Lithium: 7 Myths That May Be Keeping It Underused

Lithium remains one of psychiatry’s most effective — and most misunderstood — medications. Despite decades of clinical use, misconceptions about therapeutic blood levels, toxicity, dosing, depression, weight gain, and cognitive effects continue to influence prescribing.Here are seven common misconceptions that may contribute to the underuse of lithium.1. Lithium must be dosed to a specific blood level.Nassir Ghaemi, MD, MPHA common assumption is that in every patient, lithium should be titrated to a serum concentration of 0.6-1.0 mEq/L, often with a target of 0.8 mEq/L. That approach is not supported equally across clinical indications.The historical therapeutic range was largely established in studies of acute mania. For other indications — including bipolar depression, unipolar depression, and maintenance treatment — there is much less evidence that a particular serum concentration is required.The appropriate principle is to treat to clinical effect, using the lowest dose that produces the desired benefit. A patient who improves at a relatively low dose does not necessarily benefit from further escalation simply to reach a conventional laboratory target.Low doses are especially useful in mood disorder, such as cyclothymia or hyperthymia, where we have found a median dose of 450 mg/d to be effective and about 60% of people have no side effects. Serum lithium concentrations remain important for assessing exposure and toxicity, but they should not automatically be regarded as a measure of therapeutic success.2. Lithium is highly toxic, particularly to the kidneys.Lithium has acquired a reputation as an inherently toxic medication, especially because of concerns about chronic kidney disease. Toxicity is certainly possible, particularly at excessive serum concentrations, but toxicity and therapeutic use should not be conflated.At appropriately prescribed doses and concentrations, lithium is generally well tolerated. Clinically meaningful chronic renal impairment occurs in about 1%-5% of long-term users, and the risk is substantially related to dosing and exposure.This does not mean that kidney effects can be ignored. Renal function, thyroid function, serum lithium concentrations, hydration, and interacting medications all require appropriate monitoring. The point is that lithium should not automatically be characterized as a highly nephrotoxic drug when used at therapeutic or low concentrations.As with other medications, dose determines whether a pharmacologic effect becomes toxicity.3. Lithium needs to be taken two or three times daily.Lithium is often prescribed in divided doses, but the transcript argues that multiple daily dosing is usually unnecessary.Because lithium has a relatively long half-life, once-daily administration — often at night — is all that is needed. Nighttime dosing can also facilitate consistent serum-level measurement the following morning.Once-daily treatment may have another potential advantage: reducing the kidney’s exposure to lithium compared with divided dosing. This is one strategy that may further reduce renal effects over long-term treatment.4. Lithium works for mania but not depression.Perhaps the most persistent misconception is that lithium is primarily an antimanic medication.Lithium has substantial evidence for the prevention of depressive as well as manic episodes in bipolar disorder. The UK-based BALANCE study directly compared lithium and valproate and found lithium to be particularly effective in preventing depressive episodes.Comparisons with lamotrigine have sometimes reinforced the impression that lithium is inferior for depression. However, such studies may be affected by their design, including selection of patients who tolerated one treatment but not another.The argument presented here is that lithium should not be viewed as merely an antimanic drug. It can have antidepressant effects and can be used as monotherapy rather than being regarded solely as an adjunct to an antidepressant.5. Lithium is useful only in bipolar disorder.Lithium is strongly associated with bipolar disorder, but its potential role extends beyond it.Lithium is effective in unipolar depression, both acutely and in prevention of recurrent depressive episodes. There is reason to challenge the sharp conceptual distinction between unipolar and bipolar depression, given similarities in their genetics, biology, and clinical course.From this perspective, it is not surprising that some treatments overlap. Lithium is one such treatment.In fact, evidence supporting lithium for prevention of depressive episodes in unipolar depression may be stronger than is commonly appreciated. Thus, lithium should not automatically be excluded simply because a patient does not meet conventional criteria for bipolar disorder.6. Lithium inevitably causes substantial weight gain.Weight gain is frequently cited as a reason to avoid lithium. However, lithium is largely weight neutral at the population level, based on meta-analytic evidence.Some patients do gain weight, but this appears to be a minority. Approximately 20% of patients experience weight gain; the magnitude is generally less than that associated with several commonly used alternatives, including olanzapine, quetiapine, and valproate.Consequently, concerns about weight should be placed in context. Avoiding lithium solely because of the possibility of weight gain may not make sense when alternative treatments may carry greater metabolic consequences.7. Lithium impairs creativity and cognition.Finally, lithium is sometimes viewed as incompatible with creativity, particularly among artists, writers, and other creative professionals.Low-dose lithium generally produces little cognitive impairment and does not inherently suppress creativity. Cognitive impairment can occur with excessive lithium exposure, but that is different from an effect at appropriately selected lower doses.There is also a broader issue: Creativity and mood elevation can be related. Mild manic or hypomanic symptoms may sometimes increase subjective creativity, whereas more severe mania can impair attention, organization, judgment, and the ability to complete creative work.We should seek “sculpted creativity”: reducing the dysfunctional aspects of severe mood elevation while preserving the energy, ideas, and productivity that some patients associate with milder mood elevation.The Larger Question: Is Lithium Underused? These misconceptions share a common consequence: Lithium may be prescribed less often than its evidence base warrants.Lithium has roles extending beyond acute mania, including mood stabilization, depression, and suicide prevention. There is emerging evidence concerning possible neuroprotective and dementia-preventive effects. Human data suggesting dementia prevention are promising, although this area requires further study.The central clinical message is not that lithium is risk-free or that conventional monitoring is unnecessary, but that its risks are much lower and laboratory monitoring is much less important than presumed. For clinicians, the most useful shift may be from asking, “What serum level does this patient need?” to asking, “What is the lowest dose that produces a meaningful clinical benefit?”That approach may help reclaim lithium’s place as a versatile treatment for mood conditions — one whose benefits extend well beyond its traditional reputation as a treatment for mania. Nassir Ghaemi, MD, MPH, is founder of Psychiatry Letter, and a lecturer on psychiatry at Harvard Medical School, Cambridge Health Alliance, in Boston. Dr Ghaemi is also an employee at Bristol Myers Squibb. The views presented here are his own and do not necessarily reflect those of his employers.