Is lithium still the gold standard for bipolar?

October 14, 2025 •

3 min read

For over half a century, lithium has been a first-line treatment for bipolar disorder, but its prescription rates have been declining globally despite decades of scientific evidence confirming its efficacy. This article investigates the question: Is lithium still the gold standard for bipolar? comparing its enduring benefits against modern alternatives.

Quick Summary

Lithium remains a highly effective, first-line option for bipolar disorder, particularly for long-term maintenance and suicide prevention, despite the rise of newer medications. While its use has declined, strong evidence supports its unique benefits, including neuroprotective effects, though it requires careful management of side effects.

Key Points

Enduring Efficacy: Decades of evidence support lithium's effectiveness in preventing manic and depressive episodes in bipolar disorder, surpassing some newer medications.
Unique Anti-Suicidal Property: Lithium provides a proven, unique benefit of significantly reducing suicide risk among patients with bipolar disorder.
Neuroprotective Effects: Long-term lithium use has been linked to neuroprotective benefits, potentially helping to preserve brain volume and cognitive function.
Drawbacks and Alternatives: Lithium has drawbacks like a narrow therapeutic window and specific side effects (e.g., tremors, weight gain), leading many clinicians and patients to consider alternatives like antipsychotics or other mood stabilizers.
Declining Use but Strong Recommendations: Despite a worldwide decline in its prescription, international guidelines continue to recommend lithium as a first-line option for maintenance therapy.
Personalized Treatment Approach: The modern treatment landscape requires a personalized approach, balancing lithium's long-term advantages with the faster action or different side effect profiles of newer drugs.

Lithium's Proven Efficacy

Lithium's reputation as a "gold standard" is built on a robust foundation of clinical research and decades of real-world use. No other mood stabilizer has a longer track record of demonstrated effectiveness.

Relapse Prevention: Studies show that lithium significantly reduces the risk of mood episode recurrence, preventing both manic and depressive episodes.

The Challenges of Lithium Treatment

Despite its efficacy, lithium's use has complications that have contributed to its declining prescription rates.

Side Effect Profile: Common side effects include tremors, weight gain, increased thirst, and frequent urination. Long-term use can affect kidney and thyroid function, requiring regular lab monitoring. These side effects can impact adherence.
Lower Prescription Rates: Global prescription rates have declined, linked to newer drugs, clinician discomfort with monitoring, and patient preferences. Some perceive lithium as 'old-fashioned' or difficult.

Modern Alternatives and Their Roles

The treatment landscape includes other medications approved for bipolar disorder, often preferred for specific symptoms or phases due to different side effect profiles.

Atypical Antipsychotics: Medications like quetiapine, olanzapine, and cariprazine are FDA-approved for treating manic, depressive, and maintenance phases. They may act faster for severe mania but carry risks of weight gain and metabolic side effects.
Anticonvulsants: Valproic acid and lamotrigine are used as mood stabilizers. Lamotrigine is effective for preventing depressive episodes in bipolar I disorder, where lithium's antidepressant effect may be less pronounced.

Comparing Lithium with Newer Medications

Understanding the choice between lithium and other options is aided by comparison.


Feature	Lithium	Atypical Antipsychotics (e.g., Quetiapine)	Anticonvulsants (e.g., Lamotrigine)
Efficacy in Mania	High, especially for classic, euphoric mania.	High, often with a faster onset for severe episodes.	Variable; less effective for acute mania.
Efficacy in Depression	Moderate, often better for prevention than acute treatment.	High, often FDA-approved for bipolar depression.	High, specifically for preventing depressive episodes.
Maintenance Efficacy	Excellent, significantly reduces relapse risk.	Good for relapse prevention, often used as adjunctive therapy.	Good for depression prevention, less so for mania.
Side Effects	Tremors, weight gain, thirst, potential renal/thyroid issues.	{Link: BMJ website https://gpsych.bmj.com/content/35/4/e100760}.	Rash (risk of Stevens-Johnson syndrome), dizziness, sedation.
Monitoring	Regular blood tests for therapeutic drug levels, kidney, and thyroid function.	Less frequent monitoring than lithium, but check for metabolic changes.	Less frequent monitoring, but must watch for rash.
Unique Benefits	Strong anti-suicidal effects, neuroprotective properties.	Rapid onset of action for acute symptoms.	Better for bipolar depression and generally well-tolerated with less weight gain.

Conclusion: The Nuanced 'Gold Standard'

Is lithium still the gold standard for bipolar disorder? Yes, but its role is now part of a broader treatment landscape. While international guidelines recommend it as a first-line agent, especially for maintenance, newer medications allow for more personalized plans. Lithium's long-term efficacy, anti-suicidal, and neuroprotective effects maintain its importance. However, its narrow therapeutic window and potential side effects mean newer drugs with different profiles are also valuable options. {Link: BMJ website https://gpsych.bmj.com/content/35/4/e100760}.

For further information on lithium research, visit the National Institutes of Health website at https://www.ncbi.nlm.nih.gov/.

Frequently Asked Questions (FAQs)

Frequently Asked Questions

The decline is due to a combination of factors, including the introduction of newer antipsychotic and anticonvulsant drugs, pharmaceutical marketing for these alternatives, clinician discomfort with the required blood monitoring, and patient concerns over side effects.

Lithium has superior, long-term relapse prevention benefits, particularly in classic bipolar cases, and is associated with lower rates of suicide. However, newer antipsychotics like quetiapine can have a faster onset of action for acute mania and are also FDA-approved for bipolar depression.

Common side effects include tremors, weight gain, increased thirst, and frequent urination. Long-term use can also affect kidney and thyroid function, requiring regular monitoring.

Lithium has a narrow therapeutic window, meaning the effective dose is close to a toxic dose. Regular blood tests ensure that the lithium level stays within a safe and effective range, minimizing the risk of toxicity and managing side effects.

Lithium is very effective for treating acute mania and is the gold standard for preventing both manic and depressive episodes in the long term. However, its effectiveness for treating an ongoing depressive episode can be modest compared to some newer medications.

Yes, lithium can be used in children and, with careful management, in pregnant women. However, special considerations apply to dosing and monitoring, and potential adverse effects must be carefully weighed against the risk of untreated bipolar disorder.

Abruptly discontinuing lithium can lead to a high risk of relapse or rebound mania, often more severe than the original episodes. It is recommended to reduce the dose gradually under a doctor's supervision.