Question from a Member:
Patients often ask about the safety of drinking alcohol while on antidepressants. Recently, I have had a college-aged patient tell me that, since taking escitalopram, her response to alcohol (severity of intoxication) is exaggerated per any given amount consumed. I have heard reference to this phenomenon before, but I have had difficulty finding much useful information from trusted sources online.
What do you generally tell patients about the safety of drinking while taking commonly used antidepressants, and do you have any recommendations regarding this patient noted above? For instance, would a different antidepressant be less likely to cause this problem, or would it help to hold the dose on an evening when she plans to drink?
Yes, this is a question that comes up commonly. Alcohol use, socially and recreationally, is extremely common, at least in Western societies. So, it is not surprising that many patients who are on an antidepressant also drink alcohol. For example, in one study of patients 65 years or older who were on an antidepressant, 25% were consuming at least some alcohol (Ulrich et al., 2107).
The problem is that our patients are commonly supposed to take the antidepressant for long periods of time. Are we supposed to ask them to completely give up alcohol? If we imply that they have to choose between the antidepressant and alcohol, are we confident that they will choose the antidepressant?
What the Prescribing Information says
Let’s look at the official, FDA-approved Prescribing Information for some commonly used SSRIs (and other antidepressants) to see what they say about whether patients need to avoid drinking alcohol while taking the antidepressant.
Escitalopram (brand name Lexapro; accessed February 15, 2019):
“Although Lexapro did not potentiate the cognitive and motor effects of alcohol in a clinical trial, as with other psychotropic medications, the use of alcohol by patients taking Lexapro is not recommended.” (Emphasis added by SPMH)
“Patients should be told that, although Lexapro has not been shown in experiments with normal subjects to increase the mental and motor skill impairments caused by alcohol, the concomitant use of Lexapro and alcohol in depressed patients is not advised.” (Emphasis added by SPMH)
FDA-Approved Medication Guide: “Do not drink alcohol while using Lexapro.” (Emphasis added by SPMH)
Sertraline (brand name Zoloft; accessed February 15, 2019):
“In healthy subjects, the acute cognitive and psychomotor effects of alcohol were not potentiated by ZOLOFT.” (Emphasis added by SPMH)
Medication Guide: “Do not drink alcohol while you take ZOLOFT.” (Emphasis on the words “Do not” is in the Prescribing Information and was not added by SPMH)
That’s it. No more information is provided in the Prescribing Information for escitalopram or sertraline. To summarize, they’re saying two things that appear to be contradictory—no problem was found but we don’t recommend the use of alcohol by patients taking escitalopram. To patients, they are making a clear-cut statement without any hedging–do not drink alcohol while using Lexapro. That’s pretty clear cut, right? Seems strange. If no problem was found, why are they telling patients not to drink alcohol? This contradiction that I noted was also commented on in the past (Herxheimer and Menkes, 2011). It is not surprising that many clinicians and patients ignore these warnings.
But, our Member’s patient may not be imagining the exaggerated response to alcohol! There are many reports of patients who had different types of abnormal reactions to alcohol after starting on an antidepressant. Let’s discuss this below.
Optional: What the Prescribing Information for other antidepressants says
“Although PAXIL has not been shown to increase the impairment of mental and motor skills caused by alcohol, patients should be advised to avoid alcohol while taking PAXIL.”
Medication Guide: “Do not drink alcohol while using PAXIL.”
Duloxetine (brand name Cymbalta; accessed February 15, 2019)
“When CYMBALTA and ethanol were administered several hours apart so that peak concentrations of each would coincide, CYMBALTA did not increase the impairment of mental and motor skills caused by alcohol.” (Emphasis added by SPMH)
Vortioxetine (brand name Trintellix; accessed February 15, 2019):
“A clinical study has shown that TRINTELLIX (single dose of 20 or 40 mg) did not increase the impairment of mental and motor skills caused by alcohol (single dose of 0.6 g/kg).” (Emphasis added by SPMH)
Case reports: Patterns of abnormal reactions
More than two hundred cases have been reported in which an abnormal reaction to alcohol occurred in a person who was on an antidepressant. These have even included violence or sexual behavior (e.g., Menkes and Herxheimer, 2009; Chandler and Herxheimer, 2011). In about half the cases, memory of the event was impaired or absent (Menkes and Herxheimer, 2014).
Several types of altered responses to alcohol have been reported in persons taking an antidepressant and these have been classified into the following (Menkes and Herxheimer, 2014):
1. Increased intoxication compared to the past with the same amount of alcohol.
2. Pathological intoxication, i.e., intoxication that is qualitatively different or involves disinhibition or violence that is not characteristic of the person after drinking in the past.
