A Ssessment and Treatment of Suicide Risk in Schizophrenia

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10.1586/14737175.8.1.51 © 2008 Future Drugs Ltd ISSN 1473-7175 51

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Assessment and treatment of

suicide risk in schizophreniaExpert Rev. Neurotherapeutics 8(1), 51–74 (2008)

Maurizio Pompili†,David Lester,Marco Innamorati,Roberto Tatarelli andPaolo Girardi† Author for correspondence

Department of Psychiatry,Sant’Andrea Hospital,Via di Grottarossa, 1035,00189 Roma, Italy

Tel.: +39 06 3377 5675

Fax: +39 06 3377 5342

[email protected];[email protected]

Schizophrenic patients at risk of suicide are more likely to be young, male, white, nevermarried, with post-psychotic depression, and a history of substance abuse and suicideattempts. Hopelessness, social isolation, awareness of illness and hospitalization are alsorelated to suicide risk. Deteriorating health with a high level of premorbid functioning, recentloss or rejection, limited external support, family stress or instability are other features thathave been reported in schizophrenic patients who commit suicide. Atypical antipsychotics,especially clozapine, have emerged as important tools in the therapeutic armamentarium.Psychosocial intervention and psychotherapy may play an important role in the managementof suicide risk, especially if such interventions help the patient face daily difficulties, lonelinessand conflicts inside the family.

KEYWORDS: risk factor • schizophrenia • suicide

The first reliable data on the incidence of sui-cide among patients with schizophrenia wasprovided by Miles who, after reviewing 34 studies, concluded that 10% of patients suf-fering from this disorder eventually commitsuicide [1]. A later review by Caldwell andGottsman estimated that 10–13% of schizo-phrenia patients commit suicide [2]. Inskip et al.

performed a meta-analysis for suicide among patients diagnosed with affective disorder, alco-holism and schizophrenia, and estimated thelifetime risk to be 6% for affective disorder, 7%for alcohol dependence and 4% for schizo-phrenia [3]. More recently, a new meta-analysisby Palmer et al. estimated that 5% of thepatients die by suicide [4], a figure that sur-prised many scholars [5]. Lester pointed out therole of the sex of schizophrenia patients whensuicide rates are taken into account (men have a much higher suicide rate than do women) andproposed lower estimates compared with the

ones routinely reported [6]. Warning signs for suicidal behavior among

schizophrenic patients were mentioned in theearly years of modern psychiatry. Kraepelin saidthat, “life is threatened only very slightly” inschizophrenics but noted that suicide occurredin the acute and chronic stages [7]. He thoughtthat negativism, inadequate diet and poorcooperation with treatment of concurrent med-ical disorders also contributed to the increasedmortality in schizophrenics.

In 1911, Bleuler recognized “the suicidaldrive” as the “most serious of all schizophrenicsymptoms” [8]. He calculated that schizo-phrenia was associated with an excess mortality of 1.4:1. Death resulted from the “indirectconsequences of psychosis: refusal of food,intentional or unintentional injuries, suicide,tuberculosis and other diseases resulting from

an unhygienic way of life”. Back in 1942,Lipschutz warned that every schizophrenicpatient is a potential suicide victim, and he dis-cussed the importance of the physical setting inprevention [9].

In 1961, Beisser and Blanchette investigated75 suicides committed in mental hospitals inCalifornia (USA) [10]. A diagnosis of schizophre-nia had been made in 45% of the suicides. Sui-cide was most common in cases where depres-sion was present. A total of 27% of thesesuicides occurred during the first month follow-ing admission and 62% during the first

6 months. Half of the patients had previously threatened to commit suicide and half hadattempted suicide in the past. In 89% of thecases, the method for suicide was hanging, and52% of the patients committed suicide whilethey were in isolation. The authors felt that thedanger of suicide was greater when the patient’sclinical condition deteriorated.

Recent times have witnessed comprehensive joint and collaborative efforts between scholarsto provide up-to-date information on the topic,

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52Expert Rev. Neurotherapeutics 8(1), (2008)

Review Pompili, Lester, Innamorati, Tatarelli and Girardi

review it and implement shared treatment guidelines [11,12]. A description of the issues surrounding suicide in schizophrenia are provided in BOX 1.

Search strategy

In order to provide a new and timely review of suicide inschizophrenia, we performed careful MedLine, Excerpta Med-ica and PsycInfo searches to identify papers and book chaptersin English during the period 1966–2007, and Index Medicusand Excerpta Medica prior to 1966. The search terms used were ‘suicid*’ (which comprises suicide, suicidal, suicidality andother suicide-related terms), ‘schizophreni*’, ‘inpatient or in-patient’, ‘outpatient’, ‘psychosocial treatment or rehabilitation’,‘social skill training’, ‘cognitive techniques’, ‘social support orsocial adjustment’, ‘rehabilitation counseling or social supportnetwork’, ‘prevention’ and ‘pharmacological treatment’ (allmolecules belonging to atypical antipsychotics were considered

in separate searches). Each term was also cross-referenced withthe others using the Medical Subjects Headings (MeSH)method. Subjects included in this study suffered from schizo-phrenia and other types of schizophrenia-like psychoses(schizophreniform and schizoaffective disorders).

The selection of trials for inclusion in the review was firstly performed by the principal reviewer (M Pompili) followed by a further independent (blind to each other) review by D Lester andM Innamorati after employing the search strategy described pre-viously. Where a title or abstract appeared to describe a trial eligi-ble for inclusion, the full article was obtained and inspected toassess relevance to this review based on the inclusion criteria. Weindependently decided whether these met the review criteria. No

blinding to the names of authors, institutions and journal of publication took place. Any discrepancies between the tworeviewers were resolved by consultations with senior authors(R Tatarelli and P Girardi). When this proved impossible, wesought further information and, in the interim, added these trialsto the ‘Awaiting assessment’ list. The reference list was furthermodified on the basis of comments from peer reviewers. Afterthese consultations, the authors focused the most recent refer-ences and extended their analysis to any relevant and key paperpublished prior to this period. This was decided unanimously assome studies, despite their age, remain relevant to present issues.

The timing of suicideIt has been estimated that life expectancy among schizophrenicpersons is shortened by 9–10 years [13,14] and that the excess inmortality is chiefly accounted for by suicide as well as cardio-vascular disease, probably caused by heavy smoking associated with metabolic disturbances such as hypercholesterolemia hypertriglyceridemia and diabetes [15–18].

Several studies have determined that the greatest risk for suicidein schizophrenia occurs during the first 10 years of illness [19,20].However, other studies have reported that suicide may occur at

any point during the course of illness [13,21,22], especially if theillness is severe and there are frequent relapses and rehospitali-zations [23]. Barak et al. investigated suicidality among elderly schizophrenic patients over a 10-year period and found that theincidence of suicide attempts was approximately 5%, less thanthe figures reported for their younger counterparts [24]. Heila et al. found no evidence suggesting a rising trend in suicides overtime [25], which contrasts with other studies that found a long-term rising trend in mortality, especially due to suicide during the deinstitutionalization process [26,27].

Risk factors

Researchers routinely report a similar profile for schizophrenicpatients at risk of suicide; that is being young and male (exceptin China where schizophrenia is more prevalent among women, who are more likely commit suicide than men [28]).Patients who commit suicide are generally white, unmarried,

have good premorbid function, have post-psychotic depression,and have a history of suicide attempts and substance abuse.This latter behavior complicates the management of the patientat risk of suicide [29].

Hopelessness, lack of social support and being socially iso-lated, along with a painful awareness of being ill and being subject to hospitalization are other important risk factors forsuicide in these patients. When health deteriorates in individu-als with good premorbid functioning, suicide can result fromthe awareness that performances previously achieved cannot bemaintained. Also, individuals who experience recent loss orrejections, along with limited support from their family andthe community, are at high risk of suicide. These patients usu-

ally fear further mental deterioration and experience excessivetreatment dependence or loss of faith in treatment.

Fenton et al. [30] and Fenton [31] described the high-risk patient as a young male, with a history of good adolescent func-tioning and high aspirations, late age at first hospitalization,higher intelligence, with a paranoid or nondeficit form of schiz-ophrenia, who retains the capacity for abstract thinking and who may be painfully aware of the impact of a deteriorating ill-ness on his aspirations and life trajectory. Consistent with thesefindings, Kuo et al. investigated risk factors for suicide among 78 schizophrenic patients in a case–controlled study andreported that suicide risk was associated with later age at onsetin addition to other risk factors [32].

In a recent investigation, Pompili and colleagues found thatsuicide attempts, hopelessness and self-devaluation were thethree variables most strongly associated with completed suicide[POMPILI M, LESTER D, GRISPINI A ET AL . SUICIDE IN SCHIZOPHRENIA : EVIDENCE FROM

A CASE–CONTROL STUDY (2007), SUBMITTED]. Another important risk fac-tor that emerged from this investigation was the presence of sleep disorder, a finding rarely reported hitherto. These authorsalso found a number of variables that in their sample consti-tuted factors associated with suicide risk, such as agitation andmotor restlessness (odds ratio [OR]: 3.66; 95% confidence



ReviewAssessment and treatment of suicide risk in schizophrenia

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interval [CI]: 0.95–14.02), self-devaluation (OR: 28.49; 95%CI: 3.15–257.40), hopelessness (OR: 51.00; 95% CI:7.56–343.72), insomnia (OR: 12.66; 95% CI: 0.95–14.02),mental disintegration (OR: 3.66; 95% CI: .95–14.02) and sui-cide attempt (OR: 3.66; 95% CI: 1.40–114.41). Poor adherenceto medications was also predictive of completed suicide in oursample of schizophrenia patients.

