From the Guidelines
Ultra-low dose lithium supplementation is not recommended as a first-line treatment for depression due to limited evidence and potential risks. When considering the use of ultra-low dose lithium supplementation for depression, it is essential to weigh the potential benefits against the risks. The evidence for its effectiveness in treating depression is limited, and most studies have been small or observational, lacking rigorous clinical trials 1. Some studies suggest that lithium can be used to augment antidepressant drugs, but this is typically at higher dosages, with blood levels of 0.2 to 0.6 mEq per L (0.2 to 0.6 mmol per L) being generally adequate, usually achieved with dosages of 150 to 300 mg per day 1. However, at higher lithium dosages, elderly patients are prone to develop neurotoxicity, highlighting the need for caution and monitoring, even at low doses 1. Other evidence focuses on the treatment of bipolar disorder, where lithium is approved for use in adults and adolescents, but its efficacy in children and adolescents is less well-established 1. Given the limited evidence and potential risks, traditional antidepressants, psychotherapy, and lifestyle modifications remain better-established first-line treatments for depression, with more substantial evidence supporting their effectiveness. If ultra-low dose lithium supplementation is considered, it should be done under medical supervision, with regular monitoring of kidney and thyroid function, as well as blood lithium levels. Key points to consider when evaluating the use of ultra-low dose lithium supplementation for depression include:
- Limited evidence for its effectiveness in treating depression
- Potential risks, including neurotoxicity at higher dosages
- Need for monitoring and medical supervision
- Availability of better-established first-line treatments for depression.
From the Research
Effectiveness of Ultra-Low Dose Lithium Supplementation for Depression
- The effectiveness of ultra-low dose lithium supplementation for treating depression has been explored in several studies 2, 3, 4, 5, 6.
- A study published in 2012 found that low-dose lithium augmentation (300-450 mg/day) was effective in treating patients with resistant depression, with 51% of patients showing significant improvement after 5 weeks of treatment 2.
- Another study published in 2017 reviewed the evidence for the use of lithium in the long-term management of unipolar depression, and found that lithium was effective in preventing recurrent episodes of depression and reducing the risk of suicide 3.
- A review of lithium's effects on the brain and blood found that lithium acts through multiple pathways to inhibit glycogen synthetase kinase-3beta (GSK3 beta), leading to increased cell growth and protection programs, and may explain why lithium increases brain cell density and volume in patients with bipolar disorders 4.
- A study published in 2014 confirmed the central role of lithium in the treatment of bipolar disorder and established lithium as the drug of first choice for long-term prophylaxis in this condition, and also found that lithium augmentation was a main strategy for depressed patients not responding to an antidepressant 5.
- A clinical trial protocol published in 2013 aimed to assess the effectiveness of lithium in reducing the risk of suicidal behavior in patients with treatment-resistant depression and a history of deliberate self-harm 6.
Dosage and Safety Considerations
- The effective dose range for lithium is 0.6-1.0 mM in serum, and >1.5 mM may be toxic 4.
- Serum lithium levels of 1.5-2.0 mM may have mild and reversible toxic effects on kidney, liver, heart, and glands, while levels >2 mM may be associated with neurological symptoms, including cerebellar dysfunction 4.
- Ultra-low dose lithium supplementation may minimize the risk of side effects and drug-drug interactions, but prospective controlled studies are needed to confirm its effectiveness and safety 2.