Suicide Risk and Treatments for Patients With Bipolar Disorder
Authors: Ross J. Baldessarini
Journal: JAMA (2003)

BIPOLAR DISORDER, ONE OF THE MOST COMMON SEvere mental illnesses, includes type 1 (with mania and usually recurrent depression) and type 2 (recurrent major depression with hypomania). Lifetime prevalence for type 1 bipolar disorder is approximately 1%, but inclusion of more broadly defined conditions increases this rate to 2% to 5%. Bipolar disorder can begin in childhood or adolescence, continues throughout life, and is extraordinarily costly—financially as well as clinically and socially. The course of bipolar disorder is episodic but highly variable, with potential for high levels of severity and recurrence intensity, disproportionately high depressive morbidity, and comorbidity with substance abuse and anxiety disorders. Bipolar depression can be present during 20% to 30% of patients’ time, even during prophylactic treatment, and is closely associated with disability and mortality. Bipolar disorder proves fatal in a high proportion of patients from complications of risk-taking behavior, comorbid stress-sensitive medical illnesses, and especially suicide. These characteristics mark bipolar disorder as a major unsolved public health challenge. Treatment for bipolar disorder was revolutionized in the early 1970s by the introduction of US Food and Drug Administration (FDA)–approved long-term prophylactic treatment with lithium carbonate for preventing recurrences of mania and bipolar depression. Lithium remains the international standard of comparison for an increasing number of innovative treatments introduced in recent years, including several anticonvulsants and modern antipsychotics. However, evidence for long-term prophylactic effectiveness of agents other than lithium remains limited, and comparisons of specific agents in particular phases of bipolar disorder are needed. No currently available treatment provides full protection from recurrences of manic, mixed manic-depressive, major depressive, or highly prevalent milder depressive states. Among patients with type 1or 2 bipolar disorder, longterm lithium monotherapy can reduce mania or hypomania and depression similarly, by about two thirds. Most other agents with proposed mood-stabilizing effects appear to be more effective against mania and hypomania than against bipolar depression, with the possible exception of lamotrigine. For example, in well-designed comparisons with other agents, divalproex has yielded considerably less long-term protective effects against bipolar depression or mixed dysphoric-agitated states than against mania, although divalproex has been shown to limit depression by some measures. Addition of an antidepressant is unlikely to resolve the problem of residual depression, owing to inconsistent responsiveness of bipolar depression to antidepressants and their risk of inducing mania or emotional instability in patients with bipolar disorder. As a cause of premature death in patients with bipolar disorder, suicide represents an extraordinarily high risk, with an estimated rate of 0.40% per year vs the international general population average of 0.017% per year, with a standardized mortality ratio of 22. For comparison, the average standardized mortality ratio for suicide is about 20 among persons with unipolar major depression and 8.4 for those with schizophrenia. Moreover, suicide attempts by patients with bipolar disorder have an increased lethal potential. Among patients with bipolar disorder, rates of suicide attempts are only 5 times the rates of completed suicides, whereas in the general population, rates of suicide attempts are 10 to 20 times the rates of completed suicides. Suicide in patients with bipolar disorder is strongly associated with depressive and dysphoric-agitated (mixed) states. Suicidal risk may be greater in type 2 bipolar disorder, characterized by less severe episodes of elevated mood than type 1 but with severe recurrent depression, often misdiagnosed as nonbipolar major depression and not consistently treated with mood-stabilizing agents. Long-term use of lithium is the only treatment consistently associated with much lower rates of suicide and lifethreatening suicide attempts in bipolar disorder. In a recent meta-analysis of 22 studies with data permitting