Objectives: This review summarizes the literature on psychiatric and medical comorbidities in bipolar disorder. The coexistence of other Axis I disorders with bipolar disorder complicates psychiatric diagnosis and treatment. Conversely, symptom overlap in DSM-IV diagnoses hinders definition and recognition of true comorbidity. Psychiatric comorbidity is often associated with earlier onset of bipolar symptoms, more severe course, poorer treatment compliance, and worse outcomes related to suicide and other complications. Medical comorbidity may be exacerbated or caused by pharmacotherapy of bipolar symptoms.
Methods: Articles were obtained by searching MEDLINE from 1970 to present with the following search words: bipolar disorder AND, comorbidity, anxiety disorders, eating disorder, alcohol abuse, substance abuse, ADHD, personality disorders, borderline personality disorder, medical disorders, hypothyroidism, obesity, diabetes mellitus, multiple sclerosis, lithium, valproate, lamotrigine, carbamazepine, atypical antipsychotics. Articles were prioritized for inclusion based on the following considerations: sample size, use of standardized diagnostic criteria and validated methods of assessment, sequencing of disorders, quality of presentation.
Results: Although the literature establishes a strong association between bipolar disorder and substance abuse, the direction of causality is uncertain. An association is also seen with anxiety disorders, attention-deficit/hyperactivity disorder, and eating disorders, as well as cyclothymia and other axis II personality disorders. Medical disorders accompany bipolar disorder at rates greater than predicted by chance. However, it is often unclear whether a medical disorder is truly comorbid, a consequence of treatment, or a combination of both.
Conclusion: To ensure prompt, appropriate intervention while avoiding iatrogenic complications, the clinician must evaluate and monitor patients with bipolar disorder for the presence and the development of comorbid psychiatric and medical conditions. Conversely, physicians should have a high index of suspicion for underlying bipolar disorder when evaluating individuals with other psychiatric diagnoses (not just unipolar depression) that often coexist with bipolar disorder, such as alcohol and substance abuse or anxiety disorders. Anticonvulsants and other mood stabilizers may be especially helpful in treating bipolar disorder with significant comorbidity.
ADHD = attention-deficit/hyperactivity disorder; BMI = Body Mass Index; CADASIL = Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy; CNS = central nervous system; DSM-IV = Diagnostic and Statistical Manual of Mental Disorders, fourth edition; ECA = epidemiologic catchment area; MDQ = Mood Disorder Questionnaire; NHANES III = National Health and Nutrition Examination Survey, 1988–1994; MS = multiple sclerosis; OCD = obsessive-compulsive disorder; PCOS = polycystic ovarian syndrome; PTSD = posttraumatic stress disorder; TRH = thyrotropin-releasing hormone; TSH = thyroid-stimulating hormone; VCFS = velocardiofacial syndrome.
From the Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, North Carolina.
Address correspondence and reprint requests to Ranga Krishnan, MB, ChB, Department of Psychiatry and Behavioral Sciences, Duke University Medical Center (3050A), 4584 Hospital South, Box 3950, Durham, NC 27710. E-mail: firstname.lastname@example.org
Received for publication December 15, 2003; revision received August 17, 2004.
Supported by grants from National Institutes of Mental Health (MH60451) and GlaxoSmithKline; an additional grant have been received from Novartis. Dr. Krishnan is also a consultant to Abbott, Amgen, GlaxoSmithKline, Johnson & Johnson, Merck, NPS, Organon, Otsuka, Pfizer, Somerset, Synaptic, Vela, and Wyeth.