Evidence-Based Reviews

Reducing suicide risk in psychiatric disorders

Current Psychiatry. 2003 September;2(9):14-24

Antidepressants show little protective effect in major depression, but more promising evidence is emerging for treating patients with bipolar or psychotic disorders.

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References

1. Goldsmith SK, Pellmar TC, Kleinman AM. Bunney WE, Jr (eds). Reducing suicide: A national imperative. Washington DC: National Academies Press, 2002.

2. Harris EC, Barraclough B. Suicide as an outcome for mental disorders: a meta-analysis. Br J Psychiatry 1997;170:205-28.

3. Angst F, Stassen HH, Clayton PJ, Angst J. Mortality of patients with mood disorders: follow-up over 34-38 years. J Affect Disord 2002;68:167-81.

4. Rihmer Z, Pestality P. Bipolar II disorder and suicidal behavior. Psychiatr Clin North Am 1999;22:667-73.

5. Baldessarini RJ, Tondo L, Hennen J. Lithium treatment and suicide risk in major affective disorders: update and new findings. J Clin Psychiatry 2003;64(suppl 5):44-52.

6. Tondo L, Isacsson G, Baldessarini RJ. Suicide in bipolar disorder: risk and prevention. CNS Drugs 2003;17:491-511.

7. Ghaemi SN, Lenox MS, Baldessarini RJ. Effectiveness and safety of long-term antidepressant treatment in bipolar disorder. J Clin Psychiatry 2001;62:565-9.

8. Judd LL, Akiskal HS, Schettler PJ, et al. The long-term natural history of weekly symptomatic status of bipolar I disorder. Arch Gen Psychiatry 2002;59:530-7.

9. Baldessarini RJ, Tondo L, Hennen J, Viguera AC. Is lithium still worth using? An update of selected recent research. Harvard Rev Psychiatry 2002;10:59-75.

10. Tondo L, Baldessarini RJ, Floris G. Long-term clinical effectiveness of lithium maintenance treatment in types I and II bipolar disorders. Br J Psychiatry 2001;178(suppl 41):S184-90.

11. Tondo L, Hennen J, Baldessarini RJ. Lower suicide risk with longterm lithium treatment in major affective illness: a meta-analysis. Acta Psychiatr Scand 2001;104:163-72.

12. Baldessarini RJ, Tondo L, Hennen J. Treating the suicidal patient with bipolar disorder: reducing suicide risk with lithium. Ann NY Acad Sci 2001;932:24-43.

13. Baldessarini RJ, Tondo L, Viguera AC. Discontinuing lithium maintenance treatment in bipolar disorder: risks and implications. Bipolar Disord 1999;1:17-24.

14. Baldessarini RJ, Tondo L, Hennen J. Treatment latency and previous episodes: relationships to pretreatment morbidity and response to maintenance treatment in bipolar I and II disorders. Bipolar Disord 2003;5:169-79.

15. Bratti IM, Baldessarini RJ, Baethge C, Tondo L. Pretreatment episode count and response to lithium treatment in manic-depressive illness. Harvard Rev Psychiatry (in press).

16. Tondo L, Hennen J, Baldessarini RJ. Rapid-cycling bipolar disorder: effects of long-term treatments. Acta Psychiatr Scand 2003;108:4-14.

17. Thies-Flechtner K, Miller-Oerlinghausen B, Seibert W, et al. Effect of prophylactic treatment on suicide risk in patients with major affective disorders: data from a randomized prospective trial. Pharmacopsychiatry 1996;29:103-7.

18. Goodwin FK, Fireman B, Simon G, et al. Suicide attempts in bipolar patients on lithium vs. divalproex (abstract 45; cited with permission of Dr. Goodwin). San Juan, PR: American College of Neuropsychopharmacology annual meeting, 2002.

19. Suominen KH, Isometsa ET, Henriksson MM, et al. Inadequate treatment for major depression both before and after attempted suicide. Am J Psychiatry 1998;155:1778-880.

20. Kessler RC, Berglund P, Demler O, et al. The epidemiology of major depressive disorder: results from the National Comorbidity Survey Replication (NCS-R). JAMA 2003;289:3095-105.

21. Khan A, Khan S, Kolts R, Brown WA. Suicide rates in clinical trials of SSRIs, other antidepressants, and placebo: analysis of FDA reports. Am J Psychiatry 2003;160:790-2.

22. Baldessarini RJ, Hennen J. Reduced suicidal risk during treatment with clozapine: A meta-analysis. Manuscript in review, 2003.

23. Wahlbeck K, Cheine M, Essali A, Adams C. Evidence of clozapine’s effectiveness in schizophrenia: a systematic review and meta-analysis of randomized trials. Am J Psychiatry 1999;156:990-9.

