Risk Factors for Suicide in Patients With Schizophrenia

February 1, 2007

Risk Factors for Suicide in Patients With Schizophrenia

February 2007, Vol. XXIV, No. 2

It has long been known that persons with schizophrenia are at high risk for attempted and completed suicide. With estimates of about 5% to 15% for completed suicide1,2 and 20% to 40% for attempted suicide,3-6 the recent increase in attention to this concern is promising. Most studies have involved reviews of patient charts and reviews of psychiatric and death registries, which limits our understanding of risk factors, warning signs, and potential interventions. More recently, the assessment of suicidal behavior in patients with schizophrenia in clinical trials has added a new dimension to the research.7 Prospective longitudinal studies that directly assess baseline history of suicidal behavior and related factors will be the most informative.

Risk of completed suicide and of attempted suicide may be different. In addition, some risk factors cut across psychopathologies and some are unique to individuals with schizophrenia and schizoaffective disorder. The following is a review of the risk factors for sui-cidal behavior in patients with schizophrenia; where possible, the differentiations between those who attempt suicide and those who complete suicide will be made (Table 1).

Epidemiology and demographics
The epidemiology of suicidal behavior in patients with schizophrenia has been well documented.8,9 Like suicide in other groups, more men than women complete suicide,10 although suicide attempt rates do not differ between the sexes.6 Women with schizophrenia have higher rates of suicide relative to other women.9 In general, the period of greatest risk of suicide is early in the course of illness; therefore, patients with schizophrenia who completed suicide tended to be young and in the first 5 to 10 years of illness.9 However, unlike other groups at risk, the risk of suicide in patients with schizophrenia is elevated throughout the lifespan.9 Suicide attempts tend to be of moderate to severe lethality,6 and those who attempt suicide are likely to make multiple attempts.

In addition, factors such as unemployment,8,9 single status (unmarried),6,8,9 and living alone6 have been found more often in patients with schizophrenia who attempt and complete suicide; however, this information is minimally helpful since most people with schizophrenia are unemployed and unmarried.6 Patients with schizophrenia who attempt suicide are hospitalized almost twice as often as those who do not attempt suicide, although it is unclear whether they are hospitalized for suicidal behavior or another cause.6 Taken together, these findings indicate that efforts to reduce risk should involve increasing social supports for and a sense of productivity in patients wherever possible. Indeed, quality of life has been found to be associated with suicidal behavior.11

Previous suicidal behavior
As with most disorders, the best predictor of future behavior is past behavior. In schizophrenia, almost half of suicide completers have made a previous attempt12 and attempters typically make more than one attempt.6

When assessing risk for suicidal behavior, therefore, it is important to obtain a thorough history of past suicidal ideation and attempts, including frequency, intent, plans, persistence, and most important, factors surrounding previous suicide attempts.

There is no evidence that suicidal behavior occurs frequently in response to psychotic behavior. However, suicidal behavior frequently occurs in persons bothered by their own psychotic behavior, 6 which indicates that they are often psychotic at the time of the suicidal behavior. On the other hand, the results of a study by Siris and colleagues 13 suggest that the greatest risk of suicide is during the postpsychotic period. 13 This is typically the period following hospitalization, since most individuals still retain some level of psychotic symptoms or attenuated symptoms at discharge. The first suicide attempt typically occurs some time after the onset of psychosis. 6

The presence of command auditory hallucinations (CAH) for suicide alone cannot predict suicidal behavior, but individuals who are at risk for suicide are more likely to make an attempt when they have CAH. 14 Therefore, CAH should not be ignored.

The relationship between negative symptoms and suicidal behavior is unclear because of the major methodologic limitations of reported retrospective studies. Similarly, the relationship between positive symptoms and negative symptoms and suicidal behavior requires more research since there are significant implications for treatment and prevention. Thus, current findings highlight the need for ongoing clinical care and research as well as the aggressive treatment of psychotic symptoms.

