Lithium has a long history as a mood stabilizer for over 60 years. It was approved by the United States Food and Drug Administration (FDA) in 1970 for bipolar disorder. While primarily used for bipolar disorder, its role in addressing depression in specific contexts is well-recognized.
Understanding Lithium’s Action
The precise biochemical mechanisms by which lithium stabilizes mood are not fully understood, but current research points to its widespread interactions within the central nervous system. Lithium influences several neurotransmitter systems, including decreasing norepinephrine release and increasing serotonin synthesis. It is also thought to modulate glutamate levels, an excitatory neurotransmitter, by maintaining a healthy balance in the space between neurons. Some theories suggest that too much glutamate contributes to mania, while too little is associated with depression.
Lithium also affects enzyme activity, inhibiting enzymes like glycogen synthase kinase 3 (GSK-3) and inositol phosphatases. Lithium’s regulation of GSK-3 may influence the body’s circadian clock and cellular responses to damaged DNA. Lithium also exhibits neuroprotective properties by preventing nerve cell death and promoting cell longevity. It can increase the expression of neuroprotective factors like brain-derived neurotrophic factor (BDNF), which is important for the health and growth of nerve cells.
Lithium’s actions also extend to the gamma-aminobutyric acid (GABA) system, an inhibitory neurotransmitter that helps regulate dopamine and glutamate. Patients with bipolar disorder often have lower GABA levels, which can lead to excitotoxicity and cell loss. Lithium has been shown to increase GABA levels in the brain and spinal fluid, facilitating GABA release and upregulating GABA-B receptors, which contributes to its mood-stabilizing effects.
Depressive Conditions Lithium Addresses
Lithium is primarily recognized for its effectiveness across the spectrum of bipolar disorder. It helps reduce the severity and frequency of these episodes and can significantly lower the risk of suicide. For many, lithium serves as a long-term maintenance therapy to prevent future mood swings.
Beyond bipolar disorder, lithium is also utilized as an augmentation strategy for treatment-resistant unipolar depression. This applies to major depressive disorder when individuals have not responded adequately to at least two different antidepressant medications. Clinical guidelines recommend lithium augmentation as a first-line approach in such cases.
Studies have demonstrated that adding lithium to an antidepressant regimen can significantly improve response rates in treatment-resistant depression. Response rates are notably higher in lithium-augmented groups compared to placebo groups. While effective, lithium’s efficacy for acute depression in bipolar disorder, when used as a sole treatment, has been described as having low-quality evidence compared to atypical antipsychotics.
Navigating Lithium Treatment
Initiating lithium treatment involves careful consideration and ongoing monitoring due to its narrow therapeutic index, meaning the difference between an effective dose and a toxic dose is small. Common side effects can include increased urination and thirst. Other frequently reported side effects are a fine hand tremor, nausea, and weight gain. While mild and improving over time, these can be bothersome for some individuals.
More serious side effects can impact kidney and thyroid function, necessitating regular blood tests. Thyroid parameters should be checked regularly before and during lithium treatment.
Lithium toxicity is a serious concern if blood levels become too high. Mild toxicity symptoms include increased weakness, tremors, poor concentration, and diarrhea. As toxicity worsens, individuals may experience vomiting, more pronounced tremors, slurred speech, lethargy, and confusion. In severe cases, toxicity can lead to seizures and be fatal. Factors like dehydration, changes in salt intake, or interactions with other medications can elevate lithium levels.
Consistent dosage and adherence to the prescribed regimen are important for lithium’s effectiveness and safety. Patients are advised to maintain a stable intake of fluids and salt, as fluctuations can impact lithium levels. Regular communication with healthcare providers is necessary to discuss any side effects, changes in health, or concerns, ensuring the treatment remains safe and effective. Blood tests are performed regularly to maintain lithium levels within the therapeutic range, usually between 0.5 mEq/L and 0.8 mEq/L for balancing efficacy and side effect risk.