LATE-ONSET BIPOLAR DISORDER: A Case for Careful Appraisal

| January 15, 2010 | 0 Comments

by Deepak Prabhakar, MD, MPH, and Richard Balon, MD
From the Department of Psychiatry and Behavioral Neurosciences, Wayne State University, Detroit, Michigan

Psychiatry (Edgemont) 2010;7(1):34-37

Funding: There was no funding for the development and writing of this article.

Financial disclosure: The authors have no conflicts of interest relevant to the content of this article.

Key words: late-onset, bipolar disorder, secondary mania

Bipolar disorder is a chronic mental illness with a profound personal and public health costs attached to it. The majority of patients suffering from bipolar disorder have an onset prior to the fifth decade of their lives. However, a significant number of patients have onset of illness after age 50, commonly referred to as late-onset bipolar disorder. Age of onset can have a significant impact on the nature and course of bipolar illness. We present an interesting case of late-onset bipolar disorder while evaluating secondary mania. The patient was a 76-year-old African American woman who presented with religious and sexual preoccupations, reduced requirement of sleep, and auditory hallucinations. Magnetic resonance imaging scans of the brain revealed diffuse atrophy and two localized lesions on T2 weighted images. Diagnosing late-onset bipolar disorder requires a meticulous assessment for all the potential secondary causes. This might be challenging given the number of confounding agents and the attached cost. Nevertheless, thorough work-up to rule out secondary causes remains the centerpiece of correctly diagnosing and effectively treating late-onset bipolar disorder.

Bipolar disorder is a chronic mental illness with the peak age of onset between 20 and 40 years.[1] Yassa et al[2] proposed age 50 as a cut off for the late onset bipolar disorder. They also reported that about 90 percent of cases have onset prior to age 50. This in turn indicates that prevalence of late-onset bipolar disorder is 10 percent.[2] About five percent of patients are reported to have onset of illness after age 60.[3] In an effort to understand the impact of age of onset on bipolar disorder, several authors have looked into the salient presentation of early onset bipolar disorder.[4–7] On the other end of the age spectrum, Depp et al[8] conducted a comprehensive review of bipolar disorder in older adults. They reported an association between late-onset bipolar disorder and neurologic illness, white matter hyperintensities (WMH), and cortical atrophy. They also reported lower prevalence of substance abuse and greater degree of heterogeneity in presentation and course of bipolar disorder in older adults. Depp et al[8] did not find conclusive evidence suggesting more mixed episodes or psychotic features among older patients with bipolar disorder. However older adults with bipolar disorder are reported to have longer hospital stays compared to younger adults.[9] We present an interesting case of late-onset bipolar disorder while evaluating secondary mania.

Case Report
The patient was a 76-year old African American woman who presented to the hospital after a period of “strange behavior.” During this period of strange behavior, the patient was reported to be religiously and sexually preoccupied and she had reduced requirement of sleep and was staying up for most of the night. At night she would mumble and sing for long periods. The patient also endorsed hearing voices of her dead husband asking her to join him in heaven. The patient’s family was concerned for her safety, and hence her daughter petitioned her to psychiatric hospitalization. On the day of admission, the patient appeared her stated age, with frail body habitus, poor grooming and hygiene, poor eye contact, and she was easily distracted and restless. Her speech was spontaneous and effusive; her mood was euphoric; and her affect was wide ranging, dramatic, and labile. The patient’s thought content was delusional and was significant for religious and sexual themes simultaneously. The patient had poor insight into her illness and had poor judgment.

Three different Mini Mental Status Examinations completed during the course of hospitalization revealed the scores of 25, 28, and 27. The biochemistry profile of the patient were all within the normal limits except for creatinine, which was 1.2, and blood urea nitrogen, which was 26, both of which were attributed to the initiation of lisinopril 2.5mg daily for the patient’s blood pressure management about two weeks prior to her admission. This was not considered severe enough to warrant termination of lisinopril. The patient was encouraged to drink more water, and her subsequent labs revealed improved creatinine of 1.1. Magnetic resonance imaging (MRI) scans of the brain completed on the day of admission revealed diffuse atrophy consistent with age of the patient; it also revealed two small WMH, which are localized lesions seen on T2 weighted images, signifying local changes in cerebral composition most likely secondary to vascular changes.

The patient’s first hospital admission was at the age of 59 for similar complaints along with paranoid delusions. Her second hospital admission was at age 69. Details of this admission are not known. Since then, there were no psychiatric admissions leading up to current episode. The patient has been following up regularly for last four years in an outpatient facility, and her psychotropic medications prior to admission were mirtazapine 30mg at bedtime, trazodone 50mg at bedtime, and risperidone 0.5mg at bedtime. The rationale behind this particular pharmacologic combination was depressive episodes, delusions, and insomnia. However, the age of onset of first depressive episode is unknown. The patient had been taking risperidone and mirtazapine for over one year. Trazodone was added about one month prior to the latest hospital admission for complaints of insomnia and persistent depressed mood. In addition to her psychotropic medications, the patient was receiving lisinopril 2.5mg, furosemide 30mg, and potassium chloride 10mEq daily for hypertension and history of congestive heart failure (compensated); simvastatin 20mg daily for hyperlipidemia; glipizide 5mg daily for the management of diabetes; and latanoprost eye drops for the history of glaucoma. The patient’s daughter described the patient’s adherence to her medications as “erratic.” There was no history of anxiety disorder or substance abuse by the patient. There was no history of a head trauma or a seizure disorder. There was a positive family history of mental illnesses in two nephews, a niece, and brother of the patient, where they were known to express similar symptoms; however, their exact psychiatric diagnoses were unknown. Upon admission, we discontinued mirtazapine and trazodone, and we gradually increased the dose of risperidone to 0.5mg twice daily. The patient responded to the medication change well and there were no side effects reported or observed.

