Lithium for Depression: Unveiling Its Potential

Lithium, a medication renowned for managing mood disorders like bipolar disorder, is gradually gaining recognition for its role in treating depression. However, its utilization for depression remains relatively low in the United States compared to some European countries [8]. This article discusses how lithium can be used to treat depression and other mental health conditions, and we will also explore alternative treatments like TMS and esketamine (Spravato).

When and Why is Lithium Used to Treat Depression?

Lithium is a commonly prescribed medication for managing bipolar disorder, which has been a significant treatment for over 50 years. Even though the pharmaceutical industry hasn’t focused on it much lately, studies have shown that taking lithium can help relieve more severe depressive symptoms [5-6,8].

The decision to prescribe lithium for depression or bipolar disorder depends on the severity of the condition and the patient’s response to prior treatments. It’s important to talk to your doctor about your treatment options and consider potential risks, particularly for pregnant women, to find the best solution for your specific needs.

Effectiveness of Lithium in Treating Depression

Lithium is a medication commonly used to treat bipolar affective disorder. However, it has gained attention for its potential use in treating depression and major depressive disorder, especially in individuals who have found other antidepressant treatments ineffective [9].

One recent study examined how lithium compared to other treatments in addressing unipolar depression, and they found that when lithium was used alongside standard antidepressant therapy, it produced positive outcomes [9]. The study found on average, 1 out of 5 depressed patients treated with lithium added to their antidepressant regimen would experience significant improvements in their mood disorder compared to using a placebo [9].

Lithium can help treat depression when other approaches have failed. However, individual responses to lithium can vary. Working with a healthcare provider is important when considering lithium as a treatment option. Remember that it may take time to see the full benefits, and results can vary from person to person [6,9].

In a study, patients initially receiving various antidepressant medications were randomized into two groups. One group continued their antidepressants, while the other switched to lithium treatment. The study found that lithium was effective in reducing the risk of relapse and was well-tolerated by patients. However, the study also highlighted specific side effects of lithium compared to a placebo, including tremors and increased thirst. Adding lithium to standard antidepressant therapy is an effective way to prevent relapse in patients with depression, but it’s important to consider its potential side effects when prescribing it to patients [2]

Potential Side Effects

Lithium is a medication with proven effectiveness in managing mood disorders like bipolar disorder and, more recently, depression. However, like any medication, it can come with potential side effects. Some common side effects include[6,8i]:

  • Tremors: Some patients may experience tremors, characterized by shaky movements, often in the hands.
  • Increased Thirst: Lithium can lead to increased thirst (polydipsia).
  • Changes in Taste: Some individuals may notice changes in how things taste while on lithium treatment.
  • Nausea: Nausea is a possible side effect of lithium.
  • Diarrhea: Diarrhea can occur in some patients undergoing lithium treatment.

It’s important to note that these side effects may not affect every patient, and their intensity can vary. Diligent monitoring by healthcare professionals is essential to manage and alleviate these side effects when they arise.

More Serious Side Effects

Beyond these common side effects, there are more serious potential side effects, such as [3]:

  • Kidney Damage: Long-term lithium use can reduce kidney function (nephrotoxicity). Regular kidney function monitoring during treatment is crucial.
  • Cerebellar Damage (Ataxia): Some patients may experience cognitive and neurological deficits due to cerebellar damage, known as SILENT. This can result from lithium poisoning
  • Thyroid Side Effects: Lithium accumulates in the thyroid, causing hypothyroidism and goiter. Hypothyroidism is more common, especially in women and those with a family history of thyroid issues.
  • Metabolic Side Effects: Lithium treatment often leads to weight gain, potentially causing obesity in some, particularly women. Factors include high-calorie drinks, insulin-like actions on metabolism, and sodium retention. Lithium augmentation of antidepressants may also lead to weight gain.
  • Calcium and Bone Metabolism: Lithium may induce hyperparathyroidism and affect calcium metabolism but could positively impact bone density in bipolar disorder patients.
  • Cognitive Side Effects: Lithium treatment may cause moderate cognitive impairment, but some studies suggest potential benefits. Mental issues in bipolar patients may worsen during episodes, but lithium might not exacerbate pre-existing cognitive impairments.
  • Dermatological Side Effects: Lithium-induced dermatological effects include worsened acne and psoriasis. In some cases, it may lead to the remission of psoriatic changes due to its immunomodulatory activity.
  • Cardiological Side Effects: Lithium therapy can lead to various cardiac effects, including bradycardia, ECG changes, and potential arrhythmias. The extent of ECG changes depends on treatment duration and serum concentration.
  • Sexual Side Effects: Rarely, lithium-treated patients may experience reduced sexual thoughts, worsened erectile function, and diminished sexual satisfaction. Concomitant use of benzodiazepines may increase the risk of sexual dysfunction.

