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Completed suicide in schizophrenia: Evidence from a case-control study
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Psychiatry Research 167 (2009) 251 – 257 www.elsevier.com/locate/psychres
Completed suicide in schizophrenia: Evidence from a case-control study Maurizio Pompili a,b,⁎, David Lester c , Alessandro Grispini d , Marco Innamorati e , Fulvia Calandro d , Paolo Iliceto a , Eleonora De Pisa a , Roberto Tatarelli a , Paolo Girardi a a
Department of Psychiatry, Sant'Andrea Hospital, “Sapienza” University of Rome, Italy b McLean Hospital, Harvard Medical School, Belmont, MA, USA c The Richard Stockton College of New Jersey, Pomona, NJ, USA d Department of Mental Health “Roma E”, Italy e Universita' Europea of Rome, Italy
Received 23 May 2007; received in revised form 4 October 2007; accepted 14 March 2008
Abstract Suicide is the single major cause of death among patients with schizophrenia. Despite great efforts in the prevention of such deaths, suicide rates have remained alarming, pointing to the need for a better understanding of the phenomenon. The present sample comprised 20 male patients with schizophrenia who committed suicide and who were investigated retrospectively for a large number of characteristics. Controls were 20 living patients with schizophrenia. The results suggest that suicide attempts, hopelessness and self-devaluation were the three variables most strongly associated with completed suicide. However, a number of variables were identified which may constitute risk factors, some of which have not been identified in the past: agitation and motor restlessness (OR = 3.66; 95%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 = 0.95/14.02), and suicide attempt (OR = 3.66; 95%CI = 1.40/114.41). Poor adherence to medications was also predictive of completed suicide in our sample of schizophrenia patients, primarily because the suicide victims showed very low adherence. © 2008 Elsevier Ireland Ltd. All rights reserved. Keywords: Suicide; Schizophrenia; Risk factors
1. Introduction In the last decades, a number of studies have confirmed the first reports (Kraepelin, 1919; Lipschutz, 1942) that ⁎ Corresponding author. Department of Psychiatry, Ospedale Sant'Andrea, Via di Grottarossa, 1035, 00189 Roma, Italy. E-mail addresses: [email protected], [email protected] (M. Pompili).
patients with schizophrenia frequently commit suicide (e.g., Beisser and Blanchette, 1961; Miles, 1977; Caldwell and Gottesman, 1990; Pompili et al., 2005) and make multiple suicide attempts (e.g., Pompili, 2007), often using violent methods for committing suicide (Roy, 1982; Breier and Astrachan, 1984; Cheng et al., 1990). Kelly et al. (2004) found that 73% of their sample committed suicide by violent methods such as jumping from a height, drowning, cutting, gunshot wounds or hanging. Beisser
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and Blanchette (1961) investigated 75 suicides committed in mental hospitals in California. A diagnosis of schizophrenia had been made in around half of the cases in the series, one half of the patients had previously threatened to commit suicide, and half had attempted suicide in the past. In 89% of the cases, the method used was hanging, and 52% of the patients committed suicide while they were in isolation. Thus, restricting individuals with schizophrenia to a safe environment, where lethal methods for committing suicide are not easily available, is of utmost importance. Recently, new meta-analyses (Inskip et al., 1998; Palmer et al., 2005) have reviewed the prevalence of suicide in patients affected by schizophrenia, and estimated lower rates than had earlier studies (e.g., Caldwell and Gottesman, 1990; Miles, 1977). These authors stated that around 4–5% of individuals with schizophrenia commit suicide during their lifetime (Inskip et al., 1998; Palmer et al., 2005). Meltzer (2005) recently pointed out that the question is not resolved and, regardless of the lower recent estimates, the prevalence of suicide is still unacceptably high. However, Nordentoft et al. (2004) in a nested case-control study found a decrease in recent years in suicide deaths of schizophrenia patients when examining four longitudinal Danish registers for the period 1981 to 1997. Evidence suggests several risk factors for suicide, such as being young, male and unmarried, and having high family stress, limited external support, deteriorating health with a high level of premorbid functioning, an awareness of the illness, hospitalization, post-psychotic depression, and a history of substance abuse and suicide attempts. Hopelessness, social isolation, recent loss or rejection and instability are also important factors in individuals with schizophrenia who commit suicide. These patients usually fear further mental deterioration, and they experience either excessive treatment dependence or loss of faith in treatment (Pompili et al., 2004a; Pompili, 2007; Pompili et al., 2007). Positive symptoms are generally less often included among risk factors for suicide in schizophrenia. However, a number of studies have found that the active and exacerbated phase of the illness and the presence of psychotic symptoms (De Hert et al., 2001; Heila et al., 1997; Hu et al., 1991; Westermeyer et al., 1991), as well as paranoid delusions and thought disorder (Krupinski et al., 2000; Saarinen et al., 1999), are associated with a high risk of suicide. Patients with the paranoid subtype of schizophrenia are also more likely to commit suicide (Fenton et al., 1997; Roy, 1982). Suicides as a result of command hallucinations, although rare, have been reported in the literature (Zisook et al., 1995). Kelly
et al. (2004) reported that a large proportion of their patients affected with schizophrenia who committed suicide had poor control of thoughts/thought insertion, loose associations and flight of ideas compared with those who died by other means of death. Drug treatment of schizophrenia is generally associated with a reduced risk of suicide. In this regard, clozapine has been found to reduce suicide risk in schizophrenia (Meltzer et al., 2003; Pompili et al., 2007). However, because the administration of both clozapine and atypical antipsychotics may be accompanied by increased insight and illness awareness, and because sudden increases in insight may lead to increased suicidality in patients with schizophrenia (Turkington et al., 2002), caution is needed, and patients should be followed closely in an appropriate therapeutic relationship to monitor such abrupt increases in insight (Pompili et al., 2004b). Suicide risk among patients with schizophrenia is usually assessed retrospectively through statistical analysis. Prospective studies are rare (Sakinofsky et al., 2004). It seems that risk factors identified for samples of patients are less useful when extrapolated to the individual patient. The use of risk factors often yields too many false positives and fails to identify many of those who later turn out to have been at risk of suicide. The aim of the present study was to compare individuals suffering from schizophrenia who committed suicide with living individuals suffering from the same disorder. Differences in clinical and sociodemographic variables were examined in an attempt to identify predictive factors that might assist clinicians in identifying suicidality among patients with schizophrenia. 2. Methods 2.1. Subjects In this retrospective case-control study the sample consisted of 20 suicide victims with a diagnosis of schizophrenia and 20 living controls, who sought outpatient treatment in 1998–2003 and who were followed to 2004 at the “Rome E” psychiatric clinic (a branch of the Italian National Mental Health Service). Each control was randomly selected from patients admitted during the same period of time as the suicide victims (±15 days). Included were patients with a diagnosis of schizophrenia either using the ICD-9 or DSM-IV criteria (Italian Health Systems require official diagnoses to be conform to ICD criteria). We excluded patients whose sociodemographic variables were unavailable, and patients where ICD or DSM-IV criteria for schizophrenia were not fully met, e.g., cases diagnosable as schizophrenia by the less restrictive
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temporal criteria of ICD-9 or who were followed up for less than 6 months. One of the authors (FC) inspected a total of 3000 clinical records. Of these patients, 264 were individuals with schizophrenia whose characteristics were compatible with inclusion criteria (20 out of the 264 patients killed themselves). Suicide was confirmed by the official death certificate. The principal investigator (MP) and another investigator (FC) independently inspected all records of patients with a diagnosis of schizophrenia and charted these patients on the basis of a checklist. (When unanimous decision was difficult to reach, a third party was consulted.) The same process was applied to the control group; that is, investigators independently selected controls according to the criteria used for selecting patients. The final sample consisted of 20 male suicides (mean age 40.10 ± 14.06 S.D.; range 23–76 years) and 20 living patients diagnosed with schizophrenia as controls (mean age 45.85 ± 13.26 S.D.; range 28–76 years), 18 men and 2 women. All suicides and controls were white Italians. Sociodemographic characteristics of the patients are listed in Table 1. 2.2. Assessment of clinical and demographic variables Two authors independently reviewed selected records to identify relevant variables for the study. The symptoms were rated according to a checklist. The checklist items were included according to their relevance as defined by all the authors at the beginning of the study. The symptoms were rated as present when the full criteria were met. Change over time was not considered. Each symptom was rated as Table 1 Sociodemographic characteristics of subjects. Characteristic
Controls Cases Statistics (N = 20) (N = 20)
Male — % 100.0 Female — % – Age (years) — mean ± S.D. 45.85 ± 13.26 Married — % 5% Education (≤8 years) — 45% % Unemployed — % 85%
90.0 10.0 40.10 ± t = 1.33; 14.06 df = 38 15% 50%
0.60 a 0.74 a
75%
0.69 a
Schizophrenia subtypes according ICD-9 — N Simple 12 9 Disorganized type 2 1 Paranoid type 2 2 Residual type 2 5 Unspecified 1 1 Other subtypes 1 2 a
Fisher's exact test.
