Does low-dose lithium (Lithium, 150-400 milligrams) cause less weight gain and protect against suicidal ideation (SI) issues compared to higher doses?

From the Guidelines

Low-dose lithium (150-400 mg daily) is a viable option for patients who need lithium's mood-stabilizing and anti-suicidal properties but are concerned about metabolic side effects, as it typically causes less weight gain than higher therapeutic doses while still offering protective effects against suicidal ideation. When starting low-dose lithium, begin with 150 mg daily and gradually increase as needed, monitoring response and side effects. Unlike standard lithium doses (900-1800 mg daily), which require regular blood level monitoring, low-dose lithium may require less frequent monitoring, though baseline kidney and thyroid function tests are still recommended. The mechanism behind lithium's anti-suicidal effects involves modulation of serotonin receptors and neuroprotective actions that occur even at lower concentrations 1. While low-dose lithium causes fewer side effects overall, patients should still be monitored for thirst, tremor, and gastrointestinal issues. This approach may be particularly suitable for augmentation of other mood stabilizers or antidepressants in patients with bipolar disorder or treatment-resistant depression with suicidal features. Some studies suggest that lithium may reduce the risk for suicide in patients with unipolar depression or bipolar disorder 1. However, the most recent and highest quality study found that there is insufficient evidence to recommend for or against lithium to reduce the risk of suicide or suicide attempts for patients with mood disorders 1.

Some key points to consider when using low-dose lithium include:

• Starting with a low dose (150 mg daily) and gradually increasing as needed
• Monitoring response and side effects
• Baseline kidney and thyroid function tests are still recommended
• Less frequent monitoring may be required compared to standard lithium doses
• Patients should still be monitored for thirst, tremor, and gastrointestinal issues
• This approach may be suitable for augmentation of other mood stabilizers or antidepressants in patients with bipolar disorder or treatment-resistant depression with suicidal features.

It's also important to note that other treatments, such as ketamine infusions, may also be effective in reducing suicidal ideation in patients with major depressive disorder 1. However, the evidence for these treatments is still emerging, and more research is needed to fully understand their effects.

In terms of non-pharmacologic interventions, cognitive behavioral therapy (CBT) and dialectical behavior therapy (DBT) may also be effective in reducing suicidal ideation and behavior 1. However, the evidence for these interventions is still limited, and more research is needed to fully understand their effects.

Overall, the use of low-dose lithium, as well as other pharmacologic and non-pharmacologic interventions, should be individualized and based on a thorough assessment of the patient's needs and circumstances.

From the Research

Lithium Treatment and Weight Gain

• The relationship between low-dose lithium treatment (150-400 mg) and weight gain is not explicitly addressed in the provided studies 2, 3, 4, 5, 6.
• However, it is mentioned that lithium's clinical effectiveness is counterbalanced by its safety and tolerability profile, which may include weight gain as a potential side effect 5.

Lithium Treatment and Suicide Prevention

• Lithium treatment has been shown to reduce the risk of suicidal behavior in patients with mood disorders, particularly bipolar disorder 2, 3, 4, 5, 6.
• The mechanisms behind lithium's protective effects against suicidal behavior are uncertain, but may include anti-aggressive/anti-impulsive effects and mood-stabilizing effects 2, 3, 4.
• Low-dose lithium treatment may be effective in preventing depressive recurrences and decreasing suicide risk, especially in patients with bipolar disorder 5.

Dose-Response Relationship of Lithium Treatment

• The clinical effects of lithium are maximal for mood stabilization at concentrations higher than 0.6 mEq/L, but lower levels may be sufficient for preventing depressive recurrences and decreasing suicide risk 5.
• Microdoses of lithium could be effective in decreasing suicide risk, especially in patients with bipolar disorder 5.
• The study suggests that lithium's ability to counteract cognitive decline appears to be exerted at subtherapeutic doses, possibly corresponding to its molecular neuroprotective effects 5.