FACTS ABOUT PRESCRIBING LITHIUM
- Lithium is most effective in patients with euphoric mania, full remission between episodes, and normal interepisode functioning.
- Lithium is the only mood stabilizer that has been shown to reduce the risk of suicide during long-term treatment.
- Renal impairment, drug interactions, and unstable fluid-electrolyte balance increase the risk of lithium toxicity.
- Lithium does not adversely affect the liver or pancreas and may be the preferred mood stabilizer if these organs are diseased.
- Lithium has teratogenic potential but less than that of carbamazepine or valproate.
- Because lithium can disrupt thyroid function, baseline and ongoing thyroid function tests are recommended.
In recent years, there has been a disturbing increase in reports of elevated serum creatinine and reduced creatinine clearance associated with long-term lithium use.13 Because renal impairment has many causes, evaluation by a nephrologist is strongly advised. Then if the finger of causation points strongly at lithium, a careful risk/benefit analysis is in order. Even if lithium is discontinued—and especially if it is continued—regular renal function assessment is essential.
Rarely, lithium can cause a nephrotic syndrome (proteinuria, edema, decreased serum albumin, and increased serum lipids) that tends to be reversible with drug discontinuation.
Drug combinations
First the good news. Lithium tends to combine well with all the anticonvulsant mood stabilizers, making it the favored drug for combination therapies. Lithium/antidepressant combinations can be useful for treatment-resistant depression, although serotonin syndrome occasionally has been reported when lithium is combined with selective serotonin reuptake inhibitors.10,11 Using lithium with atypical antipsychotics is common, often effective, and usually well-tolerated.
Drug-drug interactions. Some nonpsychiatric drugs are associated with reduced renal lithium clearance and potential lithium toxicity. Because nonpsychiatrists usually prescribe these drugs, encourage patients taking lithium to ask their doctors about the possibility of interactions whenever a new drug is prescribed. Pharmacists can be particularly helpful in avoiding drug-drug interactions.
In patients taking diuretics, serum lithium concentrations are definitely increased by thiazides, possibly by potassium-sparing types, and occasionally by loop types. Osmotic and xanthine diuretics do just the opposite. Because diuretics are often used in medically unstable patients, assume that all can disrupt lithium balance.
Most nonsteroidal anti-inflammatory drugs can increase serum lithium levels, although dose and treatment duration are important variables. Aspirin and acetaminophen should not cause problems. The effect of COX-2 inhibitors on lithium levels has not been studied adequately, so these drugs should remain under suspicion.14
Lithium toxicity has been reported with angiotensin-converting enzyme (ACE) inhibitors, and their package inserts caution about this possibility. More recently, a few cases of lithium toxicity have been reported in patients taking angiotensin II receptor type-1 (AT-1) antagonists (e.g., candesartan, losartan, valsartan).15
Other, less well-substantiated pharmacokinetic and pharmacodynamic interactions that have been reported with lithium and other drugs can be researched, by using a computer-based drug interaction program or consulting with a drug information center.
Patient and clinician education
Both patients and clinicians have an obligation to ensure that lithium (or any other drug) is used safely and effectively (Box 4). Excellent sources of continuing education are listed below in “Related resources.” Rather than fall prey to the illusion that lithium therapy is a “vanishing art,” it would be better for clinicians to heed these words from the APA’s 2002 practice guidelines for bipolar disorder:
“No other treatment has performed as well as lithium in as many aspects of long-term care of bipolar disorder patients, and despite some risks and limitations lithium remains the standard against which all proposed alternatives are compared.”6
- Depression and Bipolar Support Alliance. www.dbsalliance.org
- Lithium Information Center. www.miminc.org
Drug brand names
- Chlorpromazine • Thorazine
- Divalproex • Depakote
- Gabapentin • Neurontin
- Lamotrigine • Lamictal
- Olanzapine • Zyprexa
- Primidone • Mysoline
- Propranolol • Inderal
Disclosure
Dr. Jefferson receives grant/research support from Abbott Laboratories, Bristol-Myers Squibb Co., Forest Laboratories Inc., GlaxoSmithKline, Eli Lilly and Co., Novartis Pharmaceuticals Corp., Organon, Janssen Pharmaceutica, Pfizer Inc., Solvay, and Wyeth Pharmaceuticals. He also serves as a consultant to GlaxoSmithKline, Novartis Pharmaceuticals Corp., Solvay, and UCB Pharma.