When combining prescription drugs, understanding potential drug interactions is critical to ensuring safety and effectiveness. Contrave and Lamictal drug interactions involve mechanisms that can impact bupropion hydrochloride metabolism, seizure threshold, and overall treatment outcomes.

Since both medications affect the central nervous system, their concomitant administration could heighten certain risk factors such as dizziness, nausea, and adverse events like hypertensive reactions or CNS toxicity.

Dr. Matthew Olesiak, Chief Medical Director at SANE MD, emphasizes: “Patients should work closely with their healthcare provider when starting therapy with multiple medications to avoid unexpected drug interactions and ensure they fully benefit from treatment.”

This article explores the contrave interactions with lamotrigine, aka Lamictal, providing insight into potential adverse events, how they affect the body, and what to discuss with a healthcare provider before combining these medications.

Key Takeaways

• Combining Contrave and Lamictal may increase seizure disorder risk, alter blood pressure, and heighten suicidal thoughts.
• Drug interactions between these medications could lead to CNS toxicity, nausea, and impaired alcohol tolerance.
• Patients with bipolar disorder, uncontrolled hypertension, or liver problems should consult a healthcare provider before taking Contrave with Lamictal.

What Is Contrave?

Contrave is an FDA-approved weight loss medication designed to help patients with a high initial body mass index (BMI) reduce excess weight when used alongside a reduced calorie diet and increased physical activity. It is typically prescribed for compatible adults who are overweight or obese and have at least one weight-related condition, such as high blood pressure, type 2 diabetes, or high cholesterol.

Unlike some other weight loss treatments, Contrave does not work by suppressing digestion or blocking fat absorption. Instead, it affects brain pathways related to hunger, cravings, and reward-based eating behavior, making it easier for individuals to manage their food intake.

How Contrave Works

Contrave is a combination medication that includes naltrexone hydrochloride and bupropion hydrochloride. Both of these medications target different aspects of appetite control and food cravings. Together, they reduce food-seeking behaviors and support long-term weight loss goals.

• Bupropion hydrochloride: A norepinephrine-dopamine reuptake inhibitor (NDRI) that stimulates the brain’s reward system, influencing mood and energy levels. It is also used in Wellbutrin SR to treat depression and as a smoking cessation aid. In Contrave, it helps reduce appetite and increase energy expenditure.
• Naltrexone hydrochloride: Originally developed for treating opioid dependence, naltrexone blocks opioid receptors in the brain. In Contrave, it helps regulate reward-driven eating by reducing the pleasure associated with food consumption, making cravings more manageable.

By affecting both appetite suppression and reward pathways, Contrave supports long-term weight loss for certain individuals when combined with increased physical activity and a reduced calorie diet.

Contrave Dosing and Mechanism

The contrave dosing schedule involves gradually increasing the dosage over four weeks to minimize nausea, dizziness, and other symptoms. This slow titration helps the body adjust to bupropion and naltrexone, reducing the likelihood of adverse events like vomiting or CNS toxicity.

Standard Dose Schedule:

Week	Morning Dose	Evening Dose
Week 1	1 tablet	None
Week 2	1 tablet	1 tablet
Week 3	2 tablets	1 tablet
Week 4+	2 tablets	2 tablets

Each extended-release tablet contains:

• 8 mg of naltrexone hydrochloride
• 90 mg of bupropion hydrochloride

The standard dose after titration is two tablets taken twice daily (morning and evening), but taking Contrave with high fat meals should be avoided, as it can increase the risk of seizures.

Who Should Avoid Contrave?

Although Contrave is an effective tool for weight loss, certain patients should avoid taking Contrave due to potential adverse events.

Contrave is NOT recommended for patients who:

• Have uncontrolled hypertension, as bupropion can increase blood pressure and heart rate.
• Have a seizure disorder or a history of seizures, since bupropion hydrochloride lowers the seizure threshold. This risk is highlighted in the Boxed Warning for Contrave, which underscores the serious potential for seizures.
• Are undergoing abrupt discontinuation of opioid containing medicines, as this could trigger acute opiate withdrawal.
• Are using monoamine oxidase inhibitors (MAOIs), which can interact dangerously with bupropion.
• Have bipolar disorder, as bupropion may increase the risk of suicidal thoughts or mania.
• Have a history of anorexia nervosa or bulimia, as bupropion has been linked to an increased seizure risk in patients with eating disorders.
• Are pregnant, due to the potential for fetal harm.

