Suicide in schizophrenia : how Suicide in schizophrenia : how can research influence training can research influence training

and clinical practice?and clinical practice?

Dr. Nivert ZakiDr. Nivert ZakiProfessor of PsychiatryProfessor of Psychiatry

Okasha Institute of PsychiatryOkasha Institute of PsychiatryFaculty of Medicine – Ain Shams Faculty of Medicine – Ain Shams

UniversityUniversity

The most common cause of The most common cause of premature death in premature death in schizophrenia. schizophrenia.

WHO study : 1056 patients , the WHO study : 1056 patients , the most common cause of death in most common cause of death in those with schizophrenia was those with schizophrenia was suicide suicide ((Sartorius et al, 1986Sartorius et al, 1986). ).

9-13% of patients with 9-13% of patients with schizophrenia eventually commit schizophrenia eventually commit suicide. suicide. (Caldwell and Gottesman , (Caldwell and Gottesman , 19901990) )

At least 20-40% make suicide At least 20-40% make suicide attempts attempts ((Meltzer & Meltzer & FatemiFatemi, 1995, 1995))

1-2% go on to complete in their 1-2% go on to complete in their attempt within the next 12 months attempt within the next 12 months ((Meltzer & Meltzer & OkayliOkayli 1995 1995).).

20% of suicide victims during the 20% of suicide victims during the period 1996-1998 had a period 1996-1998 had a diagnosis of schizophrenia. diagnosis of schizophrenia.

50% had contact with psychiatric 50% had contact with psychiatric services within the previous 7 services within the previous 7 days, yet 85% were thought to days, yet 85% were thought to be low risk. be low risk.

((Appleby et al, 1999Appleby et al, 1999))

What is unclear is :What is unclear is :

What risk factors have been reliably What risk factors have been reliably reported in well-controlled studiesreported in well-controlled studies

How best to incorporate these into How best to incorporate these into current assessment procedurescurrent assessment procedures

Whether when applied to clinical Whether when applied to clinical practice, such procedures can practice, such procedures can reduce suicide rates.reduce suicide rates.

Suicide in schizophrenia has long Suicide in schizophrenia has long been a major area of concern been a major area of concern and research efforts.and research efforts.

It is vital for clinicians to feel It is vital for clinicians to feel confident in their understanding confident in their understanding of risk assessment and of risk assessment and management in this particularly management in this particularly vulnerable group.vulnerable group.

Risk factorsRisk factors such as demographic & such as demographic & clinical factors clinical factors

Preventive optionsPreventive options as improved as improved recognition of vulnerability and different recognition of vulnerability and different pharmacological and psychosocial pharmacological and psychosocial intervention methods. intervention methods.

Clinical implicationsClinical implications how can research how can research expand our knowledge of the risk factors expand our knowledge of the risk factors in this group and what can clinicians do in this group and what can clinicians do to improve the care and management of to improve the care and management of their patients.their patients.

Demographic Factors :Demographic Factors : Men commit suicide more frequently & Men commit suicide more frequently &

at a younger age than women with at a younger age than women with schizophreniaschizophrenia

worsened course of illness worsened course of illness earlier onset of diseaseearlier onset of disease

both are frequently observed among men. both are frequently observed among men. This could lead to lower levels of social This could lead to lower levels of social

and occupational functioning, and and occupational functioning, and increased rates of hospitalization. increased rates of hospitalization.

(Tandon & Jibson , 2003) (Tandon & Jibson , 2003)

The mean age of patients with The mean age of patients with schizophrenia who commit schizophrenia who commit suicide is approximately 33 yearssuicide is approximately 33 years

This is not to say that elderly This is not to say that elderly people with schizophrenia are people with schizophrenia are not vulnerable, since they not vulnerable, since they commit suicide as well.commit suicide as well.

(Waern et al , 2002)(Waern et al , 2002)

Social isolationSocial isolation UnemploymentUnemployment Marital statusMarital status has not been found has not been found

to be a consistent risk factor. to be a consistent risk factor. Parental lossParental loss have produced mixed have produced mixed

results results EthnicityEthnicity remains confusing, remains confusing,

complicated by a lack of well-complicated by a lack of well-controlled studies in multiethnic controlled studies in multiethnic populations.populations.

