Relationship Between Dopamine D 2 Occupancy, Clinical Response, and Side Effects: A Double-Blind PET Study of First-Episode Schizophrenia
Abstract
OBJECTIVE: Since all antipsychotics block dopamine D(2) receptors, the authors investigated how well D(2) receptor occupancy in vivo predicts clinical response, extrapyramidal side effects, and hyperprolactinemia. METHOD: In a double-blind study, 22 patients with first-episode schizophrenia were randomly assigned to 1.0 or 2. 5 mg/day of haloperidol. After 2 weeks of treatment, D(2) receptor occupancy was determined with [(11)C]raclopride and positron emission tomography, and clinical response, extrapyramidal side effects, and prolactin levels were measured. Patients who showed adequate responses continued taking their initial doses, those who did not respond had their doses increased to 5.0 mg/day, and evaluations were repeated at 4 weeks for all patients. RESULTS: The patients showed a wide range of D(2) occupancy (38%-87%). The degree of receptor occupancy predicted clinical improvement, hyperprolactinemia, and extrapyramidal side effects. The likelihood of clinical response, hyperprolactinemia, and extrapyramidal side effects increased significantly as D(2) occupancy exceeded 65%, 72%, and 78%, respectively. CONCLUSIONS: The study confirms that D(2) occupancy is an important mediator of response and side effects in antipsychotic treatment. The data are consistent with a "target and trigger" hypothesis of antipsychotic action, i.e., that the D(2) receptor specificity of antipsychotics permits them to target discrete neurons and that their antagonist properties trigger within those neurons intracellular changes that ultimately beget antipsychotic response. While limited to haloperidol, the relationship between D(2) occupancy and side effects in this study helps explain many of the observed clinical differences between typical and atypical antipsychotics.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
A minimum threshold of D2 antagonism is required before a clinical effect or adverse effects are seen.
“There is a body of evidence that suggests that a minimum threshold of D2 antagonism is required before a clinical effect or adverse effects are seen108”
From A Method for Tapering Antipsychotic Treatment That May Minimize the Risk of Relapse (2021) · cites this paper as [108]
Cites
The Positive and Negative Syndrome Scale (PANSS) for schizophrenia.
Kay, S. R., Fiszbein, A., & Opler, L. A. (1987) · Schizophrenia Bulletin · doi:10.1093/schbul/13.2.261 · Cited by 21,378 · see citing works
A Rating Scale for Drug-Induced Akathisia
Barnes, T. R. E. (1989) · The British Journal of Psychiatry · doi:10.1192/bjp.154.5.672 · Cited by 2,179 · see citing works
Dopamine in schizophrenia: a review and reconceptualization
Davis, K. L., Kahn, R. S., Ko, G., & Davidson, M. (1991) · American Journal of Psychiatry · doi:10.1176/ajp.148.11.1474 · Cited by 2,021 · see citing works
Automated Image Registration: I. General Methods and Intrasubject, Intramodality Validation
Woods, R. P., Grafton, S. T., Holmes, C. J., Cherry, S. R., & Mazziotta, J. C. (1998) · Journal of Computer Assisted Tomography · doi:10.1097/00004728-199801000-00027 · Cited by 1,707 · see citing works
Antipsychotic drug doses and neuroleptic/dopamine receptors
