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7 - Haloperidol and Haloperidol Decanoate

Published online by Cambridge University Press:  19 October 2021

Jonathan M. Meyer
University of California, San Diego
Stephen M. Stahl
University of California, Riverside and San Diego
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Haloperidol is among the most extensively studied of all antipsychotics. By 1996, 18 fixed-dose haloperidol trials were in the literature [7, 8], and a 1998 paper noted that 50 studies had been published on haloperidol plasma levels, though many had significant methodological limitations [9]. This clinical database has been supplemented by numerous single photon (SPECT) and, later, Positron Emission Tomography (PET) imaging studies of dopamine D2 receptor occupancy, starting in 1988 [10–12, 1].

The Clinical Use of Antipsychotic Plasma Levels
Stahl's Handbooks
, pp. 157 - 173
Publisher: Cambridge University Press
Print publication year: 2021

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Van Putten, T., Marder, S. R., Wirshing, W. C., et al. (1991). Neuroleptic plasma levels. Schizophr Bull, 17, 197216.
Wei, F. C., Jann, M. W., Lin, H. N., et al. (1996). A practical loading dose method for converting schizophrenic patients from oral to depot haloperidol therapy. J Clin Psychiatry, 57, 298302.
Kapur, S., Zipursky, R., Roy, P., et al. (1997). The relationship between D2 receptor occupancy and plasma levels on low dose oral haloperidol: A PET study. Psychopharmacology, 131, 148152.
Midha, K. K., Hubbard, J. W., Marder, S. R., et al. (1994). Impact of clinical pharmacokinetics on neuroleptic therapy in patients with schizophrenia. J Psychiatry Neurosci, 19, 254264.
Regenthal, R., Kunstler, U., Junhold, U., et al. (1997). Haloperidol serum concentrations and D2 dopamine receptor occupancy during low-dose treatment with haloperidol decanoate. Int Clin Psychopharmacol, 12, 255261.
Meyer, J. M. (2014). A rational approach to employing high plasma levels of antipsychotics for violence associated with schizophrenia: Case vignettes. CNS Spectr, 19, 432438.
Van Putten, T. and Marder, S. R. (1986). Variable dose studies provide misleading therapeutic windows. J Clin Psychopharmacol, 6, 5556.
de Oliveira, I. R., de Sena, E. P., Pereira, E. L., et al. (1996). Haloperidol blood levels and clinical outcome: A meta-analysis of studies relevant to testing the therapeutic window hypothesis. J Clin Pharm Ther, 21, 229236.
Ulrich, S., Wurthmann, C., Brosz, M., et al. (1998). The relationship between serum concentration and therapeutic effect of haloperidol in patients with acute schizophrenia. Clin Pharmacokinet, 34, 227263.
Dahl, S. G. (1988). Pharmacokinetics of neuroleptic drugs and the utility of plasma level monitoring. Psychopharmacol Ser, 5, 3446.
Farde, L., Wiesel, F. A., Halldin, C., et al. (1988). Central D2-dopamine receptor occupancy in schizophrenic patients treated with antipsychotic drugs. Arch Gen Psychiatry, 45, 7176.
Smith, M., Wolf, A. P., Brodie, J. D., et al. (1988). Serial [18F]N-methylspiroperidol PET studies to measure changes in antipsychotic drug D-2 receptor occupancy in schizophrenic patients. Biol Psychiatry, 23, 653663.
Schoretsanitis, G., Kane, J. M., Correll, C. U., et al. (2020). Blood levels to optimize antipsychotic treatment in clinical practice: A joint consensus statement of the American Society of Clinical Psychopharmacology (ASCP) and the Therapeutic Drug Monitoring (TDM) Task Force of the Arbeitsgemeinschaft für Neuropsychopharmakologie und Pharmakopsychiatrie (AGNP). J Clin Psychiatry, 81,
Meyer, J. M. (2018). Pharmacotherapy of psychosis and mania. In Brunton, L. L., Hilal-Dandan, R., and Knollmann, B. C., eds., Goodman & Gilman’s The Pharmacological Basis of Therapeutics, 13th edn. Chicago, IL: McGraw-Hill, pp. 279302.
Kudo, S. and Ishizaki, T. (1999). Pharmacokinetics of haloperidol: An update. Clin Pharmacokinet, 37, 435456.
Suzuki, A., Otani, K., Mihara, K., et al. (1997). Effects of the CYP2D6 genotype on the steady-state plasma concentrations of haloperidol and reduced haloperidol in Japanese schizophrenic patients. Pharmacogenetics, 7, 415418.
Panagiotidis, G., Arthur, H. W., Lindh, J. D., et al. (2007). Depot haloperidol treatment in outpatients with schizophrenia on monotherapy: Impact of CYP2D6 polymorphism on pharmacokinetics and treatment outcome. Ther Drug Monit, 29, 417422.
Fast, D. K., Jones, B. D., Kusalic, M., et al. (1986). Effect of carbamazepine on neuroleptic plasma levels and efficacy. Am J Psychiatry, 143, 117118.
Spina, E. and Perucca, E. (2002). Clinical significance of pharmacokinetic interactions between antiepileptic and psychotropic drugs. Epilepsia, 43 Suppl2, 3744.
Mylan Institutional LLC (2019). Haloperidol package insert. Rockford, IL.
Jann, M. W., Fidone, G. S., Hernandez, J. M., et al. (1989). Clinical implications of increased antipsychotic plasma concentrations upon anticonvulsant cessation. Psychiatry Res, 28, 153159.
Raitasuo, V., Lehtovaara, R., and Huttunen, M. O. (1994). Effect of switching carbamazepine to oxcarbazepine on the plasma levels of neuroleptics: A case report. Psychopharmacology (Berl), 116, 115116.
