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Bipolar Disorder in Older Adults

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Vol. 21 •Issue 22 • Page 36
Bipolar Disorder in Older Adults

Providers need a greater awareness of this disabling condition in geriatric patients

Bipolar disorder in older adults is grossly understudied and is a growing public health problem.1,2 This disorder, which can significantly interfere with personal relationships and social functioning, may be a lifelong illness or may surface as a late-onset disorder.

Epidemiology

For diagnostic purposes, bipolar disorder is categorized with mood disorders.3 Unipolar major depression is the best known form. Mood disorders are among the top 10 causes of disability worldwide.3

There are no reliable data about the prevalence of bipolar disorder in the elderly population, but experts predict that it will increase significantly as the baby boom generation grows older.4,5 The disease affects people of all ages – about 1 to 2 percent of the population.6

Most information about the treatment of bipolar disorder in the elderly is projected from studies of younger adults.7 Fortunately, awareness about bipolar disorder in older patients is increasing due to the increasing incidence worldwide.

A recent review article summarizing 61 reports found that although bipolar disorder is less common with increasing age, it can occur de novo in late age and accounts for 6 to 10 percent of psychiatric admissions.2

One study found that 10 percent of all patients with bipolar disorder were 50 or older.7 Further, bipolar disorder accounted for 5 to 19 percent of all mood disorders in the population. In many areas of this country and the world, bipolar disorder is either misdiagnosed as unipolar depression or underdiagnosed in general.8

The estimated prevalence of mania in elders is 5 to 19 percent.5 These statistics reflect patients seen at treatment centers and do not represent community data.

Gender differences in bipolar disorder are few. The rate of depressive versus manic or mixed episodes is similar in men and women.9 One study determined that men exhibit a gradual increase of the onset of mania with increasing age, with mania peaking in the 80s and 90s.10 Women seem to have a bimodal onset of mania — one peak prior to age 30 and a second peak starting after age 40.11 The severity of episodes is similar in men and women. However, in one study, more women were treated in outpatient settings and more men were treated in hospitals.9 When women are hospitalized, they are treated for a longer period of time compared with men who are admitted. Men present with more comorbid substance abuse.

Suicide risk is a considerable problem in this population, and between 10 and 19 percent of bipolar patients complete suicide.12 Nearly half of all bipolar patients attempt suicide, and suicide risk in this population is 15 times that of the general population.13,14 Most suicides occur in the depressive phase of illness, but some occur during a period of mania.

Definitions of Bipolar Illness

A concise definition of bipolar disorder is recurrent episodes of depression with episodes of mania characterized by lack of impulse control, excess energy, delusional or grandiose thinking, elation, irritability, inappropriate behavior, pressured speech, hyperactivity and diminished need for sleep.15

Bipolar disorder can also be defined as mood swings from profound depression to mania (extreme euphoria) with periods of normalcy in between.16 Psychotic delusions and hallucinations can be evidenced clinically and seasonally. Relationship impairments often occur in social and occupational settings.

Bipolar I (BPI) disorder is the classic form of the illness. The diagnosis includes recurrent mania (pure manic) or mixed (manic features intermixed with symptoms of a major depressive episode that causes significant impairment in functioning) symptomatology.16,17 BPI patients may have episodic mania, hypomania (in which neither psychotic episodes nor marked impairment of judgment occurs) or depression. BPI is often characterized by the most recent phase of illness. A diagnosis of mania in elderly patients is uncommon but is projected to increase.18

Bipolar II (BPII) disorder is characterized by recurring bouts of major depression with episodes of hypomania.16 The elder may present with a history of depression or may describe hypomania.

Vascular mania is a new subtype that occurs in elders with a comorbid neurologic disorder, usually cerebrovascular disease.19 Elders with late-onset bipolar disorder have more associated psychosis.20 Head trauma, neuroendocrine disorders and brain tumors are other comorbid situations in which vascular mania may occur. There is little evidence of a family history of bipolar disorder in this subtype.

Some authors have suggested that the term bipolar disorder is inadequate because it cannot describe the complex and mixed states of anxiety, euphoria and depression that occur.21

Diagnosis

Four bipolar disorders are recognized in the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV): bipolar I, bipolar II, cyclothymic disorder (less common in elders) and bipolar disorder-not otherwise specified.17 An elder must meet DSM-IV criteria for the diagnosis to be made (Tables 1 and 2).

There are some parallels between bipolar disorder in elderly people and adolescents.21 Both have more common mixed affective states with very rapid cycling, mood lability, mixed mania, and psychosis. Agitated states are reported with greater frequency in adults older than 50 years who have major depressive disorder. And in both adolescents and elders, the use of antidepressants tends to accelerate agitated depression and cycling. Mixed episodes and very rapid cycling are associated with higher rates of suicidal ideation and attempts compared with patients who have classic bipolar disorder.

The onset of bipolar disorder later in life appears to occur in people who are genetically vulnerable.21 Many have a first-degree relative with a history of mania.

