Bipolar disorder (BD) in later life is a complex and confounding neuropsychiatric syndrome with diagnostic and therapeutic challenges. Complicating the clinician's approach to treatment of older patients with BD is the paucity of controlled pharmacological studies in this age group. In this article, we use a case vignette to illustrate some of the diagnostic and therapeutic difficulties presented by BD in geriatric patients. We discuss the epidemiological data, differential diagnosis, evidence-based pharmacotherapy, and psychosocial interventions available for treatment of BD in older adults.
Mrs Smith, a 74-year-old widow with a 30-year history of BD, was referred because of concerns about increasing depression. She had remained stable on lithium(Drug information on lithium) since 1979; her current dosage was 900 mg/d. Over the past few months, her family had noted increasing apathy, lack of motivation, and a decline in her functional capacity, although she had denied feeling depressed. The dosage of furosemide(Drug information on furosemide), a diuretic, was recently increased for hypertension.
On examination, Mrs Smith had a notable intention tremor of the hands, a Mini-Mental State Examination (MMSE) score of 28 of 30, and a lithium level of 0.9 mmol/L. Because lithium neurotoxicity was suspected, her lithium dosage was decreased to 450 mg/d; on follow-up her serum lithium level was 0.5 mmol/L. Within 2 weeks, Mrs Smith's daughter called to report that her mom was "no longer depressed," and had improved motivation, energy, and concentration, as well as a return to independent functioning.
Two years later, a routine check of renal function demonstrated renal insufficiency with a creatinine level of 1.4 mg/dL. Consultation with a urologist led Mrs Smith and her family to discuss gradually tapering off lithium. This possibility caused her severe anxiety and sleeplessness, leading to a brief hospitalization for a mixed episode with racing thoughts, irritable mood, and pressured speech.
Mrs Smith was discharged with the addition of olanzapine 5 mg/d at bedtime to her drug regimen. As an outpatient, lamotrigine(Drug information on lamotrigine) was prescribed, which was titrated to 100 mg/d over 2 months. Lithium was then tapered and discontinued, and olanzapine(Drug information on olanzapine) was maintained at 2.5 mg/d at bedtime. In the past 6 months, Mrs Smith's condition has been stable with no further mood episodes. Recent follow-up neuropsychological testing after 2 years indicated a stable impairment in memory retrieval and executive functioning.
This case highlights a number of important clinical issues when treating older adults with BD, including the importance of maintaining these patients at lower serum levels of medications, the development of cognitive impairment, the challenges in switching from lithium to alternative mood-stabilizing therapies, and the use of combination pharmacotherapy.EPIDEMIOLOGY
Much of what we know about the epidemiology of geriatric BD derives from data on mixed adult populations, geriatric and nongeriatric. Lifetime prevalence of BD appears uniform across cultures and similar between men and women.1 The 1-year prevalence of BD among adults aged 65 and older is 0.4%, significantly lower than in younger adults (1.4%).2 BD is highly recurrent, with 85% to 100% of patients experiencing a recurrence after the initial episode.3
In as many as 10% of patients with BD, the illness develops after the age of 50.4 Later-onset BD is associated with a lower rate of familial illness than early-onset cases, a higher rate of medical and neurological comorbidity, and an increased vulnerability to relapse.5 In patients with a history of unipolar depression, mania may not develop until later life,5 and misdiagnosis is common, especially in type II BD.DIFFERENTIAL DIAGNOSIS
The evaluation of manic symptoms or episodes in an older adult requires a thorough differential diagnosis to accurately determine the cause and to guide appropriate treatment (Table 1). Mania or major depression with anxious features should be considered when a patient is known to have had prior mood disorders. The new onset of bipolar symptoms in later years may represent secondary mania attributable to medical, pharmacological, or other organic dysfunction. Early stages of dementia may include manic symptoms such as irritable mood, emotional lability, sleep disturbance, and impaired social judgment. The co-occurrence of significant signs of confusion, fluctuation of alertness, or evidence of autonomic dysfunction may indicate the presence of delirium. In a patient with a history of BD, any change in baseline mood or functioning suggests a decompensation, warranting a workup for a concurrent medical condition.
