Clozapine for Treating Schizophrenia:

A Comparison of the States

November 2015 Clozapine for Treating Schizophrenia: A COMPARISON OF THE STATES

November 2015

E. Fuller Torrey, M.D. Founder, Treatment Advocacy Center Associate Director for Research, Stanley Medical Research Institute Chevy Chase, Maryland

Michael B. Knable, D.O. Board Member, Treatment Advocacy Center Medical Director, Clearview Communities Frederick, Maryland

Cameron Quanbeck, M.D. Board Member, Treatment Advocacy Center Medical Director, Cordilleras Mental Health Center Redwood City, California

John M. Davis, M.D. Psychiatric Advisory Board, Treatment Advocacy Center Professor of Psychiatry, University of Illinois at Chicago Chicago, Illinois

© 2015 Treatment Advocacy Center

The Treatment Advocacy Center is a national nonprofit organization dedicated exclusively to eliminating barriers to the timely and effective treatment of severe mental illness. The organization promotes laws, policies and practices for the delivery of psychiatric care and supports the development of innovative treatments for and research into the causes of severe and persistent psychiatric illnesses, such as schizophrenia and bipolar disorder. EXECUTIVE SUMMARY

UÊ -V ˆâœ« Ài˜ˆ>ʈÃʜ˜iʜvÊÌ iʓœÃÌÊ`ˆÃ>Lˆ˜}Ê«ÃÞV ˆ>ÌÀˆVÊ`ˆÃœÀ`iÀÃÊ>˜`Ê>vviVÌÃÊ>««ÀœÝˆ“>ÌiÞÊÓ°Èʓˆˆœ˜Ê American adults. Clozapine is regarded as the “gold standard” for treating schizophrenia. It is the only antipsychotic approved for treating the 20 to 30 percent of patients who do not respond to other medications, and especially those who are suicidal or violent. Although it is used to treat 20 percent or “œÀiʜvʈ˜`ˆÛˆ`Õ>ÃÊÜˆÌ ÊÃV ˆâœ« Ài˜ˆ>ʈ˜Ê“œÃÌÊ`iÛiœ«i`ÊVœÕ˜ÌÀˆiÃ]ʈÌÃÊÕÃiʈ˜ÊÌ iÊ1˜ˆÌi`Ê-Ì>ÌiÃʈÃʏiÃÃÊ than 5 percent. According to one schizophrenia expert, it should be used to treat at least 10 percent of individuals with schizophrenia who are being treated at a “bare minimum.” UÊ 1Ș}Ê`>Ì>ÊvÀœ“Ê i`ˆV>ˆ`Ê>˜`Ê« >À“>VÞÊ«ÀiÃVÀˆ«Ìˆœ˜Ã]ÊÜiÊ>ÃViÀÌ>ˆ˜i`ÊVœâ>«ˆ˜iÊÕÃiÊvœÀÊ>ÊxäÊÃÌ>ÌiÃÊ and compared them as a measure of the states’ efforts to treat individuals with schizophrenia.

œÊ "˜ÞÊ ÃˆÝÊ ÃÌ>ÌiÃÊ >V ˆiÛi`Ê Ì iÊ ºL>ÀiÊ “ˆ˜ˆ“Õ“»Ê œvÊ £äÊ «iÀVi˜ÌÊ ÕÃi\Ê -œÕÌ Ê >ŽœÌ>]Ê œ˜˜iV̈VÕÌ]Ê œœÀ>`œ]Ê7>à ˆ˜}̜˜]Ê6iÀ“œ˜ÌÊ>˜`Ê >ˆ˜i°

o The states that were using the least clozapine—to treat less than 3 percent of individuals—were iœÀ}ˆ>]Êi˜ÌÕVŽÞ]Ê œÀÌ Ê >Àœˆ˜>]Ê ˆÃÈÃÈ««ˆ]Ê
>L>“>]Ê
Àˆâœ˜>]ʜՈÈ>˜>]Ê iÛ>`>Ê>˜`Ê"Ài}œ˜° UÊ œâ>«ˆ˜iʈÃÊÕÃÕ>ÞÊ«ÀiÃVÀˆLi`ÊLÞÊ«ÃÞV ˆ>ÌÀˆÃÌÃ]ÊÀ>Ì iÀÊÌ >˜ÊœÌ iÀÊ« ÞÈVˆ>˜Ã]ÊLÕÌÊ«ÃÞV ˆ>ÌÀˆÃÌÃÊ>ÀiÊÛiÀÞÊ Õ˜iÛi˜ÞÊ`ˆÃÌÀˆLÕÌi`ÊLÞÊÃÌ>Ìi°Ê/ iÀivœÀi]ÊÜiÊ>ÃœÊiÝ>“ˆ˜i`ÊVœâ>«ˆ˜iÊÕÃiÊÌ>Žˆ˜}ʈ˜ÌœÊVœ˜Ãˆ`iÀ>̈œ˜Ê the availability of psychiatrists.

œÊ 7 i˜Ê>Û>ˆ>LˆˆÌÞʜvÊ«ÃÞV ˆ>ÌÀˆÃÌÃʈÃÊ>ÃœÊVœ˜Ãˆ`iÀi`ʈ˜ÊVœâ>«ˆ˜iÊÕÃi]Ê-œÕÌ Ê >ŽœÌ>ÊÜ>ÃÊLÞÊv>ÀÊ`œˆ˜}Ê Ì iÊLiÃÌÆÊ œ˜œÀ>Liʓi˜Ìˆœ˜Ê}œiÃÊÌœÊ œœÀ>`œ]Ê7>à ˆ˜}̜˜]ʏˆ˜œˆÃ]Ê œÀÌ Ê >ŽœÌ>Ê>˜`Ê7ޜ“ˆ˜}°

o When availability of psychiatrists is also considered in clozapine use, Oregon was doing the worst. ˆÃ œ˜œÀ>Liʓi˜Ìˆœ˜Ê}œiÃÊÌœÊ œÀÌ Ê >Àœˆ˜>]Ê i>Ü>Ài]Ê iÜÊ9œÀŽÊ>˜`Ê >ˆvœÀ˜ˆ>° UÊ / iÊÕÃiʜvÊVœâ>«ˆ˜iÊV>˜ÊLiÊÀi}>À`i`Ê>ÃÊ>ʓi>ÃÕÀiʜvÊÌ iÊivvœÀÌÊLiˆ˜}ʓ>`iÊLÞÊ>ÊÃÌ>ÌiÊ̜ÊÌÀi>ÌÊ individuals with schizophrenia who are most in need of treatment. The range of effort in the United -Ì>ÌiÃÊÛ>ÀˆiÃÊ܈`iÞÊvÀœ“Ê-œÕÌ Ê >ŽœÌ>Ê­LiÃÌ®Ê̜Ê"Ài}œ˜Ê­ÜœÀÃÌ®°

The map below illustrates the distribution of clozapine use among the states.

