Suicide attempts in schizophrenic patients: Clinical variables

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Author's personal copy 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 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. 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 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.

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