SEEMAN, P., LEE, T., CHAU-WONG, M., & WONG, K. (1976) · Nature · doi:10.1038/261717a0 · Cited by 1,622 · see citing works
Farde, L. (1992) · Archives of General Psychiatry · doi:10.1001/archpsyc.1992.01820070032005 · Cited by 1,420 · see citing works
Schotte, A., Janssen, P. F. M., Gommeren, W., Luyten, W. H. M. L., Gompel, P. V., Lesage, A. S., Loore, K. D., & Leysen, J. E. (1996) · Psychopharmacology · doi:10.1007/bf02245606 · Cited by 1,167 · see citing works
Automated Image Registration: II. Intersubject Validation of Linear and Nonlinear Models
Woods, R. P., Grafton, S. T., Watson, J. D. G., Sicotte, N. L., & Mazziotta, J. C. (1998) · Journal of Computer Assisted Tomography · doi:10.1097/00004728-199801000-00028 · Cited by 993 · see citing works
Quantitative Analysis of D2 Dopamine Receptor Binding in the Living Human Brain by PET
Farde, L., Hall, H., Ehrin, E., & Sedvall, G. (1986) · Science · doi:10.1126/science.2867601 · Cited by 831 · see citing works
Serotonin-dopamine interaction and its relevance to schizophrenia
Kapur, S., & Remington, G. (1996) · American Journal of Psychiatry · doi:10.1176/ajp.153.4.466 · Cited by 826 · see citing works
Self-citationKapur, S., Zipursky, R. B., & Remington, G. J. (1999) · American Journal of Psychiatry · doi:10.1176/ajp.156.2.286 · Cited by 711 · see citing works
Self-citationD2 Dopamine Receptors in Neuroleptic-Naive Schizophrenic Patients
Farde, L. (1990) · Archives of General Psychiatry · doi:10.1001/archpsyc.1990.01810150013003 · Cited by 529 · see citing works
Nordström, A., Farde, L., Wiesel, F., Forslund, K., Pauli, S., Halldin, C., & Uppfeldt, G. (1993) · Biological Psychiatry · doi:10.1016/0006-3223(93)90288-o · Cited by 527 · see citing works
Optimal Dose of Neuroleptic in Acute Schizophrenia
McEvoy, J. P. (1991) · Archives of General Psychiatry · doi:10.1001/archpsyc.1991.01810320063009 · Cited by 384 · see citing works
MAREK, K. L., Seibyl, J. P., Zoghbi, S. S., Zea‐Ponce, Y., Baldwin, R. M., Fussell, B., Charney, D. S., van Dyck, C. H., Hoffer, P. B., & Innis, R. B. (1996) · Neurology · doi:10.1212/wnl.46.1.231 · Cited by 365 · see citing works
Nordström, A., Farde, L., Nyberg, S., Karlsson, P., Halldin, C., & Sedvall, G. (1995) · American Journal of Psychiatry · doi:10.1176/ajp.152.10.1444 · Cited by 339 · see citing works
Meltzer, H. Y., Matsubara, S., & Lee, J. C. (1989) · PubMed · Cited by 322 · see citing works
Frost, J. J., Rosier, A., Reich, S. G., Smith, J. S., Ehlers, M., Snyder, S. H., Ravert, H. T., & Dannals, R. F. (1993) · Annals of Neurology · doi:10.1002/ana.410340331 · Cited by 320 · see citing works
Haloperidol-induced catalepsy is mediated by postsynaptic dopamine receptors
Sanberg, P. R. (1980) · Nature · doi:10.1038/284472a0 · Cited by 313 · see citing works
Dopamine blockade and clinical response: evidence for two biological subgroups of schizophrenia
Wolkin, A., Barouche, F., Wolf, A. P., Rotrosen, J., Fowler, J. S. L., Shiue, C., Cooper, T. B., & Brodie, J. D. (1989) · American Journal of Psychiatry · doi:10.1176/ajp.146.7.905 · Cited by 258 · see citing works
High levels of dopamine D2 receptor occupancy with low-dose haloperidol treatment: a PET study
Kapur, S., Remington, G. J., Jones, C. E., Wilson, A., DaSilva, J. N., Houle, S., & Zipursky, R. B. (1996) · American Journal of Psychiatry · doi:10.1176/ajp.153.7.948 · Cited by 251 · see citing works