24. Meltzer HY, Alphs L, Green AI, et al. Clozapine treatment for suicidality in schizophrenia: International Suicide Prevention Trial (InterSePT). Arch Gen Psychiatry 2003;60:82-91.

25. Glazer WM. Formulary decisions and health economics. J Clin Psychiatry 1998;59(suppl 19):23-9.

Which psychotropics reduce the risk of suicide in patients with psychiatric disorders? Although no drugs eliminate the risk, new evidence is clarifying that some therapeutic choices can make a difference:

Long-term lithium treatment apparently reduces suicide risk in patients with affective disorders; mood-altering anticonvulsants are less well studied but show less benefit than lithium.
Effects of antidepressants remain inconclusive without adequate long-term studies.
At least one atypical antipsychotic—clozapine—probably lowers suicide risk, although direct comparisons of antipsychotic agents are rare.
Surprisingly little evidence is available on nondrug interventions, including rapid hospitalization, psychotherapy, and electroconvulsive therapy.¹

Suicide is the leading cause of malpractice liability in psychiatry and of the heightened risk of death in persons with major affective and psychotic disorders (Box).^1-4 Here are the latest findings to help you choose medications for at-risk patients with bipolar disorder, major depression, or chronic psychoses.

Box

Suicide: High risk with major psychiatric disorders

Suicide is by far the most common cause of premature death among patients with major mood and psychotic disorders.^2,3 A major affective or psychotic disorder increases risk of suicide 8- to 22-fold (Table 1). A history of attempted suicide increases a person’s suicide risk 38-fold, so that the likelihood of dying by suicide becomes greater than one in four (28%).

Attempted suicide is less well-documented but may be 10 to 20 times more common than completed suicide in the general population. Persons with major affective and psychotic disorders complete suicide at an estimated rate of once in five attempts. This high rate suggests that their suicidal intent and methods are particularly lethal.⁴

BIPOLAR DISORDER AND MOOD STABILIZERS

Bipolar disorder is associated with the highest suicide rate among all major psychiatric illnesses, with an international incidence averaging 0.31% of patients per year.⁴ This rate may slightly exceed the suicide rate of patients with major depression, which averages 0.29%/year.

Risk of suicidal behavior is similar among patients with bipolar type II (depression with hypomania) and type I disorder (depression with mania), supporting the view that type II is not a milder form of bipolar illness.^4-6 Indeed, one study of suicide attempts found a higher risk among bipolar II patients (24%) than in bipolar I patients (17%) as well as a higher risk in both bipolar types than in persons diagnosed with unipolar major depression (12%).⁴

Suicidal behavior in bipolar disorder is associated almost entirely with ongoing depression or dysphoria and is especially likely to follow severe and highly recurrent depressive episodes.^5,6 Combinations of depressive-dysphoric and irritable, agitated, anxious features in “mixed states” may be particularly dangerous and can be hard to diagnose with confidence. Moreover, DSM-IV criteria for mixed states are far too narrow in requiring symptoms to simultaneously fulfill criteria for both mania and major depression. More broadly defined mixed states are very common. Underdiagnosis risks underestimation of suicidal potential, and misdiagnosis as “agitated depression” encourages potentially dangerous overuse of antidepressants.^5,7

Depression or dysphoria is the most prevalent morbidity in patients with bipolar disorder. Major and minor depressive states and mixed-dysphoric phases account for nearly one-third of time in follow-up care, exceeding time in mania or hypomania by more than 4-fold.⁸ Ironically, however, bipolar depression is one of the least-studied forms of major depression. Suicidal bipolar patients are typically excluded from antidepressant studies because of the risks of inducing greater instability, agitation, or mania while treating them with an antidepressant but without a mood stabilizer.⁷

LITHIUM’S PROTECTIVE EFFECT

Decades of research and clinical use demonstrate substantially lower risks of suicide and serious suicide attempts when patients with bipolar disorder are treated long-term with lithium salts in standard clinical doses (serum concentrations typically 0.6 to 0.8 mEq/L). Lithium is highly effective in treating all phases of bipolar disorder. A recent meta-analysis of 26 long-term trials of lithium reported between 1967 and 2001 found an average 3.2-fold sparing of morbidity or relapse risk.⁹

Benefits in types I and II. A large European sample¹⁰ compared percent-time-ill in bipolar patients before and after they received lithium as maintenance treatment. Unexpectedly, lithium therapy reduced percent-time-ill to a greater extent among patients with type II than type I bipolar disorder. Time in mania and time in depression were reduced 2.5-fold and 2.0-fold, respectively, in type I patients, compared with nearly 5-fold for time in hypomania and 2.5-fold for time in depression among type II patients.

Because depression is associated with the highest rates of suicidal behavior in all phases of bipolar disorders, lithium’s effects in preventing depressive recurrence are especially important for reducing suicide risk.⁶