Clozapine Use by State

Clozapine for Treating Schizophrenia: A COMPARISON OF THE STATES n 1 INTRODUCTION

-V ˆâœ« Ài˜ˆ>ʈÃʜ˜iʜvÊÌ iʓœÃÌÊ`ˆÃ>Lˆ˜}Ê«ÃÞV ˆ>ÌÀˆVÊ`ˆÃœÀ`iÀÃÊ>˜`Ê>vviVÌÃÊ>««ÀœÝˆ“>ÌiÞÊÓ°Èʓˆˆœ˜Ê
“iÀˆV>˜Ê>`ՏÌÃ°Ê œâ>«ˆ˜iÊLiV>“iÊ>Û>ˆ>LiÊvœÀÊÕÃiʈ˜ÊÌ iÊ1˜ˆÌi`Ê-Ì>ÌiÃʈ˜Ê£™™äÊ>˜`ʈÃÊ܈`iÞÊÀi}>À`i`Ê as the “gold standard” antipsychotic for treating schizophrenia.1 It is the only antipsychotic approved by Ì iÊœœ`Ê>˜`Ê ÀÕ}Ê
`“ˆ˜ˆÃÌÀ>̈œ˜Ê­
®ÊvœÀÊÌ iÊÌÀi>̓i˜ÌʜvÊÌ iÊÓäÊ̜ÊÎäÊ«iÀVi˜ÌʜvÊV>ÃiÃÊÌ >ÌÊ>ÀiÊÌÀi>Ì- ment resistant; approximately 50 percent of such patients improve on clozapine. It is also the only medi- V>̈œ˜Ê>««ÀœÛi`ÊLÞÊÌ iÊ
ÊvœÀÊÌ iÊ«ÀiÛi˜Ìˆœ˜ÊœvÊÃՈVˆ`i°Ê
ÃÊ«ÃÞV œ« >À“>Vœœ}ˆÃÌÊ À°ÊiÀLiÀÌÊ iÌâiÀÊ noted, “clozapine has been found in two large epidemiological studies to have the lowest mortality of >˜ÞÊ>˜Ìˆ«ÃÞV œÌˆVÊ`ÀÕ}]ʓ>ˆ˜ÞÊ`ÕiÊ̜ʈÌÃÊÛiÀÞʏ>À}iÊivviVÌÊ̜ÊÀi`ÕViÊÌ iÊÀˆÃŽÊvœÀÊÃՈVˆ`i°»2Ê iÌâiÀÊ>``i`Ê that the failure of psychiatrists to use clozapine for individuals with schizophrenia who are suicidal is a fail- ure to use evidence-based medicine.3 Finally, clozapine is the only antipsychotic which has been shown to decrease aggressive and violent actions in individuals with schizophrenia.4 One study, for example, re- ported that clozapine significantly reduced the arrest rates of psychotic patients with criminal histories.5

Clozapine also has significant side effects, including weight gain, sedation, drooling and myocarditis so that the medication must be discontinued in one out of six individuals.È The most serious side effect Vœ˜ÃˆÃÌÃʜvÊ>ÊÀi`ÕV̈œ˜Êˆ˜ÊÜ ˆÌiÊLœœ`ÊViÃÊ­˜iÕÌÀœ«i˜ˆ>®ÊÜ ˆV ʜVVÕÀÃʈ˜ÊnʜÕÌʜvÊiÛiÀÞÊ£]äääʈ˜`ˆÛˆ`Õ>ÃÆÊ ˆvÊÌ ˆÃÊ«ÀœViÃÃʈÃÊ>œÜi`Ê̜ÊVœ˜Ìˆ˜ÕiÊÌ iÊ«iÀܘʓ>ÞÊ >ÛiÊ̜œÊviÜÊÜ ˆÌiÊLœœ`ÊViÃÊ­>}À>˜ÕœVÞ̜ÈîÊ>˜`Ê `i>Ì Ê“>ÞÊÀiÃՏ̰ÊœÀÊÌ ˆÃÊÀi>ܘ]ʈ˜`ˆÛˆ`Õ>Ãʜ˜ÊVœâ>«ˆ˜iʓÕÃÌÊ >ÛiÊÌ iˆÀÊLœœ`ÊÌiÃÌi`ÊÜiiŽÞÊvœÀÊÌ iÊ wÀÃÌÊÈÝʓœ˜Ì ÃʜvÊÌÀi>̓i˜ÌÆÊÌ i˜ÊiÛiÀÞÊÌܜÊÜiiŽÃÊvœÀÊÌ iÊÃiVœ˜`ÊÈÝʓœ˜Ì ÃʜvÊÌÀi>̓i˜Ì]ÊÌ i˜Ê“œ˜Ì Þ°Ê Until recently this blood monitoring was administratively complex, but it has now been simplified and Vœ˜Ãœˆ`>Ìi`ʈ˜ÌœÊ>ÊȘ}iʓœ˜ˆÌœÀˆ˜}ÊÃÞÃÌi“ÊLÞÊÌ iÊœœ`Ê>˜`Ê ÀÕ}Ê
`“ˆ˜ˆÃÌÀ>̈œ˜°ÊvʘœÌʓœ˜ˆÌœÀi`]Ê agranulocytosis can be life-threatening, but suicidal ideation is also life-threatening, and it has been esti- mated that for individuals with schizophrenia who are suicidal the threat of dying from suicide is at least 10 times greater than the threat of dying from clozapine-induced agranulocytosis.7