Self-citationAtypical Neuroleptics Have Low Affinity for Dopamine D2 Receptors or Are Selective for D4 Receptors
Seeman, P. M. (1997) · Neuropsychopharmacology · doi:10.1016/s0893-133x(96)00187-x · Cited by 236 · see citing works
Pilowsky, L. S., Murray, R. M., Kerwin, R. W., Costa, D. C., Ell, P. J., & Verhoeff, N. P. L. G. (1992) · The Lancet · doi:10.1016/0140-6736(92)90467-h · Cited by 202 · see citing works
Farde, L., Suhara, T., Karlsson, P., Hietala, J. A., Nakashima, Y., Halldin, C., & Nyberg, S. (1997) · Psychopharmacology · doi:10.1007/s002130050420 · Cited by 177 · see citing works
Hietala, J. A. (1994) · Archives of General Psychiatry · doi:10.1001/archpsyc.1994.03950020040004 · Cited by 176 · see citing works
D2 dopamine receptor occupancy during low-dose treatment with haloperidol decanoate
Nyberg, S., Farde, L., Halldin, C., Dahl, M., & Bertilsson, L. (1995) · American Journal of Psychiatry · doi:10.1176/ajp.152.2.173 · Cited by 144 · see citing works
Kapur, S., Zipursky, R. B., Roy, P., Jones, C., Remington, G. J., Reed, K. L., & Houle, S. (1997) · Psychopharmacology · doi:10.1007/s002130050277 · Cited by 126 · see citing works
Self-citationBaron, J., Martinot, J. L., Cambon, H., Boulenger, J.-P., Poirier, M. F., Caillard, V., Blin, J., Huret, J. D., Loc’h, C., & Maziere, B. (1989) · Psychopharmacology · doi:10.1007/bf00589893 · Cited by 119 · see citing works
New antipsychotics: the present status
Gerlach, J., & Peacock, L. (1995) · International Clinical Psychopharmacology · doi:10.1097/00004850-199509000-00006 · Cited by 101 · see citing works
Pilowsky, L. S., Costa, D. C., Ell, P. J., Murray, R. M., Verhoeff, N. P. L. G., & Kerwin, R. W. (1993) · Psychological Medicine · doi:10.1017/s0033291700025575 · Cited by 100 · see citing works
Pharmacotherapy of first-episode schizophrenia
Remington, G. J., Kapur, S., & Zipursky, R. B. (1998) · The British Journal of Psychiatry · doi:10.1192/s0007125000297687 · Cited by 91 · see citing works
Self-citationDopamine D1 (SCH 23390) and D2 (haloperidol) antagonists in drug-naive monkeys
Casey, D. E. (1992) · Psychopharmacology · doi:10.1007/bf02244960 · Cited by 65 · see citing works
D2‐dopamine receptor occupancy differs between patients with and without extrapyramidal side effects
Scherer, J., Tatsch, K., Schwarz, J., et al. (1994) · Acta Psychiatrica Scandinavica · doi:10.1111/j.1600-0447.1994.tb01591.x · Cited by 60 · see citing works
Striatal dopamine D2-receptor blockade by typical and atypical neuroleptics
Brücke, T., Roth, J., Podreka, I., et al. (1992) · The Lancet · doi:10.1016/0140-6736(92)91108-k · Cited by 56 · see citing works
Wadenberg, M.-L., Salmi, P., Jimenez, P., et al. (1996) · European Neuropsychopharmacology · doi:10.1016/s0924-977x(96)00035-1 · Cited by 48 · see citing works
The Scottish First Episode Schizophrenia Study: II. Treatment: Pimozide Versus Flupenthixol
(1987) · The British Journal of Psychiatry · doi:10.1192/bjp.150.3.334 · Cited by 47 · see citing works
Optimal Haloperidol Dosage in First-Episode Psychosis
Zhang-Wong, J., Zipursky, R. B., Beiser, M., & Bean, G. (1999) · The Canadian Journal of Psychiatry · doi:10.1177/070674379904400207 · Cited by 44 · see citing works
Self-citationTreatment outcome of first episode schizophrenia.
