Bipolar Disorder Treatment with Valproate and Carbamazepine

Bipolar disorder is a recurrent mental health condition that can cause extreme and often sudden shifts in a person’s mood, energy levels, and concentration. Periods of mania (elation, irritability, and/or high energy) and depression (sadness and/or indifference) can interfere with a person’s mental health, physical health, and everyday activities^[1][2].

Valproate (valproic acid) and carbamazepine are two anticonvulsant medications commonly used as mood stabilizers in the treatment of bipolar disorder. Let’s explore how these medications are used to treat bipolar disorder, along with possible side effects, a comparison of their effectiveness, how to manage these treatment methods, and how they can be used for comprehensive bipolar disorder management.

How Is Valproate Used in Bipolar Treatment?

Valproate, or valproic acid, is a prescription-only anticonvulsant medication often used to treat bipolar disorder when more common treatments, such as lithium, are unsuccessful. Numerous studies have found a valproate mood stabilizer to be effective both as a treatment for acute manic episodes and as a maintenance therapy for preventing relapses of bipolar disorder^[2][3].

How Valproate Works

Although it’s unclear how exactly valproate treats bipolar disorder, this medication is intended to increase the amount of gamma‐aminobutyric acid (GABA) in the brain in order to reduce or prevent manic episodes. GABA is a natural chemical in your central nervous system that blocks or lessens brain transmissions, resulting in a calming effect^[2][3].

Valproate Dosage for Bipolar Disorder

Valproate for bipolar disorder typically comes in capsules or tablets. They can be taken with water or juice, with or without food, and should not be crushed or chewed. Adults are usually prescribed 750mg to 2,000mg of valproic acid for bipolar disorder, often split into 2 or 3 equal doses spread throughout the day, as instructed by a doctor. Your doctor may start you on a low dose with gradual increases over a few days or weeks^[3].

How Is Carbamazepine Used in Bipolar Treatment?

Carbamazepine is an alternate method of treating bipolar disorder, sometimes prescribed when other treatment options have been unsuccessful. Studies have shown carbamazepine to be an effective treatment method for manic or mixed episodes as well as preventing relapse of bipolar disorder as a maintenance therapy^[4][5].

How Carbamazepine Works

As an anticonvulsant medicine, carbamazepine is designed to stabilize electrical activity in the brain and nervous system. Scientists don’t fully understand how carbamazepine treats bipolar disorder, but it is thought to regulate mood by reducing the activity of glutamate – a neurotransmitter – within the brain. ^[6]

Carbamazepine Dosage for Bipolar Disorder

Carbamazepine for bipolar disorder is available as a slow-release tablet, a drinkable liquid, and a suppository. For adults, the carbamazepine dosage for bipolar disorder typically ranges from 400mg to 600mg, taken 1 to 4 times per day, as instructed by a doctor. Your doctor may prescribe you a low dose to start and gradually increase your dosage over a few days or weeks until you’ve found a dose that’s right for you^[4][7].

Side Effects of Valproate and Carbamazepine

Both valproate and carbamazepine can increase health risks and/or cause minor or major adverse effects. Before beginning any prescriptions or treatment plans, be sure to discuss your full medical history with your doctor and only take medication as prescribed.

Common Side Effects of Valproate

There are several side effects that can occur when taking valproate for bipolar disorder. The following side effects are considered common, often presenting as mild symptoms that go away on their own:

• Diarrhea
• Dry mouth
• Mouth sores
• Drowsiness
• Headache
• Irregular or delayed menstrual cycle
• Stomach ache or pain
• Swollen gums
• Thinning hair or hair loss
• Tremors in certain parts of the body
• Unusual eye movements
• Weight gain

If side effects majorly interfere with your everyday activities or do not go away on their own, speak with your doctor, but do not stop taking the medication unless instructed by your doctor to do so.^[2][3]

Rare Adverse Effects of Valproate

Although uncommon, taking valproic acid for bipolar disorder could cause more serious side effects. Speak with your doctor right away if you experience any of the following rare adverse effects of valproate:

• Signs of an allergic reaction, such as swollen mouth or throat, difficulty breathing, fainting, or a serious rash
• Severe, long-lasting nausea, vomiting, or stomach pain
• Thoughts of suicide or self-harm
• Unusual bruises or bleeding
• Unusually dark urine
• Yellowing of the eyes or skin^[2][3]

Safety Considerations of Valproate

Valproate may not be suitable for all patients with bipolar disorder. The following safety considerations should be discussed with your doctor before beginning any medications:

• Age: Valproate can be prescribed to both adults and children to treat bipolar disorder. Although studies have not shown valproate to be less effective for the elderly, some older patients may be more likely to experience adverse effects^[3].
• Pregnancy and Fertility: Valproate poses a risk to unborn children and is not recommended for women who are pregnant or could become pregnant and have other treatment options available. Valproic acid could also impact fertility in men or lead to learning or behavioral challenges in children conceived while taking this medication^[3][8].
• Allergies: Patients who have had an allergic reaction to valproate should not take this medication. Patients who have had an allergic reaction to any other medication may be at a higher risk of being allergic to valproate. Be sure to discuss all allergies with your doctor^[3].
• Liver Problems: In some rare cases, valproic acid can lead to liver problems. If you have ever had problems with your liver, be sure to discuss that with your doctor before beginning valproate^[3].
• Metabolic or Genetic Conditions: Some rare metabolic or genetic conditions, such as porphyria, urea cycle disorder, or mitochondrial disorder, can lead to increased risks and should be discussed with your doctor^[3].

