Clozapine-associated adverse drug reactions in 38,349 psychiatric inpatients: drug surveillance data from the AMSP project between 1993 and 2016.
AMSP program
Adverse drug reaction
Clozapine
Drug safety
Pharmacovigilance
Psychiatric inpatients
Journal
Journal of neural transmission (Vienna, Austria : 1996)
ISSN: 1435-1463
Titre abrégé: J Neural Transm (Vienna)
Pays: Austria
ID NLM: 9702341
Informations de publication
Date de publication:
13 Aug 2024
13 Aug 2024
Historique:
received:
14
05
2024
accepted:
31
07
2024
medline:
13
8
2024
pubmed:
13
8
2024
entrez:
13
8
2024
Statut:
aheadofprint
Résumé
Clozapine is a second-generation antipsychotic drug that offers superior treatment results in patients with schizophrenia but is also associated with significant risks. This study analyzes data on pharmacotherapy with clozapine and the associated adverse drug reactions (ADRs) in an inpatient setting including 38,349 patients. Data about the use of clozapine and reports of severe ADRs within the period 1993-2016 were obtained from the multicentered observational pharmacovigilance program "Arzneimittelsicherheit in der Psychiatrie" (AMSP). In total, 586 severe clozapine-associated ADRs were documented (1.53% of all patients exposed). Patients aged ≥65 years had a higher risk of ADRs than patients aged <65 years (1.96 vs. 1.48%; p = 0.021). Significantly more ADRs were attributed to clozapine alone (396; 67.6% of all 586 ADRs) than to a combination with other drugs. The most frequent ADRs were grand mal seizures (0.183% of all 38,349 patients exposed), delirium (0.180%), increased liver enzymes (0.120%), and agranulocytosis (0.107%). We detected 24 cases (0.063%) of clozapine-induced extrapyramidal symptoms, of which 8 (0.021%) were attributed to clozapine alone. Five ADRs resulted in death (0.013%): 2 due to agranulocytosis (41 cases total) (mortality = 4.88%) and 3 due to paralytic (sub)ileus (16 cases) (mortality = 18.75%). The median dose of clozapine in all patients treated was 300 mg/day, in patients who developed ADRs 250 mg/day. The main risk factor for an ADR was pre-existing damage of the affected organ system. Overall, the results of this study highlight the importance of alertness-especially of frequently overlooked symptoms-and appropriate monitoring during treatment with clozapine, even at low doses.
Identifiants
pubmed: 39136776
doi: 10.1007/s00702-024-02818-7
pii: 10.1007/s00702-024-02818-7
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
© 2024. The Author(s).
Références
Alvir JM, Lieberman JA, Safferman AZ et al (1993) Clozapine-induced agranulocytosis. Incidence and risk factors in the United States. N Engl J Med 329:162–167. https://doi.org/10.1056/NEJM199307153290303
doi: 10.1056/NEJM199307153290303
pubmed: 8515788
Amsler HA, Teerenhovi L, Barth E et al (1977) Agranulocytosis in patients treated with clozapine. A study of the Finnish epidemic. Acta Psychiatr Scand 56:241–248. https://doi.org/10.1111/j.1600-0447.1977.tb00224.x
doi: 10.1111/j.1600-0447.1977.tb00224.x
pubmed: 920225
Balda MV, Garay OU, Papale RM et al (2015) Clozapine-associated neutropenia and agranulocytosis in Argentina (2007–2012). Int Clin Psychopharmacol 30:109–114. https://doi.org/10.1097/YIC.0000000000000060
doi: 10.1097/YIC.0000000000000060
pubmed: 25486383
Beckmann B, Hippius H, Rüther E (1979) Treatment of schizophrenia. Prog Neuropsychopharmacol 3:47–52. https://doi.org/10.1016/0364-7722(79)90068-7
doi: 10.1016/0364-7722(79)90068-7
pubmed: 45564
Bishara D, Taylor D (2014) Adverse effects of clozapine in older patients: epidemiology, prevention and management. Drugs Aging 31:11–20. https://doi.org/10.1007/s40266-013-0144-2