Feelings of depression are considered an integral part of suicidal behavior. Several investigators have studied the role of depression in suicidal behavior by assessing depressed mood, hopelessness, and major depression. 15-19 Major depression is common in schizophrenia, regardless of whether it is as prominent a part of the illness, as in schizoaffective disorder. 20-22 More than half of patients with schizophrenia will experience at least one major depressive episode. 22-24

As with other risk factors for suicidal behavior, the presence of depression in and of itself does not automatically lead to suicidal behavior, but individuals vulnerable to suicidal behavior are at increased risk during depressive episodes. 22 Unfortunately, it is still not widely known that antidepressants and mood stabilizers can be used in combination with antipsychotic medications and that these combinations can be more effective than antipsychotics that are presumed to have antidepressant or mood-stabilizing properties.25-27 Thus, the identification and treatment of depression in persons with schizophrenia is essential and is likely to reduce the risk of suicidal behavior.28

Social factors
Social factors include premorbid social functioning, social trauma, and social support. Many investigators suggest that persons with good premorbid social functioning who have schizophrenia become demoralized by the decrease in their ability to function and therefore become suicidal. This demoralization syndrome has been demonstrated in patients who have insight about their illness. 20,29-32 Other researchers have found that individuals with poor premorbid functioning (eg, poor social skills, aggressive and/or impulsive behavior) are at greater risk for suicidal behavior. Both scenarios have some validity, depending on the characteristics and history of the individual.

In addition, good premorbid function typically means that there are more effective social skills and better social supports when the individual is ill. This may facilitate improved quality of life and better coping skills in the face of a chronic illness. Some researchers have found that awareness improves the outcome of schizophrenia.33 Therefore, assessment of social functioning and development of effective social skills are important components of suicide prevention.

A history of childhood abuse has been found to be more prevalent among patients with schizophrenia who attempt suicide compared with those who do not attempt suicide.34 It is not clear whether this fosters a sense of hopelessness and helplessness, indicates family psychopathology or impulsive/aggressive behavior, or increases risk for other reasons. As investigators focus on assessing individuals directly, more information about the role of childhood trauma in suicidal behavior in patients with schizophrenia will probably emerge.

Social support is of primary importance for suicide prevention. Feelings of belonging as well as having others to rely on help protect against suicidal behavior. Having someone to monitor a patient during high-risk periods who can remove potential means for suicide is critical. Reductions in support-whether temporary, as in therapist or family vacations, or more long-term, as in moving out of a family residence-are periods of increased risk. 9 This risk can be mitigated by working with the patient to secure interim supports or to facilitate the transition to alternative housing.

Increased attention to the patient during any adjustment period is important. In fact, one of the highest risk periods occurs when a hospitalized patient with schizophrenia learns that he or she will not be returning home; attention to the patient is crucial at this time. Perhaps patients should remain in the hospital while they adjust to such a change. This is in contrast to the typical scenario, in which patients facing discharge have increased privileges and less supervision. Regardless, it is critical to include the patient in the process. Such transitions are critical for patients and their families, and it is important to make it a positive transition for everyone.

Biological factors
Biological contributors to suicidal behavior in schizophrenia have been examined via family history, monoamine metabolites in cerebrospinal fluid (CSF), and more recently, candidate gene allele variants. Family history was found to be associated with suicidal behavior across diagnostic groups.35 Serotonin and norepinephrine have been the primary neurotransmitters investigated in suicidal behavior, and the results are inconclusive at best and more likely negative. CSF metabolites of 5-hydroxyindole acetic acid (5-HIAA), homovanillic acid and 3-methoxy-4-hydroxy-phenylglycol have not differentiated suicidal and nonsuicidal individuals with schizophrenia. 36-39 CSF 5-HIAA has, however, been found to relate to suicide intention and lethality in patients with schizophrenia who attempt suicide.40

Similar inconsistencies have been found in candidate gene allele variants that may be related to overall suicidal behavior including that in patients with schizophrenia.41-43 Many candidate genes have been identified, including serotonin transport and receptor genes, monoaminoxidase, and catechol-O-methyltransferase alleles. To date, results are typically negative or inconclusive and there has been a lack of replicability.

Additional research, including neuroimaging and gene expression studies, is necessary in order to understand the relationship between neurotransmitters and suicidal behavior.

Treatment with medication and cognitive-behavioral therapy (CBT) reduces suicidal behavior.44,45 Conversely, lack of treatment is associated with increased rates of suicidal behavior.44,45 Some investigators suggest that treatment with new generation antipsychotics, clozapine in particular, has been found to reduce suicidal behavior in those with schizophrenia.46,47 Although the effect was originally an incidental finding,48 more recent studies have specifically investigated the effects of olanzapine and clozapine on suicidal behavior in patients with schizophrenia.49 Other researchers have demonstrated that the finding is not unique to any one medication and that all antipsychotics reduce the risk of suicidal behavior.50

When treating with medication, it is important to consider adverse effects, because some researchers have suggested that side effects such as akathisia can increase the risk of suicidal behavior. 51,52 Adjunctive medication for mood and anxiety are also likely to reduce suicidal behavior in patients with schizophrenia, but this has not been formally studied. Attention to dosages and adverse effects is critical, because these have a direct impact on medication effectiveness and quality of life.

