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- Page navigation anchor for Addressing the Risks of Antidepressants in Persons with Alcohol Use DisordersAddressing the Risks of Antidepressants in Persons with Alcohol Use Disorders
We thank Bahji and colleagues and Elefante and colleagues for their interest in the guideline. We appreciate the opportunity to explain that the guideline’s cautions against prescribing certain antidepressants was based not only on the evidence that some antidepressants appear to be largely ineffective among those with alcohol use disorder (AUD),1,2 but also the literature demonstrating risks of increased alcohol use with certain antidepressants.
Bahji and colleagues cited several individual studies suggesting benefits of SSRI but the majority of these were not placebo-controlled. Conversely, various meta-analyses of antidepressants in AUD have found no effect of SSRIs on depressive symptoms.1-3 In particular, the Cochrane review by Agabio et al found no effect with SSRIs on final depression score, change in score, number of responders, or number of remissions relative to placebo.2 Similarly, the relevant Cochrane review by Ipser et al found no benefit of SSRI on anxiety symptom severity.3
Bahji and colleagues also cited a study showing efficacy for combined SSRI with naltrexone, but a subsequent meta-analysis including that study concluded SSRIs “either alone or in combination with relapse prevention medications such as naltrexone, had no significant effect on depressive symptoms.”1
Additionally, the guideline summarized an under-appreciated literature demonstrating that certain antidepressants appear to increase alcohol use in some patients. C...
Show MoreCompeting Interests: Evan Wood is a physician who works for Vancouver Coastal Health in the area of withdrawal management and undertakes work in the area of occupational addiction medicine. Dr. Wood is also a professor of medicine based at the University of British Columbia (UBC), a position supported by a Canadian Institutes of Health Research (CIHR) Tier 1 Canada Research Chair, and has received salary support from an R01 from the US National Institute on Drug Abuse, paid to UBC. Dr. Wood’s research lab is further supported by CIHR grants to the Canadian Research Initiative in Substance Misuse. Dr. Wood has also undertaken consulting work in legal matters related to substance use disorders and for a mental health company called Numinus Wellness, where Dr. Wood is former chief medical officer; Dr. Wood has also received compensation in the form of equity in Numinus. Dr. Wood reports receiving honoraria for non-industry related lectures and presentations (e.g., at academic or educational conferences), including a talk at the Canadian Society of Addiction Medicine (CSAM) paid by CSAM conference; a Rounds Presentation at Dalhousie University (paid by the University); and an educational talk for the allied health educational platform, Executive Links (all outside the submitted work). Dr. Wood has also received payment for expert reports and expert testimony in legal matters pertaining to substance use disorder, including from the Canadian Medical Protective Association and from trade unions representing workers with possible substance use disorder. Dr. Wood has received travel support from the CIHR. No other competing interests were declared.References
- 1. Stokes PRA, Jokinen T, Amawi S, et al. Pharmacological Treatment of Mood Disorders and Comorbid Addictions: A Systematic Review and Meta-Analysis: Traitement Pharmacologique... Can J Psychiatry. Nov 2020;65(11):749-769. doi:10.1177/0706743720915420
- 2. Agabio R, Trogu E, Pani PP. Antidepressants for the treatment of people with co-occurring depression and alcohol dependence. The Cochrane database of systematic reviews. Apr 24 2018;4(4):Cd008581. doi:10.1002/14651858.CD008581.pub2
- 3. Ipser JC, Wilson D, Akindipe TO, et al. Pharmacotherapy for anxiety and comorbid alcohol use disorders. The Cochrane database of systematic reviews. Jan 20 2015;1(1):Cd007505. doi:10.1002/14651858.CD007505.pub2
- 4. Kranzler HR, Armeli S, Tennen H, et al. A double-blind, randomized trial of sertraline for alcohol dependence: moderation by age of onset [corrected] and... J Clin Psychopharmacol. Feb 2011;31(1):22-30. doi:10.1097/JCP.0b013e31820465fa
- 5. Friedmann PD, Rose JS, Swift R, et al. Trazodone for sleep disturbance after alcohol detoxification: a double-blind, placebo-controlled trial. Alcoholism, clinical and experimental research. Sep 2008;32(9):1652-60. doi:10.1111/j.1530-0277.2008.00742.x
- Page navigation anchor for RE: Navigating the Nuances of the Canadian Guideline's Stance on SSRIs in Concurrent Alcohol Use Disorder and Mood or Anxiety DisordersRE: Navigating the Nuances of the Canadian Guideline's Stance on SSRIs in Concurrent Alcohol Use Disorder and Mood or Anxiety Disorders
The recently published Canadian Guideline on Alcohol Use Disorder (AUD) advances the evidence-based management of AUD in Canada.1 A novel addition is a strong recommendation that SSRIs are not to be prescribed for the treatment of concurrent anxiety or mood disorders in the context of AUD, which warrants an exploration of the nuance behind this guidance.
