Lithium vs Depakote

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For patients with bipolar disorder or other types of mood disorders, certain drugs that alter the balance of salts in the brain can help stabilize manic highs and depressive lows. Lithium and Depakote are two such medications often prescribed for these conditions. Both have effects on sodium channels in neurons, but their exact mechanisms differ somewhat. Lithium is an alkali metal that directly influences several neurotransmitter systems; however, its most significant impact appears to be on reuptake of norepinephrine and dopamine, as well as increasing serotonin synthesis. On the contrary, Depakote (valproic acid) is a fatty acid derivative primarily classified as an anticonvulsant but has been found effective in treating bipolar symptoms due to its effectiveness at stabilizing voltage-gated sodium channels and inhibiting GABA transaminase activity.

What is Lithium?

Lithium (sold under several brand names, including Lithobid) was the first mood-stabilizing drug approved by the FDA back in 1970. It has been a significant asset for treating bipolar disorder and depression. Lithium works by altering the balance of certain natural substances (neurotransmitters) in the brain which helps to stabilize abnormal activity. However, its influence is not selective; instead, it affects multiple neurotransmitters such as dopamine, norepinephrine and serotonin. This broader impact can lead to more side effects compared with other mood stabilizers.

On the other hand, Divalproex sodium or Depakote functions differently than lithium and was approved by FDA later in 1983 initially for epilepsy treatment but also found effective in managing manic episodes associated with bipolar disorder. Depakote impacts primarily on GABA- an inhibitory neurotransmitter minimizing neuronal excitability throughout nervous system leading to its calming effect with less diverse side effects compared to lithium.

What conditions is Lithium approved to treat?

Lithium is approved for the treatment of various forms of mood disorders:

  • Bipolar disorder, both as an acute treatment for manic episodes and as a maintenance therapy to prevent recurrence.
  • Acute depression in bipolar patients, although it's often used in combination with other drugs
  • Treatment-resistant depression (as an augmenting agent), when other antidepressants haven't worked.

On the other hand, Depakote (divalproex sodium) is also FDA-approved for:

  • Mania or mixed episodes associated with bipolar disorder
  • Epilepsy (including complex partial seizures, simple and complex absence seizures)
  • Prevention of migraine headaches.

How does Lithium help with these illnesses?

Lithium helps to manage bipolar disorder by affecting the flow of sodium through nerve and muscle cells in the body. Sodium affects excitation or mania which is why altering its path can aid in stabilizing moods. Lithium has been shown to decrease abnormal activity in the brain, which aids people with severe mood swings.

Depakote (valproic acid) on the other hand, is also used for treating manic episodes related to bipolar disorder. It works by increasing levels of gamma-aminobutyric acid (GABA) in the brain, a neurotransmitter that inhibits or slows down certain functions and activities within your central nervous system. By doing this, Depakote can help calm hyperactive brains and reduce seizures, stabilize moods, and limit manic episodes associated with bipolar disorder.

Both medicines offer benefits for patients dealing with mood disorders but their mechanisms are different; therefore choosing between them may depend upon individual patient factors such as other health conditions present and how they react to each medication.

What is Depakote?

Depakote, the brand name for divalproex sodium, is a medication that functions as both an anticonvulsant and mood stabilizer. It works by increasing levels of gamma-aminobutyric acid (GABA), a neurotransmitter in the brain that aids in reducing anxiety, calming nervous activity, and managing seizures. Depakote was first approved by the FDA in 1983. As it is not a lithium-based drug meant to treat bipolar disorder, it does not function through altering sodium transport in nerve and muscle cells like lithium does. Its different action means its side-effect profile also differs from that of lithium; specifically, while weight gain can occur with both medications, hair loss and tremors are less likely with Depakote compared to Lithium. The effectiveness on GABA can make Depakote beneficial for managing several conditions including bipolar disorder, epilepsy, migraines or chronic headaches - especially useful for patients who do not respond well to "typical" treatments such as Lithium.

What conditions is Depakote approved to treat?

Depakote has been approved for the treatment of several neuropsychiatric conditions, including:

  • Epilepsy: specifically, complex partial seizures and simple or complex absence seizures
  • Manic episodes associated with bipolar disorder
  • Prophylaxis of migraine headaches

How does Depakote help with these illnesses?

Depakote, like lithium, is used in the treatment of bipolar disorder and works by affecting certain substances in the body that are involved in causing seizures. Depakote acts primarily on GABA receptors, a type of neurotransmitter that inhibits brain activity. By increasing GABA levels and reducing abnormal electrical activity within the brain, it helps to stabilize mood swings associated with bipolar disorder. It's also useful for preventing migraines and treating various types of seizures when combined with other medications. Its action may be more tolerable or preferable than Lithium for some patients due to fewer side effects such as weight gain and kidney issues which are often seen with Lithium use. Because it doesn't significantly impact serotonin levels like traditional SSRI antidepressants do (like Prozac), Depakote is sometimes prescribed when a patient does not respond well to these typical treatments or it can be used in combination with them.

