Clozapine and agranulocytosis: re-assessing the risks.

OBJECTIVE: The aim of the study was to estimate the maximum incidence of agranulocytosis which clozapine would have caused between 2006 and 2010 had there been no blood monitoring system; and to determine the number of clozapine-associated cases of agranulocytosis and related deaths recorded between 1993 and 2011. METHOD: Records associating clozapine use with white blood cell deficiency (WBCD), in the Therapeutic Goods Administration's Case Line Listing of adverse drug reactions, were examined. The figure of 11,000 was used as the population on clozapine each year from 2006-2010. RESULTS: Between 2006 and 2010 there were 209 cases of clozapine-associated WBCD recorded, probably caused by clozapine in 141 cases. WBCD caused by clozapine could have progressed to agranulocytosis if clozapine had not been withdrawn. The risk of WBCD/agranulocytosis decreased with increasing duration of clozapine use. Between 1993 and 2011 there were 141 recorded cases of agranulocytosis, and four deaths, from clozapine-associated WBDC. CONCLUSIONS: During 2006-2010, without any monitoring system, the maximum annual incidence of agranulocytosis caused by clozapine would have been 0.26%. The risks of agranulocytosis, and related deaths, decreased with length of time on clozapine. During 1993-2011 141 cases of agranulocytosis, with four deaths, were recorded in association with clozapine use. The monitoring system could have successfully prevented relatively few deaths.

Improving the general health of persons with psychosis.

OBJECTIVE: A project designed to improve the quality of health care received by persons with psychosis is described. METHODS: A nurse was appointed to provide liaison between the mental health service and general practitioners, and to facilitate general health care of patients. ACT Health offered service agreements to general practices, with quarterly per capita payments. RESULTS: About half of the local general practices participated. The number of patients without a general practitioner was reduced and quality of health care improved compared with the previous year. Recurrent funding has been provided. CONCLUSIONS: Improving the general health of persons with psychosis is an important issue for psychiatry. Having a similar project in all mental health services could be valuable.

Mortality and mental illness.

BACKGROUND: The finding by Lawrence, Holman and Jablensky (Duty to Care) that mortality among the mentally ill in Western Australia was 2.5 times that of the general population, seemingly, has great significance for public policy concerning the mentally ill. 'Mortality' could be a useful outcome measure for mental health services. OBJECTIVES: To replicate that study in the Australian Capital territory (ACT), comparing mortality rates in the mentally ill with those of the total population. METHOD: A list of all people who contacted the ACT mental health services between 1985 and 2000 was compiled. Using the national register of deaths (Australian Institute of Health and Welfare), persons known to the mental health services who died between 1990 and 2000 were identified and sex, date of birth, date of death, cause of death and place of death were noted. Using Australian Bureau of Statistics data for all deaths in the ACT, deaths in the total population and in the mentally ill population were tabulated for the period 1996-2000. With 1996 data as the base, using total population data from the ABS and mental health population data derived by amending 'the list' to remove duplications, pre1996 deaths and post1996 additions, mortality rates for the period 1996-2000 were compared. RESULTS: The gender and age distribution of the mentally ill population and the total population, and of deaths in those populations, were very different. One third of all deaths in the mentally ill occurred outside of the ACT. Compared with the general population, mortality in the mentally ill (including deaths outside of the ACT) was only slightly excessive for 'all causes' and ischaemic heart disease but grossly excessive for 'suicide'. CONCLUSIONS: This study did not confirm the excessive mortality rate in the mentally ill reported by Lawrence et al. except for suicide. Many methodological issues in using population studies to attempt to measure the size of the increase were identified. Differences in method between the ACT and WA studies probably explain the differences in results. Caution is urged in using the results of mortality studies as determinants of public policy or to evaluate services.

A five year follow-up study of the use of clozapine in community practice.

OBJECTIVE: To present information about the value of clozapine in treatment-resistant schizophrenia. Data is reported on the use of clozapine in an entire cohort of (42) patients in a community, the Australian Capital Territory. It extends a 3-year study of clinical and financial outcomes to 5 years. METHOD: Experiences during the 2 years before clozapine was prescribed and those of the 5 years following prescription were compared by a records review, including hospital and hostel bed use and estimated treatment costs. Changes in dose levels, living circumstances and employment status were assessed, and treating psychiatrists reported on side-effects and their impression of clinical change since clozapine was prescribed. RESULTS: Ten subjects were excluded. The remaining cohort (32 subjects) demonstrated continuing clinical improvement and cost savings during follow-up. Those (22) remaining on clozapine after the five year period showed continuing clinical improvement, reduced hospital admissions and hospital bed usage and significantly large cost savings, and were moderately to markedly improved after 3 years. Only one patient (of 22) showed a slight deterioration in the next two years while 14 showed further improvement. After 5 years, the clinical status of four of the 10 subjects who discontinued clozapine was unchanged or deteriorated compared with their preclozapine status. There were no suicides. CONCLUSION: The findings of continuing clinical improvement and decreased costs after long-term (5 years) use of clozapine supports the selective use of clozapine in community practice.