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Suicide attempts in schizophrenic patients: Clinical variables
Asian Journal of Psychiatry 6 (2013) 421–427
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Suicide attempts in schizophrenic patients: Clinical variables M.C. Mauri *, S. Paletta, M. Maffini, D. Moliterno, A.C. Altamura Department of Neuroscience and Mental Health, University of Milan, IRCCS Foundation Ca’ Granda, Ospedale Maggiore Policlinico, Milan, Italy
A R T I C L E I N F O
A B S T R A C T
Article history: Received 13 February 2013 Received in revised form 24 June 2013 Accepted 2 July 2013
Introduction: Schizophrenia is associated with a significant risk of suicide: 40–50% of schizophrenic patients report suicidal ideation at some point in their lives, and 4–13% eventually commit suicide. In order to be able to predict and prevent suicide in schizophrenic patients, it is necessary to investigate and characterise suicide victims who meet the criteria for psychotic disorders and risk factors. Methods: The aim of this retrospective study was to verify the associations between suicide attempts (SAs) and the demographic and clinical variables of 106 patients who met the DSM-IV-TR criteria for schizophrenia. The patients were divided into two groups on the basis of the presence/absence of lifetime suicide attempts, and their main demographic and clinical characteristics were analysed and compared. Results: The patients with a history of SAs frequently had a duration of untreated psychosis (DUP) of 1 year (chi-squared test = 9.984, df = 1, p = 0.0016). They also showed significant associations with the presence of a depressive dimension (chi-squared test = 4.439, df = 1, p = 0.0351), hospitalisations before SAs (chi-squared test = 25.515, df = 1, p <0.001), and a family history of psychiatric disorders (chi-squared test = 12.668, df = 2, p = 0.0018) or suicidal behaviours (chi-squared test = 18.241, df = 2, p = 0.0001). Finally, they were more frequently prescribed typical antipsychotic agents. Conclusions: The severity of psychiatric symptoms indicates a high risk of suicide in schizophrenic patients. Further prospective studies of larger samples should investigate the role of early interventions and atypical antipsychotic treatment in reducing the risk. ß 2013 Elsevier B.V. All rights reserved.
Keywords: Suicide attempts Schizophrenia Risk factors Pharmacological treatment
1. Introduction Subjects with a diagnosis of schizophrenia are at particularly high risk of dying because of suicidal events: 40–50% of schizophrenic patients report suicidal ideation at some point in their lives, and 4–13% eventually commit suicide (Montross et al., 2005; Palmer et al., 2005). Suicide is also the leading cause of premature death in this ‘population (Fenton, 2000). Over recent years, there has been growing interest in understanding the factors that affect vulnerability to suicide (Pompili et al., 2007; Mann et al., 2005), but only a few studies have examined cases of death by suicide among schizophrenic patients (McGirr et al., 2006; Sinclair et al., 2004).
Abbreviations: CDSS, Calgary Depression Scale for Schizophrenia; DSM-IV-TR, Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision; DUP, duration of untreated psychosis; SA, suicide attempt; SAs, suicide attempts; SCID-I, Structured Clinical Interview for Axis I Disorders; SD, standard deviation. * Corresponding author at: Clinical Psychiatry, Clinical Neuropsychopharmacology Unit, IRCCS Ospedale Maggiore Policlinico, Via F. Sforza 35, 20122 Milano, Italy. Tel.: +39 0255035997; fax: +39 0255035990. E-mail address: [email protected] (M.C. Mauri). 1876-2018/$ – see front matter ß 2013 Elsevier B.V. All rights reserved. http://dx.doi.org/10.1016/j.ajp.2013.07.001
An increased risk of suicide has been associated with Caucasian race, male gender, a younger age, unemployment, living circumstances, a positive family history of suicide attempts (SAs) and psychiatric disorders, co-morbidity with substance abuse, and the lack of a supportive environment (Palmer et al., 2005; De Hert et al., 2001; Caldwell and Gottesman, 1990; Siris, 2001). The risk of suicide in patients with schizophrenia is higher in the initial period of the disease, especially within the first year (Palmer et al., 2005; Kuo et al., 2005). The results of a metaanalysis regarding the manner in which age at symptom onset affects the risk of suicide were not conclusive (Hawton and James, 2005), but two recent studies have found that the risk is higher in patients who fall ill in later life (Kuo et al., 2005; Reutfors et al., 2009). It has been observed that a particularly high risk of suicide is associated with hospitalisation. Our data are in according to the study conducted by Lee and Lin (2009) who underlined that 1/3 of the suicides of patients with schizophrenia occur during hospitalisation or within one week of discharge (Qin and Nordentoft, 2005), although the findings of a recent population study show that the risk of suicide due to schizophrenia is relatively constant during the first year after discharge (Reutfors
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et al., 2010). The number of psychiatric admissions is also associated with a higher risk of suicide (Lee and Lin, 2009). A history of SAs significantly increases the risk of suicide among patients with schizophrenia, and is reported to be the greatest risk factor for suicide (Hawton and van Heeringen, 2009). In comparison with other psychiatric disorders associated with SAs, schizophrenia materially affects the overall risk and temporal nature of the lethality of suicidal behaviour (Tidemalm et al., 2008). Other studies have investigated the role of clinical symptoms and psychopathological dimensions. A review by Hawton and van Heeringen (2009) found that death by suicide among people with schizophrenia is associated with a history of depression, symptoms of agitation or motor restlessness, worthlessness or low selfesteem, hopelessness, a family history of depression, and recent losses (Fenton, 2000; Joukamaa et al., 2001). In terms of pharmacology, there is little general evidence that antipsychotic medication has a preventive effect (Pompili et al., 2007), although long-term treatment with antipsychotic drugs seems to be associated with a lower mortality rate than no antipsychotic treatment (Tiihonen et al., 2009). In particular, clozapine seems to reduce the risk of suicide (Tiihonen et al., 2009; Altamura et al., 1999; Meltzer et al., 2003) and suicidal behaviour (Hennen and Baldessarini, 2005). For these reasons, it is clinically important to carry out further studies because the better characterisation of suicide victims who meet the criteria for psychotic disorders and other risk factors can help to predict and prevent suicide. The aim of this study was to identify the clinical or pharmacological predictors of SAs by schizophrenic patients by analysing the association between a comorbid depressive dimension, co-morbid substance abuse, and a positive family history of suicide and psychiatric disorders. We also investigated which pharmacological variables may be associated with suicide attempts, and what role is played by the duration of untreated psychosis (DUP).