P
0.19
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present either when related to impaired personal functioning (interpersonal, occupational, self-care or health behavior) and suffering, or when long lasting (2 consecutive sessions or more during the study follow-up) or frequent (3 sessions or more during the whole study follow-up). Each variable was defined by operational criteria. Low adherence to medications involved not taking regularly, suspending, or modifying treatment prescriptions either voluntarily or due to forgetfulness. The physical illness item was rated as present when any general medical condition affected the health of the patients during the study follow-up and demanded medications or counselling from a physician. The hallucination item involved sensory/perceptual distortions causing impaired functioning. Delusions involved a fixed false belief causing impaired functioning. Odd behavior included behaviors that are eccentric or peculiar and that caused impaired functioning. Thought disorders involved ideas of reference, odd beliefs or magical thinking inconsistent with subcultural norms. Affective flattening involved restrictions in the range or intensity of emotional expression causing poor functioning. Alogia involved poverty of thinking indicated either by poverty of speech or by poverty in the content of speech. Anhedonia involved a total loss of feeling of pleasure in acts that normally give pleasure. Agitation or motor restlessness involved an inability to rest, relax or be still. Self-devaluation involved ideation or speech indicating low self-esteem. Hopelessness involved ideation or speech indicating a negative view of the future. Insight involved clear perception of the patient's own situation. Fear of mental disintegration involved painful feelings of discomfort regarding growing difficulty in concentration, attention or abstract thinking. Positive symptoms included all symptoms involving altered behavior or thinking even when rated in another item, such as delusions, hallucinations, overactivity or incoherent thought and speech. Negative symptoms included all the symptoms involving lack or reduction of behaviors, even when rated in another item, such as affective flattening, alogia, anhedonia, difficulty in abstract thinking, stereotyped thinking, or attentional impairment. Depressive disorder NOS involved the presence of depressive symptoms not matching the criteria for the major depressive disorders, such a post-psychotic depressive syndrome. Insomnia involved difficulty initiating or maintaining sleep, or nonrestorative sleep causing impaired functioning or suffering that was long lasting or demanded treatment. Substance use disorders involved harmful use of or dependence on a specific psychoactive substance, including illicit drugs, alcohol or non-prescribed medications. Violence involved a lifetime history of aggressive behavior against objects or other people.
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Suicide attempts were defined as a non-habitual behavior with the intent of ending one's life which was unsuccessful in causing death. Illness history was determined retrospectively by reviewing clinical records and notes provided by the referring physicians. Because of the low rates of most schizophrenia subtypes, these were grouped in two clusters: the first group included the simple subtype, and the latter included all the other subtypes. The two groups were compared for the types of schizophrenia, and no significant differences were observed (Fisher's exact test = 0.32) (see Table 1). 2.3. Data analysis Statistical analyses included χ2 tests, Fisher's exact tests (1-FET), and t-tests. Two-tailed t-tests were used for the continuous variables. Chi-square tests and Fisher's exact tests were used to identify differences in sociodemographic characteristics. Single variable logistic regression analyses were performed; odds ratios (OR) and 95% confidence intervals (95%CI) were reported to identify relevant variables as risk factors for suicidality.
Statistical analyses were conducted with SPSS for Windows version 13.1. 3. Results There were no differences between controls and cases on sociodemographic characteristics. Almost all subjects were men, never married and unemployed, and 50% had a low level of education (≤8 years). The mean age (S.D.) at which the patients completed suicide was 40.10 (14.06) and did not significantly differ from the mean age of 45.85 (13.26) for the controls (t = 1.33, df= 38, P = 0.19). The association between suicidality and adherence to medications was statistically significant (1-FET = 0.000) primarily because the suicide victims showed very low adherence. Major factors predictive of suicidality in the bivariate associations (see Table 2), ordered by OR, were: 1) hopelessness, 2) self-devaluation, 3) suicide attempt, 4) insomnia, 5) mental disintegration, and 6) agitation or motor restlessness. Only three factors showed a tendency (NS) to be protective: absence of attention deficit (OR = 0.20; P = 0.07), insight (OR = 0.40; P = 0.19) and age (OR = 0.96; P = 0.19).
Table 2 Single variable logistic regression analysis. Factor
Controls (%)
Cases (%)
OR
95%CI
z
P
Age Age of illness when first referred Physical illness Hallucinations Delusions Odd behavior Thought disorder Positive symptoms Negative symptoms Affective flattening Alogia Anhedonia Reduction in motor activity Absence of attention deficit Depressive disorder NOS Agitation or motor restlessness Self-devaluation Hopelessness Insomnia Insight Mental disintegration Substance use disorders Hospital admissions Violence Suicide attempt Adherence to medications
45.85 ± 13.26 a 22.05 ± 9.06 a 1 (5.0) 11 (55.0) 14 (70.0) 8 (40.0) 7 (35.0) 18 (90.0) 19 (95.0) 12 (60.0) 8 (40.0) 17 (85.0) 13 (65.0) 7 (35.0) 10 (50.0) 9 (45.0) 1 (5.0) 3 (15.0) 1 (5.0) 15 (75.0) 1 (5.0) 2 (10.0) 2 (10.0) 10 (50.0) 3 (15.0) 13 (65.0)
40.10 ± 14.06 a 22.10 ± 11.29 a 2 (10.0) 16 (80.0) 19 (95.0) 14 (70.0) 12 (60.0) 19 (95.0) 19 (95.0) 12 (60.0) 10 (50.0) 19 (95.0) 16 (80.0) 2 (10.0) 15 (75.0) 15 (75.0) 12 (60.0) 18 (90.0) 8 (40.0) 11 (55.0) 7 (35.0) 7 (35.0) 5 (25.0) 14 (70.0) 14 (70.0) 2 (10.0)
0.96 1.02 2.11 3.27 8.13 3.50 2.78 2.11 1.00 1.00 1.50 3.35 2.15 0.20 3.00 3.66 28.49 51.00 12.66 0.40 10.21 4.84 3.00 2.33 13.22 0.06
0.92–1.01 0.95–1.08 0.17–25.34 0.80–13.34 0.87–75.40 0.94–12.96 0.77–10.04 0.17–25.34 0.05–17.18 0.28–3.54 0.42–5.24 0.31–35.36 0.51–8.99 0.03–1.15 0.78–11.44 0.95–14.02 3.15–257.40 7.56–343.72 1.40–114.41 0.10–1.55 1.12–93.12 0.86–27.22 0.50–17.72 0.63–8.53 2.78–62.66 0.01–.34
− 1.28 0.63 0.58 1.64 1.85 1.87 1.56 0.58 0.00 0.00 0.63 1.00 1.05 − 1.79 1.61 1.90 2.98 4.04 2.26 − 1.31 2.06 1.79 1.21 1.28 3.25 − 2.82
0.19 0.52 0.55 0.09 0.06 0.06 0.11 0.55 1.00 1.00 0.52 0.31 0.29 0.07 0.10 0.05 0.003 0.000 0.02 0.19 0.03 0.07 0.22 0.20 0.001 0.001
OR = odds ratio; CI = confidence interval. a Values shown as mean ± S.D. (median).
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4. Discussion This study compared patients with schizophrenia who completed suicide with living subjects suffering from schizophrenia. Of note is the finding that the suicides in our sample were older than is commonly reported in the international literature on suicide in schizophrenia. This was somewhat unexpected as most of our patients suffered from the simple subtype of schizophrenia. Suicide risk in schizophrenia is generally associated with the paranoid subtype of the illness whose onset is later than in the other subtypes. These patients generally manage to study and work reasonably well due to the late onset of schizophrenia and, when they become sick, they can no longer perform in the same way. Therefore, good premorbid functioning has been reported as a risk factor for suicide among these patients (Dingman and McGlashan, 1986). Previous studies have reported a number of risk factors for suicide, and some of them were confirmed in the present study. The risk factors included those that are shared with individuals in the general population (such as male gender, self-reported hopelessness, substance use disorders, and prior suicide attempts) and those that are disease-specific to schizophrenia (such as a long illness with exacerbations, awareness of illness, and a low number of negative symptoms). In the present study, the patients with schizophrenia who committed suicide were men, confirming that male gender is associated with completed suicide (Lester, 2007), but they were older than expected on the basis of previous research (Caldwell and Gottesman, 1990). Selfdevaluation (worthlessness), hopelessness and suicide attempts were the three variables most strongly associated with completed suicide, and this finding was consistent with conclusions from previous systematic reviews (Caldwell and Gottesman, 1990; Hawton et al., 2005). Poor adherence to medications was also predictive of completed suicide in our sample of schizophrenia patients, a finding consistent with the current literature (Auquier et al., 2007). In addition, mental disintegration and agitation or motor restlessness were significantly associated with suicide risk, while hallucinations and delusions, odd behavior, substance misuse and depressive disorder NOS were positively associated but the association did not reach the level of statistical significance. Hawton et al. (2005) reported mixed results for those risk factors. For example, they concluded that only drug use disorders were associated with increased suicide risk (while alcohol yielded a non-significant association with suicide risk). Hawton et al. (2005) also reported an inverse association between hallucinations and suicide risk.
