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Suicide in schizophrenia
Expert Rev. Neurother. 10(7), 11531164 (2010)

Andreas Carlborg1,
Kajsa Winnerbck1,
Erik G Jnsson1,
JussiJokinen1 and
Peter Nordstrm1
Karolinska University Hospital,
Stockholm, Sweden

Author for correspondence:

Karolinska University Hospital,
Department of Clinical Neuroscience,
Karolinska Institutet,
17176Stockholm, Sweden
Tel.: +46 858 733 535
Fax: +46 830 3706
andreas.carlborg@sll.se
1

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Schizophrenia is a disorder with an estimated suicide risk of 45%. Many factors are involved
in the suicidal process, some of which are different from those in the general population. Clinical
risk factors include attempted suicide, depression, male gender, substance abuse and
hopelessness. Biosocial factors, such as a high intelligence quotient and high level of premorbid
function, have also been associated with an increased risk of suicide in patients with schizophrenia.
Suicide risk is especially high during the first year after diagnosis. Many of the suicides occur
during hospital admission or soon after discharge. Management of suicide risk includes both
medical treatment and psychosocial interventions. Still, risk factors are crude; efforts to predict
individual suicides have not proved useful and more research is needed.
Keywords : attempted suicide risk factor schizophrenia suicidal behavior suicide suicide risk treatment

Schizophrenia

Schizophrenia is a devastating psychiatric disorder affecting approximately 1% of the population

worldwide during a lifetime. The onset of the illness occurs relatively early in life, usually in the
late teens or early adulthood, and most patients
have long-lasting adverse effects. Schizophrenia
is a clinical syndrome diagnosed on the basis
of symptom profiles, and is characterized by a
constellation of symptoms of psychosis, such as
abnormalities in the perception or expression
of reality, as well as negative symptoms, such
as affective flattening and avolition. Cognitive
deficits are also usually present, and the symptoms must have persisted continuously for a
least 6months: however, schizophrenia cannot
be diagnosed if symptoms of mood disorder are
present or the symptoms are the direct result of a
medical condition or substance abuse (Box1) [201] .
The specific causes of schizophrenia are not
known and combinations of several factors are
likely to be involved. Genetic factors play a major
role in the development of the disease[1] , and environmental factors are also of importance. These
latter factors include a history of obstetric complications, such as asphyxia [2] and prematurity [3] .
Advanced paternal age is also considered to be a
risk factor [4] , and birth during the spring and
late winter also increases the risk [5] . Prenatal viral
infections [6] , serious viral infections of the CNS
during childhood [7] , migrant status and urban
rearing [8] , and a lifetime history of cannabis
use[9] are other well-known risk factors.
10.1586/ERN.10.82

Contrary to previous interpretations, the incidence and prevalence of schizophrenia show

marked variation between sites. For example,
migrants have an increased incidence and prevalence of schizophrenia, and exposures related to
urbanicity, economic status and latitude are also
associated with various frequency measures[10] .
Men have a higher risk than women [11] , and
a recent review concluded that men have a
40% higher incidence of schizophrenia than
women[12] .
Suicide

Suicide is defined as a self-inflicted death

with evidence that the person intended to die
(Box2)[13] . Suicide is among the leading causes of
premature death in the world and it is estimated
that approximately 1 million people die by suicide every year [202] . Suicide rates vary according
to region, gender, age, time and ethnic origin,
and also according to death registration practices. The annual suicide rate in the world is
14.5 out of 10,0000 (in 2000), which is equal to
one suicide every 40s. Suicide is approximately
three- to four-times more common in men than
in women [202] . Suicide rates vary between different regions, and underestimation of suicide
rates is common due to under-reporting, lack of
epidemiological data and misclassification [14] . It
has been estimated from psychological autopsies
that more than 90% of those dying by suicide
have a diagnosable psychiatric disorder at the
time of death, and approximately 60% of the

2010 Expert Reviews Ltd

ISSN 1473-7175

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Carlborg, Winnerbck, Jnsson, Jokinen & Nordstrm

Box1. Definition of schizophrenia.

