Comorbidity in Bipolar Disorder: Page 5 of 5
Comorbidity in Bipolar Disorder: Page 5 of 5
Given the substantial overlap between symptoms of BPD and other psychiatric conditions, an accurate cross-sectional assessment is inherently difficult to achieve. A careful longitudinal assessment that establishes a chronology of onset of different conditions, a symptom and functional profile between mood episodes, the course of illness, and response to treatment are essential for a more robust diagnosis.44 Furthermore, the inherent challenge in obtaining an accurate history from a bipolar patient—especially one with comorbidities—requires corroboration from family members.
Although clinical guidelines for BPD acknowledge the complexity of treating the illness, most have limited recommendations specific to the patient with comorbidities. This may reflect the limited nature of the clinical evidence in this field.68,69 The cost of diagnostic and therapeutic uncertainty, however, is calculated through the high cost of chronicity, with elevated rates of suicide, legal and interpersonal difficulties, and repeated hospitalizations.
As the field of neurobiology of bipolar and affective disorders advances, we hope to begin to refine our view of the comorbid interface. Forging the pathophysiological links between specific medical illnesses and BPD, including the use of clinical biomarkers to help refine the understanding of bipolar subtypes, may help clarify the pathophysiology of BPD itself. This will ultimately suggest new measures for secondary prevention and long-term treatments.4,70
Dr Sagman is staff psychiatrist, Toronto East General Hospital, Toronto, and associate vice-president, clinical research, Eli Lilly Canada Inc, and Dr Tohen is Distinguished Lilly Scholar for Neurosciences, Lilly Research Laboratories, Indianapolis. The authors report that they have no other conflicts of interest concerning the subject matter of this article.
Drugs Mentioned in This Article
Carbamazepine (Carbatrol, Tegretol, others)
Lithium (Eskalith, Lithane, Lithobid)
Valproate/valproic acid (Depakote, others)
1. Kessler R. Comorbidity of unipolar and bipolar depression with other psychiatric disorders in a general population survey. In: Tohen M, ed. Comorbidity in Affective Disorders. New York: Marcel Dekker Inc; 1999:1-25.
2. 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.
3. McIntyre RS, Konarski JZ, Yatham LN. Comorbidity in bipolar disorder: a framework for rational treatment selection. Hum Psychopharmacol. 2004;19:369-386.
4. Kupfer DJ. The increasing medical burden in bipolar disorder. JAMA. 2005;293:2528-2530.
5. Osby U, Brandt L, Correia N, et al. Excess mortality in bipolar and unipolar disorder in Sweden. Arch Gen Psychiatry. 2001;58:844-850.
6. Murray CJ, Lopez AD. Global mortality, disability, and the contribution of risk factors: Global Burden of Disease Study. Lancet. 1997;349:1436-1442.
7. McIntyre RS, Soczynska JK, Bottas A, et al. Anxiety disorders and bipolar disorder: a review. Bipolar Disord. 2006;8:665-676.
8. Judd LL, Akiskal HS. The prevalence and disability of bipolar spectrum disorders in the US population: re-analysis of the ECA database taking into account subthreshold cases. J Affect Disord. 2003;73:123-131.
9. Keller MB. Prevalence and impact of comorbid anxiety and bipolar disorder. J Clin Psychiatry. 2006;67 (suppl 1):5-7.
10. Boylan KR, Bieling PJ, Marriott M, et al. Impact of comorbid anxiety disorders on outcome in a cohort of patients with bipolar disorder. J Clin Psychiatry. 2004; 65:1106-1113.
11. Simon NM, Otto MW, Wisniewski SR, et al. Anxiety disorder comorbidity in bipolar disorder patients: data from the first 500 participants in the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD). Am J Psychiatry. 2004;161:2222-2229.
12. MacQueen GM, Marriott M, Begin H, et al. Subsyndromal symptoms assessed in longitudinal, prospective follow-up of a cohort of patients with bipolar disorder. Bipolar Disord. 2003;5:349-355.