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The association between completed suicide and the presence of comorbid depressive episodes, although not statistically significant in the present study, is an important issue that has been highlighted in the international literature (McGirr et al., 2006) These authors found that in the logistic regression model current depressive disorder NOS was the independent predictor of suicide with the largest adjusted effect on risk. Positive symptoms, for which the findings of previous studies had been inconsistent, were not associated with suicide risk in the present study. This is somewhat inconsistent with a number of studies that found that the active and exacerbated phase of the illness and the presence of psychotic symptoms were associated with suicidal risk (De Hert et al., 2001; Heila et al., 1997; Hu et al., 1991; Westermeyer et al., 1991). However, our results are limited because the role of command hallucination in the precipitation of suicide was not studied (Harkavy-Friedman et al., 2003; Montross et al., 2007; Rogers et al., 2002; Zisook et al., 1995). Another important risk factor that emerged from our investigation was the presence of insomnia, a finding rarely reported hitherto. For example, Keshavan et al. (1994) found that those patients with schizophrenia who exhibited suicidal behavior had increased overall rapid eye movement (REM) activity and REM time, while Jones et al. (1994) found that nonsuppression in the dexamethasone suppression test (DST) could be related to suicidal behavior in a sample of individuals with schizophrenia. However, Lewis et al. (1996) contradicted these latter findings regarding nonsuppresion in the DST and reported that, in their sample of patients with schizophrenia, total REM sleep time was associated with suicidal behavior. These authors suggested that since serotonergic neurons act to suppress REM sleep, reduced serotonergic function in schizophrenia could explain the association between suicidal behavior and REM time/ activity that had been observed. Our results are consistent with McGirr et al. (2007), who found that insomnia was associated with a higher suicide risk in their sample of patients with major depressive disorder. Pompili et al. (2005) reviewed the literature on suicide among inpatients with schizophrenia and found that the suicide rate in cohorts of patients with schizophrenia who were followed up after the first hospitalization for periods ranging from1 to 26 years was 6.8%. Surprisingly, in our sample, the number of prior hospital admissions was not associated with suicide risk as is usually reported in the literature (Nordentoft and Mortensen, 2007; Qin and Nordentoft, 2005). Of note, however, is the finding of Preti and Miotto (2000), who reported that the incidence of hospitalizations for major psychoses is on the rise.
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These authors found that yearly first-admission rates for paranoia almost tripled from 1984 to 1994; a similarly significant rise was observed for schizophrenia and affective psychoses, with a greater increase for mania than for major depression. Nordentoft et al. (2002) found that suicidal behavior and suicidal ideation occur very frequently among patients with first-episode schizophrenic psychoses. Such findings were also confirmed by Melle et al. (2006), who reported that suicidal behavior is present in the early phases of psychotic disorders and in many cases precedes the first treatment contact. While patients from communities that did not have the early psychosis detection program showed rates of suicidal behavior in the expected range, the early detection group had significantly lower rates. In line with this, in Italy, selected groups may benefit from targeted prevention programs especially for those who are unemployed, those with low levels of education, those who are retired, and those who are single or divorced (Pavia et al., 2005; Masocco and co-workers, unpublished results). Our study focused only on a few protective factors, and none resulted in significant differences. Interestingly, the most powerful protective factors were the absence of attention deficits and insight. An earlier study (Wilson and Amador, 2007) identified a hopeless awareness of one's illness as an important predictor of completed suicide in patients with schizophrenia. Research findings to date seem to suggest that awareness of illness is associated with increased suicide risk, but only if that awareness leads to hopelessness. Lastly, we have to mention a number of limitations of our study regarding the generalization of the findings, such as the small ratio of sample variables, potentially causing an inflation of type I errors. Also, our investigation has the typical limitations of retrospective analyses of records. In fact, despite great efforts and strict selection of records included in the study, identification of variables among notes and charts in a few cases resulted in the impossibility of ascertaining beyond a reasonable doubt that a specific patient presented or did not present a given symptom. Even if we found that delusions and hallucinations were associated with suicide risk, we could not identify what was the typology of such symptoms, and this may be a limitation of the study, given the fact that some types of hallucinations and delusions, but not all of them, may be associated with increased suicide risk. Despite these caveats, our preliminary study strongly supports previous findings in the literature and highlights the role of risk factors rarely studied, helping in the assessment of suicide risk through the implementation of the knowledge of risk factors and the search for possible
new risk factors. Clinicians must be aware that it is not only the younger patients who are at risk of suicide. They should also pay attention to such cognitive, emotional and behavioral signs as hopelessness, self-devaluation, insomnia, mental disintegration, and motor restlessness. A systematic inquiry into previous instances of suicidality is also mandatory. In conclusion, suicide in schizophrenia is a complex phenomenon, requiring targeted educational activity for medical staff, proper utilization of the therapeutic armamentarium together with better access for patients to atypical antipsychotic drugs and destigmatization of the psychiatric disorders. Acknowledgment The authors are grateful to Prof. Jill Harkavy-Friedman who gave suggestions for improving the manuscript. References Auquier, P., Lancon, C., Rouillon, F., Lader, M., Holmes, C., 2007. Mortality in schizophrenia. Pharmacoepidemiology & Drug Safety 16 (12), 1308–1312. Beisser, A.R., Blanchette, J.E., 1961. A study of suicides in a mental hospital. Diseases of the Nervous System 22, 365–369. Breier, A., Astrachan, B.M., 1984. Characterization of schizophrenic patients who commit suicide. American Journal of Psychiatry 141, 206–209. Caldwell, C.B., Gottesman, I., 1990. Schizophrenics kill themselves too: a review of risk factors for suicide. Schizophrenia Bulletin 16, 571–589. Cheng, K.K., Leung, C.M., Lo, W.H., Lam, T.H., 1990. Risk factors of suicide among schizophrenics. Acta Psychiatrica Scandinavica 81, 220–224. De Hert, M., McKenzie, K., Peuskens, J., 2001. Risk factors for suicide in young people suffering from schizophrenia: a long-term follow-up study. Schizophrenia Research 47, 127–134. Dingman, C.W., McGlashan, T.H., 1986. Discriminating characteristics of suicides. Chestnut Lodge follow-up sample including patients with affective disorder, schizophrenia and schizoaffective disorder. Acta Psychiatrica Scandinavica 74, 91–97. Fenton, W.S., McGlashan, T.H., Victor, B.J., Blyler, C.R., 1997. Symptoms, subtype and suicidality in patients with schizophrenia spectrum disorders. American Journal of Psychiatry 154, 199–204. Harkavy-Friedman, J.M., Kimhy, D., Nelson, E.A., Venarde, D.F., Malaspina, D., Mann, J.J., 2003. Suicide attempts in schizophrenia: the role of command auditory hallucinations for suicide. Journal of Clinical Psychiatry 64, 871–874. Hawton, K., Sutton, L., Haw, C., Sinclair, J., Deeks, J.J., 2005. Schizophrenia and suicide: systematic review of risk factors. British Journal of Psychiatry 187, 9–20. Heila, H., Isometsa, E.T., Henriksson, M.M., Heikkinen, M.E., Marttunen, M.J., Lonnqvist, J.K., 1997. Suicide and schizophrenia: a nationwide psychological autopsy study on age- and sex-specific clinical characteristics of 92 suicide victims with schizophrenia. American Journal of Psychiatry 154, 1235–1242. Hu, W.H., Sun, C.M., Lee, C.T., Peng, S.L., Lin, S.K., Shen, W.W., 1991. A clinical study of schizophrenic suicides. 42 cases in Taiwan. Schizophrenia Research 5, 43–50.
