Is there any risk of interaction between sertraline and mirtazapine?/nThe question concerns a 55-ye

Fråga: Is there any risk of interaction between sertraline and mirtazapine? The question concerns a 55-year-old man who is being treated with Zoloft (sertraline) 100 mg x1. Addition of Remeron (mirtazapine) is under consideration.

Sammanfattning: In a literature search, we found one case of suspected sertraline-mirtazapine interaction describing a patient who developed hypomania after concomitant intake of both drugs. Mirtazapine and sertraline are relatively weak inhibitors of CYP450. However, as those drugs are metabolised by the same enzyme, CYP3A4, the possibility for a competitive inhibition can not be excluded. Moreover, since both drugs increase the synaptic level of serotonin in the brain, a pharmacodynamic interaction is not unlikely. A case of serotonin syndrome suspected to be caused by a pharmacodynamic interaction between mirtazapine and another SSRI drug, fluoxetine has been reported.

Svar: In a literature search we found a single case of suspected drug interaction between sertraline and mirtazapine. The case concerned a woman with depressive illness who was treated with sertraline 250 mg daily. Four days after the addition of mirtazapine 15 mg daily, the patient showed hypomanic symptoms that resolved after discontinuation of mirtazapine (1).

Sertraline is merely metabolised by CYP3A4 (2). The metabolism of mirtazapine is mediated by several cytochrome P450 enzymes including 1A2, 2D6 and 3A4 (3). Both sertraline and mirtazapine are relatively weak inhibitors of CYP450 and the risk of a clinically relevant metabolic drug interaction between them seems to be small (2). However, as both drugs are substrates of the same enzymes, a metabolic drug interaction can not be excluded.

More important, however, is the possibility of a pharmacodynamic interaction between the two drugs since both increase the synaptic levels of serotonin in the brain. There is a case of serotonin syndrome described which is suspected to be due to a pharmacodynamic interaction between mirtazapine and another selective serotonin re-uptake inhibitor (SSRI), fluoxetine (4). The case concerned a 75-year-old woman with chronic depressive illness. She was treated with fluoxetine, 20 mg/day, chlorpromazine, 75 mg/day, and lorazepam 2.5 mg/day. Because of poor effect, fluoxetine was discontinued and replaced with mirtazapine, 30 mg/day. A few hours after the first mirtazapine dose, the patient developed a severe syndrome with dizziness, headache, nausea, dry mouth, intense anxiety and agitation with suicidal ideas, difficulty in walking, marked resting tremor of the hands and insomnia which was interpreted as a serotonin syndrome. The symptoms disappeared after discontinuation of mirtazapine.