Lithium For Depression: What Is It, Dosage & Side Effects 2024

Depression is a debilitating mental health illness affecting at least one in every fifteen people^[1] annually. This mental health condition can afflict anyone, including your family and friends.

Despite the advancements in psychological therapies and pharmacological interventions, many individuals with symptoms of depression face challenges in achieving remission. And maintaining long-term recovery becomes an issue as well. 

Introduced as a mood stabilizer for bipolar disorder,^[2] lithium’s profile in treating depression has been of growing interest.

In this article, we’ll highlight the many facets of lithium for depression.

What Is Lithium?

Lithium is an alkali element present in the earth’s crust. Historically, the use of lithium in psychiatry dates back to the 19th century. According to some research, it is one of the most effective^[3] psychotropic medications for treating mental illness disorders.

Lithium salts, such as lithium carbonate and lithium citrate, stabilize the brain’s chemicals, reducing mood swings,^[4] improving sleep, and alleviating^[5] other depression symptoms.

How Does Lithium Treat Depression?

Lithium has been used as a first-line treatment for bipolar disorder,^[6] a condition characterized by episodes of mania and depression. You can also apply it as an adjunctive treatment in major depressive disorder when antidepressant medications are ineffective.

According to research, lithium’s antidepressant effects^[6] are due to its capacity to control various biochemical processes, including the following:

Impact On Brain Chemistry

Research suggests that lithium affects the chemical messengers^[7] in the brain, including serotonin, norepinephrine, dopamine, glutamate, and gamma-aminobutyric acid,^[8] or GABA. These neurotransmitters affect mood regulation, and lithium’s effects on these systems contribute to its therapeutic benefits.

Lithium stimulates neurotransmission by blocking glutamate reuptake and increasing serotonin levels in the brain, potentially improving mood. Lithium’s effect on dopamine varies depending on the brain region, but it modulates dopamine release and receptor sensitivity.

Lithium also influences glutamate levels and signaling, the dysregulation of which instigates mood disorders. It also increases GABA neurotransmission,^[8] contributing to its mood-stabilizing properties.

Influence On Gene Expression

Research studies propose lithium influences gene expression^[9] in specific brain regions. Lithium targets glycogen synthase kinase 3, i.e., GSK-3, which is involved in various cellular processes, including gene regulation.

Lithium works as an inhibitor of GSK-3. By doing so, GSK-3 leads to the activation of the Wnt/β-catenin pathway,^[10] resulting in changes in gene expression. This pathway is associated with the pathophysiology of mood-related disorders. And lithium’s modulation of this pathway could contribute to its anti-depressive effects.

Effect On Transcription Factors

Lithium has also been shown to impact chromatin remodeling.^[11] Chromatin remodeling influences gene expression by modifying DNA accessibility to transcription factors. Transcription factors are proteins that bind to DNA and regulate gene transcription.

Regulation of gene transcription can influence depression by altering the expression of genes. These genes are related to neurotransmitter function, neuroplasticity, stress response, and inflammation, which may impact mood, cognition, and emotional well-being.

Lithium may affect the activity of enzymes^[12] like histone deacetylases to either promote or inhibit gene expression. By altering the activity patterns of these enzymes,^[13] lithium may influence the expression of genes involved in mood regulation and synaptic plasticity.

Influence On Neurotrophic Factors

Studies suggest lithium may influence neurotrophic factors such as brain-derived neurotrophic factors, i.e., BDNF.^[14] These neurotrophic factors stimulate neuron development and survival, and BDNF is involved in neurogenesis, synaptic plasticity, and neural connection maintenance. These factors contribute to mood regulation.

Unlike other medications, lithium has a much longer half-life,  taking 18 – 36 hours^[15] to leave the bloodstream. This means lithium medicine can stabilize your mood throughout the day. 

When Should You Use Lithium For Treating Depression?

When you use lithium to treat depression, it’s often used in conjunction with additional drugs such as antidepressants or even as a monotherapy.

Treatment-Resistant Depression

When depressed patients fail to respond adequately to standard antidepressant medications, they are considered treatment-resistant major depression. In such cases, you may consider lithium augmentation therapy, and adding lithium to the existing antidepressant regimen can enhance its effectiveness.

Bipolar Spectrum Features

Some cases occur within a broader bipolar spectrum, including cyclothymic disorder^[16] and bipolar II disorder.^[17] Patients feel mood fluctuations presenting as hypomanic or manic episodes alternating with low mood states or depression. Mental health specialists may prescribe lithium as a monotherapy to treat these mood disorders and alleviate depressive and manic symptom cycling.

