Yes, lithium is still prescribed and remains a first-line treatment for bipolar disorder. It has been FDA-approved for treating manic episodes and preventing their return since the 1970s, and no newer medication has managed to dislodge it from clinical guidelines. If anything, prescription rates for bipolar disorder have been climbing in recent years, not falling.
Why Lithium Is Still a Front-Line Option
Lithium holds a unique position among psychiatric medications. It works for acute mania, long-term mood stabilization, and bipolar depression, a range that few single drugs can match. Major clinical guidelines list it alongside newer anticonvulsants and antipsychotics as a first-line choice for mania, and it stands as one of only two medications (the other being valproate) with the strongest evidence for long-term maintenance therapy. Combining lithium with an antipsychotic during acute manic episodes produces faster and stronger results than using either type of medication alone.
Data from a Bavarian psychiatric drug surveillance project found that lithium prescriptions for bipolar disorder actually increased from 28.8% of inpatients in 2014 to 34.4% in 2019. Prescription rates for treatment-resistant depression held steady at about 4.6% over the same period. The concern that lithium was being abandoned in favor of newer, more heavily marketed drugs doesn’t appear to match the data.
What Makes Lithium Unusual
Lithium is one of the simplest substances in all of psychiatry. It’s a naturally occurring element, not a complex synthetic molecule. At a cellular level, it dials down the activity of an enzyme that is normally always “on” in resting brain cells. This enzyme influences a wide range of signaling pathways tied to mood regulation, and lithium’s ability to quiet it appears to be central to its mood-stabilizing effects. Because it targets these pathways somewhat selectively, it can treat bipolar symptoms without broadly disrupting normal brain function.
Perhaps the most remarkable property of lithium is its effect on suicide risk. People with bipolar disorder attempt suicide at extraordinarily high rates, with 25 to 50 percent making at least one attempt during their lifetime. Lithium consistently reduces this risk. Patients who take it have fewer suicide attempts and fewer deaths from all causes compared to those on placebo. This protective effect holds even in people whose mood symptoms don’t respond particularly well to the drug, suggesting the anti-suicidal benefit operates through a separate mechanism. Even filling a lithium prescription just once, compared to never refilling it, is associated with lower suicide risk, and the benefit grows with each refill.
Beyond Bipolar: Boosting Antidepressants
Lithium is also used as an add-on for people with unipolar depression (standard depression, not bipolar) who haven’t responded to antidepressants alone. The large STAR*D trial, one of the biggest depression treatment studies ever conducted, found that about 16% of patients who hadn’t improved after multiple medication trials benefited from adding lithium. Canadian clinical guidelines have recommended it as a first-line augmentation strategy for stubborn depression. It works relatively quickly in this role and, when effective, should be continued for at least a year to prevent relapse.
The Monitoring It Requires
The main reason lithium has a reputation as a “difficult” medication is the monitoring involved. It has a narrow therapeutic window: blood levels need to stay between roughly 0.8 and 1.2 mEq/L during initial treatment and 0.8 to 1.0 mEq/L for maintenance. Levels above 2.0 mEq/L are toxic. That gap between helpful and harmful is smaller than for most psychiatric drugs, so regular blood draws are non-negotiable.
Most guidelines recommend checking lithium blood levels at least twice a year once you’re on a stable dose. Your kidney function (measured through creatinine levels) also needs monitoring at least every six months, because lithium is processed entirely by the kidneys. Thyroid function should be checked at least once a year, since lithium can slow thyroid activity over time. Before starting lithium, your doctor will typically run baseline kidney and thyroid tests.
Long-Term Kidney and Thyroid Effects
The kidney concern is real but often overstated. A large nationwide study from Iceland found that about 10.4% of people on lithium developed stage 3 or higher chronic kidney disease over the course of treatment, compared to 3% in a matched control group. That translates to roughly double the risk after adjusting for age, sex, and other health conditions. This is meaningful, but it also means that nearly 90% of lithium users in the study did not develop significant kidney problems. Consistent monitoring catches early changes in kidney function, which is why the blood work schedule matters.
Thyroid effects are more common but also more manageable. Lithium can cause an underactive thyroid, which is typically treated simply by adding a thyroid hormone supplement. This side effect doesn’t usually require stopping lithium.
Lithium and Pregnancy
For decades, lithium carried a reputation as extremely dangerous during pregnancy, based on early registry data suggesting a high rate of a specific heart defect called Ebstein’s anomaly. More recent research, including a large study published in the New England Journal of Medicine, found the risk is real but much smaller than originally feared. Cardiac malformations occurred in about 2.4% of lithium-exposed infants compared to 1.15% of unexposed infants, an increase of roughly 1 extra case per 100 births. The risk is dose-dependent: daily doses above 900 mg tripled the risk of certain heart defects, while doses of 600 mg or less showed no statistically significant increase.
Because lithium continuation during pregnancy also reduces the chance of mood episode relapse (which carries its own serious risks for both mother and baby), the decision to continue or stop is highly individual. It remains a first-line treatment for the roughly 1% of reproductive-age women with bipolar disorder in the U.S.
Why It Persists Despite Newer Drugs
Lithium costs very little, since it’s a generic medication with no patent. It has over 70 years of clinical data behind it. No other psychiatric drug has demonstrated the same combination of mood stabilization, relapse prevention, and suicide risk reduction. Newer antipsychotics and anticonvulsants are valuable alternatives, especially for people who can’t tolerate lithium’s side effects or monitoring demands, but they haven’t replaced it. For many people with bipolar disorder, lithium still works better than anything else available.