M. Pompili et al. / Psychiatry Research 167 (2009) 251–257 Inskip, H.M., Harris, E.C., Barraclough, B., 1998. Lifetime risk of suicide for affective disorder, alcoholism and schizophrenia. British Journal of Psychiatry 172, 35–37. Jones, J.S., Stein, D.J., Stanley, B., Guido, J.R., Winchel, R., Stanley, M., 1994. Negative and depressive symptoms in suicidal schizophrenics. Acta Psychiatrica Scandinavica 89, 81–87. Kelly, D.L., Shim, J.C., Feldman, S.M., Yu, Y., Conley, R.R., 2004. Lifetime psychiatric symptoms in persons with schizophrenia who died by suicide compared to other means of death. Journal of Psychiatric Research 38, 531–536. Keshavan, M.S., Reynolds, C.F., Montrose, D., Miewald, J., Downs, C., Sabo, E.M., 1994. Sleep and suicidality in psychotic patients. Acta Psychiatrica Scandinavica, 89, 122–125. Kraepelin, E., 1919. Dementia Praecox and Paraphrenia. Livingstone, Edimburgh. Krupinski, M., Fischer, A., Grohmann, R., Engel, R.R., Hollweg, M., Moller, H.J., 2000. Schizophrenic psychoses and suicide in the clinic. Risk factors, psychopharmacologic treatment. Nervenarzt 71, 906–911. Lester, D., 2007. Suicide mortality in schizophrenics. In: Tatarelli, R., Pompili, M., Girardi, P. (Eds.), Suicide in Schizophrenia. Nova Science Publishers Inc., New York, pp. 19–29. Lewis, C.F., Tandon, R., Shipley, J.E., DeQuardo, J.R., Jibson, M., Taylor, S.F., Goldman, M., 1996. Biological predictors of suicidality in schizophrenia. Acta Psychiatrica Scandinavica 94, 416–420. Lipschutz, L.S., 1942. Some administrative aspects of suicides in the mental hospital. American Journal of Psychiatry 99, 181–187. McGirr, A., Tousignant, M., Routhier, D., Pouliot, L., Chawky, N., Margolese, H.C., Turecki, G., 2006. Risk factors for completed suicide in schizophrenia and other chronic psychotic disorders: a case-control study. Schizophrenia Research 84, 132–143. McGirr, A., Renaud, J., Seguin, M., Alda, M., Benkelfat, C., Lesage, A., Turecki, G., 2007. An examination of DSM-IV depressive symptoms and risk for suicide completion in major depressive disorder: a psychological autopsy study. Journal of Affective Disorders 97, 203–209. Melle, I., Johannesen, J.O., Friis, S., Haahr, U., Joa, I., Larsen, T.K., Opjordsmoen, S., Rund, B.R., Simonsen, E., Vaglum, P., McGlashan, T., 2006. Early detection of the first episode of schizophrenia and suicidal behavior. American Journal of Psychiatry 163, 800–804. Meltzer, H.Y., 2005. Suicidality in schizophrenia: pharmacologic treatment. Clinical Neuropsychiatry 2, 76–83. Meltzer, H.Y., Alphs, L., Green, A.I., Altamura, A.C., Anand, R., Bertoldi, A., Bourgeois, M., Chouinard, G., Islam, M.Z., Kane, J., Krishnan, R., Lindenmayer, J.P., Potkin, S., 2003. Clozapine treatment for suicidality in schizophrenia: International Suicide Prevention Trial (InterSePT). Archives of General Psychiatry 60, 82–91. Miles, C.P., 1977. Conditions predisposing to suicide: a review. Journal of Nervous and Mental Disease 164, 231–246. Montross, L.P., Zisook, S., Kasckow, J., 2007. Command hallucinations and suicide risk. In: Tatarelli, R., Pompili, M., Girardi, P. (Eds.), Suicide in Schizophrenia. Nova Science Publishers Inc., New York, pp. 113–132. Nordentoft, M., Mortensen, P.B., 2007. Hospital admission and suicide in schizophrenia. In: Tatarelli, R., Pompili, M., Girardi, P. (Eds.), Suicide in Schizophrenia. Nova Science Publishers Inc., New York, pp. 61–76. Nordentoft, M., Jeppesen, P., Abel, M., Kassow, P., Petersen, L., Thorup, A., Krarup, G., Hemmingsen, R., Jørgensen, P., 2002. OPUS study: suicidal behaviour, suicidal ideation and hopelessness among patients with first-episode psychosis. One-year follow-up of a randomised controlled trial. British Journal of Psychiatry Supplement 43, s98–s106 (2002).
257
Nordentoft, M., Laursen, T.M., Agerbo, E., Qin, P., Hoyer, E.H., Mortensen, P.B., 2004. Change in suicide rates for patients with schizophrenia in Denmark, 1981–97: nested case-control study. British Medical Journal 329, 261. Palmer, B.A., Pankratz, V.S., Bostwick, J.M., 2005. The lifetime risk of suicide in schizophrenia: a reexamination. Archives of General Psychiatry 62, 247–253. Pavia, M., Nicotera, G., Scaramazza, G., Angelillo, I.F., 2005. Suicide mortality in Southern Italy: 1998–2002. Psychiatry Research 134, 275–279. Pompili, M., 2007. Suicide risk in schizophrenia: an overview. In: Tatarelli, R., Pompili, M., Girardi, P. (Eds.), Suicide in Schizophrenia. Nova Science Publishers Inc., New York, pp. 1–18. Pompili, M., Girardi, P., Ruberto, A., Tatarelli, R., 2004a. Toward a new prevention of suicide in schizophrenia. World Journal of Biological Psychiatry 5, 201–210. Pompili, M., Ruberto, A., Kotzalidis, G.A., Girardi, P., Tatarelli, R., 2004b. Awareness of illness and suicide in schizophrenia: an overview. Bulletin of the Menninger Clinic 68, 297–318. Pompili, M., Mancinelli, I., Ruberto, A., Kotzalidis, G.D., Girardi, P., Tatarelli, R., 2005. Where schizophrenic patients commit suicide: a review of suicide among inpatients and former inpatients. International Journal of Psychiatry in Medicine 35, 171–190. Pompili, M., Amador, X.F., Girardi, P., Harkavy-Friedman, J., Harrow, M., Kaplan, K., Krausz, M., Lester, D., Meltzer, H.Y., Modestin, J., Montross, L.P., Mortensen, P.B., Munk-Jorgensen, P., Nielsen, J., Nordentoft, M., Saarinen, P.I., Zisook, S., Wilson, S.T., Tatarelli, R., 2007. Suicide risk in schizophrenia: learning from the past to change the future. Annals of General Psychiatry 6, 10. Preti, A., Miotto, P., 2000. Increase in first admissions for schizophrenia and other major psychoses in Italy. Psychiatry Research 94, 139–152. Qin, P., Nordentoft, M., 2005. Suicide risk in relation to psychiatric hospitalization: evidence based on longitudinal registers. Archives of General Psychiatry 62, 427–432. Rogers, P., Watt, A., Gray, N.S., MacCulloch, M., Gournay, K., 2002. Content of command hallucinations predicts self-harm but not violence in a medium secure unit. Journal of Forensic Psychiatry 13, 251–262. Roy, A., 1982. Suicide in chronic schizophrenia. British Journal of Psychiatry 141, 171–177. Saarinen, P.I., Lehtonen, J., Lonnqvist, J., 1999. Suicide risk in schizophrenia: an analysis of 17 consecutive suicides. Schizophrenia Bulletin 25, 533–542. Sakinofsky, I., Heila, H., Krishnan, R., 2004. Estimating suicidality as an outcome measure in clinical trials of suicide in schizophrenia. Schizophrenia Bulletin 30, 587–598. Turkington, D., Kingdon, D., Turner, T., 2002. Effectiveness of a brief cognitive–behavioural therapy intervention in the treatment of schizophrenia. British Journal of Psychiatry 180, 523–527. Westermeyer, J.F., Harrow, M., Marengo, J.T., 1991. Risk for suicide in schizophrenia and other psychotic and nonpsychotic disorders. Journal of Nervous and Mental Disease 179, 259–266. Wilson, S.T., Amador, X.F., 2007. Awareness of illness and the risk of suicide in schizophrenia. In: Tatarelli, R., Pompili, M., Girardi, P. (Eds.), Suicide Risk in Schizophrenia. Nova Publishers Inc., New York, pp. 133–145. Zisook, S., Byrd, D., Kuck, J., Jeste, D.V., 1995. Command hallucinations in outpatients with schizophrenia. Journal of Clinical Psychiatry 56, 462–465.
