Combination therapy with haloperidol and orphenadrine in schizophrenia. A clinical and pharmacokinetic study

The use of anti-cholinergic drugs for counteracting neuroleptic induced extrapyramidal side-effects (EPS) is controversial. A possible increase in anticholinergic symptoms and a pharmacokinetic interaction are reported in literature. In order to determine these points, 22 schizophrenic patients were studied. Haloperidol (HL) was administered for 3 weeks and Orphenadrine (ORD) only in the second week of treatment. ORD reduced significantly EPS and its withdrawal led to a marked deterioration of EPS and psychopathological picture. There was an increase in HL plasma levels after starting ORD, and ORD plasma levels were positively related to EPS amelioration. Finally, prolactin seemed to be higher in those patients with EPS, particularly after ORD withdrawal.