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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 as a Domain Separate From Psychosis

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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Meltzer et al, Case Western Reserve MHCRC, unpublished data.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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Pre-InterSePT Evidence for Clozaril® Effects on Suicidal Behavior

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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