Practical Guidelines for Diagnosing and Treating Mania and Bipolar Disorder in the Elderly

William M. McDonald, MD, Charles B. Nemeroff, MD, PhD

Disclosures

Medscape Psychiatry & Mental Health eJournal. 1998;3(2) 

In This Article

Treatment of Mania in the Elderly

Lithium is the mainstay in treatment of manic symptoms in younger bipolar patients. It has a number of advantages, including easily measured blood levels with a well-defined therapeutic window, proven clinical efficacy in mania (and, to a lesser extent, depression), and a relatively low cost. However, there are no double-blind studies of the effectiveness of lithium in the elderly, and there is clear evidence that older patients have difficulty tolerating the neurologic side effects of lithium, even at low serum concentrations (0.4 to 0.6mEq/L).[27,28,29,30] Side effects include ataxia, subjective complaints of memory problems, polyuria, and tremor. These side effects are more pronounced in elderly patients, who often have concomitant medical or neurologic illnesses.[31,32,33,34]

Our clinical experience has been that patients older than 70 years have difficulty tolerating lithium, even when they have previously taken this medication with few side effects. Altering the dosing schedule is a strategy that may help some elderly better tolerate lithium (Table II).[35,36,37,38] Lowering the daily dosage, and thereby decreasing the serum concentration of lithium, results in decreased efficacy in the treatment of both mania and depressive symptoms.[37,38] Some patients better tolerate the slow-release forms of lithium carbonate (including Lithobid and Eskalith) primarily because the peak levels (and therefore side effects) are decreased.

Another strategy is to dose all of the lithium at bedtime so the primary side effects occur while the patient is asleep. However, older patients frequently get up to urinate during the night and may be at risk for falls due to lithium-induced ataxia.

Carbamazepine (CBZ) and valproic acid (VPA) have been found to be as effective as lithium in the treatment of mania in younger patients and are better tolerated in the elderly.[39,40,41,42] VPA has been approved by the Food and Drug Administration (FDA) for use in the acute (but not prophylactic) treatment of mania; CBZ has not received FDA approval for use in mania. Open trials of these medications in the elderly have shown them to be well-tolerated.[43,44,45,46,47]

Patients with dysphoric mania, rapid cycling, lithium nonresponse, and no family history of affective illness have been shown to have an increased response to CBZ.[48] VPA response has been correlated with older age, increased severity of manic symptoms (including psychosis),[49] neurologic dysfunction, dysphoria, and lithium-nonresponsiveness.[49,50,51,52,53] Two recent studies have also found that, compared with monotherapy using either lithium or CBZ, patients treated with VPA had shorter lengths of stay in their acute hospital course.[54,55]

Our own clinical experience has been that VPA and CBZ are equally efficacious and better tolerated than lithium in elderly bipolar patients. VPA, and to a lesser extent CBZ, has become the first-line treatment used in our geriatric mood disorders program for the acute treatment of mania. Many of the patients have clinical profiles similar to the patient in our clinical case study, with neurologic dysfunction, dysphoria, negative family histories of affective disorder (as is more common in patients with late-onset mania), and physical conditions such as a familial tremor, mild dementia, and arthritis that would make lithium therapy difficult. The guidelines for using VPA and CBZ are outlined in Table III.[2,10,11,56,57,58,59,60,61,62,63,64,65,66,67,68]Lamotrigine and gabapentin are 2 other anticonvulsants that have been reported to be effective in the treatment of bipolar disorder. Preliminary trials with these medications indicate that they may be effective in younger patients with treatment-resistant bipolar disorder. In addition, they are not associated with aplastic anemia, hepatotoxicity, or induction of the P450 enzyme system. However, lamotrigine is associated with a rash (up to 10% of patients), which can evolve into toxic epidermal necrolysis.[69] More common side effects include dizziness, headache, and diplopia.[70] Lamotrigine inhibits the presynaptic release of the excitatory amino acids and may be effective in both manic and depressed phases of bipolar illness.[70,71] This finding, if confirmed, could have important implications in the treatment of bipolar patients. Although VPA and CBZ are effective in decreasing manic symptoms, they are less effective in treating the depressed phase of the illness.

Gabapentin also exerts its anticonvulsant effects through inhibition of excitatory amino acids, with no significant drug interactions and only minor transient side effects, including somnolence, dizziness, ataxia, and fatigue.[70] In preliminary studies, gabapentin has been shown to be effective in treatment-resistant bipolar disease for both manic and depressed phases.[72,73] A large multicenter, randomized, placebo-controlled clinical trial is currently underway to further assess its efficacy in bipolar disorder.[70] The unique mode of activity and benign side-effect profile may make this a useful medication in the treatment of elderly bipolar patients.