Clozapine therefore has an important role to play in the treatment of individuals with treatment-resistant ÃV ˆâœ« Ài˜ˆ>]ÊiëiVˆ>ÞÊÌ œÃiÊÜ œÊ>ÀiÊÃՈVˆ`>ÊœÀÊ œ“ˆVˆ`>°Ê˜ÊÓää™ÊÌ iÊ-V ˆâœ« Ài˜ˆ>Ê*>̈i˜ÌÊ"ÕÌ- Vœ“iÃÊ,iÃi>ÀV Ê/i>“Ê­*",/®ÊÀiVœ““i˜`i`ÊÌ >ÌÊVœâ>«ˆ˜iÊà œÕ`ÊLiÊÌÀˆi`Ê>vÌiÀÊÌܜÊ>`iµÕ>ÌiÊv>ˆi`Ê trials of other antipsychotics. In most developed countries, clozapine is regularly used for some individu- als with schizophrenia; 20 percent in Germany, 30 percent in China, 35 percent in Australia. In the United -Ì>ÌiÃ]Ê œÜiÛiÀ]ÊVœâ>«ˆ˜iʈÃÊÕÃi`ÊÜˆÌ ÊxÊ«iÀVi˜ÌʜÀÊviÜiÀʈ˜`ˆÛˆ`Õ>ÃÊÜˆÌ ÊÃV ˆâœ« Ài˜ˆ>°Ê
VVœÀ`ˆ˜}Ê̜Ê>Ê Óä£äÊÀi«œÀÌ]ʺVœâ>«ˆ˜i½Ãʓ>ÀŽiÌÊà >ÀiÊ`ˆ`ʘœÌÊÀi>V Êΰx¯Êˆ˜Ê>˜Þʜ˜iʜvÊÌ iʏ>ÃÌÊ£Óʓœ˜Ì ð»nÊœÜʓ>˜ÞÊ individuals with schizophrenia should be treated with clozapine? John Kane, a psychiatrist expert on the treatment of schizophrenia, has suggested, “10 percent is a bare minimum and 20 percent would be more appropriate.”™ To ascertain whether there are significant differences among the states in the use of clo- â>«ˆ˜i]Ê>˜`Ê̜ÊÃiiÊ œÜʓ>˜ÞʓiiÌÊ>˜i½ÃÊ£äÊ«iÀVi˜ÌʺL>Àiʓˆ˜ˆ“Õ“»ÊiÛi]ÊÜiÊ՘`iÀ̜œŽÊ>ÊÃÌ>ÌiÊÃÕÀÛiÞ°Ê

METHODS >Ì>ʜ˜ÊVœâ>«ˆ˜iÊÕÃiÊvœÀʈ˜`ˆÛˆ`Õ>Ãʜ˜Ê i`ˆV>ˆ`Ê>˜`Ê`ˆ>}˜œÃi`ÊÜˆÌ ÊÃV ˆâœ« Ài˜ˆ>ÊÜ>ÃʜLÌ>ˆ˜i`ÊvœÀÊvœÕÀÊ Þi>ÀÃ]ÊÓääȇÓää™]ÊvœÀÊ{{ÊÃÌ>ÌiðÊ/ iÊ̜Ì>Ê˜Õ“LiÀʜvʈ˜`ˆÛˆ`Õ>ÃÊÀiViˆÛˆ˜}ÊVœâ>«ˆ˜iÊvœÀÊÌ iÊvœÕÀÊÞi>ÀÃÊÜ>ÃÊ £]ǙÎ]£Ç{°Ê/ iÊ`>Ì>ÊÜ>ÃʜLÌ>ˆ˜i`ÊvÀœ“ÊÌ iʘÃ̈ÌÕÌiÊvœÀÊi>Ì ]Êi>Ì Ê >ÀiÊ*œˆVÞÊ>˜`Ê
}ˆ˜}Ê,iÃi>ÀV Ê>ÌÊ Rutgers University.10Ê/ ˆÃÊ`>Ì>ÊÜ>ÃʘœÌÊ>Û>ˆ>LiÊvœÀÊÈÝÊÃÌ>ÌiÃ\Ê
Àˆâœ˜>]Ê i>Ü>Ài]Ê >ˆ˜i]Ê iÛ>`>]Ê"Ài}œ˜Ê >˜`Ê, œ`iÊÏ>˜`°Ê/ iÊ«iÀVi˜Ì>}iʜvʈ˜`ˆÛˆ`Õ>ÃÊÜˆÌ ÊÃV ˆâœ« Ài˜ˆ>ÊÜ œÊÜiÀiÊÌ>Žˆ˜}ÊVœâ>«ˆ˜iÊ>ÌÊ>˜ÞÊ Ìˆ“iÊÜ>ÃÊ>ÛiÀ>}i`ÊvœÀÊÌ iÊvœÕÀÊÞi>ÀÃÊ>˜`Êi˜ÌiÀi`ʈ˜Ê/>LiÊ£°Ê/ iÊÃÌ>ÌiÃÊÜiÀiÊÌ i˜ÊÀ>˜Ž‡œÀ`iÀi`°

>Ì>ʜ˜ÊVœâ>«ˆ˜iÊÕÃiÊLÞÊÃÌ>ÌiÊÜ>ÃÊ>ÃœÊœLÌ>ˆ˜i`ÊvœÀÊÓä䙇Ó䣣ÊvÀœ“Ê>ÊÃ>“«ˆ˜}ʜvÊÎn]äääÊÀiÌ>ˆÊ« >À“>- VˆiÃ]ÊLÞÊ -Êi>Ì ʘVœÀ«œÀ>Ìi`°11 The total number of prescriptions for a 24-month period was then V>VՏ>Ìi`Ê«iÀÊ£ää]äääÊ̜Ì>Ê«œ«Õ>̈œ˜ÊL>Ãi`ʜ˜ÊÓää™ÊVi˜ÃÕÃÊ`>Ì>°Ê œÌiÊÌ >Ì]Ê՘ˆŽiÊÌ iÊÃÌ>ÌiÊ i`ˆV>ˆ`Ê `>Ì>]ÊÌ iÊ -Ê`>Ì>Ê`ˆ`ʘœÌÊ>ÃViÀÌ>ˆ˜ÊÌ iÊ̜Ì>Ê˜Õ“LiÀʜvʈ˜`ˆÛˆ`Õ>ÃÊÌ>Žˆ˜}ÊVœâ>«ˆ˜iʜÀÊÌ iˆÀÊ`ˆ>}˜œÃˆÃ]Ê