13. MacKinnon DF, Zamoiski R. Panic comorbidity with bipolar disorder: what is the manic-panic connection? Bipolar Disord. 2006;8:648-664.
14. Simon NM, Smoller JW, Fava M, et al. Comparing anxiety disorders and anxiety-related traits in bipolar disorder and unipolar depression. J Psychiatr Res. 2003;37:187-192.
15. Kraepelin E. Manic-Depressive Insanity and Paranoia. Edinburgh: E & S Livingstone; 1921. Reprinted in: Carlson ET, ed. Dementia Praecox and Paraphrenia Together With Manic-Depressive Insanity and Paranoia. Birmingham, AL: Classics of Medicine Library; 1989:chap 7.
16. Berk M, Dodd S, Malhi GS. “Bipolar missed states”: the diagnosis and clinical salience of bipolar mixed states. Aust N Z J Psychiatry. 2005;39:215-221.
17. Perlis RH, Miyahara S, Marangell LB, et al. Long-term implications of early onset in bipolar disorder: data from the first 1000 participants in the systematic treatment enhancement program for bipolar disorder (STEP-BD). Biol Psychiatry. 2004;55:875-881.
18. Goldstein BI, Levitt AJ. The specific burden of comorbid anxiety disorders and of substance use disorders in bipolar I disorder. Bipolar Disord. 2008;10:67-78.
19. Goodwin RD, Stayner DA, Chinman MJ, et al. The relationship between anxiety and substance use disorders among individuals with severe affective disorders. Compr Psychiatry. 2002;43:245-252.
20. Nakagawa A, Grunebaum MF, Sullivan GM, et al. Comorbid anxiety in bipolar disorder: does it have an independent effect on suicidality? Bipolar Disord. 2008;10:530-538.
21. Keck PE Jr, Strawn JR, McElroy SL. Pharmacologic treatment considerations in co-occurring bipolar and anxiety disorders. J Clin Psychiatry. 2006;67(suppl 1):8-15.
22. Singh JB, Zarate CA Jr. Pharmacological treatment of psychiatric comorbidity in bipolar disorder: a review of controlled trials. Bipolar Disord. 2006;8: 696-709.
23. Holma KM, Melartin TK, Holma IA, Isometsä ET. Predictors for switch from unipolar major depressive disorder to bipolar disorder type I or II: a 5-year prospective study. J Clin Psychiatry. 2008;69:1267-1275.
24. Gao K, Muzina D, Gajwani P, Calabrese JR. Efficacy of typical and atypical antipsychotics for primary and comorbid anxiety symptoms or disorders: a review. J Clin Psychiatry. 2006;67:1327-1340.
25. 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.
26. Grant BF, Stinson FS, Dawson DA, et al. Prevalence and co-occurrence of substance use disorders and independent mood and anxiety disorders: results from the National Epidemiologic Survey on Alcohol and Related Conditions. Arch Gen Psychiatry. 2004;61:807-816.
27. Tohen M, Greenfield SF, Weiss RD, et al. The effect of comorbid substance use disorders on the course of bipolar disorder: a review. Harv Rev Psychiatry. 1998; 6:133-141.
28. Frye MA, Altshuler LL, McElroy SL, et al. Gender differences in prevalence, risk, and clinical correlates of alcoholism comorbidity in bipolar disorder. Am J Psychiatry. 2003;160:883-889.
29. Frye MA, Salloum IM. Bipolar disorder and comorbid alcoholism: prevalence rate and treatment considerations. Bipolar Disord. 2006;8:677-685.
30. Salloum IM, Cornelius JR, Mezzich JE, et al. Characterizing female bipolar alcoholic patients presenting for initial evaluation. Addict Behav. 2001;26:341-348.
31. Tohen M, Waternaux CM, Tsuang MT. Outcome in mania: a 4-year prospective follow-up of 75 patients utilizing survival analysis. Arch Gen Psychiatry. 1990; 47:1106-1111.
32. Winokur G, Coryell W, Akiskal HS, et al. Alcoholism in manic-depressive (bipolar) illness: familial illness, course of illness, and the primary-secondary distinction. Am J Psychiatry. 1995;152:365-372.