According to the revised fourth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-TR) [201] , to be diagnosed
with schizophrenia, three diagnostic criteria must be met:
Characteristic symptoms
Two or more of the following, each present for much of the time during a 1-month period (or less, if symptoms remitted with treatment):
Delusions
Hallucinations
Disorganized speech, which is a manifestation of formal thought disorder
Grossly disorganized behavior (e.g., dressing inappropriately, crying frequently) or catatonic behavior
Negative symptoms: affective flattening (lack or decline in emotional response), alogia (lack or decline in speech) or avolition (lack or
decline in motivation)
If the delusions are judged to be bizarre, or if hallucinations consist of hearing one voice participating in a running commentary on the
patients actions or of hearing two or more voices conversing with each other, only that symptom is required for diagnosis. The speech
disorganization criterion is only met if it is severe enough to substantially impair communication.
Social/occupational dysfunction
For a significant portion of the time since the onset of the disturbance, one or more major areas of functioning such as work,
interpersonal relations or self-care, are markedly below the level achieved prior to onset.
Duration
Continuous signs of the disturbance persist for at least 6 months. This 6-month period must include at least 1month of symptoms (or
less, if symptoms remitted with treatment).
Schizophrenia cannot be diagnosed if symptoms of mood disorder or pervasive developmental disorder are present, or the symptoms are
the direct result of a general medical condition or a substance, such as abuse of a drug or medication.

suicides occurred in relation to depressive disorders. Other psychiatric disorders at high risk for suicide include schizophrenia,
substance abuse, alcoholism and personality disorders [15] .
Suicide in schizophrenia

Suicide is a major cause of death among patients with schizophrenia and was already described by Eugen Bleuler as early as
1911 as the most serious of schizophrenic symptoms [16] . The
lifetime prevalence of suicide in patients with schizophrenia has
been estimated to be ten-times higher than among the average
population [17] . Earlier research has suggested suicide rates of
up to 13% among patients with schizophrenia [18] , but more
recent studies, taking into account the variable suicide risk during a life span that is, a higher risk close to illness onset and
thereafter a declining risk report a lifetime suicide mortality of 45% [19,20] . Compared to the suicide risk in the general
population, a relatively higher suicide risk in schizophrenia has
been found in younger age groups [21] . Over time, a reduction
in the suicide rate among patients with schizophrenia has been
reported, similar to that in the general population [22] , although a
recent meta-analysis suggests that the mortality gap between the
general population and patients with schizophrenia has increased
in recent decades [23] .
The excess mortality in schizophrenia is caused more by natural
than unnatural causes of death, with cardiovascular disease and
cancer being the most common [21,24] . However, the specific causes
of death giving rise to excess mortality were suicides in males and
cardiovascular disease in females in a Swedish population-based
study [21] . Aside from suicide, unnatural causes of death, such
as accidents, are more common among patients diagnosed with
schizophrenia than in the general population [21,25,26] .
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Despite the high suicide frequencies in patients with schizophrenia when compared with the general population, the real
number of patients eventually dying by suicide is low, indicating
the importance of external risk factors and a predisposition to suicidal behavior that is independent of the main psychotic disorder.
For example, an acute social crisis in a patient with schizophrenia
appears to be the most proximal stressor leading to suicidal behavior. Several factors influence this interaction: personality traits,
such as aggression and impulsivity, may be important [27,28] , in
addition to gender, genetic and environmental factors [27,29] .
The clinical assessment of suicide risk is a difficult and demanding task in everyday clinical work, given the many factors involved
in the suicidal process and the limited specificity of clinical suicide
predictors [18] . However, identification of risk factors is necessary
for predicting and preventing suicide, although few clinical suicide
assessment tools for schizophrenic patients live up to reasonable
expectations [30] .
Risk factors for suicide in schizophrenia

The risk of suicide in patients with schizophrenia is considered to

be highest in the early course of the illness, especially within the
first year of illness [20,31,32] . Studies with a first-episode cohort and
covering a period close to the onset of illness usually have higher
estimates of excess mortality from suicide than studies with longer
periods of follow-up [26] . However, hitherto, most studies have
been retrospective in nature and there is a demand for prospective
studies. In a recent prospective Finnish study, these earlier results
were confirmed, finding that a large majority of the suicides took
place during the first years of the illness [33] . White ethnicity has
been associated with a higher suicide risk [34] . To date, the results
from meta-analyses are inconclusive as to how the age at onset of
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Suicide in schizophrenia

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Box2. Classification of suicidal behavior.