Lithium remains a valuable tool in managing mood disorders, but it’s important to be aware of both common and more severe potential side effects. Open communication with your healthcare provider and regular health check-ups are key to ensuring lithium’s safe and effective use. Remember that the benefits of lithium should be weighed against potential risks, especially in long-term treatment [3,6].

Pros and Cons of Lithium for Depression

Benefits of Lithium for Depression

  • Effectiveness: Lithium can be highly effective in managing depression, especially in treatment-resistant cases [6].
  • Mood Stabilization: It not only treats depression but also helps prevent manic episodes, making it a valuable option for individuals with bipolar disorder [6].
  • Long-Term Stability: Maintaining therapeutic lithium levels strongly predicts long-term stability [6,8].
  • Effectiveness in Preventing Severe Depressive Relapses: Lithium has demonstrated effectiveness in preventing severe depressive relapses that require hospitalization in individuals with unipolar affective disorder [2]. This can be particularly beneficial for those with recurrent and severe depressive episodes. 
  • Anti-Suicidal Effects: Lithium has a significant anti-suicidal effect, reducing the risk of suicide in individuals with mood disorders [3]. This can be a crucial benefit for patients at risk of self-harm or suicide.
  • Anti-Dementia Effects: Some studies suggest potential anti-dementia effects of lithium, although more research is needed in this area [3].

Cons (Drawbacks) of Lithium Treatment for Depression:

These drawbacks should be carefully weighed against the potential benefits when considering lithium as a treatment for depression, and decisions should be made in consultation with a healthcare provider. Regular monitoring and open communication with healthcare professionals are crucial to ensure lithium’s safe and effective use.

  • Variability in Side Effects, Response, and Effectiveness: Lithium may cause several side effects, such as tremors, increased thirst, nausea, weight gain, kidney and thyroid problems, and mental/cardiological effects. The severity and likelihood of these side effects can vary among individuals. Lithium’s response and effectiveness vary among people, making it less predictable than other antidepressants. [3,4,6,9.
  • Necessity for Regular Monitoring: Lithium treatment requires regular monitoring of lithium levels and overall health, which can be burdensome for some patients [1,3,6].
  • Long-Term Risks: Long-term use of lithium may carry risks, including chronic kidney disease and metabolic effects such as weight gain [3].
  • Thyroid Dysfunction: Lithium can lead to thyroid dysfunction, particularly hypothyroidism and goiter, requiring regular thyroid function tests and potential thyroid hormone replacement therapy [3].

These drawbacks should be carefully considered and discussed with a healthcare provider when contemplating lithium as a treatment for depression. Regular monitoring and open communication with healthcare professionals are essential to ensure lithium’s safe and effective use.

Reasons to Discontinue Lithium Treatment

There are situations where discontinuing lithium treatment may be appropriate:

  • Intolerable Side Effects: If side effects become too severe or significantly affect a patient’s quality of life.
  • Ineffectiveness: If the medication fails to provide relief from depression symptoms. 
  • Pregnancy or Planning Pregnancy: Lithium is generally not recommended during pregnancy due to potential risks to the fetus [6,8].
  • Psychiatric Reasons: Patients may discontinue lithium due to various psychiatric concerns, including non-adherence, fear of adverse effects, disagreement with diagnosis, or refusal to take medication [7].
  • Physical Health Reasons: Discontinuation may be necessary for unintentional lithium intoxication, pregnancy or planned pregnancy, or the emergence of physical health problems unrelated to bipolar disorder [7].
  • Adverse Effects: Lithium treatment often causes negative side effects, so many people stop taking it. These include kidney and urinary tract issues, endocrine system effects, central nervous system effects, psychological adverse effects, cognitive adverse effects, and gastrointestinal tract problems [7].