Hawton et al. provided a systematic review of risk factors forschizophrenia and suicide [33]. They identified 29 relevant stud-ies and seven robust risk factors including previous depressivedisorder (OR: 3.03; 95% CI: 2.06–4.46), previous suicideattempts (OR: 4.09; 95% CI: 2.79–6.01), drug misuse

(OR: 3.21; 95% CI: 1.99–5.17), agitation or motor restlessness(OR: 2.61; 95% CI: 1.54–4.41), fear of mental disintegration(OR: 12.1; 95% CI: 1.89–81.3), poor treatment adherence(OR: 3.75; 95% CI: 2.20–6.37) and recent loss (OR: 4.03;95% CI: 1.37–11.8). A reduced risk of suicide was associated with hallucinations (OR: 0.50; 95% CI: 0.35–0.71). Theauthors argued that command hallucinations were not an inde-pendent risk factor, but they increased the risk in those already predisposed to suicide. Overall, suicide was less associated withthe core symptoms of psychosis and more with affective symp-toms, agitation and an awareness that the illness was affecting mental function.

Box 1. Key issues surrounding suicide in schizophrenia.

Neurobiology

Low concentrations of the serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA) in cerebrospinal fluid (CSF) are associated with

suicidal behavior in patients with depressive illness and schizophrenia. Suicide attempters have been reported as having significantly

lower concentrations of CSF 5-HIAA at initial evaluation than non-attempters. These findings provide further evidence of the relation

between serotonergic dysfunction and suicide and suggest a role for drugs with serotonergic effects in schizophrenia. Hormones known

to be under serotonergic control, such as prolactin, are measured in peripheral blood after stimulation or inhibition of the serotonergic

(5-HT) receptors. Fenfluramine is a widely used serotonin probe. Total rapid eye movement sleep seems to be altered in suicidal

schizophrenic patients but there are contradictory findings on the nature of such sleep changes and their association with increased risk

of suicide [11]

Command hallucinations

Research has shown that comparing patients with and without command hallucinations yields no significant differences in rates of

suicidal or assaultive acts. Patients with hallucinations (regardless of type) are just as likely to report suicidal ideation as those not

experiencing hallucinations. It would seem that command hallucinations may play a role in the precipitation of suicide in some patients,

but firm statistical evidence is still lacking [201]. However, individuals who are already at risk for suicidal behavior (e.g., past attempters)

may be at increased risk for a suicide attempt when experiencing command hallucinations [202]

Awareness of illness

Taken together, research findings seem to suggest that awareness of illness is associated with increased suicide risk, but only if that

awareness leads to hopelessness. The severity of the hopelessness that a person with schizophrenia experiences seems contingent, at

least in part, on the level of premorbid functioning and the magnitude of the decline in functionality relative to that premorbid capacity.

Although general awareness seems not to predict suicide, there seems to be an awareness spectrum, whose elements may or may not

lead to suicide [62]

Apparent improvement

Unnatural calm, in otherwise agitated, suicidal individuals suggest that the patient has decided to commit suicide. Patients may have

solved their conflicts whether to live or die and may feel relieved to have opted for suicide as an escape from their anguish and

despair [49,203]

Approved leave from hospital

Data indicate that schizophrenic patients may kill themselves during approved leave from hospital. Arrangements with family and

friends may be useful to protect the patient while out of the hospital [49]

Substance abuse

The literature suggests that nearly 50% of patients with schizophrenia have a co-occurring substance use disorder, most frequently

alcohol and/or cannabis (at a rate approximately three-times higher than that of the general population). Patients with dual diagnoses

are highly prone to adverse outcomes in several domains: increased symptom severity, increased rates of hospitalization, infectious

illnesses, violence, victimization, homelessness, non-adherence to medication and poor overall response to pharmacologic treatment.

The increased suicide risk of substance-abusing schizophrenic patients could be the result of a cumulative effect of many factors or

events, such as the loss of remaining control through the consumption of psychotropic substances, noncompliance with antipsychotic

medication, presence of paranoia and depression. Substance abuse worsens both the symptoms and the prognosis of the illness and are

related to higher relapse rates [200]





Traditionally, positive symptoms have been less oftenincluded as risk factors for suicide in schizophrenic individuals.Nevertheless, the active and exacerbated phase of the illness, andthe presence of psychotic symptoms [22,34–36], as well as para-noid delusions and thought disorder [37,38], have been associated with a high risk of suicide. Patients with the paranoid subtypeof schizophrenia are also more likely to commit suicide [30,39].Suicides as a result of command hallucinations, although rare,have been reported in the literature [40]. Kelly et al. reported thata large proportion of their schizophrenic patients who commit-ted suicide had poor control of thoughts or thought insertion,loose associations and flight of ideas compared with those whodied from other causes [41].

Kreyenbuhl et al. found that schizophrenic patients seemedto have planned their suicide more often compared with those without the disorder [42]. Heila et al. reported that thesepatients had more frequently communicated their suicidalintent and had a lifetime history of suicide attempts compared

with other psychiatric patients [43]. Funahashi et al. found thatthe suicide risk in schizophrenia was higher in middle-bornchildren [44]. These authors also highlighted the role of anxiety associated with suicidal ideation in determining suicide risk.

It is crucial to assess suicidality in the clinical interview by assessing trait- and state-dependent risk factors [45]. The formerare factors that can potentially be modified, the latter, on theother hand, are factors that are unchangeable (BOX 2).

Unfortunately, analysis of risk factors for suicide often yieldstoo many false positives, that is, the recognition of individualsas potential suicide victims when in fact they will never try tokill themselves. Therefore, for suicide prevention there is a needto explore a patient’s personality and their inner pain and other warning signs for suicide.

Methods of suicide

Schizophrenic patients who commit suicide die from more vio-lent means [39,46,47]. Kelly et al. found that 73% of the individu-als of their sample committed suicide by violent methods suchas jumping from height, drowning, cutting, gunshot wounds orhanging [41].

Shields et al. recently reported that 14 of their 29 schizo-phrenic suicides used a firearm to kill themselves, and themajority used violent methods [48]. Shields et al. suggested thatthe choice of violent methods implies a more serious intent to

die, but the choice of method is also determined by the meansavailable to patients.Pompili et al. investigated the methods of suicide of 560

schizophrenic inpatients and reported that 129 died by hang-ing/strangulation, 52 by gunshot, 85 by poison, 72 by drown-ing, 103 by jumping from a high place, 12 by carbon monox-ide, 6 by self-cutting, 60 by jumping in front of a train or a carand 41 by other methods [49].

Suicide among inpatients with schizophrenia

A comprehensive review of suicide among inpatients withschizophrenia that considered studies with variable follow-up

(from 1 to 26 years) yielded a suicide rate of 6.8%[49]

.Nordentoft and Mortensen, in a recent Danish register-based study, found that 37% of men and 57% of women whocommitted suicide had a history of admission to psychiatrichospitals [50], confirming previous reports that suicide risk isassociated with a history of admission to psychiatric hospitals.The risk of suicide peaked not only shortly after discharge, asreported in the literature [26,51–54], but also shortly afteradmission. For this reason, Hunt et al. stressed the role of ward safety and close supervision in both inpatient and com-munity settings, especially in cases of reduced adherence totreatment [29].

Sinclair et al., in their study of schizophrenia inpatients,

found that depressive symptoms and ongoing suicidal ideation were more predictive of suicide than florid psychotic pheno-mena [55]. Depressive symptoms were almost twice as commonin the suicide group than in the control group, but in bothgroups less than half of those with noted depressive symptoms were on any form of antidepressant medication at the time of admission. A previous history of attempted suicide was a sig-nificant predictor of suicide, especially in those patients whokilled themselves earlier in the course of their illness and whohad fewer hospital admissions.

Box 2. State- versus trait-dependent risk factors.

State-dependent risk factors

• Clinical depression

• Substance abuse

• Hopelessness

• Social isolation

• Psychotic symptoms

• Loss of faith in treatment

• Undertreatment or noncompliance with therapy and negative

attitude towards medication

• Agitation and impulsivity

Trait-dependent risk factors

• Younger age

• Male sex

• High socioeconomic family status• High intelligence

• High premorbid level of education

• Unmarried status

• Reduced self-esteem

• Enhanced awareness of illness

• Long duration of illness associated with multiple

hospitalizations, relapses combined with treatment

dependence or loss of faith in treatment





Karvonen et al. noticed that male patients with schizophrenia and concomitant depression often committed suicide immedi-ately after discharge [56]. Alarmingly, median survival time afterfinal hospitalization was only 1 day in depressive males but3 months in nondepressive males with schizophrenia. This find-ing highlighted the need for proper interventions when patientsare discharged, which is a time of high suicide risk, as reportedelsewhere (BOX 3) [49]. A recent investigation also found that risk factors for suicide in the immediate post-discharge period wereprevious deliberate self-harm, compulsory admission, living alone, work stress and being out of contact at follow-ups [57].Detailed descriptions of features for risk identification andprevention are provided in BOX 4–6.

Suicide risk in the first episode of schizophrenia

Nordentoft et al. found that suicidal behavior and suicidal ide-ation occur very frequently among patients with first-episode

schizophrenic psychoses [58]. They found that suicidal ideationand reports of a suicide attempt during the past 1 year weresignificantly reduced after treatment but were still at a highlevel compared with the general population. Melle et al. con-firmed that suicidal behavior is present in the early phases of psychotic disorders and in many cases precedes the first treat-ment contact [59]. While patients from communities that didnot have an early psychosis detection program showed rates of suicidal behavior in the expected range, the early detectiongroup had significantly lower rates. The study thus indicatesthat an early detection program, by lowering the threshold forfirst treatment contact and bringing patients into treatmentearlier, can reduce rates of serious suicidal behavior at the point

of first contact [60].Suicide prevention and the identification of specific risk fac-

tors for suicide in first-episode psychosis are of paramountimportance and point to early intervention among young schizophrenia patients [61].

Insight has been linked with increased suicide risk in schizo-phrenia [62]. Crumlish et al. reported that, in their sample of first-episode schizophrenia patients 6 months after presenta-tion, the greater the recognition by the individuals that they had a mental illness, the more depressed they were going to be4 years later, and the more likely they were to attempt suicide inthat period [63].

Suicidality in this group of young patients often coincides

with the harmful use of psychotropic substances and affectivesyndromes [11]. The situation in life of young people with first-episode schizophrenia is often much more unstable since they are not used to the disorder and since, as adolescents, they arealso facing the typical problems and conflicts of young peoplebeginning a new phase in life. In addition, other syndromes,such as mood disorders and addictive behaviors, complicate thesituation and increase the risk of suicide. Although varioustreatment approaches for first-episode schizophrenia have beendeveloped in recent years, it is still difficult for a person suffering

from symptoms of psychosis for the first time to find appropri-ate support. It usually takes several months before this person isdiagnosed correctly and treated by a psychiatrist.

Krausz et al. investigated suicide in patients showing symp-toms of schizophrenic disorders between 14 and 18 years of ageduring a follow-up of between 5 and 11 years [64]. The suiciderate of 13.1% was significantly higher than in studies of patients who developed a schizophrenic psychosis later in life.

Box 3. Risk factors and warning signs for suicide

in schizophrenic inpatients.

Risk factors

• Age under 30 years

• Pre- and intra-admission suicidal attempts• Prescription of a greater number of neuroleptics

and antidepressants

• Increased length of stay and increased number of ward changes

• Period of approved leave

• Past and present history of depression

• Deliberate self-harm

• Frequent relapses and rehospitalization

• Longer hospitalization periods than other

psychiatric inpatients

• Living alone before the past admission

• Discharge planning and period following discharge

• Early signs of a disturbed psychosocial adjustment• Dependence and incapability of working

• High number of hospital admissions

• Good premorbid functioning

• Hospitalization close to crucial sites (e.g., big roads, railway

stations or rivers)

Warning signs

Generic:

• Expressing suicidal feelings or bringing up the topic of suicide

• Giving away prized possessions settling affairs, making out

a will

• Signs of depression: loss of pleasure, sad mood, alterations in

sleeping/eating pattern and feelings of hopelessness

• Increased use of alcohol or drugs

• Social isolation

• Developing a specific plan for suicide

Specific:

• Apparent improvement

• Fluctuating suicidal ideation

• Emotional feelings about the illness and hospital admission

• Difficult relationship with staff and difficult acclimation in

ward environment

• Undertreatment or non-adherence to therapy and negative

attitude toward medication

Data from [49].





They also found a significant sex difference in the rate of sui-cide – 21.5% of the men compared with only 6% of the women – although the women made more attempts at suicide.

Thorup et al. investigated gender differences in age at first

onset, duration of untreated psychosis, psychopathology, socialfunctioning and self-esteem in a group of 578 young adults witha first-episode schizophrenia spectrum disorder [65]. They foundthat the women made more suicide attempts and experiencedlower self-esteem in spite of better social functioning.

Suicide attempts

Suicide attempts are a significant risk factor for subsequentcompleted suicide and are associated with significant medicalcosts [66]. A clear estimate of how many schizophrenia patientsattempt suicide is still lacking in the literature with estimatescovering a large range, from 20 to 40% [43,67–69]. For example,Gupta and colleagues reported that approximately 30% of patients with schizophrenia included in their sample had madeat least one suicide attempt [70]; but other estimates have beenreported. Back in 1982, Roy reported that estimates of theprevalence of suicide attempts in this group range from 18 to55% [39].

Drake reported that attempted and completed schizophrenicsuicides had similar histories of attempted suicide [71]. Only a history of explicit suicide threats differentiated the two groupsstatistically. In this study, most of the explicit threats were based

on an awareness of the illness and fears regarding the course of the illness. For example, several patients stated quite explicitly that they planned to kill themselves if they continued to haverelapses of the illness and an inability to function, that is, fears

of further mental disintegration. Patients who subsequently completed suicide also expressed higher performance expecta-tions, consistent with their awareness of the illness and accurateperceptions of their functional status. The completed suicidevictims were also clearly more depressed. During hospitaliza-tion, they reported feeling depressed, inadequate, hopeless, worthless and suicidal. Psychological symptoms of depression,rather than biological symptoms of depression, differentiatedthe suicide completers from the suicide attempters. Behaviorsduring hospitalization, such as being impulsive, demanding and agitated, failed to discriminate between completed suicidesand attempters. The only hospital-based behavior that did dis-criminate between the two groups was that the completed sui-cides were more likely to be rated as “improved” at discharge.However, Drake et al. found that those schizophrenic patients who had attempted suicide were often trying to manipulateothers, consolidate support or gain entrance to the hospital [72].

Interpersonal conflict, such as arguments with family mem-bers or housemates, rather than isolation have been reportedamong schizophrenic patients who attempt suicide [72]. Theseauthors suggested that impulsive attempts were associated withthe dysphoric side effects of medication, such as akathisia (subjective feeling of inner restlessness and the urge to move, as well

Box 4. Suicidal schizophrenic inpatients. Common features for identifying suicidal risk.

• Suicidal patients may make more demands upon hospital personnel, and may complain and criticize the treatment for which they

themselves have asked

• Patients may show marked ambivalence about leaving the security of the hospital, and have a constant need for reassurance and

support. Patients with fluctuating suicidal ideation are particularly likely to fall into these categories, which may lead to

under-reporting of suicidal ideation by the nursing staff

• Suicidal patients have been found to receive more attention from the staff

• Studies have reported that suicidal patients participate in more therapeutic activities such as individual and group psychotherapy,

educational therapy and occupational therapy. Suicide occurs, therefore, among the sicker patients, those with more serious psychiatric

symptoms and those who have a history of acting out more, including suicide attempts, suicidal threats and other suicidal behavior

• Suicide risk may increase during initial acclimation to ward life or when plans for discharge or rehabilitation are being arranged

• Patients have been reported as suffering from ‘terminal malignant alienation’, that is, some patients, particularly those with recurrent

relapses and resistance to treatment, may be perceived by staff as manipulative, provocative, unreasonable, over-dependent and

feigning disability. Patients with fluctuating suicidal ideation are particularly likely to fall into these categories, which may lead to

under-reporting of suicidal ideation by the nursing staff. This may result in criticism and a lower level of support leading to alienation.

The combination of such alienation and fluctuating suicidal ideation can lead to a failure to recognize the seriousness of suicidal risk

• The ‘dependent-dissatisfied’ person incessantly complains, demands, insists and tries to control others. These patients show

inflexibility and lack of adaptability, reiterating their complaints to others regardless of whether the others can do anything to remedy

the situation. These patients turn to the staff for support, but continually succeed in alienating them with their insatiable demands forspecial attention

• Discharge planning may be a proximal factor for suicide in long-stay patients who have to deal with the painful realization that they

are losing the hospital and the staff and/or that their family is not prepared to have them home

• A program for preventing suicide in these patients is not easy to devise for it has been found that these patients provoke rejection

and, thereby, bring about the state of affairs that they dread most – loneliness and the feeling that no one, not even the staff, cares.

It is difficult to give extra and special attention to patients who are insatiably demanding and ungrateful

Data from [49].





as objective components). Nevertheless, in a recent study, aka-thisia was not found to be linked to suicidality or depressionamong patients with treatment-resistant schizophrenia [73]. In a study comprising 500 patients with schizophrenia and/or affec-tive disorders, a history of suicide attempts was associated withcomorbidity, low scores on the Global Assessment Scale (GAS),low age at onset and poor premorbid adjustment [74]. The study showed that males affected with schizophrenia were less likely to attempt suicide when compared with males with diagnosesother than schizophrenia. Among females, suicide attempts were more common in those with lower age at onset and whohad no children. Kelly et al. found that 93% of schizophrenia patients who committed suicide had shown previous suicidalbehavior versus only 23% of the patients who died from othercauses [41].

Attempts among those with schizophrenia are serious andtypically require medical attention. Intent is generally strong,and the majority of those who attempt suicide have previously

made multiple attempts. In addition, the methods used toattempt suicide are more lethal than those used by suicidal per-sons in the general population. Gupta and colleagues reportedthat, in their sample of patients with schizophrenia, suicideattempts were associated with the number of lifetime depressiveepisodes [70]. Depression has been recognized as a major risk fac-tor among persons with schizophrenia who have attempted sui-cide. Roy and associates found that significantly more of theirsample of schizophrenic patients who had attempted suicide

had also suffered from a major depressive episode at some timeduring their illness [69]. Great caution is required in the periodafter hospital discharge because schizophrenic patients usually experience hopelessness and demoralization at that time. Forthese patients, discharge often means losing the hospitalenvironment and the people who have become central in theirlife. The number of psychiatric admissions, which is usually higher among patients who have attempted suicide, may beindicative of a severe relapsing illness.

Sevincok et al. reported that patients suffering from bothschizophrenia and obsessive–compulsive disorder (OCD) had a greater number of previous suicide attempts compared withpatients who do not have comorbid OCD [75].

Psychometric assessment

Suicide risk among patients with schizophrenia is usually assessed retrospectively through statistical analysis. Prospective

studies are scarce [76]. Furthermore, when risk factors areapplied to samples of patients, they yield too many false posi-tives and fail to identify many of those who later turn out tohave been at risk of suicide (false negatives).

A number of instruments have been developed to estimatesuicide risk in schizophrenia. Taiminen et al. proposed theresearch-based 25-item Schizophrenia Suicide Risk Scale(SSRS), although the authors noted that the scale was too insen-sitive or too nonspecific for general use as screening device [77].

Box 5. Key figures for the prevention of suicide among schizophrenic patients.

Psychiatrists and mental health professionals

Proper education on how to treat empathically and recognize suicide risk must be delivered to these personnel [38]. Dealing with suicidalpatients may lead nurses and mental health professionals to feel overwhelmed and detach themselves in an attempt to deal with the

stress. Staff must be informed and supported to cope with job stress

Medical staff (including nurses and paramedics)

Nurses and paramedics may become a proxy family, especially for inpatients with schizophrenia. They should treat the patient

accordingly in order to avoid frustration and, in turn, increased suicide risk [198]

Physicians

Both clozapine and lithium (unlike antidepressants) are employed with unusually close medical supervision and regular blood testing to

minimize the risk of potentially lethal side effects. It should not be underestimated that meeting with medical staff may play a central

role in reducing this social isolation. The fact that these patients have to follow a specific pattern of tests, which leads to interaction

with people who may provide warmth and empathy, may alleviate their ever-increasing sense of worthlessness and inadequacy.