Suicide is defined as a self-inflicted death with evidence (either explicit or implicit) that the person intended to die.
Suicide attempt is defined as self-injurious behavior with a non-fatal outcome accompanied by evidence (either explicit or implicit) that
the person intended to die.
Suicide ideation is defined as thoughts serving the agents of ones own death. It may vary in seriousness depending on the specificity
of suicide plans and the degree of suicidal intent [13] .
Deliberate self-harm is defined as willful self-inflicting of painful, destructive or injurious acts without intent to die [149] .

symptoms affects the suicide risk [34] , although two recent studies
found a higher suicide risk in patients falling ill at older ages[32,35] .
One explanation for the increased risk of suicide associated with
increased age at onset of illness might be the stress these patients
face, having established themselves during early adult years with
a family and occupation, and suddenly facing the deterioration in
function and health that the disorder brings.
Despite the risk of suicide being highest in the early phases of the
illness, the risk appears to accumulate over a long period of time[36] ,
and it is considered to be high at any point in time during the course
of the illness [37] . The suicide risk is especially high in relation to
hospitalization, which stresses the importance in clinical practice
of paying extra attention during this period. It has been estimated
that a third of the suicides among patients with schizophrenia occur
during admission or within 1week after discharge from hospital.
Several studies have reported a peak of suicide risk during these
periods [24,38,39] , indicating the importance of an immediate assessment of the suicide risk after admission and proper follow-up and
out-patient treatment immediately after discharge from hospital.
However, a recent population-based study reports that the suicide
risk for schizophrenia was relatively constant during the first year
following discharge from hospital [40] . The number of psychiatric
admissions itself has been associated with a higher risk of suicide and
has been suggested to be indicative of the severity of illness[38,41,42] .
A recent study reported a relationship between post-discharge suicide
and the psychiatrists gender and age, indicating a potential need for
quality improvement among subgroups of mental health professionals. Demand for research into this topic has been made[43] . During
the last few decades there have been changes in health systems, with
significant reductions in in-patient capacity. These changes have
been suspected to be an important factor in the rising mortality
seen in patients with schizophrenia [44,45] . However, the effect of the
reduction in in-patient capacity on the suicide rate remains unclear
due to conflicting results [46] . Figure1 summarizes the important risk
and protective factors for suicide in schizophrenia.
The articles in this review have been searched for on PubMed
using the keywords suicide AND schizophrenia. The inclusion
of relevant papers has been made by choice of the authors on the
basis of their expertise in the field. Hence it is not a comprehensive
review, but rather a selective review based on the extensive clinical
experience of the authors.
Attempted suicide in schizophrenia

In most studies, a history of self-harm or suicide attempts is the

strongest risk factor for suicide [47] . A history of attempted suicide significantly increases the risk of suicide among patients with
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schizophrenia [34,48,49] , and is reported to be the strongest clinical

risk factor for suicide [49] . Compared with other psychiatric disorders coexistent with a suicide attempt, schizophrenia substantially
influences the overall risk and temporality for completed suicide[50] .
A recent study suggests that attempted suicide is an especially strong
risk factor for suicide among male schizophrenic patients [48] .
Attempted suicide is common among patients with schizophrenia,
with estimates ranging from 20 to 40% [46] . The methods used are
often more violent and lethal than suicide attempts in the general
population, suggesting a higher intent to die [51,52] . Depression is an
important risk factor for attempted suicide in schizophrenia [53,54] .
One review examining risk factors for deliberate self-harm (i.e.,
attempted suicide and similar potentially harmful acts in which
motives other than dying may have been more prominent) found
five significant variables: past or recent suicide ideation, previous
deliberate self-harm, past depressive episodes and a higher mean
number of psychiatric admissions [55] . Suicidal ideation of a past
and recent nature has also been considered a risk factor for suicide,
although the conclusions drawn from studies examining suicide
threats as a predictor for future suicide have been contradictory [34] .
Concurrent depression & suicide risk

More than half of all people dying by suicide have a diagnosable

depression at the time of suicide [49] , and intermittent depressive
disorders are common among patients with schizophrenia [56] .
Having a depressive disorder is suggested to act as a trigger for suicidal behavior in vulnerable patients with schizophrenia [57] , and a
history of past and present depressive disorders shows a strong association with suicide [34] . Therefore, the assessment of symptoms of
depression is important for these patients, and also, in the event of a
depressive disorder, sufficient treatment of the depression. However,
depression can easily be missed in patients with schizophrenia
because symptoms of depression can be confused with negative
symptoms of psychosis or side effects of neuroleptic medication[58] .
Along with a coexisting depression, the feeling of hopelessness has
been shown to be an important risk factor for suicidal behavior
in schizophrenia [59] , and the importance of hopelessness as a risk
factor remains even without a concurrent depression [56] .
Comorbid substance abuse & suicide risk