3. Increased (or, sometimes, decreased) tendency to use alcohol.
4. Changed in the pattern of alcohol intake, e.g., drinking on weekdays as opposed to the previous habit of drinking only on weekends.
5. Increase in memory impairment that is unexpected relative to the amount of alcohol consumed.
6. Increased after-effects of alcohol, e.g., hangovers (these may also be decreased in some persons), changes in harm, self-harm behaviors.
In the cases reported in the literature, the problem typically goes away when the antidepressant is stopped and in cases where the antidepressant was restarted, tends to come back. These features increase the likelihood that the abnormal reactions to alcohol really where related to the person being on alcohol.
Which antidepressants may be worse in this regard?
Certain factors make it difficult to predict the interaction between alcohol and antidepressants.
1. As discussed below, the possible effects of drinking alcohol while on an antidepressant may be different with different antidepressants.
2. It is important to realize that the effects of acute alcohol intake and chronic alcohol use may be different.
SSRIs and SNRIs
The possible interaction between an antidepressant and alcohol is typically evaluated in healthy volunteers by looking for intoxication and for psychomotor impairment. Typically, in such studies, serotonin reuptake inhibitors do not increase the intoxicating effects of alcohol or impair psychomotor functioning (e.g., Allen and Lader, 1989; Chen et al., 2016). But, we should keep in mind that small studies are likely to miss effects that occur in a small percentage of people.
Regarding case reports, though the authors of a paper reviewing more than 200 case reports stated that pathological intoxication “occurs in a broadly similar manner across SSRIs and related drugs,” I noted that among the SSRIs/ SNRIs, the number of case reports in their paper that were related to paroxetine and fluoxetine were markedly greater than those for other SSRIs/ SNRIs (Menkes and Herxheimer, 2014). But, this could be just a coincidence.
The Maudsley Prescribing Guidelines (Taylor et al., 2015) say that in *chronic* users of alcohol when such a person takes paroxetine or fluoxetine, the metabolism of alcohol by CYP3A4 (a route that becomes important in chronic users of excessive amounts of alcohol) is potently inhibited (Taylor et al., 2015). In persons who continue to drink, the Maudsley Guidelines recommend using citalopram or sertraline rather than paroxetine or fluoxetine (Taylor et al. (2015). The problem with this explanation is that though fluoxetine does moderately inhibit CYP3A4, paroxetine inhibits CYP3A4 only mildly (Sandson et al., 2005). In the well-known “Flockhart table,” paroxetine is not listed among possible inhibitors of CYP3A4.
Some tricyclic antidepressants like amitriptyline and imipramine have been shown to potentiate the effects of alcohol in impairing psychomotor performance and memory (e.g., Seppälä et al., 1975; Tartara et al., 1985; Tiller, 1990; Frewer and Lader, 1993), but this may not be true of nortriptyline (Seppälä et al., 1975). This may be yet another reason to prefer nortriptyline compared to the other tricyclic antidepressants. The interaction between tricyclic antidepressants and alcohol may be worse with more sedating TCAs (Weller and Preskorn, 1984).
MAO inhibitors may increase sedation due to alcohol and prolong intoxication, so caution is needed with regard to combining the two (Weller and Preskorn, 1984).
Allen D, Lader M, Curran HV. A comparative study of the interactions of alcohol with amitriptyline, fluoxetine and placebo in normal subjects. Prog Neuropsychopharmacol Biol Psychiatry. 1988;12(1):63-80. PubMed PMID: 3259002. Only 12 patients. No difference between the three groups was found.
Allen D, Lader M. Interactions of alcohol with amitriptyline, fluoxetine and placebo in normal subjects. Int Clin Psychopharmacol. 1989 Jan;4 Suppl 1:7-14. PubMed PMID: 2783702.
Chandler P, Herxheimer A. Unexpected aggressive behaviour: interaction of bupropion and alcohol. Int J Risk Saf Med. 2011;23(3):133-7. doi: 10.3233/JRS-2011-0533. Erratum in: Int J Risk Saf Med. 2011;23(4):257. PubMed PMID: 22020393.
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Herxheimer A, Menkes DB. Drinking alcohol during antidepressant treatment — a cause for concern? The Pharmaceutical Journal. 20DEC 2011. Available at: https://www.pharmaceutical-journal.com/news-and-analysis/drinking-alcohol-during-antidepressant-treatment-a-cause-for-concern/11091677.article
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Menkes DB, Herxheimer A. Provocation by alcohol of violence as a side-effect of antidepressants. Drug Safety 2009;32:948–9. Article not read by me yet.
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