Psychiatry Research 167 (2009) 251 – 257 www.elsevier.com/locate/psychres
Completed suicide in schizophrenia: Evidence from a case-control study Maurizio Pompili a,b,⁎, David Lester c , Alessandro Grispini d , Marco Innamorati e , Fulvia Calandro d , Paolo Iliceto a , Eleonora De Pisa a , Roberto Tatarelli a , Paolo Girardi a a
Department of Psychiatry, Sant'Andrea Hospital, “Sapienza” University of Rome, Italy b McLean Hospital, Harvard Medical School, Belmont, MA, USA c The Richard Stockton College of New Jersey, Pomona, NJ, USA d Department of Mental Health “Roma E”, Italy e Universita' Europea of Rome, Italy
Received 23 May 2007; received in revised form 4 October 2007; accepted 14 March 2008
Abstract Suicide is the single major cause of death among patients with schizophrenia. Despite great efforts in the prevention of such deaths, suicide rates have remained alarming, pointing to the need for a better understanding of the phenomenon. The present sample comprised 20 male patients with schizophrenia who committed suicide and who were investigated retrospectively for a large number of characteristics. Controls were 20 living patients with schizophrenia. The results suggest that suicide attempts, hopelessness and self-devaluation were the three variables most strongly associated with completed suicide. However, a number of variables were identified which may constitute risk factors, some of which have not been identified in the past: agitation and motor restlessness (OR = 3.66; 95%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 = 0.95/14.02), and suicide attempt (OR = 3.66; 95%CI = 1.40/114.41). Poor adherence to medications was also predictive of completed suicide in our sample of schizophrenia patients, primarily because the suicide victims showed very low adherence. © 2008 Elsevier Ireland Ltd. All rights reserved. Keywords: Suicide; Schizophrenia; Risk factors
1. Introduction In the last decades, a number of studies have confirmed the first reports (Kraepelin, 1919; Lipschutz, 1942) that ⁎ Corresponding author. Department of Psychiatry, Ospedale Sant'Andrea, Via di Grottarossa, 1035, 00189 Roma, Italy. E-mail addresses: [email protected], [email protected] (M. Pompili).
patients with schizophrenia frequently commit suicide (e.g., Beisser and Blanchette, 1961; Miles, 1977; Caldwell and Gottesman, 1990; Pompili et al., 2005) and make multiple suicide attempts (e.g., Pompili, 2007), often using violent methods for committing suicide (Roy, 1982; Breier and Astrachan, 1984; Cheng et al., 1990). Kelly et al. (2004) found that 73% of their sample committed suicide by violent methods such as jumping from a height, drowning, cutting, gunshot wounds or hanging. Beisser
0165-1781/$ - see front matter © 2008 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.psychres.2008.03.018
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and Blanchette (1961) investigated 75 suicides committed in mental hospitals in California. A diagnosis of schizophrenia had been made in around half of the cases in the series, one half of the patients had previously threatened to commit suicide, and half had attempted suicide in the past. In 89% of the cases, the method used was hanging, and 52% of the patients committed suicide while they were in isolation. Thus, restricting individuals with schizophrenia to a safe environment, where lethal methods for committing suicide are not easily available, is of utmost importance. Recently, new meta-analyses (Inskip et al., 1998; Palmer et al., 2005) have reviewed the prevalence of suicide in patients affected by schizophrenia, and estimated lower rates than had earlier studies (e.g., Caldwell and Gottesman, 1990; Miles, 1977). These authors stated that around 4–5% of individuals with schizophrenia commit suicide during their lifetime (Inskip et al., 1998; Palmer et al., 2005). Meltzer (2005) recently pointed out that the question is not resolved and, regardless of the lower recent estimates, the prevalence of suicide is still unacceptably high. However, Nordentoft et al. (2004) in a nested case-control study found a decrease in recent years in suicide deaths of schizophrenia patients when examining four longitudinal Danish registers for the period 1981 to 1997. Evidence suggests several risk factors for suicide, such as being young, male and unmarried, and having high family stress, limited external support, deteriorating health with a high level of premorbid functioning, an awareness of the illness, hospitalization, post-psychotic depression, and a history of substance abuse and suicide attempts. Hopelessness, social isolation, recent loss or rejection and instability are also important factors in individuals with schizophrenia who commit suicide. These patients usually fear further mental deterioration, and they experience either excessive treatment dependence or loss of faith in treatment (Pompili et al., 2004a; Pompili, 2007; Pompili et al., 2007). Positive symptoms are generally less often included among risk factors for suicide in schizophrenia. However, a number of studies have found that the active and exacerbated phase of the illness and the presence of psychotic symptoms (De Hert et al., 2001; Heila et al., 1997; Hu et al., 1991; Westermeyer et al., 1991), as well as paranoid delusions and thought disorder (Krupinski et al., 2000; Saarinen et al., 1999), are associated with a high risk of suicide. Patients with the paranoid subtype of schizophrenia are also more likely to commit suicide (Fenton et al., 1997; Roy, 1982). Suicides as a result of command hallucinations, although rare, have been reported in the literature (Zisook et al., 1995). Kelly
et al. (2004) reported that a large proportion of their patients affected with schizophrenia who committed suicide had poor control of thoughts/thought insertion, loose associations and flight of ideas compared with those who died by other means of death. Drug treatment of schizophrenia is generally associated with a reduced risk of suicide. In this regard, clozapine has been found to reduce suicide risk in schizophrenia (Meltzer et al., 2003; Pompili et al., 2007). However, because the administration of both clozapine and atypical antipsychotics may be accompanied by increased insight and illness awareness, and because sudden increases in insight may lead to increased suicidality in patients with schizophrenia (Turkington et al., 2002), caution is needed, and patients should be followed closely in an appropriate therapeutic relationship to monitor such abrupt increases in insight (Pompili et al., 2004b). Suicide risk among patients with schizophrenia is usually assessed retrospectively through statistical analysis. Prospective studies are rare (Sakinofsky et al., 2004). It seems that risk factors identified for samples of patients are less useful when extrapolated to the individual patient. The use of risk factors often yields too many false positives and fails to identify many of those who later turn out to have been at risk of suicide. The aim of the present study was to compare individuals suffering from schizophrenia who committed suicide with living individuals suffering from the same disorder. Differences in clinical and sociodemographic variables were examined in an attempt to identify predictive factors that might assist clinicians in identifying suicidality among patients with schizophrenia. 2. Methods 2.1. Subjects In this retrospective case-control study the sample consisted of 20 suicide victims with a diagnosis of schizophrenia and 20 living controls, who sought outpatient treatment in 1998–2003 and who were followed to 2004 at the “Rome E” psychiatric clinic (a branch of the Italian National Mental Health Service). Each control was randomly selected from patients admitted during the same period of time as the suicide victims (±15 days). Included were patients with a diagnosis of schizophrenia either using the ICD-9 or DSM-IV criteria (Italian Health Systems require official diagnoses to be conform to ICD criteria). We excluded patients whose sociodemographic variables were unavailable, and patients where ICD or DSM-IV criteria for schizophrenia were not fully met, e.g., cases diagnosable as schizophrenia by the less restrictive
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temporal criteria of ICD-9 or who were followed up for less than 6 months. One of the authors (FC) inspected a total of 3000 clinical records. Of these patients, 264 were individuals with schizophrenia whose characteristics were compatible with inclusion criteria (20 out of the 264 patients killed themselves). Suicide was confirmed by the official death certificate. The principal investigator (MP) and another investigator (FC) independently inspected all records of patients with a diagnosis of schizophrenia and charted these patients on the basis of a checklist. (When unanimous decision was difficult to reach, a third party was consulted.) The same process was applied to the control group; that is, investigators independently selected controls according to the criteria used for selecting patients. The final sample consisted of 20 male suicides (mean age 40.10 ± 14.06 S.D.; range 23–76 years) and 20 living patients diagnosed with schizophrenia as controls (mean age 45.85 ± 13.26 S.D.; range 28–76 years), 18 men and 2 women. All suicides and controls were white Italians. Sociodemographic characteristics of the patients are listed in Table 1. 2.2. Assessment of clinical and demographic variables Two authors independently reviewed selected records to identify relevant variables for the study. The symptoms were rated according to a checklist. The checklist items were included according to their relevance as defined by all the authors at the beginning of the study. The symptoms were rated as present when the full criteria were met. Change over time was not considered. Each symptom was rated as Table 1 Sociodemographic characteristics of subjects. Characteristic
Controls Cases Statistics (N = 20) (N = 20)
Male — % 100.0 Female — % – Age (years) — mean ± S.D. 45.85 ± 13.26 Married — % 5% Education (≤8 years) — 45% % Unemployed — % 85%
90.0 10.0 40.10 ± t = 1.33; 14.06 df = 38 15% 50%
0.60 a 0.74 a
75%
0.69 a
Schizophrenia subtypes according ICD-9 — N Simple 12 9 Disorganized type 2 1 Paranoid type 2 2 Residual type 2 5 Unspecified 1 1 Other subtypes 1 2 a
Fisher's exact test.