Contrave can also potentially interact with GLP-1 medications. For example, taking Contrave and Mounjaro together can lead to drug interactions and accompanying symptoms.

Patients should seek medical attention if they experience severe nausea, vomiting, or hypertensive reactions while on Contrave.

Dr. Olesiak advises: “Since Contrave contains bupropion, patients should be cautious when taking it alongside certain antidepressants, beta blockers, or other bupropion containing products, as these combinations can increase the risk of CNS toxicity, hypertensive reactions, and skin rash.”

Patients can safely incorporate Contrave into their weight loss journey by following the Contrave dosing guidelines and discussing potential Contrave interactions with a healthcare provider.

What Is Lamictal?

Lamictal (lamotrigine) is an antiepileptic drug used primarily for treating epilepsy and bipolar disorder. It is classified as an anticonvulsant, working by stabilizing electrical activity in the brain to prevent seizures and regulate mood swings.

Lamictal is commonly prescribed as either monotherapy (used alone) or in combination with other antiepileptic drugs to enhance seizure control.

How Lamictal Works

Lamictal primarily affects sodium channels in the brain, reducing excessive nerve signaling. This makes it effective for:

• Epilepsy: Preventing partial seizures, generalized tonic-clonic seizures, and Lennox-Gastaut syndrome.
• Bipolar Disorder: Stabilizing mood and preventing episodes of depression, particularly in individuals with bipolar I disorder.

Lamictal is not typically used to treat acute mania in bipolar disorder, but it is highly effective at reducing the frequency and severity of depressive episodes.

Lamictal Dosing and Considerations

Lamictal is administered gradually, starting with a low dose to minimize adverse events such as skin rash.

Patients initiating treatment must follow a carefully titrated schedule to reduce the risk of severe allergic reactions, including erythema multiforme.

Lamictal Standard Dose Schedule

Week	Dose (mg/day)
Week 1-2	25 mg
Week 3-4	50 mg
Week 5	100 mg
Week 6+	200 mg

For epilepsy, the standard dose is generally 200-400 mg daily, whereas for bipolar disorder, the maintenance dose typically falls between 100-200 mg daily.

The Risk of Skin Rash

One of the most serious concerns with taking Lamictal is the development of skin rash, which can progress into Stevens-Johnson syndrome (SJS) or toxic epidermal necrolysis (TEN). The likelihood of these reactions increases if:

• The dose is increased too rapidly.
• Other drugs that affect Lamictal metabolism are introduced.
• The patient is on systemic corticosteroids, which can alter immune response.

Patients should seek medical attention immediately if they experience a skin rash, fever, or blistering while taking Lamictal.

Lamictal and Drug Interactions

Since Lamictal is metabolized by the liver, various drug interactions can affect its efficacy and increase the risk of adverse events.

Key Interactions to Consider

1. Bupropion Hydrochloride (Wellbutrin, Contrave)
   • Bupropion hydrochloride can increase seizure risk, which may counteract Lamictal’s antiepileptic effects. Additionally, bupropion’s interaction with nicotine can lead to heightened CNS stimulation, increased blood pressure, and mood instability. Learn more about Contrave and nicotine drug interactions here.
   • Combining bupropion and lamotrigine may also lead to dizziness, suicidal thoughts, and impaired concentration.
2. Naltrexone Hydrochloride (Contrave)
   • Naltrexone hydrochloride alters opioid receptor activity and, when combined with lamotrigine, may affect brain neurotransmitter balance, potentially leading to mood instability.
3. Other Antiepileptic Drugs (AEDs)
   • Valproic acid (Depakote) increases Lamictal levels, raising the risk of skin rash and toxicity.
   • Carbamazepine (Tegretol) and phenytoin (Dilantin) reduce Lamictal levels, possibly leading to breakthrough seizures.
4. Monoamine Oxidase Inhibitors (MAOIs)
   • These other drugs can cause hypertensive reactions when combined with Lamictal, requiring caution.
5. Beta Blockers
   • Beta blockers used for blood pressure control can interact with lamotrigine, leading to dizziness and fatigue.