((PeuskensPeuskens et al, 1997 et al, 1997) )

Clinical Factors :Clinical Factors : Presence of previous attemptsPresence of previous attempts Greater lethality of attemptsGreater lethality of attempts Hopelessness (comorbid or postpsychotic Hopelessness (comorbid or postpsychotic

depression)depression) Substance abuse (impulsivity , social isolation) Substance abuse (impulsivity , social isolation) Early age of onsetEarly age of onset Long duration of illnessLong duration of illness Long duration of index hospitalizationLong duration of index hospitalization Frequent hospitalizations and relapsesFrequent hospitalizations and relapses Use of high doses of antipsychotic medications Use of high doses of antipsychotic medications Lack of social support Lack of social support Positive F/H of suicide or depressionPositive F/H of suicide or depression

(Kasckow et al , 2011)(Kasckow et al , 2011)

Majority of suicides in schizophrenia are Majority of suicides in schizophrenia are within the first 10 years after illness onset within the first 10 years after illness onset

50% occur within the first 2 years. 50% occur within the first 2 years. Not only following initial diagnosis, but Not only following initial diagnosis, but

more likely to happen within the first few more likely to happen within the first few weeks or months after a hospital weeks or months after a hospital discharge. discharge.

For example, 80% of patients with For example, 80% of patients with schizophrenia who committed suicide did schizophrenia who committed suicide did so while in the hospital or within 6 so while in the hospital or within 6 months of discharge. months of discharge.

(Montross et al , 2005)(Montross et al , 2005)

Postpsychotic depressionPostpsychotic depression Symptoms improve while in the hospital :Symptoms improve while in the hospital :

gain a better awareness of their gain a better awareness of their life circumstancelife circumstance

experience a corresponding experience a corresponding increase in despairincrease in despair

increase the risk for suicide on increase the risk for suicide on discharge from hospital. discharge from hospital.

Increased monitoring with diligent clinical Increased monitoring with diligent clinical care from clinicians is needed.care from clinicians is needed.

(Palmer et al , 2005)(Palmer et al , 2005)

Systematic reviewSystematic review of world literature on patients of world literature on patients with schizophrenia or related conditions in which with schizophrenia or related conditions in which suicide was reported.suicide was reported.

Key risk factorsKey risk factors are: depression, previous suicide are: depression, previous suicide attempts, drug misuse, agitation or restlessness, attempts, drug misuse, agitation or restlessness, fear of mental disintegration, poor compliance with fear of mental disintegration, poor compliance with treatment and recent loss.treatment and recent loss.

Suicide risk related Suicide risk related Less to the core psychotic symptoms of the Less to the core psychotic symptoms of the

disorder, such as hallucinations and delusionsdisorder, such as hallucinations and delusions More to affective symptoms, agitation or More to affective symptoms, agitation or

restlessness, and to awareness that the illness restlessness, and to awareness that the illness was affecting mental functioning.was affecting mental functioning.

(Hawton et al , 2005)(Hawton et al , 2005)

Assessment and Initial ManagementAssessment and Initial ManagementPatients require a thorough assessment of :Patients require a thorough assessment of : Nature of their suicidal ideation or behaviourNature of their suicidal ideation or behaviour Suicide risk Suicide risk What factors are contributing to the suicidal What factors are contributing to the suicidal

symptoms. symptoms. Once this is accomplished, a clinical decision must be Once this is accomplished, a clinical decision must be

made as to the appropriate setting for treating the made as to the appropriate setting for treating the patient, i.e. either inpatient or outpatient. patient, i.e. either inpatient or outpatient.

The goals of treatment are to The goals of treatment are to reduce psychotic symptomsreduce psychotic symptoms reduce depressive symptomsreduce depressive symptoms alleviate the patient’s sense of demoralization and alleviate the patient’s sense of demoralization and

despairdespair install hopeinstall hope address any other issues such as substance abuse address any other issues such as substance abuse

and anxiety disorders.and anxiety disorders.(Mamo , 2007) (Mamo , 2007)

Staff Education in the Management of Staff Education in the Management of the Suicidal Patient with the Suicidal Patient with

SchizophreniaSchizophreniaMedical staff should be well aware of :Medical staff should be well aware of : How best to interact with a suicidal patient How best to interact with a suicidal patient

with schizophrenia. with schizophrenia. Risk factors include poor relationships with Risk factors include poor relationships with

the staff and difficulty acclimatizing to the the staff and difficulty acclimatizing to the ward environment.ward environment.

Ready to deal with patients’ anxiety and Ready to deal with patients’ anxiety and despair. despair.

More (More (withdrawn or paranoidwithdrawn or paranoid) patient ) patient should be regarded as one having an should be regarded as one having an increased risk of suicide.increased risk of suicide.

(Pompili(Pompili et al , 2003) et al , 2003)

Patients are more likely to express Patients are more likely to express ambivalenceambivalence about leaving the security about leaving the security of the hospital and needed a great deal of the hospital and needed a great deal of reassurance and support. of reassurance and support.

““Terminal Malignant Alienation”Terminal Malignant Alienation”fluctuating suicidality fluctuating suicidality excessive demandsexcessive demandsdistancing from the staffdistancing from the staffrejection rejection

It is important for staff to maintain good It is important for staff to maintain good morale in these situations.morale in these situations.