Lieberman, J. A., Jody, D. N., Geisler, S., Vital-Herne, J., Alvir, J., Walsleben, J. A., & Woerner, M. G. (1989) · PubMed · Cited by 44 · see citing works
Prinssen, E. P. M., Ellenbroek, B. A., & Cools, A. R. (1994) · European Journal of Pharmacology · doi:10.1016/0014-2999(94)90041-8 · Cited by 43 · see citing works
Palermo‐Neto, J. (1997) · Psychiatric Clinics of North America · doi:10.1016/s0193-953x(05)70341-5 · Cited by 42 · see citing works
The D2 Receptor Occupancy Profile of Loxapine Determined Using PET
Kapur, S. (1996) · Neuropsychopharmacology · doi:10.1016/s0893-133x(96)00100-5 · Cited by 37 · see citing works
Self-citationPET measurement of neuroreceptor occupancy by typical and atypical neuroleptics.
Goyer, P. F., Berridge, M. S., Morris, E. D., Semple, W. E., Compton-Toth, B. A., Schulz, S. C., Wong, D. F., Miraldi, F. D., & Meltzer, H. Y. (1996) · PubMed · Cited by 37 · see citing works
Prolactin plasma levels and D2-dopamine receptor occupancy measured with IBZM-SPECT
Schlegel, S., Schlösser, R. G. M., Hiemke, C., et al. (1996) · Psychopharmacology · doi:10.1007/bf02246671 · Cited by 33 · see citing works
Gerlach, J., & Peacock, L. (1995) · International Clinical Psychopharmacology · doi:10.1097/00004850-199509003-00006 · Cited by 5 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Kapur, S. (2003) · American Journal of Psychiatry · doi:10.1176/appi.ajp.160.1.13 · Cited by 2,813 · see citing works
Self-citationThe Dopamine Hypothesis of Schizophrenia: Version III--The Final Common Pathway
Howes, O. D., & Kapur, S. (2009) · Schizophrenia Bulletin · doi:10.1093/schbul/sbp006 · Cited by 2,693 · see citing works
Self-citationKapur, S., & Seeman, P. (2001) · American Journal of Psychiatry · doi:10.1176/appi.ajp.158.3.360 · Cited by 1,140 · see citing works
Self-citationMiyamoto, S., Duncan, G. E., Marx, C. E., & Lieberman, J. A. (2005) · Molecular Psychiatry · doi:10.1038/sj.mp.4001556 · Cited by 988 · see citing works
Glutamate and dopamine in schizophrenia: An update for the 21 <sup>st</sup> century
Howes, O., McCutcheon, R., & Stone, J. (2015) · Journal of Psychopharmacology · doi:10.1177/0269881114563634 · Cited by 702 · see citing works
Half a century of antipsychotics and still a central role for dopamine D2 receptors
Kapur, S., & Mamo, D. (2003) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2003.09.004 · Cited by 638 · see citing works
Self-citationAntipsychotic-Induced Hyperprolactinaemia: Mechanisms, Clinical Features and Management
Haddad, P. M., & Wieck, A. (2004) · Drugs · doi:10.2165/00003495-200464200-00003 · Cited by 634 · see citing works
Meyer, J. H., Wilson, A. A., Sagrati, S., Hussey, D., Carella, A., Potter, W. Z., Ginovart, N., Spencer, E. P., Cheok, A., & Houle, S. (2004) · American Journal of Psychiatry · doi:10.1176/appi.ajp.161.5.826 · Cited by 517 · see citing works
Self-citationKellendonk, C., Simpson, E. H., Polan, H. J., Malleret, G., Vronskaya, S., Winiger, V., Moore, H., & Kandel, E. R. (2006) · Neuron · doi:10.1016/j.neuron.2006.01.023 · Cited by 520 · see citing works
Treatment resistance in psychiatry: state of the art and new directions
Howes, O. D., Thase, M. E., & Pillinger, T. (2022) · Molecular Psychiatry · doi:10.1038/s41380-021-01200-3 · Cited by 413 · see citing works
Neurobiology of Dopamine in Schizophrenia
Guillin, O., Abi‐Dargham, A., & Laruelle, M. (2007) · International Review of Neurobiology · doi:10.1016/s0074-7742(06)78001-1 · Cited by 365 · see citing works
Antipsychotic Drugs: A New Risk Factor for Osteoporosis in Young Women With Schizophrenia?
