[Postgraduate Medicine]
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[SYMPOSIUM]

COMMENTARY

Bipolar disorder is a potentially fatal disease

Leslie Citrome, MD, MPH; Joseph F. Goldberg, MD

VOL 117 / NO 2 / FEBRUARY 2005 / POSTGRADUATE MEDICINE

Dr Citrome has received research support or honoraria for speaking or has been a consultant for Abbott, AstraZeneca, Lilly, Janssen, Pfizer, Novartis, and Bristol-Myers Squibb. Dr Goldberg has received research grants from Abbott, GlaxoSmithKline, and Lilly; is on the speakers' bureau for Abbott, AstraZeneca, Bristol-Myers Squibb, Lilly, GlaxoSmithKline, and Pfizer; and is on the scientific advisory board for Abbott, AstraZeneca, Bristol-Myers Squibb, Lilly, GlaxoSmithKline, Pfizer, Ortho-McNeil, Organon, Johnson & Johnson, UCB Pharma, and Amgen. The authors disclose no unlabeled uses for any product mentioned in this article.

Citrome L, Goldberg JF. Bipolar disorder is a potentially fatal disease. Postgrad Med 2005;117(2):9-11

Suicide is among the top five causes of death in the United States for persons aged 5 to 44 years (1). In the Epidemiologic Catchment Area survey (2), the lifetime rate of suicide attempts in persons with bipolar disorder was 29.2%, compared with 15.9% in persons with unipolar depression and 4.2% in those with other major psychiatric disorders (excluding personality disorders).

In this study, persons with bipolar disorder were six times more likely to attempt suicide than those with a psychiatric disorder other than depression and about twice as likely as those with unipolar depression (2).

Although many persons with bipolar disorder who attempt suicide never actually complete it, the annual average suicide rate in men and women with diagnosed bipolar disorder (0.4%) is more than 20 times that in the general population (3). From another perspective, about half of all suicides can be attributed to bipolar disorder (4).

Risk factors for suicide among patients with bipolar disorder include early age at disease onset, high number of depressive episodes, comorbid alcohol abuse, personal history of antidepressant-induced mania, and family history of suicidal behavior (5). Impulsivity and hostility traits also elevate suicide risk (6). Impulsivity may be the reason why patients with bipolar disorder who abuse substances are twice as likely to attempt suicide as those who do not (7). About two thirds of patients who attempt suicide make multiple attempts (8). In those with bipolar disorder, 1 out of 5 suicide attempts is lethal, in contrast to 1 out of 10 to 1 out of 20 in the general population (9).

Physician intervention

What can primary care physicians do in the face of such daunting statistics? First, recognition of the possibility of bipolar disorder in a patient presenting with depressive symptoms is key. The patient may be at higher risk than a patient with unipolar depression. Second, questions about suicidal ideation, intent, and plans should be part of every assessment of patients with depressed or irritable mood.

It is a myth that asking about suicide places the idea into a patient's mind, and often, patients are grateful for the opportunity to discuss their fears about suicide (10). A gradual approach to such questioning often works well:

  • Do you ever feel that life is not worth living?
  • Have you ever thought about ending your life?
  • What methods have you thought about?

Suicidal ideation should be taken seriously; emergency consultation with a psychiatrist is highly desirable. If prompt evaluation by a psychiatrist is not logistically possible, telephone consultation with a local mental health center is an option. Steps that ensure the protection of the patient are paramount.

The role of antidepressants

Medications can be helpful in decreasing suicide risk, but not all medications have the same antisuicide properties (11). In a recent and influential report (12), the risks of suicide attempt and suicide death during treatment with lithium were compared with those for divalproex sodium. The investigators conducted a retrospective analysis of patients in two large, integrated health plans in California and Washington (N = 20,638 patients with bipolar disorder). After adjustment for age, sex, health plan, year of diagnosis, comorbid medical and psychiatric conditions, and concomitant use of other psychotropic drugs, risk of suicide death was almost three times higher in patients taking divalproex than in those taking lithium. Risk of nonfatal attempts was almost double.

With the exception of clozapine (Clozaril, FazaClo), less is known about the ability of second-generation antipsychotic agents to reduce suicidal ideation and behavior (11). Combinations of antipsychotic agents and antidepressants are used for treatment of bipolar I depression (depressive episode and a history of mania), and the combination drug of olanzapine and fluoxetine hydrochloride (Symbyax) has received US Food and Drug Administration (FDA) approval for that indication (13). Use of antidepressant monotherapy for bipolar disorder remains controversial, but recent evidence suggests it may be useful in treatment of bipolar II depression (depressive episode and a history of hypomania) (14).

The FDA's response

In February 2004, an FDA advisory panel identified apparent risks associated with several antidepressants for increasing suicide-related behaviors in children and adolescents with depression. Although no specific risks of these behaviors were observed among adult patients with depression, the FDA extended a warning label advisory about the potential association between antidepressant use and suicidality in adults as well as children and adolescents.

The relationship between antidepressant use and suicide is complex. Suicidal features are commonly associated with severe depression, and most completed suicides among depressed patients seem to occur in the context of undertreatment or nonadherence to effective antidepressant therapy (11). Another important consideration involves the potential for antidepressants to unmask a biologic vulnerability to bipolar illness in children and adolescents. Such a reaction could result in the induction of agitation or a mixed state of both depression and mania, during which impulsivity and suicidal features may become active.

Use of mood-stabilizing pharmacotherapies, rather than antidepressants, may warrant consideration in children and adolescents with depression who have signs of bipolar diathesis. Physicians who treat depressed patients in this age-group also should remain watchful for indicators of potential vulnerability to bipolar illness, such as early age at disease onset, prepubescent depression, psychosis, family history of bipolar disorder, or prior "activation"--including symptoms such as anxiety, agitation, panic attacks, insomnia, irritability, hostility (aggressiveness), impulsivity, akathisia (psychomotor restlessness), hypomania, and mania--in response to antidepressant use (15).

