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The Relationship Between Plasma Haloperidol Concentrations and Clinical Results-Reply

Jan Volavka, MD, PhD; Thomas B. Cooper, MA; Pai Czobor, PhD; Morris Meisner, PhD
Arch Gen Psychiatry. 1996;53(12):1168-1169. doi:10.1001/archpsyc.1996.01830120108020
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Palao et al believe that a "clear lower limit for the antipsychotic activity of plasma concentrations of haloperidol" exists and that this limit may be found in our data with appropriate analyses. They support this contention by a χ2 test using our data; our patients with plasma concentrations of haloperidol lower than the alleged lower limit or threshold (ie, 5.5 ng/mL) were less likely to improve than those with plasma concentrations greater than this limit. We computed essentially the same χ2 statistic and obtained a similar result,1(p842) but it did not occur to us that this finding would necessarily imply the existence of a threshold. Why should it? This is a surprising inference.

Palao et al believe that the existence of a threshold is "consistent with the finding that an antipsychotic effect occurs when D2 dopamine receptor occupancy reaches approximately 65% to 75%." However, an

REFERENCES

Volavka J, Cooper TB, Czobor P, Meisner M.  Plasma haloperidol levels and clinical effects in schizophrenia and schizoaffective disorder . Arch Gen Psychiatry . 1995;;52:837-845.
Farde L, Nordstrom AL, Wiesel FA, Pauli S, Halldin C, Sedvall G.  Positron emission tomographic analysis of central D1 and D2 dopamine receptor occupancy in patients treated with classical neuroleptics and clozapine: relation to extrapyramidal side effects . Arch Gen Psychiatry . 1992;;49:538-544.
Palao DJ, Arauxo A, Brunet M, Bernardo M, Haro JM, Ferrer J, Gonzalez-Monclus E.  Haloperidol: therapeutic window in schizophrenia . J Clin Psychopharmacol . 1994;;14:303-310.

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Volavka J, Cooper TB, Czobor P, Meisner M.  Plasma haloperidol levels and clinical effects in schizophrenia and schizoaffective disorder . Arch Gen Psychiatry . 1995;;52:837-845.
Farde L, Nordstrom AL, Wiesel FA, Pauli S, Halldin C, Sedvall G.  Positron emission tomographic analysis of central D1 and D2 dopamine receptor occupancy in patients treated with classical neuroleptics and clozapine: relation to extrapyramidal side effects . Arch Gen Psychiatry . 1992;;49:538-544.
Palao DJ, Arauxo A, Brunet M, Bernardo M, Haro JM, Ferrer J, Gonzalez-Monclus E.  Haloperidol: therapeutic window in schizophrenia . J Clin Psychopharmacol . 1994;;14:303-310.

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