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Suicidal Behavior in Schizophrenia and
Schizoaffective Disorder
Herbert Y. Meltzer, MD
Bixler Professor ofPsychiatry and Pharmacology
Vanderbilt University
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Overview of Presentation
Suicidal behavior in schizophrenia and schizoaffective disorder
Suicidal behavior as a separate domain from psychosis
Pre-InterSePT evidence for Clozaril® effects on suicidal behavior
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Suicidal Behavior in Schizophrenia
“ Patients with dementia praecox often need hospitalization to prevent aggression against others and suicide.”
Emil Kraepelin, 1897
“ The suicidal drive is clearly the most serious of schizophrenic symptoms.”
Eugen Bleuler, 1911
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The Spectrum of Suicidal Behavior
20% to 40% of patients with schizophrenia and schizoaffective disorder attempt suicide§
4% to 13% die by suicide||
Annual number of suicides in US for schizophrenia is 3,600¶
Suicidal thoughts
Suicide plans
Suicide attempts
Suicide
Communicated behaviorCommunicated behaviorCommunicated behaviorCommunicated behavior Observed behaviorObserved behaviorObserved behaviorObserved behavior
§Roy et al, 1984; Landmark et al, 1987; Heila et al, 1998; Harkavy-Friedman et al, 1999.||Tsuang, 1978; Heila et al, 1997; Osby et al, 2000; ¶US Surgeon General.
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Suicidal Behavior Is a Separate Domain from Psychosis
Successful treatment of positive symptoms does not eliminate the risk of suicide attempts or completion.
Lifetime and current suicidal behavior not significantly different between neuroleptic-resistant and neuroleptic-responsive patients.§
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§Meltzer, 1997.
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Schizophrenia and Schizoaffective Disorder Lifetime Suicidal Ideation and Attempts
0
10
20
30
40
50
60
70
80
Never suicidal Suicidal plans Attempters
Pat
ien
ts,
%
SchizophreniaSchizoaffective
N =
Meltzer et al, Case Western Reserve MHCRC, unpublished data.
164164 44 8787 99 148148 2727
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CO-8No Significant Correlation Between Psychopathology and Suicidal Behavior(N = 390)
Psychopathology Measures Rho P value
HAM-Depression Total 0.418 .0001BPRS-Anxiety/Depression 0.349 .0001
BPRS-Positive Symptoms 0.086 .09BPRS-Negative Symptoms –0.005 .9Quality of Life Scale –0.009 .8 Global Assessment of
Function Scale –0.052 .2
Meltzer and Okayli, 1995 and unpublished data.
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The Burden of Suicidal Behavior
Psychosocial
Physical and mental disability
Disruption of personal and family life
Financial
Average cost for suicide attempt in US, mostly due to cost of hospitalization: $33,000§
§Palmer et al, 1995.
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Reduction of Suicidal Behavior During Clozaril® Treatment§
Compared suicidal behavior 2 yr before and 2 to 5 yr on Clozaril
N = 88: 73 schizophrenia15 schizoaffective disorder
Retrospective and prospective information from patients, informants, medical records
Clozaril monotherapy, weekly monitoring, assessment, and psychosocial treatment program
§Meltzer and Okayli, 1995.
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Treatment With Clozaril® Affects Suicidal Behavior§
0
10
20
30
40
50
60
70
80
Nu
mb
er o
f p
atie
nts
Before Clozaril
During Clozaril
§Meltzer and Okayli, 1995.
47 77N = 9 7 10 1 17 3 5 0None Ideation Unintended
self harmLow
probabilityof success
Highprobabilityof success
53%
88%
10% 8%1%
11%19%
3% 6%0
Suicide attempts
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Registry Data for the Effect of Clozaril® on Suicidal Behavior
US Clozaril Registry (2 studies, 1994 to 1998) reported that Clozaril reduced the rate of completed suicide compared with treatment as usual§
Reviews of data from treatment registries (Texas and UK) also showed that treatment with Clozaril reduced the rate of completed suicide||
§Meltzer and Okayli, 1995; Reid et al, 1998. ||Reid et al, 1998; Munro et al, 1999.
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Epidemiologic Evidence for Anti-Suicidal Effects of Clozaril®
Prior to InterSePT
Walker et al, 1997
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Study Objectives
Determine death due to all causes associated with Clozaril® use
Subjects: patients in the Clozaril National Registry (CNR) from 1991 until end of 1993
– Patients age 10 to 54 yrs
– 67,072 current and former Clozaril users§
– 85,399 patient-years of exposure to Clozaril
§Maximum duration of Clozaril use was < 4 years.
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Study Methods
Clozaril® users were grouped into
– “current” (0 - 14 days since last WBC record)
– “recent” (15 - 106 days)
– “past” (> 107 days)
Mortality data from the CNR were matched with National Death Index and Social Security Administration Death Master Files
CNR = Clozaril National Registry.
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Deaths Due to Suicide as a Function of Clozaril® Exposure
39
246222
0
50
100
150
200
250
300
Current Recent Past
Ra
te p
er
10
0,0
00
pe
rso
n y
ea
rs
Walker et al, 1997.
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Standardized Mortality Ratios for Current and Recent Exposure
Current CI Recent CI
All causes 0.46 0.37-0.59 1.69 1.28-2.25
Suicide 0.17 0.10-0.30 1.11 0.62-1.99
Current Clozaril® users had a 54% lower risk of death from any cause than past Clozaril users
The risk of death by suicide was reduced by 83%
Suicide accounted for 19% of all deaths
Walker et al, 1997.
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Conclusion of Walker et al Study
Clozaril® reduced the risk of completed suicide
Data are consistent with previous findings
The reduced suicide rate was the largest contributor to the lower overall mortality rate in the Clozaril current-user group
The beneficial effect of Clozaril on suicide did not persist after it was discontinued
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Overall Considerations (1)
Attempted suicide is an important public health issue, occurring in 20% to 40% of patients with schizophrenia and schizoaffective disorder
Attempted suicide is a major burden on patients, families, and society
Suicidal behavior is a separate domain from psychosis
Extensive previous research suggested that Clozaril® reduces suicidal behavior
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Overall Considerations (2)
InterSePT (International Suicide Prevention Trial) was designed to provide a controlled, prospective test of the hypothesis that Clozaril reduces the risk of suicidal behavior
Innovative design of an extremely important public health problem in a very high-risk population
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