2. Materials and methods 2.1. Study sample We retrospectively studied patients consecutively admitted to the Psychiatric Diagnosis and Care Service of the Department of Psychiatry of Ospedale Maggiore (Milan, Italy), between January 2009 and July 2011. The protocol was approved by our local Ethics Committee and written informed consent was obtained from the patients or their relatives after the study had been fully described. The study involved 106 in-patients, aged 24–79 years, with a diagnosis of schizophrenia. The diagnosis was formulated at admission by expert clinicians using the Structured Clinical Interview for Axis I Disorders (SCID-I) (Spitzer et al., 1992) based on the criteria of the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR). The patients were divided into two groups on the basis of the presence/absence of SAs. The main demographic and clinical variables compared between the two groups were:
Age Gender Education Marital status Living situation Employment situation Psychiatric diagnoses based on the criteria of the DSM-IV TR (including diagnostic subtype)
Age at onset Duration of illness DUP, defined as the time between the onset of psychiatric symptoms and the first antipsychotic treatment Hospitalisations (within the six months preceding an SA) Presence/absence of the depressive dimension (within the six months preceding an SA) Family history of psychiatric disorders and/or suicidal behaviour Co-morbid substance abuse Pharmacological therapy. Clinical symptoms and the presence of suicidal ideation and/or behaviour were evaluated by means of a clinical interview or by reviewing the patients’ medical records. Psychiatric depressive symptoms were assessed using the Calgary Depression Scale for Schizophrenia (CDSS) (Addington et al., 1990): the patients with a total CDSS score of >6 points were considered to be ‘‘depressed’’ and those with <6 points were considered to be ‘‘non-depressed.’’ The cases for which it was not possible to obtain information about possible suicidal behaviour or for which there was no clear intent (e.g. a suspicion of manipulative behaviour) were excluded. 2.2. Statistical analysis A comparison was made of the main demographic and clinical characteristics of the schizophrenic subjects who presented suicidal behaviour during the observation period or at any time in their lives, and those without a history of suicidal behaviour. The data were statistically analysed by means of descriptive methods, analysis of variance (ANOVA), and multifactor analysis of variance (Tukey’s test). The continuous variables were analysed using the t test for independent samples, and the categorical variables using the chi-squared test. The alpha level of significance was set at 0.05 and did not undergo any change. The results of the descriptive statistical analysis were investigated by means of logistic regression, with the presence or absence of lifetime suicidal behaviour as the dependent variable, and gender, the presence of a depressive dimension, co-morbid substance abuse and previous hospitalisations, therapy (typical vs atypical antipsychotics), DUP (<1 or >1 year), and the corresponding interactions as covariates. All of the statistical analyses were made using the Statgraphic Centurion programme, version XV (Statpoint Inc., Warrenton, VA, USA; www.statgraphics.com). 3. Results Table 1 shows the main demographic and clinical variables of the sample as a whole. The average age of the 106 patients (45 males and 61 females) was 48.25 years (+12.68 SD). Age at the time of our first interview and age at the onset of schizophrenia were significantly lower among the men (respectively t = 2.89, p < 0.01; t = 3.10, p = 0.002). The women were more often married or divorced (chi-squared test = 13.060, df = 2, p < 0.01). A significant percentage of the patients (46.22%) lived at home (chi-squared test = 12.649, df = 4, p = 0.0131). Forty-five (42.45%) patients received a diagnosis of Paranoid Schizophrenia, 28 (26.42%) of Undifferentiated Schizophrenia, 15 (14.17%) of Residual Schizophrenia, and 18 (16.98%) of Disorganised Schizophrenia. In men it was observed an equal percentage of patients with Paranoid and Undifferentiated Schizophrenia (36.58%), while in females the diagnosis of Paranoid Schizophrenia (46.15%) prevailed on the others. The men showed significantly more co-morbidities of abuse (chi-square = 13.524, df = 1, p = 0.0002), particularly abuse of
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Table 1 Demographic and clinical characteristics of the whole sample studied.
*
Age Schooling Civil status Never married Married Divorced@ Widower Living situation Alone Family§ Partner Institutionalisation Homeless Not received Occupation Student Worker Unemployed Invalid Retired Diagnosis Paranoid Schizophrenia Undifferentiated Schizophrenia Residual Schizophrenia Disorganised Schizophrenia Age at onseta,# Duration of illnessa Age at first treatmenta Duration of untreated psychosisa <1 year >1 year Abuse/dependence of substances Cannabinoidsc¸ Cocaine Amphetamines Alcohol Multi-drug abusers Presence of depressive dimensionb Previous hospitalization Family history Depression Schizophrenia Alcoholism Delusional Disorder Psychosis Family history Suicidal behaviour Therapyc Typical antipsychotics Atypical antipsychotics
Total sample (N = 106)
Men (N = 41)
Women (N = 65)
48.25 (12.68) 10.59 (3.90)
43.75 (11.67) 11.61 (3.41)
51.09 (12.55) 10.00 (4.07)
60 23 16 7
(56.60%) (21.69%) (15.09%) (6.60%)
29 (70.73%) 8 (19.51%) 2 (4.87%) 0
31 15 14 7
(47.69%) (23.07%) (21.53%) (10.76%)
30 49 9 12 2 4
(28.30%) (46.22%) (8.49%) (11.32%) (1.88%) (3.77%)
13 19 2 5 1 1
(31.7%) (46.34%) (4.87%) (12.19%) (2.43%) (2.43%)
17 30 7 7 1 3
(26.15%) (46.15%) (10.76%) (10.76%) (1.53%) (4.61%)
4 21 35 36 10
(3.77%) (20.58%) (34.31%) (35.29%) (9.8%)
3 8 17 13 2
(7.3%) (19.51%) (41.46%) (31.70%) (4.88%)
1 13 18 23 8
(1.54%) (20.00%) (27.69%) (35.38%) (12.31%)
45 (42.45%) 28 (26.42%) 15 (14.17%) 18 (16.98%) 24.21 (5.83) 21.74 (10.56) 22.9 (7.3)
15 (36.58%) 15 (36.58%) 5 (11.90%) 6 (14.63%) 21.81 (5.00) 20.59 (11.19) 21.4 (6.2)
30 (46.15%) 13 (19.99%) 10 (15.38%) 12 (18.46%) 25.69 (5.86) 22.47 (10.19) 26.1 (8.6) (19.51%)
27 (32.53%) 29 (34.93%)
12 (29.26%) 12 (29.26%)
15 (23.07%) 17 (26.15%)
10 1 0 10 3 21 83
(9.43%) (0.94%)
(19.51%) (2.44%)
(9.43%) (2.83%) (19.81%) (78.30%)
8 1 0 5 3 5 29
2 0 0 5 0 16 54
14 2 2 2 5
(13.20%) (1.89%) (1.89%) (1.89%) (4.71%)
6 2 1 0 2
(14.63%) (4.88%) (2.43%)
(12.19%) (7.32%) (11.12%) (70.73%)
(4.88%)
8 0 1 2 3
(3.07%)
(7.69%) (26.23%) (83.07%) (12.30%) (1.59%) (3.07%) (4.61%)
32 (30.19%)
17 (41.46%)
15 (23.08%)
34 (32.07%) 54 (50.94%)
12 (36.36%) 21 (63.63%)
22 (40.00%) 33 (60.00%)
SD or percentages are shown in parentheses. Data were available for 83 patients. b Number of subjects with at least one episode of depressive symptomatology lifetime. c Data were available for 88 patients. * t = 2.89, p < 0.01. @ Chi-square = 13.060, df = 2, p < 0.01. § Chi-square = 12.649, df = 4, p = 0.0131. # t = 3.10, p = 0.02. c ¸ Chi-square = 8.183, df = 1, p < 0.01. a
cannabinoids (chi-square = 8.183, df = 1, p < 0.01), whereas the women were prevalently alcohol abusers. The duration of untreated psychosis (DUP) has been considered as a categorical variable with two levels, DUP < 1 year or > 1 year. The two groups were similar in terms of DUP: of the 83 patients for whom data were available, 27 (48.21%) had a DUP of <1 year and 29 (51.78%) a DUP of >1 year. Twenty-one patients (19.81%) (M = 5; F = 16) were classified as being depressed: i.e. they had a CDSS score of >6 in the six months preceding a suicide attempt. Eighty-three patients (78%) had been admitted to hospital at least once before showing suicidal behaviour.
Thirty-two patients (30.19%) had a family history of suicidal behaviour, and 14 (13.20%) a history of depressive disorders. Thirty-five patients (33.02%; 15 men and 20 women) had attempted suicide at least once in their lives (SA). Table 2 shows the main demographic and clinical variables of the suicide attempters and non-attempters. There were no significant differences between the two groups with regard to age, age at the onset of clinical symptoms, the duration of illness, or co-morbid abuse. Attempters more frequently lived with their families, but this difference did not reach statistical significance (chi-square = 5.616, df = 2, p = 0.07).
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Table 2 Demographic and clinical characteristics of attempters and not-attempters patients.
