From the FDA Drug Label
ADVERSE REACTIONS Lithium toxicity: The likelihood of toxicity increases with increasing serum lithium levels. ... The following adverse reactions have been reported and do not appear to be directly related to serum lithium levels ... Thyroid Abnormalities: Euthyroid goiter and/or hypothyroidism (including myxedema) accompanied by lower T3 and T4. ... Miscellaneous reactions unrelated to dosage are: Transient electroencephalographic and electrocardiographic changes, leucocytosis, headache, diffuse non-toxic goiter with or without hypothyroidism, transient hyperglycemia, generalized pruritis with or without rash, cutaneous ulcers, albuminuria, worsening of organic brain syndromes, excessive weight gain, edematous swelling of ankles or wrists, and thirst or polyuria, sometimes resembling diabetes insipidus, and metallic taste.
The long-term risks of low-dose lithium treatment for Major Depressive Disorder (MDD) include:
- Thyroid abnormalities: such as euthyroid goiter and/or hypothyroidism
- Renal and cardiovascular risks: although not directly stated for low-dose, the overall risk of lithium toxicity is high in patients with significant renal or cardiovascular disease 1
- Neuromuscular and central nervous system effects: such as tremor, muscle hyperirritability, ataxia, and psychomotor retardation
- Other adverse reactions: including headache, generalized pruritis, cutaneous ulcers, albuminuria, and edematous swelling of ankles or wrists It is essential to monitor serum lithium levels and adjust the dose accordingly to minimize the risk of toxicity 1.
From the Research
Long-term low-dose lithium treatment for Major Depressive Disorder carries several potential risks that require monitoring, including kidney function impairment and thyroid dysfunction, but its effectiveness in preventing depressive episodes and reducing suicide risk makes it a valuable treatment option. The most significant concerns with long-term low-dose lithium treatment include:
- Kidney function impairment, with possible development of chronic kidney disease after years of use
- Thyroid dysfunction, particularly hypothyroidism which affects 5-35% of patients on long-term lithium 2
- Cognitive effects, such as mild memory problems or mental slowing in some patients
- Disruption of calcium metabolism, potentially leading to hyperparathyroidism and increased risk of hypercalcemia in 10-25% of patients
- Weight gain, affecting approximately 20% of patients Low-dose lithium (typically 150-600 mg daily, maintaining blood levels of 0.4-0.8 mEq/L) generally has fewer side effects than standard doses used for bipolar disorder, but still requires regular monitoring of kidney function, thyroid function, and lithium levels every 3-6 months 3. Patients should maintain consistent salt and fluid intake to avoid fluctuations in lithium levels. The risk-benefit profile must be individually assessed, as lithium has demonstrated effectiveness in preventing depressive episodes and reducing suicide risk in MDD, particularly in treatment-resistant cases, despite these potential long-term risks 4, 5.
Some key points to consider when prescribing low-dose lithium for MDD include:
- Regular monitoring of kidney function, thyroid function, and lithium levels
- Maintaining consistent salt and fluid intake to avoid fluctuations in lithium levels
- Individual assessment of the risk-benefit profile, taking into account the patient's medical history and treatment goals
- Consideration of alternative treatment options, such as other antidepressants or augmentation therapies, if lithium is not effective or is not tolerated well. It's also important to note that lithium has been shown to be effective in preventing depressive episodes and reducing suicide risk in MDD, particularly in treatment-resistant cases, as stated in the study published in the Journal of psychopharmacology (Oxford, England) 4.
In terms of treatment patterns, a study published in BMC psychiatry found that patients with MDD and suicidal ideation or attempt often receive multiple treatment classes simultaneously, and may require four or more unique class-based regimens within a year 6. This highlights the complexity of treating MDD, particularly in patients with suicidal ideation or attempt, and the need for individualized treatment approaches.
Overall, while long-term low-dose lithium treatment for MDD carries potential risks, its effectiveness in preventing depressive episodes and reducing suicide risk makes it a valuable treatment option, particularly in treatment-resistant cases. Regular monitoring and individual assessment of the risk-benefit profile are essential to ensure safe and effective treatment.