doi: 10.1007/s40266-013-0144-2
pubmed: 24338220
Centorrino F, Albert MJ, Drago-Ferrante G et al (2003) Delirium during clozapine treatment: incidence and associated risk factors. Pharmacopsychiatry 36:156–160. https://doi.org/10.1055/s-2003-41201
doi: 10.1055/s-2003-41201
pubmed: 12905102
Chandru P, Gunja N (2023) Toxicity and adverse effects in clozapine-related presentations to a medical toxicology service in Western Sydney. J Med Toxicol 19:374–380. https://doi.org/10.1007/s13181-023-00963-1
doi: 10.1007/s13181-023-00963-1
pubmed: 37624540
Choudhury S, Banerjee S, Chatterjee K et al (2021) Low-dose clozapine-induced agranulocytosis in patients with movement disorders-retrospective study from India. Ann Indian Acad Neurol 24:831–832. https://doi.org/10.4103/aian.AIAN_522_20
doi: 10.4103/aian.AIAN_522_20
pubmed: 35002172
Chung S-J, Jeong S-H, Ahn Y-M et al (2002) A retrospective study of clozapine and electroencephalographic abnormalities in schizophrenic patients. Prog Neuropsychopharmacol Biol Psychiatry 26:139–144. https://doi.org/10.1016/s0278-5846(01)00238-x
doi: 10.1016/s0278-5846(01)00238-x
pubmed: 11853104
Cohen D (2017) Clozapine and Gastrointestinal Hypomotility. CNS Drugs 31:1083–1091. https://doi.org/10.1007/s40263-017-0481-5
doi: 10.1007/s40263-017-0481-5
pubmed: 29230675
Cohen BM, Keck PE, Satlin A, Cole JO (1991) Prevalence and severity of akathisia in patients on clozapine. Biol Psychiatry 29:1215–1219. https://doi.org/10.1016/0006-3223(91)90329-k
doi: 10.1016/0006-3223(91)90329-k
pubmed: 1888803
Conley RR, Kelly DL (2001) Management of treatment resistance in schizophrenia. Biol Psychiatry 50:898–911. https://doi.org/10.1016/s0006-3223(01)01271-9
doi: 10.1016/s0006-3223(01)01271-9
pubmed: 11743944
Curto M, Girardi N, Lionetto L et al (2016) Systematic review of clozapine cardiotoxicity. Curr Psychiatry Rep 18:68. https://doi.org/10.1007/s11920-016-0704-3
doi: 10.1007/s11920-016-0704-3
pubmed: 27222142
Demler TL, Morabito NE, Meyer CE, Opler L (2016) Maximizing clozapine utilization while minimizing blood dyscrasias: evaluation of patient demographics and severity of events. Int Clin Psychopharmacol 31:76–83. https://doi.org/10.1097/YIC.0000000000000108
doi: 10.1097/YIC.0000000000000108
pubmed: 26565383
Doane MJ, Bessonova L, Friedler HS et al (2022) Weight gain and comorbidities associated with oral second-generation antipsychotics: analysis of real-world data for patients with schizophrenia or bipolar I disorder. BMC Psychiatry 22:114. https://doi.org/10.1186/s12888-022-03758-w
doi: 10.1186/s12888-022-03758-w
pubmed: 35164737
pmcid: 8842889
Druschky K, Bleich S, Grohmann R et al (2019) Seizure rates under treatment with antipsychotic drugs: data from the AMSP project. World J Biol Psychiatry 20:732–741. https://doi.org/10.1080/15622975.2018.1500030
doi: 10.1080/15622975.2018.1500030
pubmed: 30058414
Farde L, Wiesel FA, Halldin C, Sedvall G (1988) Central D2-dopamine receptor occupancy in schizophrenic patients treated with antipsychotic drugs. Arch Gen Psychiatry 45:71–76. https://doi.org/10.1001/archpsyc.1988.01800250087012
doi: 10.1001/archpsyc.1988.01800250087012
pubmed: 2892477
Fox SH, Katzenschlager R, Lim S-Y et al (2018) International Parkinson and movement disorder society evidence-based medicine review: Update on treatments for the motor symptoms of Parkinson’s disease. Mov Disord 33:1248–1266. https://doi.org/10.1002/mds.27372
doi: 10.1002/mds.27372
pubmed: 29570866
Friedrich M-E, Winkler D, Konstantinidis A et al (2020) Cardiovascular adverse reactions during antipsychotic treatment: results of AMSP, a drug surveillance program between 1993 and 2013. Int J Neuropsychopharmacol 23:67–75. https://doi.org/10.1093/ijnp/pyz046