Age Gender Schooling Living situation Alone Family Partner Institutionalisation Homeless Not received Civil status Never married Married Divorced Widower Diagnosis Paranoid Schizophrenia Undifferentiated Schizophrenia Residual Schizophrenia Disorganised Schizophrenia Age at onseta Duration of illnessa Age at first treatmenta Duration of untreated psychosisa,* <1 year >1 year Abuse/dependence of substances Cannabinoids Cocaine Amphetamines Alcohol Multi-drug abusers Presence of depressive dimensionb,@ Previous hospitalization# Family historyc¸ Depression Schizophrenia Alcoholism Delusional Disorder Psychosis Family history§ Suicidal behaviour Therapyc Typical antipsychotics Atypical antipsychotics
Patients with suicide attempts (N = 35)
Patients without suicide attempts (N = 71)
47.42 (14.02) 15 M 20 F 9.85 (3.40)
48.66 (12.04) 26 M 45 F 10.92 (4.08)
7 (20%) 23 (65.71%) 0 2 (5.71%) 0 3 (8.57%)
23 (32.39%) 26 (36.62%) 9 (25.71%) 10 (14.10%) 2 (2.81%) 1 (1.41%)
19 (54.28%) 9 (25.71%) 6 (17.14%) 1 (2.85%)
41 (57.74%) 14 (19.72%) 10 (14.10%) 6 (8.45%)
15 (42.85%) 11 (31.42%) 5 (14.28%) 4 (11.42%) 23.60 (7.11) 21.33 (12.39) 24.4 (8.4)
30 (42.25%) 17 (23.94%) 10 (14.08%) 14 (19.71%) 24.51 (5.12) 21.94 (9.68) 22.5 (7.0)
0 9 (25.71%)
27 (38.03%) 20 (28.17%)
3 (8.57%) 0 0 5 (14.28%) 1 (2.86%) 11 (31.43%) 20 (57.14%)
7 (9.86%) 1 (1.41%) 0 5 (7.04%) 2 (2.81%) 10 (14.08%) 63 (88.73%)
5 2 1 1 3
9 0 1 1 2
(14.28%) (5.71%) (2.86%) (2.86%) (8.57%)
(12.67%) (1.41%) (1.41%) (2.81%)
19 (54.28%)
13 (18.31%)
10 (28.57%) 8 (22.86%)
24 (33.80%) 46 (64.79%)
SD or percentages are shown in parentheses. a Data were available for 83 patients. b Number of subjects with at least one episode of depressive symptomatology lifetime. c Data were available for 88 patients. Includes patients treated with typical antipsychotics plus antidepressants, benzodiazepines, mood stabilisers (N = 10 among the attempters and N = 14 among the not attempters). * Chi-square = 9.984, df = 1, p = 0.0016. @ Chi-square = 4.439, df = 1, p = 0.0351. § Chi-square = 18.241, df = 2, p = 0.0001. # Chi-square = 25.515, df = 1, p < 0.001. c ¸ Chi-square = 12.668, df = 2, p = 0.0018.
Fig. 1. Antipsychotic therapy assumed by suicide attempters and non attempters. The atypical antipsychotics (clozapine, olanzapine, quetiapine, risperidone, aripiprazole) were more frequently prescribed to patients who have not experienced suicide attempts than typical antipsychotics (haloperidol, zuclopentixol, fluphenazine) (chi-square = 12.497, df = 7, p = 0.0854).
(chi-square = 4.439, df = 1, p = 0.0351), although age at the time of the manifestation was not significantly relevant. Auditory hallucinations were equally distributed among the patients who had made suicide attempts (n = 15, 68.2%) and those who had not (n = 43, 53.5%), as were active delusions (respectively n = 17, 77.2% vs n = 62, 76.5%). There was a significant association between SA and a family history of psychiatric disorders (chi-square = 12.668, df = 2, p = 0.0018) or suicidal behaviours (chi-square = 18.241, df = 2, p = 0.0001). The data relating to drug therapies were extracted from the medical charts of 18 patients in the SA group and 70 in the control group. The latter were more frequently prescribed atypical antipsychotics (clozapine, olanzapine, quetiapine, risperidone and aripiprazole) than typical antipsychotics (haloperidol, zuclopentixol, fluphenazine) (chi-square = 12.497, df = 7, p = 0.0854) (Fig. 1). Furthermore the controls were more frequently prescribed combination therapy with antipsychotics and mood stabilisers (lithium, valproate) (chi-square = 5.746, df = 2, p = 0.05) or benzodiazepines (clonazepam, flurazepam), whereas there was no significative difference between the two groups in terms of combined therapy with antipsychotics and antidepressants (sertraline, paroxetine, fluoxetine, or clomipramine) (Fig. 2). Reliable data concerning the daily doses and duration of drug treatment were available for only a few patients, and so they were not considered in the analysis. Logistic regression was used to explore the results of the statistical analysis, with the presence of suicidal behaviour as the dependent variable, and age, age at onset of psychosis, gender, a DUP of >1 year, substance abuse, hospitalisations, and the presence of a lifetime depressive dimension as covariates (Table 3). There was a trend towards significance with regard to the age of onset of psychiatric illness (chi-square = 3.42402, df = 1, p = 0.0643) and a DUP of >1 year (chi-square = 3.32514, df = 1, p = 0.0682), and a high level of significance in relation to the presence of previous hospitalisations for suicide attempts (chi-square = 11.4661, df = 1, p = 0.0007). 4. Discussion
There were no significant between-group differences in the distribution of the diagnostic subcategories, but the attempters were more frequently diagnosed as having Paranoid Schizophrenia (42.85%) or Undifferentiated Schizophrenia (31.42%). However, the attempters were characterised by a DUP of >1 year (chi-square = 9.984, df = 1, p = 0.0016), and 20 (57%) had been previously hospitalised (chi-square = 25.515, df = 1, p < 0.001). The patients with SAs also manifested a depressive dimension (>6 points on the CDSS) more often than the control group
We retrospectively evaluated a sample of patients with a diagnosis of schizophrenia in order to investigate the associations between their demographic and clinical variables and suicide attempts occurring during the course of their illness. The presence of a depressive dimension was found to be an important risk factor in schizophrenic patients as 30% of those attempting suicide showed depressive symptoms immediately before the attempt, a rate lower but compatible with those observed in other studies (Meltzer et al., 2000). It has been
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Fig. 2. Combination therapy with antipsychotics and antidepressants, benzodiazepines or mood stabilisers assumed by suicide attempters and not attempters. Not attempters were more frequently prescribed combination therapy with antipsychotics and mood stabilisers (lithium, valproate) (chi-square = 5.746, df = 2, p = 0.05) or benzodiazepines (clonazepam, flurazepam). There was no significative difference between the two groups in terms of combined therapy with antipsychotics and antidepressants (sertraline, paroxetine, fluoxetine, or clomipramine).
