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Treatment of the elderly population with bipolar disorder represents a distinct challenge in modern psychiatry, especially as the number of geriatric patients continues to grow. This review will highlight the demographics and characterization of bipolar disorder in the elderly as well as the pharmacologic management of the disease. A symposium on the long-term care and treatment of elderly patients with bipolar disorder was conducted at the 2006 APA meeting this year, at which Dr. Helen Kyomen of McLean Hospital in Boston, Massachusetts, discussed the impact of elderly patients with bipolar disorder on the healthcare system.[1]

Demographics

Data from the National Institute of Mental Health (NIMH) Epidemiological Catchment Area (ECA) survey estimate that approximately 0.1% of people over 65 years of age meet the criteria for bipolar disorder. This is in comparison to rates of 0.4% for those aged 45-64 years and 1.4% for those aged 18-44.[2] Data from HMO treatment records estimate that about 0.25% of the elderly (≥ 65 years) are treated for bipolar disorder, compared with about 0.45% of patients younger than 65 years of age.[3] A more recent screening suggests up to 0.5% of the elderly over age 65 may have bipolar disorder.[4]

Nearly 25% of veterans being treated with bipolar disorder[5] and 9.2% of patients with bipolar disorder in a San Diego county population study[6] are over the age of 60. Needless to say, even if these percentages remain constant, the absolute number of elderly patients with bipolar disorder will continue to increase as the number of Americans over 65 years of age grows during the next few decades. On the basis of current estimates, the number of Americans over the age of 65 with a psychiatric illness is expected to more than double, from the approximately 7 million currently to a projected total of 15 million by 2030.[1]

Utilization of Healthcare Resources

Although the overall percentage of elderly patients with bipolar disorder is relatively small, these individuals have a disproportionate impact on the healthcare system. Although bipolar disorder is more prevalent in younger populations, elderly patients with bipolar disorder account for the same proportion of diagnoses in psychiatric emergency room visits[7,8] and inpatient psychiatric hospitals[9] as younger patients. Elderly patients and veterans with bipolar disorder have longer hospital stays than younger patients[10] and are more likely to use outpatient services,[5,10] emphasizing this population's increased utilization of healthcare resources.

It is also important to mention that one can further subdivide the geriatric bipolar disorder patient population into 2 subsets of patients: those with early-onset bipolar disorder who have had the disease since childhood or young adulthood, and those with late-onset bipolar disorder, generally defined as those who developed the disease after 50 years of age.

Elderly, late-onset bipolar patients differ from younger patients in many ways that may affect treatment strategies. Generally, disease status in the elderly, late-onset population is characterized by less genetic predisposition and a less severe course of illness,[11] as demonstrated by fewer days spent with bipolar illness symptoms.[12] However, this does not necessarily mean that these patients are easier to manage than younger patients with bipolar disorder, partially owing to higher rates of psychiatric and medical comorbidities. Unfortunately, both psychiatric and nonpsychiatric clinicians often fail to diagnose these comorbid conditions,[13] thereby missing opportunities to improve patients' quality of life and, possibly, treatment outcomes. Dr. Kyomen ended her talk by stressing other issues affecting the treatment for elderly patients that should be considered by clinicians, including access to transportation, financial difficulties, and recognition of the patients' need for treatment by professional caregivers.[1]

Treatment Strategies in Elderly Patients With Bipolar Disorder

Dr. Stephen L. Pinals[14] gave an overview of strategies for treating bipolar disorder in the elderly population and discussed the special considerations clinicians must bear in mind with regard to pharmacotherapy and treatment. Dr. Pinals emphasized that metabolism of drugs can change with aging, and dramatic pharmacokinetic differences result from changes in adipose tissue, free water, protein binding, and drug distribution. A narrowing of therapeutic index often occurs with age, and comorbid disease states are a factor as well. Also, the concomitant use of other drugs can lead to pharmacodynamic drug-drug interactions.

Table. FDA-Approved Agents for the Treatment of Bipolar Disorder

Agent

Mania

Depression

Maintenance

Lithium

Divalproex

Carbamazepine ER

Lamotrigine

Risperidone

Olanzapine

Quetiapine

Ziprasidone

Aripiprazole

Olanzapine-Fluoxetine

Treatment of Mania in Older Adults

Although lithium is one of the oldest and best-studied agents in the management of bipolar disorder, its use in the elderly presents a number of challenges. In older adults taking lithium, decreased renal clearance leads to a half-life that is double that in younger adults, and this can be exacerbated by renal disease and cardiac insufficiency.[15] Lithium levels are increased by angiotensin-converting enzyme inhibitors, COX-2 inhibitors, diuretics, nonsteroidal anti-inflammatory drugs, and dehydration, and decreased by caffeine, theophylline, aminophylline, mannitol, and excess fluid intake.[16] Although no placebo-controlled studies have been performed to assess the efficacy of lithium for mania in older adults, evidence from retrospective studies indicates that lithium is effective for this population.[17-19] Dr. Pinals indicated that clinical evidence suggests that elderly patients require lower blood levels of lithium (0.4-0.8 mEq/L).

