Clinical Neuroscience

Receptor occupancy and drug response: Understanding the relationship

Current Psychiatry. 2018 September;17(9):8-13

References

1. Farde L, Nordström AL, Wiesel FA, et al. 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(7):538-544.
2. Kapur S, Zipursky R, Jones C, et al. Relationship between dopamine D(2) occupancy, clinical response, and side effects: a double-blind PET study of first-episode schizophrenia. Am J Psychiatry. 2000;157(4):514-520.
3. Roberts RJ, Lohano KK, El-Mallakh RS. Antipsychotics as antidepressants. Asia Pacific Psychiatry. 2016;8(3):179-188.
4. Quitkin FM, Rabkin JG, Gerald J, et al. Validity of clinical trials of antidepressants. Am J Psychiatry. 2000;157(3):327-337.
5. Meyer JH, Wilson AA, Sagrati S, et al. Serotonin transporter occupancy of five selective serotonin reuptake inhibitors at different doses: an [11C]DASB positron emission tomography study. Am J Psychiatry. 2004;161(5):826-835.
6. Lundberg J, Tiger M, Landén M, et al. Serotonin transporter occupancy with TCAs and SSRIs: a PET study in patients with major depressive disorder. Int J Neuropsychopharmacol. 2012;15(8):1167-1172.
7. Takano H, Arakawa R, Nogami T, et al. Norepinephrine transporter occupancy by nortriptyline in patients with depression: a positron emission tomography study with (S,S)-[¹⁸F]FMeNER-D2. Int J Neuropsychopharmacol. 2014;17(4):553-560.
8. Johnson M, Kozielska M, Pilla Reddy V, et al. Dopamine D2 receptor occupancy as a predictor of catalepsy in rats: a pharmacokinetic-pharmacodynamic modeling approach. Pharm Res. 2014;31(10):2605-2617.
9. Allen MH, Citrome L, Pikalov A, et al. Efficacy of lurasidone in the treatment of agitation: a post hoc analysis of five short-term studies in acutely ill patients with schizophrenia. Gen Hosp Psychiatry. 2017;47:75-82.
10. Sekine M, Maeda J, Shimada H, et al. Central nervous system drug evaluation using positron emission tomography. Clin Psychopharmacol Neurosci. 2011;9(1):9-16.
11. Ma GF, Raivio N, Sabrià J, et al. Agonist and antagonist effects of aripiprazole on D2-like receptors controlling rat brain dopamine synthesis depend on the dopaminergic tone. Int J Neuropsychopharmacol. 2014;18(4):pii: pyu046. doi: 10.1093/ijnp/pyu046.
12. Yokoi F, Gründer G, Biziere K, et al. Dopamine D2 and D3 receptor occupancy in normal humans treated with the antipsychotic drug aripiprazole (OPC 14597): a study using positron emission tomography and [11C]raclopride. Neuropsychopharmacology. 2002;27(2):248-259.
13. Gründer G, Carlsson A, Wong DF. Mechanism of new antipsychotic medications: occupancy is not just antagonism. Arch Gen Psychiatry. 2003;60(10):974-977.
14. Mamo D, Graff A, Mizrahi R, et al. Differential effects of aripiprazole on D(2), 5-HT(2), and 5-HT(1A)receptor occupancy in patients with schizophrenia: a triple tracer PET study. Am J Psychiatry. 2007;164(9):1411-1417.
15. Weiden PJ, Preskorn SH, Fahnestock PA, et al. Translating the psychopharmacology of antipsychotics to individualized treatment for severe mental illness: a roadmap. J Clin Psychiatry. 2007;68(suppl 7):1-48.
16. Abi-Dargham A, Rodenhiser J, Printz D, et al. Increased baseline occupancy of D2 receptors by dopamine in schizophrenia. Proc Natl Acad Sci U S A. 2000;97(14):8104-8109.
17. Kane JM, Carson WH, Saha AR, et al. Efficacy and safety of aripiprazole and haloperidol versus placebo in patients with schizophrenia and schizoaffective disorder. J Clin Psychiatry. 2002;63(9):763-771.
18. Potkin SG, Saha AR, Kujawa MJ, et al. Aripiprazole, an antipsychotic with a novel mechanism of action, and risperidone vs placebo in patients with schizophrenia and schizoaffective disorder. Arch Gen Psychiatry. 2003;60(7):681-690.
19. Cutler AJ, Marcus RN, Hardy SA, et al. The efficacy and safety of lower doses of aripiprazole for the treatment of patients with acute exacerbation of schizophrenia. CNS Spectr. 2006;11(9):691-702; quiz 719.
