Taking Contrave and Nardil Together: Drug Interaction Guide

Combining prescription medications can be risky—especially when it involves drugs that affect brain chemistry. If you’re considering taking Contrave and Nardil together, it’s essential to understand how these medications might interact.

Both are powerful in their own right: Contrave is prescribed for weight loss for compatible individuals, while Nardil is a monoamine oxidase inhibitor (MAOI) used to treat depression. But taken together, they can increase the risk of side effects, including extremely high blood pressure, serious skin reactions, or even life-threatening events.

“Nardil is a very potent MAOI, and combining it with drugs like Contrave—particularly due to the bupropion component—can be dangerous without careful oversight,” explains Dr. Matthew Olesiak, Chief Medical Director at SANE MD. “This isn’t a casual combination—it requires clear justification and close monitoring by a qualified medical doctor.”

This guide breaks down the potential drug interactions, side effects to watch for, and why it’s crucial to talk with your doctor before combining these two medications.

Key Takeaways

• Combining Contrave and Nardil can cause serious or even life-threatening effects, including extremely high blood pressure, seizures, and allergic reaction symptoms.
• Contrave treatment is designed for certain individuals pursuing long-term weight management and should not be taken with MAOIs like Nardil without physician supervision.
• Always talk with your doctor about other medications you’re taking, especially if you’re being treated for mental disease, bipolar disorder, or eating disorders.

Understanding Contrave and Nardil

What Is Contrave?

Contrave is an FDA-approved prescription weight loss medication designed for long-term weight management in certain adults with a high body mass index (BMI), or those who are overweight with at least one weight-related condition like type 2 diabetes or high cholesterol.

It contains a combination of naltrexone and bupropion, two medications that affect different parts of the brain. Bupropion is a norepinephrine-dopamine reuptake inhibitor (NDRI) commonly used to treat depression and support smoking cessation, while naltrexone is an opioid antagonist used to reduce cravings in alcohol and opioid dependence.

Together, naltrexone and bupropion help regulate the brain’s reward system and hunger cues, making it easier for people to control food intake, resist emotional eating, and lose weight. Contrave is typically prescribed as part of a broader weight management strategy that includes a reduced-calorie diet, behavioral changes, and physical activity. However, these two medications can make Contrave drug interactions much more likely.

The medication is available in extended-release tablets to ensure consistent dosing throughout the day and minimize abrupt changes in blood concentration that could increase side effects.

What Is Nardil?

Nardil (phenelzine sulfate) is a monoamine oxidase inhibitor (MAOI) used to treat depression, particularly treatment-resistant or atypical forms that haven’t responded to SSRIs, SNRIs, or tricyclic antidepressants. MAOIs work by inhibiting the enzyme monoamine oxidase, which breaks down neurotransmitters like serotonin, dopamine, and norepinephrine. By blocking this enzyme, Nardil increases the levels of these neurotransmitters in the brain, improving mood and emotional stability.

However, MAOIs come with strict limitations due to their extensive and potentially dangerous drug interactions. They interact with numerous foods, over-the-counter medications, and other prescription drugs—especially those that also affect neurotransmitters.

These interactions can lead to severe complications, including extremely high blood pressure, serotonin syndrome, or hypertensive crisis, which is why careful oversight is required when prescribing or transitioning off an MAOI.

Why the Combination Is Risky

When you take naltrexone and bupropion together in Contrave, the bupropion component becomes a major concern if paired with MAOIs like Nardil. Both drugs influence dopamine and norepinephrine levels, and when combined, the resulting chemical overload can dangerously overstimulate the central nervous system.

The Most Serious Risks Include:

• Extremely high blood pressure: This can occur rapidly and may lead to stroke, heart attack, or other life-threatening cardiovascular events.
• Severe seizures: Bupropion already lowers the seizure threshold; pairing it with an MAOI further increases this risk, especially in patients with eating disorders, bipolar disorder, or a history of substance misuse.
• Sudden high body temperature: An early warning sign of serotonin syndrome or autonomic dysregulation.
• Pulse frequent urge changes: Fluctuations in heart rate or blood pressure may point to a developing crisis.
• Neck sweating vomiting rare symptoms: These may be part of a hypertensive reaction or early signs of neurological distress.

