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Martha Sajatovic, MD
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Bipolar Disorder"Costs and Comorbidity
Robert M.A. Hirschfeld, MD; and Lana A. Vornik, MSc

Bipolar Disorder"Costs and Comorbidity

Robert M.A. Hirschfeld, MD; and Lana A. Vornik, MSc

Cassidy and colleagues25 conducted a general review of the literature and demonstrated that estimates of comorbid substance abuse in bipolar patients range from 6% to 69%, with most authors reporting rates of 30% and greater. Estimates of comorbid drug abuse range from 14% to 60%.25 In their own study of 392 hospitalized patients with manic or mixed episodes of bipolar disorder, Cassidy and colleagues found that 48.5% had a lifetime history of alcohol abuse and 43.9% had a lifetime history of drug abuse. Overall, nearly 60% of the patients had a history of some substance abuse.25 Whether substance abuse follows bipolar disorder or vice versa remains unresolved.19,26 Drug abuse may lead to misdiagnosis of bipolar disorder, because patients who are intoxicated with stimulants can appear manic.27 Complications of substance abuse in bipolar disorder include higher rates of mixed and rapid cycling, prolonged recovery time, higher prevalence of medical disorders, including liver disease, more suicide attempts, and suicide.27 Comorbidity with alcohol and drug abuse is often associated with poor adherence and poor treatment response compared with patients without comorbidity.17

Anxiety Disorders

Community Studies. Symptoms of anxiety often occur in patients with bipolar disorder. Therefore, the high rates of comorbidity of anxiety disorders in patients with bipolar disorder are not surprising. For example, the ECA study reported that 21% of patients with bipolar I and II disorder had comorbid lifetime panic disorder and 21% had comorbid lifetime OCD compared with 0.8% and 2.6%, respectively, in the general population.19,20 In the NCS study, 92% of patients with bipolar I disorder also met the criteria for a lifetime anxiety disorder compared with 25% in the general population.2,21

Clinical Studies. As with substance abuse, comorbid anxiety hinders treatment response in patients with bipolar disorder. It has been reported that bipolar patients with anxiety have significantly poorer response to treatment, specifically to lithium therapy, than patients without anxiety.28,29 In an analysis of 124 patients with bipolar I disorder, history of panic attacks proved to be significantly correlated with nonremission, whereas past or present anxiety was significantly correlated with longer time to remission.28 Moreover, Young and colleagues29 reported a trend for bipolar patients with high anxiety to be less likely to respond to lithium. Bipolar patients with high anxiety scores were more likely to have suicidal behavior (44% vs 19%), alcohol abuse (28% vs 6%), cyclothymia (44% vs 21%), and an anxiety disorder (56% vs 25%) with a trend toward lithium nonresponsiveness than bipolar patients with low anxiety scores.29 In the report from the Stanley Foundation,22 42% of subjects diagnosed with bipolar I and II disorder also met the criteria for comorbid anxiety disorder, including panic disorder/agoraphobia (20%) and social phobia (16%).

Other Comorbid Psychiatric Disorders

Other psychiatric disorders that have a high rate of comorbidity with bipolar disorder are eating disorders, sexual disorders, impulse-control disorders, attention- deficit/hyperactivity disorder (ADHD), autism spectrum disorders, conduct disorder, Tourette's syndrome (TS), and personality disorders.16,27

Eating Disorders. In the Zurich cohort study, individuals with DSM-IV hypomania and those with recurrent brief hypomania had higher lifetime prevalence rates of binge eating (12.8% and 22.2%, respectively) compared with controls (4.6%).5 In another study of 61 adults with bipolar disorder, 13% met criteria for binge-eating disorder, whereas 25% more subjects exhibited partial binge-eating syndrome.30 In the Stanley Foundation study of 288 patients with bipolar I and II disorder, the lifetime comorbidity of eating disorders with bipolar I or II disorder was estimated at 5% for bipolar I and 12% for bipolar II disorder.22 The rate of eating disorder comorbidity in 39 bipolar patients with first lifetime hospitalization was 15%. Notably, the diagnosis of bipolar disorder was antecedent to eating disorders in 13% of cases.15

ADHD. Childhood bipolar disorder is often comorbid with ADHD and conduct disorder. Features of bipolar disorder often overlap with those of ADHD, leading to misdiagnosis and consequent treatment with psychostimulants, which may induce mania or rapid cycling in bipolar patients. Systematic studies of pediatric patients with mania demonstrate rates of comorbidity with ADHD in the range of 60% to 90%.31 In a study of 104 pediatric patients referred to a community mental health clinic for the treatment of ADHD, 60% met the criteria for a mood disorder; moreover, 13% of these referrals met the standard criteria for mania, and 41% of the children met the modified criteria for mania, which required the presence of euphoria and/or flight of ideas.32

TS. Although literature on the comorbidity of TS with bipolar disorder is limited, at least 1 study suggests co-occurrence of TS with bipolar disorder. In a study of 246 patients with TS, 17 patients with attention-deficit disorder, 15 patients with attention-deficit disorder associated with TS, and 47 controls, none of the control patients had above normal mania scores compared with 19% of the total patients with TS.33

Personality Disorders. Personality disorders may complicate the diagnosis and course of bipolar disorder, as well as impede treatment. Most studies report the rate of comorbid personality disorders in patients with bipolar disorder in the range of 30% to 45%, and as high as 65% in some studies.34-36 Dramatic/emotionally erratic and fearful/avoidant personality disorders were more common than odd/eccentric disorders. Patients with bipolar disorder with personality disorders differed from patients with bipolar disorder without personality disorders in the severity of their residual mood symptoms, even during remission. The presence of comorbid personality disorders, specifically borderline personality disorder, may also significantly increase the utilization of mental health services, as it has been previously shown that patients with personality disorders tend to have more extensive histories of psychiatric outpatient, inpatient, and psychopharmacologic treatment than patients with affective disorders.37