suggested that having a depressive disorder acts as a trigger of suicidal behaviour in vulnerable patients with schizophrenia (Schennach-Wolff et al., 2011), and a history of past and present depressive disorders is closely associated with suicide (Hawton and James, 2005). These data indicate the critical role of depressive symptoms in the risk of suicide in schizophrenic patients and the need to assess depressive features carefully in a bid to prevent suicide attempts. Our findings also confirm that a history of hospitalisation(s) is closely associated with a suicide attempts (Lee and Lin, 2009). Furthermore, a recent population-based study found that the risk of suicide in schizophrenia patients is relatively constant during the first year following hospital discharge (Reutfors et al., 2010). Regarding prevention of suicide risk, it must especially focus on improving assessment of suicide risk during impatient treatment and the first week after discharge, and special attention must be paid to patients with one or more of the identified risk factors (Nordentoft, 2007). On the basis of our findings, the severity of psychiatric illness seems to play an important role in the risk of suicide, especially during the acute phase. This underlines the importance of immediately assessing the risk upon admission and ensuing appropriate follow-up and outpatient treatment upon discharge. One of the most interesting findings of our study is the significant association between a suicide attempt and a DUP of >1 year (p = 0.0016). Some studies have found a correlation between a longer DUP and suicidal behaviour before presentation (Altamura et al., 2003; Harvey et al., 2008; Preti et al., 2009). This highlights the fact that the early detection of schizophrenia symptoms and early intervention are important not only in improving the overall outcomes, but also in preventing suicide attempts. Furthermore there was a significant association between SAs and a family history of psychiatric disorders (chi-square = 12.668, df = 2, p = 0.0018) or suicidal behaviours (chi-square = 18.241,
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df = 2, p = 0.0001). A parental history of psychiatric illness could increase risk for suicide either through genetic transmission of vulnerability associated with psychiatric illness, or through its negative influence on family life, e.g. reduced care to the children (Qin et al., 2002; Pawlak et al., 2013). Previous studies have consistently documented that both personal and familial psychiatric history, and a family history of suicide and suicidal ideation are important risk factors for completed suicide among psychiatric in-patients (Large et al., 2011; Qin et al., 2002). However, few studies have been able to explore this association in detail by taking into account these aspects simultaneously to examine their relative importance (Qin et al., 2002). The results of analysis of the data concerning pharmacological treatment showed that the patients who did not attempt suicide were more frequently prescribed atypical antipsychotics (especially clozapine) than those who did. Despite the limitations of the pharmacological data (the treatments were not standardised, the data were collected retrospectively, and reliable information about doses and treatment duration was only available for a few patients), our findings seem to confirm that the use of antipsychotics agents decreases all-cause mortality, as found in most of the other studies published to date (Tiihonen et al., 2009; Altamura et al., 1999). In particular, clozapine seems to be the most beneficial in terms of reducing the risk of suicide (Tiihonen et al., 2009; Meltzer et al., 2000; Altamura et al., 2003; De Hert et al., 2010; Wasserman et al., 2012) and suicidal behaviour (Meltzer et al., 2003; Hennen and Baldessarini, 2005). Although these results are not in according with the study conducted by Sernyak et al. (2001) that fails to support the hypothesis that clozapine treatment is associated with significantly fewer deaths due to suicide. We also found that the not-attempters more frequently received antipsychotics combined with mood stabilisers or benzodiazepines, which suggests that these drugs also reduce the risk of suicide, especially in patients with depressive symptoms (Wasserman et al., 2012; Cipriani et al., 2005). In addition to stabilising mood, mood stabilisers also have effects on impulsiveness and aggression, whereas benzodiazepines reduce the rate of anxiety, insomnia and agitation although, to the best of our knowledge, there are no published data concerning the specific role of benzodiazepines in reducing the risk of suicide in schizophrenic patients. Lithium is the only other drug that has been shown to prevent suicide, and is primarily used in patients with bipolar disorder (Wasserman et al., 2012; Leucht et al., 2007; Mauri et al., 1990). However, its effect on suicidal behaviour among schizophrenic patients is less clear (Leucht et al., 2007). Even though we have not found significative difference between attempters and not attempters regarding the use of antipsychotics combined with antidepressants, a recent review reports that selective serotonin receptor inhibitors (SSRIs) not only ameliorate depressive symptoms in patients with schizophrenia, but they also appear to attenuate suicidal thoughts (Kasckow et al., 2011; Wasserman et al., 2012). Although further researches are needed to
Table 3 Summary of the statistics for the best-fit logistic regression model applied to our data. Variable Age Age at onset Gender DUP 1 anno Substance abuse Previous hospitalization Depressive dimension
Coefficient 0.0088 0.2119 0.4542 16.1707 14.5157 32.2928 1.2673
Standard error
df
p-Value
Odds ratio
0.0599 0.1386 1.1438 1180.16 1552.4 3389.2 1.1446
1 1 1 1 1 1 1
0.8816 0.0643 0.6911 0.0682 0.4861 0.0007 0.2629
1.0089 0.8090 1.5749 9.4877E 2.0180 0.0582 0.2815
In this analysis, the dependent variable was the occurrence of suicide attempts lifetime. df = degrees of freedom; p-value = significance level; DUP = duration of untreated psychosis.
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more effectively personalise the treatment of suicidal thoughts and behaviours and the prevention of suicide in patients with schizophrenia. Some of the limitations of this study deserve comment. First of all, the total sample size and the size of the group of patients attempting suicide were quite small, and this may have reduced the power of the analyses. Secondly, the study only included patients who had been regularly followed up in our clinic: as this obviously excluded patients who made lethal attempts, the prevalence of suicide attempts may be underestimated and the sample itself may be biased by the inclusion of only less severe cases. However, it is comparable to the samples in previous studies of the clinical correlates of suicidal behaviour in schizophrenia, in which suicide completers were excluded or only represented a minority of the patients (Hawton and van Heeringen, 2009). Finally, the study was retrospective and based on a review of the clinical charts of schizophrenic patients followed up in a nonstandardised setting, whereas it has been suggested that prospective, controlled studies may be better for investigating the role of clinical and pharmacological variables in predicting suicide risk. Further prospective studies of larger samples are warranted, particularly when investigating the role of early detection strategies and atypical antipsychotic treatment in reducing the risk of suicide. Funding No forms of financial support were received for this study. Conflict of interests The authors disclose no conflict of interests. No financial support or compensation has been received from any individual or corporate entity for research or professional service and there are no personal financial holdings that could be perceived as constituting a potential conflict of interest. Ethics committee review The protocol received agreement by our Ethics Committee and the patients or their relatives, acknowledged about the details of the study, and provided their written informed consent. Acknowledgement The authors wish to acknowledge the patients included in the study. References Addington, D., Addington, J., Schissel, B., 1990. A depression rating scale for schizophrenics. Schizophrenia Research 3, 247. Altamura, A.C., Bassetti, R., Bignotti, S., Pioli, R., Mundo, E., 2003. Clinical variables related to suicide attempts in schizophrenic patients: a retrospective study. Schizophrenia Research 60 (1) 47–55. Altamura, A.C., Bignotti, S., Pioli, R., Tura, G., Mannu, P., Soddu, A., La Croce, L., 1999. Suicidal behavior in schizophrenia: a retrospective study. European Neuropsychopharmacology 9 (Suppl. 5) S271. Caldwell, C.B., Gottesman, I.I., 1990. Schizophrenics kill themselves too: a review of risk factors for suicide. Schizophrenia Bulletin 16 (4) 571–589. Cipriani, A., Pretty, H., Hawton, K., Geddes, J.R., 2005. Lithium in the prevention of suicidal behavior and all-cause mortality in patients with mood disorders: a systematic review of randomized trials. American Journal of Psychiatry 162, 1805–1819. De Hert, M., Correll, C.U., Cohen, D., 2010. Do antipsychotic medications reduce or increase mortality in schizophrenia? A critical appraisal of the FIN-11 study. Schizophrenia Research 117 (1) 68–74. 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.
Fenton, W.S., 2000. Depression, suicide, and suicide prevention in schizophrenia. Suicide and Life-Threatening Behavior 30, 34–49. Harvey, S.B., Dean, K., Morgan, C., Walsh, E., Demjaha, A., Dazzan, P., Morgan, K., Lloyd, T., Fearon, P., Jones, P.B., Murray, R.M., 2008. Self-harm in first-episode psychosis. British Journal of Psychiatry 192, 178–184. Hawton, K., James, A., 2005. Suicide and deliberate self harm in young people. British Medical Journal 330, 891–894. Hawton, K., van Heeringen, K., 2009. Suicide. Lancet 373, 1372–1381. Hennen, J., Baldessarini, R.J., 2005. Suicidal risk during treatment with clozapine: a meta-analysis. Schizophrenia Research 73, 139–145. Joukamaa, M., Helio¨vaara, M., Knekt, P., Aromaa, A., Raitasalo, R., Lehtinen, V., 2001. Mental disorders and cause-specific mortality. British Journal of Psychiatry 179, 498–502. Kasckow, J., Felmet, K., Zisook, S., 2011. Managing suicide risk in patients with schizophrenia. CNS Drugs 25 (2) 129–143. 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Suicide among patients with schizophrenia: a consideration of risk and protective factors. Annals of Clinical Psychiatry 17, 173–182. Nordentoft, M., 2007. Prevention of suicide and attempted suicide in Denmark. Epidemiological studies of suicide and intervention studies on selected risk groups. Danish Medical Bulletin 54 (4) 306–369. Palmer, B.A., Pankratz, V.S., Bostwick, J.M., 2005. The lifetime risk of suicide in schizophrenia: a reexamination. Archives of General Psychiatry 62 (3) 247– 253. Pawlak, J., Dmitrzak-We˛glarz, M., Skibin´ska, M., Szczepankiewicz, A., Leszczyn´skaRodziewicz, A., Rajewska-Rager, A., Zaremba, D., Czerski, P., Hauser, J., May 2, 2013. Suicide attempts and clinical risk factors in patients with bipolar and unipolar affective disorders. General Hospital Psychiatry, [Epub ahead of print]. Pompili, M., Amador, X.F., Girardi, P., et al., 2007. Suicide risk in schizophrenia: learning from the past to change the future. Annals of General Psychiatry 6, 10. Preti, A., Meneghelli, A., Pisano, A., Cocchi, A., Programma 2000 Team, 2009. Risk of suicide and suicidal ideation in psychosis: results from an Italian multi-modal pilot program on early intervention in psychosis. Schizophrenia Research 113 (2/3) 145–150. Qin, P., Agerbo, E., Mortensen, P.B., 2002. Suicide risk in relation to family history of completed suicide and psychiatric disorders: a nested case–control study based on longitudinal registers. Lancet 360 (9340) 1126–1130. Qin, P., Nordentoft, M., 2005. Suicide risk in relation to psychiatric hospitalization: evidence based on longitudinal registers. Archives of General Psychiatry 62 (4) 427–432. ¨ sby, U., 2010. Suicide and Reutfors, J., Brandt, L., Ekbom, A., Isacsson, G., Sparen, P., O hospitalization for mental disorders in Sweden: a population-based case– control study. Journal of Psychiatric Research 44 (12) 741–747. Reutfors, J., Brandt, L., Jo¨nsson, E.G., Ekbom, A., Spare´n, P., Osby, U., 2009. Risk factors for suicide in schizophrenia: findings from a Swedish population-based case– control study. Schizophrenia Research 108 (1–3) 231–237. Schennach-Wolff, R., Obermeier, M., Seemu¨ller, F., Ja¨ger, M., Messer, T., Laux, G., Pfeiffer, H., Naber, D., Schmidt, L.G., Gaebel, W., Klosterko¨tter, J., Heuser, I., Maier, W., Lemke, M.R., Ru¨ther, E., Klingberg, S., Gastpar, M., Mo¨ller, H.J., Riedel, M., 2011. Evaluating depressive symptoms and their impact on outcome in schizophrenia applying the Calgary Depression Scale. Acta Psychiatrica Scandinavica 123, 228–238. Sernyak, M.J., Desai, R., Stolar, M., Rosenheck, R., 2001. Impact of clozapine on completed suicide. American Journal of Psychiatry 158, 931–937. Sinclair, J., Mullee, M.A., King, E.A., Baldwin, D.S., 2004. Suicide in schizophrenia: a retrospective case–control study of 51 suicides. Schizophrenia Bulletin 30 (4) 803–811. Siris, S.G., 2001. Suicide and schizophrenia. Journal of Psychopharmacology 15 (2) 127–135.