Kapur, S. and Seeman, P. (2001). Does fast dissociation from the dopamine d(2) receptor explain the action of atypical antipsychotics? A new hypothesis. Am J Psychiatry, 158, 360369.
Giegling, I., Drago, A., Schafer, M., et al. (2010). Interaction of haloperidol plasma level and antipsychotic effect in early phases of acute psychosis treatment. J Psychiatr Res, 44, 487492.
Meyer, J. M. (2017). Converting oral to long acting injectable antipsychotics: A guide for the perplexed. CNS Spectr, 22, 1428.
Chang, W. H., Lin, S. K., Juang, D. J., et al. (1993). Prolonged haloperidol and reduced haloperidol plasma concentrations after decanoate withdrawal. Schizophr Res, 9, 3540.
Harasko-van der Meer, C., Brucke, T., Wenger, S., et al. (1993). Two cases of long term dopamine D2 receptor blockade after depot neuroleptics. J Neural Transm, 94, 217221.
Kurose, S., Mimura, Y., Uchida, H., et al. (2020). Dissociation in pharmacokinetic attenuation between central dopamine D2 receptor occupancy and peripheral blood concentration of antipsychotics: A systematic review. J Clin Psychiatry, 81, 19r13113.
Haddad, P., Lambert, T., and Lauriello, J., eds. (2016). Antipsychotic Long-Acting Injections, 2nd edn. New York: Oxford University Press.
Deberdt, R., Elens, P., Berghmans, W., et al. (1980). Intramuscular haloperidol decanoate for neuroleptic maintenance therapy: Efficacy, dosage schedule and plasma levels. An open multicenter study. Acta Psychiatr Scand, 62, 356363.
Ereshefsky, L., Toney, G., Saklad, S. R., et al. (1993). A loading-dose strategy for converting from oral to depot haloperidol. Hosp Community Psychiatry, 44, 11551161.
Jann, M. W., Wei, F. C., Lin, H. N., et al. (1996). Haloperidol and reduced haloperidol plasma concentrations after a loading dose regimen with haloperidol decanoate. Prog Neuropsychopharmacol Biol Psychiatry, 20, 7386.
Van Putten, T., Marder, S. R., Mintz, J., et al. (1992). Haloperidol plasma levels and clinical response: A therapeutic window relationship. Am J Psychiatry, 149, 500505.
Pilla Reddy, V., Kozielska, M., Johnson, M., et al. (2013). Population pharmacokinetic–pharmacodynamic modeling of haloperidol in patients with schizophrenia using positive and negative syndrome rating scale. J Clin Psychopharmacol, 33, 731739.
Van Putten, T., Marder, S. R., May, P. R., et al. (1985). Plasma levels of haloperidol and clinical response. Psychopharmacol Bull, 21, 6972.
Marder, S. R., Davis, J. M., and Janicak, P. G., eds. (1993). Clinical Use of Neuroleptic Plasma Levels. Washington, DC: American Psychiatric Press Inc.
Kapur, S., Zipursky, R., Jones, C., et al. (2000). Relationship between dopamine D(2) occupancy, clinical response, and side effects: A double-blind PET study of first-episode schizophrenia. Am J Psychiatry, 157, 514520.
Merlo, M. C., Hofer, H., Gekle, W., et al. (2002). Risperidone, 2 mg/day vs. 4 mg/day, in first-episode, acutely psychotic patients: Treatment efficacy and effects on fine motor functioning. J Clin Psychiatry, 63, 885891.
Fitzgerald, P. B., Kapur, S., Remington, G., et al. (2000). Predicting haloperidol occupancy of central dopamine D2 receptors from plasma levels. Psychopharmacology, 149, 15.
Lim, H. S., Kim, S. J., Noh, Y. H., et al. (2013). Exploration of optimal dosing regimens of haloperidol, a D2 antagonist, via modeling and simulation analysis in a D2 receptor occupancy study. Pharm Res, 30, 683693.
de Haan, L., van Bruggen, M., Lavalaye, J., et al. (2003). Subjective experience and D2 receptor occupancy in patients with recent-onset schizophrenia treated with low-dose olanzapine or haloperidol: A randomized, double-blind study. Am J Psychiatry, 160, 303309.
Veselinovicć, T., Scharpenberg, M., Heinze, M., et al. (2019). Dopamine D2 receptor occupancy estimated from plasma concentrations of four different antipsychotics and the subjective experience of physical and mental well-being in schizophrenia: Results from the randomized NeSSy Trial. J Clin Psychopharmacol, 39, 550560.
Simpson, G. M. and Kunz-Bartholini, E. (1968). Relationship of individual tolerance, behavior and phenothiazine produced extrapyramidal system disturbance. Dis Nerv System, 29, 269274.
Nyberg, S., Dencker, S. J., Malm, U., et al. (1998). D(2)- and 5-HT(2) receptor occupancy in high-dose neuroleptic-treated patients. Int J Neuropsychopharmacol, 1, 95101.
Meyer, J. M. (2020). Monitoring and improving antipsychotic adherence in outpatient forensic diversion programs. CNS Spectr, 25, 136144.
Samara, M. T., Leucht, C., Leeflang, M. M., et al. (2015). Early improvement as a predictor of later response to antipsychotics in schizophrenia: A diagnostic test review. Am J Psychiatry, 172, 617629.
Leucht, S., Kane, J. M., Etschel, E., et al. (2006). Linking the PANSS, BPRS, and CGI: Clinical implications. Neuropsychopharmacology, 31, 23182325.
Marder, S. R. and Meibach, R. C. (1994). Risperidone in the treatment of schizophrenia. Am J Psychiatry, 151, 825835.

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