(Saarinen et al , 1999)(Saarinen et al , 1999)

Prevention optionsPrevention options

Improved recognition of Improved recognition of vulnerabilityvulnerability

The fact that suicide is a relatively The fact that suicide is a relatively rare event has hampered not only rare event has hampered not only the study of disease-specific risk the study of disease-specific risk factors, but also the generation of factors, but also the generation of risk assessment tools. risk assessment tools.

The majority of suicide victims are The majority of suicide victims are thought of as low risk at prior thought of as low risk at prior psychiatric evaluation. psychiatric evaluation.

Psychosocial ModalitiesPsychosocial Modalities An An (integrated approach)(integrated approach) using several using several

psychosocial modalities is regarded as psychosocial modalities is regarded as standard practice in treating patients with standard practice in treating patients with schizophrenia.schizophrenia.

2-year trial, which compared an integrated 2-year trial, which compared an integrated biomedical/psychosocial treatment with biomedical/psychosocial treatment with standard pharmacotherapy and case standard pharmacotherapy and case management in patients with recent-onset management in patients with recent-onset schizophrenia, has also supported the use schizophrenia, has also supported the use of integrated care as a way to improve of integrated care as a way to improve outcomes, including positive and negative outcomes, including positive and negative symptom outcomes.symptom outcomes.

(Grawe et al , 2006)(Grawe et al , 2006)

Other approaches include :Other approaches include : Supportive employmentSupportive employment Family interventionFamily intervention PsychoeducationPsychoeducation Assertive community treatmentAssertive community treatment Social skills training Social skills training Cognitive behavioural treatment; to Cognitive behavioural treatment; to

improve insight, positive symptoms improve insight, positive symptoms and depressive symptoms and also and depressive symptoms and also suicidal behaviour.suicidal behaviour.

(Bateman et al , 2007)(Bateman et al , 2007)

Pharmacological ApproachesPharmacological Approaches

First-Generation AntipsychoticsFirst-Generation Antipsychotics Successful in treating positive symptoms, not Successful in treating positive symptoms, not

necessarily associated with a decreased necessarily associated with a decreased suicide risk. suicide risk.

The suicide rates determined in 1975 and in The suicide rates determined in 1975 and in 1992 indicate that there was no appreciable 1992 indicate that there was no appreciable change, despite the increasing use of change, despite the increasing use of antipsychotics during this time period.antipsychotics during this time period.

In general, no clear dose-effect relationship In general, no clear dose-effect relationship with suicidal behaviour has been found for with suicidal behaviour has been found for first-generation antipsychotic medications. first-generation antipsychotic medications.

(Axelsson et al , 1992) (Axelsson et al , 1992)

More severely ill patients are receiving More severely ill patients are receiving the higher doses and there may be more the higher doses and there may be more adverse effects (extrapyramidal adverse effects (extrapyramidal symptoms) symptoms)

The higher rate of extrapyramidal The higher rate of extrapyramidal adverse effects observable with higher adverse effects observable with higher doses can be associated with dysphoria, doses can be associated with dysphoria, worsening subjective distress, agitation worsening subjective distress, agitation and suicidal behaviour.and suicidal behaviour.

(Cem Atbaşoglu et al , 2001)(Cem Atbaşoglu et al , 2001)

Second-Generation AntipsychoticsSecond-Generation Antipsychotics Appear to be more effective in reducing Appear to be more effective in reducing

suicidal risk. suicidal risk. No prospective, randomized, controlled No prospective, randomized, controlled

studies comparing the effect of first- and studies comparing the effect of first- and second-generation antipsychotic drugs on second-generation antipsychotic drugs on suicidal behavioursuicidal behaviour

One small retrospective study suggested One small retrospective study suggested that patients that patients attempting suicideattempting suicide were were more likely to be taking first-generation more likely to be taking first-generation antipsychotic medication, while antipsychotic medication, while non-non-attemptersattempters were more likely to be taking were more likely to be taking second-generation antipsychotic agents.second-generation antipsychotic agents.

(Altamura et al , 2003)(Altamura et al , 2003)

Two meta-analyses examined rates Two meta-analyses examined rates of suicide attempts or completed of suicide attempts or completed suicide from randomized, double-suicide from randomized, double-blind, placebo-controlled studies blind, placebo-controlled studies involving either risperidone, involving either risperidone, quetiapine or olanzapine treatment: quetiapine or olanzapine treatment: no differences were noted. no differences were noted.

(Storosum et al , 2003)(Storosum et al , 2003)

Clozapine was first reported to reduce rates Clozapine was first reported to reduce rates of suicidality in a study among 88 of suicidality in a study among 88 treatment-refractory patients with treatment-refractory patients with schizophrenia or schizoaffective disorder. schizophrenia or schizoaffective disorder.