There are no double-blind trials comparing antipsychotics in elderly patients with mania, and only 1 trial with equivocal outcomes in younger patients.[45] Elderly bipolar patients have been found to have a high rate of tardive dyskinesia (approaching 20%), and the prevalence of tardive dyskinesia increases with age.[74] Elderly patients are more sensitive to the anticholinergic and orthostatic hypotension associated with low-potency antipsychotics as well as the EPS of high-potency neuroleptics. Additionally, the traditional neuroleptics are ineffective in treating the depressed phase of bipolar illness. The traditional antipsychotics are, therefore, infrequently used as the sole therapy of manic patients.

Neuroleptics are often used as adjunctive medication in the treatment of bipolar disorder.[75] The increasing pressure to reduce length of stay and to discharge patients early in the course of treatment, before they have been stabilized on monotherapy, has increased the use of neuroleptics and other mood-stabilizing medications. In a naturalistic study of younger bipolar patients, 96% were continued on neuroleptic medications 6 months after they were discharged from the hospital.[75] In the elderly, the side effects of the traditional neuroleptics, including the increased risk for tardive dyskinesia, have led to the practice of substituting the atypical antipsychotics for traditional neuroleptics in the prophylactic therapy of bipolar patients.

Risperidone, clozapine, and olanzapine are atypical antipsychotics because they exert their antipsychotic effect as mixed dopamine-serotonin antagonists (Table IV). The primary advantage of these atypical antipsychotics is a marked reduction or elimination of EPS (and the potential for tardive dyskinesia). Preliminary data show a greater antipsychotic effectiveness and improved resolution of the deficit symptoms of schizophrenia compared with the traditional neuroleptics.[76]

Risperidone and clozapine have been shown to be effective in the treatment of mania.[77,78,79,80] However, these medications have not been directly compared in double-blind trials with more traditional mood-stabilizing medications such as lithium and the anticonvulsants.

Clozapine is more efficacious in the manic than in the depressed phase of illness. However, clozapine is associated with significant orthostatic hypotension, sedation, increased risk of seizures, and a 1% to 3% rate of agranulocytosis. The weekly blood monitoring required to determine the patient's white blood cell count adds to the cost of the medication and decreases patient compliance.

Risperidone has been shown to be effective in the treatment of mania in younger patients, but has also been associated with a worsening of manic symptoms.[81,82] Risperidone has a higher affinity for the alpha-adrenergic receptors than olanzapine (comparable to clozapine) and is associated with significant orthostatic hypotension. Risperidone has a decreased affinity for muscarinic receptors and relatively fewer anticholinergic side effects than either clozapine or olanzapine.[83]

More clinical experience and controlled studies of these medications in older bipolar patients are needed, particularly to assess their efficacy in dysphoric manic states and depression. However, our own clinical experience has been that these medications are useful as adjunctive pharmacotherapy and offer a number of advantages over traditional neuroleptics. Another area that needs further exploration is the effect of these medications on cognition. Preliminary data in the treatment of schizophrenia have demonstrated an improvement in cognitive function of patients treated with clozapine.[84]

These agents, especially verapamil, are as effective as lithium in the treatment of mania (although not as effective as lithium in drug-resistant patients). However, they are useful as adjunctive medications, as well as antidepressants, in unipolar and bipolar patients.[63] The dosage of verapamil in these studies was approximately 240 to 480mg/day.

The elderly are particularly vulnerable to the potential side effects of calcium-channel blockers, such as hypotension, sinus bradycardia, and atrioventricular block. Yet some patients, as in our case study, may already be using a calcium-channel blocking agent and may benefit from changing to verapamil. Dubovsky and Buzan[63] caution that the rate of side effects may be increased when combining calcium-channel blockers with other agents used to treat mania, including lithium (neurotoxicity, choreoathetosis, parkinsonism, bradycardia), CBZ (increased CBZ levels, neurotoxicity), and neuroleptics (parkinsonism).

Electroconvulsive therapy (ECT) may be the ideal treatment for bipolar disorder. Reviews of the literature on ECT have shown that the response rate to ECT is approximately 80% for depressive and manic symptoms.[85] ECT therefore has an advantage over the traditional mood-stabilizing treatments in providing effective treatment for both phases of the illness as well as a faster response compared with lithium.[86,87] However, patient acceptance of the procedure has limited ECT to a third-line treatment in bipolar disorder.

The primary controversy in the application of ECT has centered on the administration of bilateral versus unilateral treatments. Bilateral treatments are associated with increased interictal confusion and long-term memory problems compared with unilateral treatments. Although some researchers have found bilateral ECT to be more effective than right unilateral treatments,[88,89] others have argued that right unilateral treatments using the D'Elia placement method are as effective as bilateral treatments[85,90] and produce fewer cognitive side effects. Our own experience in treating elderly bipolar patients is that suprathreshold stimulus (150% to 200% over the stimulus threshold) using the D'Elia placement method is as effective as bilateral treatment. Maintenance ECT may also provide prophylactic therapy for both the manic and depressed phases of bipolar disorder.[91,92,93]

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