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

Notice to readers: This article has been edited from its original version to include additional clarifications from the cited literature. These additions reflect the recognized complexities and the nuanced approach to care for those with alcohol use, mood and anxiety disorders.

Original publication date: November 26, 2025

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 a meta-analysis of depression and substance use among individuals with alcohol use disorders, 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 alcohol use disorder (AUD), even when there is a concurrent depressive or anxiety disorder. The guideline authors justified their recommendations by citing data that suggested a link between serotonergics and worse outcomes in select populations with a concurrent AUD diagnosis^5-8 and several meta-analyses which have not demonstrated a consistent effect of SSRIs on mood disorders with comorbid addictions.^9-12

The recommendation generated a variety of responses, including a number of calls for nuance in its interpretation.^13,14 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.¹⁵ Further, CANMAT go so far as to make specific recommendations on first-line medical management for these common co-morbid disorders.¹⁶

Nonetheless, the caution expressed by the AUD guideline is not novel. Although the language and strength of the CRISM recommendation are new, the principles are consistent with previous guidance from Psychiatry Choosing Wisely.¹⁷ 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 data supporting this recommendation, only limited conclusions can be drawn about how best to support patients with concurrent AUD and depressive or anxiety disorders.

Two of the cited randomized controlled trials examined SSRIs in the context of alcohol dependence or AUD, rather than as treatment for a clearly established depressive or anxiety disorder. The citalopram trial by Charney et al. found that citalopram was associated with worse drinking outcomes compared to placebo.⁶ The trial enrolled both depressed and non-depressed individuals, excluded patients already taking psychiatric medications, and had a high rate of attrition during treatment and follow-up. The sertraline trial by Kranzler et al. similarly examined sertraline as a treatment for alcohol dependence rather than as treatment for a primary depressive or anxiety disorder.⁷ Its findings were heterogeneous: the effect of sertraline on alcohol outcomes varied by age of onset and serotonin transporter genotype, with late-onset patients who were L′ homozygotes drinking less with sertraline, while early-onset patients had better outcomes with placebo. Furthermore, the trial excluded participants with a current diagnosis of major depressive disorder, though those with a history of depression were permitted to enroll. A third cited trial examined trazodone (not an SSRI) for sleep disturbance following alcohol detoxification and found worse abstinence outcomes and increased drinks per drinking day after discontinuation compared to placebo, though its relevance to prescribing serotonergic agents for concurrent depressive or anxiety disorders is limited given that it addressed sleep rather than mood or anxiety as its primary indication.⁸ These studies, taken together, have significant design limitations that constrain their applicability to patients with concurrent depressive or anxiety disorders, but do collectively signal the importance of close monitoring for harm when serotonergic agents are considered in the context of alcohol use.

The guideline also cited four systematic reviews examining SSRIs and other antidepressants in patients with co-occurring depressive or anxiety disorders and AUD. A Cochrane systematic review of pharmacotherapy for anxiety disorders with comorbid alcohol use disorders found very low-quality evidence that paroxetine may improve global clinical response as measured by the Clinical Global Impressions-Improvement scale, but found no evidence that paroxetine reduced anxiety symptom severity.⁹ This review found little evidence that any of the pharmacological agents examined had a meaningful impact on alcohol use outcomes in either direction. A second Cochrane systematic review focused on patients with both a current depressive disorder and alcohol dependence and found low-quality evidence that antidepressants had positive effects on some outcomes related to depression and alcohol use, but not others; the authors nevertheless concluded that antidepressants may be useful for treating depression, alcohol dependence, or both.¹⁰ A third systematic review and meta-analysis by Stokes et al. examined pharmacological treatment of mood disorders with comorbid addictions more broadly and did not demonstrate a significant effect of SSRIs on mood disorder outcomes in this population.¹¹ A fourth systematic review and network meta-analysis examined adults with comorbid alcohol use and depressive disorders and found low-confidence evidence that SSRIs may produce a small reduction in alcohol use, and moderate-confidence evidence that SSRIs may improve functional status. However, SSRIs were also associated with a likely increase in adverse events, a finding that did not reach statistical significance.¹²

Taken together, these systematic reviews suggest that the evidence base for antidepressant use in patients with concurrent AUD and depressive or anxiety disorders is limited and heterogeneous. For SSRIs specifically, the available meta-analytic data has been mixed with regards to benefits and harms in this population.^9-12 These findings underscore the need for a cautious, individualized approach when considering antidepressant treatment for patients with these co-occurring disorders.

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 address severe psychiatric conditions when prescribing these medications (according to on-label indications) may be appropriate.”⁴ A careful clinical assessment is 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.¹⁵ 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.¹⁷ For moderately to severely depressed patients 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 in these cases with concurrent treatment with gold-standard AUD approaches is recommended.
4. We recommend consideration of factors such as patient preference and engagement, chronicity of symptoms, recurrence of depressive episodes, 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 #13.¹⁵
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.

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
4. Canadian Network for Mood and Anxiety Treatments (CANMAT) 2016 clinical guidelines for the management of adults with major depressive disorder: section 3. pharmacological treatments
5. CPA Position Statement: Concurrent Disorders: Treatment of Comorbid Alcohol Use Disorder and Major Depressive Disorder

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. 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)
10. 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)
11. Stokes PRA, Jokinen T, Amawi S, et al. Pharmacological Treatment of Mood Disorders and Comorbid Addictions: A Systematic Review and Meta-Analysis: Traitement Pharmacologique des Troubles de L’humeur et des Dépendances Comorbides: Une Revue Systématique et une Méta-Analyse. Can J Psychiatry. 2020;65(11):749-769. doi:10.1177/0706743720915420 (View)
12. 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)
13. 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)
14. 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)
15. 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)
16. Beaulieu S, Saury S, Sareen J, et al. The Canadian Network for Mood and Anxiety Treatments (CANMAT) task force recommendations for the management of patients with mood disorders and comorbid substance use disorders. Ann Clin Psychiatry. 2012;24(1):38-55. (View with UBC)
17. Choosing Wisely Canada. Thirteen things physicians and patients should question. 2018. Accessed June 6^th, 2025. (View PDF)

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