O'Keane, V., & Meaney, A. M. (2005) · Journal of Clinical Psychopharmacology · doi:10.1097/01.jcp.0000150223.31007.e0 · Cited by 307 · see citing works
Antipsychotic-Induced Dopamine Supersensitivity Psychosis: Pharmacology, Criteria, and Therapy
Chouinard, G., Samaha, A.-N., Chouinard, V.-A., Peretti, C.-S., Kanahara, N., Takase, M., & Iyo, M. (2017) · Psychotherapy and Psychosomatics · doi:10.1159/000477313 · Cited by 270 · see citing works
Samaha, A.-N., Seeman, P., Stewart, J., Rajabi, H., & Kapur, S. (2007) · The Journal of Neuroscience · doi:10.1523/jneurosci.5416-06.2007 · Cited by 262 · see citing works
Self-citationDopaminergic basis of salience dysregulation in psychosis
Winton-Brown, T. T., Fusar-Poli, P., Ungless, M. A., & Howes, O. D. (2014) · Trends in Neurosciences · doi:10.1016/j.tins.2013.11.003 · Cited by 231 · see citing works
Dopamine hypothesis of schizophrenia: Making sense of it all
Toda, M., & Abi-Dargham, A. (2007) · Current Psychiatry Reports · doi:10.1007/s11920-007-0041-7 · Cited by 235 · see citing works
Meaney, A. M., Smith, S., Howes, O. D., O'Brien, M., Murray, R. M., & O'Keane, V. (2004) · British Journal of Psychiatry · doi:10.1192/bjp.184.6.503 · Cited by 217 · see citing works
Imaging glutamate in schizophrenia: review of findings and implications for drug discovery
Poels, E. M. P., Kegeles, L. S., Kantrowitz, J. T., Slifstein, M., Javitt, D. C., Lieberman, J. A., Abi-Dargham, A., & Girgis, R. R. (2014) · Molecular Psychiatry · doi:10.1038/mp.2013.136 · Cited by 205 · see citing works
Determinants of treatment response in first-episode psychosis: an 18F-DOPA PET study
Jauhar, S., Veronese, M., Nour, M. M., Rogdaki, M., Hathway, P., Turkheimer, F. E., Stone, J., Egerton, A., McGuire, P., Kapur, S., et al. (2019) · Molecular Psychiatry · doi:10.1038/s41380-018-0042-4 · Cited by 183 · see citing works
Self-citationNeuronal defects in a human cellular model of 22q11.2 deletion syndrome
Khan, T. A., Revah, O., Gordon, A., Yoon, S.-J., Krawisz, A. K., Goold, C., Sun, Y., Kim, C. H., Tian, Y., Li, M.-Y., et al. (2020) · Nature Medicine · doi:10.1038/s41591-020-1043-9 · Cited by 186 · see citing works
Abi-Dargham, A., & Laruelle, M. (2005) · European Psychiatry · doi:10.1016/j.eurpsy.2004.11.003 · Cited by 179 · see citing works
Translating Glutamate: From Pathophysiology to Treatment
Javitt, D. C., Schoepp, D., Kalivas, P. W., Volkow, N. D., Zarate, C., Merchant, K., Bear, M. F., Umbricht, D., Hajos, M., Potter, W. Z., et al. (2011) · Science Translational Medicine · doi:10.1126/scitranslmed.3002804 · Cited by 168 · see citing works
