Linezolid Injection and Sertraline: Interaction Details

a) In a retrospective cohort study in older adults who were prescribed oral linezolid 600 mg twice daily (N=1134), serotonin syndrome occurred in fewer than 6 patients (less than 0.5%) who were taking a concomitant antidepressant (n=215). In the propensity score-matched cohort (n=332), there was no difference in the risk of clinically significant serotonin syndrome in patients taking concomitant antidepressants and linezolid compared with patients taking linezolid without antidepressants (adjusted risk difference, -1.2%; 95% CI, -2.9% to 0.5%). There was also no difference in the rate of altered mental status or confusion, hospitalization, or death from any cause between groups. Patients were aged 66 years or older, and of those taking an antidepressant, 47.9% were taking an SSRI, 16.7% were taking an SNRI, 7% were taking a tricyclic antidepressant, 3.3% were taking a norepinephrine and dopamine reuptake inhibitor, and none were taking an MAOI ¹.

b) Serotonin syndrome was reported in a 47-year-old woman on 2 occasions following the addition of linezolid 600 mg twice daily to her medication regimen (which included sertraline 100 mg daily) for the treatment of a stump wound infection after an above the knee amputation. On the first occasion, confusion, hypertension, and incoordination were noted following on day 4 of linezolid therapy; the symptoms subsided 4 days after vancomycin was substituted for linezolid. On the second occasion, delirium, confusion, myoclonus, and incoordination developed on day 9 of linezolid therapy despite sertraline being discontinued on day 1; cardiopulmonary arrest occurred, along with diarrhea and tachycardia, and left the patient in a coma with an anoxic brain injury. Linezolid was discontinued and cyproheptadine (a serotonin antagonist) was started, and within 4 days the tachycardia and diarrhea resolved. The patient subsequently died after not recovering from brain injury; the ventilator and dialysis were stopped ³.

c) A case of serotonin syndrome occurred in a patient who was prescribed linezolid and sertraline. A 45-year-old man with a history of schizoaffective disorder was admitted to the trauma service after an acute suicide attempt that resulted in a T6 level spinal cord injury and paraplegia. Pharmacotherapy with sertraline (200 mg daily) and risperiDONE (1 mg twice daily) was initiated after the patient was diagnosed with acute depression and psychosis. BuPROPion 75 mg twice daily, traZODone 50 mg every evening, and lithium 300 mg twice daily were added to his therapy. The patient underwent sacral flap closure with a bilateral gluteal myocutaneous flap and then developed a deep sacral decubitus ulcer. His temperature and WBC count remained elevated for several days. Culture of the ulcer revealed a vancomycin-resistant Enterococcus faecalis. He was started on linezolid 600 mg IV every 12 hours and metroNIDAZOLE 500 mg every 6 hours. Lithium was discontinued after the patient's lithium level was found to be elevated at 1.1 mEq/L. Ten days after linezolid therapy was initiated, the patient complained of increasing tremor, nausea, vomiting, diarrhea, and dry mouth. Sertraline, buPROPion, and traZODone were discontinued. His concurrent medications included baclofen, promethazine, docusate sodium, bisacodyl, megestrol, lansoprazole, and risperiDONE. The following day, the patient became delirious marked by acute confusion, visual hallucinations, and delusions. His temperature was elevated to 100.1 degrees F, pulse 101, respirations 20/min, and blood pressure 100/71 mmHg. He displayed coarse tremor and myoclonus. His pupils were dilated to 6 mm and minimally reactive. A diagnosis of serotonin syndrome was considered. Symptoms of serotonin syndrome resolved with cyproheptadine treatment ⁴.

d) In one case report, a 36-year-old man experienced symptoms of serotonin syndrome after concomitant treatment with linezolid and sertraline. The patient underwent an allogeneic stem cell transplant after receiving high-dose cycloPHOSphamide, total body irradiation, and antithymocyte globulin. His recovery was hindered by severe hemorrhagic cystitis, steroid-refractory graft-versus-host disease, thrombotic thrombocytic purpura, renal failure, and multiple pulmonary infections. On day 137, the patient received linezolid 600 mg IV every 12 hours. Current medications included tacrolimus, corticosteroids, thalidomide 100 mg daily, sertraline 50 mg daily, morphine, and ALPRAZolam. On day 5 of linezolid therapy, the patient experienced confusion, restlessness, delirium, and agitation. He developed hypertension and a high fever (40 degrees C). WBC and platelet counts began to diminish considerably. On day 6 of therapy, all medications with neurological effects were discontinued, including sertraline, thalidomide, ALPRAZolam, and morphine. The patient's symptoms subsided within a day. Thalidomide, ALPRAZolam, and morphine were reinstated with no reoccurrence of symptoms ⁵.