2 n Clozapine for Treating Schizophrenia: A COMPARISON OF THE STATES LÕÌʜ˜ÞÊÌ iʘՓLiÀʜvÊ«ÀiÃVÀˆ«Ìˆœ˜Ã°Ê iëˆÌiÊÌ ˆÃ]ÊÌ iÊVœ“«>ÀˆÃœ˜ÊœvÊVœâ>«ˆ˜iÊÕÃiÊÕȘ}Ê i`ˆV>ˆ`Ê`>Ì>Ê œÀÊ« >À“>VÞÊ`>Ì>ÊÜ>ÃÊÃÕÀ«ÀˆÃˆ˜}ÞÊVœ˜}ÀÕi˜ÌÆÊvœÀÊiÝ>“«i]ÊÌ iÊ̜«Ê£äÊ>˜`ÊLœÌ̜“Ê£äÊÃÌ>ÌiÃÊÕȘ}Ê i`- icaid data each included six of the top 10 and bottom 10 states using the pharmacy data. For this reason, vœÀÊÌ iÊÈÝÊÃÌ>ÌiÃÊvœÀÊÜ ˆV Ê i`ˆV>ˆ`Ê`>Ì>ÊÜ>ÃʘœÌÊ>Û>ˆ>Li]ÊÜiÊÕÃi`ÊÌ iÊ« >À“>VÞÊ`>Ì>°ÊœÀÊiÝ>“«i]Ê >ˆ˜iÊÜ>ÃÊÀ>˜Ži`ÊÈÝÌ Ê>“œ˜}ÊÌ iÊÃÌ>ÌiÃʜ˜ÊVœâ>«ˆ˜iÊÕÃiÊL>Ãi`ʜ˜Ê« >À“>VÞÊ`>Ì>]ÊÜÊÜiÊ«>Vi`ʈÌÊ ÃˆÝÌ Êœ˜ÊÌ iʏˆÃÌÊ>˜`Ê>ÃÈ}˜i`Ê >ˆ˜iÊ>ÊVœâ>«ˆ˜i‡ÕÃiʘՓLiÀʓˆ`Ü>ÞÊLiÌÜii˜ÊÌ iÊÃÌ>ÌiÃÊÀ>˜Ži`ÊwvÌ Ê>˜`Ê ÃiÛi˜Ì °Ê/ iʘՓLiÀÃÊvœÀÊÌ iÊÈÝÊÃÌ>ÌiÃÊvœÀÊÜ ˆV Ê« >À“>VÞÊ`>Ì>ÊÜ>ÃÊÕÃi`Ê>ÀiÊLÀ>VŽiÌi`ʜ˜ÊÌ iÊÌ>LiÊÌœÊ indicate that their origin is not the same as those for the other states.

,>˜Žˆ˜}ÊÌ iÊÃÌ>ÌiÃÊLÞÊÌ iÊ«iÀVi˜Ì>}iʜvʈ˜`ˆÛˆ`Õ>ÃÊÜˆÌ ÊÃV ˆâœ« Ài˜ˆ>ÊÜ œÊ>ÀiÊÌ>Žˆ˜}ÊVœâ>«ˆ˜i]Ê œÜ- ever, is not sufficient. Because clozapine use must be monitored by blood tests, it is most commonly prescribed by psychiatrists rather than by family physicians or other physicians. But because psychiatrists are not uniformly distributed by population, states with proportionately more psychiatrists should be expected to use more clozapine compared to states with fewer psychiatrists. To test this assumption, we obtained data on the number of psychiatrists and the number of people per psychiatrist for each state for 2012.12Ê/ ˆÃÊ`>Ì>ÊÜ>ÃÊi˜ÌiÀi`ʜ˜Ê/>LiÊ£Ê>˜`ÊÀ>˜ŽÊœÀ`iÀi`ÊLÞÊÃÌ>Ìi°

Table 1. Clozapine Use and Number of Psychiatrists

PERCENTAGE OF MEDICAID INDIVIDUALS WITH NUMBER OF PEOPLE PER STATE SCHIZOPHRENIA TAKING RANK ORDER PSYCHIATRISTS, 2012 PSYCHIATRIST RANK ORDER CLOZAPINE, 2006-2009 -œÕÌ Ê >ŽœÌ> £x°È 1 57 £{]ÈÓä {È Connecticut 13.4 2 näÈ 4,455 4 Colorado ££°n 3 xǙ n]™Èä £n Washington 11.4 4 731 ™]{Îx 21 Vermont 10.7 5 144 4,347 3 >ˆ˜i {10.2} È 217 È]£Óx 7 Illinois ™°n 7 £]Ι£ ™]ÓxÈ £™ œÀÌ Ê >ŽœÌ> n°™ n ÈÇ 10,442 ÓÈ >ÃÃ>V ÕÃiÌÌà n°È ™ £]nÇx 3,545 1 iÜÊ>“«Ã ˆÀi 7.2 10 175 7, 547 11 Wyoming 7 11 41 £{]äx™ 43 Kansas È°{ 12 Ó{™ ££]x™ä 32 œ˜Ì>˜> È°Ó 13 nx ££]nÓx ÎÈ West Virginia È°£ 14 157 ££]n£n 35 Utah x°™ 15 £™{ £{]Ç£n 47 *i˜˜ÃޏÛ>˜ˆ> x°È £È £]Çnn Ç]£În 10 Iowa 5.4 17 231 £Î]Îän Ι ˆV ˆ}>˜ 5.1 £n ™™Ó ™]™ÈÎ 22 iLÀ>Î> {°™ £™ 137 13,544 40 Rhode Island O{°™P £™ Óä™ 5,025 5 Idaho {°n 21 n{ £n]™™Ç 50 iÜÊ i݈Vœ {°n 21 Ó{n n]{ä™ 15 Brackets indicate numbers derived from pharmacy data; all others derived from Medicaid data.

