Posted on September 25th, 2022

Linezolid is an oxazolidinone antibiotic that is active against many gram-positive organisms including those that are resistant to multiple other agents such as methicillin-resistant staphylococci, penicillin-resistant streptococci, and vancomycin-resistant enterococci. Linezolid is also a weak, reversible, inhibitor of monoamine oxidase (MAO), predominantly MAO-A, which is responsible for the metabolism of neurotransmitters such as serotonin, in the brain.  

This effect has led to an increased risk of serotonin syndrome in patients taking other medications that increase serotonergic tone. SSRIs fall in this category as they increase synaptic serotonin concentrations by preventing transport into the presynaptic neuron. They are commonly prescribed for numerous psychiatric conditions. Due to the high prevalence of both depressive disorders and nosocomial infections in patients with chronic medical illnesses, this medication combination may be encountered in the hospital setting. 

Though case reports are few, deaths have been reported due to serotonin syndrome and a Food and Drug Administration Safety Alert was issued in 2011 specifically warning about the linezolid-SSRI interaction.

Because of the risk of serotonin syndrome with this medication combination, linezolid should not be given to patients taking serotonergic drugs (generally contraindicated in the prescribing information).  If linezolid is necessary, abrupt discontinuation of SSRIs may be justified, though it can result in withdrawal effects.  Because of the long half-life of many of the SSRIs, a washout period of two weeks is generally recommended before administering linezolid.  Certain clinical situations may require administering linezolid without this washout period and close monitoring for the development of serotonin syndrome should be ensured.

Other medications/classes with serotonergic properties that share this interaction with linezolid include serotonin norepinephrine reuptake inhibitors, tricyclic antidepressants, monoamine oxidase inhibitors, “triptans”, amphetamines, tramadol, and methadone.

Tip:  Use the mnemonic “FINISH” to remember the SSRI withdrawal syndrome

F – Flu-like symptoms

I – Insomnia

N – Nausea

I – Imbalance

S – Sensory disturbances

H – Hyperarousal (anxiety/agitation)

References:

1. Lawrence KR, Adra M, Gillman PK. Serotonin Toxicity Associated with the Use of Linezolid: A Review of Postmarketing Data. CID 2006;42:1578-83.

2. Quinn DK, Stern TA.  Linezolid and Serotonin Syndrome.  Prim Care Companion J Clin Psychiatry 2009;11(6):353-6.

3. www.fda.gov Zyvox (linezolid): Drug Safety Communication - Serious CNS Reactions Possible When Given to Patients Taking Certain Psychiatric Medications.  Updated 10/21/2011.  Accessed 8/23/2012.

4. Berber MJ. FINISH: remembering the discontinuation syndrome. J Clin Psychiatry 1998;59(5):255.

Original article: Interaction between linezolid (Zyvox®) and SSRIs