General principles of therapeutic monitoring of psychoactive drugs

Psychiatric disorders contribute significantly to worldwide morbidity and mortality. In depression and schizophrenia, effective drug therapy

is available, but 30–50 % of all patients do not respond sufficiently to the initial treatment regime. On the other hand, severe side effects

from correctly applied drug therapy have been repeatedly shown to be a major problem of drug therapy with considerable health burden

and cost. The major reason is the considerable interindividual variability in the pharmacokinetic properties of the patient. At the very same

dose of psychotropic drugs, a more than 20-fold interindividual variation in the medication’s steady state concentration in the body may

result, as patiens differ in their ability to absorb, distribute, metabolize and excrete drugs due to concurrent disease, age, gender, smoking

or eating habits, concomitant medication or genetic peculiarities. In clinical practice, the effort to determine an individual psychotropic

agents drug dose optimum is often guided by a trial-and-error dose titration strategy. A valuable tool for tailoring the dosage of the

psychoactive drugs to the individual characteristics of a patient are therapeutic drug monitoring (TDM), phenotyping and if necessary

genotyping. With the tricyclic antidepressant drugs, lithium and anticonvulsants used in psychiatry, TDM is a long-established tool for

finding the individual dose optimum. For SSRIs, TDM is also recommend. Evidence for a statistically significant relationship between drug

concentration and therapeutic outcome is lacking for the tetracyclic antidepressants maprotiline, mianserin and mirtazapine and also

for trazodone, reboxetine and the monoamine oxidase inhibitors. Clear evidence of the benefits of TDM has been given for a number of

old (haloperidol, trifluoperazine and fluphenazine) and new (especially for clozapine and olanzapine) antipsychotic drugs.

Keywords: psychoactive drugs, therapeutic monitoring, personalized pharmacotherapy