Is there a need for a washout period when changing from mirtazapine (Remeron ) to sertraline (Zolof

Fråga: Is there a need for a washout period when changing from mirtazapine (Remeron ) to sertraline (Zoloft)?

Sammanfattning: It seems unlikely that a clinically significant risk for interaction will occur when changing from mirtazapine to sertraline based on data available. However, a washout period of 3 days would minimize any possible risk for interaction between the drugs. The decision must depend on the patients condition.

Svar: Mirtazapine is a new antidepressant drug with both noradrenergic and serotonergic potentiating effects (1). It is extensively metabolised in the liver. Major pathways of biotransformation in humans are demethylation and oxidation, followed by conjugation (1). Mirtazapine and its metabolites are eliminated in the urine (85 per cent) and faeces (15 per cent). The elimination half-life of mirtazapine is approximately 20-40 hours(1).

In vitro data on human liver microsomes indicate that isoenzymes CYP2D6, CYP3A4 and CYP1A2 are involved in the metabolism (3). One in vivo study (3) indicates that CYP2D6 plays a minor role in the total elimination of mirtazapine in humans.

Furthermore mirtazapine is a weak competitive inhibitor of CYP2D6, CYP3A4 and CYP1A2 (3).

Sertraline has a serotonergic potentiating effect. It is metabolised mainly in the liver and excreted in the urine (44 per cent) and faeces (45 per cent) (2). The half-life of sertraline is approximately 35 hours (2).

Studies suggest that CYP3A is involved in the biotransformation of sertraline to norsertraline (4) and sertraline is considered to be a weak inhibitor of CYP2D6, CYP2C19 and CYP3A4 (5).

When combining drugs that increase the serotonergic levels in the brain there is a potential risk for development of a serotonergic syndrome. The risk increases if the drugs use the same metabolic pathways which could lead to increasing plasma levels of both drugs.

In this case, however, the question concerns changing from one drug to another. Considering the pharmacokinetic data available, in combination with the fact that steady-state conditions of sertraline will not be reached until one to two weeks after initiation of the treatment, it seems unlikely that a clinically significant risk for interaction will occur when changing from mirtazapine to sertraline. However, it should be noted that in vivo interaction studies are lacking. If a washout period of approximately three days is used, the amount of mirtazapine in the body will be negligible.