Most schizophrenia patients experience social isolation, even within their families, and are eager to establish even a tiny interpersonal

contact [116,204]

Family members

Family members are often stigmatized by having connections with a schizophrenic individual. Their social interaction may be

dramatically reduced and frustration may be overwhelming. They may, therefore, show hostility toward the sick member and hinder a

possible positive outcome. Specific programs for families should be delivered [205]

Community

Members of the community can play an important role in whether they support or fight stigmatization. Accepting these patients is

crucial for improving the patients’ adherence to treatment, to promote positive outcome and to reduce suicide risk [206]





Turner et al. proposed a semi-structured Interview for Suicidein Schizophrenia (ISIS) based on chart review, staff reports andinformation from families [78]. The 140-item third revision of the ISIS was tested on 270 schizophrenia patients [79], yielding satisfactory sensitivity and specificity.

Recently Hansen and Kingdon investigated 40 patients (39

with a diagnosis of schizophrenia, one with a diagnosis of schizoaffective disorder according to the International Classifi-cation of Diseases [ICD]-10). Patients were tested using theHealth of the Nation Outcome Scale (HoNOS), the Compre-hensive Psychopathological Rating Scale (CPRS) and a vali-dated suicidality rating scale – the International Suicide Preven-tion Trial (InterSePT) Scale for Suicidal Thinking (ISST), a new instrument for the assessment of current suicidal ideationin patients with schizophrenia [80]. These authors demonstrateda highly robust association between the two suicidality itemsfrom the CPRS, HoNOS and the InterSePT scale.

The ISST was derived from the Scale for Suicide Ideation, a 19-item scale, which has been validated and has proven reliablein a depressed population [81], but not in patients with schizo-phrenia. The present version is a 12-item scale, which is ratedon three levels of increasing intensity (0, 1 or 2). The total scoreis computed by adding the 12 individual item scores. It quanti-

fies current conscious and overtly expressed suicidal thinking inschizophrenic patients by assessing various suicidal thoughtsand wishes during a 20–30-min semistructured interview. Theinstrument proved to be a reliable and valid instrument for theassessment of current suicidal thinking in patients with schizo-phrenia and schizoaffective disorder when used by cliniciansand researchers [80].

The development of high-quality suicide risk instruments forschizophrenia patients has aroused a great deal of interestamong researchesr. A systematic review of suicide risk rating scales in schizophrenia was provided by Preston and Harsen [82],

Box 6. The role of staff in the prevention of suicide.

• The impact of staff variables, such as low morale and the absence of key personnel, is critical, as well as the need for effective

communication among the relevant staff about patients judged to be at increased risk of suicide

• Discharge plans should be organized carefully. A supportive, supervised living arrangement is ideal. Adverse circumstances, such as

single-occupancy rooms or return to a family in which the patient’s presence represents a severe emotional or financial strain,

probably increase the suicide risk for a schizophrenic patient

• Staff should be self-confident and unworried, and should have confidence with suicide-related issues. Suicide risk seems to increase

when the organization of the ward, as well as the personal problems of the staff seem not to allow for proper caring of the patients.

On the other hand, empathic staff that can establish good relationships with patients in general and with suicidal patients in

particular are extremely important in reducing suicide risk. Nurses are generally trained to develop empathic skills, but it is difficult

teaching how to respond to the particular condition that each patient with schizophrenia presents. Above all, it is extremely hard to

deal with these patients when they are suicidal

• The risk for suicide is greatest during the first 6 months after discharge, However, suicide risk has also been reported to be very high

in the 5 days following discharge, as well as in the first 28 days after leaving the hospital

• Patients and their families should be instructed on the advisability of a return to the hospital if another disturbance occurs, and they

should be encouraged to consider such a return as neither a failure nor a serious setback. Easy channels of communication need to

be established, especially if different staff members are involved

• Staff, and especially nurses, have a crucial role in the process of suicide prevention by delivering information about preventive

measures. Many of the suicides during inpatient treatment may be associated with periods during which there are lower levels ofstaffing than usual. Moreover, increased personnel turnover in psychiatric hospitals may result in staff who are less experienced

• Saarinen and colleagues noted various elements that compromise a staff’s ability to identify suicidal indicators in patients with

schizophrenia [38]:

- Lack of knowledge and skills in relation to treatment of self-destructiveness

- The professional’s own losses or absence of concern

- Acceptance of the patient’s suicide as a solution to the patient’s problems

- Wishes that the patient would commit suicide as a solution to his or her problems

- Degree of familiarity with patients

- Unfounded optimism in relation to treatment

- Fear of the patient

- Defects or problems associated with the treatment system

- Sadism toward the patient- Denial of the patient’s psychiatric problems

• A program for preventing suicide in these patients is not easy to devise for it has been found that these patients provoke rejection

and, thereby, bring about the state of affairs that they dread most – loneliness and the feeling that no-one, not even the staff, cares.

It is difficult to give extra and special attention to patients who are insatiably demanding and ungrateful

Data from [207,208].





which provided good examples of the research to develop relia-ble instruments for clinicians to evaluate suicide risk among these patients.

Protective factors

The literature abounds with descriptions of risk factors for suicidein individuals with schizophrenia, but possible protective factorsfor suicide in schizophrenia have been neglected (BOX 7). Recently,Huguelet et al. reported that religion played a role in preventionof suicide in their sample of outpatients suffering from schizo-phrenia or schizoaffective disorders [83]. Jarbin and Von Knorring reported that, in their sample of adolescent-onset psychotic disor-ders, satisfaction with religion, health, family relations and safety at follow-up were inversely associated to attempting suicide, butonly satisfaction with religious belief remained after controlling for concurrent symptoms of anxiety and depression [84].

Hawton et al. found no association between negative symp-

toms and suicide [33], but a protective association for flat affect was reported in one study [31]. This should not lead to a rush tothe conclusion that negative symptoms are protective factors.Negative symptoms, in general, and the so-called persistent nega-tive symptoms as well as secondary negative symptoms [85] resultin great difficulties for schizophrenia patients and have beenreported as playing a possible central role in mediating suiciderisk in patients with schizophrenia [86–88]. Moreover, Hawtonet al. found conflicting associations between positive symptomsand suicide risk [33]. Therefore, it would appear that, according tometa-analytic reviews, the core symptoms of schizophrenia areneither good indicators of risk factors nor good indicators of protective factors.

Suicide, therapeutics & stigmatization

The promise of improved efficacy and tolerability of the atypi-cal antipsychotics compared with typical or first-generationantipsychotics remains only partially fulfilled. As consensusgrows around the need to treat specific symptom domains of schizophrenia, such as negative and cognitive symptoms, theshortcomings of available medications has become evident. Inparticular, there are no treatments with proven efficacy for pri-mary negative symptoms [89]. Negative symptoms are burden-some for family members and contribute to poor long-termtreatment outcomes for patients with schizophrenia.

A comprehensive review by Nasrallah and Newcomer [90] notedthat, since the 1950s, pharmacotherapy for schizophrenia involved administration of dopaminergic receptor antagonists with antipsychotic activity, for example, conventional antipsy-chotics such as haloperidol or chlorpromazine [91]. During the lastdecade, however, atypical antipsychotics with unique pharmaco-

logic profiles involving modulation of not only dopamine butother neurotransmitters, including serotonin (5-hydroxytryp-tamine; 5-HT), have become available [92]. With the significantand possibly broader spectrum of clinical efficacy seen with atypi-cal antipsychotics, coupled with a lower risk of extrapyramidalsymptoms (EPS), these agents have rapidly gained acceptance andhave become the standard of care for patients with schizophrenia or a schizoaffective disorder. Atypical antipsychotics must be usedin the context of appropriate periodic clinical re-evaluation andmedical monitoring to assess the risk/benefit equation.

Data from a large, national cohort (n = 63,214) confirm previ-ous reports of poor adherence among these patients. A total of 40% of patients with schizophrenia receiving one antipsychotic

Box 7. Protective factors for suicide in schizophrenia.

• Adherence to therapy

• Family support for the illness and against the stigma that arises from it

• Suitable antidepressant therapy

• Possibility of talking about the intention to commit suicide

• Family history negative for suicide

• Simplex and hebephrenic subtypes of schizophrenia

• Psychological well-being – specific treatments for hopelessness and psychological pain

• Training in the development of social and cognitive skills

• Not being stigmatized

Protective factors related to interventions

• Support and programs of aftercare at discharge

• Use of atypical antipsychotics

• Regular sessions of family therapy that are able contribute to reducing the number and the duration of hospitalizations, the number

of the relapses and increased compliance to therapy

• Possibility of working and carrying out pleasant activities

• Limited access to the more common methods of suicide

• Programs of prevention about substance abuse

• Live in an environment adjusted to the patient’s needs

Modified from [102].





and 38% of those receiving two antipsychotics were poorly adherent with their medication regimen. This finding is consist-ent with previous studies that have used a variety of methods toassess adherence among patients with schizophrenia [93]. Thehigh rates of poor adherence are troubling, given the conse-quences of antipsychotic discontinuation and haphazard antipsy-chotic use. Previous studies have reported that patients who dis-continue antipsychotics may be two- to five-times as likely torelapse as other patients, leading to unnecessary suffering andincreased costs [94–96], as well as an increased risk of suicide [97].

The effect of poor compliance with antipsychotics on suiciderates among patients with schizophrenia was noted by an early review [19], as well as by a recent meta-analysis that concluded thatpoor compliance with antipsychotics more than triples the suiciderisk in these patients. Long-term compliance with atypical antipsy-chotics has been reported as being fundamental in reducing therisk of serious adverse outcomes, including suicide [98]. In a recentinvestigation, poor compliance was predictive of completed sui-

cide in our sample of schizophrenia patients [POMPILI

M, LESTER

D,GRISPINI A ET AL . SUICIDE IN SCHIZOPHRENIA : EVIDENCE FROM A CASE–CONTROL STUDY

(2007), SUBMITTED], a finding consistent with the current literature [17].Melle et al. had reported that participants from communities

that have an early psychosis detection program were younger,less symptomatic and had shorter durations of untreated psy-chosis than participants from communities without the pro-gram [59]. These findings suggest that, when people are edu-cated about psychosis, they are more likely to seek treatment when symptoms occur. This finding underscores the potentialutility of psychoeducational approaches leading to decreasedmorbidity and mortality.