M.C. Mauri et al. / Asian Journal of Psychiatry 6 (2013) 421–427 Spitzer, R.L., Williams, J.B., Gibbon, M., First, M.B., 1992. The Structured Clinical Interview for DSM-III-R (SCID). I. History, rationale, and description. Archives of General Psychiatry 49 (8) 624–629. Tidemalm, D., La˚ngstro¨m, N., Lichtenstein, P., Runeson, B., 2008. Risk of suicide after suicide attempt according to coexisting psychiatric disorder: Swedish cohort study with long term follow-up. British Medical Journal 337 (November) a2205.
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Suicide attempts in schizophrenic patients: Clinical variables M.C. Mauri *, S. Paletta, M. Maffini, D. Moliterno, A.C. Altamura Department of Neuroscience and Mental Health, University of Milan, IRCCS Foundation Ca’ Granda, Ospedale Maggiore Policlinico, Milan, Italy
A R T I C L E I N F O
A B S T R A C T
Article history: Received 13 February 2013 Received in revised form 24 June 2013 Accepted 2 July 2013
Introduction: Schizophrenia is associated with a significant risk of suicide: 40–50% of schizophrenic patients report suicidal ideation at some point in their lives, and 4–13% eventually commit suicide. In order to be able to predict and prevent suicide in schizophrenic patients, it is necessary to investigate and characterise suicide victims who meet the criteria for psychotic disorders and risk factors. Methods: The aim of this retrospective study was to verify the associations between suicide attempts (SAs) and the demographic and clinical variables of 106 patients who met the DSM-IV-TR criteria for schizophrenia. The patients were divided into two groups on the basis of the presence/absence of lifetime suicide attempts, and their main demographic and clinical characteristics were analysed and compared. Results: The patients with a history of SAs frequently had a duration of untreated psychosis (DUP) of 1 year (chi-squared test = 9.984, df = 1, p = 0.0016). They also showed significant associations with the presence of a depressive dimension (chi-squared test = 4.439, df = 1, p = 0.0351), hospitalisations before SAs (chi-squared test = 25.515, df = 1, p <0.001), and a family history of psychiatric disorders (chi-squared test = 12.668, df = 2, p = 0.0018) or suicidal behaviours (chi-squared test = 18.241, df = 2, p = 0.0001). Finally, they were more frequently prescribed typical antipsychotic agents. Conclusions: The severity of psychiatric symptoms indicates a high risk of suicide in schizophrenic patients. Further prospective studies of larger samples should investigate the role of early interventions and atypical antipsychotic treatment in reducing the risk. ß 2013 Elsevier B.V. All rights reserved.
Keywords: Suicide attempts Schizophrenia Risk factors Pharmacological treatment
1. Introduction Subjects with a diagnosis of schizophrenia are at particularly high risk of dying because of suicidal events: 40–50% of schizophrenic patients report suicidal ideation at some point in their lives, and 4–13% eventually commit suicide (Montross et al., 2005; Palmer et al., 2005). Suicide is also the leading cause of premature death in this ‘population (Fenton, 2000). Over recent years, there has been growing interest in understanding the factors that affect vulnerability to suicide (Pompili et al., 2007; Mann et al., 2005), but only a few studies have examined cases of death by suicide among schizophrenic patients (McGirr et al., 2006; Sinclair et al., 2004).
Abbreviations: CDSS, Calgary Depression Scale for Schizophrenia; DSM-IV-TR, Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision; DUP, duration of untreated psychosis; SA, suicide attempt; SAs, suicide attempts; SCID-I, Structured Clinical Interview for Axis I Disorders; SD, standard deviation. * Corresponding author at: Clinical Psychiatry, Clinical Neuropsychopharmacology Unit, IRCCS Ospedale Maggiore Policlinico, Via F. Sforza 35, 20122 Milano, Italy. Tel.: +39 0255035997; fax: +39 0255035990. E-mail address: [email protected] (M.C. Mauri). 1876-2018/$ – see front matter ß 2013 Elsevier B.V. All rights reserved. http://dx.doi.org/10.1016/j.ajp.2013.07.001
An increased risk of suicide has been associated with Caucasian race, male gender, a younger age, unemployment, living circumstances, a positive family history of suicide attempts (SAs) and psychiatric disorders, co-morbidity with substance abuse, and the lack of a supportive environment (Palmer et al., 2005; De Hert et al., 2001; Caldwell and Gottesman, 1990; Siris, 2001). The risk of suicide in patients with schizophrenia is higher in the initial period of the disease, especially within the first year (Palmer et al., 2005; Kuo et al., 2005). The results of a metaanalysis regarding the manner in which age at symptom onset affects the risk of suicide were not conclusive (Hawton and James, 2005), but two recent studies have found that the risk is higher in patients who fall ill in later life (Kuo et al., 2005; Reutfors et al., 2009). It has been observed that a particularly high risk of suicide is associated with hospitalisation. Our data are in according to the study conducted by Lee and Lin (2009) who underlined that 1/3 of the suicides of patients with schizophrenia occur during hospitalisation or within one week of discharge (Qin and Nordentoft, 2005), although the findings of a recent population study show that the risk of suicide due to schizophrenia is relatively constant during the first year after discharge (Reutfors
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et al., 2010). The number of psychiatric admissions is also associated with a higher risk of suicide (Lee and Lin, 2009). A history of SAs significantly increases the risk of suicide among patients with schizophrenia, and is reported to be the greatest risk factor for suicide (Hawton and van Heeringen, 2009). In comparison with other psychiatric disorders associated with SAs, schizophrenia materially affects the overall risk and temporal nature of the lethality of suicidal behaviour (Tidemalm et al., 2008). Other studies have investigated the role of clinical symptoms and psychopathological dimensions. A review by Hawton and van Heeringen (2009) found that death by suicide among people with schizophrenia is associated with a history of depression, symptoms of agitation or motor restlessness, worthlessness or low selfesteem, hopelessness, a family history of depression, and recent losses (Fenton, 2000; Joukamaa et al., 2001). In terms of pharmacology, there is little general evidence that antipsychotic medication has a preventive effect (Pompili et al., 2007), although long-term treatment with antipsychotic drugs seems to be associated with a lower mortality rate than no antipsychotic treatment (Tiihonen et al., 2009). In particular, clozapine seems to reduce the risk of suicide (Tiihonen et al., 2009; Altamura et al., 1999; Meltzer et al., 2003) and suicidal behaviour (Hennen and Baldessarini, 2005). For these reasons, it is clinically important to carry out further studies because the better characterisation of suicide victims who meet the criteria for psychotic disorders and other risk factors can help to predict and prevent suicide. The aim of this study was to identify the clinical or pharmacological predictors of SAs by schizophrenic patients by analysing the association between a comorbid depressive dimension, co-morbid substance abuse, and a positive family history of suicide and psychiatric disorders. We also investigated which pharmacological variables may be associated with suicide attempts, and what role is played by the duration of untreated psychosis (DUP).
