Evidence-Based Reviews

Reducing suicide risk in psychiatric disorders

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

References

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

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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).

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In a review of 22 studies¹¹—some including patients with bipolar or recurrent unipolar major depression—risk of death by suicide was reduced at least 5-fold, based on an informal comparison of pooled rates in treated versus untreated samples. Based on quantitative meta-analysis, the pooled risk of death by suicide was reduced nearly 9-fold (or by 89%) in patients who received lithium maintenance treatment compared with those who did not. The risk for suicide attempts fell nearly 10-fold in a compilation of 33 studies (Table 2).¹² Available studies do not permit separate analysis of lithium’s effects on suicidal behavior among patients with bipolar disorder and recurrent unipolar depression, leaving the relative benefit by diagnosis uncertain.

Table 1

Suicide risks in selected psychiatric disorders*

Condition	Relative risk	Incidence (%/year)	Lifetime risk (%)
Prior suicide attempt	38.4	0.549	27.5
Bipolar disorder	21.7	0.310	15.5
Major depression	20.4	0.292	14.6
Mixed drug abuse	19.2	0.275	14.7
Dysthymia	12.1	0.173	8.65
Obsessive-compulsive disorder	11.5	0.143	8.15
Panic disorder	10.0	0.160	7.15
Schizophrenia	8.45	0.121	6.05
Personality disorders	7.08	0.101	5.05
Alcohol abuse	5.86	0.084	4.20
Cancer	1.80	0.026	1.30
General population	1.00	0.014	0.72
* Estimated relative risks compared with the general population,² with recently updated information about bipolar disorders.⁶ Annual rates are based on international general population average (14.3/100,000/year) × standardized mortality ratio; lifetime estimates are based on annual rates × 50 years as an estimate of lifetime exposure for years at major risk.

Dangers of stopping lithium. In our study⁵ of more than 200 patients with DSM-IV bipolar I or II disorder, prophylactic lithium treatment for an average of 4 years reduced the risk of completed and attempted suicide by 6.5-fold. A subgroup of more than 100 patients discontinued lithium, usually after prolonged stability, and we excluded from analysis any cases of suspected emerging illness associated with discontinuation. Within 6 to 12 months after stopping treatment, this subgroup’s rates of suicidal behavior increased markedly—by 20-fold above treated rates.⁵ Thereafter, their rates returned to prelithium treatment levels.

Of particular clinical importance:

discontinuing lithium gradually—over at least 2 weeks—was associated with a 2-fold lower suicide risk than more-abrupt discontinuation
suicidal behavior after lithium discontinuation was almost always associated with emerging depression, which can provide an early warning of impending suicidal risk.

Table 2

Effect of lithium treatment on risk of completed and attempted suicide in patients with bipolar and recurrent depressive disorders*

Treatment or sample	Suicides	Attempts	All acts	A/S ratio
With lithium	0.16	0.41	0.57	2.6
Without lithium	0.88	4.02	4.90	4.6
Off/on lithium ratio	5.5	9.8	8.6	—
General population	0.014	0.21	0.22	15.3
Off lithium/general population ratio	56.4	19.1	22.3	—
On lithium/general population ratio	11.4	2.0	2.6	—
A/S ratio: Attempts versus completed suicides
* Rates (acts/year/100 persons, or %/year), based on previously reported averages derived from analyses of data from 33 studies with 55 treatment-arms,¹² from a more selected analysis of 22 studies of completed suicides,¹¹ and updated estimates for general population rates.⁶

This is not the first time we have found evidence of a dramatic—but time-limited—increase in risk of recurrent bipolar illness when lithium treatment was discontinued.¹³ Bipolar disorder patients who discontinue long-term lithium treatment abruptly are at high risk of recurrent depression and mania.¹³

Incomplete protection. Lithium’s protection against suicidal risk is incomplete, as one can see by comparing lithium-treated versus untreated bipolar patients’ suicide rates with those of the general population (Table 2).⁶

With lithium:

suicides plus attempts declined 8.6-fold to levels 2.6 times greater than those of the general population
suicide attempts fell 10-fold to levels that are about twice that of the general population
risk of completed suicides declined 5.5-fold with lithium treatment but remained 11 times higher than that of the general population.

Without lithium:

risk of suicide in bipolar patients is approximately 22 times greater than that of the general population
ratio of attempts to suicides among bipolar disorder patients averages 4.6, suggesting that suicide attempts by patients with bipolar disorder are relatively lethal.⁶

Effect of delayed lithium therapy. Many patients with bipolar disorder do not receive sustained prophylactic treatment early in the illness.

Studies typically show an average 5- to 10-year gap between illness onset and the start of sustained lithium maintenance treatment. This delay averages more than 3 years longer among women with bipolar II disorder than men with bipolar I disorder, evidently reflecting major clinical dissimilarities between these groups.^6,14 In contrast, we found that nearly one-quarter of long-term risk of suicidal behavior emerges within the first year of bipolar illness.⁵ Clearly, patients with recurrent major affective illness require earlier intervention and more consistent clinical care.

We have also found that delayed maintenance treatment or the number of prior episodes of bipolar illness do not seem to limit therapeutic response to lithium.^14,15 These findings support the conclusion that prophylactic lithium treatment can be worthwhile, even after years of illness and many recurrences. Moreover, our recent meta-analysis of treatment options for rapid-cycling bipolar illness indicates that—even though all treatments have yielded inferior results compared with nonrapidly-cycling patients—no alternative has outperformed lithium.¹⁶