Bipolar disorder imposes a substantial economic burden on society. Much of the cost is indirect and related to factors such as work loss. Patients with bipolar disorder have higher rates of healthcare utilization compared with individuals without the disorder, and those higher rates of utilization are associated with higher healthcare costs. Appropriate treatment of bipolar disorder can help reduce the associated costs. Other psychiatric conditions frequently occur with bipolar disorder. Comorbid anxiety disorders and substance abuse are especially prevalent.

1. Murray CJL, Lopez AD, eds. The Global Burden of Disease and Injury Series, Volume 1: A Comprehensive Assessment of Mortality and Disability from Diseases, Injuries, and Risk Factors in 1990 and Projected to 2020. Cambridge, Mass: Published by the Harvard School of Public Health on behalf of the World Health Organization and the World Bank; Harvard University Press; 1996.

2. Kessler RC, McGonagle KA, Zhao S, et al. Lifetime and 12-month prevalence of DSM-III-R psychiatric disorders in the United States. Results from the National Comorbidity Survey. Arch Gen Psychiatry. 1994;51:8-19.

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14. Li J, McCombs JS, Stimmel GL. Cost of treating bipolar disorder in the California Medicaid (Medi-Cal) program. J Affect Disord. 2002;71:131-139.

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18. Regier DA, Farmer ME, Rae DS, et al. Comorbidity of mental disorders with alcohol and other drug abuse. Results from the Epidemiologic Catchment Area (ECA) Study. JAMA. 1990;264:2511-2518.

19. Chen YW, Dilsaver SC. Comorbidity of panic disorder in bipolar illness: evidence from the Epidemiologic Catchment Area Survey. Am J Psychiatry. 1995;152:280-282.

20. Chen YW, Dilsaver SC. Comorbidity for obsessive-compulsive disorder in bipolar and unipolar disorders. Psychiatry Res. 1995;59:57-64.

21. Kessler RC, Rubinow DR, Holmes C, Abelson JM, Zhao S. The epidemiology of DSM-III-R bipolar I disorder in a general population survey. Psychol Med. 1997;27:1079-1089.

22. McElroy SL, Altshuler LL, Suppes T, et al. Axis I psychiatric comorbidity and its relationship to historical illness variables in 288 patients with bipolar disorder. Am J Psychiatry. 2001;158:420-426.

23. Strakowski SM, Tohen M, Stoll AL, Faedda GL, Goodwin DC. Comorbidity in mania at first hospitalization. Am J Psychiatry. 1992;149:554-556.

24. Kessler RC, Crum RM, Warner LA, Nelson CB, Schulenberg J, Anthony JC. Lifetime co-occurrence of DSM-III-R alchohol abuse and dependence with other psychiatry disorders in the National Comorbidity Survey. Arch Gen Psychiatry. 1997;54:313-321.

25. Cassidy F, Ahearn EP, Carroll BJ. Substance abuse in bipolar disorder. Bipolar Disord. 2001;3:181-188.

26. Chengappa KN, Levine J, Gershon S, Kupfer DJ. Lifetime prevalence of substance or alcohol abuse and dependence among subjects with bipolar I and II disorders in a voluntary registry. Bipolar Disord. 2000;2:191-195.

27. Krishnan KR. Psychiatric and medical comorbidities of bipolar disorder. Psychosom Med. 2005;67:1-8.

28. Feske U, Frank E, Mallinger AG, et al. Anxiety as a correlate of response to the acute treatment of bipolar I disorder. Am J Psychiatry. 2000;157:956-962.

29. Young LT, Cooke RG, Robb JC, Levitt AJ, Joffe RT. Anxious and non-anxious bipolar disorder. J Affect Disord. 1993;29:49-52.

30. Kruger S, Shugar G, Cooke RG. Comorbidity of binge eating disorder and the partial binge eating syndrome with bipolar disorder. Int J Eat Disord. 1996;19:45-52.

31. Biederman J, Mick E, Faraone SV, Spencer T, Wilens TE, Wozniak J. Pediatric mania: a developmental subtype of bipolar disorder? Biol Psychiatry. 2000;48:458-466.

32. Dilsaver SC, Henderson-Fuller S, Akiskal HS. Occult mood disorders in 104 consecutively presenting children referred for the treatment of attention-deficit/hyperactivity disorder in a community mental health clinic. J Clin Psychiatry. 2003;64:1170-1176.

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34. George EL, Miklowitz DJ, Richards JA, Simoneau TL, Taylor DO. The comorbidity of bipolar disorder and axis II personality disorders: prevalence and clinical correlates. Bipolar Disord. 2003;5:115-122.

35. Brieger P, Ehrt U, Marneros A. Frequency of comorbid personality disorders in bipolar and unipolar affective disorders. Compr Psychiatry. 2003;44:28-34.

36. Preston GA, Marchant BK, Reimherr FW, Strong RE, Hedges DW. Borderline personality disorder in patients with bipolar disorder and response to lamotrigine. J Affect Disord. 2004;79:297-303.

37. Bender DS, Dolan RT, Skodol AE, et al. Treatment utilization by patients with personality disorders. Am J Psychiatry. 2001;158:295-302.

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