CONCOMITANT USE OF ANTIDEPRESSANTS AND ALCOHOL: PHARMACOLOGICAL PITFALLS AND CLINICAL CONSEQUENCES
DOI:
https://doi.org/10.32689/2663-0672-2025-3-14Keywords:
alcohol, ethanol, antidepressants, drug interactions, pharmacokinetics, pharmacodynamicsAbstract
The high comorbidity of depressive disorders and alcohol use disorder (AUD) is a complex clinical challenge. Patients receiving antidepressant pharmacotherapy often continue to consume alcohol. This creates a "clinical pitfall" where the interaction between ethanol and psychotropic drugs not only neutralizes the therapeutic effect but also poses a direct threat to the patient's health. Analysis of recent research and publications. Scientific literature confirms the existence of hazardous pharmacokinetic (competition for CYP450 enzymes) and pharmacodynamic (additive CNS depression) interactions. While classic risks like the tyramine reaction (MAOIs) or cardiotoxicity (TCAs) are well-known, the dangers of newer generations (SSRIs, SNRIs) are often underestimated, even though their combination with alcohol leads to significant cognitive and psychomotor impairment. A comprehensive review of risks across all drug classes is needed. Aim of the article. The aim of this review is to comprehensively analyze and systematize scientific data on the pharmacokinetic and pharmacodynamic mechanisms of interaction between ethanol and the main classes of antidepressants (TCAs, MAOIs, SSRIs, SNRIs) and to critically evaluate the associated clinical consequences. Research findings. Two main interaction pathways were analyzed. Pharmacokinetically, chronic alcohol use (CYP450 induction) can lead to therapeutic failure, while acute intoxication (CYP450 inhibition) causes a risk of antidepressant toxicity. Pharmacodynamically, the primary problem is additive CNS depression. The combined sedative effects of ethanol and many antidepressants result in profound sedation, impaired memory, attention, and psychomotor retardation. A specific risk analysis was conducted: SSRIs/SNRIs significantly enhance sedation; TCAs pose a lethal threat by potentiating cardiotoxicity (arrhythmia risk); MAOIs combined with tyramine-containing beverages (beer, red wine) provoke a hypertensive crisis. Conclusions. The combination of ethanol with any class of antidepressants is clinically hazardous and counterproductive. It creates a risk of acute toxic reactions and compromises the efficacy of depression treatment. Complete abstinence from alcohol is a mandatory condition of therapy. Proactive education by clinicians regarding the specific risks of each drug class plays a crucial role.
References
Blackwell B. Hypertensive crisis due to monoamine-oxidase inhibitors. The Lancet. 1963. Vol. 282, № 7312. P. 849–851. URL: https://doi.org/10.1016/s0140-6736(63)92591-6
Bush K. et al. The AUDIT alcohol consumption questions (AUDIT-C): an effective brief screening test for problem drinking. Archives of Internal Medicine. 1998. Vol. 158, № 16. P. 1789–1795. https://doi.org/10.1001/archinte.158.16.1789
Ciraulo D. A., Shader R. I. The effects of antidepressants on the brain: interactions with alcohol. Journal of Clinical Psychopharmacology. 1990. Vol. 10, № 3 (Suppl). P. 48S–55S.
Ebrahim I. O. et al. Alcohol and sleep I: effects on normal sleep. Alcoholism, Clinical and Experimental Research. 2013. Vol. 37, № 4. P. 539–549. https://doi.org/10.1111/acer.12006
Food and Drug Administration. Wellbutrin (bupropion hydrochloride) prescribing information. FDA, 2020.
Foulds J. A. et al. Depression in patients with alcohol use disorders: systematic review and meta-analysis of outcomes for independent and substance-induced disorders. Journal of Affective Disorders. 2015. Vol. 185. P. 47–59. https://doi.org/10.1016/j.jad.2015.06.024
Fraser A. G., MacLeod J. Four clinical scenarios of drug interaction in palliative care. BMJ Supportive & Palliative Care. 2012. Vol. 2, № 3. P. 221–226. https://doi.org/10.1136/bmjspcare-2012-000213
Grant B. F. et al. Prevalence and co-occurrence of substance use disorders and independent mood and anxiety disorders: results from the National Epidemiologic Survey on Alcohol and Related Conditions. Archives of General Psychiatry. 2004. Vol. 61, № 8. P. 807–816. https://doi.org/10.1001/archpsyc.61.8.807
Henry J. A., Alexander C. A. Symmetrical analysis of antidepressant poisoning. Drug Safety. 1995. Vol. 13, № 6. P. 360–370. https://doi.org/10.2165/00002018-199513060-00003
Hindmarch I., Bhatti J. Z. Psychomotor effects of paroxetine, alone and combined with ethanol. Neuropsychobiology. 1988. Vol. 19, № 4. P. 209–215. https://doi.org/10.1159/000118469
Kelly J. F., Westerberg V. S. Predictors of remission from alcohol use disorder with and without the help of Alcoholics Anonymous. Journal of Studies on Alcohol and Drugs. 2014. Vol. 75, № 1. P. 74–83. https://doi.org/10.15288/jsad.2014.75.74
Kruse G., Lader M. H. Citalopram and alcohol: a placebo-controlled study of their interaction in healthy male volunteers. European Journal of Clinical Pharmacology. 1993. Vol. 44, № 4. P. 335–341. https://doi.org/10.1007/BF00271383
Lobo I. A., Kennedy S. H. The mechanism of action of antidepressants. The effective management of depression. Cambridge : Cambridge University Press, 2009. P. 20–33.
Miller W. R., Rollnick S. Motivational interviewing: Helping people change. 3rd ed. Guilford Press, 2013.
Nutt D. J., Lingford-Hughes A. R. The clinical pharmacology of addiction. British Journal of Pharmacology. 2008. Vol. 154, № 2. P. 316–326. https://doi.org/10.1038/bjp.2008.106
Petracca A., Wentsel R., N'Da K. The use of selective serotonin reuptake inhibitors in patients with comorbid major depressive disorder and alcohol use disorders. Expert Opinion on Pharmacotherapy. 2013. Vol. 14, № 3. P. 307–319. https://doi.org/10.1517/14656566.2013.764350
Sher L. Alcohol consumption and suicide. American Journal of Psychiatry. 2006. Vol. 163, № 8. P. 1349–1357. https://doi.org/10.1176/ajp.2006.163.8.1349
Shulman K. I., Walker S. E., MacKenzie S. Dietary restriction, tyramine, and the use of monoamine oxidase inhibitors. Journal of Psychiatry & Neuroscience. 2007. Vol. 32, № 6. P. 395–397.
Spina E., de Leon J. Clinical applications of CYP450 pharmacogenetics. Journal of Neural Transmission. 2015. Vol. 122, № 1. P. 5–28. https://doi.org/10.1007/s00702-014-1311-6
Vengeliene V. et al. Neuropharmacology of alcohol addiction. British Journal of Pharmacology. 2008. Vol. 154, № 2. P. 299–315. https://doi.org/10.1038/bjp.2008.30
Weathermon R., Crabb D. W. Alcohol and medication interactions. Alcohol Research & Health. 1999. Vol. 23, № 1. P. 40–54.
Wong J. et al. Off-label indications for antidepressants in primary care: a cross-sectional study. BMJ Open. 2017. Vol. 7, № 1. Art. e013140. https://doi.org/10.1136/bmjopen-2016-013140
World Health Organization. Global status report on alcohol and health 2023. WHO, 2023.