In that trial, in the 2 years prior to initiation In that trial, in the 2 years prior to initiation of clozapine therapy, 22 suicide attempts of clozapine therapy, 22 suicide attempts were reported, while in the 2 years after the were reported, while in the 2 years after the start of clozapine treatment, the rate of start of clozapine treatment, the rate of suicide decreased by 88%.suicide decreased by 88%.

(Modestin et al , 2005)(Modestin et al , 2005)

Treating Depressive Symptoms in Treating Depressive Symptoms in Patients with SchizophreniaPatients with Schizophrenia

(SSRIs) were the most frequently (SSRIs) were the most frequently prescribed antidepressants, and the prescribed antidepressants, and the preferred combination with second-preferred combination with second-generation antipsychotic. generation antipsychotic.

Interestingly, one-fourth of practicing Interestingly, one-fourth of practicing psychiatrists rarely or never psychiatrists rarely or never prescribed antidepressant prescribed antidepressant medications in patients with medications in patients with schizophrenia.schizophrenia.

American Psychiatric Association American Psychiatric Association guidelines for the treatment of guidelines for the treatment of depression in patients with depression in patients with schizophrenia 2003schizophrenia 2003 recommend that recommend that clinicians use antidepressant medications clinicians use antidepressant medications for co-morbid syndromal major for co-morbid syndromal major depressive disorder; this also applies to depressive disorder; this also applies to patients with schizoaffective disorder. patients with schizoaffective disorder.

The guidelines state that an The guidelines state that an antidepressant should be used when the antidepressant should be used when the major depressive disorder is severe, major depressive disorder is severe, when it causes significant distress or if it when it causes significant distress or if it interferes with functioning. interferes with functioning.

Clinicians should maximize the dose and Clinicians should maximize the dose and duration of antipsychotic medications duration of antipsychotic medications first, especially if patients are taking first, especially if patients are taking second-generation antipsychotic second-generation antipsychotic medications, since second-generation medications, since second-generation agents may have antidepressant agents may have antidepressant properties. properties.

The clinician should also be alert to the The clinician should also be alert to the possibility of pharmacokinetic possibility of pharmacokinetic interactions. As an example, clozapine interactions. As an example, clozapine and fluvoxamine can exhibit significant and fluvoxamine can exhibit significant interactions.interactions.

(Furtado et al , 2009)(Furtado et al , 2009)

SertralineSertraline : for patients with remitted : for patients with remitted schizophrenia and major depressionschizophrenia and major depression

Fluoxetine Fluoxetine : two studies also showed no : two studies also showed no benefit over placebo in the treatment benefit over placebo in the treatment of depressive symptoms.of depressive symptoms.

FluoxetineFluoxetine : slight and statistically : slight and statistically significant decrease in depressive significant decrease in depressive symptoms. symptoms.

FluvoxamineFluvoxamine showed a positive effect showed a positive effect on negative symptoms only. on negative symptoms only.

CitalopramCitalopram : salutary effect on : salutary effect on severity of illness and subjective severity of illness and subjective sense of wellbeing, decreased the sense of wellbeing, decreased the frequency of aggressive incidents in frequency of aggressive incidents in 19 chronically violent patients with 19 chronically violent patients with schizophrenia. schizophrenia.

Suicidal behaviour was not directly Suicidal behaviour was not directly assessed in these trials.assessed in these trials.

(Zisook et al , 2010)(Zisook et al , 2010)

Clinical implicationsClinical implications

So how can research expand So how can research expand our knowledge of the risk our knowledge of the risk factors in this group and factors in this group and what can clinicians do to what can clinicians do to

improve the care and improve the care and management of their management of their

patients? patients?

All staff should receive All staff should receive formal formal trainingtraining in the recognition and in the recognition and management of suicide every 3 management of suicide every 3 years. years.

Prospective studiesProspective studies with strict with strict diagnostic criteria, suitable control diagnostic criteria, suitable control groups and blind ratings. groups and blind ratings.

Longitudinal studiesLongitudinal studies would allow would allow a more complete analysis of a more complete analysis of contributing risk factorscontributing risk factors

Greater evaluation of the impact of Greater evaluation of the impact of drug and psychological treatments on drug and psychological treatments on suicide suicide

Training should emphasize the Training should emphasize the importance of addressing comorbid importance of addressing comorbid conditions that heighten risk, as conditions that heighten risk, as depression and loss of functioning.depression and loss of functioning.

Need for good communication between Need for good communication between the patient's multi-disciplinary team, the patient's multi-disciplinary team, general practitioner, carers and general practitioner, carers and relativesrelatives

It is essential we try to implement It is essential we try to implement these kinds of proposals in both these kinds of proposals in both

future research and current future research and current practice given the fact that suicide practice given the fact that suicide

in schizophrenia remains one of in schizophrenia remains one of the greatest unmet challenges for the greatest unmet challenges for

psychiatrypsychiatry