Recurrent Depression

If a person suffers two failed medication treatments or episodes of recurring major depression,^[18] taking lithium may be a preventive measure. It helps by reducing the frequency and severity of depressive episodes, thus, acting as a long-term mood stabilizer.

Personalized Considerations

Individual factors may influence the decision to use lithium for treating depression. They include a positive response to lithium in the past or a possible family history of positive response to lithium.^[19]

What About Lithium And Breastfeeding?

Lithium can pass into breast milk, potentially affecting your nursing infant. Breastfeeding while taking lithium^[20] should be carefully considered since every pregnancy and mom is different. It carries potential risks and benefits that you should discuss with a healthcare professional to make an informed decision.

Note: Lithium requires careful monitoring and dosage adjustments to maintain therapeutic levels and minimize side effects. It has a narrow therapeutic range, so regular blood level monitoring^[21] is necessary to check lithium levels and maintain effective dose levels.

Lithium Dosage For Depression

The dosage of lithium antidepressants varies depending on several factors, including:

• The severity of symptoms.
• Treatment history.
• Age and weight.
• Existing health conditions like kidney disease.
• Lifestyle.
• Other medications.
• Presence of breastfeeding.^[22]

Too much lithium leads to lithium toxicity^[23] which is aggravated in hot weather. This makes it essential to avoid dehydration and to drink the right amount of fluids throughout the day.

Here’s the recommended lithium dosage for depression:^[24]

Dosage Form	Acute Mania	Long-Term Treatment of Mania
Forms of Oral Dosage (Capsules, Solution, Tablets)
Adults and children 7+, weighing more than 30 kg	2-3 times per day, 600 mg or 10 mL.	2-3 times daily, 300-600 mg or 5-10 mL.
Children 7+ years  weighing 20-30 kg	Consume 600-1500 mg or 10-25 mL in divided daily doses.	Consume 600-1200 mg or 10-20 mL in divided daily doses.
Children 7 years+ weighing <20 kg	Use and dose are determined by the doctor.	Use and dose are determined by the doctor.
Children under 7	Not recommended.	Not recommended.
Oral Dosage Form (Extended-Release Tablets)
Adults and children 12+	900 mg twice a day or 600 mg three times a day	600 mg twice a day or three times a day. Maximum of 1200 mg per day.
Children 12 years and younger	Not recommended.	Not recommended.
Breastfeeding women	600-1200 mg/day

Note: It’s not recommended to stop taking lithium suddenly, as it leads to a relapse of mania^[25] and mood instability. But, if you experience relapsed symptoms, you should call your doctor immediately as you may have to stop suddenly.  

Side Effects Of Lithium

Lithium is an effective and safe treatment for most people with major depression. But as with any medication, be aware of lithium’s potential adverse side effects,^[26] which include:

• Nausea or vomiting.
• Diarrhea.
• Fatigue and drowsiness, dizziness.
• Increased urination and excessive weight gain.
• Dry mouth^[27] and excess thirst.^[27]
• Muscle weakness or cramps.
• Interference with the production of^[28] thyroid hormones.
• Unstable lithium levels due to possible interactions with caffeine,^[29] so keep caffeine intake consistent.
• Mild hand tremors.

Less commonly, some people may experience more severe side effects^[26] such as:

• Severe hand tremors.
• Low sodium levels^[30] in the blood. Note that it is important to maintain stable sodium^[29] intakes as this can affect blood lithium levels.
• Low blood pressure or pulse.
• Blurred vision.
• Skin rashes, redness, and itching.

You should see a doctor immediately if you experience any adverse side effects They may need to adjust your dosage or try other treatment options. Note that excessive weight gain^[26] and extreme fatigue experienced by many lithium users are the primary reasons for medication noncompliance.

Conclusion

Lithium is a potent medication for the treatment of depression diagnosis. It helps by reducing the more severe depressive symptoms, alleviating suicidal thoughts, and improving quality of life. However, you must take lithium correctly with the help of a physician. This includes having regular laboratory tests to monitor for toxicity and the presence of effective blood lithium levels.

Although lithium has side effects, you can usually manage the symptoms by adequate dosing. 

But as always, seek professional help and talk to your doctor to analyze your situation and design a suitable treatment strategy. For example, planning for unwanted weight gain prevention or trying yoga for depression would be wise.

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