33. Strakowski SM, DelBello MP, Fleck DE, et al. Effects of co-occurring alcohol abuse on the course of bipolar disorder following a first hospitalization for mania. Arch Gen Psychiatry. 2005;62:851-858.
34. Goldberg JF, Garno JL, Leon AC, et al. A history of substance abuse complicates remission from acute mania in bipolar disorder. J Clin Psychiatry. 1999;60: 733-740.
35. Goldberg JF. Bipolar disorder with comorbid substance abuse: diagnosis, prognosis, and treatment. J Psychiatr Pract. 2001;7:109-122.
36. Swann AC, Pazzaglia P, Nicholls A, et al. Impulsivity and phase of illness in bipolar disorder. J Affect Disord. 2003;73:105-111.
37. Salloum IM, Cornelius JR, Daley DC, et al. Efficacy of valproate maintenance in patients with bipolar disorder and alcoholism: a double-blind placebo-controlled study. Arch Gen Psychiatry. 2005;62:37-45.
38. Johnson BA, Ait-Daoud N, Bowden CL, et al. Oral topiramate for treatment of alcohol dependence: a randomised controlled trial. Lancet. 2003;361:1677-1685.
39. Brady KT, Sonne SC, Malcolm RJ, et al. Carbamazepine in the treatment of cocaine dependence: subtyping by affective disorder. Exp Clin Psychopharmacol. 2002;10:276-285.
40. Brown ES, Nejtek VA, Perantie DC, et al. Lamotrigine in patients with bipolar disorder and cocaine dependence. J Clin Psychiatry. 2003;64:197-201.
41. Brown ES, Nejtek VA, Perantie DC, Bobadilla L. Quetiapine in bipolar disorder and cocaine dependence. Bipolar Disord. 2002;4:406-411.
42. Brown ES, Jeffress J, Liggin JD, et al. Switching outpatients with bipolar or schizoaffective disorders and substance abuse from their current antipsychotic to aripiprazole. J Clin Psychiatry. 2005;66:756-760.
43. Vornik LA, Brown ES. Substance-abuse comorbidity in bipolar disorder: general considerations and treatment approaches. Clin Approaches Bipolar Disord. 2008;6:3-11.
44. Zarate C, Tohen M. Bipolar disorder and comorbid axis I disorders: diagnosis and management. In: Yatham L, Kusumakar V, Kutcher S, eds. Bipolar Disorder: A Clinician’s Guide to Biological Treatments. New York: Brunner-Routledge; 2002:115-138.
45. National Institute of Mental Health research roundtable on prepubertal bipolar disorder. J Am Acad Child Adolesc Psychiatry. 2001;40:871-878.
46. Massat I, Victoor L. Early bipolar disorder and ADHD: differences and similarities in pre-pubertal and early adolescence. Clin Approaches Bipolar Disord. 2008;6:20-28.
47. Elia J, Ambrosini P, Berrettini W. ADHD characteristics, I: concurrent co-morbidity patterns in children & adolescents. Child Adolesc Psychiatry Ment Health. 2008;2:15.
48. Singh MK, DelBello MP, Kowatch RA, Strakowski SM. Co-occurrence of bipolar and attention-deficit hyperactivity disorders in children. Bipolar Disord. 2006;8:710-720.
49. George EL, Miklowitz DJ, Richards JA, et al. The comorbidity of bipolar disorder and axis II personality disorders: prevalence and clinical correlates. Bipolar Disord. 2003;5:115-122.
50. Bieling PJ, MacQueen GM, Marriot MJ, et al. Longitudinal outcome in patients with bipolar disorder assessed by life-charting is influenced by DSM-IV personality disorder symptoms. Bipolar Disord. 2003;5: 14-21.
51. Stormberg D, Ronningstam E, Gunderson J, Tohen M. Brief communication: pathological narcissism in bipolar disorder patients. J Personal Disord. 1998;12: 179-185.
52. Garno JL, Goldberg JF, Ramirez PM, Ritzler BA. Bipolar disorder with comorbid cluster B personality disorder features: impact on suicidality. J Clin Psychiatry. 2005;66:339-345.