Who Should Avoid Lamictal?

While Lamictal is well-tolerated in most patients, certain risk factors make it unsuitable for some individuals.

Lamictal is NOT recommended for:

• Patients with a seizure disorder who have frequent medication changes.
• Those with a history of erythema multiforme or other severe skin rash conditions.
• Pregnant women, as there is a potential for fetal harm.
• Patients with liver problems, since Lamictal is processed in the liver and may accumulate in cases of hepatic impairment.
• Patients with a history of seizures should also avoid bupropion, a component of Contrave, as it is contraindicated in such cases due to its potential to lower the seizure threshold.

• Patients with a seizure disorder who have frequent medication changes.
• Those with a history of erythema multiforme or other severe skin rash conditions.
• Pregnant women, as there is a potential for fetal harm.
• Patients with liver problems, since Lamictal is processed in the liver and may accumulate in cases of hepatic impairment.

Dr. Olesiak advises: “Careful medication adjustments are needed when combining Lamictal with other drugs that affect the brain’s neurotransmitter balance. Patients should work closely with a healthcare provider to prevent unnecessary side effects.”

Contrave and Lamictal Drug Interactions

When taking Contrave and Lamictal together, patients must be aware of potential drug interactions that could lead to adverse events. These two medications influence brain chemistry, neurotransmitter activity, and metabolic processes, which may increase the risk of serious side effects.

Additionally, bupropion significantly increases the plasma and brain concentrations of lamotrigine, which could amplify its effects and potential side effects.

The interaction between Contrave (containing bupropion hydrochloride and naltrexone hydrochloride) and Lamictal (lamotrigine) primarily affects seizure risk, CNS toxicity, and blood pressure regulation. Due to their combined impact on the nervous system, patients should consult a healthcare provider before combining them, especially if they have underlying risk factors such as seizure disorder, uncontrolled hypertension, or liver problems.

Potential Risks and Side Effects

The combination of Contrave interactions with Lamictal may lead to several adverse events, including:

1. Lowered Seizure Threshold

One of the most concerning interactions between Contrave and Lamictal is the potential for lowering the seizure threshold, making seizures more likely.

However, chronic administration of bupropion has been shown to significantly potentiate the protective activity of lamotrigine against seizures, which may provide some benefit in seizure management under careful medical supervision.

• Bupropion hydrochloride, a key component of Contrave, is known to increase seizure risk, especially at higher doses or when taken with other bupropion containing products.
• Lamotrigine, while an antiepileptic drug, requires stable levels in the body for effective seizure prevention. If its metabolism is affected by naltrexone hydrochloride or bupropion hydrochloride, the balance may be disrupted, making seizure control more difficult.

Patients with seizure disorder should be extra cautious when starting therapy with these medications, as even a low dose of bupropion can increase seizure susceptibility.

2. Increased Blood Pressure and Hypertensive Reactions

Contrave has been associated with increases in blood pressure and heart rate, particularly in patients with uncontrolled hypertension or those sensitive to monoamine oxidase inhibitors (MAOIs).

• Bupropion hydrochloride can affect cardiovascular function, leading to hypertensive reactions.
• Naltrexone hydrochloride influences the nervous system, which may contribute to blood pressure fluctuations.
• Beta blockers, often prescribed for blood pressure control, may interact negatively with Contrave, heightening the risk of dizziness, fatigue, and CNS toxicity.

Patients with pre-existing heart conditions should have their blood pressure monitored closely when starting Contrave while taking Lamictal.

3. CNS Toxicity and Neuropsychiatric Effects

Since both Contrave and Lamictal impact the central nervous system (CNS), their combination may lead to CNS toxicity, especially in individuals using systemic corticosteroids or those with liver problems.