“There’s a boxed warning that alerts doctors about the increased risk of suicidal thoughts and behaviors when using naltrexone and bupropion in patients with mental disease or mood disorders,” says Dr. Matthew Olesiak. “Combining them with MAOIs further elevates that risk, particularly in vulnerable individuals.”

In addition to these serious risks, the combination of Contrave and Nardil may increase the risk of side effects such as:

• Discomfort, nausea, pain
• Serious skin reactions, including blistering or peeling
• Skin rash or hives
• Chest pain, agitation, or dizziness
• Low blood sugar or irregular blood sugar fluctuations in patients with diabetes

These effects are more likely in elderly patients or those with existing liver disease or kidney disease, where drug clearance is already compromised. Because both drugs are metabolized and excreted by these organs, toxic accumulation can occur quickly without close monitoring.

Potential Side Effects of Taking Contrave and Nardil Together

Category	Possible Side Effects
Cardiovascular	High blood pressure, extremely high blood pressure, chest pain, rare chest pain, increased heart rate
Neurological	Severe seizures, severe spinning, nausea, headache, irritability, sudden or strong feelings
Psychiatric	Suicidal thoughts, mood changes, mental disease flare-ups, anxiety, agitation
Gastrointestinal	Discomfort, nausea, bowel symptoms, stomach pain, indigestion
Dermatological	Serious skin reactions, skin rash, severe acne, allergic reaction, skin reactions
Renal and Urinary	Common bladder pain, bloody, age-related kidney problems, end-stage kidney disease
Endocrine / Metabolic	Low blood sugar, fluctuations in blood sugar, weight changes
General / Systemic	Sudden high body temperature, neck sweating, vomiting rare, indigestion
Musculoskeletal	Sitting position muscle cramps, muscle tension, or weakness
Allergic / Immune Response	Allergic reaction, immediate medical attention required, accidental overdose

Drug Interactions: What You Need to Know

MAOIs like Nardil are known to interact with a wide range of medications and substances, including naltrexone and bupropion, the two active ingredients in Contrave. This combination poses a serious risk due to overlapping mechanisms that affect neurotransmitters such as dopamine, norepinephrine, and serotonin.

What Can Happen When These Drugs Are Combined?

1. Increase blood pressure rapidly, sometimes to dangerous levels.
Combining bupropion with an MAOI can result in a hypertensive crisis—a sudden and extremely high blood pressure spike that may lead to stroke or cardiac complications. This occurs because both drugs elevate norepinephrine levels, which can overstimulate the cardiovascular system.

2. Trigger severe seizures.
Bupropion lowers the seizure threshold, particularly at higher doses or when combined with interacting drugs. When taken with an MAOI, this risk is amplified, especially in people with predisposing conditions like eating disorders, bipolar disorder, or a history of substance abuse.

3. Lead to suicidal thoughts or sudden or strong feelings.
The risk of suicidal thoughts is already heightened when taking naltrexone and bupropion, especially in young adults or people with mental illness. Adding an MAOI may intensify mood swings, emotional instability, or behavioral agitation.

4. Cause chest pain, agitation, or severe nausea.
People may experience a cluster of distressing symptoms such as rare chest pain, racing heart, dizziness, or severe nausea. These could indicate serotonin syndrome, autonomic instability, or other acute reactions that require immediate medical attention.

The U.S. Food and Drug Administration (FDA) provides specific guidelines regarding the interaction between monoamine oxidase inhibitors (MAOIs) and bupropion. According to the FDA, a minimum 14-day washout period should occur between discontinuing an MAOI intended to treat depression and starting therapy with bupropion. Conversely, at least 14 days should also elapse after stopping bupropion before initiating an MAOI. This washout period is necessary due to the increased risk of hypertensive reactions when bupropion is used concurrently with MAOIs.

“Even a single overlapping dose of Nardil and bupropion could lead to serious neurological or cardiovascular events,” warns Dr. Matthew Olesiak. “It’s not just about avoiding a bad reaction—it’s about preventing a true medical emergency.”

Side Effects to Watch For

Even if you’re not taking Contrave and Nardil together, being prescribed them close in time—or switching from one to the other—requires extra caution. These medications can cause overlapping or compounding side effects. Some may be mild at first, but others may signal a more serious issue developing under the surface.

