The power of the life force is striking—in even among the most abominable conditions, like concentration camps, suicide remains relatively uncommon. Yet some human beings appear to harbor a powerful destructive force, which can under certain conditions manifest itself in violence, homicide, or suicide. Suicide has been with us since the beginning of history; it has often been romanticized, or viewed as an understandable escape from an intolerable situation. Philosophers and writers from William James to Albert Camus to Goethe have tended to view suicide as a window into the human condition, perhaps extreme but nevertheless a reflection of our shared humanity. However, highly reliable research has shown that suicide is, by and large, not a window into the human condition, but rather a manifestation of a disturbance—an abnormality of the human condition—a mental disorder.

Physicians know that the primary goal of medical treatment (after first doing no harm) is to prevent death. Death is the ultimate enemy in medical illness. In psychiatric illness, this enemy usually appears in the guise of suicide; the illness uses the hands of patients to wreak its havoc. To reduce mortality in psychiatric conditions, then, means to reduce suicide. It is indeed striking how little this matter has been analyzed. Little data are available on mortality with medications that are researched and approved for psychiatric illness. This would not be acceptable for medical illnesses outside of psychiatry today; it should not be the case in psychiatric illnesses either.

Can timely diagnosis and treatment of depression reduce the risk of suicide? Studies of treatment effects on mortality in major mood disorders remain rare and are widely considered difficult to carry out ethically. Despite close associations of suicide with major affective disorders and related comorbidity, the available evidence provides little support for sustained reductions of suicide risk by most mood-altering treatments, including antidepressants. Studies designed to evaluate clinical benefits of mood-stabilizing treatments in bipolar disorders, however, provide comparisons of suicidal rates with and without treatment or under different treatment conditions. This emerging body of research provides consistent evidence of reduced rates of suicides and attempts during long-term treatment with lithium. This effect may not generalize to proposed alternatives, particularly carbamazepine. Our recent international collaborative studies found compelling evidence for prolonged reduction of suicidal risks during treatment with lithium, as well as sharp increases soon after its discontinuation, all in close association with depressive recurrences. Depression was markedly reduced, and suicide attempts were less frequent, when lithium was discontinued gradually. These findings indicate that studies of the effects of long-term treatment on suicide risk are feasible and that more timely diagnosis and treatment for all forms of major depression, but particularly for bipolar depression, should further reduce suicide risk.

Which mood stabilizers are the most effective in reducing suicide rates in patients with bipolar disorder? This paper reviews the literature and compares the data on two types of mood-stabilizing agents, lithium and anticonvulsants. Compared with the large amount of data on lithium, there is surprising little information available on the effects of anticonvulsants on mortality in manic-depressive illness. Each was also assessed in terms of suicide risk factors such as depression and mixed episodes, rapid cycling, substance abuse, anxiety and panic, and central serotonergic function. Only two studies that provide data demonstrating anticonvulsant efficacy in preventing suicide in bipolar disorder are available, and the data are incomplete at best. Further research in this area should include an emphasis on the outcome of mortality in patients treated with any of the anticonvulsants or with lithium-anticonvulsant combinations.

Standard pharmacotherapy for the maintenance of treatment of patients with bipolar I disorder consists of lithium, valproate, or carbamazepine. However, many patients fail to respond to monotherapy with any of these agents, and as a result, psychiatrists often resort to polypharmacy. Findings from some open-label trials and retrospective chart reviews suggest this approach may be useful, but in the few controlled trials that have been conducted, the results have been negative. One drug combination that warrants further study as maintenance therapy is lithium plus valproate. Each is approved by the U.S. Food and Drug Administration for treatment of acute mania, and lithium has demonstrated efficacy for maintenance treatment as well. Some preliminary evidence suggests that the combination can be effective for patients who do not respond to monotherapy, and it seems to be no more dangerous than monotherapy. Concomitant administration of lithium plus valproate does not significantly alter lithium pharmacokinetics, and statistically significant changes that arise in valproate pharmacokinetics are not clinically significant. Although it is not known whether the drugs interact to augment response, many of their effects in the central nervous system do differ, and there is no indication of pharmacodynamic interactions that oppose each other. Finally, some evidence suggests that lithium and valproate may differ with regard to clinical variables that predict response to treatment. (J Clin Psychopharmacol 1998;18:38–49)

Bipolar I disorder afflicts approximately 1% of the U.S. adult population, with a median age at onset of 19 years. In many respects, it is a disabling disease. Acute episodes of mania and depression are often protracted with 24% of patients still acutely ill after 1 year has elapsed, 16% after 2 years, and 9% after 5 years. Subsyndromal symptoms, which impose significant morbidity that falls short of meeting full criteria for a mood episode, may occur frequently. Patients with bipolar I disorder are more likely than not to be unemployed or underemployed, less likely to marry and more likely to divorce than matched control subjects, and almost every family perceives the illness as a burden. Even remitted patients manifest poor psychosocial functioning, Ultimately, nearly 19% of patients die from suicide.

The materials in the following section are speaker comments from an educational symposium entitled Suicide: Clinical/Risk Management Issues for Psychiatrists sponsored by the American Psychiatric Association, May 16, 1999. The program chairpersons were Drs. Douglas Jacobs and Ross J. Baldessarini. The symposium was supported by an unrestricted educational grant from Solvay Pharmaceuticals.

The symposium focused on critical clinical and risk management issues about suicide as they impact clinical practice. Dr. Douglas G. Jacobs presented a suicide assessment protocol with suggestions on how to include current understanding about suicide in treatment planning. Dr. Kay Redfield Jamison reviewed bipolar disorder with an emphasis on early diagnosis, aggressive treatment, and the phenomenology of suicidal behavior. Dr. Ross J. Baldessarini discussed the lethality of bipolar depression and the effectiveness of lithium maintenance therapy to limit bipolar depression and reduce suicide risk. Dr. Jan A. Fawcett presented four clinical profiles of completed suicide and reviewed suggested treatment approaches appropriate for each that may help psychiatrists reduce the risk of suicide among their patients. Dr. Herbert Hendin explored the role psychiatrists play in performing comprehensive assessments of patients who request assisted suicide. Finally, Dr. Thomas G. Gutheil reviewed the basis for malpractice litigation and provided guidelines for preventing liability following a patient's suicide.