There are few noteworthy issues with this case. First, though there is a strong family history of mental illness, most likely of affective disorders, the patient had her first clinical outbreak at the age of 59. The patient’s MRI scan of her brain revealed two WMH; there is evidence correlating WMH with the presence of late-onset bipolar disorder.[10] However, it is important to mention that the younger group of bipolar I patients over the age of 30 are also reported to have increased hyperintensities as compared to normal subjects and those with bipolar II disorder.[11] The role that these two lesions played in the patient’s presentation is still not clear as the lesions were considered too few and too small to be contributing to the patient’s clinical presentation. Since her first presentation at the age of 59, the patient was cognitively intact, and even during the described episode, her cognition was very much intact and this was consistent with her baseline status.

Krauthammer and Klerman[12] described the concept of secondary mania in the late 1970s. They suggested that secondary mania, as opposed to primary mania, might be characterized by late onset and negative family history. Our patient had a late onset but there was strong history of mental illness in her family. Furthermore, Krauthammer and Klerman examined and reported on several cases of mania that were thought to be brought on by secondary precipitants, such as drugs, infections, metabolic disturbances, neoplasm, epilepsy, infections, and toxins. They suggest that when dealing with episodes of mania due to organic causes one has to make sure one is dealing with latent manic-depressive illness that just happens to be correlated to or precipitated by the organic injury. The patient also had transitional elevation of creatinine and blood urea nitrogen; however, both were for short a period and would have not contributed to the earlier presentations as well as the baseline symptoms. Mood-elevating effects of captopril, an angiotensin-converting enzyme inhibitor, are noted in the literature.[13] Our patient was recently started on lisinopril, another drug from the same class. However, it is unlikely that this contributed to the patient’s presentation given the relatively small dose (2.5mg daily) and that she continued to receive the medication after her hospitalization and subsequent clinical improvement in presenting symptoms. The patient responded well to risperidone 0.5mg twice daily, which was one of her baseline medications in addition to trazodone and mirtazapine. We discontinued trazodone and mirtazapine and this in and of itself might have contributed to clinical improvement, considering that antidepressants may make patients with underlying bipolar disorder have manic outbreaks.

Bipolar disorder is one of the most heritable conditions. Most of the studies put the concordance rate among identical twins at 50 to 60 percent. Another noteworthy fact is that not all bipolar disorder patients have first-degree relatives who have similar illness. This leaves room for the possibility that environmental factors play a role in the expression of bipolar disorder among some individuals.[14] Adverse environmental exposure, such as physical and sexual abuse in early childhood, is associated with early onset of bipolar disorder. These adverse exposures are also associated with complicated courses of bipolar illness when compared to courses of illness in individuals who were not exposed to adverse environmental events.[14] As we work toward identifying specific genes responsible for manifestation of bipolar disorder, it is important that we continue to identify the role that gene environment interaction plays in the manifestation and variable expression of bipolar disorder.

Diagnosing late-onset bipolar disorder requires a meticulous assessment for all the potential secondary causes. This might be challenging, especially with numerous confounding, organic causes, such as concomitant use of therapeutic agents, infections, metabolic disturbances, neoplasm, toxins, and vascular infarcts. Thorough work up to rule out each of the above mentioned secondary causes remains the center piece of correctly diagnosing late-onset bipolar disorder. The index of suspicion must remain high for any life-threatening concurrent events when confronted with such a case.

1. Yassa R, Nair V, Nastase C, et al. Prevalence of bipolar disorder in a psychogeriatric population. J Affect Disord. 1988;14(3):197–201.
2. Yassa R, Nair NP, Iskandar H. Late-onset bipolar disorder. Psychiatr Clin North Am. 1988;11(1):117–131.
3. Depp CA, Jin H, Mohamed S, et al. Bipolar disorder in middle-aged and elderly adults: Is age of onset important? J Nerv Ment Dis. 2004;192(11):796–799.
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9. Depp CA, Lindamer LA, Folsom DP, et al. Differences in clinical features and mental health service use in bipolar disorder across the lifespan. Am J Geriatr Psychiatry. 2005;13(4):290–298.
10. Zanetti MV, Cordeiro Q, Busatt G. Late onset bipolar disorder associated with white matter hyperintensities: A pathophysiological hypothesis progress. Prog Neuropsychopharmacol Biol Psychiatry. 2007; 31(2):551–556.
11. Altshuler LL, Curran JG, Hauser P, et al. T-2 hyperintensities in bipolar disorder—magnetic-resonance—imaging comparison and literature metaanalysis. Am J Psychiatry. 1995;152:1139–1144.
12. Krauthammer C, Klerman GL. Secondary mania: manic syndromes associated with antecedent physical illness or drugs. Arch Gen Psychiatry. 1978;35(11):1333–1338
13. Gajula RP, Berlin RM. Captopril-induced mania. Am J Psychiatry. 1993;150(9):1429–1430.
14. Post RM, Leverich GS. The role of psychosocial stress in the onset and progression of bipolar disorder and its comorbidities: The need for earlier and alternative modes of therapeutic intervention. Dev Psychopathol. 2006;18:1181–1211.

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Category: Bipolar Disorder, Case Report, Past Articles, Psychiatry

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