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 â« Ài>ÊÃÊiÊvÊÌ iÊÃÌÊ`Ã>L}Ê«ÃÞV >ÌÀVÊ`ÃÀ`iÀÃÊ>`Ê>vviVÌÃÊ>««ÀÝ>ÌiÞÊÓ°ÈÊÊ 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 ÀiÊvÊ`Û`Õ>ÃÊÜÌ ÊÃV â« Ài>ÊÊÃÌÊ`iÛi«i`ÊVÕÌÀiÃ]ÊÌÃÊÕÃiÊÊÌ iÊ1Ìi`Ê-Ì>ÌiÃÊÃÊiÃÃÊ 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 1Ã}Ê`>Ì>ÊvÀÊi`V>`Ê>`Ê« >À>VÞÊ«ÀiÃVÀ«ÌÃ]ÊÜiÊ>ÃViÀÌ>i`ÊVâ>«iÊÕÃiÊvÀÊ>ÊxäÊÃÌ>ÌiÃÊ and compared them as a measure of the states’ efforts to treat individuals with schizophrenia. Ê "ÞÊ ÃÝÊ ÃÌ>ÌiÃÊ >V iÛi`Ê Ì iÊ ºL>ÀiÊ Õ»Ê vÊ £äÊ «iÀViÌÊ ÕÃi\Ê -ÕÌ Ê >Ì>]Ê iVÌVÕÌ]Ê À>`]Ê7>à }Ì]Ê6iÀÌÊ>`Ê>i° o The states that were using the least clozapine—to treat less than 3 percent of individuals—were iÀ}>]ÊiÌÕVÞ]Ê ÀÌ Ê >À>]ÊÃÃÃë«]Ê>L>>]ÊÀâ>]ÊÕÃ>>]Ê iÛ>`>Ê>`Ê"Ài}° UÊ â>«iÊÃÊÕÃÕ>ÞÊ«ÀiÃVÀLi`ÊLÞÊ«ÃÞV >ÌÀÃÌÃ]ÊÀ>Ì iÀÊÌ >ÊÌ iÀÊ« ÞÃV>Ã]ÊLÕÌÊ«ÃÞV >ÌÀÃÌÃÊ>ÀiÊÛiÀÞÊ ÕiÛiÞÊ`ÃÌÀLÕÌi`ÊLÞÊÃÌ>Ìi°Ê/ iÀivÀi]ÊÜiÊ>ÃÊiÝ>i`ÊVâ>«iÊÕÃiÊÌ>}ÊÌÊVÃ`iÀ>ÌÊ the availability of psychiatrists. Ê 7 iÊ>Û>>LÌÞÊvÊ«ÃÞV >ÌÀÃÌÃÊÃÊ>ÃÊVÃ`iÀi`ÊÊVâ>«iÊÕÃi]Ê-ÕÌ Ê >Ì>ÊÜ>ÃÊLÞÊv>ÀÊ`}Ê Ì iÊLiÃÌÆÊ À>LiÊiÌÊ}iÃÊÌÊ À>`]Ê7>à }Ì]ÊÃ]Ê ÀÌ Ê >Ì>Ê>`Ê7Þ}° o When availability of psychiatrists is also considered in clozapine use, Oregon was doing the worst. à À>LiÊiÌÊ}iÃÊÌÊ ÀÌ Ê >À>]Ê i>Ü>Ài]Ê iÜÊ9ÀÊ>`Ê >vÀ>° UÊ / iÊÕÃiÊvÊVâ>«iÊV>ÊLiÊÀi}>À`i`Ê>ÃÊ>Êi>ÃÕÀiÊvÊÌ iÊivvÀÌÊLi}Ê>`iÊLÞÊ>ÊÃÌ>ÌiÊÌÊÌÀi>ÌÊ individuals with schizophrenia who are most in need of treatment. The range of effort in the United -Ì>ÌiÃÊÛ>ÀiÃÊÜ`iÞÊvÀÊ-ÕÌ Ê >Ì>Ê­LiÃÌ®ÊÌÊ"Ài}Ê­ÜÀÃÌ®° 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 â« Ài>ÊÃÊiÊvÊÌ iÊÃÌÊ`Ã>L}Ê«ÃÞV >ÌÀVÊ`ÃÀ`iÀÃÊ>`Ê>vviVÌÃÊ>««ÀÝ>ÌiÞÊÓ°ÈÊÊ iÀV>Ê>`ÕÌÃ°Ê â>«iÊLiV>iÊ>Û>>LiÊvÀÊÕÃiÊÊÌ iÊ1Ìi`Ê-Ì>ÌiÃÊÊ£äÊ>`ÊÃÊÜ`iÞÊÀi}>À`i`Ê as the “gold standard” antipsychotic for treating schizophrenia.1 It is the only antipsychotic approved by Ì iÊ`Ê>`Ê ÀÕ}Ê`ÃÌÀ>ÌÊ­ ®ÊvÀÊÌ iÊÌÀi>ÌiÌÊvÊÌ iÊÓäÊÌÊÎäÊ«iÀViÌÊvÊV>ÃiÃÊÌ >ÌÊ>ÀiÊÌÀi>Ì- ment resistant; approximately 50 percent of such patients improve on clozapine. It is also the only medi- V>ÌÊ>««ÀÛi`ÊLÞÊÌ iÊ ÊvÀÊÌ iÊ«ÀiÛiÌÊvÊÃÕV`i°ÊÃÊ«ÃÞV « >À>V}ÃÌÊ À°ÊiÀLiÀÌÊiÌâiÀÊ noted, “clozapine has been found in two large epidemiological studies to have the lowest mortality of >ÞÊ>Ì«ÃÞV ÌVÊ`ÀÕ}]Ê>ÞÊ`ÕiÊÌÊÌÃÊÛiÀÞÊ>À}iÊivviVÌÊÌÊÀi`ÕViÊÌ iÊÀÃÊvÀÊÃÕV`i°»2ÊiÌâiÀÊ>``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 VÃÃÌÃÊvÊ>ÊÀi`ÕVÌÊÊÜ ÌiÊL`ÊViÃÊ­iÕÌÀ«i>®ÊÜ V ÊVVÕÀÃÊÊnÊÕÌÊvÊiÛiÀÞÊ£]äääÊ`Û`Õ>ÃÆÊ vÊÌ ÃÊ«ÀViÃÃÊÃÊ>Üi`ÊÌÊVÌÕiÊÌ iÊ«iÀÃÊ>ÞÊ >ÛiÊÌÊviÜÊÜ ÌiÊL`ÊViÃÊ­>}À>ÕVÞÌÃîÊ>`Ê `i>Ì Ê>ÞÊÀiÃÕÌ°ÊÀÊÌ ÃÊÀi>Ã]Ê`Û`Õ>ÃÊÊVâ>«iÊÕÃÌÊ >ÛiÊÌ iÀÊL`ÊÌiÃÌi`ÊÜiiÞÊvÀÊÌ iÊ wÀÃÌÊÃÝÊÌ ÃÊvÊÌÀi>ÌiÌÆÊÌ iÊiÛiÀÞÊÌÜÊÜiiÃÊvÀÊÌ iÊÃiV`ÊÃÝÊÌ ÃÊvÊÌÀi>ÌiÌ]ÊÌ iÊÌ Þ°Ê Until recently this blood monitoring was administratively complex, but it has now been simplified and VÃ`>Ìi`ÊÌÊ>ÊÃ}iÊÌÀ}ÊÃÞÃÌiÊLÞÊÌ iÊ`Ê>`Ê ÀÕ}Ê`ÃÌÀ>Ì°ÊvÊÌÊÌÀi`]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 â« Ài>]ÊiëiV>ÞÊÌ ÃiÊÜ Ê>ÀiÊÃÕV`>ÊÀÊ V`>°ÊÊÓääÊÌ iÊ-V