Corrigan provided a comprehensive analysis on how stigma

interferes with mental healthcare [99]. He stressed that, despitethe plethora of evidence-based interventions, many people withmental illness never pursue treatment and others begin treat-ment but fail to fully adhere to the prescribed services. Stigma isone of the reasons for this. Mentally ill people may be subjectedto stigma derived from stereotypes, prejudice and discrimina-tion. These people also face self-stigma derived from self-preju-dice and internalization of the stigmatizing ideas that are widely endorsed within the society. Therefore, they come to believethat they are less valued because of their psychiatric disorder.Self-stigma can result in decreased treatment participation.

Pharmacological treatmentExisting data suggest that, for the most part, pharmacotherapy forschizophrenia has not affected the rate of suicide among patients with psychotic disorders.

Antipsychotics

Carone et al. followed-up 80 young people with schizophrenia who were receiving typical antipsychotics for up to 5 years [100]. After 2.5 and 5 years there was an overall 10% incidence of suicide,and as many people committed suicide as had a good outcome.

Montout et al. investigated causes of death (e.g, suicide orcardiovascular) and exposure to neuroleptics in a cohort of 3474patients with schizophrenia followed from 1993 to 1997 [101].They found that the risk of all causes of death (OR: 1.59; 95%CI: 1.02–2.50; p = 0.04) and of suicide (OR: 2.22; 95%CI: 1.24–3.97; p = 0.006) were increased in users of thioxanthenes(alone or associated with other medications), whereas an increasedrisk of ‘‘other causes’’ of death was associated with use of atypicalneuroleptics (OR: 2.06; 95% CI: 1.15–3.70; p = 0.0016).

Pompili et al. highlighted the importance of a balancedpharmacological treatment in patients with schizophrenia inorder to prevent suicide [102]. Atypical antipsychotics have someimpact on suicidality in schizophrenic patients [101,103]. The dis-tinguishing characteristics of atypical antipsychotic drugs aretheir EPS, lower risk of tardive dyskinesia and minimal serumprolactin increases compared with typical antipsychotic drugs[104]. Therefore, one important implication for the atypicalantipsychotics and their reduction of suicide risk lies in the low

incidence of EPS akathisia during treatment with these agents. Another important advantage of atypical antipsychotics is theirlower association with depression-like side effects [105].

Whether or not akathisia should be part of the EPS syn-drome is still a matter of debate, but its possible role in the pre-cipitation of suicide risk for patients both treated with anti-depressants and antipsychotics has been reported [106].Nevertheless, Hansen et al. found no association betweenakathisia and suicidality in treatment-resistant schizophrenia [73]. However, emerging akathisia during pharmacological treat-ment and suicide risk has been investigated, especially in thecase of selective serotonin reuptake inhibitors (SSRIs) [107], andemphasis should be placed upon its role as a key risk factor for

suicide in schizophrenia. Also of note is the role of akinesia (impaired body movement;

without movement or without much movement, often used todenote the absence or poverty of movement) in the determina-tion of a clear clinical picture. According to Siris, “sincereduced ability to initiate and sustain motor behaviors com-monly leads to a lack of pleasurable experiences (indistinguisha-ble from anhedonia) and self-recrimination about laziness (anequivalent of reduced self-esteem or guilt), a diagnosis of depression could essentially result” [108]. This led to the ques-tion of whether this state was a phenocopy of depression ordepression itself [109,110]. This makes the proper assessment of these patients difficult since clinicians need to distinguish

between the two states and consider whether a reduced ability to initiate and sustain behavior can be a protective factor forputting a suicidal wish into action [108].

Both a reduction of neuroleptic dosage and adjunct treatment with benzodiazepines or β-blockers is beneficial for akinesia, inaddition to anticholinergic antiparkinsonian medication [111].In this discussion, it is also worthwhile mentioning that neuro-leptic drugs can potentially induce depression as a side effect, which can contribute to the aforementioned difficulties relatedto akathisia and akinesia. However, despite some research





reporting depression as a side effect of traditional antipsychotictreatment, indepth observations lead to the conclusion thatthere is no direct association between the treatment and onsetof depression in patients with schizophrenia [108].

Despite great efforts, both on the side of drug treatment andpsychosocial strategies, the number of suicides among schizo-phrenic patients has remained unchanged [112], although Nor-dentoft et al. have shown that, in Denmark, suicide among patients with schizophrenia has fallen, paralleling the reduc-tion of suicide in the general population [113]. According tothese authors, this was probably due to better psychiatric treat-ment, reduced access to means of suicide and improvements intreatment after suicide attempts.

With regard to the atypical antipsychotics, clozapine, olanza-pine, risperidone and quetiapine have shown some power inreducing suicidality among schizophrenic patients [103,114].

According to some reports, the potential decrease in suicidemortality with clozapine treatment is estimated to be as high as

85%. In terms of benefit versus risk, while 1.5 of every 10,000patients with schizophrenia who were treated with clozapine would be expected to die from agranulocytosis (evidence suggestsan even lower percentage), 1000–1300 would have been expectedto complete suicide with standard treatment [115–117]. In fact, theUS FDA recently approved clozapine for the treatment of suicidalbehavior in patients with schizophrenia or schizoaffective disorder[118,119]. Modestin et al., in a retrospective analysis of patientstreated with clozapine, reported a significant reduction of suicidalbehavior and serious suicidal acts among schizophrenic patientstreated with clozapine as compared with other treatments [120];however, the preventive effect disappeared after clozapine discon-tinuation. Hennen and Baldessarini provided a meta-analysis sup-

porting the antisuicidal effect of clozapine [121], including thestudies of Meltzer and Okayli [116], Walker et al. [122], Reid et al.

[123], Munro et al. [124], Sernyak et al. [125] and Meltzer et al. [119]. A random-effects analysis indicated a substantially lower overallrisk of suicidal behaviors favoring clozapine (risk ratio [RR]: 3.3;95% CI: 1.7–6.3; p < 0.001). For completed suicides, the RR was 2.9 (95% CI: 1.5–5.7; p = 0.002). An update of this meta-analysis, including the study by Modestin et al. [120], also providedstronger support for the antisuicidal effect of clozapine (pooledOR: 4.64; p < 0.0001) [126].

A possible negative outcome associated with clozapine treat-ment was reported by Sernyak et al. who, for the first time, used a matched control group and found that the treatment was not

associated with significantly fewer deaths due to suicide [125].However, one third of the sample received clozapine for less than6 months, even though the follow-up period was 5–6 years.

Studies on clozapine [116,125] have a number of limitationsthat prevent a definite conclusion. Meltzer and Okayli did notmatch cases with a control group and so each patient acted astheir own comparison subject. This design is not as robust as a randomized, parallel-group, double-blind study [127]. The study by Sernyak et al. also had several limitations. The effect of cloza-pine on all causes of mortality, including suicide, was compared

with a group chosen by the use of ‘propensity scaling’, a poten-tially problematic method that has severe limitations in this con-text [128]. The authors failed to consider the variables availablefor subject matching and did not include the four most impor-tant characteristics necessary for matching for suicide (thenumber, timing and lethality of prior suicide attempts, and theseverity of depression at index admission). The variables that were used to create a comparison group had no connection withsuicidality. Despite the fact that some studies have suggestedthat treatment with clozapine might reduce suicidality among patients with schizophrenia, future studies are needed to fill themethodological gaps mentioned previously, although a synthesisrelated to the evidence-based medical treatment of clozapine hasbeen reported [129].

As with lithium, the reduction of suicide risk may partly reflect the close medical supervision required to minimize risksof potentially lethal adverse effects, facilitating social interactionin patients otherwise often isolated from daily interpersonal con-

tacts. Atypical antipsychotics, as reported earlier in this paper,have the advantage of improving adherence to treatment as they are not generally associated with EPS or tardive dyskinesia, which may be associated with an increased risk of suicide [5].

It may be that some side effects, such as weight gain, may increase suicide risk owing to increased stigmatization and uneas-iness with body image or reduce the patient’s quality of life as inthe case of diabetes [130]. Moreover, since the administration of newer atypical antipsychotics may be accompanied by increasedinsight and illness awareness, and since sudden increases ininsight by more than 25% may lead to increased suicidality inschizophrenic patients [131], caution is needed, and patientsshould be followed-up closely to contain such abrupt insight

increases within an appropriate therapeutic relationship.In 2003, a panel of experts in suicide prevention held a consen-

sus conference and provided an algorithm for effective treatmentof suicidal schizophrenic and schizoaffective patients [132]. FIGURE 1

reports full details of such guidelines. In this algorithm, there isno reference to the presence/absence of akathisia which, asreported previously, should be carefully evaluated and treated. Westress, therefore, the need to share updated guidelines in which,early in the algorithm, there is an akathisia yes/no branch. Basedon the available literature, propranolol or other lipophilicβ-blockers seem to be the most consistently effective treatmentfor acute akathisia. There is nothing in the literature to guide a clinician when treatment with β-blockers fails. Addition of

benzodiazepines would appear to be a sensible second choice,especially if subjective distress persists. If all of these drugs areunsuccessful, amantadine or clonidine can be tried. Other agentsthat have been investigated include ritanserin, piracetam, valproicacid (sodium valproate) and tricyclic antidepressants. Evidence onthe treatment of tardive akathisia is unsatisfactory [133]. Moreover,on the basis of the existing literature, we strongly suggestimprovement of the present algorithm by introducing a place fortricyclics and for monoamine oxidase inhibitors (MAOIs) as a further option when other antidepressants have failed.





Meltzer et al. organized the InterSePT, a prospective, ran-domized, masked (blinded) parallel-group study to comparethe effects of treatment with clozapine versus another atypicalantipsychotic drugs in which patients were seen equally fre-quently, with equal access to other psychotropic drugs and withpsychosocial treatment [119]. During this trial, clozapine wascompared with olanzapine in patients with schizophrenia orschizoaffective disorder, regardless of whether they had persis-tent psychotic symptoms or prior treatments, but who were atmore than the average risk for a subsequent suicide attemptbased primarily on having made at least one suicide attempt inthe 3 years prior to study entry or on being currently suicidal.The primary outcome measures for the InterSePT was eithertime to a suicide attempt (including death by suicide), or a hos-pitalization to prevent suicide as determined by an indepen-dent, blind, Suicide Monitory Board (SMB) or time to much worsening/very much worsening from baseline on a clinicalglobal impression of suicidality scale as rated by a blind rater.