20. Gründer G, Landvogt C, Vernaleken I, et al. The striatal and extrastriatal D2/D3 receptor-binding profile of clozapine in patients with schizophrenia. Neuropsychopharmacology. 2006;31(5):1027-1035.
21. Mizuno Y, Bies RR, Remington G, et al. Dopamine D2 receptor occupancy with risperidone or olanzapine during maintenance treatment of schizophrenia: a cross-sectional study. Prog Neuropsychopharmacol Biol Psychiatry. 2012;37(1):182-187.
22. Moriguchi S, Bies RR, Remington G, et al. Estimated dopamine D2 receptor occupancy and remission in schizophrenia: analysis of the CATIE data. J Clin Psychopharmacol. 2013;33(5):682-685.
23. Pilowsky LS, Mulligan RS, Acton PD, et al. Limbic selectivity of clozapine. Lancet. 1997;350(9076):490-491.
24. Ito H, Arakawa R, Takahashi H, et al. No regional difference in dopamine D2 receptor occupancy by the second-generation antipsychotic drug risperidone in humans: a positron emission tomography study. Int J Neuropsychopharmacol. 2009;12(5):667-675.
25. Arakawa R, Ito H, Okumura M, et al. Extrastriatal dopamine D(2) receptor occupancy in olanzapine-treated patients with schizophrenia. Eur Arch Psychiatry Clin Neurosci. 2010;260(4):345-350.
26. Xiberas X, Martinot JL, Mallet L, et al. Extrastriatal and striatal D(2) dopamine receptor blockade with haloperidol or new antipsychotic drugs in patients with schizophrenia. Br J Psychiatry. 2001;179:503-508.
27. Cutler AJ, Tran-Johnson T, Kalali A, et al. A failed 6-week, randomized, double-blind, placebo-controlled study of once-daily extended release quetiapine fumarate in patients with acute schizophrenia: lessons learned. Psychopharmacol Bull. 2010;43(4):37-69.
28. Marder SR, Meibach RC. Risperidone in the treatment of schizophrenia. Am J Psychiatry. 1994;151(6):825-835.
29. Meltzer HY, Cucchiaro J, Silva R, et al. Lurasidone in the treatment of schizophrenia: a randomized, double-blind, placebo- and olanzapine-controlled study. Am J Psychiatry. 2011;168(9):957-967.
30. Wong DF, Kuwabara H, Brašic JR, et al. Determination of dopamine D2 receptor occupancy by lurasidone using positron emission tomography in healthy male subjects. Psychopharmacology (Berl). 2013;229(2):245-252.
31. Potkin SG, Keator DB, Kesler-West ML, et al. D2 receptor occupancy following lurasidone treatment in patients with schizophrenia or schizoaffective disorder. CNS Spectr. 2014;19(2):176-181.
32. de Leon J, Susce MT, Pan RM, et al. The CYP2D6 poor metabolizer phenotype may be associated with risperidone adverse drug reactions and discontinuation. J Clin Psychiatry. 2005;66(1):15-27.
33. de Leon J, Susce MT, Pan RM, et al. A study of genetic (CYP2D6 and ABCB1) and environmental (drug inhibitors and inducers) variables that may influence plasma risperidone levels. Pharmacopsychiatry. 2007;40(3):93-102.
34. Narahari A, El-Mallakh RS, Kolikonda MK, et al. How coffee and cigarettes can affect the response to psychopharmacotherapy. Current Psychiatry. 2015;14(10):79-80.
35. Calabrese JR, Keck PE Jr, Macfadden W, et al. A randomized, double-blind, placebo-controlled trial of quetiapine in the treatment of bipolar I or II depression. Am J Psychiatry. 2005;162(7):1351-1360.
36. Loebel A, Cucchiaro J, Silva R, et al. Lurasidone monotherapy in the treatment of bipolar I depression: a randomized, double-blind, placebo-controlled study. Am J Psychiatry. 2014;171(2):160-168.
37. Lindenmayer JP, Brown D, Liu S, et al. The efficacy and tolerability of once-daily extended release quetiapine fumarate in hospitalized patients with acute schizophrenia: a 6-week randomized, double-blind, placebo-controlled study. Psychopharmacol Bull. 2008;41(3):11-35.

Receptor occupancy and drug response: Understanding the relationship

References

Clinical implications

Pages

Recommended Reading