Managing Geriatric Bipolar Disorder: Use of Lithium and Anticonvulsants

Sandra A. Jacobson, M.D.

Research Associate Professor
University of Arizona College of Medicine-Phoenix

Last updated: April 2, 2018

This presentation discusses selected concepts on the use of mood stabilizers in the elderly.

Lithium serum levels are kept low (0.4 and 0.8 mEq/L), even for the treatment of mania in elders. Lithium should be dosed on a once nightly basis with an immediate-acting formulation.

The extended-release valproate formulation (Depakote ER) and sprinkles provide steadier serum levels with reduced peak level side effects.

Lamotrigine has a long titration period in elderly patients. This can limit the its value as monotherapy but lamotrigine can be very useful used early in combination therapy.

 

Now, we will talk about mood stabilizers. Selected concepts.
If a patient is presenting with a first manic episode in late life, a medical cause should be considered.


In the case of a primary mania, the patient will have a history of treatment with first-line drugs and that history will give you some guidance as to what was effective in the past and what adverse effects could be expected. It is an unfortunate fact, however, that most elders will have to be treated with more than one drug to achieve remission from mania.


Treatment algorithms for mania and bipolar depression in geriatrics are the same as for the general adult population.


For mania, valproate, lithium and atypical antipsychotics are first line drugs. Drug combinations are introduced early and ECT is considered when first line combinations have failed.


For bipolar depression, valproate and atypical antipsychotics are first-line drugs with lithium and lamotrigine used early in combination therapy.


For maintenance phase treatment, acute treatments that were well tolerated can be continued for prophylaxis. For this purpose, atypical antipsychotics, valproate and lithium are used. It is important that you look at published treatment algorithms for further details.


When mood stabilizers are used chronically in older patients, a gradual reduction in dose over time (meaning years) usually is required because of reduced renal and hepatic function.


In general, drug interactions are very problematic for mood stabilizers. For valproate and lithium, treatment is closely monitored with trough drug levels. Adverse effects of mood stabilizers are common and can be serious.


Let’s take a look a little more closely at each one of these drugs. Lithium first. This is a first line drug for the treatment of acute mania in geriatrics and this is despite concerns about renal effects and toxicity with rapid dose escalation.


Clearance of lithium is directly proportional to GFR. You are advised to dose this drug in the elderly on a once nightly basis with an immediate acting formulation to allow the kidneys time to recover before the next nightly dose.


Serum levels are checked seven days after a dose change from eight to 12 hours after the last dose. That is a trough level.


In geriatrics, lithium serum levels are kept on the low side, between 0.4 and 0.8 mEq/L, even for the treatment of acute mania. This is so despite a poor correlation of serum levels with brain levels in elders.


Valproate. This also is a first line drug for bipolar disorder in elders.


The drug is very rapidly absorbed. Both food and the use of the enteric-coated form of Depakote slow absorption.


The extended-release formulation that is Depakote ER and sprinkles provide steadier serum levels with reduced peak level adverse effects.


Lamotrigine. It has actually been controversial whether lamotrigine should be considered a first line drug in the treatment of bipolar depression and for maintenance treatment in elders. The titration period for initiating this drug is lengthy in elderly patients and this limits its value as monotherapy.


The drug is mostly renally excreted so drug exposure is significantly increased in elders because of reduced renal function. Lamotrigine interacts with both valproate and carbamazepine.


Carbamazepine. Now, this is not in fact a first-line drug for the treatment of elderly patients because of its adverse effects and drug interactions. The pharmacokinetics of this drug are complicated because of autoinduction.


The drug is also the great inducer, a significant CYP450 enzyme inducer, and so affects the levels of many other drugs, both psychotropic and non-psychotropic.


And then further, carbamazepine is associated with blood dyscrasias and dermatologic reactions, among many, many other adverse effects.


Alternative formulations of mood stabilizers. Alternative formulations include several IV products that are generally not used in psychiatric practice and oral solutions and suspensions and orally disintegrating form of lamotrigine.


So these latter formulations are probably better avoided in elders because of the rapid onset of action which puts frail elders at risk of adverse effects. More detailed information about dosing and titration is available for all of these medications in the Clinical Manual.


Key points here. For lithium, serum levels are kept low, even for the treatment of mania in elders. Between 0.4 and 0.8 mEq/L.


Lithium should be dosed on a once nightly basis with an immediate-acting formulation.


For valproate, the extended-release formulation, Depakote ER and sprinkles, provide steadier serum levels with reduced peak level side effects.


For lamotrigine, the long titration period in elderly patients limits its value as monotherapy but it can be very useful used early in combination therapy.

References

  1. Al Jurdi RK, Marangell LB, Petersen NJ, et al: Prescription patterns of psychotropic medications in elderly compared with younger participants who achieved a “recovered” status in the systematic treatment enhancement program for bipolar disorder. Am J Geriatr Psychiatry 16:922-933, 2008
  2. Jacobson SA. Clinical Manual of Geriatric Psychopharmacology, 2nd Ed. Washington, DC: American Psychiatric Publishing, Inc., 2014.
  3. D’Souza R, Rajji TK, Mulsant BH, et al: Use of lithium in the treatment of bipolar disorder in late-life. Curr Psychiatry Rep 13:488-492, 2011
  4. Singh LK, Nizamie SH, Akhtar S, et al.: Improving tolerability of lithium with a once-daily dosing schedule. Am J Ther 18:288-291, 2011

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