Substance abuse is common in individuals with schizophrenia, particularly in men. Nearly 50% of patients with schizophrenia have a
substance-abuse-related disorder at some point during their illness.
In a review, drug abuse was reported to considerably increase the risk
of suicide [34] . These authors could not find any association between
alcohol abuse and suicide risk. Limosin and coworkers reported that
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Adherence to
treatment

Restriction of
means for suicide

Living with family/

social support

Adequate
medication

Prior attempted suicide

Concurrent depression

Protective factors
Male gender

Hopelessness

Impulsivity

Substance abuse
Recent onset of illness

Clinical risk
factors

Suicide

Biosocial
risk factors

High number of
hospital admissions

Family history of suicide

High intelligence quotient
High level of education

Recent hospital
discharge/admission

White ethnicity

Awareness of illness

Figure1. Important risk and protective factors for suicide in schizophrenia.

illicit drug use, in contrast to alcohol abuse, was one of four significant independent risk factors for suicide [60] . Substance abuse has
also been associated with impulsiveness and suicidality [61] . Heil
etal. reported that alcoholism was found among a fifth of suicide
victims with schizophrenia, and the proportion of comorbid alcohol
abuse was highest among middle-aged men [37] .
Besides alcohol, cannabis is the most frequently abused drug
among patients with schizophrenia [62] . Drug abuse, particularly of cannabis, is frequent among patients with first-episode
schizophrenia, and the age of onset of schizophrenia appears to
be lower among cannabis abusers compared with both cannabis
non-abusers and alcohol abusers [63,64] . Cannabis use appears to
be associated with an increased risk for schizophrenia [65] .
Comorbidity between schizophrenia and substance abuse could
lead to consequences such as noncompliance with medication, loss
of control, violence and economic problems. As a result, worsened
psychotic symptoms and increased use of psychiatric services has
been reported in schizophrenic patients with concurrent substance
abuse. However, the studies have reported conflicting results. Miller
and coworkers reported that cannabis use was a risk factor for nonadherence to medication and dropout from treatment [66] . Cantwell
reported that substance-abusing psychotic patients were younger,
more likely to be men and had an earlier age at psychosis onset[67] .
No marked difference was found with regard to symptoms, social
function and service use compared with nonabusive schizophrenic
patients. Nor did Gut-Fayand and coworkers report any marked
effects on symptoms, social functioning and service use between
substance-abusing and non-abusing patients with schizophrenia [61] . Zisook etal. reported that schizophrenic patients with a
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history of substance abuse did not have more symptoms and were not
more impaired than schizophrenic patients who had never abused
drugs[68] . However, an association has been reported between dual
diagnosis and homelessness [69,70] . Other studies report that patients
with severe mental illnesses who had substance abuse spent more days
in hospital [71], have higher rates of anxiety, depression and hallucinations [72] and were more likely to report aggression or hostile behavior [73] . An association between violent crime and substance abuse
has also been reported among patients with schizophrenia [74,75] .
Psychosocial factors & suicide risk

Several personal and social factors have been found to influence the
risk of suicide among patients with schizophrenia. A high intelligence
quotient has been associated with an increased risk of suicide[76,77], as
well as a high level of education [34,35,78] . Good school performance
at the age of 16years has been associated with an increased risk of
suicide (before the age of 35years) in persons who develop psychosis,
whereas in persons who do not develop psychosis, it is associated with
a lower suicide risk [79] . Higher education may contribute to a greater
sense of loss due to the illness and may, therefore, increase the suicide
risk [80] . The concept of insight that is, the patients awareness of
the disease and the need for treatment, as well as the consequences
of the disease have been thoroughly investigated and suggested
to be associated with an increased risk of suicide. However, this
association is only valid if the awareness leads to hopelessness[81,82] .
These findings suggest that a person with a high level of premorbid
functioning facing the deterioration of health following the disease
has an increased risk of suicide. An assessment of the awareness
of illness, along with feelings of hopelessness, is, therefore, of vital
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Suicide in schizophrenia

importance when evaluating the suicide risk. Compliance with

treatment, which is related to the patients awareness of the need
for treatment, is crucial over time to reduce the risk of attempted
suicide [83,84] and suicide [85,86] . Consequently, poor adherence to
treatment is an important risk factor for suicide [34] . Personality
traits such as aggression and impulsivity have been associated with
suicidal behavior in psychiatric patients when ratings of the objective severity of the depression or psychosis have also been taken into
account [27] . In patients with schizophrenia, an association between
impulsivity, but not with aggression, and suicidal behavior has been
reported[56,87] . Other social factors, such as living alone or not living
with ones family, and the experience of a recent loss, have been associated with an increased risk of suicide, indicating the importance of
social support; subsequent living with ones family might be a protective factor against suicide. Being married or single was not associated
with an increased risk of suicide in a recent meta-analysis [34] .
Gender & suicide risk in schizophrenia

