Diagnosis matters
Lithium is most effective in patients with euphoric mania, full remission between episodes, and normal interepisode functioning. Its potential benefits, however, clearly extend to all other aspects of bipolar disorder, to augmentation for treatment-resistant major depressive disorder, to schizoaffective disorder, and—at times—to aggressive states. As the bipolar spectrum expands, it is hardly surprising that the effectiveness of lithium (or any other drug) lessens as we approach the periphery of the spectrum.
Blood levels and dosing
Recommended lithium serum concentrations are given as ranges, realizing that individual variability makes exact numbers impractical. Package inserts for lithium products list serum concentrations between 1.0 and 1.5 mEq/L for acute mania and 0.6 and 1.2 mEq/L for maintenance therapy. The APA’s revised guidelines are a bit more conservative, recommending 0.5 to 1.2 mEq/L for acute mania and waffling somewhat on maintenance.4 Many patients on maintenance therapy do well at levels between 0.6 and 0.8 mEq/L, and some prosper at even lower levels.
To avoid obtaining a misleading blood level:
- Samples should be drawn in the morning as close as possible to 12 hours after the last dose.
- Steady state conditions should exist, usually meaning 4 or 5 days on the same dosage without any missed or extra doses (Box 2).
Start treatment using divided dosages, but—following stabilization—once-daily dosing is possible for many patients. If lithium is taken as a single daily dose, 12-hour blood levels will be somewhat higher than with multiple daily dosing. Single and multiple daily dosing are similarly effective, but once-daily dosing may have a compliance and tolerability edge in some patients.
Considering individual patient variability, a lithium carbonate dosage of 1,200 to 1,800 mg/d is likely to be therapeutic for mania and 900 to 1,200 mg/d for maintenance in otherwise healthy, nongeriatric adults.
Starting and maintaining lithium
Medical history. Assuming that lithium theapy is indicated, obtain a detailed medical history. Focus on findings that increase the risk of lithium toxicity, such as renal impairment, drug interactions, and unstable fluid-electrolyte balance.
Although lithium is not contraindicated in patients with renal disease, using an alternate drug is probably preferable. On the other hand, because lithium does not adversely affect the liver or pancreas, it may be preferred to some other mood stabilizers if these organs are diseased.
A thorough diet and drug history is also important. Because low-sodium diets reduce renal lithium clearance, lower doses may be required to reach a given serum concentration. Some drugs alter lithium excretion and can increase or decrease blood levels (see “Drug combinations,”).
Advise women of childbearing age about lithium’s teratogenic potential (which is considerably less than that of carbamazepine or valproate). The risk of cardiovascular malformation of the fetus has been estimated at 1/1,000 to 1/2,000 births among women who took lithium during the first trimester of pregnancy.8
TWO KEYS TO OBTAINING A MEANINGFUL LITHIUM SERUM LEVEL
- Draw samples in the morning, as close as possible to 12 hours after the last dose.
- Measure serum levels at steady state, at least 4 or 5 days on the same dosage without any missed or extra doses.
Baseline lab tests. Assessing renal function is essential. A serum creatinine level will usually suffice, unless a history of renal disease suggests the need for a more extensive evaluation, such as creatinine clearance, renal ultrasound, or nephrology consultation.
A urinalysis is often part of the package. Because thyroid dysfunction can alter mood and lithium can disrupt thyroid function, baseline TSH and T4 tests are recommended. CBC is optional (lithium can cause leukocytosis). The medical history should determine whether additional blood work is necessary. An ECG is sometimes advised in older patients, especially if the history suggests cardiovascular disease. Finally, don’t forget a pregnancy test in women of childbearing potential (Box 3).
Monitoring. Early in the course of therapy, lithium blood levels are usually obtained at 5- to 7-day intervals until the patient is stabilized. After that, assuming all is well, routine monitoring can occur every 3, 4, or even 6 months, depending on the individual’s reliability and stability. Because ongoing assessment of renal and thyroid function is also important, it makes sense to obtain:
- a serum creatinine measurement linked to each lithium level
- and a serum TSH yearly or at the slightest indication of thyroid dysfunction, such as fatigue, weight gain, cognitive impairment, cold intolerance, or depression.
Stopping lithium. Lithium can be discontinued abruptly without side effects if it is ineffective or not tolerated. Stopping lithium after successful long-term use is another story. There is a high likelihood of illness recurrence and a small but real possibility that lithium will be ineffective when restarted. Also, abrupt or rapid discontinuation (within 1 to 14 days) is believed to increase the likelihood of earlier recurrence, compared with more gradual discontinuation.9