IS THERE A THERAPEUTIC WINDOW FOR PLASMA-CONCENTRATION OF MIANSERIN PLUS DESMETHYLMIANSERIN

The relationship between clinical effects and plasma concentrations of mianserin and desmethylmianserin was studied in 29 cases of major depression during 3 weeks of mianserin treatment. The daily dose of mianserin was 30 mg in 27 cases and 20 mg in two cases. There was a significant U-shaped relationship between the final Montgomery Asberg Depression Rating Scale (MADRS) score and the steady-state plasma concentration of mianserin (p < 0.05) or desmethylmianserin (p < 0.05). A much stronger relationship was observed for mianserin plus desmethylmianserin (p < 0.001). A theoretical therapeutic window (where a final MADRS score was expected to be 10 or less) was 71-128 nmol/l for mianserin, 34-61 nmol/l for desmethylmianserin, and 101-183 nmol/l for mianserin plus desmethylmianserin. The proportion of responders was significantly higher inside than outside the window for mianserin plus desmethylmianserin (p = 0.0033), but not for mianserin (p = 0.063) or for desmethylmianserin (p = 0.077). The occurrence of subjective side-effects was not dependent on the plasma concentrations of these compounds. The present study suggests that desmethylmianserin contributes substantially to the overall antidepressant effects of mianserin treatment, and that the therapeutic response is most dependent on the combined plasma concentration of mianserin and desmethylmianserin, with an optimal therapeutic response occurring in the intermediate range.