When to suspect bipolar disorder

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Applied Evidence

When to suspect bipolar disorder

J Fam Pract. 2010 December;59(12):682-688

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References

1. Hirschfeld RM, Lewis L, Vornik LA. Perceptions and impact of bipolar disorder: how far have we really come? Results of the national depressive and manic-depressive association 2000 survey of individuals with bipolar disorder. J Clin Psychiatry. 2003;64:161-174.

2. Stewart C, El-Mallakh RS. Is bipolar disorder over diagnosed among patients with substance abuse? Bipolar Disord. 2007;9:646-648.

3. El-Mallakh RS, Karippot A. Chronic depression in bipolar disorder. Am J Psychiatry. 2006;163:1137-1341.

4. Goodwin FK, Jamison KR. Manic-Depressive Illness: Bipolar Disorders and Recurrent Depression, 2nd ed. Oxford University Press: New York; 2007.

5. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 4th ed, text rev (DSM-IV-TR). American Psychiatric Association: Arlington, VA; 2000.

6. Baldessarini RJ, Salvatore P, Khalsa HM, et al. Dissimilar morbidity following initial mania versus mixed-states in type-I bipolar disorder. J Affect Disord. 2010;126:299-302.

7. Kilbourne AM, Cornelius JR, Hans X, et al. Burden of general medical conditions among individuals with bipolar disorder. Bipolar Disord. 2004;6:368-373.

8. Shah A, Shen N, El-Mallakh RS. Weight gain occurs after onset of bipolar illness in overweight bipolar patients. Ann Clin Psychiatry. 2006;18:239-241.

9. Kessler RC, Nelson CB, McGonagle KA, et al. The epidemiology of co-occurring addictive and mental disorders: implications for prevention and service utilization. Am J Orthopsychiatry. 1996;66:17-31.

10. Mantere O, Melartin TK, Suominen K, et al. Differences in Axis I and II comorbidity between bipolar I and II disorders and major depressive disorder. J Clin Psychiatry. 2006;67:584-593.

11. Calabrese JR, Hirschfeld RM, Reed M, et al. Impact of bipolar disorder on a US community sample. J Clin Psychiatry. 2003;64:425-432.

12. Collins JC, McFarland BH. Divalproex, lithium and suicide among Medicaid patients with bipolar disorder. J Affect Disord. 2008;107:23-28.

13. Hirschfeld RM, Williams JB, Spitzer RL, et al. Development and validation of a screening instrument for bipolar spectrum disorder: the Mood Disorder Questionnaire. Am J Psychiatry. 2000;157:1873-1875.

14. Surja AAS, Tamas RL, El-Mallakh RS. Antipsychotic medications in the treatment of bipolar disorder. Curr Drug Targets. 2006;7:1217-1224.

15. Scherk H, Pajonk FG, Leucht S. Second-generation antipsychotic agents in the treatment of acute mania: a systematic review and meta-analysis of randomized controlled trials. Arch Gen Psychiatry. 2007;64:442-455.

16. Suppes T, Vieta E, Liu S, et al; Trial 127 Investigators. Maintenance treatment for patients with bipolar I disorder: results from a North American study of quetiapine in combination with lithium or divalproex (trial 127). Am J Psychiatry. 2009;166:476-488.

17. Judd LL, Akiskal HS, Schettler PJ. The long-term natural history of the weekly symptomatic status of bipolar I disorder. Arch Gen Psychiatry. 2002;59:530-537.

18. Judd LL, Akiskal HS, Schettler PJ, et al. A prospective investigation of the natural history of the long-term weekly symptomatic status of bipolar II disorder. Arch Gen Psychiatry. 2003;60:261-269.

19. El-Mallakh RS, Karippot A. Antidepressant-associated chronic irritable dysphoria (ACID) in bipolar disorder. J Affect Disord. 2005;84:267-272.

