Lithium in the episode and suicide prophylaxis and in augmenting strategies in patients with unipolar depression

The scientific paper Lithium in the Episode and Suicide Prophylaxis and in Augmenting Strategies in Patients with Unipolar Depression by Abou-Saleh et al. explores the critical role of lithium in managing unipolar depression. As a widely studied mood stabilizer, lithium has demonstrated significant efficacy in reducing depressive episodes, preventing relapses, and uniquely lowering suicide risk. The authors critically review decades of evidence, including randomized trials and international guidelines, to highlight lithium’s effectiveness as a long-term treatment and augmentation strategy. Despite its proven benefits, they address the underutilization of lithium in clinical practice, emphasizing the need for personalized monitoring and its potential to transform outcomes for patients with severe or recurrent unipolar depression.

Depression is one of the leading causes of illness worldwide, affecting approximately 350 million people and significantly contributing to premature death. Alongside high suicide rates, depression is linked to other serious health problems like cardiovascular disease. While antidepressants are commonly used, they often fall short in fully addressing long-term needs, such as preventing relapses or reducing suicidal behavior. Lithium, a naturally occurring mineral and mood stabilizer, has been studied extensively for its unique benefits in these areas. This scientific paper examines lithium’s role in preventing depressive episodes, its proven antisuicidal effects, and its effectiveness as an augmentation therapy for treatment-resistant cases.

The authors emphasize lithium’s potential by stating: “Lithium is unique in being the only medicine with proven antisuicidal effects and hence a lethal disease is no longer lethal.”

Unipolar depression, unlike bipolar disorder, is characterized by repeated episodes of severe low mood without the manic phases seen in bipolar disorder. It is often episodic, meaning that symptoms may remit but typically return, becoming more frequent and harder to treat over time. Some patients can spend a large portion of their lives in depressive states, with the risk of recurrence increasing after each episode. According to the study, lithium works particularly well in "carefully selected patients with unipolar depression," especially those experiencing melancholic or psychotic features.

However, modern diagnostic systems like ICD-10 and DSM-5 have broadened the definition of unipolar depression to include a broader spectrum of disorders. This has made it more challenging to identify patients who may benefit most from lithium. “Lithium will hardly work in a patient with ‘unipolar depression spectrum disease,’” the authors warn.

The scientific paper draws from a range of evidence, including randomized controlled trials (RCTs), systematic reviews, and international guidelines. Notably, the study incorporates findings from the World Federation of Societies of Biological Psychiatry (WFSBP) on maintenance treatment for major depressive disorder. The review evaluates lithium’s efficacy in preventing depressive episodes, reducing suicide risk, augmenting antidepressants, and maintaining stability following electroconvulsive therapy (ECT).

Lithium has been shown to significantly reduce the recurrence of depressive episodes. In a controlled trial, patients taking lithium spent only 4.7% of their time in depressive episodes over 27 months, compared to 30% for those on placebo. The study highlights that lithium’s benefits are most apparent after six months of treatment, underscoring the need for sustained therapy.

The authors note: “Patients with melancholic and psychotic depression, particularly those with episodic patterns, benefit the most from lithium prophylaxis.”

Lithium’s ability to reduce suicide risk is unmatched. In long-term studies, patients on lithium had a suicide rate of just 1.3 per 1,000 patient-years, compared to 5.4–10.2 per 1,000 patient-years in untreated individuals. According to the study, lithium reduces not only depressive relapses but also traits like aggression and impulsivity, which are linked to suicidal behavior.

The authors emphasize, “If patients are adequately treated with lithium, one can observe a significant reduction of up to 75% in the suicide rate.”

For patients who do not respond to standard antidepressants, adding lithium can significantly improve outcomes. A meta-analysis of lithium augmentation trials revealed a strong effect size, with a "number-needed-to-treat" of just five to achieve significant improvement. This makes lithium a highly effective option for treatment-resistant depression.

Electroconvulsive therapy (ECT) is a powerful treatment for severe, medication-resistant depression, but relapse rates are high without ongoing management. Lithium has proven effective in maintaining stability after ECT, especially when combined with antidepressants. In one trial, relapse rates were significantly lower for patients receiving both lithium and nortriptyline (39%) compared to nortriptyline alone (60%).

The authors conclude: “ECT is a very effective form of treatment for severe depression but must be accompanied by continuation therapy for its optimum effect; this continuation therapy should be maintained for up to 1 year after ECT.”

Lithium is safe when prescribed within recommended plasma levels (0.6–0.8 mmol/L) and monitored regularly to avoid side effects such as kidney issues or thyroid dysfunction. Despite these manageable risks, lithium’s life-saving benefits far outweigh its potential complications.

Despite decades of evidence, lithium remains underutilized in treating unipolar depression. Many clinicians hesitate to prescribe it due to concerns about side effects or a lack of familiarity with its use. This is troubling, as lithium is the only treatment with proven antisuicidal effects and significant relapse prevention.

The study highlights specific criteria for starting lithium, recommending its use after two depressive episodes within five years or after a single severe episode with high suicide risk. The authors also suggest that lithium might be particularly beneficial in patients with suspected bipolar features, even if they are primarily diagnosed with unipolar depression.

“Lithium treatment has the advantage that it can be easily controlled to ensure adequate dosage and compliance,” the study states. Regular monitoring and patient education are key to addressing any side effects.

Lithium stands out as a game-changer in the treatment of unipolar depression. Its ability to prevent relapses, reduce suicide risk, and enhance the effectiveness of other treatments makes it a vital option for long-term mental health management. Patients with recurrent or severe depression, especially those at high risk of suicide, should consider lithium as part of their treatment plan.

The study emphasizes that lithium’s benefits extend beyond mood stabilization, offering life-saving potential through its unique antisuicidal effects. The authors urge mental health professionals to re-evaluate lithium’s role in clinical practice and advocate for its inclusion in international guidelines.

With careful monitoring and a personalized approach, lithium has the power to transform the lives of millions affected by unipolar depression. If you or someone you know is struggling with recurrent depression or treatment-resistant symptoms, talk to a mental health professional about whether lithium could be the right choice.