# Presentation: 910493

## Suicidal Behavior in Schizophrenia and Schizoaffective Disorder

**Herbert Y. Meltzer, MD**
**Bixler Professor of****Psychiatry 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 behavior**

**Observed 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.**

## Schizophrenia and Schizoaffective Disorder Lifetime Suicidal Ideation and Attempts

**N =**

**Meltzer et al, Case Western Reserve MHCRC, unpublished data.**

**164**

**4**

**87**

**9**

**148**

**27**

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## No Significant Correlation Between Psychopathology and Suicidal Behavior(N = 390)

**Psychopathology Measures        Rho      *****P***** value**
**HAM-Depression Total****	****0.418****	****.0001**
**BPRS-Anxiety/Depression****	****0.349****	****.0001**
**BPRS-Positive Symptoms****	****0.086****	****.09**
**BPRS-Negative Symptoms****	****–****0.005****	****.9**
**Quality 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 schizophrenia****	****15 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§

** ****§Meltzer and Okayli, 1995.**

**47**

**77**

**N =**

**9**

**7**

**10**

**1**

**17**

**3**

**5**

**0**

**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**

## 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.**

## 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.**

## Deaths Due to Suicide as a Function of Clozaril® Exposure

**Walker et al, 1997.**

## 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.**

## 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**

## 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**