Tauscher, J., Hussain, T., Agid, O., Verhoeff, N. P. L. G., Wilson, A. A., Houle, S., Remington, G., Zipursky, R. B., & Kapur, S. (2004) · American Journal of Psychiatry · doi:10.1176/appi.ajp.161.9.1620 · Cited by 159 · see citing works
Self-citationMeyer, J. H., McNeely, H. E., Sagrati, S., Boovariwala, A., Martin, K., Verhoeff, N. P. L. G., Wilson, A. A., & Houle, S. (2006) · American Journal of Psychiatry · doi:10.1176/ajp.2006.163.9.1594 · Cited by 160 · see citing works
Self-citationA Method for Tapering Antipsychotic Treatment That May Minimize the Risk of Relapse
Horowitz, M. A., Jauhar, S., Natesan, S., Murray, R. M., & Taylor, D. (2021) · Schizophrenia Bulletin · doi:10.1093/schbul/sbab017 · Cited by 157 · see citing works
Byerly, M., Suppes, T., Tran, Q.-V., & Baker, R. A. (2007) · Journal of Clinical Psychopharmacology · doi:10.1097/jcp.0b013e31815ac4e5 · Cited by 153 · see citing works
DISC1: Structure, Function, and Therapeutic Potential for Major Mental Illness
Soares, D. C., Carlyle, B. C., Bradshaw, N. J., & Porteous, D. J. (2011) · ACS Chemical Neuroscience · doi:10.1021/cn200062k · Cited by 129 · see citing works
Estimating Dopamine D2 Receptor Occupancy for Doses of 8 Antipsychotics: A Meta-Analysis
Lako, I. M., van den Heuvel, E. R., Knegtering, H., Bruggeman, R., & Taxis, K. (2013) · Journal of Clinical Psychopharmacology · doi:10.1097/jcp.0b013e3182983ffa · Cited by 125 · see citing works
Takahashi, H., Yahata, N., Koeda, M., Takano, A., Asai, K., Suhara, T., & Okubo, Y. (2005) · NeuroImage · doi:10.1016/j.neuroimage.2005.05.039 · Cited by 114 · see citing works
Leucht, S., Priller, J., & Davis, J. M. (2024) · American Journal of Psychiatry · doi:10.1176/appi.ajp.20240738 · Cited by 117 · see citing works
Uchida, H., Takeuchi, H., Graff-Guerrero, A., Suzuki, T., Watanabe, K., & Mamo, D. C. (2011) · Journal of Clinical Psychopharmacology · doi:10.1097/jcp.0b013e318218d339 · Cited by 94 · see citing works
Jauhar, S., Veronese, M., Nour, M. M., Rogdaki, M., Hathway, P., Natesan, S., Turkheimer, F., Stone, J., Egerton, A., McGuire, P., et al. (2019) · Biological Psychiatry · doi:10.1016/j.biopsych.2018.07.003 · Cited by 75 · see citing works
Self-citationMiller, A. H., & Raison, C. L. (2023) · Molecular Psychiatry · doi:10.1038/s41380-022-01887-y · Cited by 67 · see citing works
Tadori, Y., Kitagawa, H., Forbes, R. A., McQuade, R. D., Stark, A., & Kikuchi, T. (2007) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2007.07.031 · Cited by 69 · see citing works
Coppola, D., Liu, Y., Gopal, S., Remmerie, B., Samtani, M. N., Hough, D. W., Nuamah, I., Sulaiman, A., & Pandina, G. (2012) · BMC Psychiatry · doi:10.1186/1471-244x-12-26 · Cited by 61 · see citing works
“This is within the range (60-80%) associated with antipsychotic efficacy [29-33].”
