Editing Clozapine (section)

=== Underuse of clozapine ===
Clozapine is widely recognised as being underused with wide variation in prescribing,<ref>{{Cite journal| vauthors = Mistry H, Osborn D |date=July 2011|title=Underuse of clozapine in treatment-resistant schizophrenia |journal=Advances in Psychiatric Treatment|volume=17|issue=4|pages=250–255|doi=10.1192/apt.bp.110.008128|issn=1355-5146|doi-access=free}}</ref><ref>{{cite journal | vauthors = Stroup TS, Gerhard T, Crystal S, Huang C, Olfson M | title = Geographic and clinical variation in clozapine use in the United States | journal = Psychiatric Services | volume = 65 | issue = 2 | pages = 186–192 | date = February 2014 | pmid = 24233347 | doi = 10.1176/appi.ps.201300180 }}</ref><ref>{{Cite journal| vauthors = Downs J, Zinkler M |date=October 2007|title=Clozapine: national review of postcode prescribing |journal=Psychiatric Bulletin|language=en|volume=31|issue=10|pages=384–387|doi=10.1192/pb.bp.106.013144|issn=0955-6036|doi-access=free}}</ref><ref>{{Cite journal| vauthors = Purcell H, Lewis S |date=November 2000|title=Postcode prescribing in psychiatry |journal=Psychiatric Bulletin|volume=24|issue=11|pages=420–422|doi=10.1192/pb.24.11.420|issn=0955-6036|doi-access=free}}</ref><ref>{{cite journal | vauthors = Hayhurst KP, Brown P, Lewis SW | title = Postcode prescribing for schizophrenia | journal = The British Journal of Psychiatry | volume = 182 | issue = 4 | pages = 281–283 | date = April 2003 | pmid = 12668398 | doi = 10.1192/bjp.182.4.281 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Nielsen J, Røge R, Schjerning O, Sørensen HJ, Taylor D | title = Geographical and temporal variations in clozapine prescription for schizophrenia | journal = European Neuropsychopharmacology | volume = 22 | issue = 11 | pages = 818–824 | date = November 2012 | pmid = 22503785 | doi = 10.1016/j.euroneuro.2012.03.003 | s2cid = 40842497 }}</ref><ref>{{cite journal | vauthors = Latimer E, Wynant W, Clark R, Malla A, Moodie E, Tamblyn R, Naidu A | title = Underprescribing of clozapine and unexplained variation in use across hospitals and regions in the Canadian province of Québec | journal = Clinical Schizophrenia & Related Psychoses | volume = 7 | issue = 1 | pages = 33–41 | date = April 2013 | pmid = 23367500 | doi = 10.3371/csrp.lawy.012513 }}</ref><ref>{{cite journal | vauthors = Whiskey E, Barnard A, Oloyede E, Dzahini O, Taylor DM, Shergill SS | title = An evaluation of the variation and underuse of clozapine in the United Kingdom | journal = Acta Psychiatrica Scandinavica | volume = 143 | issue = 4 | pages = 339–347 | date = April 2021 | pmid = 33501659 | doi = 10.2139/ssrn.3716864 | s2cid = 235854803 | url = https://kar.kent.ac.uk/96371/1/Acta%20Psychiatr%20Scand%20-%202021%20-%20Whiskey%20-%20An%20evaluation%20of%20the%20variation%20and%20underuse%20of%20clozapine%20in%20the%20United%20Kingdom.pdf }}</ref> especially in patients with African heritage.<ref>{{cite journal | vauthors = Kelly DL, Kreyenbuhl J, Dixon L, Love RC, Medoff D, Conley RR | title = Clozapine underutilization and discontinuation in African Americans due to leucopenia | journal = Schizophrenia Bulletin | volume = 33 | issue = 5 | pages = 1221–1224 | date = September 2007 | pmid = 17170061 | pmc = 2632351 | doi = 10.1093/schbul/sbl068 }}</ref><ref name="Racial disparities in the use of se">{{cite journal | vauthors = Mallinger JB, Fisher SG, Brown T, Lamberti JS | title = Racial disparities in the use of second-generation antipsychotics for the treatment of schizophrenia | journal = Psychiatric Services | volume = 57 | issue = 1 | pages = 133–136 | date = January 2006 | pmid = 16399976 | doi = 10.1176/appi.ps.57.1.133 }}</ref><ref name="Racial disparity in the use of atyp">{{cite journal | vauthors = Copeland LA, Zeber JE, Valenstein M, Blow FC | title = Racial disparity in the use of atypical antipsychotic medications among veterans | journal = The American Journal of Psychiatry | volume = 160 | issue = 10 | pages = 1817–1822 | date = October 2003 | pmid = 14514496 | doi = 10.1176/appi.ajp.160.10.1817 }}</ref><ref>{{cite journal | vauthors = Kelly DL, Dixon LB, Kreyenbuhl JA, Medoff D, Lehman AF, Love RC, Brown CH, Conley RR | title = Clozapine utilization and outcomes by race in a public mental health system: 1994-2000 | journal = The Journal of Clinical Psychiatry | volume = 67 | issue = 9 | pages = 1404–1411 | date = September 2006 | pmid = 17017827 | doi = 10.4088/jcp.v67n0911 }}</ref><ref>{{cite journal | vauthors = Whiskey E, Olofinjana O, Taylor D | title = The importance of the recognition of benign ethnic neutropenia in black patients during treatment with clozapine: case reports and database study | journal = Journal of Psychopharmacology | volume = 25 | issue = 6 | pages = 842–845 | date = June 2011 | pmid = 20305043 | doi = 10.1177/0269881110364267 | s2cid = 28714732 }}</ref>