2. Materials and methods 2.1. Study sample We retrospectively studied patients consecutively admitted to the Psychiatric Diagnosis and Care Service of the Department of Psychiatry of Ospedale Maggiore (Milan, Italy), between January 2009 and July 2011. The protocol was approved by our local Ethics Committee and written informed consent was obtained from the patients or their relatives after the study had been fully described. The study involved 106 in-patients, aged 24–79 years, with a diagnosis of schizophrenia. The diagnosis was formulated at admission by expert clinicians using the Structured Clinical Interview for Axis I Disorders (SCID-I) (Spitzer et al., 1992) based on the criteria of the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR). The patients were divided into two groups on the basis of the presence/absence of SAs. The main demographic and clinical variables compared between the two groups were:
Age Gender Education Marital status Living situation Employment situation Psychiatric diagnoses based on the criteria of the DSM-IV TR (including diagnostic subtype)
Age at onset Duration of illness DUP, defined as the time between the onset of psychiatric symptoms and the first antipsychotic treatment Hospitalisations (within the six months preceding an SA) Presence/absence of the depressive dimension (within the six months preceding an SA) Family history of psychiatric disorders and/or suicidal behaviour Co-morbid substance abuse Pharmacological therapy. Clinical symptoms and the presence of suicidal ideation and/or behaviour were evaluated by means of a clinical interview or by reviewing the patients’ medical records. Psychiatric depressive symptoms were assessed using the Calgary Depression Scale for Schizophrenia (CDSS) (Addington et al., 1990): the patients with a total CDSS score of >6 points were considered to be ‘‘depressed’’ and those with <6 points were considered to be ‘‘non-depressed.’’ The cases for which it was not possible to obtain information about possible suicidal behaviour or for which there was no clear intent (e.g. a suspicion of manipulative behaviour) were excluded. 2.2. Statistical analysis A comparison was made of the main demographic and clinical characteristics of the schizophrenic subjects who presented suicidal behaviour during the observation period or at any time in their lives, and those without a history of suicidal behaviour. The data were statistically analysed by means of descriptive methods, analysis of variance (ANOVA), and multifactor analysis of variance (Tukey’s test). The continuous variables were analysed using the t test for independent samples, and the categorical variables using the chi-squared test. The alpha level of significance was set at 0.05 and did not undergo any change. The results of the descriptive statistical analysis were investigated by means of logistic regression, with the presence or absence of lifetime suicidal behaviour as the dependent variable, and gender, the presence of a depressive dimension, co-morbid substance abuse and previous hospitalisations, therapy (typical vs atypical antipsychotics), DUP (<1 or >1 year), and the corresponding interactions as covariates. All of the statistical analyses were made using the Statgraphic Centurion programme, version XV (Statpoint Inc., Warrenton, VA, USA; www.statgraphics.com). 3. Results Table 1 shows the main demographic and clinical variables of the sample as a whole. The average age of the 106 patients (45 males and 61 females) was 48.25 years (+12.68 SD). Age at the time of our first interview and age at the onset of schizophrenia were significantly lower among the men (respectively t = 2.89, p < 0.01; t = 3.10, p = 0.002). The women were more often married or divorced (chi-squared test = 13.060, df = 2, p < 0.01). A significant percentage of the patients (46.22%) lived at home (chi-squared test = 12.649, df = 4, p = 0.0131). Forty-five (42.45%) patients received a diagnosis of Paranoid Schizophrenia, 28 (26.42%) of Undifferentiated Schizophrenia, 15 (14.17%) of Residual Schizophrenia, and 18 (16.98%) of Disorganised Schizophrenia. In men it was observed an equal percentage of patients with Paranoid and Undifferentiated Schizophrenia (36.58%), while in females the diagnosis of Paranoid Schizophrenia (46.15%) prevailed on the others. The men showed significantly more co-morbidities of abuse (chi-square = 13.524, df = 1, p = 0.0002), particularly abuse of
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Table 1 Demographic and clinical characteristics of the whole sample studied.
*
Age Schooling Civil status Never married Married Divorced@ Widower Living situation Alone Family§ Partner Institutionalisation Homeless Not received Occupation Student Worker Unemployed Invalid Retired Diagnosis Paranoid Schizophrenia Undifferentiated Schizophrenia Residual Schizophrenia Disorganised Schizophrenia Age at onseta,# Duration of illnessa Age at first treatmenta Duration of untreated psychosisa <1 year >1 year Abuse/dependence of substances Cannabinoidsc¸ Cocaine Amphetamines Alcohol Multi-drug abusers Presence of depressive dimensionb Previous hospitalization Family history Depression Schizophrenia Alcoholism Delusional Disorder Psychosis Family history Suicidal behaviour Therapyc Typical antipsychotics Atypical antipsychotics
Total sample (N = 106)
Men (N = 41)
Women (N = 65)
48.25 (12.68) 10.59 (3.90)
43.75 (11.67) 11.61 (3.41)
51.09 (12.55) 10.00 (4.07)
60 23 16 7
(56.60%) (21.69%) (15.09%) (6.60%)
29 (70.73%) 8 (19.51%) 2 (4.87%) 0
31 15 14 7
(47.69%) (23.07%) (21.53%) (10.76%)
30 49 9 12 2 4
(28.30%) (46.22%) (8.49%) (11.32%) (1.88%) (3.77%)
13 19 2 5 1 1
(31.7%) (46.34%) (4.87%) (12.19%) (2.43%) (2.43%)
17 30 7 7 1 3
(26.15%) (46.15%) (10.76%) (10.76%) (1.53%) (4.61%)
4 21 35 36 10
(3.77%) (20.58%) (34.31%) (35.29%) (9.8%)
3 8 17 13 2
(7.3%) (19.51%) (41.46%) (31.70%) (4.88%)
1 13 18 23 8
(1.54%) (20.00%) (27.69%) (35.38%) (12.31%)
45 (42.45%) 28 (26.42%) 15 (14.17%) 18 (16.98%) 24.21 (5.83) 21.74 (10.56) 22.9 (7.3)
15 (36.58%) 15 (36.58%) 5 (11.90%) 6 (14.63%) 21.81 (5.00) 20.59 (11.19) 21.4 (6.2)
30 (46.15%) 13 (19.99%) 10 (15.38%) 12 (18.46%) 25.69 (5.86) 22.47 (10.19) 26.1 (8.6) (19.51%)
27 (32.53%) 29 (34.93%)
12 (29.26%) 12 (29.26%)
15 (23.07%) 17 (26.15%)
10 1 0 10 3 21 83
(9.43%) (0.94%)
(19.51%) (2.44%)
(9.43%) (2.83%) (19.81%) (78.30%)
8 1 0 5 3 5 29
2 0 0 5 0 16 54
14 2 2 2 5
(13.20%) (1.89%) (1.89%) (1.89%) (4.71%)
6 2 1 0 2
(14.63%) (4.88%) (2.43%)
(12.19%) (7.32%) (11.12%) (70.73%)
(4.88%)
8 0 1 2 3
(3.07%)
(7.69%) (26.23%) (83.07%) (12.30%) (1.59%) (3.07%) (4.61%)
32 (30.19%)
17 (41.46%)
15 (23.08%)
34 (32.07%) 54 (50.94%)
12 (36.36%) 21 (63.63%)
22 (40.00%) 33 (60.00%)
SD or percentages are shown in parentheses. Data were available for 83 patients. b Number of subjects with at least one episode of depressive symptomatology lifetime. c Data were available for 88 patients. * t = 2.89, p < 0.01. @ Chi-square = 13.060, df = 2, p < 0.01. § Chi-square = 12.649, df = 4, p = 0.0131. # t = 3.10, p = 0.02. c ¸ Chi-square = 8.183, df = 1, p < 0.01. a
cannabinoids (chi-square = 8.183, df = 1, p < 0.01), whereas the women were prevalently alcohol abusers. The duration of untreated psychosis (DUP) has been considered as a categorical variable with two levels, DUP < 1 year or > 1 year. The two groups were similar in terms of DUP: of the 83 patients for whom data were available, 27 (48.21%) had a DUP of <1 year and 29 (51.78%) a DUP of >1 year. Twenty-one patients (19.81%) (M = 5; F = 16) were classified as being depressed: i.e. they had a CDSS score of >6 in the six months preceding a suicide attempt. Eighty-three patients (78%) had been admitted to hospital at least once before showing suicidal behaviour.