Be Especially Alert For These Symptoms:

• Headache, irritability, and lack of energy
Often mistaken for fatigue or stress, these could be early signs of a reaction to naltrexone and bupropion, or signs your brain chemistry is being disrupted.

• Lips, stomach pain
This vague cluster can be a symptom of gastrointestinal upset, but when paired with skin flushing or chest pressure, it may indicate an early allergic reaction or autonomic issue.

• Allergic reaction (e.g., hives, swelling of the face, lips, or throat)
These reactions may seem minor at first but can escalate quickly into anaphylaxis. Seek immediate medical attention if you notice swelling, rashes, or trouble breathing.

• Bowel symptoms like nausea, vomiting, or diarrhea
Nausea is a common side effect of extended-release tablets, especially in the first weeks of starting Contrave treatment, but if paired with dizziness or frequent pulse issues, it may signal something more serious.

• Common bladder pain, bloody urine
Unusual urinary symptoms could point to an adverse renal reaction—especially in people with kidney disease or those taking high doses of naltrexone and bupropion.

• Chest pain or rare chest pain
Both medications can affect the heart. Any sensation of tightness, heaviness, or radiating pain in the chest should not be ignored, especially if you’re also feeling faint, dizzy, or nauseous.

If you experience any of the above, contact a medical professional immediately. These symptoms may indicate a severe risk of side effects, ranging from hypertensive crises to serotonin syndrome or even life-threatening reactions.

“No side effect should ever be dismissed as minor if it feels out of place for your body or your baseline,” notes Dr. Olesiak. “The key is to talk with your doctor early—before things escalate.”

Special Precautions

You should always talk with your doctor before starting Contrave treatment, stopping, or combining medications. This is critical to reduce the risk of side effects, particularly in individuals with preexisting health conditions or those taking other medications.

Here are some scenarios where increased risk is likely—and where extreme caution and medical oversight are required:

1. You Have Bipolar Disorder, Mental Disease, or a History of Suicidal Thoughts

People with mood disorders or mental disease, including bipolar disorder, are at greater risk for emotional instability and suicidal thoughts when taking naltrexone and bupropion.

These medications affect brain chemicals linked to mood regulation and can trigger sudden or strong feelings, mood swings, or even psychosis in sensitive individuals.

2. You Suffer from Liver Disease, Kidney Disease, or Age-Related Kidney Problems

Naltrexone and bupropion are metabolized by the liver and excreted through the kidneys. If you have liver disease, kidney disease, or age-related kidney problems, the drugs can build up in your system and lead to toxicity.

In these cases, your healthcare professional may need to adjust your dose or avoid Contrave altogether.

3. You Use Alcoholic Beverages or Drink Alcohol Regularly

Alcohol lowers the seizure threshold and may worsen side effects like dizziness, drowsiness, and nausea pain. It also increases the chances of experiencing accidental overdose or withdrawal-related symptoms if you’re taking naltrexone and bupropion to help reduce alcohol use.

“People with a history of alcohol abuse or dependency should be especially cautious,” says Dr. Matthew Olesiak. “Drink alcohol in moderation if at all, and never combine it with these medications unless cleared by your medical doctor.”

4. You Take Narcotic Drugs, Other Narcotic Medicine, or Other Habit-Forming Painkillers

Naltrexone is an opioid antagonist, meaning it blocks the effects of opioids. If you are taking narcotic drugs, other narcotic medicine, or other habit-forming painkillers, Contrave could cause sudden withdrawal symptoms or reduce the effectiveness of your pain medication.

You should never combine these without direct supervision by a healthcare professional.

5. You Have Eating Disorders Like Bulimia or Anorexia

Individuals with eating disorders often have electrolyte imbalances and a history of purging behaviors, which significantly increases the risk of severe seizures when taking bupropion, one of the active ingredients in Contrave.

This population is generally advised not to take Contrave due to the elevated seizure risk.

Drug Interactions to Watch For

Naltrexone and bupropion should not be taken with certain anxiety medicines (Xanax), antidepressant medications (Paxil, Lexapro, Effexor, Prozac, Cymbalta, Zoloft), over-the-counter sleep aids, or cold remedies containing stimulants (Ephedrine) or serotonin-affecting ingredients without the approval of your healthcare professional.