Psychiatrists' prescribing practices have been found to be the most significant variable regarding variance in its use.{{citation needed|date=September 2021}} Surveys of psychiatrists' attitudes to clozapine have found that many had little experience in its use, overestimated the incidence of side effects, and did not appreciate that many patients prefer to take clozapine over other antipsychotics.<ref>{{Cite journal| vauthors = Cirulli G |date=October 2005|title=Clozapine prescribing in adolescent psychiatry: survey of prescribing practice in in-patient units |journal=Psychiatric Bulletin |volume=29 |issue=10 |pages=377–380 |doi=10.1192/pb.29.10.377 |doi-access=free }}</ref><ref>{{cite journal | vauthors = Nielsen J, Dahm M, Lublin H, Taylor D | title = Psychiatrists' attitude towards and knowledge of clozapine treatment | journal = Journal of Psychopharmacology | volume = 24 | issue = 7 | pages = 965–971 | date = July 2010 | pmid = 19164499 | doi = 10.1177/0269881108100320 | s2cid = 34614417 }}</ref><ref>{{cite journal | vauthors = Hodge K, Jespersen S | title = Side-effects and treatment with clozapine: a comparison between the views of consumers and their clinicians | journal = International Journal of Mental Health Nursing | volume = 17 | issue = 1 | pages = 2–8 | date = February 2008 | pmid = 18211398 | doi = 10.1111/j.1447-0349.2007.00506.x }}</ref> In contrast to many psychiatrists' expectations most patients believe that the blood testing and other difficulties are worth the multiple benefits that they perceive.<ref name="Taylor_2000">{{cite journal| vauthors = Taylor D, Shapland L, Laverick G, Bond J, Munro J |date=December 2000|title=Clozapine – a survey of patient perceptions|journal=Psychiatric Bulletin |language=en |volume=24 |issue=12 |pages=450–452|doi=10.1192/pb.24.12.450|issn=0955-6036|doi-access=free}}</ref><ref name="Waserman 666–668">{{cite journal | vauthors = Waserman J, Criollo M | title = Subjective experiences of clozapine treatment by patients with chronic schizophrenia | journal = Psychiatric Services | volume = 51 | issue = 5 | pages = 666–668 | date = May 2000 | pmid = 10783189 | doi = 10.1176/appi.ps.51.5.666 }}</ref> Whilst psychiatrists fear the severe adverse effects such as [[agranulocytosis]], patients are more concerned about hypersalivation.<ref>{{cite journal | vauthors = Angermeyer MC, Löffler W, Müller P, Schulze B, Priebe S | title = Patients' and relatives' assessment of clozapine treatment | journal = Psychological Medicine | volume = 31 | issue = 3 | pages = 509–517 | date = April 2001 | pmid = 11305859 | doi = 10.1017/S0033291701003749 | s2cid = 20487762 | url = https://qmro.qmul.ac.uk/xmlui/handle/123456789/289 }}</ref> Clozapine is no longer actively marketed and this may also be one of the explanations for its underuse.<ref>{{cite journal| vauthors = Kelly D, Kreyenbuhl J, Buchanan R, Malhotra A |date=April 2007|title=Why Not Clozapine? |journal=Clinical Schizophrenia & Related Psychoses|volume=1|issue=1|pages=92–95|doi=10.3371/csrp.1.1.8 }}</ref>