Thirty-two patients (30.19%) had a family history of suicidal behaviour, and 14 (13.20%) a history of depressive disorders. Thirty-five patients (33.02%; 15 men and 20 women) had attempted suicide at least once in their lives (SA). Table 2 shows the main demographic and clinical variables of the suicide attempters and non-attempters. There were no significant differences between the two groups with regard to age, age at the onset of clinical symptoms, the duration of illness, or co-morbid abuse. Attempters more frequently lived with their families, but this difference did not reach statistical significance (chi-square = 5.616, df = 2, p = 0.07).
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Table 2 Demographic and clinical characteristics of attempters and not-attempters patients.
Age Gender Schooling Living situation Alone Family Partner Institutionalisation Homeless Not received Civil status Never married Married Divorced Widower Diagnosis Paranoid Schizophrenia Undifferentiated Schizophrenia Residual Schizophrenia Disorganised Schizophrenia Age at onseta Duration of illnessa Age at first treatmenta Duration of untreated psychosisa,* <1 year >1 year Abuse/dependence of substances Cannabinoids Cocaine Amphetamines Alcohol Multi-drug abusers Presence of depressive dimensionb,@ Previous hospitalization# Family historyc¸ Depression Schizophrenia Alcoholism Delusional Disorder Psychosis Family history§ Suicidal behaviour Therapyc Typical antipsychotics Atypical antipsychotics
Patients with suicide attempts (N = 35)
Patients without suicide attempts (N = 71)
47.42 (14.02) 15 M 20 F 9.85 (3.40)
48.66 (12.04) 26 M 45 F 10.92 (4.08)
7 (20%) 23 (65.71%) 0 2 (5.71%) 0 3 (8.57%)
23 (32.39%) 26 (36.62%) 9 (25.71%) 10 (14.10%) 2 (2.81%) 1 (1.41%)
19 (54.28%) 9 (25.71%) 6 (17.14%) 1 (2.85%)
41 (57.74%) 14 (19.72%) 10 (14.10%) 6 (8.45%)
15 (42.85%) 11 (31.42%) 5 (14.28%) 4 (11.42%) 23.60 (7.11) 21.33 (12.39) 24.4 (8.4)
30 (42.25%) 17 (23.94%) 10 (14.08%) 14 (19.71%) 24.51 (5.12) 21.94 (9.68) 22.5 (7.0)
0 9 (25.71%)
27 (38.03%) 20 (28.17%)
3 (8.57%) 0 0 5 (14.28%) 1 (2.86%) 11 (31.43%) 20 (57.14%)
7 (9.86%) 1 (1.41%) 0 5 (7.04%) 2 (2.81%) 10 (14.08%) 63 (88.73%)
5 2 1 1 3
9 0 1 1 2
(14.28%) (5.71%) (2.86%) (2.86%) (8.57%)
(12.67%) (1.41%) (1.41%) (2.81%)
19 (54.28%)
13 (18.31%)
10 (28.57%) 8 (22.86%)
24 (33.80%) 46 (64.79%)
SD or percentages are shown in parentheses. a Data were available for 83 patients. b Number of subjects with at least one episode of depressive symptomatology lifetime. c Data were available for 88 patients. Includes patients treated with typical antipsychotics plus antidepressants, benzodiazepines, mood stabilisers (N = 10 among the attempters and N = 14 among the not attempters). * Chi-square = 9.984, df = 1, p = 0.0016. @ Chi-square = 4.439, df = 1, p = 0.0351. § Chi-square = 18.241, df = 2, p = 0.0001. # Chi-square = 25.515, df = 1, p < 0.001. c ¸ Chi-square = 12.668, df = 2, p = 0.0018.
Fig. 1. Antipsychotic therapy assumed by suicide attempters and non attempters. The atypical antipsychotics (clozapine, olanzapine, quetiapine, risperidone, aripiprazole) were more frequently prescribed to patients who have not experienced suicide attempts than typical antipsychotics (haloperidol, zuclopentixol, fluphenazine) (chi-square = 12.497, df = 7, p = 0.0854).
(chi-square = 4.439, df = 1, p = 0.0351), although age at the time of the manifestation was not significantly relevant. Auditory hallucinations were equally distributed among the patients who had made suicide attempts (n = 15, 68.2%) and those who had not (n = 43, 53.5%), as were active delusions (respectively n = 17, 77.2% vs n = 62, 76.5%). There was a significant association between SA and a family history of psychiatric disorders (chi-square = 12.668, df = 2, p = 0.0018) or suicidal behaviours (chi-square = 18.241, df = 2, p = 0.0001). The data relating to drug therapies were extracted from the medical charts of 18 patients in the SA group and 70 in the control group. The latter were more frequently prescribed atypical antipsychotics (clozapine, olanzapine, quetiapine, risperidone and aripiprazole) than typical antipsychotics (haloperidol, zuclopentixol, fluphenazine) (chi-square = 12.497, df = 7, p = 0.0854) (Fig. 1). Furthermore the controls were more frequently prescribed combination therapy with antipsychotics and mood stabilisers (lithium, valproate) (chi-square = 5.746, df = 2, p = 0.05) or benzodiazepines (clonazepam, flurazepam), whereas there was no significative difference between the two groups in terms of combined therapy with antipsychotics and antidepressants (sertraline, paroxetine, fluoxetine, or clomipramine) (Fig. 2). Reliable data concerning the daily doses and duration of drug treatment were available for only a few patients, and so they were not considered in the analysis. Logistic regression was used to explore the results of the statistical analysis, with the presence of suicidal behaviour as the dependent variable, and age, age at onset of psychosis, gender, a DUP of >1 year, substance abuse, hospitalisations, and the presence of a lifetime depressive dimension as covariates (Table 3). There was a trend towards significance with regard to the age of onset of psychiatric illness (chi-square = 3.42402, df = 1, p = 0.0643) and a DUP of >1 year (chi-square = 3.32514, df = 1, p = 0.0682), and a high level of significance in relation to the presence of previous hospitalisations for suicide attempts (chi-square = 11.4661, df = 1, p = 0.0007). 4. Discussion
There were no significant between-group differences in the distribution of the diagnostic subcategories, but the attempters were more frequently diagnosed as having Paranoid Schizophrenia (42.85%) or Undifferentiated Schizophrenia (31.42%). However, the attempters were characterised by a DUP of >1 year (chi-square = 9.984, df = 1, p = 0.0016), and 20 (57%) had been previously hospitalised (chi-square = 25.515, df = 1, p < 0.001). The patients with SAs also manifested a depressive dimension (>6 points on the CDSS) more often than the control group
We retrospectively evaluated a sample of patients with a diagnosis of schizophrenia in order to investigate the associations between their demographic and clinical variables and suicide attempts occurring during the course of their illness. The presence of a depressive dimension was found to be an important risk factor in schizophrenic patients as 30% of those attempting suicide showed depressive symptoms immediately before the attempt, a rate lower but compatible with those observed in other studies (Meltzer et al., 2000). It has been
M.C. Mauri et al. / Asian Journal of Psychiatry 6 (2013) 421–427
Fig. 2. Combination therapy with antipsychotics and antidepressants, benzodiazepines or mood stabilisers assumed by suicide attempters and not attempters. Not attempters were more frequently prescribed combination therapy with antipsychotics and mood stabilisers (lithium, valproate) (chi-square = 5.746, df = 2, p = 0.05) or benzodiazepines (clonazepam, flurazepam). There was no significative difference between the two groups in terms of combined therapy with antipsychotics and antidepressants (sertraline, paroxetine, fluoxetine, or clomipramine).
