Linezolid SSRIs

Drugs that may interact with linezolid include monoamine oxidase inhibitors, SSRIs, and adrenergic agents (eg, dopamine, epinephrine). 

Serotonin syndrome SSRIs, second generation antidepressants, MAOIs, linezolid, tramadol, meperidine, fentanyl, ondansetron, sumatriptan, MDMA, LSD, St. John s wort, ginseng Hypertension, hyperreflexia, tremor, clonus, hyperthermia, hyperactive bowel sounds, diarrhea, mydriasis, agitation, coma onset within hours Sedation (benzodiazepines), paralysis, intubation and ventilation consider 5-HT2 block with cyproheptadine or chlorpromazine... 

SSRIs can provoke 5HT neurotoxicity (the 5HT syndrome) through pharmacodynamic interactions with other drugs that also potentiate 5HT function. Often the ability of the interacting drug to facilitate 5HT function is well known, as is the case, for example, when SSRIs are combined with monoamine oxidase inhibitors or lithium. In other cases, however, the potential 5HT activity of the co-administered drug is not widely known. The ability of the antibiotic linezolid to inhibit MAO and thereby to cause 5HT neurotoxicity in combination with SSRIs has been noted previously (SEDA-27, 14), and further cases have now been reported. 

Linezolid inhibits monoamine oxidase activity and has been reported to cause serotonin toxicity in combination with paroxetine. While some patients have apparently taken the combination of linezolid and an SSRI safely, this report suggests that patients taking combined treatment should be monitored for serotonin toxicity. 

Antidepressant drugs of various classes (tricyclics, MAO inhibitors, SSRIs) have broad efficacy in generalized anxiety and in panic disorder, but SSRIs are now the treatments of choice (2,3). Selegiline has been used to treat Parkinson s disease. Other drugs that have MAO inhibitory activity, but are not used as such, include deb-risoquine, linezolid, and isoniazid. 

Clinically important, potentially hazardous interactions with acyclovir, alcohol, amphetamines, barbiturates, CNS depressants, fluoxetine, furazolidone, general anesthetics, glycopyrrolate, glycopyrronium, isocarboxazid, linezolid, lithium, MAO inhibitors, moclobemide, phenelzine, phenobarbital, phenothiazines, rasagiline, ritonavir, selegiline, sibutramine, SSRIs, tranquilizers, tranylcypromine, tricyclic antidepressants, val acyclovir... 

The serotonin syndrome has been reported in patients taking linezolid with an SSRI or venlafaxine. The serotonin syndrome is also predicted to occur if linezolid is given with tricyclic antidepressants. 

Not fully understood. Linezolid has weak MAOI effects, and the serotonin syndrome is known to occur when MAOIs are given with SSRIs , (p.l 142), tricyclics , (p.ll49) and venlafaxine , (p.ll56). In the case of the patient taking linezolid with amitriptyline and paroxetine, it is possible that an interaction between amitriptyline and paroxetine contributed to the development of the serotonin syndrome. Consider also Tricyclic and related antidepressants + SSRIs , p.l241. 

Information on the reaction between linezolid and the SSRIs, tricyclics, mirtazapine or venlafaxine appears to be limited, but what is known suggests that the interaction is probably rare. The manufacturers of linezolid say that patients taking SSRIs and tricyclic antidepressants should have their blood pressure monitored and be closely observed if given linezolid. They say that if this is not possible, concurrent use should be avoided. If linezolid is used with a drug with serotonergic actions it would seem prudent to monitor for symptoms of the serotonin syndrome, which may take several weeks to manifest. See The serotonin syndrome , (p.9), for further details. 

Linezolid associated serotonin syndrome has been reviewed. Combination with an SSRI increases the risk. Of 29 reports of serotonin syndrome in the FDA database, the most common co-medications were SSRIs, and in 17 published case reports of serotonin syndrome linezolid was combined with an SSRI. The time to onset was <24 hours to 3 weeks and the symptoms resolved at 1-5 days. 

In a retrospective chart review the incidence of serotonin toxicity in patients taking linezolid and SSRIs was 3%. No conclusions about incidence can be drawn from this small review, but the authors suggested that the combination of linezolid and an SSRI should be administered based on an analysis of the benefit to harm balance [170 ]. 

In four other cases linezolid caused serotonin syndrome when it was combined with serotonergic drugs, such as SSRIs [171, 172, 173 ], and in one case metoclopra-mide plus enteral administration of tryptophan-rich nutrition [174 ]. 

Schwan S, Hallberg P. Serotonergt syndrom vid kombination av linezolid (Zyvoxid) och SSRI. [Serotonergic syndrome in combination of linezolid (Zyvixid) and SSRI.] Lakartidningen 2009 106(44) 2856. 

---