Divalproex has also been widely used for the management of bipolar disorder for well over 20 years, but similarly lacks any evidence from large, randomized clinical trials in the elderly.[15] Divalproex has a prolonged half-life in older adults, and blood levels are decreased by interactions with other medications, including phenytoin and carbamazepine. Divalproex inhibits lamotrigine metabolism and can cause a variety of side effects that may be significant for older patients, including sedation, tremor, ataxia, weight gain, hair thinning, and thrombocytopenia. Several retrospective and open-label studies have demonstrated that divalproex has an antimanic effect in older adults,[19-21] with apparently better results at blood levels of 65-90 mcg/mL than at lower levels.[19] Carbamazepine has also been shown to have efficacy in older adults.[22,23] Side effects to be considered include sedation, tremor, ataxia, nausea, hyponatremia, leukopenia, hepatic toxicity, bradycardia, and conduction delays.

In addition to lithium and antiepileptic drugs, atypical antipsychotics are also being increasingly used for the treatment of mania in elderly patients with bipolar disorder, especially as augmentation to other drugs. However, Dr. Pinals stressed that monotherapy is the ultimate goal in treating elderly patients.

Other Considerations for Treatment of Geriatric Bipolar Patients

In Dr. R.C. Young's[24] presentation at the APA meeting, several other issues pertaining to the treatment of bipolar disease in this particularly complex and heterogeneous population were discussed. Bipolar disorder in late life is often associated with high risk for poor outcomes, including emergent dementia[25] and a higher mortality rate than for depression.[26] As most studies for bipolar disorder have been conducted in younger cohorts, there is limited research to guide proper management of patient care.

GERI-BD Study

To begin to address this problem, Dr. Young and colleagues have begun enrollment for a randomized, double-blind, concentration-controlled parallel-group trial in bipolar manic, mixed, and hypomanic patients ≥ 60 years of age. The study, GERI-BD, is an NIMH U01 and includes collaboration between experts in early-life bipolar disorder and geriatric psychiatrists, to compare the efficacy of 2 commonly used mood stabilizers, lithium and divalproate. Patients will be randomized to receive monotherapy with either lithium or divalproate, followed by the addition of risperidone at 3 weeks, if necessary.

Treatment of Depression in Older Adults

As with mania, there is very little randomized clinical trial data available to guide the treatment of depression in older adults. Antidepressant medications are often used, but should always be prescribed in conjunction with mood stabilizers. Selective serotonin reuptake inhibitors and bupropion are generally used to minimize the risk of switching into mania.[14] However, these medications are associated with a high incidence of diverse events in older adults, including neuropsychiatric effects which can look like mania in this population. Therefore, in his review of treatments for elderly patients with bipolar disorder, Dr. Pinals stressed that great caution should be taken when adding an antidepressant to the regimen.

In a small study in older adults, lamotrigine was well tolerated, appeared to be useful for maintenance therapy, and was shown to have possible antidepressant efficacy as well. In addition, the risk for Stevens-Johnson syndrome is low for older patients (0.03%), thereby making lamotrigine a potential treatment option.[27] Electroconvulsive therapy is another option that is very effective and well tolerated in the elderly; it should be considered in refractory cases, especially suicidal and nutritionally compromised patients.[14]

Maintenance Treatment

A recent secondary analysis of 2 placebo-controlled trials of maintenance therapy for bipolar I disorder showed both lithium and lamotrigine had efficacy and good tolerability in adults over the age of 55 years. Lithium treatment delayed time to manic, hypomanic, and mixed episodes, while lamotrigine delayed time to any mood episode.[28] In a recent review, Dr. Young recommended that mood stabilizers be continued indefinitely, while adjunctive treatment, such as antidepressants, anxiolytics, and antipsychotics, should only be used episodically for the treatment of mania or depression over a period of 6-12 months and then slowly tapered.[29,30]

Other Treatment Modalities

Psychoeducation is another important aspect of the treatment armamentarium for bipolar disorder. The role of family and caregivers is particularly important in the case of elderly patients. One study showed lower relapse rates, improved lithium levels, and increased time to recurrence in patients with standard pharmacotherapy plus psychoeducation.[31,32] A study currently under way under the direction of Dr. Sarah Pratt and Meghan McCarthy, MSW, at Dartmouth Medical School, is evaluating the effect of a 24-month rehabilitation and health management intervention on patient outcome in the elderly who have functional impairment from severe mental illness, including bipolar disorder. The study, called HOPES (Helping Older People Experience Success), includes a skills training class for participants that meets once a week for 12 months and then once a month for the following 12 months. The intervention also includes community practice trips and home practice to solidify skills learned in class. Results from this study will provide further support for the role of education and skills training in the overall health and well-being of elderly patients with severe psychiatric disorders.[33]

Conclusions

While the treatment strategies for geriatric bipolar disorder patients are similar to those for younger patients, it is clear that special consideration must be given to the elderly patient. This is particularly relevant with regard to pharmacologic interventions because of the pharmacokinetic differences in drug metabolism in older individuals. In addition, elderly patients may have greater difficulty with issues such as transportation and accessibility and may have complicated financial situations that present further challenges to treatment. More attention is being placed on the treatment of elderly patients with bipolar disorder, and new studies, such as GERI-BD, will further enhance our ability to properly manage and care for this patient population.