InterSePT provided a 2-year randomized, open-label trial withblind ratings by trained raters and a blind psychiatrist who hadno direct contact with the participating sites or the sponsor of the study, and determination of whether potential endpointsmet the criteria for a suicide attempt or a hospitalization to pre-vent suicide. Treatment was prescribed by a psychiatrist whohad full knowledge of the drugs prescribed as well as control of ancillary therapies to reduce the risk of suicide.

A significant difference was demonstrated between clozapineand olanzapine in reducing suicidality, with a 24% differencein favor of clozapine. The number of patients needed to betreated with clozapine in order to reduce the risk of one event was 13. It was concluded that clozapine was superior to olanza-

pine in male and female patients with schizophrenia orschizoaffective disorder, regardless of whether they were neu-roleptic resistant or neuroleptic responsive. The two drugs didnot differ in overall efficacy in reducing total psychopathology,positive or negative symptoms or depression. Thus, the differ-ence between the drugs on suicidality was not secondary toother effects, confirming the view of suicide as a separatedimension of the schizophrenia syndrome [5].

The main criticism of this study is that there was no clear evi-dence of a reduced risk of completed suicide per se . A descrip-tion of the limitations of clozapine-related studies for reducing suicide in schizophrenia are provided in BOX 8.

The only study comparing the antisuicidal effects of olanzap-

ine found that significantly less suicidal thinking occurredamong olanzapine-treated patients relative to those whoreceived haloperidol [134]; no differences between olanzapine,haloperidol and placebo occurred in self-directed aggression.

In a 5-year retrospective case–control study of records for756 individuals with schizophrenia or schizoaffective disorder,Barak et al. reported a reduced rate of suicide attempts associ-ated with the use of atypical antipsychotics (OR: 3.54; 95%CI: 2.4–5.3) [135]. Although a larger effect size was calculated forrisperidone relative to olanzapine (3.16 vs 1.76), the difference

was not statistically significant. Tran et al. conducted an interna-tional, multicenter, double-blind, parallel-group, 28-week pro-spective study of 339 patients who met the Diagnostic and Sta-tistical Manual of Mental Disorders, 4th Edition (DSM-IV)criteria for schizophrenia, schizophreniform disorder or schizoaf-fective disorder [136]. Results of the study indicated that botholanzapine and risperidone were safe and effective for the man-agement of psychotic symptoms. However, olanzapine demon-strated significantly greater efficacy for negative symptoms andoverall response rate. For suicide attempts, this study found thatolanzapine-treated patients had a statistically lower risk (0.6%;one patient with one attempt) than risperidon-treated patients(4.2%; p = 0.029; seven patients, each with one attempt).

No direct, systematic investigations of potential antisuicidaleffects of quetiapine, ziprasidone and aripiprazole have beenpublished to date. The documented antisuicidal potential of these agents rests chiefly in their positive effects on known risk factors for suicide in schizophrenia, namely depressive and anx-

iety symptoms [137–142], aggression [137,143], cognitive dysfunc-tion [144,145], impulsivity [103] and perceived quality of life andsocial functioning [146–148].

Mood stabilizers

Mood stabilizer medications may be effective in reducing depression, aggression and impulsivity in patients with schizo-phrenia, typically as adjuncts to antipsychotic therapy. Thebiological basis for mood stabilizer effects on suicidal risk hasnot been established. Lithium is known to improve centralserotonin transmission, while valproate and carbamazepinemay reduce aggressiveness and impulsivity by enhancing GABAergic activity [149]. The potential of other mood stabiliz-

ing agents, such as lamotrigine, which has established antide-pressant activity, is less well understood than that of lithium,valproate or carbamazepine.

Lithium

Together with clozapine, lithium is the only drug that showsantisuicidal properties in bipolar and major affective disorderpatients. Baldessarini et al. recently performed a comprehensivemeta-analysis of studies of lithium as a treatment for reducing suicide risk [150]. Risks for both completed and attempted suicide were reduced by nearly fivefold, or 80%. These authors reporteda strong association of lithium treatment with the ratio of attempted suicide to completed suicide, which they suggest may

be an index of the lethality of suicidal acts. Recently, Guzzetta et al. performed a meta-analysis on suicide risk reduction withlithium in current major depressive disorder [151]. Theseauthors found antisuicidal effects of lithium in recurrent majordepressive disorder to be similar in magnitude to that found inbipolar disorders.

The role of lithium as an adjunctive treatment for schizo-phrenia is less well established. In a recent systematic review of 20 studies where lithium was used alone or as an adjunct toantipsychotic therapy, lithium was found to be ineffective in





schizophrenia as a single agent treatment [152]. As an augment-ing agent, an overall modest clinical benefit was observed(n = 244; RR: 0.8; 95% CI: 0.7–0.96). However, this effect

became less apparent when individuals with schizoaffective dis-order were excluded, and drop-out rates tended to be higheramong those who received lithium augmentation rather thanantipsychotic monotherapy (n = 320; RR: 2.0; 95%CI: 1.3–3.1). Therefore, it is presently unknown whether lith-ium exerts antisuicidal effects among individuals with schizo-phrenia. Although caution is warranted when combining lith-ium with some typical neuroleptic agents owing to thepossibility of neurotoxic reactions and enhanced extrapyrami-dal side effects, the strategy of adding lithium to ongoing atyp-ical antipsychotic treatment for antisuicidal effect is an area worthy of further investigation [153].

Considerably less information concerning the antisuicidal

effects of valproate and carbamazepine are available. Both medi-cations are associated with mood stabilizing effects in both theshort and the long term and have been employed with successfor reducing aggression, physical violence and suicidal behaviorsin disorders other than schizophrenia. Baldessarini et al. foundlithium to be superior as an antisuicidal agent compared withthese drugs [150]. At the present time, sound evidence for theirpossible role in prevention of suicide in schizophrenia is sill lack-ing. The same conclusion applies also to the role of lamotrigineand topiramate [153].

Antidepressants

Recent studies on the role of antidepressants in reducing suiciderisk have failed to provide strong evidence regarding their possi-ble role in increasing or decreasing suicide risk. It would appearthat pooling trials of antidepressants (including both tricyclicsand SSRIs versus placebo) yielded a nonsignificant figure which was not in favor for one side or the other [126,154].

Overall, the use of antidepressants, especially tricyclics, asadjunctive agents for patients suffering from schizophrenia hasbeen reviewed extensively [105,155–157]. Antidepressants have beenespecially used in nonflorid psychotic patients presenting typicalfeatures of depression. Siris reported that such treatments are

much more successful with outpatients rather than with inpa-tients due to the fact that consistent treatment is a key elementin this contest [108]. Siris et al. [156,158] demonstrated that adjunc-

tive antidepressant medication, especially in the case of imi-pramine, was associated with better outcome in schizophrenia patients with fewer relapses into depression and less exacerba-tion of psychosis and, overall, tricyclics proved to be particularly useful in treating depressed schizophrenics. Therefore, it appearsthat, although antidepressants may have a role as add-on therapy in amelioration of negative, depressive and obsessive–compul-sive symptoms in schizophrenia [159–161], their specific role inpreventing suicide is unclear. Combination therapy with antide-pressants appears to be well tolerated, although pharmacokineticdrug–drug interactions may result in unintended elevations of antipsychotic drug concentrations, especially in the case of clozapine combined with either fluoxetine or fluvoxamine [153].

Research suggests that MAOIs may have a role in the treat-ment of depression and negative symptoms in schizophrenia.In contrast to MAOIs, which strongly potentiate the catecho-lamine-releasing effect of tyramine, (-)deprenyl (selegiline)inhibits it and is free of the ‘cheese effect’, which makes it a safe drug. Selegiline, a selective inhibitor of MAO-B, hasbecome a universally used research tool for selectively blocking B-type MAO and is still the only selective MAO-B inhibitor in worldwide clinical use. Data suggest that add-on therapy withselegiline is particularly helpful in schizophrenic patientspresenting negative symptoms as well as depression [162,163].

Anxiolytics

Anxiolytics have been employed in tandem with antipsychotictherapy, mostly on an as-needed basis in the case of benzo-diazepines. These medicines are typically used for themanagement of acute anxiety or agitation, particularly during theacute phase treatment of schizophrenia [164]. In general, their useshould be limited to managing acute symptoms, which may include self-directed aggression. Long-term use of these agentsexposes patients to a number of risks, including synergistic seda-tive or hypotensive effects with antipsychotics, disinhibitionreactions, addiction and fatality from overdoses [165].

Box 8. Limitations of clozapine-related studies on reducing suicide in schizophrenia.

• Retrospective data

• Possible differences in the risk of suicide between clozapine and comparison groups because subjects were not randomly assigned to

the treatments

• Possible differences in dosages of clozapine and the comparison antipsychotic drug(s) relative to optimal dose for reduction of suicidality

• Uncontrolled and possibly differential use of concomitant psychotropic medications such as antidepressants, mood stabilizers, anxiolytic

drugs and drugs to reduce extrapyramidal symptoms

• Weekly and biweekly clinical contact during treatment with clozapine to examine white blood cell count compared with less frequent

visits for those not taking clozapine

• Lack of examination of compliance with clozapine or prior treatment

• Lack of control of possible differential access to psychosocial support programs

• Lack of comparison with other atypical antipsychotic drugs that may have greater benefit for treating suicidality than typical antipsychotics

Data from [5].





Buspirone, an alternative serotonergic anxiolytic medicationthat lacks these limiting factors, was tested as an adjuvant therapy to neuroleptic treatment in a very small 6-week open trial [166]. At a mean dose of 23.8 mg/day, add-on buspirone was associ-ated with significant improvement on the Brief Psychiatric Rat-ing Scale (BPRS), the Simpson Angus Scale for ExtrapyramidalSymptoms and the Global Assessment of Functioning Scale.Interpretation of these results is limited by the study’s opendesign and very small sample size. In addition, suicide risk wasnot taken into account.