More recently, CBT has been used to reduce suicidal behavior in patients with schizophrenia.53-56 While the results are equivocal, this may be because such therapies are in the early stages of development. With more research, the effectiveness of CBT for suicidal behavior in patients with schizophrenia may be improved. As in other areas of mental health, it is likely that a combination of medication and psychotherapy will be most effective.

In fact, it may be that any intervention has the possibility of reducing immediate risk. For example, Melle and colleagues57 found that individuals with schizophrenia who were identified through an early detection program received treatment earlier, were less symptomatic, and had less suicidal behavior than those who were not exposed to an early detection program. In addition, there was a decrease in suicidal ideation in the nonintervention group between the time of identification and enrollment in treatment. This suggests that treatment engagement alone can have a positive impact on reducing suicidal behavior.

Summary and conclusions
Individuals with schizophrenia and schizoaffective disorder are at increased risk for attempted and completed suicide throughout their lifespan. No one factor can be highlighted as essential for increasing or reducing this risk. In fact, vulnerable individuals tend to have increased periods of risk, such as during depression, during stressful times, and during changes in support. After a comprehensive evaluation of symptoms, social functioning, and past suicidal behavior, a continual multifaceted evaluation of suicidal behavior and potentially associated factors is necessary for early and effective suicide risk reduction (Table 2). Suicidal behavior recurs and passes, especially when intervention is available. Although it may be impossible to prevent every suicide, effective intervention with attention to quality of life is essential for suicide risk reduction.

Dr Harkavy-Friedman is associate professor of clinical psychology in the department of psychiatry at Columbia University, New York, and research scientist at the New York State Psychiatric Institute. She reports that she has no conflicts of interest concerning the subject matter of this article.

Drugs Mentioned in This Article
Clozapine (Clozaril)
Olanzapine (Zyprexa)