53. Akiskal HS, Hantouche EG, Allilaire JF. Bipolar II with and without cyclothymic temperament: “dark” and “sunny” expressions of soft bipolarity. J Affect Disord. 2003;73:49-57.
54. Perugi G, Toni C, Travierso MC, Akiskal HS. The role of cyclothymia in atypical depression: toward a data-based reconceptualization of the borderline-bipolar II connection. J Affect Disord. 2003;73:87-98.
55. Frankenburg FR, Zanarini MC. Divalproex sodium treatment of women with borderline personality disorder and bipolar II disorder: a double-blind placebo-controlled pilot study. J Clin Psychiatry. 2002;63:442-446.
56. Kutcher SP, Marton P, Korenblum M. Adolescent bipolar illness and personality disorder. J Am Acad Child Adolesc Psychiatry. 1990;29:355-358.
57. Preston GA, Marchant BK, Reimherr FW, et al. Borderline personality disorder in patients with bipolar disorder and response to lamotrigine. J Affect Disord. 2004;79:297-303.
58. Bogenschutz MP, George Nurnberg H. Olanzapine versus placebo in the treatment of borderline personality disorder. J Clin Psychiatry. 2004;65:104-109.
59. Rocca P, Marchiaro L, Cocuzza E, Bogetto F. Treatment of borderline personality disorder with risperidone. J Clin Psychiatry. 2002;63:241-244.
60. Zanarini MC, Frankenburg FR. Olanzapine treatment of female borderline personality disorder patients: a double-blind, placebo-controlled pilot study. J Clin Psychiatry. 2001;62:849-854.
61. Zullino DF, Quinche P, Häfliger T, Stigler M. Olanzapine improves social dysfunction in cluster B personality disorder. Hum Psychopharmacol. 2002;17: 247-251.
62. Krishnan KR. Psychiatric and medical comorbidities of bipolar disorder. Psychosom Med. 2005;67:1-8.
63. McIntyre RS, Konarski JZ, Misener VL, Kennedy SH. Bipolar disorder and diabetes mellitus: epidemiology, etiology, and treatment implications. Ann Clin Psychiatry. 2005;17:83-93.
64. Fagiolini A, Kupfer DJ, Houck PR, et al. Obesity as a correlate of outcome in patients with bipolar I disorder. Am J Psychiatry. 2003;160:112-117.
65. Katon WJ. Clinical and health services relationships between major depression, depressive symptoms, and general medical illness. Biol Psychiatry. 2003;54:216-226.
66. Musselman DL, Betan E, Larsen H, Phillips LS. Relationship of depression to diabetes types 1 and 2: epidemiology, biology, and treatment. Biol Psychiatry. 2003;54:317-329.
67. Low NC, Du Fort GG, Cervantes P. Prevalence, clinical correlates, and treatment of migraine in bipolar disorder. Headache. 2003;43:940-949.
68. Yatham LN, Kennedy SH, O’Donovan C, et al. Canadian Network for Mood and Anxiety Treatments (CANMAT) guidelines for the management of patients with bipolar disorder: update 2007. Bipolar Disord. 2006;8:721-739.
69. Ghaemi SN, Bauer M, Cassidy F, et al. Diagnostic guidelines for bipolar disorder: a summary of the International Society for Bipolar Disorders Diagnostic Guidelines Task Force Report. Bipolar Disord. 2008; 10:117-128.
70. Evans DL, Charney DS. Mood disorders and medical illness: a major public health problem. Biol Psychiatry. 2003;54:177-180.
Kessler R. Comorbidity of unipolar and bipolar depression with other psychiatric disorders in a general population survey. In: Tohen M, ed. Comorbidity in Affective Disorders. New York: Marcel Dekker Inc; 1999: 1-25.
Perlis RH, Miyahara S, Marangell LB, et al. Long-term implications of early onset in bipolar disorder: data from the first 1000 participants in the systematic treatment enhancement program for bipolar disorder (STEP-BD). Biol Psychiatry. 2004;55:875-881.