Lithium is a mood-stabilizing medication used primarily to treat bipolar disorder. It was the first drug approved for this purpose and remains a first-line treatment decades later. What makes lithium unusual is that it’s one of the few psychiatric medications proven to significantly reduce the risk of suicide, lowering attempts and completions by roughly 80% compared to not taking it.
How Lithium Works in the Brain
Lithium is a simple element, just three protons on the periodic table, yet it influences several complex signaling systems in the brain simultaneously. Scientists still don’t fully understand why it stabilizes mood, but two mechanisms stand out. First, lithium depletes a molecule called inositol that brain cells use to relay signals. When inositol levels drop, overactive signaling pathways quiet down. Second, lithium blocks an enzyme called GSK-3, which regulates everything from cell survival to how neurons communicate with each other.
These two effects appear to be connected rather than separate. Together, they dampen the kind of runaway neural activity that drives manic episodes while also supporting pathways that protect brain cells from damage. This dual action helps explain why lithium works for both the highs and lows of bipolar disorder, something many other medications struggle to do.
What Lithium Treats
The FDA approves lithium for bipolar I disorder in patients aged 7 and older. It’s used in two ways: to bring down acute manic or mixed episodes and to prevent future episodes over the long term. For many people, the maintenance role is where lithium shines. Staying on it reduces the frequency and severity of mood swings over months and years.
Doctors also prescribe lithium off-label as an add-on for major depression that hasn’t responded to antidepressants alone, for certain vascular headaches, and occasionally for other conditions. These off-label uses are typically reserved for situations where other treatments have failed. Despite strong evidence behind it, lithium is often underutilized because clinicians worry about its side effects and the monitoring it requires.
Lithium and Suicide Risk
One of lithium’s most remarkable properties is its effect on suicidal behavior. A large meta-analysis covering over 85,000 person-years of data found that the overall risk of suicides and suicide attempts was about five times lower in people taking lithium compared to those not on it. This effect held across both bipolar disorder and other major mood disorders, with an average treatment duration of 18 months. No other psychiatric medication has this level of evidence for suicide prevention, and it’s one of the strongest arguments for choosing lithium over newer alternatives.
Common Side Effects
Lithium affects multiple organ systems, so side effects can show up in several ways. Early on, the most common complaints include increased thirst, frequent urination, mild nausea, and a fine tremor in the hands. Many of these ease as your body adjusts over the first few weeks.
Weight gain is a frequent concern, but the data is more reassuring than most people expect. A systematic review and meta-analysis found that average weight gain on lithium was less than half a kilogram (about one pound), and the result wasn’t even statistically significant. Some individuals do gain more, but lithium is not in the same category as medications known to cause substantial weight changes. Interestingly, shorter treatment durations were associated with more weight gain, suggesting the body may adjust over time.
Long-term use carries risks to the thyroid and kidneys. Lithium can slow thyroid function, sometimes enough to require thyroid hormone replacement. It can also gradually reduce kidney function over years, particularly in people who experience episodes of high lithium levels. These risks are real but manageable with regular monitoring.
Blood Monitoring and Therapeutic Levels
Lithium has a narrow window between a dose that works and one that becomes dangerous. This is why regular blood tests are non-negotiable for anyone taking it. The target range for maintenance therapy is typically 0.40 to 0.79 mmol/L, though doctors may aim higher during acute manic episodes.
When you first start lithium or change your dose, blood levels are checked frequently, often weekly. Once your levels have been stable for about 12 months, testing can often be stretched to every six months. Alongside lithium levels, your doctor will periodically check kidney function, thyroid hormones, and calcium levels to catch any organ-related changes early.
Lithium Toxicity
Because the therapeutic window is so narrow, lithium toxicity is a real concern. It’s divided into three tiers based on blood levels:
- Mild toxicity (1.5 to 2.5 mmol/L): tremors, agitation, muscle weakness, and exaggerated reflexes. You might feel jittery or unsteady on your feet.
- Moderate toxicity (2.5 to 3.5 mmol/L): confusion, muscle rigidity, and involuntary jerking movements. Thinking becomes noticeably sluggish.
- Severe toxicity (above 3.5 mmol/L): seizures, loss of consciousness, and coma. This is a medical emergency.
Toxicity most often happens when something changes how your body handles lithium. Dehydration is a major trigger, whether from illness, hot weather, or intense exercise. Anything that causes you to lose sodium (through sweat, vomiting, or diarrhea) concentrates lithium in the blood because the kidneys reabsorb lithium in place of sodium.
Medications That Raise Lithium Levels
Several widely prescribed medications can push lithium levels into dangerous territory. The most common culprits are blood pressure drugs (ACE inhibitors and ARBs), diuretics (especially thiazide-type water pills), and NSAIDs like ibuprofen and naproxen.
NSAIDs are particularly important to know about because they’re available over the counter. They reduce blood flow to the kidneys, which slows lithium excretion. Occasional use is less problematic than regular use, but if you take lithium, it’s worth choosing acetaminophen for routine aches instead. Thiazide diuretics are also high-risk because they increase sodium reabsorption in the kidneys, which directly decreases lithium clearance and can significantly spike blood levels.
If any of these medications need to be started or stopped while you’re on lithium, your lithium levels should be rechecked and your dose may need to be adjusted.
Lithium During Pregnancy
Lithium crosses the placenta, which raises concerns about fetal development, particularly heart defects. For decades, the risk of a specific heart malformation called Ebstein’s anomaly dominated the conversation. In reality, the absolute numbers are small. Ebstein’s anomaly occurs in about 7 out of every 100,000 unexposed births, and while lithium exposure does increase the relative risk, the condition remains rare in absolute terms.
A broader concern is right ventricular outflow tract defects, a category of heart malformations. A study published in the New England Journal of Medicine found these occurred in 0.60% of lithium-exposed pregnancies compared to 0.18% of unexposed pregnancies, roughly a threefold increase. That means the vast majority of lithium-exposed pregnancies don’t result in cardiac malformations, but the risk is elevated enough that the decision to continue, taper, or stop lithium during pregnancy involves weighing fetal risk against the serious consequences of untreated bipolar disorder during and after pregnancy.