Depakote (divalproex sodium) and lithium are medications frequently prescribed to manage mood disorders, particularly bipolar disorder. Both are recognized for their mood-stabilizing properties. While they share some applications, their distinct profiles lead to different considerations in their use.
Primary Uses and Effectiveness
Depakote and lithium serve as distinct treatments for various conditions, with a notable focus on bipolar disorder. Lithium is a standard treatment for classic euphoric mania, characterized by elevated mood, increased energy, and irritability. It is also effective in preventing future manic and depressive episodes, making it a common choice for long-term maintenance therapy in bipolar disorder. It also reduces the risk of suicide in bipolar patients.
Depakote is often preferred for managing mixed episodes, which involve simultaneous symptoms of mania and depression, including rapid mood shifts. It is frequently selected for individuals experiencing rapid-cycling bipolar disorder, characterized by four or more mood episodes within a single year, where lithium may sometimes be less effective. Studies indicate Depakote can be as effective as lithium in reducing acute mania symptoms.
Beyond bipolar disorder, Depakote has additional approved uses that distinguish it from lithium. It is prescribed as an anticonvulsant for various types of seizures, including complex partial and absence seizures, serving as both monotherapy and adjunctive therapy. It is also approved as a preventative treatment for migraine headaches, offering broader applications beyond mood stabilization.
How They Work in the Brain
The ways Depakote and lithium influence brain activity to stabilize mood differ considerably. Depakote is understood to increase levels of gamma-aminobutyric acid (GABA) in the brain. GABA is an inhibitory neurotransmitter, calming excessive neuronal activity, which contributes to seizure control and mood stabilization. Depakote also affects voltage-gated sodium channels and T-type calcium channels, helping to prevent hyperexcitability of neurons.
Lithium’s mechanism of action is complex and not fully understood, involving multiple brain pathways. It is thought to influence intracellular signaling pathways, such as inhibiting enzymes like glycogen synthase kinase-3 (GSK-3) and inositol monophosphatase. These actions can alter protein phosphorylation and modify gene expression, leading to neuroplastic changes associated with mood stabilization. Lithium also modulates various neurotransmitter systems, including dopamine, glutamate, and serotonin, and can enhance GABA-mediated neurotransmission, contributing to mood regulation.
Side Effects and Safety Profiles
Both Depakote and lithium have distinct side effect profiles that require careful consideration and monitoring. Understanding these differences is important for managing treatment.
Depakote
Common side effects of Depakote include weight gain, drowsiness, and gastrointestinal issues such as nausea, abdominal pain, and diarrhea. Hair loss and tremors are also reported. More serious risks include potential liver damage, which can be severe and, rarely, fatal, especially in young children or patients with mitochondrial disorders. This risk is highest within the first six months of treatment, but liver problems can occur at any time.
Pancreatitis, a life-threatening inflammation of the pancreas, and elevated blood ammonia levels leading to hyperammonemic encephalopathy (confusion, tiredness, vomiting) are also serious effects. A significant concern is its potential to cause severe birth defects, particularly neural tube defects like spina bifida, if taken during pregnancy. It can also lead to decreased IQ and increased risks for autism and ADHD in children exposed in utero, making it a high-risk option for women of childbearing age.
Lithium
Common side effects of lithium include increased thirst, frequent urination, and a fine hand tremor. Gastrointestinal disturbances like nausea and diarrhea are also common, especially when starting treatment. Weight gain is also frequently observed. Long-term use of lithium can affect kidney function, potentially leading to a slight reduction in glomerular filtration rate and, in some cases, progressive renal impairment.
Lithium can also impact thyroid function, often causing hypothyroidism. This condition is usually managed with thyroid hormone supplementation and is not typically a reason to discontinue lithium. A significant concern is its narrow therapeutic window, meaning the difference between an effective and toxic dose is small. Lithium toxicity can manifest with symptoms such as severe nausea, vomiting, confusion, slurred speech, gross tremors, and unsteadiness, requiring immediate medical intervention.
Treatment Monitoring and Administration
Regular monitoring is a necessary component of treatment with both Depakote and lithium due to their specific safety profiles. For lithium, routine blood tests are performed to ensure the drug remains within its narrow therapeutic range, typically 0.6 to 1.2 mEq/L. These tests also monitor kidney and thyroid function at regular intervals, often every 6 to 12 months. Patients are advised to maintain consistent salt and fluid intake and avoid dehydration, as these factors can influence lithium levels.
Depakote therapy also requires regular blood tests to monitor drug levels, liver function, and blood cell counts, particularly platelets. Liver function tests are especially important within the first six months of treatment due to the risk of liver damage. Depakote is available in various oral forms, including delayed-release tablets, extended-release tablets, and sprinkle capsules, and is typically taken once or twice daily. Lithium is also available in immediate-release pills, oral liquid, and extended-release tablets, usually taken one to three times a day.