advertisement
advertisement

Lithium and Suicide Risk in Bipolar Disorder

SUICIDE RATES ON AND OFF LITHIUM

We recently evaluated all available studies of lithium and suicide since the emergence of long-term lithium maintenance treatment in manic depressive disorders in the early 1970s. Studies were identified by computerized literature searches and cross-referencing from publications on the topic, as well as by discussing the aims of the study with colleagues who have conducted research on lithium treatment or who may have had access to unpublished data on suicide rates in bipolar disorder patients. We sought data permitting estimates of rates of attempted or completed suicides in bipolar patients or mixed samples of patients with major affective disorders that included bipolar manic-depressives. Suicide rates during maintenance lithium treatment were compared with rates after discontinuation of lithium or in similar untreated samples when such data were available.

Suicide rates during long-term lithium treatment were determined for each study, and, when available, rates for patients discontinued from lithium or for comparable patients not treated with a mood stabilizer were also determined. Suicide rates during lithium treatment were not significantly greater with larger numbers of subjects or longer follow-up. However, many of the available reports were flawed in one or more respects. Limitations included: (1) a common lack of control over treatments other than lithium; (2) incomplete separation by diagnosis or provision of separate rates for suicide attempts and completions in some studies; (3) a lack of comparisons of treated and untreated periods within subjects or between groups; (4) study of fewer than 50 subjects/treatment conditions despite the relatively low frequency of suicide; (5) inconsistent or imprecise reporting of time-at-risk (the amount of time the patient was absent); and (6) selection of patients with previous suicide attempts that may show bias toward increased suicide rates in some studies. Some of these deficiencies were resolved by contacting authors directly. Despite their limitations, we believe that the available data are of sufficient quality and importance to encourage further evaluation.

Table 1 summarizes available data concerning rates of suicides and attempts among manic-depressive patients on or off lithium, based on previously reported (6) and new, unpublished meta-analyses. The results indicate an overall reduction of risk by nearly seven fold, from 1.78 to 0.26 suicide attempts and suicides per 100 patient-years at risk (or percent of persons/year). In another more recent, quantitative meta-analysis (L.T., unpublished, 1999), we evaluated fatality rates ascribed to suicide in the same studies as well as in additional previously unreported data kindly provided by international collaborators. In the latter analysis, based on results from 18 studies and more than 5,900 manic-depressive subjects, we found a similar reduction of risk from a suicide rate averaging 1.83 ± 0.26 suicides per 100 patient-years in patients not treated with lithium (either after discontinuing or in parallel groups not given lithium) to 0.26 ± 0.11 suicides per 100 patient-years in patients on lithium.

IMPLICATIONS OF FINDINGS

The present findings derived from the research literature on lithium and suicide risk indicate substantial protection against suicide attempts and fatalities during long-term lithium treatment in patients with bipolar manic-depressive disorders, or in mixed groups of major affective disorder subjects that included bipolar patients. While this evidence is strong and consistent overall, the relative infrequency of suicide and limited size of many studies required pooling of data to observe statistically significant effect that was not found in several individual studies. Large samples and lengthy times-at-risk, or pooling of data across studies, are likely to be required in future studies of treatment effects on suicide rates.

It is also important to emphasize that the observed, pooled, residual risk of suicides while on lithium, though much lower than without lithium treatment, is still large, and greatly exceeds general population rates. The average suicide rate during lithium maintenance treatment, at 0.26% per year (Table 1), is more than 20 times greater than the annual general population rate of about 0.010% to 0.015%, which also includes suicides associated with psychiatric illnesses.(11, 40) The evidently incomplete protection against suicide associated with lithium treatment may reflect limitations in the effectiveness of the treatment itself and, very likely, potential noncompliance to long-term maintenance therapy.

Since suicidal behavior is closely associated with concurrent depressive or dysphoric mixed states in bipolar disorder patients (9, 11, 20), it is likely that residual risk for suicide is associated with incomplete protection against recurrences of bipolar depressive or mixed mood states. Lithium has traditionally been considered to provide better protection against mania than against bipolar depression.(27, 38) In a recent study of more than 300 bipolar I and II subjects, we found that depressive morbidity was reduced from 0.85 to 0.41 episodes per year (a 52% improvement) and time ill was reduced from 24.3% to 10.6% (a 56% reduction) before vs during lithium maintenance treatment.(23) Improvements in mania or hypomania were somewhat larger, at 70% for episode rates and 66% for percentage of time manic, with even greater improvement in hypomania in type 11 cases (84% fewer episodes and 80% less time hypomanic). Corresponding suicide rates fell from 2.3 to 0.36 suicide attempts per 100 patient-years (an 85% improvement) during vs before lithium maintenance treatment. (9, 20) The present findings indicate an 85% to crude sparing of completed suicides and attempts (1.78 to 0.26% per year; see Table 1). These comparisons suggest that protective effects of lithium rank: suicide attempts or suicides ³ hypomania>mania>bipolar depression. Since suicide is closely associated with depression (11, 20), it follows that better protection against bipolar depression must be a key to limiting suicidal risk in bipolar disorders.

It is not clear whether reduction of suicide rates during lithium maintenance reflects simply the mood-stabilizing effect of lithium, or if other properties of lithium also contribute. In addition to protection from recurrences of bipolar depressive and mixed-mood states closely associated with suicidal behavior, important associated benefits of lithium treatment possibly also contribute to reduction of suicide risk. These may include improvements in overall emotional stability, interpersonal relationships and sustained clinical follow-up, vocational functioning, self-esteem, and perhaps reduced comorbid substance abuse.

An alternative possibility is that lithium may have a distinct psychobiological action on suicidal and perhaps other aggressive behaviors, possibly reflecting serotonin-enhancing actions of lithium in limbic forebrain. (38, 57) This hypothesis accords with growing evidence of an association between cerebral deficiency of serotonin functioning and suicidal or other aggressive behaviors. (58-59) If lithium protects against suicide through its central serotonergic activity, then proposed alternatives to lithium with dissimilar pharmacodynamics may not be equally protective against suicide. Specifically, mood-stabilizing agents that lack serotonin enhancing properties, including most anti-convulsants (27, 38), might not protect against suicide as well as lithium. It would be unwise clinically to assume that all putative mood-stabilizing agents provide similar protection against suicide or other impulsive or dangerous behaviors.

Last Updated: 06 April 2017
Reviewed by Harry Croft, MD

Related Articles

Support Group

Log in

Login to your account

Username *
Password *
Remember Me

Create an account

Fields marked with an asterisk (*) are required.
Name *
Username *
Password *
Verify password *
Email *
Verify email *

Follow Us

advertisement

Bipolar Videos

Mental Health Newsletter

Sign up for the HealthyPlace mental health newsletter for latest news, articles, events.

Mental Health
Newsletter Subscribe Now!

Mental Health Newsletter

Sign up for the HealthyPlace mental health newsletter for latest news, articles, events.

Log in

Login to your account

Username *
Password *
Remember Me
advertisement
X
advertisement
X
advertisement
X
Back To Top