suggested that having a depressive disorder acts as a trigger of suicidal behaviour in vulnerable patients with schizophrenia (Schennach-Wolff et al., 2011), and a history of past and present depressive disorders is closely associated with suicide (Hawton and James, 2005). These data indicate the critical role of depressive symptoms in the risk of suicide in schizophrenic patients and the need to assess depressive features carefully in a bid to prevent suicide attempts. Our findings also confirm that a history of hospitalisation(s) is closely associated with a suicide attempts (Lee and Lin, 2009). Furthermore, a recent population-based study found that the risk of suicide in schizophrenia patients is relatively constant during the first year following hospital discharge (Reutfors et al., 2010). Regarding prevention of suicide risk, it must especially focus on improving assessment of suicide risk during impatient treatment and the first week after discharge, and special attention must be paid to patients with one or more of the identified risk factors (Nordentoft, 2007). On the basis of our findings, the severity of psychiatric illness seems to play an important role in the risk of suicide, especially during the acute phase. This underlines the importance of immediately assessing the risk upon admission and ensuing appropriate follow-up and outpatient treatment upon discharge. One of the most interesting findings of our study is the significant association between a suicide attempt and a DUP of >1 year (p = 0.0016). Some studies have found a correlation between a longer DUP and suicidal behaviour before presentation (Altamura et al., 2003; Harvey et al., 2008; Preti et al., 2009). This highlights the fact that the early detection of schizophrenia symptoms and early intervention are important not only in improving the overall outcomes, but also in preventing suicide attempts. Furthermore there was a significant association between SAs and a family history of psychiatric disorders (chi-square = 12.668, df = 2, p = 0.0018) or suicidal behaviours (chi-square = 18.241,
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df = 2, p = 0.0001). A parental history of psychiatric illness could increase risk for suicide either through genetic transmission of vulnerability associated with psychiatric illness, or through its negative influence on family life, e.g. reduced care to the children (Qin et al., 2002; Pawlak et al., 2013). Previous studies have consistently documented that both personal and familial psychiatric history, and a family history of suicide and suicidal ideation are important risk factors for completed suicide among psychiatric in-patients (Large et al., 2011; Qin et al., 2002). However, few studies have been able to explore this association in detail by taking into account these aspects simultaneously to examine their relative importance (Qin et al., 2002). The results of analysis of the data concerning pharmacological treatment showed that the patients who did not attempt suicide were more frequently prescribed atypical antipsychotics (especially clozapine) than those who did. Despite the limitations of the pharmacological data (the treatments were not standardised, the data were collected retrospectively, and reliable information about doses and treatment duration was only available for a few patients), our findings seem to confirm that the use of antipsychotics agents decreases all-cause mortality, as found in most of the other studies published to date (Tiihonen et al., 2009; Altamura et al., 1999). In particular, clozapine seems to be the most beneficial in terms of reducing the risk of suicide (Tiihonen et al., 2009; Meltzer et al., 2000; Altamura et al., 2003; De Hert et al., 2010; Wasserman et al., 2012) and suicidal behaviour (Meltzer et al., 2003; Hennen and Baldessarini, 2005). Although these results are not in according with the study conducted by Sernyak et al. (2001) that fails to support the hypothesis that clozapine treatment is associated with significantly fewer deaths due to suicide. We also found that the not-attempters more frequently received antipsychotics combined with mood stabilisers or benzodiazepines, which suggests that these drugs also reduce the risk of suicide, especially in patients with depressive symptoms (Wasserman et al., 2012; Cipriani et al., 2005). In addition to stabilising mood, mood stabilisers also have effects on impulsiveness and aggression, whereas benzodiazepines reduce the rate of anxiety, insomnia and agitation although, to the best of our knowledge, there are no published data concerning the specific role of benzodiazepines in reducing the risk of suicide in schizophrenic patients. Lithium is the only other drug that has been shown to prevent suicide, and is primarily used in patients with bipolar disorder (Wasserman et al., 2012; Leucht et al., 2007; Mauri et al., 1990). However, its effect on suicidal behaviour among schizophrenic patients is less clear (Leucht et al., 2007). Even though we have not found significative difference between attempters and not attempters regarding the use of antipsychotics combined with antidepressants, a recent review reports that selective serotonin receptor inhibitors (SSRIs) not only ameliorate depressive symptoms in patients with schizophrenia, but they also appear to attenuate suicidal thoughts (Kasckow et al., 2011; Wasserman et al., 2012). Although further researches are needed to
Table 3 Summary of the statistics for the best-fit logistic regression model applied to our data. Variable Age Age at onset Gender DUP 1 anno Substance abuse Previous hospitalization Depressive dimension
Coefficient 0.0088 0.2119 0.4542 16.1707 14.5157 32.2928 1.2673
Standard error
df
p-Value
Odds ratio
0.0599 0.1386 1.1438 1180.16 1552.4 3389.2 1.1446
1 1 1 1 1 1 1
0.8816 0.0643 0.6911 0.0682 0.4861 0.0007 0.2629
1.0089 0.8090 1.5749 9.4877E 2.0180 0.0582 0.2815
In this analysis, the dependent variable was the occurrence of suicide attempts lifetime. df = degrees of freedom; p-value = significance level; DUP = duration of untreated psychosis.
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more effectively personalise the treatment of suicidal thoughts and behaviours and the prevention of suicide in patients with schizophrenia. Some of the limitations of this study deserve comment. First of all, the total sample size and the size of the group of patients attempting suicide were quite small, and this may have reduced the power of the analyses. Secondly, the study only included patients who had been regularly followed up in our clinic: as this obviously excluded patients who made lethal attempts, the prevalence of suicide attempts may be underestimated and the sample itself may be biased by the inclusion of only less severe cases. However, it is comparable to the samples in previous studies of the clinical correlates of suicidal behaviour in schizophrenia, in which suicide completers were excluded or only represented a minority of the patients (Hawton and van Heeringen, 2009). Finally, the study was retrospective and based on a review of the clinical charts of schizophrenic patients followed up in a nonstandardised setting, whereas it has been suggested that prospective, controlled studies may be better for investigating the role of clinical and pharmacological variables in predicting suicide risk. Further prospective studies of larger samples are warranted, particularly when investigating the role of early detection strategies and atypical antipsychotic treatment in reducing the risk of suicide. Funding No forms of financial support were received for this study. Conflict of interests The authors disclose no conflict of interests. No financial support or compensation has been received from any individual or corporate entity for research or professional service and there are no personal financial holdings that could be perceived as constituting a potential conflict of interest. Ethics committee review The protocol received agreement by our Ethics Committee and the patients or their relatives, acknowledged about the details of the study, and provided their written informed consent. Acknowledgement The authors wish to acknowledge the patients included in the study. References Addington, D., Addington, J., Schissel, B., 1990. A depression rating scale for schizophrenics. Schizophrenia Research 3, 247. Altamura, A.C., Bassetti, R., Bignotti, S., Pioli, R., Mundo, E., 2003. Clinical variables related to suicide attempts in schizophrenic patients: a retrospective study. Schizophrenia Research 60 (1) 47–55. Altamura, A.C., Bignotti, S., Pioli, R., Tura, G., Mannu, P., Soddu, A., La Croce, L., 1999. Suicidal behavior in schizophrenia: a retrospective study. European Neuropsychopharmacology 9 (Suppl. 5) S271. Caldwell, C.B., Gottesman, I.I., 1990. Schizophrenics kill themselves too: a review of risk factors for suicide. Schizophrenia Bulletin 16 (4) 571–589. Cipriani, A., Pretty, H., Hawton, K., Geddes, J.R., 2005. Lithium in the prevention of suicidal behavior and all-cause mortality in patients with mood disorders: a systematic review of randomized trials. American Journal of Psychiatry 162, 1805–1819. De Hert, M., Correll, C.U., Cohen, D., 2010. Do antipsychotic medications reduce or increase mortality in schizophrenia? A critical appraisal of the FIN-11 study. Schizophrenia Research 117 (1) 68–74. 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.
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