Most studies report that male patients with schizophrenia have a

higher risk for suicide than females [34,88] . In the general population, the risk for suicide is higher in men than in women in most
countries [89] . One exception is China, where the suicide rates
for men and women are equal, or even higher for women [90] .
In general, the suicide rate is approximately three- to four-times
higher for men than for women [45,9092] . The gender difference
seems to be less marked among patients with schizophrenia. In
a review, the ratio for men compared with women was 1.57 [34] .
Perhaps the gender difference in the suicide rate is mainly driven
by the effect of gender in the general population without a history
of psychiatric disorders. Severe clinical conditions can override
some, but not all, of the gender effect. That might provide the
explanation as to why some studies found no gender difference in
suicide among schizophrenic patients [35,91] . However, the suicide
standardized mortality rate of schizophrenic patients is equal or
higher for women compared with men in some studies [21,24,25,60] .
Women who die by suicide appear to be older than men who die
due to the same cause. This may be related to the later age at the
onset of illness in females [93] . It is also possible that schizophrenia
affects the sexes differently. Salokangas found only small differences
in clinical conditions between the sexes [94] . However, with regard to
social conditions and work adjustments, men performed poorer than
women diagnosed with schizophrenia. Important predictive factors
for suicide in female, but not male, schizophrenic patients are a history of sexual abuse, intimate partner abuse and loss of children[95] ,
suggesting that risk factors might differ between the genders.
The methods of suicide vary between the genders. Men often
use more violent methods than women, such as hanging, shooting
and jumping from high places [36,93] . Young age (1632years)
appears to increase the risk of violent suicide in both sexes [37] .
Psychotic symptoms & suicide risk in schizophrenia

Schizophrenia is not a homogeneous illness, but a syndrome that

comprises of a wide variety of symptoms; consequently, there are
substantial differences in clinical symptom presentations between
patients, despite the need for certain core symptoms to make the
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diagnosis. The question is whether any of these symptoms are related

to suicidal behavior. Depression and hopelessness, which are not core
symptoms of schizophrenia, are important risk factors and have been
discussed earlier. Depression-related symptoms, such as agitation or
motor restlessness, as well as fear of mental disintegration [34] and
anxiety [96] , have been associated with suicide. Positive (hallucinations, delusions and disorganization) and negative symptoms of
schizophrenia have been investigated in association with suicide
risk in several studies, and the results have been conflicting. In a
meta-analysis, Hawton and coworkers reported that studies investigating command hallucinations and suicide risk showed significant
heterogeneity with both positive and negative associations[34] . No
overall association with suicide risk was reported. However, several
studies reported association between positive symptoms and suicide risk[77,97] , as well as attempted suicide in the context of command hallucinations [98] . An association between the total number
of positive symptoms and suicide risk has also been reported [76] .
Fewer studies have investigated the relationship between suicide
risk and negative symptoms in schizophrenia, and any association
remains unclear. In summary, the risk factors for suicide in schizophrenia appear to be less associated with typical core symptoms
of psychosis, such as delusions and hallucinations, but more with
depressive symptoms, such as agitation, hopelessness and feelings
of worthlessness [34] .
Biomarkers of suicide risk in schizophrenia