Symptoms of CNS toxicity include:

• Severe dizziness
• Confusion and difficulty concentrating
• Mood swings and suicidal thoughts
• Increased sensitivity to alcohol

Additionally, patients with bipolar disorder should be cautious, as bupropion hydrochloride may trigger manic episodes or worsen suicidal thoughts.

4. Gastrointestinal Side Effects: Nausea, Vomiting, and Dizziness

Both Contrave and Lamictal have been linked to nausea, vomiting, and dizziness, particularly during starting therapy.

• Contrave dosing follows a gradual titration schedule to help mitigate these effects, but taking Contrave on an empty stomach or with high fat meals can increase nausea.
• Lamictal can also cause gastrointestinal distress, especially during the first few weeks of treatment.

To minimize these adverse events, patients should:

• Take Contrave and Lamictal with food (but avoid high fat meals).
• Stay hydrated to counteract nausea and dizziness.
• Follow a low dose titration schedule to allow their body to adjust.

5. Drug Metabolism and Liver Considerations

Both Contrave and Lamictal are metabolized by the liver, meaning their combination may affect how quickly the body processes these medications.

• Patients with liver problems may experience higher blood levels of bupropion hydrochloride or lamotrigine, increasing the risk of toxicity.
• Concomitant administration of opioid containing medicines with Contrave can lead to acute opiate withdrawal, further straining liver function.

Patients with pre-existing liver conditions should work with their healthcare provider to determine whether taking Contrave with Lamictal is appropriate.

Who Is at the Highest Risk?

Certain groups of patients are at a higher risk for adverse events when combining Contrave and Lamictal:

1. Individuals with seizure disorder – due to bupropion hydrochloride’s impact on the seizure threshold.
2. Patients with bipolar disorder – as bupropion may worsen mood instability.
3. People with uncontrolled hypertension – because Contrave can elevate blood pressure.
4. Patients with liver problems – as both medications require hepatic metabolism.
5. Those taking beta blockers or systemic corticosteroids – due to potential CNS toxicity and cardiovascular concerns.

Precautionary Measures

To minimize contrave interactions with Lamictal, follow these safety measures:

• Consult a healthcare provider before making any medication adjustments.
• Start with a low dose and gradually increase as tolerated.
• Monitor blood pressure regularly to detect hypertensive reactions.
• Be aware of mood changes—report worsening suicidal thoughts or anxiety.
• Avoid alcohol to prevent excessive dizziness or CNS toxicity.
• Do not take Contrave with opioid containing medicines, as this can lead to acute opiate withdrawal.

When to Seek Medical Attention

Patients should seek medical attention immediately if they experience:

• Severe nausea, vomiting, or dizziness
• Sudden mood changes or suicidal thoughts
• Seizure activity or unexplained blackouts
• Dangerously high blood pressure or irregular heart rate
• Signs of acute opiate withdrawal (if stopping opioids)

Consulting a Healthcare Provider

Before taking Contrave with Lamictal, consult a healthcare provider about:

• Other symptoms like severe nausea, vomiting, or dizziness.
• Adjusting contrave dosing to minimize adverse events.
• The potential need for a low dose initiation to prevent seizure disorder complications.
• Interactions with other drugs, including certain antidepressants, beta blockers, and many tricyclics. Although Contrave can be used to treat depression, the combination of these two drugs with certain antidepressants can cause distressing symptoms.

If symptoms are concerning, patients should seek medical attention immediately.

Frequently Asked Questions (FAQ)

When considering Contrave and Lamictal drug interactions, it’s essential to understand how these medications may impact your treatment plan.

Below are answers to some of the most common questions about Contrave, Lamictal, and their interactions with other prescription drugs and over the counter drugs.

1. Can I take bupropion and Lamictal together?

Bupropion hydrochloride, a key ingredient in Contrave, is also found in Wellbutrin SR and other bupropion-containing products. While bupropion and Lamictal (lamotrigine) can be taken together, their combination carries certain risks.

• Bupropion hydrochloride lowers the seizure threshold, meaning it can increase the likelihood of seizures, especially in patients with a seizure disorder.
• Lamictal is an antiepileptic drug, used to prevent seizures, so combining it with bupropion hydrochloride could make seizure management more challenging.
• There is a risk of mood instability, particularly in patients with bipolar disorder, as bupropion may trigger manic episodes or suicidal thoughts.
• Patients should be cautious of CNS toxicity, including dizziness, confusion, and difficulty concentrating when combining these medications.