20. Suppes T, Datto C, Minkwitz M, et al. Effectiveness of the extended release formulation of quetiapine as monotherapy for the treatment of acute bipolar depression. J Affect Disord. 2010;121:106-115.

21. Corya SA, Perlis RH, Keck PE, Jr, et al. A 24-week open-label extension study of olanzapine-fluoxetine combination and olanzapine monotherapy in the treatment of bipolar depression. J Clin Psychiatry. 2006;67:798-806.

22. Frey MA, Grunze H, Suppes T, et al. A placebo-controlled evaluation of adjunctive modafinil in the treatment of bipolar depression. Am J Psychiatry. 2007;164:1242-1249. .

23. Goldberg JF, Burdick KE, Endick CJ. Preliminary randomized, double-blind, placebo-controlled trial of pramipexole added to mood stabilizers for treatment-resistant bipolar depression. Am J Psychiatry. 2004;161:564-566.

24. Zarate CA, Jr, Payne JL, Singh J, et al. Pramipexole for bipolar II depression: a placebo-controlled proof of concept study. Biol Psychiatry. 2004;56:54-60.

25. Sienaert P, Vansteelandt K, Demyttenaere K, et al. Ultra-brief pulse ECT in bipolar and unipolar depressive disorder: differences in speed of response. Bipolar Disord. 2009;11:418-424.

26. Valenti M, Benabarre A, Garcia-Amador M, et al. Electroconvulsive therapy in the treatment of mixed states in bipolar disorder. Eur Psychiatry. 2008;23:53-56.

27. Barekatain M, Jahangard L, Haghighi M, et al. Bifrontal versus bitemporal electroconvulsive therapy in severe manic patients. J ECT. 2008;24:199-202.

28. Calabrese JR, Vieta E, El-Mallakh R, et al. Mood state at study entry as predictor of the polarity of relapse in bipolar disorder. Biol Psychiatry. 2004;56:957-963.

29. Fujiwara Y, Honda T, Tanaka Y, et al. Comparison of early- and late-onset rapid cycling affective disorders: clinical course and response to pharmacotherapy. J Clin Psychopharmacol. 1998;18:282-288.

30. Bellivier F, Golmard J, Rietschel M, et al. Age at onset in bipolar I affective disorder: further evidence for three subgroups. Am J Psychiatry. 2003;160:999-1001.

31. Thiruvengadam AP, Chandrasekaran K. Evaluating the validity of blood-based membrane potential changes for the identification of bipolar disorder I. J Affect Disord. 2007;100:75-82.

32. National Institute of Mental Health. How is bipolar disorder treated? Available at: http://www.nimh.nih.gov/health/publications/bipolar-disorder/how-is-bipolar-disorder-treated.shtml. Accessed November 9, 2010.

33. US Food and Drug Administration. FDA approves Saphris to treat schizophrenia and bipolar disorder. Aug. 14, 2009. Available at: http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm177401.htm. Accessed November 17, 2010.

Considerable evidence suggests that lithium significantly reduces the risk of relapse, particularly in classic euphoric mania. Other agents that are approved for maintenance therapy include aripiprazole, lamotrigine, and olanzapine as monotherapy, and olanzapine, quetiapine, and ziprasidone as addon agents to lithium or divalproex. Combining a mood stabilizer and an antipsychotic agent generally leads to better outcomes, both in acute mania¹⁵ and relapse prevention,¹⁶ compared with a mood stabilizer alone. However, bipolar depression, which is more common than either mania¹⁷ or hypomania,¹⁸ is the major clinical challenge.

TABLE 4
FDA-approved treatments for bipolar disorder^32,33

Treatment	Mania	Bipolar depression	Maintenance
Aripiprazole	√		√
Asenapine	√
Carbamazepine ER	√
Chlorpromazine	√
Divalproex; divalproex ER	√
Lamotrigine			√
Lithium	√*		√
Olanzapine	√	√^†	√
Quetiapine; quetiapine XR	√	√	√
Risperidone	√
Ziprasidone	√		√
ER, extended release; FDA, US Food and Drug Administration; XR, extended release. *Not approved for mixed mania. ^† Approved for bipolar depression in combination with fluoxetine.