Comment

One important issue in drug studies concerns sponsorshipsfrom pharmaceutical industries. Heres et al. reviewed trialsinvolving second-generation antipsychotics and investigated42 reports of which 33 were sponsored by a pharmaceuticalcompany [167]. In 90% of the studies, the reported overall out-come was in favor of the sponsor’s drug. Moreover, Montgom-

ery et al. reported that industry-funded studies significantly favor second- over first-generation antipsychotics when com-pared with nonindustry-funded studies [168]. Procyshyn et al.also stress in their review paper that a third of the publishedclinical trials involving clozapine, risperidone or olanzapine were funded by their respective manufacturers and that thereported outcomes of the sponsored trials highly favored themanufacturers’ product [169].

Other biological interventions

Electroconvulsive therapy (ECT) has been recognized as one of the most successful interventions for mood disorders, particu-larly depression with psychotic features [170]. ECT has been

associated with more modest effects for a host of other condi-tions, including use as an adjunct to antipsychotic medicationtreatment in schizophrenia [171]. Regardless of diagnosis, thereappears to be a significant tradeoff between short-term efficacy and cognitive side effects [172]. This, along with the significantsocial stigma associated with the treatment, has relegated ECTto use only in the most urgent of circumstances or for the mostrefractory of clinical cases.

ECT as monotherapy or as an adjunct to antipsychotic medi-cation is not more effective in schizophrenic patients thanantipsychotic medication alone [172]. ECT’s long-term effects incontrolling psychotic symptoms, as well as its impact on suicid-ality, are unknown. More research is needed to examine the

long-term efficacy of ECT and the effectiveness of post-ECTpharmacotherapy, the short- and long-term cognitive sideeffects of ECT, and the impact of ECT on suicide and all-causemortality among patients with schizophrenia.

Nonpharmacological treatments

Combining drug treatment with psychosocial–psychothera-peutic interventions may be very important for a better out-come. The daily difficulties faced by schizophrenic patients

can be addressed with specific programs, and having a psycho-therapist as a key figure may give these patients the possibility of overcoming difficult periods as well as coping better withtheir conflicts.

Clinicians should acknowledge the patient’s despair, discusslosses and daily difficulties, and help to establish new andaccessible goals. Social isolation and work impairment havebeen reported as risk factors for suicide in individuals withschizophrenia [173]. Individuals with good premorbid function-ing are at greater risk of suicide. Interventions such as socialskills training, vocational rehabilitation and supportiveemployment are, therefore, probably very important in theprevention of suicide in schizophrenic patients. Hogarty et al.proposed Personal Therapy, which includes three levels of treatment with defined criteria for progression from basic tomore challenging levels [174–176]. Treatment spans from early months after discharge, which aims at clinical stabilization andtherapeutic joining, to a later phase, which promotes intro-

spection and an understanding of the relationship betweenstressors and maladaptive response. An intermediate phasepromotes skills remediation, relaxation training, role playing and psychoeducation.

These kinds of therapies focus on working out daily prob-lems rather than achieving psychological insight. It has becomeincreasingly clear that supportive, reality-orientated therapiesare generally of great value in the treatment of patients withschizophrenia. In particular, supportive psychotherapy aims atoffering the patient the opportunity to meet with the therapistand discuss the difficulties encountered in daily activities.Patients are encouraged to discuss concerns about medicationsand side effects, as well as issues such as social isolation, money

and stigma. The therapist plays an active role, giving sugges-tions and sharing good and bad periods empathically. Thenature of these treatments and their availability vary greatly from place to place. However, psychosocial approaches havelimited value for acutely psychotic patients.

De Leo and Spathonis [177] and Pompili et al. [90] reviewedsuicide prevention intervention in schizophrenia, questioning whether psychosocial treatment is associated with a reductionof suicidal risk. These authors took into considerationapproaches such as case management (including social skillstraining and vocational rehabilitation), psychotherapy andcommunity treatments. These treatments have benefits forschizophrenic patients but, as for their impact on suicide risk

reduction, data are still scarce and further research is needed.The importance of providing care was demonstrated by Mottoand Bostrom who showed that a systematic program of contact with persons who are at risk of suicide and who refuse toremain in the healthcare system appears to exert a significantpreventive influence for at least 2 years [178]. In other words, thefact that these people were feeling that somebody else was taking care of them prevented suicide to some extent compared withthose people that refused to remain in the healthcare system and who were not reached by any message.





Lack of evidence-based data should not, however, lead us toignore these approaches that can make a difference when dealing with human misery. Such approaches can also improve adherenceto treatment, which is a key element in mediating the reductionof suicide risk. Also, the lack of evidence-based results should notlead us to dismiss the approach. Strict rules, such as randomizedcontrolled trials or other trials at the top of the hierarchical pyra-mid of evidence, are often hard to apply to real-world settings of psychosocial interventions compared with pharmacological tri-als. For these reasons, more funding opportunities should beavailable to better evaluate these treatments.

A further issue refers to housing as well as homelessness, which are major sources of stress that can contribute to hopeless-ness and helplessness which, in turn, are major contributors tosuicide risk. Offering an environment that provides support,comfort, stability and protection is a potential protective factorfor suicide in schizophrenia. In patients with multiple brief hos-pitalizations, the experience of ‘revolving door’ discharges

impairs stability and is a great source of distress [108]. Cliniciansshould, therefore, monitor patients’ living conditions after dis-charge and make efforts to provide support and care thatstrengthen self-worth and hopefulness.

Tarrier et al. suggested that factors that may inhibit suicideschemata should reduce suicide behavior [179]. Thus, factors thatmight reduce emotional reactivity should be associated withreduced suicide behavior because of the reduced potential toelaborate and activate suicide schemata. However, Tarrier et al.,found that there is no beneficial effect on suicidal behavior fromcognitive–behavioral therapy for schizophrenics (CBTp) [180].This is disappointing but may have been due to the genericnature of the CBTp that was targeted at psychotic symptom

reduction and not suicidal behavior per se or its possible directantecedents. Conversely, there is no indication that exposure toCBTp increases suicidal thoughts or behavior as has been sug-gested. Bateman et al. recently provided further evidence on theusefulness of CBT in reducing suicidal ideation in patients withschizophrenia [181].

It would appear that reality-orientated psychotherapy is supe-rior to a dynamic, insight-orientated approach. However, explora-tory psychotherapy may have some benefits as it gives patients who have achieved stable remission the opportunity to under-stand inner conflicts and discuss, within a solid therapeutic alli-ance, suicidal thoughts or suicidal behavior. Patients learn to usesymbolism and thinking rather than action (suicide). However,

any psychotherapeutic technique with schizophrenic patientsrequires modifications of the standard approach. Treatmentshould begin in the early months after discharge and aim at clini-cal stabilization and establishing rapport, and move in later phasesto promoting introspection and an understanding of the relation-ship between stressors and maladaptive responses. An intermedi-ate phase promotes skills training, relaxation training, role-playing and psychoeducation. There is evidence to suggest that the com-bination of psychosocial and pharmacological treatments increasescompliance and helps to achieve a better outcome [102]. Gradual

gains in insight brought about by successful drug treatmentand/or psychotherapy may decrease suicidality and may furthercontribute to compliance, which may protect the patients fromrelapses and recurrences. In turn, the benefit from adhering totreatment may make the patient’s outlook on his or her illnessmore positive, thereby reducing suicidality. (The extent to whicha person’s behavior – taking medication, following a diet, and/orexecuting lifestyle changes, corresponding with recommendationsfrom a healthcare provider – is called adherence [182].)

The high rates of poor adherence demonstrated in variousstudies are troubling, given the consequences of antipsychoticdiscontinuation and haphazard antipsychotic use. Previous stud-ies have reported that patients who discontinue antipsychoticsmay be two- to five-times as likely to relapse as other patients,leading to unnecessary suffering and increased costs [94,95,183].Disappointingly, in one study, the authors did not find substan-tially higher levels of adherence among patients treated withatypical antipsychotics, with the important exception of clozap-

ine [184]. Compared with the use of conventional antipsychotics,the use of atypical antipsychotic medications was associated withsignificantly less treatment switching and less use of concomitantmedications. However, undertreatment, indicated by a lack of prescription refills, occurred among patients taking both medica-tion classes, which highlights the need for further research onnonadherence [185].

Despite the widespread use of atypical antipsychotic medica-tions, alarmingly high rates of both under-use and excessive filling of antipsychotic prescriptions were found in Medicaid beneficiar-ies with schizophrenia. The high rates of antipsychotic nonadher-ence and associated negative consequences suggest interventionson multiple levels. Those who were adherent had significantly

lower hospital costs than the other groups; pharmacy costs werehigher among those who were adherent than among those who were nonadherent or partially adherent and were highest forexcess fillers. Total costs for excess fillers (US$14,044) weresubstantially higher than total costs for any other group [186].

Antipsychotic treatment for schizophrenia should focus onimproving real-world outcomes, including functional capacity and health-related quality of life, which are important from thepatient’s perspective. A growing number of naturalistic clinical tri-als are generating effectiveness data that can inform prescribing decisions [187,188]. At present, the state of the art can only indicatea more favorable trend for second-generation antipsychotics inregard to improving medication adherence behavior, quality of life

and subjective tolerability [146].One of the most important issues in treatments of schizo-

phrenia is the cost of antipsychotics. Cost–effectiveness of second-generation antipsychotics is important since their higher costscompared with traditional antipsychotics should lead to betteroutcomes and therefore reduced utilization of mental health serv-ices. Yet, metabolic side effects lead to increased usage of healthfacilities. Also, suicide attempts are an important burden for thecommunity. A new treatment for schizophrenia should be costeffective through efficacy and safety and should provide protection





from suicide risk. The introduction of new drugs should,therefore, take into account what kind of innovation a certainmolecule promises to provide in the treatment armamentarium.

Given the side effects associated with second-generationantipsychotics, such as weight gain and the resulting stigma, webelieve that that reduction of stigmatization may improvepatients’ adherence to medication. On the other hand, new antipsychotics may dramatically improve a patient’s complianceowing to reduced metabolic side effects, as well as effectivenessfor negative symptoms [189,190].