References1. Winokur G, Tsuang M. The Iowa 500: suicide in mania, depression, and schizophrenia. Am J Psychiatry. 1975; 132:650-651.
2. Palmer BA, Pankratz VS, Bostwick JM. The lifetime risk of suicide in schizophrenia: a reexamination. Arch Gen Psychiatry. 2005;62:247-253.
3. Planansky K, Johnston R. The occurrence and characteristics of suicidal preoccupation and acts in schizophrenia. Acta Psychiatr Scand. 1971;47:473-483.
4. Roy A, Mazonson A, Pickar D. Attempted suicide in chronic schizophrenia. Br J Psychiatry. 1984;144:303-306.
5. Heila H, Isometsa ET, Henriksson MM, et al. Antecedents of suicide in people with schizophrenia. Br J Psychiatry. 1998;173:330-333.
6. Harkavy-Friedman JM, Restifo K, Malaspina D, et al. Suicidal behavior in schizophrenia: characteristics of individuals who had and had not attempted suicide. Am J Psychiatry. 1999;156:1276-1278.
7. Alphs L, Anand R, Islam M, et al. The international suicide prevention trial (interSePT): rationale and design of a trial comparing the relative ability of clozapine and olanzapine to reduce suicidal behavior in schizophrenia and schizoaffective patients. Schizophr Bull. 2004;30: 577-586.
8. Tandon R. Suicidal behavior in schizophrenia. Expert Rev Neurother. 2005;5:95-99.
9. Caldwell BC, Gottesman II. Schizophrenics kill themselves too: a review of the risk factors for suicide. Schizophr Bull. 1990;16:571-589.
10. Lester D. Sex differences in completed suicide by schizophrenic patients: a meta-analysis. Suicide Life Threat Behav. 2006;36:50-56.
11. Ponizovsky AM, Grinshpoon A, Levav I, Ritsner MS. Life satisfaction and suicidal attempts among persons with schizophrenia. Compr Psychiatry. 2003;44:442-447.
12. Heila H, Isometsa ET, Henriksson MM, et al. Suicide and schizophrenia: a nationwide psychological autopsy study on age- and sex-specific clinical characteristics of 92 suicide victims with schizophrenia. Am J Psychiatry. 1997;154:1235-1242.
13. Siris SG, Harmon GK, Endicott J. Postpsychotic depressive symptoms in hospitalized schizophrenic patients. Arch Gen Psychiatry. 1981;38:1122-1123.
14. Harkavy-Friedman JM, Kimhy D, Nelson EA, et al.
Suicide attempts in schizophrenia: the role of command auditory hallucinations for suicide. J Clin Psychiatry. 2003; 64:871-874.
15. Beck AT, Steer RA, Kovacs M, Garrison B. Hopelessness and eventual suicide: a 10-year prospective study of patients hospitalized with suicidal ideation. Am J Psychiatry. 1985;142:559-563.
16. Osman A, Gifford J, Jones T, et al. Psychometric evaluation of the reasons for living inventory. Psychol Assess. 1993;5:154-158.
17. Ran MS, Chan CL, Xiang MZ, Wu QH. Suicide attempts among patients with psychosis in a Chinese rural community. Acta Psychiatr Scand. 2003;107:430-435.
18. Roy A. Depression, attempted suicide, and suicide in patients with chronic schizophrenia. Psychiatr Clin North Am. 1986;9:193-2006.
19. Strosahl K, Chiles JA, Linehan M. Prediction of suicide intent in hospitalized parasuicides: reasons for living, hopelessness, and depression. Compr Psychiatry. 1992;33:366-373.
20. Drake RE, Gates C, Cotton PG, et al. Suicide among schizophrenics: who is at risk? J Ment Nerv Dis. 1984; 172:613-618.
21. Drake RE, Gates C, Whitaker A, Cotton PG. Suicide among schizophrenics: a review. Compr Psychiatry. 1985;26:90-100.
22. Harkavy-Friedman JM, Nelson EA, Venarde DF, Mann JJ. Suicidal behavior in schizophrenia and schizoaffective disorder: examining the role of depression. Suicide Life Threat Behav. 2004;34:66-76.
23. Guze SB, Robbins E. Suicide and primary affective disorders. Br J Psychiatry. 1970;117:437-438.
24. Fawcett J, Scheftner W, Clark D, et al. Clinical predictors of suicide in patients with major affective disorders: a controlled prospective study. Am J Psychiatry. 1987;144:35-40.
25. Keck PE Jr, Strakowski SM, McElroy SL. The efficacy of antipsychotics in the treatment of depressive symptoms, hostility, and suicidality in patients with schizophrenia. J Clin Psychiatry. 2000;1:4-9.
26. Mazeh D, Shahai B, Saraf R, Melamed Y. Venlafaxine for the treatment of depressive episode during the course of schizophrenia. J Clin Psychopharm. 2004;24:653-655.
27. Whitehead C, Moss S, Cardno A, Lewis G. Antidepressants for the treatment of depression in people with schizophrenia: a systematic review. Psychol Med. 2003;33:589-599.
28. Siris SG. Depression in schizophrenia: perspective in the era of “atypical” antipsychotic agents. Am J Psychiatry. 2000;157:1379-1389.
29. Farberow NL, Shneidman ES, Leonard CV. Suicide among schizophrenia mental hospital patients In: Farberow NL, Shneidman ES, eds. The Cry for Help. New York: McGraw-Hill; 1961.
30. Haas GL, Sweeney JA. Premorbid and onset features of first-episode schizophrenia. Schizophr Bull. 1992;18: 373-386.