doi: 10.1093/ijnp/pyz046
pubmed: 31504560
Frogley C, Taylor D, Dickens G, Picchioni M (2012) A systematic review of the evidence of clozapine’s anti-aggressive effects. Int J Neuropsychopharmacol 15:1351–1371. https://doi.org/10.1017/S146114571100201X
doi: 10.1017/S146114571100201X
pubmed: 22339930
Gerlach J, Lublin H, Peacock L (1996) Extrapyramidal symptoms during long-term treatment with antipsychotics: special focus on clozapine and D1 and D2 dopamine antagonists. Neuropsychopharmacology 14:35S-39S. https://doi.org/10.1016/0893-133X(95)00203-P
doi: 10.1016/0893-133X(95)00203-P
pubmed: 8866742
Gill SS, Rochon PA, Herrmann N et al (2005) Atypical antipsychotic drugs and risk of ischaemic stroke: population based retrospective cohort study. BMJ 330:445. https://doi.org/10.1136/bmj.38330.470486.8F
doi: 10.1136/bmj.38330.470486.8F
pubmed: 15668211
pmcid: 549652
Global Burden of Disease Study (2013) Collaborators (2015) Global, regional, and national incidence, prevalence, and years lived with disability for 301 acute and chronic diseases and injuries in 188 countries, 1990–2013: a systematic analysis for the Global Burden of Disease Study 2013. Lancet 386:743–800. https://doi.org/10.1016/S0140-6736(15)60692-4
doi: 10.1016/S0140-6736(15)60692-4
Glocker C, Grohmann R, Engel R et al (2021) Galactorrhea during antipsychotic treatment: results from AMSP, a drug surveillance program, between 1993 and 2015. Eur Arch Psychiatry Clin Neurosci 271:1425–1435. https://doi.org/10.1007/s00406-021-01241-3
doi: 10.1007/s00406-021-01241-3
pubmed: 33768297
pmcid: 8563638
Glocker C, Grohmann R, Burkhardt G et al (2023) Antipsychotic drug-induced neutropenia: results from the AMSP drug surveillance program between 1993 and 2016. J Neural Transm (vienna) 130:153–163. https://doi.org/10.1007/s00702-023-02589-7
doi: 10.1007/s00702-023-02589-7
pubmed: 36653686
Grohmann R, Engel RR, Rüther E, Hippius H (2004) The AMSP drug safety program: methods and global results. Pharmacopsychiatry 37(Suppl 1):S4-11. https://doi.org/10.1055/s-2004-815505
doi: 10.1055/s-2004-815505
pubmed: 15052509
Grohmann R, Engel RR, Möller H-J et al (2014) Flupentixol use and adverse reactions in comparison with other common first- and second-generation antipsychotics: data from the AMSP study. Eur Arch Psychiatry Clin Neurosci 264:131–141. https://doi.org/10.1007/s00406-013-0419-y
doi: 10.1007/s00406-013-0419-y
pubmed: 23835526
Grover S, Sahoo S (2015) Clozapine induced akathisia: a case report and review of the evidence. Indian J Pharmacol 47:234–235. https://doi.org/10.4103/0253-7613.153441
doi: 10.4103/0253-7613.153441
pubmed: 25878393
pmcid: 4386142
Günther W, Baghai T, Naber D et al (1993) EEG alterations and seizures during treatment with clozapine. A retrospective study of 283 patients. Pharmacopsychiatry 26:69–74. https://doi.org/10.1055/s-2007-1014345
doi: 10.1055/s-2007-1014345
pubmed: 8415896
Hatano M, Yamada K, Matsuzaki H et al (2023) Analysis of clozapine-induced seizures using the Japanese Adverse Drug Event Report database. PLoS ONE 18:e0287122. https://doi.org/10.1371/journal.pone.0287122
doi: 10.1371/journal.pone.0287122
pubmed: 37307250
pmcid: 10259781
Ingimarsson O, MacCabe JH, Sigurdsson E (2018) Constipation, ileus and medication use during clozapine treatment in patients with schizophrenia in Iceland. Nord J Psychiatry 72:497–500. https://doi.org/10.1080/08039488.2018.1517189
doi: 10.1080/08039488.2018.1517189
pubmed: 30348045
Ismail Z, Wessels AM, Uchida H et al (2012) Age and sex impact clozapine plasma concentrations in inpatients and outpatients with schizophrenia. Am J Geriatr Psychiatry 20:53–60. https://doi.org/10.1097/JGP.0b013e3182118318