There appears to be a relationship between seasons and hospital admission rates for bipolar disorder.22 In Tel Aviv, patients had higher spring and summer admissions compared with winter. The higher the mean monthly temperature, the greater the number of admissions. The authors of that study concluded that increased environmental temperature may be a risk factor for major depressive episodes that require hospital admission. No similar trend has been documented in studies of patients with unipolar depression.

Pathophysiology

Over the past 20 years, much progress has been made toward identifying changes in the brain that are related to mental disorders.23 Magnetic resonance imaging (MRI) and postmortem examinations demonstrate loss of brain volume in patients with bipolar illness. Aberrant perfusion and metabolism in the anterior cingulate cortex (ACC) are present. Additionally, there is diminished gray matter volume in the prefrontal cortex of people with bipolar disorder.

Microscopically, loss of interneurons (25 to 35 percent) occurs in the ACC when bipolar disorder is present. Glial cell density is decreased. Apoptosis (cell death from aging [normal cell turnover] and cell excess, as opposed to necrosis [cell death from trauma]), results in cell death, explaining the volume loss.24

New research at the National Institute on Aging is using rat and mathematical models to further explore lithium's effects.25 Lithium reduces turnover of arachidonate within brain phospholipids, downregulating gene expression at the mRNA level and reducing enzyme activity of a specific phospholipase A2. Scientists have found that valproic acid and carbamazepine have these same lithium-like effects on metabolism. This knowledge will allow new drugs to be designed with a wide therapeutic window and less toxicity.

People with bipolar disorder often have thyroid problems.26 Elevated or diminished levels of thyroid hormone cause mood and energy problems. Assessment and treatment of thyroid problems are essential to the management of bipolar disorder.

Pharmacologic Management

Few studies have been conducted to determine the most effective clinical management of bipolar disorder in elderly patients.21 Providers mainly rely on guidelines developed for younger adults. Pharmacologic management is the critical intervention, no matter what the age of the patient. This section briefly summarizes the medication categories most commonly used in the elderly.

Mood stabilizers. These are usually effective in managing symptoms in elderly patients. Lithium, which is most widely used in younger patients, is less often used in elderly people because it is excreted renally and kidney function is often compromised in older adults. Lithium's narrow therapeutic range renders toxicity a potential problem in older patients.

Divalproex or valproic acid (Depakote) was approved by the FDA for the treatment of mania in 1995.26 It seems to be an effective, well-tolerated mood stabilizer for older adult patients.21 In recent years, divalproex has been used more often in older patients than lithium.

Gabapentin (Neurontin), an anticonvulsant, was well tolerated and effective in one small trial of elderly manic patients.27 The patients were treated with antipsychotic medications dosed in combination with gabapentin. One patient was also treated with valproate. Gabapentin has few side effects alone or in combination with these other drugs. More research is needed to provide further detail.

Relapse prevention. Lamotrigine (Lamictal), an anticonvulsant, has an FDA-approved indication for relapse prevention.28 Lithium is the only other drug approved for this use. Lamotrigine is superior to lithium in preventing relapse into depressive episodes, however lithium is superior in preventing manic episodes.8

Acute-stage management. Antipsychotics and the atypical antipsychotics (such quetiapine [Seroquel], olanzapine [Zyprexa] and risperidone [Risperdal]) are used to manage mania. One study found that quetiapine administered with divalproex or lithium had superior efficacy compared with divalproex or lithium alone as monotherapy.29 The combination was well tolerated and adverse effects were mild and comparable to monotherapy.

Olanzapine has an FDA-approved indication for the management of acute mania and is also useful in the relief of psychotic depression.26

Intramuscular (IM) agents may be required for elders who are severely agitated and cannot or will not take oral medications. Haloperidol (Haldol) IM is commonly used, as is lorazepam (Ativan), to achieve rapid control.30 Olanzapine IM has an FDA-approved indication for agitation associated with mania. Dystonias have not been reported with IM olanzapine.

Liquid formulations can be used in less acute elders with mania. In the recent past, the first-generation antipsychotics were given in this manner. Liquid risperidone is now available, as is liquid olanzapine.

Depression. Antidepressant monotherapy is the most common treatment for BPI depression throughout the world.8 Yet little evidence demonstrates that antidepressants are effective in the management of bipolar disorder. Rather, antidepressant therapy can induce mania in bipolar I patients and thus monotherapy with antidepressants is to be avoided in bipolar illnesses. However, an antidepressant-mood stabilizer combination is effective in preventing depressive relapses. Fluoxetine (Prozac) with olanzapine is superior to olanzapine alone in the management of depression in bipolar patients.8

Antidepressant-induced hypomania (AIH) is a classification in the DSM-IV. One researcher examined this classification and concluded that AIH is a misdiagnosis of major depressive disorder.31 Patients who become hypomanic with antidepressant therapy are bipolar.