In patients with MMSE scores of less than 15, the diagnosis of mania is especially problematic, particularly in distinguishing mania from dementia, delirium, or agitated depression.6 The following pearls may help with the differential diagnosis for patients who present with a combination of manic and cognitive symptoms.7
- The onset of a manic episode may be indicated by a rapid decline in cognitive functioning in a patient who has dementia, along with fluctuations in mood, energy, and sleep.
- Mixed manic and depressive symptoms are common in older patients who are manic.
- Dementia is typically associated with focal neurological findings, such as aphasia, apraxia, or impaired visuospatial functioning.
- It is typical for dementia or delirium to be associated with nighttime agitation and confusion in patients ("sundowning").
- A negative family history of BD may be unreliable, as family members may have received a diagnosis (or misdiagnosis) before the modern diagnostic classification.8
Unfortunately, the literature is lacking regarding the clinical presentation of geriatric bipolar depression and how or whether it may be distinguished from bipolar depression in a younger population.5PHARMACOTHERAPY
Most of what we know about the treatment of BD comes from randomized, controlled clinical trials in adult or mixed-age populations. There are no double-blind, placebo-controlled studies of geriatric BD. Our current guidelines for treating BD in the elderly are derived from uncontrolled studies and findings reported in younger and mixed-age populations (Table 2).Treatment of geriatric mania
Antipsychotic medications. In treating older adults with mania, conventional antipsychotic medications have been used during the acute phase of the disorder.6 Atypical agents have supplanted conventional antipsychotic medications as first-line treatments in geriatric clinical practice largely because of the adverse effects associated with conventional antipsychotics, including a heightened risk of tardive dyskinesia with long-term use in older adults.9 In controlled and uncontrolled trials, clozapine, risperidone, olanzapine, quetiapine, ziprasidone, and aripiprazole(Drug information on aripiprazole) have each been shown to be beneficial in younger patients who are manic.10 All atypical antipsychotic medications, except clozapine(Drug information on clozapine) and paliperidone, have been FDA-approved for the treatment of acute mania, both as monotherapy and in combination with lithium or divalproex sodium(Drug information on divalproex sodium) (DVP), and may be used in the elderly as well.11
Dosing of atypical antipsychotics in the elderly is generally one half to one third the dose recommended for younger patients, although it varies with factors such as comorbid medical illness and age.12 Studies of mixed-age patients have shown benefit from adjunctive risperidone(Drug information on risperidone) with DVP or lithium.13,14 Olanzapine monotherapy has demonstrated superior effectiveness compared with placebo for the treatment of mania in mixed-age patients, and a preliminary analysis of manic patients aged 50 years and older also suggests effectiveness.15 Preliminary open-label experience with quetiapine(Drug information on quetiapine) in older adults suggests that it may also have a role in treatment.16
Lithium remains a first-line treatment for acute mania in younger adults.17 It has not been studied in the elderly under double-blind conditions but has been reported to be as effective as acute or prophylactic treatments in several open trials.10 Because lithium pharmacokinetics are altered in the elderly—resulting in increased serum levels and elimination half-life—lithium can be associated with adverse effects even at lower serum levels.18 The presence of cognitive impairment or preexisting tremor increases the likelihood of adverse effects. Finally, recovery from lithium-induced delirium can be prolonged in older patients.19 Lithium's serum level can be raised by many NSAIDs, angiotensin-converting enzyme inhibitors, and even more strongly by thiazide diuretics. Thus, pretreatment workup should include a thorough list of current medications, as well as ECG and assessment of electrolytes, blood urea(Drug information on urea) nitrogen, creatinine, and thyroid-stimulating hormone levels.