Bipolar Disorder in the Elderly: Differential Diagnosis and Treatment

Mood stabilizing anticonvulsants. DVP is effective for the acute treatment of mania in younger adults and appears to be at least modestly effective and well-tolerated in elderly patients who are manic.^20,21 A mixed-age population of lithium-refractory patients and those who have neurological abnormalities appear particularly responsive to DVP.²² Some older patients with mania may require higher doses, and measurement of serum levels of DVP during acute illness and after stabilization is recommended. Toxic adverse effects, including sedation and gait instability, may develop during an acute phase and during maintenance therapy. Although hepatic and pancreatic toxicity are infrequent in the elderly, baseline liver functions should be obtained. DVP interacts with other highly protein-bound medications such as warfarin,²³ is a modest cytochrome P450 enzyme inhibitor, and also strongly inhibits certain glucuronidation enzymes, thus increasing levels of lamotrigine.

Other anticonvulsants have been used in elderly patients who have BD, with limited support from controlled studies. DVP and oxcarbazepine have replaced carbamazepine because of fewer adverse effects and better tolerability, although there is far less efficacy data for treatment of mania with oxcarbazepine. Serum sodium levels should be monitored for patients taking oxcarbazepine because it can cause hyponatremia. Several newer anticonvulsants may have more tolerable adverse-effect profiles, including gabapentin, topiramate, tiagabine, zonisamide, lamotrigine, and levetiracetam. However, as with gabapentin, topiramate and levetiracetam have failed in industry-supported studies of acute mania. Zonisamide still appears to hold some promise of efficacy in studies of adults with BD. Overall, these newer anticonvulsants have yet to be studied sufficiently in elderly patients with BD and mania to justify an authoritative recommendation for use.

Electroconvulsive therapy. Electroconvulsive therapy (ECT) remains an important intervention in the treatment of acute mania in later life and is often reserved for patients whose illness is resistant to medication or who require a rapid symptomatic resolution because of risks of dangerousness or malnutrition. Most responders can then be switched to pharmacotherapeutic maintenance, with or without continued ECT maintenance.⁷ Bilateral treatments may be more effective in mania,²⁴ while unilateral placement may be associated with reduced cognitive disturbance.²⁵ The co-administration of ECT and lithium has been associated with increased confusion and should generally be avoided.⁵

Bipolar depression is a complex and difficult-to-treat condition that remains seriously understudied.¹³ Antidepressants can provide short-term benefit but may increase the risk of mania and rapid cycling over the long-term.^26,27 Minimizing the use of antidepressants in bi- polar depression may be possible since some newer mood stabilizers appear to have stronger antidepressant properties than conventional mood stabilizers.

The combination of olanzapine and fluoxetine was the first FDA-approved medication for the treatment of bipolar depression,²⁸ although research and clinical experience for its use in geriatric BD is limited. Quetiapine was recently approved for bipolar depression in adults. The combination of a standard mood stabilizer, such as lithium or DVP, with an antidepressant is a common and accepted form of treatment.²⁹

"Switching" to mania while receiving tricyclic antidepressants (TCAs) and other antidepressant agents can occur in older adults.^30,31 SSRIs and bupropion are favored in younger patients who have bipolar depression to reduce rates of switching. Monoamine oxidase inhibitors (MAOIs) can benefit younger patients with bipolar depression³² and are effective in older patients with unipolar depression.³³ In general, TCAs and MAOIs have higher rates of switching than SSRIs and bupropion, but they have not been studied in geriatric bipolar depression.

For a moderate to severe or treatment-refractory episode of major depression, more aggressive pharmacotherapy or ECT is indicated. Highly refractory and protracted depressive episodes in BD have not been studied systematically in adult populations or in the elderly. Because of the risk of death and continued morbidity, the physician must make decisions based on clinical judgment or consensus guidelines.²⁹ Some of these measures include lowering the dosage or even discontinuing a mood stabilizer; sleep deprivation; ECT; or combination therapies, including tranylcypromine plus risperidone³⁴ or venlafaxine plus mirtazapine.³⁵

Little information is available regarding maintenance treatment and prevention of subsequent episodes of late-life mania. Lithium has demonstrated efficacy as maintenance therapy in younger adults,³⁶ and, although often used for maintenance, DVP has not received an FDA indication for that use.

Lamotrigine, olanzapine, and aripiprazole have been FDA-approved for the prevention of recurrent episodes of bipolar mania and depression.^37,38 Lamotrigine has been shown to have acute and prophylactic antidepressant effects in patients with acute bipolar depression³⁹ and in delaying relapse of bipolar depression.³⁷ Among the major mood stabilizers, lamotrigine stands out as the best-tolerated medication; the only serious adverse effect is risk of Stevens-Johnson syndrome. It is attractive for treatment in older adults. Maintenance ECT is an option for patients who show poor response to maintenance medication regimens.¹⁰

A number of studies have demonstrated the efficacy of psychotherapy in improving medication adherence in adult bipolar patients,^40-42 although it has not been addressed in the geriatric population. In some promising preliminary studies, interventions in which bipolar patients are taught to monitor and manage stress have been effective in reducing rates of recurrence.^43-45 Recent studies have demonstrated the efficacy of family interventions focused on reducing "expressed emotion," or negative familial attitudes of criticism, hostility, and emotional overinvolvement.^46-50

Studies of group interventions over the past 3 decades for patients with BD have yielded positive results, including reduced re-admissions and improved medication adherence.^41,42,51 Pollack⁵² conducted a study of inpatient group treatment for BD with 3 therapeutic goals: sharing information, learning strategies of coping, and improving interpersonal relationships. Other researchers have reported effective group treatments that include psycho-education on triggers, confrontation of denial about the illness, and restoration of patients' identity and capacity for intimacy.^53,54 In addition, interpersonal psychotherapy, social rhythm therapy,⁴³ and cognitive-behavioral therapy have demonstrated promising results.^55,56

Researchers stress the relative power of combined psychosocial and pharmacological treatments in older adults with depression⁵⁷ compared with either form of treatment alone. Gerocognitive behavior therapy combines a developmental perspective with cognitive interventions modified for older adults.⁵⁸ This integrative model offers preventive strategies, including management of stress, attention to biological rhythms, and improved medication compliance, as well as reparative measures to deal with the interpersonal, social, and practical aftermath of the manic or depressive episode.

BD presents complex diagnostic and treatment challenges in later life. Confounding syndromes of delirium and dementia often present difficulties in accurate diagnosis. The occurrence of manic symptoms in the older adult must prompt careful evaluation to identify treatable medical conditions. Pharmacological approaches and ECT can be helpful in acute and maintenance treatment of late life mania and bipolar depression, although prospective, randomized, controlled trials in geriatric BD of all phases are currently lacking. Psychotherapy has much to offer in enhancing treatment compliance, addressing relapse risks, and helping patients cope with the implications of a chronic mental disorder. Controlled clinical research, in partnership with the technologies of genetics, molecular biology, and functional neuroimaging, will provide a better understanding of the neurobiological causes of geriatric BD and will promote more specific and effective treatment strategies.