Recent research published in Acta Psychiatrica Scandinavica showed that serum concentrations of second-generation antipsychotic medications were significantly higher in patients over the age of 70, indicating a need for dose decreases in this population.

To determine the effect of age and gender on serum concentrations of second-generation antipsychotic medications, researchers evaluated the results of routine therapeutic drug monitoring from 43,079 samples obtained from 11,968 patients receiving clozapine (n=17,249), olanzapine (n=16,171), risperidone (n=5343), and quetiapine (n=4316). The primary outcome was dose-adjusted concentration.

For all 4 treatments, age was significantly associated with concentration. Dose-adjusted drug concentrations were twice as high in 80-year-old patients compared with 40-year-old patients. By age 90, concentrations were 2- to 3-fold higher than at age 40.

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Clozapine was associated with the highest age-related increases (+108% at 80 years; +197% at 90 years). In contrast, olanzapine was associated with the lowest age-related increases (+28% at 80 years; +106% at 90 years).

The researchers also noted that dose-adjusted concentrations were 20% to 30% higher in women compared with men. For quetiapine, gender association of dose-adjusted concentrations increased with age, with no gender association in younger patients and a 33% increase in women relative to men by age 80.

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The researchers concluded that the study results “[indicate] that when prescribing clozapine, olanzapine, risperidone, and quetiapine to elderly patients, no more than half the dose usually administered to younger patients should be used, and in many cases, particularly [for] the oldest individuals, even lower doses should be used.”


Castberg I, Westin AA, Skogvoll E, Spigset O. Effects of age and gender on the serum levels of clozapine, olanzapine, risperidone, and quetiapine [published online September 2, 2017]. Acta Psychiatr Scand. doi:10.1111/acps.12794