What’s best for bipolar depression?
For the acutely depressed bipolar patient, optimizing mood stabilization therapy is typically the first step. If the depression doesn’t resolve in 4 or 5 weeks, adding an agent with relapse prevention properties is a preferred approach. Antidepressants may be harmful to patients with bipolar disorder (possibly triggering manic episodes, rapid cycling, or a chronic dysphoric state),^3,19 and are usually tried only after other options have been exhausted.

Quetiapine, which is effective for the treatment of mania at doses around 600 mg daily, appears to also be effective for the treatment of acute bipolar depression at doses around 300 mg/d.²⁰ In 2-year studies in which quetiapine was added to either lithium or divalproex, the 2-drug combination was found to reduce the risk for relapse approximately 3-fold compared with the mood stabilizer alone.¹⁶

Olanzapine/fluoxetine. Besides quetiapine, this drug combination is the only other agent with FDA approval for the treatment of bipolar depression. A 24-week open extension trial found that the risk for a manic episode due to the coadministration of fluoxetine was low, but 27% of those studied relapsed into depression.²¹

Drugs that do not have FDA approval specifically for bipolar depression may also be used to treat it.

FAST TRACK

In addition to having antidepressant qualities, lithium appears to have an antisuicide effect.

Lithium, which has antidepressant activity, particularly at levels exceeding 0.8 mEq/L, is one such drug. In addition to its effectiveness in treating bipolar depression, lithium appears to have an antisuicide effect.¹²

In a recent study of patients with bipolar disorder, lithium was found to be more protective than other mood stabilizers. The hazard ratio (HR) for suicide attempts was significantly greater for patients taking divalproex (HR=2.7; P<.001) or carbamazepine (HR=2.8; P<.001) compared with patients taking lithium.¹²

Modafinil, a nonstimulant used to increase alertness in patients with daytime sleepiness due to a variety of conditions, has been tested as an adjunctive agent in depressed bipolar patients. In a blinded study, patients were randomly assigned to have modafinil (n=41) or placebo (n=44) added to their existing treatment regimen.²² Response, defined as ≥50% improvement in mood, occurred at twice the rate in those treated with modafinil (44%) compared with those on placebo (23%; P<.05).²² In the brief (6 week) study, modafinil did not appear to cause an increase in manic or hypomanic episodes.²²

Pramipexole, a dopamine agonist used for early-stage Parkinson’s disease, has been tested in patients with bipolar depression in 2 small, short-term placebo-controlled trials. A total of 15 patients with type I disease and 28 patients with type II disease were studied for a 6-week period. The results: 60% to 67% of patients taking pramipexole responded, vs 9% to 20% of those on placebo.^23,24

Electroconvulsive therapy (ECT) is an underutilized treatment that is effective for depressed patients who are resistant to pharmacological treatment. In fact, bipolar depression may improve more rapidly than unipolar depression with ultra-brief pulse treatment—a therapy in which the pulse width of the electrical stimulus is much briefer (<0.5 msec) than that of standard ECT.²⁵ ECT has also been shown to be effective for mixed states, in which depression and mania coexist.²⁶ The cognitive adverse effects associated with ECT can be reduced while maintaining the same efficacy by using bifrontal (instead of the typical bitemporal) electrode replacement.²⁷

A blood test for bipolar disorder?

Although the DSM-IV identifies bipolar disorder on the basis of symptoms, there have been increasing attempts to diagnose the disease biologically. Most have been unsuccessful. However, an initial study found that a recently developed blood test (PsychNostics LLC, Baltimore, Md; http://psychnostics.com) that uses the membrane potential as a biological marker had a specificity of 0.88 and a sensitivity of 0.78. The blood test is a promising approach, but is still not ready for prime time.³¹