Suicide in schizophrenia

Abstract

Schizophrenia is a disorder with an estimated suicide risk of 4–5%. 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

Figure 1. Important risk and protective factors for suicide in schizophrenia.

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 6 months: 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 (Box 1)[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.

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 (Box 2)[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 40 s. 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 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 4–5% [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].

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 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 1 week 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]. Figure 1 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 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 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]. Heilä et al. 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 et al. reported that schizophrenic patients with a 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 16 years has been associated with an increased risk of suicide (before the age of 35 years) 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 patient’s 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 importance when evaluating the suicide risk. Compliance with treatment, which is related to the patient’s 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 one’s 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 one’s 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 [45,90–92]. 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 (16–32 years) 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 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 [99–101]. 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 [103–105]. 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].

Dysfunctions in the hypothalamo–pituitary–adrenal (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 underlying 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 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 antipsychotic 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 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 patient’s 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 1 million cases per year and an enormous social and economic burden worldwide. 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.

Box 1. 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 patient’s 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 1 month 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.

Box 2. 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 one’s 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].

Box 3. Clinical assessment of suicide risk.

• • Assessment of risk factors, especially if there is a recent suicide attempt.

• • 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.

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.

Acknowledgements

The authors thank Johannes Kriisa for help with the figure.

Financial & competing interests disclosure

Erik G Jönsson 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.