Bottom Line: While bupropion and Lamictal can be prescribed together, they should be used under close medical supervision, especially in patients with seizure disorder, bipolar disorder, or those taking other medications that affect CNS function.

2. What medications should not be taken with Contrave?

Contrave drug interactions can occur with various medications, potentially leading to adverse events such as hypertensive reactions, seizure risk, and mood disturbances.

Avoid taking Contrave with the following:

• Opioid containing medicines – Since naltrexone hydrochloride is an opiate antagonist, it can cause acute opiate withdrawal in patients currently taking opioid-containing medicines or partial agonists like buprenorphine.
• Monoamine oxidase inhibitors (MAOIs) – These drugs (e.g., phenelzine, tranylcypromine) can lead to hypertensive reactions and serious cardiovascular issues when combined with bupropion hydrochloride.
• Other bupropion containing products – Taking additional bupropion (such as Wellbutrin SR) alongside Contrave increases the risk of seizures and CNS toxicity.
• Beta-blockers—These drugs lower blood pressure. However, they can interact with Contrave, potentially increasing heart rate, dizziness, and fatigue.
• Systemic corticosteroids – These can increase the risk of seizure threshold reduction when taken with bupropion hydrochloride.
• High-fat meals – Although not a medication, consuming high fat meals while taking Contrave can cause bupropion levels to spike, increasing the risk of nausea, dizziness, and seizures.

Bottom Line: If you are taking Contrave, consult your healthcare provider about any other drugs you’re using, including over the counter drugs, to fully benefit from treatment while minimizing risks.

3. Can people with bipolar disorder take Contrave?

Patients with bipolar disorder should be cautious when taking Contrave, as it contains bupropion hydrochloride, which affects neurotransmitter levels in the brain.

• Bupropion can trigger manic episodes in patients with bipolar disorder, especially those who are not also taking a mood stabilizer.
• Contrave interactions with Lamictal (lamotrigine) may further impact mood stability, as both medications influence brain chemistry.
• Some patients may experience suicidal thoughts, requiring medical attention if mood changes occur.

Bottom Line: Contrave is not generally recommended for patients with bipolar disorder unless closely monitored by a healthcare provider. If prescribed, it should be used with caution, ideally in combination with a mood stabilizer like Lamictal to reduce mood-related adverse events.

4. What should you not mix with Lamictal?

Several other drugs can interact with Lamictal, potentially affecting its metabolism, increasing side effects, or reducing seizure control.

Avoid taking Lamictal with:

• Bupropion hydrochloride (Contrave, Wellbutrin SR) – Can increase seizure risk and CNS toxicity, leading to dizziness, nausea, and confusion.
• Valproic acid (Depakote) – Increases lamotrigine levels, raising the risk of severe skin rash (including erythema multiforme) and other adverse events.
• Carbamazepine (tegretol) and Phenytoin (dilantin) are antiepileptic drugs that lower Lamictal levels, potentially reducing its effectiveness.
• Alcohol and CNS depressants – May increase CNS toxicity, causing dizziness, drowsiness, and impaired motor function.
• Beta blockers – Can affect blood pressure regulation and increase the risk of cardiovascular adverse events.
• Systemic corticosteroids – These drugs can affect the metabolism of lamotrigine, leading to increased side effects.

Bottom Line: If you are prescribed Lamictal, review your entire list of medications with a healthcare provider to avoid harmful contrave interactions and ensure the medication is working effectively.

Conclusion

Contrave interactions with Lamictal require careful monitoring due to overlapping effects on seizure threshold, blood pressure, and CNS toxicity. Patients should discuss their complete prescription drug list, including over-the-counter drugs, with a healthcare provider before combining these medications. They will help you determine if Contrave is the right fit for you.

By maintaining increased physical activity, following a reduced-calorie diet, and adhering to proper contravene dosing, patients can maximize safety while effectively managing weight loss and neurological conditions.