doi: 10.1097/JGP.0b013e3182118318
pubmed: 21422906
Jann MW, Grimsley SR, Gray EC, Chang WH (1993) Pharmacokinetics and pharmacodynamics of clozapine. Clin Pharmacokinet 24:161–176. https://doi.org/10.2165/00003088-199324020-00005
doi: 10.2165/00003088-199324020-00005
pubmed: 8453823
Joy G, Whiskey E, Bolstridge M et al (2017) Hearts and minds: real-life cardiotoxicity with clozapine in psychosis. J Clin Psychopharmacol 37:708–712. https://doi.org/10.1097/JCP.0000000000000792
doi: 10.1097/JCP.0000000000000792
pubmed: 29049078
Kapur S, Agid O, Mizrahi R, Li M (2006) How antipsychotics work-from receptors to reality. NeuroRx 3:10–21. https://doi.org/10.1016/j.nurx.2005.12.003
doi: 10.1016/j.nurx.2005.12.003
pubmed: 16490410
pmcid: 3593357
Kar N, Barreto S, Chandavarkar R (2016) Clozapine monitoring in clinical practice: beyond the mandatory requirement. Clin Psychopharmacol Neurosci 14:323–329. https://doi.org/10.9758/cpn.2016.14.4.323
doi: 10.9758/cpn.2016.14.4.323
pubmed: 27776383
pmcid: 5083942
Kikuchi YS, Sato W, Ataka K et al (2014) Clozapine-induced seizures, electroencephalography abnormalities, and clinical responses in Japanese patients with schizophrenia. Neuropsychiatr Dis Treat 10:1973–1978. https://doi.org/10.2147/NDT.S69784
doi: 10.2147/NDT.S69784
pubmed: 25342906
pmcid: 4206387
Kurisu K, Miyabe D, Furukawa Y et al (2020) Association between polypharmacy and the persistence of delirium: a retrospective cohort study. Biopsychosoc Med 14:25. https://doi.org/10.1186/s13030-020-00199-3
doi: 10.1186/s13030-020-00199-3
pubmed: 33042216
pmcid: 7541288
Lavrador M, Castel-Branco MM, Cabral AC et al (2021) Association between anticholinergic burden and anticholinergic adverse outcomes in the elderly: Pharmacological basis of their predictive value for adverse outcomes. Pharmacol Res 163:105306. https://doi.org/10.1016/j.phrs.2020.105306
doi: 10.1016/j.phrs.2020.105306
pubmed: 33248197
Leslie DL, Rosenheck RA (2002) From conventional to atypical antipsychotics and back: dynamic processes in the diffusion of new medications. Am J Psychiatry 159:1534–1540. https://doi.org/10.1176/appi.ajp.159.9.1534
doi: 10.1176/appi.ajp.159.9.1534
pubmed: 12202274
Leucht S, Cipriani A, Spineli L et al (2013) Comparative efficacy and tolerability of 15 antipsychotic drugs in schizophrenia: a multiple-treatments meta-analysis. Lancet 382:951–962. https://doi.org/10.1016/S0140-6736(13)60733-3
doi: 10.1016/S0140-6736(13)60733-3
pubmed: 23810019
Lorenzo-Villalba N, Alonso-Ortiz MB, Maouche Y et al (2020) Idiosyncratic drug-induced neutropenia and agranulocytosis in elderly patients. J Clin Med 9:1808. https://doi.org/10.3390/jcm9061808
doi: 10.3390/jcm9061808
pubmed: 32531979
pmcid: 7356965
Mahendran R, Hendricks M, Chan YH (2010) Weight gain in Asian patients on second-generation antipsychotics. Ann Acad Med Singap 39:118–121
doi: 10.47102/annals-acadmedsg.V39N2p118
pubmed: 20237733
McEvoy JP, Lieberman JA, Stroup TS et al (2006) Effectiveness of clozapine versus olanzapine, quetiapine, and risperidone in patients with chronic schizophrenia who did not respond to prior atypical antipsychotic treatment. Am J Psychiatry 163:600–610. https://doi.org/10.1176/ajp.2006.163.4.600
doi: 10.1176/ajp.2006.163.4.600
pubmed: 16585434
McIlwain ME, Harrison J, Wheeler AJ, Russell BR (2011) Pharmacotherapy for treatment-resistant schizophrenia. Neuropsychiatr Dis Treat 7:135–149. https://doi.org/10.2147/NDT.S12769
doi: 10.2147/NDT.S12769
pubmed: 21552316
pmcid: 3083987
Meltzer HY, Bastani B, Ramirez L, Matsubara S (1989) Clozapine: new research on efficacy and mechanism of action. Eur Arch Psychiatry Neurol Sci 238:332–339. https://doi.org/10.1007/BF00449814