Tricyclics, which are rarely used in elderly patients today, are known to induce mania in bipolar disorder. SSRIs are superior, having lower mania-induction rates.8

Knowledge of BPII management is limited by the small number and poor quality of published studies.32 A research review found that lamotrigine has the strongest evidence for long-term management of BPII. The old mainstay of bipolar treatment, lithium, is by far the most studied therapy and continues to be a primary choice for younger patients. Short-term therapy may be provided using risperidone to treat hypomania. For depressive episodes, divalproex, fluoxetine and venlafaxine are recommended — although broad recommendations are difficult with so little study. Management decisions should be made on a case-by-case basis.

Newer agents. A number of off-label treatments are used to manage bipolar disorder.28 The natural compounds omega-3-fatty acid and SAMe are two that have been studied. One study found omega-3 fatty acid to be useful, but other studies have not replicated the result. SAMe may be useful for major depression at high doses, however, it has a high risk for inducing mania and hypomania.

Tamoxifen has been studied for bipolar disorder.28 It acts similarly to lithium and divalproex. In a study of seven patients, four had a significant reduction in mania.

Inositol, a sugar, has also been studied for use in bipolar disorder.28 In a 6-week pilot study, it reduced depressive symptoms when added to divalproex or carbamazepine.

Calcium channel blockers are also being studied for possible applications in bipolar disorder. Verapamil (Calan) is a subject of particular focus.28 In addition, donepezil (Aricept), clonidine (Catapres), zonisamide, the dopamine agonist pramipexole (Mirapex), and levitiracetam (Keppra) are subjects of research.

Nonpharmacologic Therapies

Psychotherapy may help provide support to elders with bipolar disorder and their families. This is a lifelong, recurring illness that has high rates of relapse.33 It has high social (and economic) costs.

Psychotherapy contributes considerably to prevention of the disability that can accompany this illness. Psychotherapy as part of the treatment program can help restore patient function and reduce depression. Useful interventions for bipolar disorder include cognitive behavioral therapy, education and family therapy.

Social support has an important role in bipolar disease management as well. In one study comparing elderly bipolar patients with peer controls and younger patients, researchers found that compared with other subjects, elders perceived their social support to be more inadequate even though no difference was found in the number of social interactions, social network size, race, marital status or education levels.34

Electroconvulsive therapy (ECT) may be an option for elders who do not respond to other interventions. Patients who are suicidal may particularly benefit. In a psychotic episode in which interventions act too slowly, ECT may be used.

Herbal supplements such as St. John's wort are not useful in bipolar disorder. The FDA does not regulate the production of herbal remedies and the amount of the active ingredient in each is unknown. Further, herbals may interfere with the function of drugs that are necessary for disease management, and little is known about these effects. The National Institute of Mental Health has stated that St. John's wort (like prescription antidepressants) can cause manic episodes in bipolar disease, especially when no mood stabilizer has been prescribed.26

More Research Needed

Bipolar disorder in the elderly is often misdiagnosed and mismanaged. This is not the result of carelessness by health care providers, but rather inadequate research and limited understanding. The illness is associated with considerable loss of function and increased disability, diminished quality of life, and a high mortality from suicide.35 These sequelae demand that we support research about bipolar disorder in the elderly and make every effort to learn more and do more for these patients. A multimodal approach to management is recommended.8

References available at www.advanceweb.com/OT or upon request.

Ann Schmidt Luggen, NP, is a gerontologic nurse practitioner with a PhD who is a professor of nursing at Northern Kentucky University in Highland Heights, KY. She is a former president of the Ohio Gerontological Nurse Practitioners Association and a former president of the National Gerontological Nurses Association.

Table 1: DSM-IV Criteria for Manic Episode

A distinct period of abnormally and persistently elevated, expansive or irritable mood that lasts at least 1 week (or any time frame if hospitalization is required).

During the mood disturbance period, three or more of the following symptoms persisted (four symptoms if the mood is "irritable") and have been present to a significant degree:

• grandiosity or inflated self-esteem

• diminished need for sleep (feel rested after 3 hours of sleep)

• pressured speech or more talkative than usual

• flight of ideas or subjective feeling of racing thoughts

• distracted (attention drawn easily to irrelevant or unimportant stimuli)

• increased goal-directed activity (socially, at work, school or sexually) or psychomotor agitation

• excessive involvement in pleasurable activities with a high potential for painful consequences, such as engaging in unrestrained buying sprees, sexual indiscretions or foolish business investments

The symptoms do not meet the criteria for a mixed episode.

The mood disturbance is sufficiently severe to cause marked impairment in functioning at work, in social activities or relationships, or necessitates hospitalization to prevent harm to self or others, or psychotic features are present.

The symptoms are not due to direct physiologic effects of a substance such as illicit drugs, medication, treatments or a medical condition such as hyperthyroidism.

Table 2: Differential Diagnosis List for Mood Disorders

• Depressive syndromes associated with strokes

• Hypothyroidism

• Cushing's disease

• Pancreatic cancer

• Antihypertensive medications

• Alcohol withdrawal syndromes

• Withdrawal from drugs of abuse

• High-dose glucocorticosteroids

• Lupus

• HIV

• Tumors

• Cultural influences (somatization prevalent in ethnic minority backgrounds)

• Multiple sclerosis




     

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