Common Side Effects of Carbamazepine

As with valproate, taking carbamazepine for bipolar disorder may also cause some adverse effects. The following common side effects of carbamazepine are typically mild and often go away on their own:

• Dizziness or drowsiness
• Dry mouth
• Headaches
• Mild skin rash
• Nausea or vomiting
• Weight gain

If these side effects severely interfere with your daily activities or do not go away by themselves, consult your doctor. Do not stop taking your prescribed medication unless instructed to do so by a medical professional^[9].

Rare Adverse Effects of Carbamazepine

Some side effects from carbamazepine are uncommon but could pose a serious health risk. Be sure to speak with your doctor immediately if any of the following rare adverse effects occur while taking carbamazepine:

• Breathing difficulties such as shortness of breath
• Fever or sore throat
• Joint or muscle pain
• Mouth sores
• Severe rash
• Stevens-Johnson Syndrome (characterized by flu-like symptoms and a severe rash that may blister)
• Unusual bleeding, bruising, or infections
• Yellowing of the eyes or skin^[9][10]

Safety Considerations of Carbamazepine

Carbamazepine is not a suitable treatment for everyone with bipolar disorder. The following safety considerations should be discussed with your doctor before beginning any medications:

• Age: Adults and children at least 1-month-old can be prescribed carbamazepine for bipolar disorder; however, elderly patients may be more likely to experience adverse effects and should closely monitor any symptoms.^[11]
• Pregnancy, Fertility, and Breastfeeding: Carbamazepine can lead to increased risks during pregnancy and generally is not recommended for women who are pregnant or planning to become pregnant unless absolutely necessary. If breastfeeding, speak with your doctor, as carbamazepine can pass into breast milk but is generally considered safe for feeding babies. Although carbamazepine does not impact female fertility, it may affect male fertility in some rare cases^[11][12].
• Allergies: Patients who have ever experienced an allergic reaction to carbamazepine should not take this medication. Patients who have had an allergic reaction to any other medications may be at a higher risk for allergic reactions to carbamazepine and should consult their doctor^[11].
• Heart Conditions: Carbamazepine may not be the best treatment option for patients with heart conditions. Carbamazepine may cause cardiovascular concerns such as arrhythmia (an irregular heart rate) and bradycardia, which is a slowed heart rate. Therefore, this medication may worsen heart conditions for people who have them^[11].
• Preexisting Disorders and Conditions: Porphyria – a rare blood disorder – and bone marrow problems could both pose additional risks with carbamazepine, which should be discussed with your doctor before beginning this medication^[11].

Valproate vs Carbamazepine: Which Is More Effective?

Efficacy

Studies have shown valproate and carbamazepine to be equally effective in treating and managing bipolar disorder both to one another and to traditional lithium therapy, which is considered to be the gold standard for managing bipolar disorder long-term^[13][14].

Typical Usage

In most cases, doctors will only prescribe valproic acid for bipolar disorder if lithium therapy is not or will not be an effective or ideal treatment method for the patient. Similarly, carbamazepine may only be prescribed if the patient doesn’t respond well to both lithium and valproate, as carbamazepine’s side effects may be more severe than other treatment methods^[15].

Depending on the patient and case of bipolar disorder, either valproate or carbamazepine may be preferable over one another or other treatment methods for bipolar disorder. For example, research shows that valproate may be more tolerable for short-term use, while carbamazepine may be better for long-term treatment. Additionally, potential side effects and a patient’s preexisting conditions may make one medication more suitable than the other^[16].

Managing Valproate and Carbamazepine Treatment

If you’ve been prescribed either valproate or carbamazepine for bipolar disorder, consider the following information on how to best manage your treatment plan.

Testing and Monitoring

Regular blood tests are typically recommended for patients prescribed medications to treat bipolar disorder. These tests can help monitor the impact of the medications and catch symptoms of any adverse effects they may cause, such as liver problems. Doctors will need to make medication adjustments in the event this occurs, so early identification of any problems is key^[17].

Managing Side Effects

Most minor side effects will resolve on their own. Staying hydrated can help mitigate headaches and dry or sore mouth, as well as prevent dehydration. Additionally, a nutritious diet can help manage weight gain. Speak with your doctor if symptoms persist or become unbearable^[3][6].

Lifestyle Factors

Limiting alcohol and recreational drug use can help ensure your medications work as intended with minimal side effects. If you ever feel drowsy or dizzy, do not operate a vehicle or heavy machinery. Additionally, patients taking carbamazepine should avoid drinking grapefruit juice, as it can increase the risk of side effects^[3][6][9].

Potential Drug Interactions

Although acetaminophen and ibuprofen are safe to take with carbamazepine in the short term, speak with your doctor if you need to take either for more than a few days or are considering stronger painkillers. Carbamazepine may prevent contraceptives from working properly, so discuss your birth control plans with your doctor or be prepared to use an alternative method while taking this medication. Various other medicines (both prescription and over-the-counter, such as supplements and herbal remedies) may also affect how carbamazepine and valproate work, so be sure to discuss your current medications with your doctor before beginning any new prescriptions^[3][6][18].

Combining Valproate and Carbamazepine with Other Bipolar Medications

Depending on the symptoms and how the patient responds to different types of treatment, doctors may prescribe a combination of bipolar medications in order to create a comprehensive bipolar disorder management plan^[19].

Valproate and lithium have proven to be an effective combination in managing bipolar disorder, particularly for rapid cycling and for mania that has an inadequate response to one medication or the other. Carbamazepine can also be combined with lithium to treat mania refractory to lithium therapy by itself, although that combination is becoming less common. Although valproate and carbamazepine can be effective together, it may be unsafe for some patients, so blood levels must be closely monitored throughout treatment^[19].

The right bipolar disorder treatment plan for you will depend on your symptoms, preexisting conditions, and overall response to different treatment methods. Always consult with a doctor before starting, stopping, or changing any medications to treat bipolar disorder.