Clozapine for Treating Schizophrenia: A COMPARISON OF THE STATES n 3 Table 1. Clozapine Use and Number of Psychiatrists

PERCENTAGE OF MEDICAID INDIVIDUALS WITH NUMBER OF PEOPLE PER STATE SCHIZOPHRENIA TAKING RANK ORDER PSYCHIATRISTS, 2012 PSYCHIATRIST RANK ORDER CLOZAPINE, 2006-2009 ˆ˜˜iÜÌ> 4.7 23 532 10,111 23 >Àޏ>˜` {°È 24 1,153 5,104 È Virginia 4.5 25 ™{ä n]Çän £È
>Î> 4.3 ÓÈ n™ n]Ó£™ 13 >Ü>ˆˆ 4.2 27 Ó£È È]{{È n iÜÊiÀÃiÞ 4.2 27 £]£xÈ Ç] ÈÈn 12 "Ž> œ“> 4.2 27 әΠ13,020 În Indiana 4.1 30 455 £{]ÎÈn 45 Wisconsin 4.1 30 554 £ä]ÎÎÈ 24 California 4 32 5,373 Ç]ä n ä ™ iÜÊ9œÀŽ 4 32 {]nxÓ 4,033 2 -œÕÌ Ê >Àœˆ˜> 4 32 403 11,721 33 Tennessee 4 32 545 ££]n{È 37
ÀŽ>˜Ã>à ΰ™ ÎÈ 214 £Î]Çn£ 41 Ohio ΰ™ ÎÈ 1,100 £ä]{™x 27 Texas ΰn În £]nÈn £Î]™xä 42 Florida 3.2 Ι £]ș™ 11,370 31 i>Ü>Ài {3.2} Ι 104 n]n£n 17 ˆÃÜÕÀˆ 3.2 Ι xnä £ä]ÎnÎ 25 Georgia Ó°™ 42 nnÓ 11,247 ә i˜ÌÕVŽÞ Ó°™ 42 372 11,775 34 œÀÌ Ê >Àœˆ˜> Ó°n 44 1,053 ™]ÓÈ£ 20 ˆÃÈÃÈ««ˆ 2.4 45 £™ä 15,710 {™ Alabama 2.2 {È 340 £{]£nÓ 44 Arizona {2.2} {È ÈäÓ £ä]nnÈ Ón œÕˆÃˆ>˜> 2 {n {äÈ 11,335 30 iÛ>`> {2} {n £n{ £{]™™{ {n Oregon {2} {n {È{ n]{ä{ 14 Brackets indicate numbers derived from pharmacy data; all others derived from Medicaid data.

RESULTS "˜ÞÊÈÝÊÃÌ>ÌiÃÊ­-œÕÌ Ê >ŽœÌ>]Ê œ˜˜iV̈VÕÌ]Ê œœÀ>`œ]Ê7>à ˆ˜}̜˜]Ê6iÀ“œ˜ÌÊ>˜`Ê >ˆ˜i®Ê“iÌÊ À°Ê>˜i½ÃÊ “bare minimum” level of at least 10 percent use of clozapine for individuals diagnosed with schizophrenia.
˜œÌ iÀÊwÛiÊÃÌ>ÌiÃÊ­ˆ˜œˆÃ]Ê œÀÌ Ê >ŽœÌ>]Ê >ÃÃ>V ÕÃiÌÌÃ]Ê iÜÊ>“«Ã ˆÀiÊ>˜`Ê7ޜ“ˆ˜}®Ê >`ÊLiÌÜii˜Ê 7 and 10 percent of individuals with schizophrenia on clozapine. At the other end of the list, nine states ­iœÀ}ˆ>]Êi˜ÌÕVŽÞ]Ê œÀÌ Ê >Àœˆ˜>]Ê ˆÃÈÃÈ««ˆ]Ê
>L>“>]Ê
Àˆâœ˜>]ʜՈÈ>˜>]Ê iÛ>`>Ê>˜`Ê"Ài}œ˜®Ê >`Ê fewer than 3 percent of individuals with schizophrenia on clozapine.

/ iÃiÊÀiÃՏÌÃÊÜiÀiÊÌ i˜ÊVœ“«>Ài`ÊÜˆÌ ÊÌ iÊ>Û>ˆ>LˆˆÌÞʜvÊ«ÃÞV ˆ>ÌÀˆÃÌÃ°Ê >ÃÃ>V ÕÃiÌÌÃÊ >`ÊÌ iʓœÃÌÊ«ÃÞ- V ˆ>ÌÀˆÃÌÃÊ­£ÊvœÀÊiÛiÀÞÊÎ]x{xÊ«iœ«i®Ê>˜`Ê`> œÊÌ iʏi>ÃÌÊ­£ÊvœÀÊiÛiÀÞÊ£n]™™ÇÊ«iœ«i®]ʓœÀiÊÌ >˜Ê>ÊwÛi‡vœ`Ê `ˆvviÀi˜Vi°Ê7 i˜ÊÌ iÊ>Û>ˆ>LˆˆÌÞʜvÊ«ÃÞV ˆ>ÌÀˆÃÌÃÊÜ>ÃÊÌ>Ži˜Êˆ˜ÌœÊ>VVœÕ˜Ì]ÊÌ iÀiÊÜ>ÃÊvœÕ˜`Ê̜ÊLiÊÀi>̈ÛiÞÊ

