Haloperidol plasma 'threshold' levels for relapse prevention in schizophrenia: a study with haloperidol decanoate

Forty-eight schizophrenic outpatients treated with flexible doses of haloperidol decanoate were followed up in a naturalistic fashion for 3 years with periodic monitoring of clinical symptoms, side effects and haloperidol plasma concentrations. There was no relationship between plasma level and clinical response, however categorical data analysis showed that patients with plasma levels over 4 ng/ml had a significantly reduced relapse rate compared with patients with plasma levels below this plasma 'threshold' level. This effect could be observed during the first, second as well as third year of treatment. The relapse rate did not change significantly in relation to time (during years 1, 2, 3), when patients with haloperidol plasma levels below and equal to or over 4 ng/ml were considered separately. In patients with haloperidol equal to or over 4 ng/ml, the variability (measured as coefficient of variation %) in the total scores of SAPS and SANS was lower, indicating a better clinical stability. These data are in fairly good agreement with other literature findings showing that an indiscriminate dose reduction strategy during long-term treatment of schizophrenic disorders with haloperidol decanoate should be discouraged, since it leads to an increase in the relapse rate. Before deciding about a dose reduction, clinicians should take into careful consideration some clinically relevant variables (i.e. frequency of previous relapses, severity of symptoms, iatrogenic depression, risk for development of extrapyramidal side effects) for each patient. A better clinical stability during treatment with haloperidol decanoate can be obtained when plasma 'threshold' levels for response are reached.