The effect of age on the serum concentrations of the antipsychotics studied becomes pronounced with advanced age. The patient population aged above 70 should be subdivided according to exact age, and considerable dose reductions are recommended.

Although pregnancy is known to cause changes in drug pharmacokinetics, little is known about its impact on serum levels of antipsychotics. In this study we retrospectively assessed 201 routine serum antipsychotic therapeutic drug monitoring concentration measurements obtained from a total of 110 pregnancies in 103 women, and 512 measurements from the same women before and after pregnancy. Serum concentrations in the third trimester were significantly lower than baseline for quetiapine (−76%; confidence interval (CI), −83%, −66%; P < 0.001) and aripiprazole (−52%; CI, −62%, −39%; P < 0.001), but not for olanzapine (−9%; CI, −28%, +14%; P = 0.40). For the remaining antipsychotics (perphenazine, haloperidol, ziprasidone, risperidone, and clozapine), our dataset was limited, but it indicates that concentrations may decline at least for perphenazine and possibly also for haloperidol. Even though the clinical consequence of the serum concentrations decline remains to be elucidated, our results warrant close clinical monitoring throughout pregnancy, preferentially supported by therapeutic drug monitoring.

No abstract

Although the study is small and the results should be interpreted very cautiously, it indicates that comedication with drugs inhibiting or inducing CYP2D6 or CYP3A4 affects the serum concentrations of aripiprazole. The other findings should be considered as preliminary and have to be replicated in a larger setting before firm conclusions can be drawn.

There is limited documentation on the pharmacokinetics of long-acting intramuscular risperidone in a naturalistic setting. The objective of this study was to investigate the concentrations of risperidone and its active metabolite 9-hydroxyrisperidone as well as the concentration/dose (C/D) ratios achieved after intramuscular depot administration in a routine therapeutic drug monitoring setting. Thirty samples were collected from 10 female and 20 male patients receiving depot injections of risperidone. For 6 of the patients, the results could be compared with corresponding data available after previous oral administration of risperidone. In addition, data from a group of 278 patients using oral risperidone were retrieved. The median serum concentrations of risperidone plus 9-hydroxyrisperidone were 38 nmol/L 12-14 days after a intramuscular dose of 25 mg/14 days, 67 nmol/L after a dose of 37.5 mg/14 days, 99 nmol/L after a dose of 50 mg/14 days, and 148 nmol/L after a dose of 75 mg/14 days. The median C/D ratio for risperidone plus 9-hydroxy-risperidone was 22.2 (nmol/L)/(mg/d). In the group on oral medication, the median C/D ratio was 18.6 (nmol/L)/(mg/d). In the 6 patients previously using oral risperidone, switching to depot injections gave an average increase of 33% (range 12%-68%) in the C/D ratio. In conclusion, the authors' data indicate that there are great interindividual differences in the extent to which the daily dose has to be reduced when switching from oral to intramuscular depot administration to achieve the same serum concentrations of risperidone plus 9-hydroxyrisperidone. Because the degree of dose adjustment required for the individual patient so far cannot be predicted, guidance by therapeutic drug monitoring might be helpful.