BackgroundKimura, H., Kanahara, N., Komatsu, N., Ishige, M., Muneoka, K., Yoshimura, M., Yamanaka, H., Suzuki, T., Komatsu, H., Sasaki, T., et al. (2014) · Schizophrenia Research · doi:10.1016/j.schres.2014.02.022 · Cited by 55 · see citing works
Yilmaz, Z., Zai, C. C., Hwang, R., Mann, S., Arenovich, T., Remington, G., & Daskalakis, Z. J. (2012) · Schizophrenia Research · doi:10.1016/j.schres.2012.06.027 · Cited by 52 · see citing works
Self-citationDetermining the optimal dose of haloperidol in first-episode psychosis
Oosthuizen, P., Emsley, R. A., Turner, J., & Keyter, N. (2001) · Journal of Psychopharmacology · doi:10.1177/026988110101500403 · Cited by 48 · see citing works
The role of the prolactin/vasoinhibin axis in rheumatoid arthritis: An integrative overview
Clapp, C., Adán, N., Ledesma-Colunga, M. G., Solís-Gutiérrez, M., Triebel, J., & Martínez de la Escalera, G. (2016) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-016-2187-0 · Cited by 38 · see citing works
Evolution of neuroleptic-induced extrapyramidal syndromes under long-term neuroleptic treatment.
Modestin, J., Wehrli, M. V., Stephan, P. L., & Agarwalla, P. (2008) · Schizophrenia Research · doi:10.1016/j.schres.2007.10.018 · Cited by 38 · see citing works
Jauhar, S., & Howes, O. D. (2019) · Clinical Pharmacology & Therapeutics · doi:10.1002/cpt.1357 · Cited by 32 · see citing works
Krivoy, A., Hochman, E., Sendt, K.-V., Hollander, S., Vilner, Y., Selakovic, M., Weizman, A., & Taler, M. (2018) · Schizophrenia Research · doi:10.1016/j.schres.2017.05.040 · Cited by 33 · see citing works
Role of aripiprazole in treating mood disorders
García-Amador, M., Pacchiarotti, I., Valentí, M., Sanchez, R. F., Goikolea, J. M., & Vieta, E. (2006) · Expert Review of Neurotherapeutics · doi:10.1586/14737175.6.12.1777 · Cited by 25 · see citing works
Adverse effects associated with antipsychotic use in older adults
Khalid, J., & Aparasu, R. R. (2024) · Expert Opinion on Drug Safety · doi:10.1080/14740338.2024.2386377 · Cited by 17 · see citing works
- Authors
- Kapur, S., Zipursky, R., Jones, C., Remington, G., & Houle, S.
- Affiliations
- University of Toronto (CA)
- Venue
- American Journal of Psychiatry
- Published
- 2000-04-01
- Volume
- 157
- Issue
- 4
- Pages
- 514-520
- ISSN
- 0002-953X (ISSN-L)
- 1535-7228
- OpenAlex
- W2099185967
- Cited by
- 1,090
- References
- 44
- Citations by year
- 2026: 28 · 2025: 31 · 2024: 37 · 2023: 31 · 2022: 35 · 2021: 44 · 2020: 37 · 2019: 37 · 2018: 37 · 2017: 36 · 2016: 45 · 2015: 36 · 2014: 34 · 2013: 58 · 2012: 57
- FWCI
- 25.12
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- American Journal of Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Social Sciences › Arts and Humanities › Philosophy › Mental Health and Psychiatry
- Keywords
- dopamine D2 receptor occupancy, first-episode schizophrenia, haloperidol, extrapyramidal symptoms, hyperprolactinemia, [11C]raclopride PET, typical and atypical antipsychotics, dose-response relationship
- MeSH terms
- Adolescent, Adult, Basal Ganglia Diseases, Carbon Radioisotopes, Corpus Striatum, Double-Blind Method, Female, Haloperidol, Humans, Hyperprolactinemia, Male, Middle Aged, Schizophrenia, Tomography, Emission-Computed, Antipsychotic Agents, Treatment Outcome, Receptors, Dopamine D2, Raclopride, Dopamine D2 Receptor Antagonists
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