P
0.19
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present either when related to impaired personal functioning (interpersonal, occupational, self-care or health behavior) and suffering, or when long lasting (2 consecutive sessions or more during the study follow-up) or frequent (3 sessions or more during the whole study follow-up). Each variable was defined by operational criteria. Low adherence to medications involved not taking regularly, suspending, or modifying treatment prescriptions either voluntarily or due to forgetfulness. The physical illness item was rated as present when any general medical condition affected the health of the patients during the study follow-up and demanded medications or counselling from a physician. The hallucination item involved sensory/perceptual distortions causing impaired functioning. Delusions involved a fixed false belief causing impaired functioning. Odd behavior included behaviors that are eccentric or peculiar and that caused impaired functioning. Thought disorders involved ideas of reference, odd beliefs or magical thinking inconsistent with subcultural norms. Affective flattening involved restrictions in the range or intensity of emotional expression causing poor functioning. Alogia involved poverty of thinking indicated either by poverty of speech or by poverty in the content of speech. Anhedonia involved a total loss of feeling of pleasure in acts that normally give pleasure. Agitation or motor restlessness involved an inability to rest, relax or be still. Self-devaluation involved ideation or speech indicating low self-esteem. Hopelessness involved ideation or speech indicating a negative view of the future. Insight involved clear perception of the patient's own situation. Fear of mental disintegration involved painful feelings of discomfort regarding growing difficulty in concentration, attention or abstract thinking. Positive symptoms included all symptoms involving altered behavior or thinking even when rated in another item, such as delusions, hallucinations, overactivity or incoherent thought and speech. Negative symptoms included all the symptoms involving lack or reduction of behaviors, even when rated in another item, such as affective flattening, alogia, anhedonia, difficulty in abstract thinking, stereotyped thinking, or attentional impairment. Depressive disorder NOS involved the presence of depressive symptoms not matching the criteria for the major depressive disorders, such a post-psychotic depressive syndrome. Insomnia involved difficulty initiating or maintaining sleep, or nonrestorative sleep causing impaired functioning or suffering that was long lasting or demanded treatment. Substance use disorders involved harmful use of or dependence on a specific psychoactive substance, including illicit drugs, alcohol or non-prescribed medications. Violence involved a lifetime history of aggressive behavior against objects or other people.
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Suicide attempts were defined as a non-habitual behavior with the intent of ending one's life which was unsuccessful in causing death. Illness history was determined retrospectively by reviewing clinical records and notes provided by the referring physicians. Because of the low rates of most schizophrenia subtypes, these were grouped in two clusters: the first group included the simple subtype, and the latter included all the other subtypes. The two groups were compared for the types of schizophrenia, and no significant differences were observed (Fisher's exact test = 0.32) (see Table 1). 2.3. Data analysis Statistical analyses included χ2 tests, Fisher's exact tests (1-FET), and t-tests. Two-tailed t-tests were used for the continuous variables. Chi-square tests and Fisher's exact tests were used to identify differences in sociodemographic characteristics. Single variable logistic regression analyses were performed; odds ratios (OR) and 95% confidence intervals (95%CI) were reported to identify relevant variables as risk factors for suicidality.
Statistical analyses were conducted with SPSS for Windows version 13.1. 3. Results There were no differences between controls and cases on sociodemographic characteristics. Almost all subjects were men, never married and unemployed, and 50% had a low level of education (≤8 years). The mean age (S.D.) at which the patients completed suicide was 40.10 (14.06) and did not significantly differ from the mean age of 45.85 (13.26) for the controls (t = 1.33, df= 38, P = 0.19). The association between suicidality and adherence to medications was statistically significant (1-FET = 0.000) primarily because the suicide victims showed very low adherence. Major factors predictive of suicidality in the bivariate associations (see Table 2), ordered by OR, were: 1) hopelessness, 2) self-devaluation, 3) suicide attempt, 4) insomnia, 5) mental disintegration, and 6) agitation or motor restlessness. Only three factors showed a tendency (NS) to be protective: absence of attention deficit (OR = 0.20; P = 0.07), insight (OR = 0.40; P = 0.19) and age (OR = 0.96; P = 0.19).
Table 2 Single variable logistic regression analysis. Factor
Controls (%)
Cases (%)
OR
95%CI
z
P
Age Age of illness when first referred Physical illness Hallucinations Delusions Odd behavior Thought disorder Positive symptoms Negative symptoms Affective flattening Alogia Anhedonia Reduction in motor activity Absence of attention deficit Depressive disorder NOS Agitation or motor restlessness Self-devaluation Hopelessness Insomnia Insight Mental disintegration Substance use disorders Hospital admissions Violence Suicide attempt Adherence to medications
45.85 ± 13.26 a 22.05 ± 9.06 a 1 (5.0) 11 (55.0) 14 (70.0) 8 (40.0) 7 (35.0) 18 (90.0) 19 (95.0) 12 (60.0) 8 (40.0) 17 (85.0) 13 (65.0) 7 (35.0) 10 (50.0) 9 (45.0) 1 (5.0) 3 (15.0) 1 (5.0) 15 (75.0) 1 (5.0) 2 (10.0) 2 (10.0) 10 (50.0) 3 (15.0) 13 (65.0)
40.10 ± 14.06 a 22.10 ± 11.29 a 2 (10.0) 16 (80.0) 19 (95.0) 14 (70.0) 12 (60.0) 19 (95.0) 19 (95.0) 12 (60.0) 10 (50.0) 19 (95.0) 16 (80.0) 2 (10.0) 15 (75.0) 15 (75.0) 12 (60.0) 18 (90.0) 8 (40.0) 11 (55.0) 7 (35.0) 7 (35.0) 5 (25.0) 14 (70.0) 14 (70.0) 2 (10.0)
0.96 1.02 2.11 3.27 8.13 3.50 2.78 2.11 1.00 1.00 1.50 3.35 2.15 0.20 3.00 3.66 28.49 51.00 12.66 0.40 10.21 4.84 3.00 2.33 13.22 0.06
0.92–1.01 0.95–1.08 0.17–25.34 0.80–13.34 0.87–75.40 0.94–12.96 0.77–10.04 0.17–25.34 0.05–17.18 0.28–3.54 0.42–5.24 0.31–35.36 0.51–8.99 0.03–1.15 0.78–11.44 0.95–14.02 3.15–257.40 7.56–343.72 1.40–114.41 0.10–1.55 1.12–93.12 0.86–27.22 0.50–17.72 0.63–8.53 2.78–62.66 0.01–.34
− 1.28 0.63 0.58 1.64 1.85 1.87 1.56 0.58 0.00 0.00 0.63 1.00 1.05 − 1.79 1.61 1.90 2.98 4.04 2.26 − 1.31 2.06 1.79 1.21 1.28 3.25 − 2.82
0.19 0.52 0.55 0.09 0.06 0.06 0.11 0.55 1.00 1.00 0.52 0.31 0.29 0.07 0.10 0.05 0.003 0.000 0.02 0.19 0.03 0.07 0.22 0.20 0.001 0.001
OR = odds ratio; CI = confidence interval. a Values shown as mean ± S.D. (median).
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4. Discussion This study compared patients with schizophrenia who completed suicide with living subjects suffering from schizophrenia. Of note is the finding that the suicides in our sample were older than is commonly reported in the international literature on suicide in schizophrenia. This was somewhat unexpected as most of our patients suffered from the simple subtype of schizophrenia. Suicide risk in schizophrenia is generally associated with the paranoid subtype of the illness whose onset is later than in the other subtypes. These patients generally manage to study and work reasonably well due to the late onset of schizophrenia and, when they become sick, they can no longer perform in the same way. Therefore, good premorbid functioning has been reported as a risk factor for suicide among these patients (Dingman and McGlashan, 1986). Previous studies have reported a number of risk factors for suicide, and some of them were confirmed in the present study. The risk factors included those that are shared with individuals in the general population (such as male gender, self-reported hopelessness, substance use disorders, and prior suicide attempts) and those that are disease-specific to schizophrenia (such as a long illness with exacerbations, awareness of illness, and a low number of negative symptoms). In the present study, the patients with schizophrenia who committed suicide were men, confirming that male gender is associated with completed suicide (Lester, 2007), but they were older than expected on the basis of previous research (Caldwell and Gottesman, 1990). Selfdevaluation (worthlessness), hopelessness and suicide attempts were the three variables most strongly associated with completed suicide, and this finding was consistent with conclusions from previous systematic reviews (Caldwell and Gottesman, 1990; Hawton et al., 2005). Poor adherence to medications was also predictive of completed suicide in our sample of schizophrenia patients, a finding consistent with the current literature (Auquier et al., 2007). In addition, mental disintegration and agitation or motor restlessness were significantly associated with suicide risk, while hallucinations and delusions, odd behavior, substance misuse and depressive disorder NOS were positively associated but the association did not reach the level of statistical significance. Hawton et al. (2005) reported mixed results for those risk factors. For example, they concluded that only drug use disorders were associated with increased suicide risk (while alcohol yielded a non-significant association with suicide risk). Hawton et al. (2005) also reported an inverse association between hallucinations and suicide risk.
