Comorbidities in bipolar disorder management
MedWire - APA (San Diego, California, USA) - May 20, 2007: Bipolar disorder is a chronic complex condition strongly associated with several medical and psychiatric comorbidities, ranging from cardiovascular disease to post-traumatic stress disorder (PTSD) and substance abuse disorder (SUD).
In this session, chaired by Dr. Gary S. Sachs (Boston, Massachusetts, USA), leading experts discussed this constellation of comorbidities, and highlighted how psychiatrists who treat people with bipolar disorder need to be aware of these associated illnesses in order to take responsibility for treating the whole patient.
Two important psychiatric conditions, PTSD and SUD, are found at an increased rate in patients with bipolar disorder. Those with comorbid SUD often have an earlier onset of mood disorder and experience worse outcomes, according to Dr. Michael J. Ostacher (Boston, Massachusetts, USA).
Nearly 40% of patients with bipolar disorder have a lifetime risk of developing PTSD, reported Dr. Lori L. Davis (Birmingham, Alabama, USA). However, although this overlap has implications regarding both the pathogenesis and treatment of both conditions, there is a paucity of research on these comorbidities, she said.
Medical comorbidities in bipolar disorder may have an inflammatory pathogenesis
Dr. Gary S. Sachs; Associate Professor of Psychiatry, Harvard Medical School; Director, Bipolar Clinic and Research Program, Massachusetts General Hospital; Boston, Massachusetts, USA
Patients with bipolar disorder have an increased risk of certain medical comorbidities that affect their longevity and complicate the management of their psychiatric condition, according to Dr. Sachs.
“Cardiovascular disease is the primary natural cause of excessive mortality in bipolar disorder,” he said, noting that men with bipolar disorder are 1.9 times and women are 2.6 times more likely than their counterparts in the general population to die of cardiovascular disease. [1]
The reasons for these medical comorbidities are not clear. However, investigators may get closer to understanding the link if they see bipolar disorder as a continuous chronic illness with persistent pathology rather than a series of discrete manic and depressive episodes, Dr. Sachs said.
Bipolar patients have difficulty with sustained attention, verbal memory, executive function, and visual-spatial processing even in the absence of mood symptoms, for example.
The underlying pathology may eventually be found to involve an inherited inflammatory component, he said. For example, he noted that asthma is 1.93 times more likely to occur in patients with bipolar disorder than in the general population (p=0.009). [2]
Although the inflammatory link has not yet been fully elucidated, psychiatrists can monitor patients with bipolar disorder for medical conditions for which they are known to be at risk, he commented.
“We are coming to view bipolar disorder as a dysregulation syndrome that is associated with medical conditions that need to be monitored,” Dr. Sachs concluded.
Comorbid substance abuse with early-onset bipolar disorder
Dr. Michael J. Ostacher; Instructor in Psychiatry, Harvard Medical School; Associate Medical Director, Bipolar Clinic and Research Programme, Massachusetts General Hospital; Boston, Massachusetts, USA
Patients with bipolar disorder are more likely to have SUD than any other mood disorder, according to Dr. Ostacher. “Estimates of 42% to 70% of patients with bipolar disorder have a history of substance use disorders,” he said. [3, 4]
“Conversely,” he said, “Fifteen percent of patients in the United States who report alcohol dependence within the past year also had an episode of mania or hypomania in that time period.” [4]
This association is important to recognize as patients with comorbid bipolar disorder and SUD often have a more severe course, including an increase in suicide attempts, he said. [5]
Furthermore, associations which are less obvious between bipolar disorder and SUD have been reported. For example, the course of the patient’s disorder is influenced by whether the onset of the bipolar disorder occurred before the substance use - cases in which the bipolar disorder occurred first are associated with worse outcomes. [6]
Furthermore, bipolar disorder exacerbations can persist even in patients who are no longer using substances, Dr. Ostacher said. In the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) study, investigators found that patients with bipolar disorder who experienced prolonged remission from SUD had a poorer prognosis than those with no history of SUD. [7] “Therefore,” he said, “psychiatrists need to know that bipolar disorder does not go away when the substance use does.”