4 n Clozapine for Treating Schizophrenia: A COMPARISON OF THE STATES ˆÌ̏iÊVœÀÀi>̈œ˜ÊLiÌÜii˜ÊVœâ>«ˆ˜iÊÕÃiÊ>˜`ÊÌ iÊ>Û>ˆ>LˆˆÌÞʜvÊ«ÃÞV ˆ>ÌÀˆÃÌðÊ-œÕÌ Ê >ŽœÌ>ÊÃÌ>˜`ÃʜÕÌÊ>ÃÊ Liˆ˜}ÊÌ iÊLiÃÌÊÃÌ>Ìiʈ˜ÊÕȘ}ÊVœâ>«ˆ˜iÊiÛi˜ÊÌ œÕ} ʈÌʈÃÊÀ>˜Ži`Ê{ÈÌ Ê­£Ê«ÃÞV ˆ>ÌÀˆÃÌÊvœÀÊiÛiÀÞÊ£{]ÈÓäÊ«iœ- «i®Êœ˜ÊÌ iÊ>Û>ˆ>LˆˆÌÞʜvÊ«ÃÞV ˆ>ÌÀˆÃÌðÊ"Ì iÀÊÃÌ>ÌiÃÊÌ >ÌÊ`iÃiÀÛiÊVœ““i˜`>̈œ˜ÊvœÀÊÕȘ} Vœâ>«ˆ˜iÊ>ÌÊ>Ê higher rate than the availability of psychiatrists in that state would predict include Colorado, Washington, ˆ˜œˆÃ]Ê œÀÌ Ê >ŽœÌ>]Ê7ޜ“ˆ˜}]Ê>˜Ã>Ã]Ê œ˜Ì>˜>]Ê7iÃÌÊ6ˆÀ}ˆ˜ˆ>]Ê1Ì> ]ÊœÜ>]Ê iLÀ>Î>Ê>˜`Ê`> œ°

ÌÊÌ iÊLœÌ̜“Êi˜`ʜvÊÌ iʏˆÃÌ]Ê
>L>“>]Ê ˆÃÈÃÈ««ˆ]Ê
ÀŽ>˜Ã>ÃÊ>˜`Ê/iÝ>ÃÊ>ÊÕÃiÊÀi>̈ÛiÞʏˆÌ̏iÊVœâ>«ˆ˜iÊ but also have relatively few psychiatrists. By contrast, Oregon is tied for the lowest use of clozapine yet À>˜ŽÃÊ£{Ì Ê­£Ê«ÃÞV ˆ>ÌÀˆÃÌÊvœÀÊiÛiÀÞÊn]{ä{Ê«iœ«i®Êˆ˜ÊÌ iÊ>Û>ˆ>LˆˆÌÞʜvÊ«ÃÞV ˆ>ÌÀˆÃÌÃ°Ê œÀÌ Ê >Àœˆ˜>Ê>˜`Ê i>Ü>ÀiÊ>ÃœÊÕÃiʓÕV ʏiÃÃÊVœâ>«ˆ˜iÊÌ >˜ÊÌ iˆÀʘՓLiÀÃʜvÊ«ÃÞV ˆ>ÌÀˆÃÌÃÊܜՏ`ÊÃÕ}}iÃÌ°Ê/ÜœÊœÌ iÀÊ ÃÌ>ÌiÃÊÌ >ÌÊ`iÃiÀÛiÊ`ˆÃ œ˜œÀ>Liʓi˜Ìˆœ˜Ê>ÀiÊ iÜÊ9œÀŽÊ>˜`Ê >ˆvœÀ˜ˆ>ÆÊÌ iÞÊ>ÀiÊ̈i`ÊvœÀÊÎӘ`ʈ˜ÊÃÌ>ÌiÊ Vœâ>«ˆ˜iÊÕÃi]ÊÞiÌÊ iÜÊ9œÀŽÊˆÃÊÀ>˜Ži`ÊӘ`Ê>˜`Ê >ˆvœÀ˜ˆ>Ê™Ì Êˆ˜ÊÌ iÊ>Û>ˆ>LˆˆÌÞʜvÊ«ÃÞV ˆ>ÌÀˆÃÌð

DISCUSSION As the “gold standard” antipsychotic for individuals with treatment-resistant schizophrenia, especially those individuals who are suicidal or violent, clozapine use can be regarded as a measure of a state’s ef- vœÀÌÊ̜ÊÌÀi>ÌÊÌ iÊÈVŽiÃÌÊ>˜`ʓœÃÌÊ`ˆvwVՏ̜̇‡ÌÀi>ÌÊ«>̈i˜ÌðÊ/ ˆÃÊÃÌÕ`ÞÊ >ÃÊÀiÛi>i`Ê>Ê܈`iÊ`ˆÃVÀi«>˜VÞÊ ˆ˜ÊVœâ>«ˆ˜iÊÕÃiÊLÞÊÃÌ>ÌiÃ]ÊvÀœ“Ê£x°ÈÊ«iÀVi˜Ìʈ˜Ê-œÕÌ Ê >ŽœÌ>Ê̜ÊÓÊ«iÀVi˜Ìʈ˜ÊœÕˆÃˆ>˜>]Ê iÛ>`>Ê>˜`Ê "Ài}œ˜°Ê-œÕÌ Ê >ŽœÌ>ÊÃÌ>˜`ÃʜÕÌÊ>ÃÊÌ iÊÃÌ>Ìiʓ>Žˆ˜}ÊÌ iÊ}Ài>ÌiÃÌÊivvœÀÌÊ̜ÊÕÃiÊVœâ>«ˆ˜iÊ>««Àœ«Àˆ>ÌiÞ]Ê >˜`ʈÃÊÌ ÕÃÊÌ iÊÃÌ>Ìiʈ˜ÊÜ ˆV ʈ˜`ˆÛˆ`Õ>ÃÊÜˆÌ ÊÃiÛiÀiÊÃV ˆâœ« Ài˜ˆ>Ê>ÀiʓœÃÌʏˆŽiÞÊ̜ÊÀiViˆÛiÊÌ iʓœÃÌÊ efficacious pharmacological treatment.