31. Sletten IW, Brown ML, Evenson RC, Altman H. Suicide in mental hospital patients. Dis Nerv Syst. 1972;33: 328-335.
32. Pompili M, Ruberto A, Kotzalidis GD, et al. Suicide and awareness of illness in schizophrenia: an overview. Bull Menninger Clin. 2004;68:297-318.
33. Bourgeois M, Swendsen J, Young F, et al. InterSePT Study Group. Awareness of disorder and suicide risk in the treatment of schizophrenia: results of the international suicide prevention trial. Am J Psychiatry. 2004; 161:1494-1496.
34. Roy A. Reported childhood trauma and suicide attempts in schizophrenic patients. Suicide Life Threat Behav. 2005;35:690-693.
35. Tremeau F, Staner L, Duval F, et al. Suicide attempts and family history of suicide in three psychiatric populations. Suicide Life Threat Behav. 2005;35:702-713.
36. Ninan PT, van Kammen DP, Scheinin M, et al. CSF 5-hydroxyindoleacetic acid levels in suicidal schizophrenic patients. Am J Psychiatry. 1984;141:566-569.
37. Roy A, Ninan P, Mazonson A, et al. CSF monoamine metabolites in chronic schizophrenic patients who attempt suicide. Psychol Med. 1985;15:335-340.
38. Cooper SJ, Kelly CB, King DJ. 5-Hydroxyindoleacetic acid in cerebrospinal fluid and prediction of suicidal behaviour in schizophrenia. Lancet. 1992;340:940-941.
39. Lemus CZ, Lieberman JA, Johns CA, et al. CSF 5-hydroxyindoleacetic acid levels and suicide attempts in schizophrenia. Biol Psychiatry. 1990;27:926-929.
40. Harkavy-Friedman JM, Haas GL, Nelson E, et al. CSF metabolites and clinical features of schizophrenia: relationship to suicidal behavior. Paper presented at: American College of Neuropsychopharmacology; December 14, 1998; Las Croabas, Puerto Rico.
41. De Luca V, Tharmalingam S, Muller DJ, et al. Gene-gene interaction between MAOA and COMT in suicidal behavior: analysis in schizophrenia. Brain Res. 2006; 1097:26-30.
42. De Luca V, Zai G, Tharmalingam S, et al. Association study between the novel functional polymorphism of the serotonin transporter gene and suicidal behaviour in schizophrenia. Eur Neuropsychopharmacol. 2006;16: 268-271.
43. Li D, Duan Y, He L. Association study of serotonin 2A receptor (5-HT2A) gene with schizophrenia and suicidal behavior using systematic meta-analysis. Biochem Biophys Res Commun. 2006;340:1006-1015.
44. Tiihonen J, Walhbeck K, Lonnqvist J, et al. Effectiveness of antipsychotic treatments in a nationwide cohort of patients in community care after first hospitalisation due to schizophrenia and schizoaffective disorder: observational follow-up study. BMJ. 2006;333:224.
45. Leucht S, Heres S. Epidemiology, clinical consequences, and psychosocial treatment of nonadherence in schizophrenia. J Clin Psychiatry. 2006;67:3-8.
46. Hennen J, Baldessarini RJ. Suicidal risk during treatment with clozapine: a meta-analysis. Schizophr Res. 2005;73:139-145.
47. Meltzer HY. Suicidality in schizophrenia: a review of the evidence for risk factors and treatment options. Curr Psychiatry Rep. 2002;4:279-283.
48. Meltzer HY, Okayli G. Reduction of suicidality during clozapine treatment of neuroleptic-resistent schizophrenia: impact on risk-benefit assessment. Am J Psychiatry.1995;152:183-190.
49. Meltzer HY, Alphs L, Green AI, et al. International Suicide Prevention Trial Study Group. Arch Gen Psychiatry. 2003;60:82-91.
50. Keck PE JR, Strakowski SM, McElroy SL. The efficacy of antipsychotics in the treatment of depressive symptoms, hostility, and suicidality in patients with schizophrenia. J Clin Psychiatry. 2000;61:4-9.
51. Drake RE, Ehrlich J. Suicide attempts associated with akathisia. Am J Psychiatry. 1985;142:499-501.
52. Shear MK, Frances A, Weiden P. Suicide associated with akathisia and depot fluphenazine treatment. J Clin Psychopharmacol. 1983;3:235-236.
53. Brown GK, Have TT, Henriques GR, et al. Cognitive therapy for the prevention of suicide attempts. JAMA. 2005;294:563-576.
54. Hawton K, Townsend E, Arensman E, et al. Psychosocial versus pharmacological treatments for deliberate self-harm. Cochrane Database Syst Rev. 2000(2): CD001764.
55. Jones C, Cormac I, Silveira da Mota Neto JI, Campbell C. Cognitive behavior therapy for schizophrenia. Cochrane Database Syst Rev. 2004(4):CD000524.
56. Salkovskis PM, Atha C, Storer D. Cognitive-behavioural problem solving in the treatment of patients who repeatedly attempt suicide. A controlled trial. Br J Psychiatry. 1990;157:871-876.
57. Melle I, Johannesen JO, Friis S, et al. Early detection of the first episode of schizophrenia and suicidal behavior. Am J Psychiatry. 2006;163:800-804.

Evidence-Based References

  • Hawton K, Townsend E, Arensman E, et al. Psychosocial versus pharmacological treatments for deliberate self-harm. Cochrane Database Syst Rev. 2000(2): CD001764.

  • Jones C, Cormac I, Silveira da Mota Neto JI, Campbell C. Cognitive behavior therapy for schizophrenia. Cochrane Database Syst Rev. 2004(4):CD000524.