â« Ài>Ê*>ÌiÌÊ"ÕÌ- ViÃÊ,iÃi>ÀV Ê/i>Ê­*",/®ÊÀiVi`i`ÊÌ >ÌÊVâ>«iÊà Õ`ÊLiÊÌÀi`Ê>vÌiÀÊÌÜÊ>`iµÕ>ÌiÊv>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 ÜiÛiÀ]ÊVâ>«iÊÃÊÕÃi`ÊÜÌ ÊxÊ«iÀViÌÊÀÊviÜiÀÊ`Û`Õ>ÃÊÜÌ ÊÃV â« Ài>°ÊVVÀ`}ÊÌÊ>Ê Óä£äÊÀi«ÀÌ]ʺVâ>«i½ÃÊ>ÀiÌÊà >ÀiÊ``ÊÌÊÀi>V Êΰx¯ÊÊ>ÞÊiÊvÊÌ iÊ>ÃÌÊ£ÓÊÌ Ã°»nÊÜÊ>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>«i]Ê>`ÊÌÊÃiiÊ ÜÊ>ÞÊiiÌÊ>i½ÃÊ£äÊ«iÀViÌʺL>ÀiÊÕ»ÊiÛi]ÊÜiÊÕ`iÀÌÊ>ÊÃÌ>ÌiÊÃÕÀÛiÞ°Ê METHODS >Ì>ÊÊVâ>«iÊÕÃiÊvÀÊ`Û`Õ>ÃÊÊi`V>`Ê>`Ê`>}Ãi`ÊÜÌ ÊÃV â« Ài>ÊÜ>ÃÊLÌ>i`ÊvÀÊvÕÀÊ Þi>ÀÃ]ÊÓääÈÓää]ÊvÀÊ{{ÊÃÌ>ÌiðÊ/ iÊÌÌ>ÊÕLiÀÊvÊ`Û`Õ>ÃÊÀiViÛ}ÊVâ>«iÊvÀÊÌ iÊvÕÀÊÞi>ÀÃÊÜ>ÃÊ £]ÇÎ]£Ç{°Ê/ iÊ`>Ì>ÊÜ>ÃÊLÌ>i`ÊvÀÊÌ iÊÃÌÌÕÌiÊvÀÊi>Ì ]Êi>Ì Ê >ÀiÊ*VÞÊ>`Ê}}Ê,iÃi>ÀV Ê>ÌÊ Rutgers University.10Ê/ ÃÊ`>Ì>ÊÜ>ÃÊÌÊ>Û>>LiÊvÀÊÃÝÊÃÌ>ÌiÃ\ÊÀâ>]Ê i>Ü>Ài]Ê>i]Ê iÛ>`>]Ê"Ài}Ê >`Ê, `iÊÃ>`°Ê/ iÊ«iÀViÌ>}iÊvÊ`Û`Õ>ÃÊÜÌ ÊÃV â« Ài>ÊÜ ÊÜiÀiÊÌ>}ÊVâ>«iÊ>ÌÊ>ÞÊ ÌiÊÜ>ÃÊ>ÛiÀ>}i`ÊvÀÊÌ iÊvÕÀÊÞi>ÀÃÊ>`ÊiÌiÀi`ÊÊ/>LiÊ£°Ê/ iÊÃÌ>ÌiÃÊÜiÀiÊÌ iÊÀ>À`iÀi`° >Ì>ÊÊVâ>«iÊÕÃiÊLÞÊÃÌ>ÌiÊÜ>ÃÊ>ÃÊLÌ>i`ÊvÀÊÓääÓ䣣ÊvÀÊ>ÊÃ>«}ÊvÊÎn]äääÊÀiÌ>Ê« >À>- ViÃ]ÊLÞÊ-Êi>Ì ÊVÀ«À>Ìi`°11 The total number of prescriptions for a 24-month period was then V>VÕ>Ìi`Ê«iÀÊ£ää]äääÊÌÌ>Ê««Õ>ÌÊL>Ãi`ÊÊÓääÊViÃÕÃÊ`>Ì>°Ê ÌiÊÌ >Ì]ÊÕiÊÌ iÊÃÌ>ÌiÊi`V>`Ê `>Ì>]ÊÌ iÊ-Ê`>Ì>Ê``ÊÌÊ>ÃViÀÌ>ÊÌ iÊÌÌ>ÊÕLiÀÊvÊ`Û`Õ>ÃÊÌ>}ÊVâ>«iÊÀÊÌ iÀÊ`>}ÃÃ]Ê 2 n Clozapine for Treating Schizophrenia: A COMPARISON OF THE STATES LÕÌÊÞÊÌ iÊÕLiÀÊvÊ«ÀiÃVÀ«ÌÃ°Ê iëÌiÊÌ Ã]ÊÌ iÊV«>ÀÃÊvÊVâ>«iÊÕÃiÊÕÃ}Êi`V>`Ê`>Ì>Ê ÀÊ« >À>VÞÊ`>Ì>ÊÜ>ÃÊÃÕÀ«ÀÃ}ÞÊV}ÀÕiÌÆÊvÀÊiÝ>«i]ÊÌ iÊÌ«Ê£äÊ>`ÊLÌÌÊ£äÊÃÌ>ÌiÃÊÕÃ}Êi`- icaid data each included six of the top 10 and bottom 10 states using the pharmacy data. For this reason, vÀÊÌ iÊÃÝÊÃÌ>ÌiÃÊvÀÊÜ V Êi`V>`Ê`>Ì>ÊÜ>ÃÊÌÊ>Û>>Li]ÊÜiÊÕÃi`ÊÌ iÊ« >À>VÞÊ`>Ì>°ÊÀÊiÝ>«i]Ê >iÊÜ>ÃÊÀ>i`ÊÃÝÌ Ê>}ÊÌ iÊÃÌ>ÌiÃÊÊVâ>«iÊÕÃiÊL>Ãi`ÊÊ« >À>VÞÊ`>Ì>]ÊÃÊÜiÊ«>Vi`ÊÌÊ ÃÝÌ ÊÊÌ iÊÃÌÊ>`Ê>ÃÃ}i`Ê>iÊ>ÊVâ>«iÕÃiÊÕLiÀÊ`Ü>ÞÊLiÌÜiiÊÌ iÊÃÌ>ÌiÃÊÀ>i`ÊwvÌ Ê>`Ê ÃiÛiÌ °Ê/ iÊÕLiÀÃÊvÀÊÌ iÊÃÝÊÃÌ>ÌiÃÊvÀÊÜ V Ê« >À>VÞÊ`>Ì>ÊÜ>ÃÊÕÃi`Ê>ÀiÊLÀ>ViÌi`ÊÊÌ iÊÌ>LiÊÌÊ indicate that their origin is not the same as those for the other states. ,>}ÊÌ iÊÃÌ>ÌiÃÊLÞÊÌ iÊ«iÀViÌ>}iÊvÊ`Û`Õ>ÃÊÜÌ ÊÃV â« Ài>ÊÜ Ê>ÀiÊÌ>}ÊVâ>«i]Ê Ü- 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/ ÃÊ`>Ì>ÊÜ>ÃÊiÌiÀi`ÊÊ/>LiÊ£Ê>`ÊÀ>ÊÀ`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 -ÕÌ Ê >Ì> £x°È 1 57 £{]ÈÓä {È Connecticut 13.4 2 näÈ 4,455 4 Colorado ££°n 3 xÇ n]Èä £n Washington 11.4 4 731 ]{Îx 21 Vermont 10.7 5 144 4,347 3 >i {10.2} È 217 È]£Óx 7 Illinois °n 7 £]Σ ]ÓxÈ £ ÀÌ Ê >Ì> n° n ÈÇ 10,442 ÓÈ >ÃÃ>V ÕÃiÌÌà n°È £]nÇx 3,545 1 iÜÊ>«Ã Ài 7.2 10 175 7, 547 11 Wyoming 7 11 41 £{]äx 43 Kansas È°{ 12 Ó{ ££]xä 32 Ì>> È°Ó 13 nx ££]nÓx ÎÈ West Virginia È°£ 14 157 ££]n£n 35 Utah x° 15 £{ £{]Ç£n 47 *iÃÞÛ>> x°È £È £]Çnn Ç]£În 10 Iowa 5.4 17 231 £Î]Îän Î V }> 5.1 £n Ó ]ÈÎ 22 iLÀ>Ã> {° £ 137 13,544 40 Rhode Island O{°P £ Óä 5,025 5 Idaho {°n 21 n{ £n]Ç 50 iÜÊiÝV {°n 21 Ó{n n]{ä 15 Brackets indicate numbers derived from pharmacy data; all others derived from Medicaid data.