[Use of antidepressants: pharmacokinetic basis (author's transl)]

It is evident from a number of studies that "antidepressants" may be effective in the treatment of various depressive disorders, but also that failures are quite common. The reasons are manifold, but an important source of variation is the pharmacokinetics of these drugs. An adequate concentration of the drug at the cerebral receptors is a reasonable prerequisite for success. This concentration is likely to be reflected by the plasma level of the drug that may display great variations in different individuals receiving the same dosage, mainly due to variations in drug metabolism. The metabolism of the drug depends both on genetic factors and on induction by other drugs such as barbiturates. Whereas most side effects have a fairly simple, linear relation to the blood level, this does not hold true for all drugs as regards their therapeutic effect. Nortriptyline and possibly also mianserin show a curvilinear relation between level and therapeutic outcome. The effect is optimal within a certain concentration range, worse with both lower and with higher concentration. Monitoring treatment by means of measuring blood concentration may thus be desirable in certain situations. -With dimethylated drugs the effects may be complicated if the drug itself and some metabolite act on different transmittor systems. This holds true for, e.g., chlorimipramine and zimelidine. However, the clinical implications are still obscure.