7 ÞʈÃÊVœâ>«ˆ˜iÊÕÃiÊÜʏœÜʈ˜ÊÌ iÊ1˜ˆÌi`Ê-Ì>ÌiÃÊVœ“«>Ài`Ê̜ʓ>˜ÞÊœÌ iÀÊVœÕ˜ÌÀˆiÃ¶Ê œÃÌʈÃʘœÌÊ>Êv>V̜À]Ê since clozapine has been generic for many years. Indeed, cost studies of clozapine use have reported major savings, especially because of decreased hospitalization.13-15 The main reason for low clozapine use is apparently a reluctance of psychiatrists and other physicians to use it because of the blood tests and >``ˆÌˆœ˜>Ê>`“ˆ˜ˆÃÌÀ>̈ÛiÊÌ>ÎÃÊ>ÃÜVˆ>Ìi`ÊÜˆÌ Ê“œ˜ˆÌœÀˆ˜}ÊÌ ˆÃÊ`ÀÕ}ÊÌ >ÌÊ>ÀiʘœÌÊ>ÃÜVˆ>Ìi`ÊÜˆÌ ÊœÌ iÀÊ >˜Ìˆ«ÃÞV œÌˆVðÊœÜiÛiÀ]ÊÌ iʓœ˜ˆÌœÀˆ˜}ʜvÊVœâ>«ˆ˜iÊÜ>ÃÊÀiVi˜ÌÞÊȓ«ˆwi`ÊÜÊÌ ˆÃÊà œÕ`ʘœÜÊLiʏiÃÃÊ œvÊ>˜Êˆ“«i`ˆ“i˜Ì°Ê
Êvi>Àʜvʏi}>Êˆ>LˆˆÌÞʓ>ÞÊ>ÃœÊ«>ÞÊ>ÊÀœiÊȘViÊÌ iÊ1˜ˆÌi`Ê-Ì>ÌiÃÊ >ÃÊv>ÀʓœÀiʏ>ÜÞiÀÃÊ Ì >˜ÊœÌ iÀÊVœÕ˜ÌÀˆiðÊ
ÃÜVˆ>Ìi`ÊÜˆÌ ÊÌ ˆÃÊÀiÕVÌ>˜ViʈÃÊÌ iÊ«Àœ“ˆ˜i˜ÌÊÀœiÊ«>Þi`ʈ˜ÊÌ iÊ1˜ˆÌi`Ê-Ì>ÌiÃÊ by pharmaceutical company advertising and detailing; they have successfully convinced the majority of psychiatrists that they should prescribe the latest antipsychotic despite clear evidence that some of the older—and much less expensive—antipsychotics, especially clozapine, are superior.

Another reason for the low utilization of clozapine is reluctance by some patients to agree to the neces- Ã>ÀÞÊLœœ`ÊÌiÃ̈˜}°Ê-ÌÕ`ˆiÃÊ >ÛiÊà œÜ˜ÊÌ >ÌÊVˆ˜ˆVˆ>˜ÃʜÛiÀiÃ̈“>ÌiÊÌ iʈ˜Vœ˜Ûi˜ˆi˜ViʜvÊ >ۈ˜}ÊÀi}Տ>ÀÊ blood monitoring for patients; clinicians estimated that 52 percent of patients would feel inconvenienced, LÕÌʜ˜ÞÊ£™Ê«iÀVi˜ÌÊ>VÌÕ>ÞÊ`ˆ`°£È Thus, as Kane noted, “the biggest obstacle [to clozapine use] appears ˜œÌÊ̜ÊLiÊ«>̈i˜ÌÊÀivÕÃ>]ÊLÕÌÊ« ÞÈVˆ>˜ÊÀiiVÌ>˜Vi°»£ÈÊ

The limitations of this study include the use of pharmacy prescription data, rather than the more inclusive i`ˆV>ˆ`Ê`>Ì>]ÊvœÀÊ
Àˆâœ˜>]Ê i>Ü>Ài]Ê >ˆ˜i]Ê iÛ>`>]Ê"Ài}œ˜Ê>˜`Ê, œ`iÊÏ>˜`ÆÊÌ iÊÀiÃՏÌÃÊvœÀÊÌ iÃiÊ states should thus be regarded as less accurate than for the other states. A second limitation is that the i`ˆV>ˆ`Ê`>Ì>ÊVœÛiÀÃÊÓääȇÓää™ÆÊܓiÊÃÌ>ÌiýÊVœâ>«ˆ˜iÊÕÃ>}iʓ>ÞÊ >Ûiʈ“«ÀœÛi`ÊȘViÊÓä䙰ʈ˜>Þ]Ê Ì iÊ`>Ì>ʈÃÊÀi«œÀÌi`Ê>ÌÊÌ iÊÃÌ>ÌiʏiÛi]ÊÜ iÀi>Ãʈ˜Ê>ʏ>À}iÊÃÌ>ÌiʏˆŽiÊ >ˆvœÀ˜ˆ>ÊÌ iÀiʓ>ÞÊLiʓ>œÀÊ`ˆvviÀ- i˜ViÃʈ˜ÊVœâ>«ˆ˜iÊÕÃiÊVœÕ˜ÌÞÊ̜ÊVœÕ˜ÌÞ°Ê/ iÊ i`ˆV>ˆ`Ê`>Ì>ʈÃÊ>Û>ˆ>LiÊvœÀÊVœÕ˜ÌˆiÃÊÜÊÃÕV Ê>ÊÃÌÕ`ÞÊVœÕ`Ê be done.