The biology of suicide includes a broad area of research comprising, among other things, studies on neurotransmitters, neuroendocrinology, neuroimaging and genetics. Most of the studies
involving biological research on suicide have focused on patients
with mood disorders.
Low concentrations of the cerebrospinal fluid (CSF) serotonin
metabolite 5-hydroxyindoleacetic acid (5-HIAA) have been associated with attempted suicide and death by suicide among patients
with depressive disorders [99101] . The relationship between the
major dopamine metabolite homovanillic acid in the CSF and
suicidal behavior has also been investigated, but without firm
evidence for an association [102] . An association between a low
CSF homovanillic acid:5-HIAA ratio and suicidal behavior and
intent has been reported [103105] . However, most of these patients
were diagnosed with depressive disorders, and only a few had a
diagnosis within the psychotic spectrum. Suicide attempters in
general are more impulsive than psychiatric controls[27] , and low
concentrations of CSF 5-HIAA have been associated with aggressiveness from a lifetime perspective, as well as with lethality of
suicide attempts [106,107] . Serotonin dysfunction, as measured by
CSF, has been linked to traits of aggressiveness and depression,
which may be clinical mediators of suicidal behavior, an important
risk factor for suicide in schizophrenia [108] . However, to date,
studies analyzing suicidal behavior and CSF monoamine metabolites in patients with schizophrenia are few in number, and, in the
largest study, no association was reported[109] . Platelet serotonin
and serum cholesterol concentrations have been associated with
suicidality in patients with their first episode of psychosis and have
been suggested to be useful biological markers of suicidality [110] .
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Dysfunctions in the hypothalamopituitaryadrenal (HPA)

axis, as measured by the dexamethasone suppression test, have
been reported to have predictive power for suicide in depressive
disorders[111] . Some studies have reported an association between
dysfunction of the HPA axis and suicidal behavior in patients with
schizophrenia [58,112] , whereas others have failed to detect such a
relationship[113,114] .
Epidemiological studies investigating genetic influences have suggested that there is a genetic basis to suicidal behavior [115] . It has been
suggested that these genetic influences are specific and independent
from the genetic factors implicated in predisposition to psychiatric
disorders in general [116] . Suicide and psychiatric illness in relatives
are general risk factors for suicide [77] , and the effect of a family
history of suicide is independent of the familial cluster of mental
disorders [117,118] . Genetic association studies on suicide have mainly
focused on serotonin-related genes. Meta-analyses have reported an
association between variants in the serotonin transporter [119] and the
tryptophan hydroxylase 1 (TPH1) genes [120], although the latter was
not associated within patient groups, suggesting that the association
between the TPH1 genes and suicide behavior was confounded by
association with the disease [121] . With regard to another frequently
analyzed gene, the serotonin transporter 2A (HTR2A), there seems
to be no firm evidence for an association [120,122] . In the area of less
well-studied genes, a report analyzing patients with schizophrenia
found an association between some genes involved in the HPA axis
and suicidal behavior [123] . Another study reported differences in
expression of the DARPP-32 gene, which is involved in dopamine,
and possibly serotonin, regulation, between schizophrenic patients
who died by suicide and due to other causes [124] . However, the
specificity of these findings is very low, and a lot of work remains to
be done until clinical benefits can be gained [125] . The last decade has
seen an increasing use of neuroimaging in schizophrenia research on
structural changes in the brains of patients. An association between
structural changes in areas such as the left orbitofrontal and superior
temporal gyrus [126] , as well as in the inferior frontal volume [127] ,
and suicidal behavior has been reported. However, more studies are
needed to expand our knowledge of biological mechanisms under
lying suicide in schizophrenia, and the clinical implications of these
findings are yet to be investigated.
Prevention & treatment of suicide risk in schizophrenia

Reducing the risk of suicide in patients with schizophrenia is of

vital importance, but it is challenging because of the many factors
involved. Suicide research has produced numerous false-negatives
and far too many false-positives to be useful in identifying which
schizophrenic patients require extraordinary suicide prevention
precautions [18] . However, the identification of risk factors is important for initiating preventive measures. The reduction of the number of new cases of individuals committing suicide is the ideal
method of protection and requires modification of a wide range of
social, economic and biological conditions to prevent members of
a population from becoming suicidal. This might include addressing factors such as reduction of poverty and promotion of general
health [128] . Restriction of the means for suicide is an important
part of preventive strategies and has been shown to be effective
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in the reduction of suicide [129] . Suicide prevention also includes