These combinations can lead to serious skin reactions, serotonin syndrome, or an increase in blood pressure.

Contrave Dosage and Safety Tips

Contrave comes as extended-release tablets, which are designed to maintain a steady release of naltrexone and bupropion in your system over time. According to the FDA-approved prescribing information, using these tablets as directed can reduce the risk of side effects and improve overall success in weight loss and weight management.

Here are key tips to ensure safe use:

Follow Your Doctor’s Instructions Carefully

Your medical doctor will start you on a gradually increasing dose to minimize side effects such as nausea pain, dizziness, or headaches. You should never adjust your dose on your own or take more than prescribed, even if you feel your progress has stalled.

“Many of the more severe issues we see stem from misuse,” warns Dr. Olesiak. “People often think more medication means faster weight loss, but it just increases the risk of complications.”

Never Take Double Doses If You Miss a Missed Dose

If you forget to take your dose, skip it and continue with your next scheduled one. Do not take double doses—taking extra to “make up” can trigger severe seizures, headache irritability lack, or confusion. Always follow your prescribed schedule.

Avoid High-Fat Meals

High fat meals can increase the absorption rate of bupropion, raising the chance of side effects like chest pain, discomfort nausea pain, or dizziness. Stick to a reduced calorie diet that supports your weight loss goals without compromising drug safety.

Sit or Stand Slowly

Some people may experience lightheadedness or muscle cramps in the sitting position when rising too quickly from sitting. This can be a result of fluctuating blood pressure, which is a known side effect of naltrexone and bupropion.

Should You Ever Take Contrave and Nardil Together?

In almost all cases, taking Contrave and Nardil together is not recommended due to the increased risk of life-threatening reactions. Most healthcare professionals will avoid prescribing them together unless absolutely necessary—and even then, only under tightly controlled conditions.

If you’re switching from one medication to another (e.g., stopping Nardil to begin starting Contrave treatment), you may need to wait 14–28 days, depending on your personal medical history.

Additional Safety Reminders

Even if you are following your prescribed dosage of Contrave, maintaining open communication with your healthcare team and staying vigilant about symptoms can help prevent serious complications.

Below are essential precautions to follow throughout your Contrave treatment, especially if you’re managing coexisting conditions or taking other medications.

1. Always Disclose Other Medicines or Other Medications You Take Regularly

Whether prescription, over the counter, or herbal supplements, every substance you take can potentially lead to certain drug interactions. Some may increase the risk of side effects, while others may reduce the effectiveness of naltrexone and bupropion.

Make a full list of all your other medications and share it with your healthcare professional at each appointment.

2. Notify Your Provider About Any Medical Tests You Have Scheduled

Both naltrexone and bupropion can interfere with lab test results, especially those measuring liver function or hormone levels.

Always talk with your doctor ahead of time if you have blood work, imaging, or any medical tests coming up, so they can advise you appropriately or adjust your treatment plan if needed.

3. Be Alert for Symptoms of Accidental Overdose

Taking too much Contrave—either intentionally or due to taking double doses after a missed dose—can lead to dangerous outcomes. Signs of an accidental overdose include tremors, severe seizures, confusion, blurred vision, and agitation.

These symptoms can escalate quickly and require immediate medical attention, so it’s vital to use the medication exactly as prescribed.

4. Don’t Mix Contrave with Narcotic Medicines Unless Your Medical Doctor Has Cleared It

Naltrexone, one of the active ingredients in Contrave, blocks the effects of opioids. If you’re taking narcotic medicines, narcotic drugs, or other narcotic medicines (codeine, methadone, morphine, fentanyl), combining them with Contrave could cause sudden withdrawal, intense pain, or a life-threatening reaction.

Your medical doctor must assess whether it’s safe for you to use Contrave in these circumstances.

5. Monitor Blood Sugar Closely, Especially if You Have Diabetes

Both naltrexone and bupropion can affect blood sugar regulation. You may experience episodes of low blood sugar, particularly if you’re on insulin or other glucose-lowering drugs. Keep a log of your blood sugar readings and report any unusual patterns to your healthcare professional.

Adjustments to your diabetes regimen or diet may be needed.