doi: 10.1007/BF00449814
pubmed: 2569975
Meltzer HY, Alphs L, Green AI et al (2003) Clozapine treatment for suicidality in schizophrenia: international suicide prevention trial (InterSePT). Arch Gen Psychiatry 60:82–91. https://doi.org/10.1001/archpsyc.60.1.82
doi: 10.1001/archpsyc.60.1.82
pubmed: 12511175
Möller HJ (2000) State of the art of drug treatment of schizophrenia and the future position of the novel/atypical antipsychotics. World J Biol Psychiatry 1:204–214. https://doi.org/10.3109/15622970009150593
doi: 10.3109/15622970009150593
pubmed: 12607217
Moore TA, Buchanan RW, Buckley PF et al (2007) The Texas Medication Algorithm Project antipsychotic algorithm for schizophrenia: 2006 update. J Clin Psychiatry 68:1751–1762. https://doi.org/10.4088/jcp.v68n1115
doi: 10.4088/jcp.v68n1115
pubmed: 18052569
Moschny N, Hefner G, Grohmann R et al (2021) Therapeutic drug monitoring of second- and third-generation antipsychotic drugs-influence of smoking behavior and inflammation on pharmacokinetics. Pharmaceuticals (basel) 14:514. https://doi.org/10.3390/ph14060514
doi: 10.3390/ph14060514
pubmed: 34071813
Myles N, Myles H, Xia S et al (2018) Meta-analysis examining the epidemiology of clozapine-associated neutropenia. Acta Psychiatr Scand 138:101–109. https://doi.org/10.1111/acps.12898
doi: 10.1111/acps.12898
pubmed: 29786829
Nielsen J, Correll CU, Manu P, Kane JM (2013) Termination of clozapine treatment due to medical reasons: when is it warranted and how can it be avoided? J Clin Psychiatry 74:603–613. https://doi.org/10.4088/JCP.12r08064 . (quiz 613)
doi: 10.4088/JCP.12r08064
pubmed: 23842012
Palmer SE, McLean RM, Ellis PM, Harrison-Woolrych M (2008) Life-threatening clozapine-induced gastrointestinal hypomotility: an analysis of 102 cases. J Clin Psychiatry 69:759–768. https://doi.org/10.4088/jcp.v69n0509
doi: 10.4088/jcp.v69n0509
pubmed: 18452342
Pisani F, Oteri G, Costa C et al (2002) Effects of psychotropic drugs on seizure threshold. Drug Saf 25:91–110. https://doi.org/10.2165/00002018-200225020-00004
doi: 10.2165/00002018-200225020-00004
pubmed: 11888352
Schmauss M, Wolff R, Erfurth A, Rüther E (1989) Tolerability of long term clozapine treatment. Psychopharmacology 99(Suppl):S105-108. https://doi.org/10.1007/BF00442572
doi: 10.1007/BF00442572
pubmed: 2813663
Schneider M, Pauwels P, Toto S et al (2020) Severe weight gain as an adverse drug reaction of psychotropics: Data from the AMSP project between 2001 and 2016. Eur Neuropsychopharmacol 36:60–71. https://doi.org/10.1016/j.euroneuro.2020.05.001
doi: 10.1016/j.euroneuro.2020.05.001
pubmed: 32536570
Shirazi A, Stubbs B, Gomez L et al (2016) Prevalence and predictors of clozapine-associated constipation: a systematic review and meta-analysis. Int J Mol Sci 17:863. https://doi.org/10.3390/ijms17060863
doi: 10.3390/ijms17060863
pubmed: 27271593
pmcid: 4926397
Siafis S, Wu H, Wang D et al (2023) Antipsychotic dose, dopamine D2 receptor occupancy and extrapyramidal side-effects: a systematic review and dose-response meta-analysis. Mol Psychiatry 28:3267–3277. https://doi.org/10.1038/s41380-023-02203-y
doi: 10.1038/s41380-023-02203-y
pubmed: 37537284
pmcid: 10618092
Siskind D, Sharma M, Pawar M et al (2021) Clozapine levels as a predictor for therapeutic response: a systematic review and meta-analysis. Acta Psychiatr Scand 144:422–432. https://doi.org/10.1111/acps.13361
doi: 10.1111/acps.13361
pubmed: 34374073
Skokou M, Karavia EA, Drakou Z et al (2022) Adverse drug reactions in relation to clozapine plasma levels: a systematic review. Pharmaceuticals (basel) 15:817. https://doi.org/10.3390/ph15070817