Monitoring Lithium Levels and Toxicity

Before starting lithium, it’s crucial to get some tests done, like kidney and thyroid function tests and, for those over 50, an electrocardiogram (ECG). These tests should be repeated regularly during lithium treatment. Doctors must also check the lithium level in a person’s blood regularly to ensure they get the correct dose. If the levels of the medication are too high at any point, this may result in lithium toxicity. Too much lithium can be harmful, potentially leading to severe problems like kidney issues, heart rhythm disturbances, and even seizures [1].

Effectiveness of Lithium in Treating Depression

The efficacy of lithium in treating major depressive disorder is evident when added to standard antidepressant therapy [9]. Lithium had the highest odds ratio (OR) compared to other treatments studied, indicating superior effectiveness [9]. The Number Needed to Treat (NNT) for lithium was 5, suggesting that approximately one out of five patients treated would respond to adding lithium to an antidepressant compared to a placebo [9].

Alternative Treatment Options

While lithium is a valuable option for depression treatment, it’s worth noting that other innovative therapies have emerged in recent years. Two notable examples include Esketamine and Transcranial Magnetic Stimulation (TMS). These alternatives offer individuals additional avenues for finding relief from depression when standard treatments have proven ineffective.

Esketamine: esketamine is an NMDA receptor antagonist that received FDA approval for treating treatment-resistant major depression. Administered as a nasal spray, esketamine, also known as Spravato, can rapidly relieve severe depressive symptoms, making it a promising option for individuals who have not responded to traditional antidepressants after two failed medication treatments.

 Transcranial Magnetic Stimulation (TMS): TMS therapy is a non-invasive procedure that uses magnetic fields to stimulate nerve cells in the brain. It has been approved for treating depression when standard treatments have proven ineffective. TMS offers a well-tolerated alternative for individuals seeking relief from depression.

Explore Treatment Options

While lithium is primarily associated with bipolar disorder, it can also be crucial in managing treatment-resistant depression, especially in cases where other treatments have proven ineffective. Its effectiveness varies among individuals, and potential side effects must be weighed against the benefits. Additionally, TMS therapy represents a promising alternative for those seeking relief from depression.

Don’t let severe depression hold you back from living a fulfilling life. Contact Neuro Wellness Spa today to explore our treatment options for depression and learn more about alternative treatments such as TMS therapy. Our compassionate team is ready to listen, support, and guide you towards a brighter future.


  1. Chokhawala K, Lee S, Saadabadi A. Lithium. [Updated 2023 Feb 26]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan-. Available from:
  2. Cipriani, A., Smith, K., Burgess, S., Carney, S., Goodwin, G., & Geddes, J. (2006). Lithium versus antidepressants in the long-term treatment of unipolar affective disorder. The Cochrane database of systematic reviews, 2006(4), CD003492. 
  3. Ferensztajn-Rochowiak, E., & Rybakowski, J. K. (2023). Long-Term Lithium Therapy: Side Effects and Interactions. Pharmaceuticals (Basel, Switzerland), 16(1), 74.
  4. Gitlin M. (2016). Lithium side effects and toxicity: prevalence and management strategies. International journal of bipolar disorders, 4(1), 27.
  5. Licht R. W. (2012). Lithium still a major option in the management of bipolar disorder. CNS neuroscience & therapeutics, 18(3), 219–226.
  6. Malhi, G. S., Bell, E., Outhred, T., & Berk, M. (2020). Lithium therapy and its interactions. Australian prescriber, 43(3), 91–93.
  7. Öhlund, L., Ott, M., Oja, S., Bergqvist, M., Lundqvist, R., Sandlund, M., Salander Renberg, E., & Werneke, U. (2018). Reasons for lithium discontinuation in men and women with bipolar disorder: a retrospective cohort study. BMC psychiatry, 18(1), 37.
  8. Post R. M. (2018). The New News about Lithium: An Underutilized Treatment in the United States. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 43(5), 1174–1179.
  9. Vázquez, G. H., Bahji, A., Undurraga, J., Tondo, L., & Baldessarini, R. J. (2021). Efficacy and Tolerability of Combination Treatments for Major Depression: Antidepressants plus Second-Generation Antipsychotics vs. Esketamine vs. Lithium. Journal of psychopharmacology (Oxford, England), 35(8), 890–900.
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