How effective are both Lithium and Depakote?

Both lithium and divalproex sodium (Depakote) have established histories of success in treating patients with bipolar disorder. Lithium was approved by the FDA in 1970, while Depakote was initially approved for epilepsy treatment in 1983 and later for bipolar mania treatment in 1995. Since they act on different neurological pathways, they may be prescribed under different circumstances.

The effectiveness of lithium and Depakote at alleviating episodes of mania has been extensively studied; both drugs exhibit similar efficacy managing symptoms as well as comparable safety profiles. A clinical trial conducted in 2001 compared lithium to Depakote head-to-head, revealing that neither drug outperformed the other when it came to reducing manic symptoms or improving overall functioning.

A substantial body of literature supports the use of lithium not only as a mood stabilizer but also as a suicide prevention measure among those with bipolar disorder: this is an aspect where it stands apart from many other mood-stabilizing agents including Depakote. The optimal therapeutic dose often requires individual titration but generally falls between 900 mg/day to 1200 mg/day for adults.

Conversely, studies indicate that Depakote might be more effective than placebo at preventing new episodes among rapid-cycling individuals - those who experience four or more mood episodes within one year - where lithium may struggle somewhat. Much like with lithium, dosing is individualized based on response and tolerability but typically ranges from approximately 500-1500mg per day divided into two doses.

Nonetheless, due to their unique pharmacologies both drugs can play pivotal roles depending upon patient-specific factors such as prior medication history, co-existing medical conditions or potential side effects profile considerations such as weight gain commonly associated with depakote usage.

abstract image of a researcher studying a bottle of drug.

At what dose is Lithium typically prescribed?

Oral dosages of Lithium for adults usually range from 900-1800 mg/day, while the effective dosage varies from person to person. It is crucial to regularly monitor lithium levels in the blood as it has a narrow therapeutic index and can lead to toxicity if not properly managed. For children and adolescents, the dosage must be carefully adjusted by a healthcare provider as per individual response and tolerability. When comparing with Depakote, which also varies significantly in dosing (from 250 mg to 1000 mg or more daily), it's essential that each patient's physical health, age, weight, kidney function and overall mental status are taken into account before establishing an appropriate dose regimen. As always, these medications should only be used under direct supervision of a healthcare professional.

At what dose is Depakote typically prescribed?

Depakote treatment typically begins at a dosage of 250 mg twice a day. Depending on the individual's response and tolerance, the dose may be increased up to 1000 mg per day. This is often divided into two doses taken approximately 12 hours apart to maintain steady levels in the bloodstream. In some instances, if there is no significant improvement or if side effects become problematic, your doctor might test increasing your daily dosage beyond this limit but not exceeding 60mg/kg/day. Always remember that changes to medication should only be made under medical supervision and never exceed the prescribed maximum dose.

What are the most common side effects for Lithium?

Common side effects of Lithium can include:

  • Tremor (unintentional trembling or shaking)
  • Diarrhea
  • Vomiting, nausea
  • Increased thirst and urination
  • Dry mouth
  • Weight gain
  • Changes in appetite or eating patterns
  • Fatigue, drowsiness, lethargy (somnolence)
  • Muscle weakness (asthenia)

On the other hand, Depakote may cause:

  • Nausea and vomiting
  • Dizziness
  • Weight gain
  • Hair loss
  • Shaking tremors
  • Somnolence (sleepiness/drowsiness)
  • Weakness (asthenia).

Always consult your doctor if you experience any of these symptoms while taking either medication.

abstract image of a patient experiencing side effect

Are there any potential serious side effects for Lithium?

While both Lithium and Depakote are effective mood stabilizers, they may cause different side effects. For lithium:

  • Increased thoughts about suicide or self-harm
  • Signs of an allergic reaction like rash, hives, itching; red or swollen skin with fever; wheezing; tightness in the chest or throat; difficulty breathing, swallowing or talking.
  • Blurred vision, ringing in ears
  • Irregular heartbeat
  • Loss of balance control
  • Muscle weakness/ trembling hands
  • Low sodium levels - symptoms include headache, confusion, severe weakness, vomiting & feeling unsteady.

For Depakote:

  • Severe liver damage which can manifest as nausea/vomiting that doesn't stop, loss of appetite etc.
  • Pancreatitis (swelling of pancreas)
  • Multi-system organ failure leading to fatal outcomes has been reported in patients using valproate derivatives (Depakote being one).

In case you experience any adverse reactions from these drugs consult your doctor immediately.

What are the most common side effects for Depakote?