The complete AUD guideline provides an expanded rationale, stating there is a “lack of high-quality evidence supporting the effectiveness of SSRIs for those with concurrent AUD and depression, a potentially higher risk of adverse events including worsening drinking outcomes, and [that] research [demonstrates] a rapid reduction of depressive symptoms following a period of abstinence from alcohol use.”2 For these reasons we agree prescribers should pause before initiating SSRIs in the context of this comorbidity. Similar recommendations have been made by the Canadian Psychiatric Association, which discourages prescribing of antidepressants as first-line treatment in this group,3 as well as the Canadian Network for Mood and Anxiety Treatments task force (though the latter cite data suggesting that sertraline has shown benefit when combined with naltrexone).4
In reviewing the cited evidence,1 however, the risk of worsening drinking outcomes is inconsistent, and the cited RCTs have significant limitations that prevent definitive conclusions. The study of citalopram showing increased alcohol consumption compared t...
Show MoreCompeting Interests: None declared.References
- 1. Wood E et al. Canadian guideline for the clinical management of high-risk drinking and alcohol use disorder. CMAJ. 2023 Oct 16;195(40):E1364-E1379. doi: 10.1503/cmaj.230715. PMID: 37844924; PMCID: PMC10581718.
- 2. Canadian Research Initiative in Substance Misuse. Canadian Guideline for the Clinical Management of High-Risk Drinking and Alcohol Use Disorder. October 2023. www.helpwithdrinking.ca. Retrieved November 21, 2023
- 3. https://choosingwiselycanada.org/recommendation/psychiatry/. Retrieved November 21, 2023
- 4. Beaulieu S 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 Feb;24(1):38-55.
- Page navigation anchor for RE: Concerns Regarding the Recommendation against Prescribing SSRIs in the Canadian Guideline for the Clinical Management of High-Risk Drinking and Alcohol Use Disorder (AUD)RE: Concerns Regarding the Recommendation against Prescribing SSRIs in the Canadian Guideline for the Clinical Management of High-Risk Drinking and Alcohol Use Disorder (AUD)
The Canadian guideline by Wood et al. on high-risk drinking and AUD management highlights an undertreated issue. Most recommendations are supported, but Recommendation 13's caution against SSRIs for individuals with AUD with non-substance-induced MDD or anxiety warrants further consideration due to potential unexplored issues.
The guidelines cite studies by Charney et al. and Friedmann et al., along with a systematic review by Stokes et al., to support Recommendation 13.(1-3) However, these studies have limitations. For example, Charney's study primarily focused on AUD treatment, not depression, making it challenging to conclude SSRIs for AUD with comorbid depression. Friedmann's study used low-dose trazodone, not an SSRI, and did not effectively distinguish between substance-induced and primary depression or anxiety disorders. In essence, these studies weren't designed to assess SSRIs' efficacy for AUD with primary MDD or anxiety disorders, so using them to recommend against SSRIs in these cases is inappropriate.
Unlike studies using antidepressant monotherapy for AUD patients, combining SSRIs with AUD treatment in those also experiencing depression has shown significant benefits. For instance, Pettinati et al. found improved outcomes with sertraline and naltrexone combination.(5) Similarly, Moak et al. reported fewer daily drinks with sertraline and CBT for AUD compared to placebo plus CBT.(4) Integrated care models that integrate s...
Show MoreCompeting Interests: Dr. Bahji’s work was supported by CIHR and Calgary Health Trust research grants. Dr. Danilewitz reports personal fees from the industry for advisory board/speaker fees/consultation/education grants from Eisai Ltd, Otsuka, Lundbeck, Winterlight Labs, Rapids Health Ltd and the Ontario Brain Institute. He receives a stipend from the Canadian Psychiatric Association for administrative work and has received support for academic meeting attendance and presentations. Dr. Sloan receives research funding from the CIHR and the Centre for Addiction and Mental Health Discovery Fund. Dr. Sloan is also supported in part by an Academic Scholar Award from the Department of Psychiatry, University of Toronto. The remaining authors have no conflicts of interest to disclose.References
- 1. https://doi.org/10.1111/acer.12802. 2. https://doi.org/10.1111/j.1530-0277.2008.00742.x. 3. https://doi.org/10.1177/070674372091542. 4. https://doi.org/10.1097/01.jcp.0000095346.32154.41
- 5. Samokhvalov et al. https://doi.org/10.1186/s12888-018-1770-3. 6. Samokhvalov https://doi.org/10.1097/CXA.0000000000000125. 7. Agabio et al. https://doi.org/10.1002%2F14651858.CD008581.pub2
- 8. Ipser et al. https://doi.org/10.1002/14651858.cd007505.pub2. 9. https://doi.org/10.1016/s0306-4603(00)00152-0. 10. https://doi.org/10.1016/s0306-4603(99)00065-9
- 11. https://doi.org/10.1016/j.addbeh.2009.03.008. 12. https://doi.org/10.1016/j.addbeh.2004.08.025. 13. Tang et al. https://doi.org/10.1016/j.jad.2023.07.049
- 14. Davis et al. https://doi.org/10.1016/j.drugalcdep.2009.10.003. 15. Davis et al. https://doi.org/10.1002/da.20918. 16. https://doi.org/10.1111/j.1360-0443.2012.04010.x