Despite the strong evidence and universal endorsement by national and international treatment guidelines and the experiences of patients themselves, most people eligible for clozapine are not treated with it.<ref name="Taylor_2000" /> A large study in England found that approximately 30% of those eligible for clozapine were being treated with it.<ref>{{cite journal| vauthors = Downs J, Zinkler M |date=October 2007|title=Clozapine: national review of postcode prescribing|journal=Psychiatric Bulletin|volume=31|issue=10|pages=384–387|doi=10.1192/pb.bp.106.013144|issn=0955-6036|doi-access=free}}</ref> Those patients that do start clozapine usually face prolonged delay, multiple episodes of psychosis and treatments such as high dose antipsychotics or polypharmacy. Instead of two previous antipsychotics many will have been exposed to ten or more drugs which were not effective. A study of 120 patients conducted in four hospitals in South-East London found a mean of 9.2 episodes of antipsychotic prescription before clozapine was initiated and the mean delay in using clozapine was 5 years.<ref>{{cite journal | vauthors = Taylor DM, Young C, Paton C | title = Prior antipsychotic prescribing in patients currently receiving clozapine: a case note review | journal = The Journal of Clinical Psychiatry | volume = 64 | issue = 1 | pages = 30–34 | date = January 2003 | pmid = 12590620 | doi = 10.4088/jcp.v64n0107 }}</ref> Treatments that have no evidence base or are regarded as actively harmful are used instead.<ref>{{cite journal | vauthors = Fayek M, Flowers C, Signorelli D, Simpson G | title = Psychopharmacology: underuse of evidence-based treatments in psychiatry | journal = Psychiatric Services | volume = 54 | issue = 11 | pages = 1453–4, 1456 | date = November 2003 | pmid = 14600298 | doi = 10.1176/appi.ps.54.11.1453 }}</ref>

As well as variation within counties there is massive variation in the use of clozapine internationally. An international study of 17 counties found greatest use in Finland (189/100,000 persons) and New Zealand (116/100,000), and least in the Japanese cohort (0.6/100,000) and in the privately insured US cohort (14/100,000).<ref>{{cite journal | vauthors = Bachmann CJ, Aagaard L, Bernardo M, Brandt L, Cartabia M, Clavenna A, Coma Fusté A, Furu K, Garuoliené K, Hoffmann F, Hollingworth S, Huybrechts KF, Kalverdijk LJ, Kawakami K, Kieler H, Kinoshita T, López SC, Machado-Alba JE, Machado-Duque ME, Mahesri M, Nishtala PS, Piovani D, Reutfors J, Saastamoinen LK, Sato I, Schuiling-Veninga CC, Shyu YC, Siskind D, Skurtveit S, Verdoux H, Wang LJ, Zara Yahni C, Zoëga H, Taylor D | title = International trends in clozapine use: a study in 17 countries | journal = Acta Psychiatrica Scandinavica | volume = 136 | issue = 1 | pages = 37–51 | date = July 2017 | pmid = 28502099 | doi = 10.1111/acps.12742 | url = https://pure.rug.nl/ws/files/48214818/Bachmann_et_al_2017_Acta_Psychiatrica_Scandinavica.pdf }}</ref>

====Racial disparity in the use of clozapine====
A general finding in healthcare provision is that minority groups receive inferior treatment; this is a particular finding in the US.<ref>{{Cite web| vauthors = Pearl R |title=Why Health Care Is Different If You're Black, Latino Or Poor|url=https://www.forbes.com/sites/robertpearl/2015/03/05/healthcare-black-latino-poor/|access-date=16 September 2021|website=Forbes|language=en}}</ref><ref>{{Cite web|date=17 September 2020|title=Racism in healthcare: Statistics and examples|url=https://www.medicalnewstoday.com/articles/racism-in-healthcare|access-date=16 September 2021|website=www.medicalnewstoday.com|language=en}}</ref><ref>{{Cite book| vauthors = Bulatao RA, Anderson NB |url=https://www.ncbi.nlm.nih.gov/books/NBK24685/|title=Stress| collaboration = National Research Council (US) Panel on Race, Ethnicity, and Health in Later Life |date=2004|publisher=National Academies Press (US)|language=en}}</ref><ref>{{cite journal | vauthors = Obermeyer Z, Powers B, Vogeli C, Mullainathan S | title = Dissecting racial bias in an algorithm used to manage the health of populations | journal = Science | volume = 366 | issue = 6464 | pages = 447–453 | date = October 2019 | pmid = 31649194 | doi = 10.1126/science.aax2342 | s2cid = 204881868 | bibcode = 2019Sci...366..447O | url = https://escholarship.org/uc/item/6h92v832 | doi-access = free }}</ref> In the US a general finding is that compared to their white peers African American people are less likely to be prescribed the second generation antipsychotics, which are more expensive than alternatives and this was even apparent and especially so for clozapine when comparison was made in the [[Veterans Affairs Medical Center|Veterans Affairs]] medical system and when differences regarding socioeconomic factors were taken into account.<ref name="Racial disparities in the use of se" /><ref name="Racial disparity in the use of atyp" /><ref>{{cite journal | vauthors = Kelly DL, Dixon LB, Kreyenbuhl JA, Medoff D, Lehman AF, Love RC, Brown CH, Conley RR | title = Clozapine utilization and outcomes by race in a public mental health system: 1994-2000 | journal = The Journal of Clinical Psychiatry | volume = 67 | issue = 9 | pages = 1404–1411 | date = September 2006 | pmid = 17017827 | doi = 10.4088/JCP.v67n0911 }}</ref> As well as being less likely to start clozapine black patients are more likely to stop clozapine, possibly on account of [[benign ethnic neutropenia]].