Current treatment options

Electroconvulsive therapy may be an excellent form of intervention--particularly for patients with mixed states--when medication is inadequate in controlling symptoms. Despite the negative public attitude in the United States about electroconvulsive therapy, the technology has advanced greatly in recent years, and this therapy can literally be a lifesaver (16).

A patient's adherence to a medication regimen provides hope that episodes of depression can be prevented, or at least reduced in severity. This, in turn, reduces the risk of suicide. Special attention is warranted for patients with comorbid substance abuse who demonstrate impulsive traits.

Lithium has the most evidence of capability as an antisuicide agent. However, some patients may not be able to tolerate its short- or long-term side effects. Some evidence suggests that anticonvulsants such as valproate are superior to lithium for patients who exhibit rapid cycling or mixed states (17). Regardless, polypharmacy with multiple mood stabilizers in addition to lithium is not uncommon (18). The emergence of new treatments, including second-generation antipsychotic agents and the newer anticonvulsants, may offer useful alternatives, but these medications have not been as well studied in suicide prevention.

The following articles in this symposium address the current approach to diagnosis and treatment of bipolar disorder. "The Many Faces of Bipolar Disorder: How to Tell Them Apart" discusses underdiagnosis of bipolar disorder in the clinical setting, as well as the potential morbidity and mortality associated with misdiagnosed bipolar disorder. "Latest Therapies for Bipolar Disorder: Looking Beyond Lithium" provides an overview of the wide range of pharmacologic therapies available to treat bipolar disorder, from traditional mainstays such as lithium to emerging treatments, including combination therapies and second-generation antipsychotic agents. As the understanding of bipolar disorder grows, so may the medical options for its treatment and hence the hope that episodes of both mania and depression, and the increased risk of suicide, can be curtailed.

References

  1. Kochanek KD, Smith BL. Deaths: preliminary data for 2002. Hyattsville, Md: National Center for Health Statistics, 2004; National vital statistics report, vol 52, No. 13
  2. Chen YW, Dilsaver SC. Lifetime rates of suicide attempts among subjects with bipolar and unipolar disorders relative to subjects with other Axis I disorders. Biol Psychiatry 1996;39(10):896-9
  3. Tondo L, Isacsson G, Baldessarini R. Suicidal behaviour in bipolar disorder: risk and prevention. CNS Drugs 2003;17(7):491-511
  4. Goodwin FK, Jamison KR. Manic-depressive illness. New York: Oxford Univ Press, 1990:227-44
  5. Slama F, Bellivier F, Henry C, et al. Bipolar patients with suicidal behavior: toward the identification of a clinical subgroup. J Clin Psychiatry 2004;65(8):1035-9
  6. Michaelis BH, Goldberg JF, Davis GP, et al. Dimensions of impulsivity and aggression associated with suicide attempts among bipolar patients: a preliminary study. Suicide Life Threat Behav 2004;34(2):172-6
  7. Dalton EJ, Cate-Carter TD, Mundo E, et al. Suicide risk in bipolar patients: the role of co-morbid substance use disorders. Bipolar Disord 2003;5(1):58-61
  8. Michaelis BH, Goldberg JF, Singer TM, et al. Characteristics of first suicide attempts in single versus multiple suicide attempters with bipolar disorder. Compr Psychiatry 2003;44(1):15-20
  9. 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
  10. Citrome L. Management of depression: current options for this highly treatable disorder. Postgrad Med 1994;95(1):137-45
  11. Ernst CL, Goldberg JF. Antisuicide properties of psychotropic drugs: a critical review. Harv Rev Psychiatry 2004;12(1):14-41
  12. Goodwin FK, Fireman B, Simon GE, et al. Suicide risk in bipolar disorder during treatment with lithium and divalproex. JAMA 2003;290(11):1467-73
  13. Tohen M, Vieta E, Calabrese J, et al. Efficacy of olanzapine and olanzapine-fluoxetine combination in the treatment of bipolar I depression. Arch Gen Psychiatry 2003;60(11):1079-88 [Erratum, Arch Gen Psychiatry 2004;61(2):176]
  14. Amsterdam JD, Brunswick DJ. Antidepressant monotherapy for bipolar type II major depression. Bipolar Disord 2003;5(6):388-95
  15. Goldberg JF, Truman CJ. Antidepressant-induced mania: an overview of current controversies. Bipolar Disord 2003;5(6):407-20
  16. Ciapparelli A, Dell'Osso L, Tundo A, et al. Electroconvulsive therapy in medication-nonresponsive patients with mixed mania and bipolar depression. J Clin Psychiatry 2001;62(7):552-5
  17. Lennkh C, Simhandl C. Current aspects of valproate in bipolar disorder. Int Clin Psychopharmacol 2000;15(1):1-11
  18. Post RM, Frye MA, Denicoff KD, et al. Emerging trends in the treatment of rapid cycling bipolar disorder: a selected review. Bipolar Disord 2000;2(4):305-15

Dr Citrome, coordinator of this symposium, is professor of psychiatry, New York University School of Medicine, New York, and director, clinical research and evaluation facility, Nathan S. Kline Institute for Psychiatric Research, Orangeburg, New York. Dr Goldberg is director, bipolar disorders research program, department of psychiatry research, Zucker Hillside Hospital, North Shore Long Island Jewish Health System, Glen Oaks, New York. Correspondence: Leslie Citrome, MD, MPH, Nathan S. Kline Institute for Psychiatric Research, 140 Old Orangeburg Rd, Orangeburg, NY 10962. E-mail: citrome@nki.rfmh.org.

Symposium Index

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