The trend in the psychopharmacology of schizophrenia lies inproper psychoeducation programs including behavioral inter-ventions as well as multimodal approaches [191–193]. With suchinterventions clinicians can monitor attitudes to therapy andintervene with the most suitable approach [194,195]. The unmetneeds of patients suffering from schizophrenia is a neglectedissue. Interventions such as social skills training, vocational reha-bilitation and supportive employment are, therefore, very

important in the prevention of relapses and suicide and inincreasing adherence to treatment in schizophrenic patients.

Limitations of this review

Although we performed a systematic review of the literature, theinclusions and exclusions of papers cited in this paper may reflectthe authors’ choice both on the basis of their expertize and theconsultations that they engaged with experts in the field. Thisstudy does not provide meta-analytic results that would be of greatvalue in evaluating a complex phenomenon such as suicide inschizophrenia. This narrative review is thus a comprehensive anal-ysis of issues, but might possess biases as a number of additional

papers could have been added as useful sources of information.Despite other relevant reviews, this further attempt to summarizethe literature in this field focuses on new issues related to thephenomenon and attempts to present key topics in order to offerthe reader an easy tool when facing suicide risk in schizophrenia.

Expert commentary

Despite intense efforts to better understand suicide risk in schizo-phrenia, major difficulties remain. Suicidality, coupled with a chronic and sometimes difficult illness, often results in improperclinical interventions. Although reducing risk factors offers thefirst line of action to prevent suicide, this often leads to many

false positives. Evidence-based practice in suicidology has to beincorporated in the caring for patients. Pharmacological treat-ment, especially in the case of clozapine, and other preventivemeasures (such as proper discharge planning, proper education formedical staff and adequate intervention for families) may be ableto dramatically reduce suicides among schizophrenic patients.

Psychosocial interventions in general may help these patients,reducing suicide risk indirectly. In other words, patients may feelless hopeless when they manage to cope with their daily activities,especially if such activities involve social exchanges.

One major challenge is reducing suicide attempts. These arereported as an alarming phenomenon, and suicide attemptersshould not be discharged or their attempt ignored withoutproper evaluation for further suicidal behavior and without fol-low-up plans. Too often, patients end their lives after severalattempts which were not taken seriously.

Stigmatization is also an important issue for schizophrenicpatients. Stigma may reduce adherence to therapy and, therefore,increase suicide risk as a result of the untreated disorder. Stigma also accompanies suicidality, and both clinicians and patientsoften avoid direct investigation or reference to suicide. At thepresent time we do not have clear evidence of how stigma medi-ates suicide risk. It seems reasonable to acknowledge that stigma-tization does make patients more hopeless and reduces theirpotential for improvement. Stigma fosters isolation and reducesfaith in treatment. We have evidence on how stigma can impairoutcome by increasing hospitalizations and by facilitating relapsesespecially through reduced adherence to treatment. It would

appear that stigma impacts suicide risk, increasing some state-dependent risk factors for suicide. In a study exploring barriers tomedication adherence in schizophrenia, Hudson et al. found thatstigma was the number one factor identified by patients whenreferring to barriers for antipsychotic treatment [196]. A compre-hensive analysis of how stigma reduces adherence to treatment was also provided by Corrigan [99]. Many people with mental ill-ness never pursue treatment, while many others begin treatmentbut discontinue it or are poorly adherent to it and stigma is a main factor in mediating this events. Stigmatization is pervasiveand it may exist in the family, in medical settings and in a numberof environments where patients at risk of suicide are not ade-quately treated [197,198], and stigma toward suicide can be a poten-

tial contributor to suicidal behavior [199]. Appropriate programsof education can make the difference in creating a new culture intreating patients with schizophrenia and in dealing with their sui-cide risk. Key persons that can benefit from such programs aremental health professionals, physicians and family members.

Five-year view

Over the past few decades, scholars worldwide have dedicatedgreat resources to the study and prevention of suicide in schizo-phrenia, and our feeling is that such efforts will eventually lead toa dramatic decrease in suicides among these patients. However, itshould not be forgotten that a great deal of research is generally

devoted to retrospective analysis, correlations among variables andopen-label treatment trials. One of the risks of this is an enormousnumber of studies but no real change in knowledge. Apart fromprospective trials involving evidence-based approaches, as well asgood practice approaches, scholars should bear in mind that weneed to broaden our horizons for proper interventions for suicide.Only active efforts involving suicide risk assessment and interven-tion will lead to a reduction in suicide. We also need to overcomethe science–practice gap. The state-of-the-art treatments identi-fied after years of research are not being transferred into actual





practice in community settings. One major effort needed, there-fore, is to bridge the gap that currently lies between research andclinical practice. Evidence-based mental health may be a goodopportunity for clinicians to get to understand suicide risk inschizophrenia both theoretically and in daily-based clinics. Theaforementioned need for assessment and intervention can be deliv-ered if proper and shared guidelines are taken into account. Inte-grating personal experience with data from systematic research may be the key element in this field. We are still too much involved with our personal opinions when treating suicidal patients, and infact we too often do what we believe is better. Instead, over thenext 5–10 years, we should follow recommendations and data from reliable sources, as well as deliver caring, empathic andsensitive treatments to suicidal schizophrenia patients.

One possible intervention is to select those people that may have the right skills to deal with suicidal patients. In health envi-ronments, those in charge of human resources should pay partic-ular attention of the role played by each member of the medical

team. Skilled nurses and doctors may deliver high-standard pro-fessional service in any kind of outpatient and inpatient clinicbut may be unsuitable for treating psychiatric patients who are athigh risk of suicide. For these reasons, decision-makers shouldemploy people who are engaged in suicide prevention activities.

Furthermore, regular updates and educational activities shouldbe part of the inhouse training of each individual involved intaking care of patients at risk of suicide.

The struggle against stigmatization is already a part of somemental health plans, but talking about stigma towards psychiatricpatients is not enough. Most people will continue to think thatschizophrenics are just ‘mad people’ to be pitied. They are not.They are patients just like those suffering from diabetes, heartdisease or measles, and they deserve our full understanding. Sui-cide is often the result of a deep rift between these patients andsociety, resulting in painful alienation.

Our view, in conclusion, is that we are in the middle of thestruggle, with many battles already won but with many more stillto combat.

Financial & competing interests disclosure

The authors have no 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. This

includes employment, consultancies, honoraria, stock ownership or options,

expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.

Key issues

• A recent meta-analysis reported a lifetime suicide rate for patients with schizophrenia varying between 4 and 5%. However, despite this,

there is evidence to suggest that more patients suffering from schizophrenia die by suicide, pointing to the need to take into account the

limitations of meta-analytic investigations.

• Suicide risk is greater in the first 10 years of the illness. Frequently suicidal behavior precedes the first contact with mental health

professionals. However, suicide behavior is not infrequent later in the course of the disorder, especially in patients with frequent relapses

and rehospitalization.• Post-admission and discharge from a psychiatric ward are times associated with high risk for suicidal behavior. Great caution is required in

the period after hospital discharge because patients with schizophrenia often experience hopelessness and demoralization at this time. For

these patients, discharge often means losing the hospital environment and the people who, in some way, have become central in their life.

• Lower functioning and good insight, post-psychotic depression and hopelessness, substance abuse and previous attempts are all good

predictors of suicidal risk. The greater the recognition by individuals that they have a mental illness, the more depressed and the more at

risk they are for suicide.

• Suicide attempts among patients with schizophrenia are serious and typically require medical attention. Intent is generally strong, and the

majority of those who attempt suicide have made multiple previous attempts. Depression has been recognized as a major risk factor among

persons with schizophrenia who have attempted suicide. Patients with schizophrenia frequently choose violent methods for suicide.

• Patients with schizophrenia are poorly adherent to antipsychotic treatments. Those patients who discontinue treatments are at

risk for relapses and suicide. Stigmatization may reduce adherence to therapy and, therefore, increase suicidal risk as a result of the

untreated disorder.

• Only clozapine has been recognized by the US FDA as an effective drug for the treatment of schizophrenic patients with suicidal risk. Effectson suicide behavior are appreciable, especially for long-term treatment plans.

• Psychoeducation interventions, such as social skills training, vocational rehabilitation and supportive employment, are very important in

the prevention of suicide in chronic schizophrenic patients. Patients feel less hopeless when they are capable of dealing with daily

activities, especially if such activities involve social exchanges.

• There is evidence to suggest that the combination of psychosocial and pharmacological treatments increases compliance and helps to

achieve a better outcome.

• One major effort for the next few years is to bridge the gap that currently exists between research and clinical practice. Evidence-based

mental health may be a good opportunity for clinicians to understand suicidal risk in schizophrenia, both theoretically and in

daily-based practice.





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Affiliations

• Maurizio Pompili, MD

Department of Psychiatry, Sant’Andrea

Hospital, Sapienza University of Rome,Via di Grottarossa, 1035, 00189 Roma,

Italy; McLean Hospital, Harvard Medical

School, Boston, MA, USATel.: +39 06 3377 5675Fax: +39 06 3377 [email protected];

[email protected]

• David Lester, PhD

The Richard Stockton College of

New Jersey, Pomona, NJ 08240, USA Tel.: +1 609 652 4512

Fax: +1 609 626 5559

[email protected]

• Marco Innamorati, PsyDUniversità Europea, Roma, Italy;

Piazza Filattiera 12, 00139 Roma, Italy

Tel./Fax: +39 06 810 [email protected]

• Roberto Tatarelli, MD

Department of Psychiatry, Sant’Andrea

Hospital, Sapienza University of Rome,

Via di Grottarossa, 1035, 00189 Roma,Italy Tel.: +39 06 3377 5687

Fax: +39 06 3377 5342

[email protected]

• Paolo Girardi, MD

Department of Psychiatry, Sant’AndreaHospital, Sapienza University of Rome,

Via di Grottarossa, 1035, 00189 Roma,

Italy Tel.: +39 06 3377 5951Fax: +39 06 3377 [email protected]



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A Ssessment and Treatment of Suicide Risk in Schizophrenia

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