Effects of trihexyphenidyl on plasma chlorpromazine in young schizophrenics

This study investigated the effects of trihexyphenidyl on chlorpromazine (CPZ) plasma levels and clinical state in 20 relatively young schizophrenic patients diagnosed using the DSM-III. Spontaneous changes in CPZ plasma levels over time were also examined. Trihexyphenidyl significantly increased CPZ plasma levels (average 41%) but did not produce clinical change. The trihexphenidyl-induced increase in CPZ plasma levels was independent of CPZ oral dosage and of CPZ plasma levels. Chlorpromazine plasma levels decreased non significantly (about 13%) over the four weeks following steady state, but there was marked inter-subject variability, and CPZ levels rose in some subjects. Although identical CPZ doses produced widely variable plasma levels, CPZ plasma levels correlated significantly with oral dose. The views that antiparkinsonian drugs interfere with neuroleptic efficacy, and do so by lowering neuroleptic plasma levels, are questioned.