Strategies for Optimizing Antiepileptic Drug Therapy in Elderly People

Thomas E. Lackner, Pharm.D., FASCP


Pharmacotherapy. 2002;22(3) 

In This Article

Bipolar Disorder

The elderly have a reported prevalence of bipolar disorder ranging from less than 1% to 19%, with a higher frequency of rapid cycling and mixed states than younger adults.[139] First-line therapies for acute mania are traditional and possibly atypical antipsychotics and adjunctive benzodiazepines, valproate, and possibly carbamazepine.[139] Lithium, a first-line agent for short-term and maintenance therapy in younger adults, is less effective than valproate and carbamazepine in many elderly individuals with dysphoric mania or rapid-cycling mania, or without a family history of affective illness.[139] These characteristics are especially common in elderly people with late-onset bipolar disease. Lithium is poorly tolerated by the elderly. It can cause or worsen nocturia, cerebellar dysfunction with associated tremors and falls, delirium, hyperglycemia, cardiac conduction disturbances, peripheral edema, and arthritis.[139,140] Risk factors predisposing these individuals to toxicity are diminished renal excretion of lithium due to advanced age-related renal impairment and lithium retention secondary to nonsteroidal antiinflammatory drugs, thiazide diuretics, and syndrome of inappropriate secretion of antidiuretic hormone (SIADH). Many drugs including antidepressants (selective serotonin reuptake inhibitors, tricyclic agents), AEDs (oxcarbazepine, carbamazepine), and antipsychotics can cause SIADH. In elderly people, lithium toxicity often occurs at SDCs within or even lower than the usual therapeutic range, particularly in those with neurologic diseases. This can necessitate maintaining low lithium SDCs for optimal control of bipolar symptoms.[139] In young adults, traditional antipsychotics are effective in managing acute mania but ineffective as maintenance therapy, and they can cause extrapyramidal symptoms, anticholinergic toxicity, and orthostatic hypotension. Although generally safer than traditional antipsychotics, atypical antipsychotics generally are not effective in mitigating the depressive phase of bipolar disorder in young adults. Controlled studies in the elderly, particularly those with dysphoric symptoms, should be conducted to clarify the role of atypical antipsychotics.

Although approved only for acute mania, valproate is effective as maintenance therapy, alone or combined with lithium, in both young adult and elderly patients.[141] In young adults, valproate is more effective than lithium for manic and mixed bipolar disease. Several open trials, retrospective case series, and individual case reports of elderly people suggest that it is well tolerated and effective in acute mania and as maintenance therapy of both classic and mixed types of bipolar disorder.[142,143,144,145,146,147,148,149,150] In addition, it appears to be at least as effective as lithium in improving acute and mixed bipolar disorders in the elderly.[142] The recommended initial dosage of valproate for bipolar disorder is 125 or 250 mg once or twice/day. A larger dosage, including a loading dose of 15-20 mg/kg total body weight, can be considered in hospitalized patients or those in an other reliably supervised settings. The dosage may be increased rapidly as tolerated until desired symptom control is achieved, at valproate SDCs of approximately 45-125 µg/ml.[141]

The effectiveness of carbamazepine for bipolar disorder has not been studied specifically in elderly people. In an open study, 44% of 16 patients (mean age 64 yrs) with electroconvulsive therapy- and lithium-refractory bipolar (3 patients) and unipolar (13 patients) disorder showed moderate (4 of 16 patients) and marked (3 of 16 patients) improvement with carbamazepine.[151] However, the drug was discontinued in 44% of patients due to skin rash (2), hyponatremia (2), and gastrointestinal distress or liver failure (3). The recommended initial dosage of carbamazepine and dosage escalation are the same as those for seizure disorders. A therapeutic SDC for bipolar disorder has not been established. Therefore a conservative initial target SDC in the subnormal or low end of the usual therapeutic range for seizures in younger adults is recommended (4-12 µg/ml).[141]

To my knowledge, there are no published studies of other AEDs in elderly people with bipolar disorder. In a single case report, gabapentin 300 mg twice/day controlled bipolar symptoms of recurring major depression with suicidal ideation for at least several months in a 73-year-old woman. Concurrent agents were venlafaxine and zopiclone (hypnotic).[132]