6. Report Any Skin Reactions or Severe Acne

Watch for signs of skin reactions, such as redness, blistering, rash, or severe acne. These could indicate an allergic reaction or even serious skin reactions that require stopping the medication.

If you notice any changes to your skin, no matter how minor, talk with your doctor right away.

7. Stay Hydrated and Monitor for Digestive Discomfort

Contrave may cause indigestion, nausea, or bloating, particularly during the early phases of treatment. Drinking enough water, eating smaller meals, and avoiding high-fat meals can help minimize symptoms like nausea, pain, stomach upset, or decreased appetite.

8. Use Contrave Only as Part of a Reduced Calorie Diet and Lifestyle Changes

Contrave is not a magic pill—it works best when combined with a reduced-calorie diet, increased physical activity, and healthy behavioral habits. If your goal is to lose weight or improve long-term weight management, following your full treatment plan is essential.

Taking Contrave without lifestyle changes may increase the risk of side effects without delivering the intended weight loss benefits.

Frequently Asked Questions (FAQ)

When it comes to prescription medications like Contrave and Nardil, understanding how they interact with other substances is key to staying safe.

Below are answers to some of the most common questions people ask about combining these drugs with other treatments, especially when managing weight loss, mood disorders, or chronic conditions.

1. What medications should not be taken with Contrave?

Several medications can interact dangerously with Contrave, especially those that affect the brain, liver, or blood pressure. Monoamine oxidase inhibitors (MAOIs) like Nardil must not be taken with Contrave due to the risk of extremely high blood pressure, severe seizures, and other life-threatening side effects.

In addition, narcotic drugs, other habit-forming painkillers, and drugs that lower the seizure threshold, like antipsychotics or certain anxiety medicines, can increase the risk of side effects. Over-the-counter products containing decongestants or stimulants may also raise blood pressure and should be avoided.

Always talk with your doctor before adding new medications while on Contrave.

2. What can you not take with Nardil?

Nardil is a powerful MAOI, and it comes with a long list of restricted substances. You should avoid all other antidepressants (especially SSRIs, SNRIs, and tricyclics), naltrexone and bupropion (found in Contrave), and any drugs that affect serotonin, dopamine, or norepinephrine.

Common cold medications, over-the-counter decongestants, and certain pain relievers like meperidine or tramadol can also cause serious skin reactions, serotonin syndrome, or dangerously high blood pressure. Even certain foods high in tyramine can trigger hypertensive episodes.

Because of these risks, it’s critical to talk with your doctor and review any other medications or supplements before using Nardil.

3. Can I take Contrave and Zoloft together?

Combining Contrave with Zoloft (sertraline), a selective serotonin reuptake inhibitor (SSRI), is not typically recommended without close medical supervision. Both medications influence brain neurotransmitters, and using them together may raise the risk of serotonin syndrome, severe seizures, and worsening mental disease symptoms like anxiety or suicidal thoughts. In some cases, a doctor may decide the benefits outweigh the risks, but this requires regular monitoring.

Be sure to talk with your doctor about any history of bipolar disorder, liver disease, or eating disorders, which may increase the likelihood of complications.

4. Can Contrave worsen depression?

Yes, Contrave can worsen symptoms of depression in some individuals, particularly those with a history of mood disorders or mental disease. The bupropion component is sometimes used to treat depression, but when combined with naltrexone, the emotional response can vary, especially during the initial weeks of treatment. There’s a boxed warning that alerts doctors about the possibility of suicidal thoughts, especially in young adults.

If you notice a change in mood, increased anxiety, or sudden or strong feelings, it’s important to talk with your doctor immediately. Monitoring and possible dosage adjustments can help reduce the risk of side effects.

Final Thoughts

The combination of Contrave and Nardil together can be dangerous without proper oversight. Given the potential for serious side effects, it’s crucial to talk with your doctor and follow up regularly.

“I advise patients to always keep an open line with their healthcare professional,” says Dr. Olesiak. “Even minor side effects can sometimes signal something bigger, especially with complex medications like naltrexone and bupropion or MAOIs.”

Always prioritize safety and long-term health outcomes over short-term weight loss goals. Remember, medications are tools—not substitutes for a broader weight management plan.

References

FDA

FDA Prescribing Information for Contrave