Depakote, an alternative to Lithium, comes with its own set of potential side effects. These can include:

  • Nausea or vomiting
  • Dizziness or drowsiness
  • Hair loss
  • Changes in weight
  • Tremors
  • Blurred vision or double vision
  • Unusual bleeding or bruising
  • Diarrhea or constipation
    These symptoms may be mild at first but could become more severe over time. It's essential for patients taking Depakote to maintain regular contact with their healthcare provider and report any new symptoms immediately.

Are there any potential serious side effects for Depakote?

While Depakote, just like any other medication, can potentially cause side effects, it's crucial to be aware of the more serious ones. These may include:

  • Signs of a severe allergic reaction such as hives; difficulty breathing; swelling of your face, lips, tongue or throat
  • The emergence or worsening of depression and suicidal thoughts
  • A sudden and unexplained illness including nausea, vomiting, headache and confusion (which might signal pancreatitis)
  • Unusual changes in mood or behavior
  • Easy bruising or bleeding along with signs of liver problems that could manifest through stomach pain on the upper right side, loss of appetite and jaundice (yellowing eyes/skin)
  • Visual disturbances such as blurred vision
  • Rapid heart rate or palpitations Uncontrolled muscle movements in your face (chewing movements, lip smacking)

If you notice any these symptoms while taking Depakote immediately seek medical help.

Contraindications for Lithium and Depakote?

Both Lithium and Depakote, as with many other mood stabilizers, may exacerbate symptoms of depression or bipolar disorder in some individuals. If you notice your condition worsening, or an increase in suicidal ideation, thoughts, or behavior while taking these medications, please seek immediate medical attention.

Neither Lithium nor Depakote should be taken if you are currently on diuretics (water pills), angiotensin-converting enzyme (ACE) inhibitors for high blood pressure, non-steroidal anti-inflammatory drugs (NSAIDs), certain antibiotics such as metronidazole and isoniazid among others. Always inform your doctor about all the medicines you are taking; these drugs can interact dangerously with both Lithium and Depakote.

How much do Lithium and Depakote cost?

For the brand name versions of these drugs:

  • The price of 60 tablets of Lithobid (300 mg), a branded version of lithium, averages around $130, which equates to approximately $2–$8 per day depending on your dose.
  • The price for the brand-name Depakote (500mg) is about $240 for 60 tablets, which calculates to roughly $4/day.

Thus, if you're using lithium within a higher dosage range (i.e., 1200 mg/day or more), then brand-name Depakote can be less costly on a daily treatment basis. However, cost should not be your primary consideration in determining which medication suits you best.

As for the generic versions of lithium and Depakote (divalproex sodium):

  • Generic lithium costs significantly less with prices ranging from $0.10-$0.40 per day based on typical dosages between 600 and 1800 mg/day.
  • Divalproex sodium also shows significant savings over its branded counterpart; it costs around $1–$2 per day assuming usual doses between 750 and 2000 mg/day.

Please note that actual costs may vary due to several factors including location and insurance coverage status among others.

Popularity of Lithium and Depakote

Lithium, whether in generic form or as brands such as Lithobid, is a long-standing cornerstone of bipolar disorder treatment and was prescribed to approximately 1.3 million people in the US during 2020. This accounted for nearly 8% of all mood stabilizer prescriptions nationally that year. Despite its age (it has been used medically since the late-19th century), lithium remains highly prevalent due to its proven effectiveness against manic episodes.

In comparison, Divalproex sodium - popularly known by one brand name Depakote - was prescribed to about 2.5 million people in the USA during 2020. In this country, it accounts for just under 16% of overall mood stabilizer prescriptions – significantly more than lithium despite being a newer medication (first approved by FDA in late '90s). The prevalence of divalproex sodium use has remained steady over the last decade.


Both lithium and Depakote (valproic acid) have a long history of usage in patients with bipolar disorder, supported by extensive clinical trials and studies indicating their effectiveness over placebo treatments. Occasionally, these medications may be prescribed together under the careful supervision of a physician due to potential drug interactions. Lithium primarily works on dopamine and serotonin neurotransmitters while Depakote influences GABA levels as well as sodium channels, leading to different prescribing scenarios based on individual patient needs.

Lithium is often considered the gold standard for treating bipolar disorder, particularly for mania prevention. On the other hand, Depakote may offer more benefits in managing rapid cycling or mixed mood episodes and might be preferred when quicker symptom control is required.

Both drugs are available in generic forms presenting significant cost savings especially for those paying out-of-pocket. Both medications require close monitoring including regular blood tests to ensure therapeutic ranges are maintained without reaching toxic levels.

The side effect profiles between lithium and Depakote differ somewhat with both having potential risks if not carefully managed. Lithium can affect kidney function while Depakote may impact liver function; both can cause tremors but weight gain tends to be more associated with use of Depakote than lithium. It's crucial that individuals taking these medications monitor any changes in health closely – starting treatment or adjusting dosages - seeking immediate medical help if experiencing signs such as severe nausea/vomiting/diarrhea (lithium) or symptoms like jaundice/fatigue/abdominal pain (Depakote).