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The association between completed suicide and the presence of comorbid depressive episodes, although not statistically significant in the present study, is an important issue that has been highlighted in the international literature (McGirr et al., 2006) These authors found that in the logistic regression model current depressive disorder NOS was the independent predictor of suicide with the largest adjusted effect on risk. Positive symptoms, for which the findings of previous studies had been inconsistent, were not associated with suicide risk in the present study. This is somewhat inconsistent with a number of studies that found that the active and exacerbated phase of the illness and the presence of psychotic symptoms were associated with suicidal risk (De Hert et al., 2001; Heila et al., 1997; Hu et al., 1991; Westermeyer et al., 1991). However, our results are limited because the role of command hallucination in the precipitation of suicide was not studied (Harkavy-Friedman et al., 2003; Montross et al., 2007; Rogers et al., 2002; Zisook et al., 1995). Another important risk factor that emerged from our investigation was the presence of insomnia, a finding rarely reported hitherto. For example, Keshavan et al. (1994) found that those patients with schizophrenia who exhibited suicidal behavior had increased overall rapid eye movement (REM) activity and REM time, while Jones et al. (1994) found that nonsuppression in the dexamethasone suppression test (DST) could be related to suicidal behavior in a sample of individuals with schizophrenia. However, Lewis et al. (1996) contradicted these latter findings regarding nonsuppresion in the DST and reported that, in their sample of patients with schizophrenia, total REM sleep time was associated with suicidal behavior. These authors suggested that since serotonergic neurons act to suppress REM sleep, reduced serotonergic function in schizophrenia could explain the association between suicidal behavior and REM time/ activity that had been observed. Our results are consistent with McGirr et al. (2007), who found that insomnia was associated with a higher suicide risk in their sample of patients with major depressive disorder. Pompili et al. (2005) reviewed the literature on suicide among inpatients with schizophrenia and found that the suicide rate in cohorts of patients with schizophrenia who were followed up after the first hospitalization for periods ranging from1 to 26 years was 6.8%. Surprisingly, in our sample, the number of prior hospital admissions was not associated with suicide risk as is usually reported in the literature (Nordentoft and Mortensen, 2007; Qin and Nordentoft, 2005). Of note, however, is the finding of Preti and Miotto (2000), who reported that the incidence of hospitalizations for major psychoses is on the rise.
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These authors found that yearly first-admission rates for paranoia almost tripled from 1984 to 1994; a similarly significant rise was observed for schizophrenia and affective psychoses, with a greater increase for mania than for major depression. Nordentoft et al. (2002) found that suicidal behavior and suicidal ideation occur very frequently among patients with first-episode schizophrenic psychoses. Such findings were also confirmed by Melle et al. (2006), who reported that suicidal behavior is present in the early phases of psychotic disorders and in many cases precedes the first treatment contact. While patients from communities that did not have the early psychosis detection program showed rates of suicidal behavior in the expected range, the early detection group had significantly lower rates. In line with this, in Italy, selected groups may benefit from targeted prevention programs especially for those who are unemployed, those with low levels of education, those who are retired, and those who are single or divorced (Pavia et al., 2005; Masocco and co-workers, unpublished results). Our study focused only on a few protective factors, and none resulted in significant differences. Interestingly, the most powerful protective factors were the absence of attention deficits and insight. An earlier study (Wilson and Amador, 2007) identified a hopeless awareness of one's illness as an important predictor of completed suicide in patients with schizophrenia. Research findings to date seem to suggest that awareness of illness is associated with increased suicide risk, but only if that awareness leads to hopelessness. Lastly, we have to mention a number of limitations of our study regarding the generalization of the findings, such as the small ratio of sample variables, potentially causing an inflation of type I errors. Also, our investigation has the typical limitations of retrospective analyses of records. In fact, despite great efforts and strict selection of records included in the study, identification of variables among notes and charts in a few cases resulted in the impossibility of ascertaining beyond a reasonable doubt that a specific patient presented or did not present a given symptom. Even if we found that delusions and hallucinations were associated with suicide risk, we could not identify what was the typology of such symptoms, and this may be a limitation of the study, given the fact that some types of hallucinations and delusions, but not all of them, may be associated with increased suicide risk. Despite these caveats, our preliminary study strongly supports previous findings in the literature and highlights the role of risk factors rarely studied, helping in the assessment of suicide risk through the implementation of the knowledge of risk factors and the search for possible
new risk factors. Clinicians must be aware that it is not only the younger patients who are at risk of suicide. They should also pay attention to such cognitive, emotional and behavioral signs as hopelessness, self-devaluation, insomnia, mental disintegration, and motor restlessness. A systematic inquiry into previous instances of suicidality is also mandatory. In conclusion, suicide in schizophrenia is a complex phenomenon, requiring targeted educational activity for medical staff, proper utilization of the therapeutic armamentarium together with better access for patients to atypical antipsychotic drugs and destigmatization of the psychiatric disorders. Acknowledgment The authors are grateful to Prof. Jill Harkavy-Friedman who gave suggestions for improving the manuscript. References Auquier, P., Lancon, C., Rouillon, F., Lader, M., Holmes, C., 2007. Mortality in schizophrenia. Pharmacoepidemiology & Drug Safety 16 (12), 1308–1312. Beisser, A.R., Blanchette, J.E., 1961. A study of suicides in a mental hospital. Diseases of the Nervous System 22, 365–369. Breier, A., Astrachan, B.M., 1984. Characterization of schizophrenic patients who commit suicide. American Journal of Psychiatry 141, 206–209. Caldwell, C.B., Gottesman, I., 1990. Schizophrenics kill themselves too: a review of risk factors for suicide. Schizophrenia Bulletin 16, 571–589. Cheng, K.K., Leung, C.M., Lo, W.H., Lam, T.H., 1990. Risk factors of suicide among schizophrenics. Acta Psychiatrica Scandinavica 81, 220–224. De Hert, M., McKenzie, K., Peuskens, J., 2001. Risk factors for suicide in young people suffering from schizophrenia: a long-term follow-up study. Schizophrenia Research 47, 127–134. Dingman, C.W., McGlashan, T.H., 1986. Discriminating characteristics of suicides. Chestnut Lodge follow-up sample including patients with affective disorder, schizophrenia and schizoaffective disorder. Acta Psychiatrica Scandinavica 74, 91–97. Fenton, W.S., McGlashan, T.H., Victor, B.J., Blyler, C.R., 1997. Symptoms, subtype and suicidality in patients with schizophrenia spectrum disorders. American Journal of Psychiatry 154, 199–204. Harkavy-Friedman, J.M., Kimhy, D., Nelson, E.A., Venarde, D.F., Malaspina, D., Mann, J.J., 2003. Suicide attempts in schizophrenia: the role of command auditory hallucinations for suicide. Journal of Clinical Psychiatry 64, 871–874. Hawton, K., Sutton, L., Haw, C., Sinclair, J., Deeks, J.J., 2005. Schizophrenia and suicide: systematic review of risk factors. British Journal of Psychiatry 187, 9–20. Heila, H., Isometsa, E.T., Henriksson, M.M., Heikkinen, M.E., Marttunen, M.J., Lonnqvist, J.K., 1997. Suicide and schizophrenia: a nationwide psychological autopsy study on age- and sex-specific clinical characteristics of 92 suicide victims with schizophrenia. American Journal of Psychiatry 154, 1235–1242. Hu, W.H., Sun, C.M., Lee, C.T., Peng, S.L., Lin, S.K., Shen, W.W., 1991. A clinical study of schizophrenic suicides. 42 cases in Taiwan. Schizophrenia Research 5, 43–50.
