[Use of haloperidol in high doses in schizophrenia. Clinical, biochemical and pharmacokinetic study]

The effect of high doses of haloperidol on the clinical status, plasma neuroleptic and prolactin concentrations as well as on CSF HVA and GABA levels was investigated in 3 paranoid schizophrenic patients over a 6 weeks period. When the study was initiated patients had been on haloperidol (10 mg a day) for 4-10 weeks. Oral doses were increased at weekly intervals from 10 (day 0) to 100 (day 7) and 200 (days 14 to 28) mg a day and then reduced to 100 (day 35) and 10 (day 42) mg/day. A linear relationship was observed between plasmatic levels and daily doses of haloperidol. In neither patient, the increase in haloperidol dosage affected paranoid symptoms. Neurological side effects were slightly increased in 2 cases and moderately reduced in one case. Prolactin plasma levels, already high at the onset of the study rose when increasing the dose to 100 mg a day but did not increase further despite increment in the haloperidol dosage. CSF levels of HVA and GABA rose from day 0 to day 7 but were back to the initial values on day 28 in 2 patients and were decreased from day 0 to day 28 in one patient. For the 3 patients a close correlation was observed between changes in CSF HVA and GABA levels. It is concluded that high doses of haloperidol, although causing biochemical changes compatible with the occurrence of dopamine target cell supersensitivity, do not lead to any clinical improvement in the 3 studied schizophrenic patients.