Do you prescribe linezolid to patients who are concomitantly on an SSRI?

Yes, cautiously, especially when LZD is the best or only option. Recent Eur J Clin Pharmacol July 2023 meta-analysis involving 84 publications found an observed rate of < .01%; another study Shi et al., PMID 37301313 found a similar rate (1/1743 persons, 0.06%). Holding an SSRI for a day or two prior to LZD therapy is not likely to reduce the risk; so your options may be limited.

This is the paper I routinely cite when challenged by Pharmacy. Thanks to all for some newer citations. (Of course, the conclusion remains the same)

Bai et al., PMID 36534400

Key Points

Question: Are patients who take antidepressants at increased risk for serotonin syndrome when receiving linezolid treatment compared with patients not taking antidepressants?

Findings: In this population-based cohort study of 1134 patients who were prescribed linezolid, 215 patients (19.0%) were taking antidepressant...

Yes, if there is no other contraindication, but continue to be watchful for the potential of a drug interaction. The data on the risk for serotonin syndrome with linezolid is sparse and linezolid drug trials found no conclusive evidence that it increases the risk for serotonin syndrome. A recent large retrospective cohort study (Bai et al., PMID 36534400) in over 1100 older patients, of which 19% were on antidepressants, indicates that the incidence of serotonin syndrome is rare in those who wer...

Yes, in most scenarios. However, I avoid this approach in the frail patient population, where serotonin syndrome could have more devastating consequences.

Yes. I have experience using LZD with one serotonergic agent in young adults. Before discharge, I tend to challenge them, and I have not seen patients experiencing ST (serotonin toxicity). Whether LZD can be given with multiple SAs is unclear.

A recent systematic review and meta-analysis by SanFilippo et al., PMID 37987392 estimated an incidence rate for ST as 12.3 per 1000 patients for those treated with LZD + a serotonergic agent versus 11 per 1000 patients treated with LZD monotherapy. Concomi...

I have used Linezolid in ICU patients with MRSA pneumonia and have failed IV Vanco. I do stop SSRIs but have not seen any serotonergic reaction so far irrespective of their half-lives. I chose the option benefits outweigh the risks and have been practicing medicine for 25 plus years.

I find it interesting that all four respondents use Linezolid in patients who take SSRIs. The bulk of our practice consists of inpatients, so outpatient use of Linezolid is not a frequent issue. This question taps into a broader issue of antibiotic-drug interactions. Many of us feel that these interactions are contrived and/or over-rated. Does TMP/SMX really cause QTc prolongation, for instance?

I have tried to use Linezolid in several ICU pts, but they were all on fentanyl or other opioids and ...

Cautiously, occasionally on inpatients, so I can monitor them (I have had AEs). My preference, when I can get it, is tedizolid, though cost and FDA label are a challenge when treating outpatients.