general preventive strategies, such as restricted availability of alcohol and drugs, barriers at bridges and observation by cameras at
railways, as well as suicide risk management for the specific individual. This involves the use of appropriate treatments including
medication, psychosocial interventions and psychotherapy [130] .
Early detection programs that bring patients with symptoms of
psychosis into treatment at lower symptom levels may also reduce
the suicide risk [131] .
There is little evidence in general that antipsychotic medication
has a suicidal preventive effect [46] . However, there is evidence
that long-term treatment with antipsychotic drugs is associated
with lower mortality in schizophrenia compared with no anti
psychotic treatment [132] . Clozapine in particular seems to reduce
the risk of suicide [132,133] and suicidal behavior [134] . However,
methodological questions have been raised concerning the results
reporting the antisuicidal properties of clozapine, and the validity
of these results needs to be confirmed in future studies [135] . In
addition to clozapine, the only other drug shown to prevent suicide
is the mood stabilizer lithium, used primarily in patients with
bipolar disorder [136] . However, the effect of lithium on suicidal
behavior among patients with schizophrenia is less clear, and it
is unknown whether this drug exerts antisuicidal effects among
these patients[137] .
Electroconvulsive therapy (ECT) is an effective treatment of
severe depression, and an acute risk of suicide has been cited as
one of the indications for the use of ECT in patients with depression[138] . ECT has been suggested to exert a profound short-term
beneficial effect on suicidality [139] . However, there is still no evidence for a direct reduction in completed suicide [140] and there is
also a lack of studies among patients with schizophrenia undergoing
ECT for the prevention of suicidal behavior. Concurrent depression is a very important risk factor for suicide in schizophrenia,
and recent studies have suggested an association between a general decline in suicide risk and usage of antidepressant medication[141,142] . Although the treatment of depression in schizophrenia
is crucial, the role of antidepressants in preventing suicide among
these patients has not been established [86] . However, antidepressants have been associated with lower all-cause mortality when used
in combination with antipsychotics [85] . To facilitate the clinical
assessment and treatment of suicide risk in schizophrenia, a

treatment algorithm and models showing different pathways to suicide

can be used [143,144] . This may be a valuable tool for the clinician.
See Box 3 for key issues in clinical assessment of suicide risk.
Together with proper medication, psychosocial interventions
and psychotherapy may also be important in addressing specific risk factors and help with coping skills. Bateman reported
that cognitive behavioral therapy decreased suicide ideation in
patients with schizophrenia [145] . However, to date, there is a lack
of empirical evidence on the impact of psychotherapy and related
issues, such as therapeutic relationship and counter transference,
on suicidal behavior in schizophrenia.
Since suicide risk has been found to be particularly high during
the first days after discharge from hospital, a focus on close monitoring and better psychosocial support may be needed during this
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Suicide in schizophrenia

period [146] . Psychosocial intervention has been found to increase

adherence among schizophrenic patients [83]. There is little doubt that
these interventions are helpful to improve quality of life, but a direct
antisuicidal effect is yet to be proven [147]. There is a need for large randomized clinical trials evaluating the effect of psychosocial treatment
on suicide and suicide attempt [129] . Investigation of schizophrenic
patients divided into subgroups according to their suicidal motivation has been suggested as one way to use appropriate differentiated
preventive and/or treatment measures against suicidal behavior [148] .
Expert commentary

Although patients with schizophrenia have the highest mortality

risk from suicide, and also high mortality from natural causes of
death, the absolute number of suicides is low, and the everyday assessment and prevention of suicide, in both the short- and long-term,
remains a difficult and demanding task for the clinician, as well as
for society in general. Many well-known risk factors are used for
predicting suicide among patients with schizophrenia. However,
their limited specificity makes the prediction of future suicide difficult. It is important to recognize that some risk factors among these
patients differ compared with risk factors in the general population.
Patients with schizophrenia die by suicide at an earlier age, often in
close proximity to the onset of illness, and a realistic awareness of
the deteriorative effects of the illness and a history of a high level of
premorbid function are distinctive and characteristic risk factors for
these patients. The suicide risk also appears to remain over a long
period of time and since schizophrenia is a chronic disorder, continuous assessment of the suicide risk is important. Comorbid depression
and substance abuse is common, and together with male gender and
a history of attempted suicide, these are all important risk factors
for suicide in schizophrenia. The diagnosis and proper treatment
of depression, with both medication and evidence-based psychotherapy, among these patients may be crucial in reducing the suicide
risk. Interventions to reduce substance abuse are also important and
constitute a major challenge in the clinical setting. Growing evidence
for the antisuicidal effect of clozapine places the focus on whether
or not the restrictions on the use of clozapine should be reassessed.
Use of adequate medication, continuous working on establishing adherence to medication and special vigilance at periods of
high risk are important. The reduction of the number of beds in
psychiatric hospitals observed in recent decades and the growing
mortality gap between patients with schizophrenia and the general
population have to be addressed and discussed with policy makers.
Although schizophrenia itself elevates the risk of suicide, it is the
presence of additional risk factors that further increase the patients
risk of suicide. Targeting these individuals at an extra high risk
with proper intervention is essential for reducing the overall suicide risk, and constant monitoring of suicide rates in schizophrenia
is essential when evaluating the effects of new interventions.
Five-year view

Despite advances in the treatment of psychiatric diseases in recent

decades and a general decline in suicides in the western world, suicide
is still a major health problem, with approximately 1million cases
per year and an enormous social and economic burden worldwide.
www.expert-reviews.com

Review

Box3. Clinical assessment of suicide risk.

