Major Research Findings

Lithium is a commonly prescribed drug for treating bipolar disorder, and its efficacy in alleviating acute mania has been confirmed by several studies. 23 While it is considered a gold standard for maintaining treatment, the potential side effects and risks associated with long-term use can make implementation challenging. 3 These side effects can include renal issues, thyroid problems, weight gain, and neurological side effects. 2 Research has also shown that side effects can vary depending on gender. 18 Furthermore, lithium can affect collagenous tissues, causing structural changes in collagen fibrils. 20

Reasons for Side Effects

The side effects of lithium can be attributed to its interaction with various tissues and organs in the body, including the kidneys, thyroid gland, nervous system, and collagenous tissues. 17 It is known that lithium can affect these organs, leading to various side effects such as renal insufficiency, hypothyroidism, weight gain, and neurological symptoms. 4 The specific side effects may vary depending on the dosage and duration of treatment, as well as the individual's health condition.

Common Side Effects

Kidney

Lithium can affect the kidneys and potentially lead to renal insufficiency or even renal failure. 17 A study found that rats given lithium exhibited impaired kidney function. 2 Moreover, research suggests an increased risk of renal failure in patients on lithium therapy. 8 This systematic review provides an overview of preventive and management strategies for lithium-induced nephrogenic diabetes insipidus and lithium nephropathy. It emphasizes the importance of monitoring for these conditions as early diagnosis and treatment can prevent further damage.

Thyroid

Lithium can interfere with thyroid function, potentially causing hypothyroidism. 17 Animal studies have shown reduced thyroid hormone levels in rats given lithium. 2 A systematic review and meta-analysis confirmed the well-known suppressive effects of lithium on the thyroid. It recommended regular monitoring of serum calcium levels during lithium therapy.

Weight

Lithium is associated with weight gain. 2 A systematic review and meta-analysis found that weight gain is more frequent under lithium treatment than placebo. However, the rate of weight gain is less frequent than under olanzapine.

Neurological

Lithium can also cause neurological side effects, including tremor, cognitive impairment, and motor deficits. 16 The study reported induction of neuronal apoptosis in various brain regions and the presence of motor deficits in mice treated chronically with lithium. It also suggested that lithium-induced apoptosis and motor deficits could be prevented by administration of cyclosporin A. 10 This review summarizes the knowledge base on side effects and toxicity of lithium and suggests optimal management of these problems. It highlights that lithium can cause cognitive impairment and recommends strategies for minimizing side effects.

Other Side Effects

Lithium can affect various other systems in the body. It can cause gastrointestinal issues like nausea, diarrhea, and thirst. 10 It can also affect the skin, leading to skin disorders. 9 Lithium can also affect sexual function, leading to reduced testosterone levels in men and increased estradiol levels in women. 17 In addition, lithium can cause cognitive side-effects, impacting memory and speed of information processing. 21 However, these side effects often occur without subjective complaints, and it is crucial to assess for them, especially when considering driving performance.

Countermeasures for Side Effects

Kidney

Regular blood tests are essential for monitoring kidney function during lithium therapy. 15 Early diagnosis and treatment are crucial to prevent further damage. It is also recommended to use a once-daily dosing schedule, target the lowest effective serum lithium level, and prevent lithium intoxication. 8 If renal insufficiency progresses, discontinuation of lithium therapy or switching to a different mood stabilizer should be considered. 8 In some cases, off-label therapy with amiloride might be helpful. 8

Thyroid

Regular monitoring of thyroid function through blood tests is essential. Hypothyroidism can be easily diagnosed and treated with L-thyroxine substitution therapy. 2 It is not an indication to stop lithium administration. 2

Weight

Lifestyle changes, including dietary modifications and exercise, can help mitigate weight gain associated with lithium. 2

Neurological

Dosage reduction, use of sustained-release preparations, or combination therapy with other mood stabilizers can help manage neurological side effects. 23 In some cases, the use of side effect antidotes may be necessary. 10

Comparison Between Studies

Commonalities Between Studies

Multiple studies have identified renal issues, thyroid problems, weight gain, and neurological side effects as common side effects of lithium therapy. 2 17 18 Research has consistently shown that lithium can negatively affect these organs, emphasizing the importance of monitoring and management.

Differences Between Studies

The specific side effects and their prevalence may differ between studies due to variations in patient populations, dosages, treatment duration, and research methodologies. 18 3

Things to Keep in Mind for Real-Life Applications

While lithium is a valuable treatment for bipolar disorder, it's important to be aware of its potential side effects and risks. Open communication with your doctor is crucial to assess the risks and benefits, manage potential side effects, and ensure adherence to treatment. Regular monitoring of kidney function and thyroid function is essential, and adjustments to dosage or alternative medications may be necessary. 8 2

Limitations of Current Research

Research on the long-term effects of lithium therapy is limited, and more comprehensive studies are needed to better understand these potential impacts. 3 Additionally, further research is required to determine the genetic factors influencing an individual's response to lithium treatment and the likelihood of experiencing side effects. 7

Future Research Directions

Future research should focus on developing new therapeutic approaches to mitigate lithium's side effects and prevent them altogether. This includes investigating potential biomarkers that can predict the occurrence of side effects. Furthermore, research on the long-term consequences of lithium therapy is crucial for understanding its long-term impact on patients' health. 3

Conclusion

Lithium remains a valuable treatment for bipolar disorder, but its side effects must be considered. Understanding the potential risks and benefits, open communication with your healthcare provider, and regular monitoring are essential for managing these side effects effectively. Further research is needed to improve our understanding of the long-term effects of lithium and to develop strategies for preventing and managing these side effects. 3