M. Pompili et al. / Psychiatry Research 167 (2009) 251–257 Inskip, H.M., Harris, E.C., Barraclough, B., 1998. Lifetime risk of suicide for affective disorder, alcoholism and schizophrenia. British Journal of Psychiatry 172, 35–37. Jones, J.S., Stein, D.J., Stanley, B., Guido, J.R., Winchel, R., Stanley, M., 1994. Negative and depressive symptoms in suicidal schizophrenics. Acta Psychiatrica Scandinavica 89, 81–87. Kelly, D.L., Shim, J.C., Feldman, S.M., Yu, Y., Conley, R.R., 2004. Lifetime psychiatric symptoms in persons with schizophrenia who died by suicide compared to other means of death. Journal of Psychiatric Research 38, 531–536. Keshavan, M.S., Reynolds, C.F., Montrose, D., Miewald, J., Downs, C., Sabo, E.M., 1994. Sleep and suicidality in psychotic patients. Acta Psychiatrica Scandinavica, 89, 122–125. Kraepelin, E., 1919. Dementia Praecox and Paraphrenia. Livingstone, Edimburgh. Krupinski, M., Fischer, A., Grohmann, R., Engel, R.R., Hollweg, M., Moller, H.J., 2000. Schizophrenic psychoses and suicide in the clinic. Risk factors, psychopharmacologic treatment. Nervenarzt 71, 906–911. Lester, D., 2007. Suicide mortality in schizophrenics. In: Tatarelli, R., Pompili, M., Girardi, P. (Eds.), Suicide in Schizophrenia. Nova Science Publishers Inc., New York, pp. 19–29. Lewis, C.F., Tandon, R., Shipley, J.E., DeQuardo, J.R., Jibson, M., Taylor, S.F., Goldman, M., 1996. Biological predictors of suicidality in schizophrenia. Acta Psychiatrica Scandinavica 94, 416–420. Lipschutz, L.S., 1942. Some administrative aspects of suicides in the mental hospital. American Journal of Psychiatry 99, 181–187. McGirr, A., Tousignant, M., Routhier, D., Pouliot, L., Chawky, N., Margolese, H.C., Turecki, G., 2006. Risk factors for completed suicide in schizophrenia and other chronic psychotic disorders: a case-control study. Schizophrenia Research 84, 132–143. McGirr, A., Renaud, J., Seguin, M., Alda, M., Benkelfat, C., Lesage, A., Turecki, G., 2007. An examination of DSM-IV depressive symptoms and risk for suicide completion in major depressive disorder: a psychological autopsy study. Journal of Affective Disorders 97, 203–209. Melle, I., Johannesen, J.O., Friis, S., Haahr, U., Joa, I., Larsen, T.K., Opjordsmoen, S., Rund, B.R., Simonsen, E., Vaglum, P., McGlashan, T., 2006. Early detection of the first episode of schizophrenia and suicidal behavior. American Journal of Psychiatry 163, 800–804. Meltzer, H.Y., 2005. Suicidality in schizophrenia: pharmacologic treatment. Clinical Neuropsychiatry 2, 76–83. Meltzer, H.Y., Alphs, L., Green, A.I., Altamura, A.C., Anand, R., Bertoldi, A., Bourgeois, M., Chouinard, G., Islam, M.Z., Kane, J., Krishnan, R., Lindenmayer, J.P., Potkin, S., 2003. Clozapine treatment for suicidality in schizophrenia: International Suicide Prevention Trial (InterSePT). Archives of General Psychiatry 60, 82–91. Miles, C.P., 1977. Conditions predisposing to suicide: a review. Journal of Nervous and Mental Disease 164, 231–246. Montross, L.P., Zisook, S., Kasckow, J., 2007. Command hallucinations and suicide risk. In: Tatarelli, R., Pompili, M., Girardi, P. (Eds.), Suicide in Schizophrenia. Nova Science Publishers Inc., New York, pp. 113–132. Nordentoft, M., Mortensen, P.B., 2007. Hospital admission and suicide in schizophrenia. In: Tatarelli, R., Pompili, M., Girardi, P. (Eds.), Suicide in Schizophrenia. Nova Science Publishers Inc., New York, pp. 61–76. Nordentoft, M., Jeppesen, P., Abel, M., Kassow, P., Petersen, L., Thorup, A., Krarup, G., Hemmingsen, R., Jørgensen, P., 2002. OPUS study: suicidal behaviour, suicidal ideation and hopelessness among patients with first-episode psychosis. One-year follow-up of a randomised controlled trial. British Journal of Psychiatry Supplement 43, s98–s106 (2002).
257
Nordentoft, M., Laursen, T.M., Agerbo, E., Qin, P., Hoyer, E.H., Mortensen, P.B., 2004. Change in suicide rates for patients with schizophrenia in Denmark, 1981–97: nested case-control study. British Medical Journal 329, 261. Palmer, B.A., Pankratz, V.S., Bostwick, J.M., 2005. The lifetime risk of suicide in schizophrenia: a reexamination. Archives of General Psychiatry 62, 247–253. Pavia, M., Nicotera, G., Scaramazza, G., Angelillo, I.F., 2005. Suicide mortality in Southern Italy: 1998–2002. Psychiatry Research 134, 275–279. Pompili, M., 2007. Suicide risk in schizophrenia: an overview. In: Tatarelli, R., Pompili, M., Girardi, P. (Eds.), Suicide in Schizophrenia. Nova Science Publishers Inc., New York, pp. 1–18. Pompili, M., Girardi, P., Ruberto, A., Tatarelli, R., 2004a. Toward a new prevention of suicide in schizophrenia. World Journal of Biological Psychiatry 5, 201–210. Pompili, M., Ruberto, A., Kotzalidis, G.A., Girardi, P., Tatarelli, R., 2004b. Awareness of illness and suicide in schizophrenia: an overview. Bulletin of the Menninger Clinic 68, 297–318. Pompili, M., Mancinelli, I., Ruberto, A., Kotzalidis, G.D., Girardi, P., Tatarelli, R., 2005. Where schizophrenic patients commit suicide: a review of suicide among inpatients and former inpatients. International Journal of Psychiatry in Medicine 35, 171–190. Pompili, M., Amador, X.F., Girardi, P., Harkavy-Friedman, J., Harrow, M., Kaplan, K., Krausz, M., Lester, D., Meltzer, H.Y., Modestin, J., Montross, L.P., Mortensen, P.B., Munk-Jorgensen, P., Nielsen, J., Nordentoft, M., Saarinen, P.I., Zisook, S., Wilson, S.T., Tatarelli, R., 2007. Suicide risk in schizophrenia: learning from the past to change the future. Annals of General Psychiatry 6, 10. Preti, A., Miotto, P., 2000. Increase in first admissions for schizophrenia and other major psychoses in Italy. Psychiatry Research 94, 139–152. Qin, P., Nordentoft, M., 2005. Suicide risk in relation to psychiatric hospitalization: evidence based on longitudinal registers. Archives of General Psychiatry 62, 427–432. Rogers, P., Watt, A., Gray, N.S., MacCulloch, M., Gournay, K., 2002. Content of command hallucinations predicts self-harm but not violence in a medium secure unit. Journal of Forensic Psychiatry 13, 251–262. Roy, A., 1982. Suicide in chronic schizophrenia. British Journal of Psychiatry 141, 171–177. Saarinen, P.I., Lehtonen, J., Lonnqvist, J., 1999. Suicide risk in schizophrenia: an analysis of 17 consecutive suicides. Schizophrenia Bulletin 25, 533–542. Sakinofsky, I., Heila, H., Krishnan, R., 2004. Estimating suicidality as an outcome measure in clinical trials of suicide in schizophrenia. Schizophrenia Bulletin 30, 587–598. Turkington, D., Kingdon, D., Turner, T., 2002. Effectiveness of a brief cognitive–behavioural therapy intervention in the treatment of schizophrenia. British Journal of Psychiatry 180, 523–527. Westermeyer, J.F., Harrow, M., Marengo, J.T., 1991. Risk for suicide in schizophrenia and other psychotic and nonpsychotic disorders. Journal of Nervous and Mental Disease 179, 259–266. Wilson, S.T., Amador, X.F., 2007. Awareness of illness and the risk of suicide in schizophrenia. In: Tatarelli, R., Pompili, M., Girardi, P. (Eds.), Suicide Risk in Schizophrenia. Nova Publishers Inc., New York, pp. 133–145. Zisook, S., Byrd, D., Kuck, J., Jeste, D.V., 1995. Command hallucinations in outpatients with schizophrenia. Journal of Clinical Psychiatry 56, 462–465.