Assessment of risk factors, especially if there is a recent
suicideattempt.
Assessment of current medication for treatment of psychoses
and depression.
If the risk of suicide is high, proper interventions should be
made, such as imminent follow-up in an outpatient setting or
admittance to hospital.

The mortality gap between the general population and patients with
schizophrenia turns the focus not only to the treatment of the psychiatric disorder itself, but also to somatic diseases and general health
interventions with population strategies. Suicide is a major challenge
among patients with schizophrenia and, because of the complexity of
suicidal behavior, it has become increasingly clear that an integrated
approach is needed to attack the problem. Empirically based intervention programs focusing on well-known risk factors, especially
for individuals with risk behaviors such as a history of attempted
suicide, as well as appropriate use of antipsychotic medication, might
help to reduce the mortality and suicide rate. For example, several studies have reported that the use of clozapine reduces suicidal
behavior among patients with schizophrenia. The development of
psychological interventions, inclusion of biological suicide research,
involving neurochemical and genetic phenotypes, development of
effective medical treatment and improvement of clinical risk markers of suicide are all important areas of research in the near future.
The importance of violent crime and neuropsychiatric diagnoses
among patients with schizophrenia as risk factors for suicidal behavior has not been investigated and remain important areas of research.
Clinical studies on suicide prevention are, however, often hindered
by methodological and ethical problems; for example, the evaluation
of risk factors often takes place a long time before suicide occurs
and these factors might have changed in the intervening period.
Therefore, there is a demand for large randomized clinical trials,
as well as prospective trials involving evidence-based approaches. It
is also of great importance that the development of evidence-based
interventions to prevent suicidal behavior is transferred into the
clinical setting and used by those working with patients at risk. The
use and development of functional brain imaging techniques make
it possible to investigate biochemical alterations and brain circuitry
in relation to suicidal behavior. The discovery of neurochemical correlates underlying suicidal behavior may open up new possibilities
for pharmacologically acting agents.
Acknowledgements

The authors thank Johannes Kriisa for help with the figure.
Financial & competing interests disclosure

Erik G Jnsson and Jussi Jokinen were partly financed by the Swedish
Research Council (K2008-62P-20597-01-3 and K2009-61P-21304-04-4,
respectively). The authors have no other relevant affiliations or financial
involvement with any organization or entity with a financial interest in or
financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.
No writing assistance was utilized in the production of this manuscript.
1159

Review

Carlborg, Winnerbck, Jnsson, Jokinen & Nordstrm

Key issues
Schizophrenia is an illness with a high risk of suicide, and the lifetime suicide risk is estimated at 5%.
The risk of suicide is highest during the first year after the onset of illness and increases in relation to admissions to and discharges from
the hospital. The risk of suicide remains over a long period of time.
Important risk factors are depression and hopelessness, a previous suicide attempt, male gender, poor adherence to treatment and
substance abuse.
High premorbid function, high intelligence quotient and a high level of education increase the risk of suicide.
An assessment of risk factors is essential to prevent suicidal behavior; however, the low predictive specificity for suicide makes the
prevention of future suicide difficult.
Treatment of depression and substance abuse in patients with schizophrenia is crucial in reducing the risk of suicide. A combination of
evidence-based psychosocial intervention and adequate medical treatment might help to reduce suicide rates.
Clozapine treatment seems to decrease the risk of suicide in patients with schizophrenia. There is a lack of studies among patients with
schizophrenia using electroconvulsive therapy and lithium in the prevention of suicide.
It is crucial that interventions are assessed empirically, and, if found to be effective, transferred into the clinical settings. Continuous
assessment of suicide risk is crucial and targeting high-risk individuals is essential.
Improvements in clinical risk markers for suicide are needed. Future research should focus on the many aspects of suicidal behavior,
with a scientific approach and evaluation.

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