Clozapine for Treating Schizophrenia: A COMPARISON OF THE STATES n 5 REFERENCES

Ê£°Ê ˆiÃi˜Ê]ÊiÌÊ>\Ê"«Ìˆ“ˆâˆ˜}ÊVœâ>«ˆ˜iÊÌÀi>̓i˜Ì°ÊActa Psychiatrica Scandinavica 2011; 123: 411-422. ÊÓ°Ê iÌâiÀÊ9°Ê œâ>«ˆ˜i\ÊL>>˜Vˆ˜}ÊÃ>viÌÞÊÜˆÌ ÊÃÕ«iÀˆœÀÊ>˜Ìˆ«ÃÞV œÌˆVÊivwV>VÞ°ÊClinical Schizophrenia & Related Psychoses°ÊÓä£ÓÆÊȭή\Ê£Î{‡£{{° ÊÎ°Ê iÌâiÀÊ9°Ê-ՈVˆ`iʈ˜ÊÃV ˆâœ« Ài˜ˆ>]ÊVœâ>«ˆ˜i]Ê>˜`Ê>`œ«Ìˆœ˜ÊœvÊiۈ`i˜Vi‡L>Ãi`ʓi`ˆVˆ˜i° Journal of Clinical Psychiatry°ÊÓääxÆÊÈÈ\ÊxÎä‡xÎΰ Ê{°Ê ÕVŽiÞÊ*] ÊiÌÊ>°Ê*ÃÞV œ« >À“>Vœœ}ÞʜvÊ>}}ÀiÃȜ˜Êˆ˜ÊÃV ˆâœ« Ài˜ˆ>°ÊSchizophrenia Bulletin. Ó䣣ÆÊÎÇ\ʙÎ䇙ÎÈ° Êx°ÊÀ>˜ŽiÊ7]ÊiÌÊ>°Ê œâ>«ˆ˜i‡>ÃÜVˆ>Ìi`ÊÀi`ÕV̈œ˜Êˆ˜Ê>ÀÀiÃÌÊÀ>ÌiÃʜvÊ«ÃÞV œÌˆVÊ«>̈i˜ÌÃÊÜˆÌ ÊVÀˆ“ˆ˜>Ê histories. American Journal of Psychiatry°ÊÓää£ÆÊ£xn\ÊÓÇä‡ÓÇ{° ÊÈ°Ê9œÕ˜}Ê ,]ÊiÌÊ>°Ê >˜>}i“i˜ÌʜvÊÌ iÊ
`ÛiÀÃiÊ vviVÌÃʜvÊ œâ>«ˆ˜i°ÊSchizophrenia Bulletin°Ê£™™nÆÊ Ó{­Î®\ÊÎn£‡Î™ä° ÊÇ°Ê-ˆ˜ÞœÀÊ Ê>˜`Ê,i“ˆ˜}̜˜Ê°ÊÃÊ«ÃÞV ˆ>ÌÀÞʈ}˜œÀˆ˜}ÊÃՈVˆ`i¶Ê/ iÊV>ÃiÊvœÀÊVœâ>«ˆ˜i°ÊJournal of Clinical Psychiatry°ÊÓä£ÓÆÊÎÓ\ÊÎäLJÎän° Ên°Ê>˜}Ê8]Ê-ˆ“«Ãœ˜Ê °Ê œâ>«ˆ˜i\ʓœÀiÊÈ`iÊivviVÌÃÊLÕÌÊÃ̈ÊÌ iÊLiÃÌÊ>˜Ìˆ«ÃÞV œÌˆV°ÊJournal of Clinical Psychiatry°ÊÓä£äÆÊÇ£\ʙnӇ™nΰ ʙ°Ê>˜iÊ°Ê*iÀܘ>ÊVœ““Õ˜ˆV>̈œ˜ÆÊՏÞÊÓÎ]ÊÓä£Ó° Ê£ ä ° Ê "  v à œ ˜ Ê ]ÊiÌÊ>°Ê œâ>«ˆ˜iÊvœÀÊÃV ˆâœ« Ài˜ˆ>\Ê-Ì>ÌiÊÛ>Àˆ>̈œ˜Êˆ˜Êiۈ`i˜Vi‡L>Ãi`Ê«À>V̈Vi°ÊPsychiatric Services°ÊÓä£xÆÊÈÈ­££®\ʫð«ÃÞV ˆ>ÌÀޜ˜ˆ˜i°œÀ}° ££°Ê -Êi>Ì ʘVœÀ«œÀ>Ìi`ʘvœÀ“>̈œ˜Ê-iÀۈVi\Ê8«œ˜i˜Ì/ ]ÊÓä䙇Ó䣣]Ê>ÊÀˆ} ÌÃÊÀiÃiÀÛi`° £Ó°Ê-Ì>ÌiÊ* ÞÈVˆ>˜Ê7œÀŽvœÀViÊ >Ì>Ê œœŽ]Ê
“iÀˆV>˜Ê
ÃÜVˆ>̈œ˜ÊœvÊ i`ˆV>Ê œi}iÃÊ i˜ÌiÀÊvœÀÊ 7œÀŽvœÀViÊ-ÌÕ`ˆiÃ]ÊÓä£Î° £Î°Ê ˆi`i˜Ê ]ÊiÌÊ>°Êi>Ì Ê-Ì>ÌÕÃÊ>˜`Êi>Ì Ê >ÀiÊ œÃÌÃÊvœÀÊ*ÕLˆVÞÊ՘`i`Ê*>̈i˜ÌÃÊÜˆÌ Ê -V ˆâœ« Ài˜ˆ>Ê-Ì>ÀÌi`ʜ˜Ê œâ>«ˆ˜i°ÊPsychiatric Services°Ê£™™nÆÊ{™­£Ó®\£x™ä‡£x™Î°

£{°Ê,œÃi˜ iVŽÊ,]ÊiÌÊ>°Ê œÃ̇ivviV̈Ûi˜iÃÃʜvÊVœâ>«ˆ˜iʈ˜Ê«>̈i˜ÌÃÊÜˆÌ Ê ˆ} Ê>˜`ʏœÜʏiÛiÃʜvÊ œÃ«ˆÌ>Ê use. Archives of General Psychiatry°Ê£™™™ÆÊxÈ\xÈx‡xÇÓ° 15. Aitchison KJ, Kerwin RW. Cost-effectiveness of clozapine. British Journal of Psychiatry. £™™ÇÆʣǣ\Ê£Óx‡£Îä° £È°Ê>˜iÊ °Ê
ÊÕÃiÀ½ÃÊ}Ո`iÊ̜ÊVœâ>«ˆ˜i°ÊActa Psychiatrica Scandinavica°ÊÓ䣣ÆÊ£ÓÎ\Ê{äLJ{än°

6 n REFERENCES