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Mirtazapine Can Be Added To Clozapine, Risperidone Or Olanzapine Without Pharmacokinetic Interaction, In Treatment Of Schizophrenia

Mirtazapine, the first in a new class of noradrenergic and specific serotonergic antidepressants, can be safely added to the antipsychotics clozapine, risperidone or olanzapine, in the treatment of chronic schizophrenia, without pharmacokinetic interaction, according to an Italian clinical trial.

The results suggest that mirtazapine has a low potential for metabolically based drug interactions. "This may represent an advantage as compared to other new antidepressants such as some selective serotonin re-uptake inhibitors [fluvoxamine, fluoxetine and paroxetine, for example] that markedly inhibit the activity of different cytochrome P450 enzymes, possibly resulting in clinically relevant interactions when co-administered with these antipsychotics," the researchers noted.

In the open-label trial, which was led by Dr Rocco Zoccali of the University of Messina, Italy, 26 patients with chronic schizophrenia, who were receiving clozapine 200 to 650 mg/day (n=9), risperidone 3 to 8 mg/day (n=8) or olanzapine 10 to 20 mg/day (n=7), each received adjunctive mirtazapine 30 mg/day for 6 weeks.

Analysis of blood samples taken at 3 and 6 weeks showed that mirtazapine did not significantly modify the plasma concentrations of clozapine, its metabolite nordozapine, risperidone, or its metabolite 9-OH-risperidone. There was an insignificant increase in plasma concentrations of olanzapine at week 6.

The combinations were well tolerated, with adverse events reported during the first few days of mirtazapine treatment being generally mild and decreasing during the course of treatment. During the six weeks there was no change in extrapyramidal symptoms.

While positive symptoms (as assessed by the scale for assessment of positive symptoms) did not change greatly during treatment with mirtazapine, mean scale for assessment of negative symptoms (SANS) scores decreased from 48.9 at baseline to 41.7 at 6 weeks. Two patients in each group were classified as responders.

The researchers said that they believed their study to be the first documentation of the effects of mirtazapine on the plasma concentrations of clozapine and olanzapine. Their results concurred with a previous study of risperidone.
Pharmacol Res 2003;48:4:411. "Lack of a pharmacokinetic interaction between mirtazapine and the newer antipsychotics clozapine, risperidone and olanzapine in patients with chronic schizophrenia"

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