doi: 10.3390/ph15070817
pubmed: 35890117
Spina E, de Leon J (2007) Metabolic drug interactions with newer antipsychotics: a comparative review. Basic Clin Pharmacol Toxicol 100:4–22. https://doi.org/10.1111/j.1742-7843.2007.00017.x
doi: 10.1111/j.1742-7843.2007.00017.x
pubmed: 17214606
Stroup TS, Gerhard T, Crystal S et al (2016) Comparative effectiveness of clozapine and standard antipsychotic treatment in adults with schizophrenia. Am J Psychiatry 173:166–173. https://doi.org/10.1176/appi.ajp.2015.15030332
doi: 10.1176/appi.ajp.2015.15030332
pubmed: 26541815
Toto S, Grohmann R, Bleich S et al (2019) Psychopharmacological treatment of schizophrenia over time in 30 908 inpatients: data from the AMSP study. Int J Neuropsychopharmacol 22:560–573. https://doi.org/10.1093/ijnp/pyz037
doi: 10.1093/ijnp/pyz037
pubmed: 31263888
pmcid: 6754736
Treves IA, Neufeld MY (1996) EEG abnormalities in clozapine-treated schizophrenic patients. Eur Neuropsychopharmacol 6:93–94. https://doi.org/10.1016/0924-977x(95)00057-v
doi: 10.1016/0924-977x(95)00057-v
pubmed: 8791033
Umbricht DS, Pollack S, Kane JM (1994) Clozapine and weight gain. J Clin Psychiatry 55(2):157–160
pubmed: 7961563
van der Horst MZ, Meijer Y, de Boer N et al (2023) Comprehensive dissection of prevalence rates, sex differences, and blood level-dependencies of clozapine-associated adverse drug reactions. Psychiatry Res 330:115539. https://doi.org/10.1016/j.psychres.2023.115539
doi: 10.1016/j.psychres.2023.115539
pubmed: 37988817
van der Zalm Y, Foldager L, Termorshuizen F et al (2021) Clozapine and mortality: a comparison with other antipsychotics in a nationwide Danish cohort study. Acta Psychiatr Scand 143:216–226. https://doi.org/10.1111/acps.13267
doi: 10.1111/acps.13267
pubmed: 33306211
Varma S, Bishara D, Besag FMC, Taylor D (2011) Clozapine-related EEG changes and seizures: dose and plasma-level relationships. Ther Adv Psychopharmacol 1:47–66. https://doi.org/10.1177/2045125311405566
doi: 10.1177/2045125311405566
pubmed: 23983927
pmcid: 3736902
Wagner E, Siafis S, Fernando P et al (2021) Efficacy and safety of clozapine in psychotic disorders-a systematic quantitative meta-review. Transl Psychiatry 11:487. https://doi.org/10.1038/s41398-021-01613-2
doi: 10.1038/s41398-021-01613-2
pubmed: 34552059
pmcid: 8458455
West S, Rowbotham D, Xiong G, Kenedi C (2017) Clozapine induced gastrointestinal hypomotility: a potentially life threatening adverse event. A review of the literature. Gen Hosp Psychiatry 46:32–37. https://doi.org/10.1016/j.genhosppsych.2017.02.004
doi: 10.1016/j.genhosppsych.2017.02.004
pubmed: 28622812
Wheeler AJ (2008) Treatment pathway and patterns of clozapine prescribing for schizophrenia in New Zealand. Ann Pharmacother 42:852–860. https://doi.org/10.1345/aph.1K662
doi: 10.1345/aph.1K662
pubmed: 18477732
Wohkittel C, Gerlach M, Taurines R et al (2016) Relationship between clozapine dose, serum concentration, and clinical outcome in children and adolescents in clinical practice. J Neural Transm (vienna) 123:1021–1031. https://doi.org/10.1007/s00702-016-1573-y
doi: 10.1007/s00702-016-1573-y
pubmed: 27221285
Wong J, Pang T, Cheuk NKW et al (2022) A systematic review on the use of clozapine in treatment of tardive dyskinesia and tardive dystonia in patients with psychiatric disorders. Psychopharmacology 239:3393–3420. https://doi.org/10.1007/s00213-022-06241-2
doi: 10.1007/s00213-022-06241-2
pubmed: 36180741
Xu Y, Amdanee N, Zhang X (2021) Antipsychotic-induced constipation: a review of the pathogenesis, clinical diagnosis, and treatment. CNS Drugs 35:1265–1274. https://doi.org/10.1007/s40263-021-00859-0
doi: 10.1007/s40263-021-00859-0
pubmed: 34427901