Based on this natural experiment we were not able to document statistically significant differences in total costs between treatment sites that had guidelines recommending pharmacogenetic testing, relative to sites without such guidelines, over a period of one year. However, guidelines of pharmacogenetic testing and possibly also therapeutic drug monitoring seem to lead to reductions in costs for primary care services. In the case of the former, reductions do, however, seem to be outweighed by increases in costs for psychiatric and non-psychiatric inpatient stays. In conclusion, no statistically significant differences in total direct costs across sites with different treatment strategies were found.