Adequate treatment is elusive yet important, he noted, stating that current SUD is associated with an elevated risk of 3.33 for suicide, and that a lifetime history of substance use disorder is associated with an elevated risk of 2.73 (p=0.0004 and p=0.0047, respectively). [8]
The use of both mood stabilizers and integrated group therapy has shown promise, although the research is scant, he said. “Few specific treatments exist for such patients, and under-treatment is common.”
Overlap of PTSD and bipolar disorder is common
Dr. Lori L. Davis; Clinical Associate Professor, Department of Psychiatry and Behavioural Neurobiology; University of Alabama School of Medicine; Birmingham, Alabama, USA
Patients with bipolar disorder are more likely to have post-traumatic stress disorder (PTSD), according to Dr. Davis, and although the two are separate conditions there may be an overlap in the underlying pathophysiology and susceptibility, she said.
For example, childhood abuse is reported by 50% of both veteran and civilian bipolar patients, she said. [9] Conversely, approximately 30% of abused bipolar individuals develop PTSD, and such patients have more lifetime episodes of depression and a higher risk of attempting suicide. [9]
On a biochemical level, both disorders are associated with dysregulation of the noradrenergic system, the serotonergic system, or the dopaminergic system, as well as a reduction in gamma-aminobutyric acid (GABA) or excessive glutamatergic activity, she said.
Treating PTSD is challenging because the studies regarding patients with comorbid bipolar disorder and PTSD are so sparse, according to Dr. Davis. Pharmaceutical agents that have been used in such patients include the anticonvulsants divalproex, topiramate, and tiagabine, as well as second-generation neuroleptics olanzapine, quetiapine, risperidone, ziprasidone, and aripiprazole. [10]
Another study has shown that cognitive behavioural therapy (CBT) is more effective at reducing symptoms than either supportive psychotherapy or remaining on a treatment wait list. [11]
However, Dr. Davis noted that few of the studies on treatment for comorbid bipolar disorder and PTSD are randomized, blinded, and controlled. Therefore, she concluded, more studies are needed in order to determine effective treatments for such patients.
References:
1. Osby U, Brandt L, Correia N, Ekbom A, Sparen P. Excess mortality in bipolar and unipolar disorder in Sweden. Schizophr Res 2001; 58:844-50.
2. Farrelly N, Calabrese JR, Hirschfeld R, et al Medical and psychiatric history: Predictors of bipolar disorder risk in patients treated for unipolar depression. Poster presented at APA 2006.
3. 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; 264:2511-18.
4. Grant BF, Stinson FS, Hasin DS, et al. Prevalence, correlates, and comorbidity of bipolar I disorder and axis I and II disorders: results from the National Epidemiologic Survey on Alcohol and Related Conditions. J Clin Psychiatry 2005; 66:1205-15.
5. Dalton EJ, Cate-Carter TD, Mundo E, et al. Suicide risk in bipolar patients: the role of co-morbid substance Bipolar Disord 2003; 5:58-61.
6. Fossey MD, Otto MW, Yates WR, et al. Validity of the distinction between primary and secondary substance use disorder in patients with bipolar disorder: data from the first 1000 STEP-BD participants. Am J Addict 2006; 15:138-43.
7. Weiss RD, Ostacher MJ, Otto MW, et al. Does recovery from substance use disorder matter in patients with bipolar disorder? J Clin Psychiatry 2005; 66:730-5.
8. Marangell LB, Bauer MS, Dennehy EB, et al. Prospective predictors of suicide and suicide attempts in 1,556 patients with bipolar disorders followed up for up to 2 years. Bipolar Disord 2006; 8:566-75.
9. Brown GR, McBride L, Bauer MS, et al. Impact of childhoos abuse on the course of bipolar disorder: a replication study in U.S veterans. J Affect Disord 2005; 89:57-67.
10. Davis LL, Frazier E, Saunders D, et al. The use of second generation neuroleptics for the treatment of posttraumatic stress disorder in VISN-7 FY1999-2005. HSR&D National Meeting 2007; Abstract no. 3017.
11. Blanchard EB, Hickling EJ, Devineni T, et al. A controlled evaluation of cognitive behavioural therapy for posttraumatic stress in motor vehicle accident survivors. Behav Res There 2003; 41:79-96.
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