res. 2015;39(9):1756–1765. doi:10.1111/acer.12802 (View)
7. Kranzler HR, Armeli S, Tennen H, et al. A double-blind, randomized trial of sertraline for alcohol dependence: moderation by age of onset and 5-hydroxytryptamine transporter-linked promoter region genotype [published correction appears in J Clin Psychopharmacol. 2011;31(5):576]. J Psychopharmacol. 2011;31(1):22–30. doi:10.1097/JCP.0b013e31820465fa (View article or view correction with UBC)
8. Friedmann PD, Rose JS, Swift R, Stout RL, Millman RP, Stein MD. Trazodone for sleep disturbance after alcohol detoxification: a double-blind, placebo-controlled trial. Alcohol Clin Exp Res. 2008;32(9):1652–1660. doi:10.1111/j.1530-0277.2008.00742.x (View)
9. Agabio R, Trogu E, Pani PP. Antidepressants for the treatment of people with co-occurring depression and alcohol dependence. Cochrane Database Syst Rev. 2018;4(4), CD008581. doi:10.1002/14651858.CD008581.pub2 (View)
10. Grant S, Azhar G, Han E, et al. Clinical interventions for adults with comorbid alcohol use and depressive disorders: A systematic review and network meta-analysis. PLoS Med. 2021;18(10):e1003822. doi:10.1371/journal.pmed.1003822 (View)
11. Ipser JC, Wilson D, Akindipe TO, Sager C, Stein DJ. Pharmacotherapy for anxiety and comorbid alcohol use disorders. Cochrane Database Syst Rev. 2015;1(1):CD007505. doi:10.1002/14651858.CD007505.pub2 (View)
12. Bahji A, Danilewitz M, Sloan M, Tang V, Crockford D. Concerns regarding the recommendation against prescribing selective serotonin reuptake inhibitors in the Canadian guideline for the clinical management of high-risk drinking and alcohol use disorder. CMAJ. 2024;196(10):E346-E347. doi:10.1503/cmaj.149917-l (View)
13. Elefante RJO, Lu C, Bach PJ. Navigating the nuances of the Canadian guideline’s stance on selective serotonin reuptake inhibitors in concurrent alcohol use disorder and mood or anxiety disorders. CMAJ. 2024;196(10):E348. doi: 10.1503/cmaj.150034-l (View)
14. Kennedy SH, Lam RW, McIntyre RS et al. Canadian Network for Mood and Anxiety Treatments (CANMAT) 2016 clinical guidelines for the management of adults with major depressive disorder: section 3. pharmacological treatments [Published correction appears in Can J Psychiatry. 2017;62(5):356]. Can J Psychiatry. 2016;61(9):540-560. doi:10.1177/0706743716659417 (View article or view correction)
15. Choosing Wisely Canada. Thirteen things physicians and patients should question. 2018. Accessed June 6^th, 2025. (View PDF)

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