Therapeutic Drug Monitoring of Long-Acting Injectable Antipsychotic Drugs.

BACKGROUND: The use of therapeutic drug monitoring (TDM) to guide treatment with long-acting injectable (LAI) antipsychotics, which are increasingly prescribed, remains a matter of debate. The aim of this review was to provide a practical framework for the integration of TDM when switching from an oral formulation to the LAI counterpart, and in maintenance treatment. METHODS: The authors critically reviewed 3 types of data: (1) positron emission tomography data evaluating dopamine (D2/D3) receptor occupancy related to antipsychotic concentrations in serum or plasma; D2/D3 receptors are embraced as target sites in the brain for antipsychotic efficacy and tolerability, (2) pharmacokinetic studies evaluating the switch from oral to LAI antipsychotics, and (3) pharmacokinetic data for LAI formulations. Based on these data, indications for TDM and therapeutic reference ranges were considered for LAI antipsychotics. RESULTS: Antipsychotic concentrations in blood exhibited interindividual variability not only under oral but also under LAI formulations because these concentrations are affected by demographic characteristics such as age and sex, genetic peculiarities, and clinical variables, including comedications and comorbidities. Reported data combined with positron emission tomography evidence indicated a trend toward lower concentrations under LAI administration than under oral medications. However, the available evidence is insufficient to recommend LAI-specific therapeutic reference ranges. CONCLUSIONS: Although TDM evidence for newer LAI formulations is limited, this review suggests the use of TDM when switching an antipsychotic from oral to its LAI formulation. The application of TDM practice is more accurate for dose selection than the use of dose equivalents as it accounts more precisely for individual characteristics.

The use of ziprasidone in clinical practice: analysis of pharmacokinetic and pharmacodynamic aspects from data of a drug monitoring survey.

This study related clinical effects to daily doses and serum concentrations of ziprasidone by retrospective analysis of data from a therapeutic drug monitoring (TDM) survey established for patients treated with the new antipsychotic drug. In the total sample of 463 patients ziprasidone doses ranged between 20 and 320 mg/d and correlated significantly (r(2)=0.093, P<0.01) with serum concentrations. The latter were highly variable within and between individual patients (between patients median 67 ng/ml, 25-75th percentile 40-103 ng/ml). Pharmacokinetic interactions with comedication played a minor role. According to the clinical global impressions (CGI) scale most of the 348 patients who were under antipsychotic monotherapy with ziprasidone were either much or very much improved (43.3 and 17.3%, respectively). The previously proposed therapeutic range of 50-130 ng/ml ziprasidone in serum or plasma, which can in effect be used interchangeable, was confirmed. In patients who were at least much improved and defined as "responders" mean serum concentrations of ziprasidone were 80 ng/ml and 78 ng/ml in patients who did not reach this improvement score. In patients with serum levels above or below 50 ng/ml, the number of responders was 66 or 63%, respectively. The difference between the two groups was not significant (P=0.375), and improvement or side effects did not correlate significantly (P>0.05) with doses or serum levels. It is concluded that TDM of ziprasidone may be useful for treatment optimization because of highly variable serum concentrations resulting under therapeutically recommended doses of the drug.