Celexa and Contrave drug interactions portrayd by two capsule side by side with scientific elements in the background.

Celexa and Contrave Drug Interactions: What to Know

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Celexa (citalopram) and Contrave (bupropion-naltrexone) are medications used for different purposes—Celexa to treat depression and Contrave for chronic weight management for compatible individuals.

However, Celexa and Contrave drug interactions can occur if these two medications are taken together, affecting safety and efficacy. Understanding these risks is essential before combining these medications.

Key Takeaways

  • Celexa and Contrave drug interactions can increase the risk of serious adverse reactions such as seizures and high blood pressure.
  • Taking Contrave with Celexa may require dose adjustment to minimize the risk of seizures and other side effects.
  • Patients with bipolar disorder, a seizure disorder, eating disorders, or other risk factors should consult their doctor before taking these medications together.

Understanding Celexa and Contrave Drug Interactions

Celexa (citalopram) is a selective serotonin reuptake inhibitor (SSRI) commonly prescribed to treat depression and other mood disorders. It works by increasing serotonin levels in the brain, improving mood regulation and emotional stability. Contrave, on the other hand, is a weight loss medication that combines naltrexone and bupropion to influence appetite and cravings by acting on the brain’s reward system. Naltrexone is an opioid antagonist used to treat alcohol and opioid dependence, while bupropion is an atypical antidepressant that affects dopamine and norepinephrine levels. Contrave helps promote weight loss in certain individuals.

When Celexa and Contrave are taken together, their interaction can have unintended effects due to the way both medications alter neurotransmitter activity. Bupropion, a key component of Contrave, inhibits the reuptake of dopamine and norepinephrine, while Celexa primarily affects serotonin. The combination can create an imbalance in neurotransmitter regulation, increasing the likelihood of adverse reactions such as serotonin syndrome, nervous system overstimulation, and mood instability.

One of the most significant concerns with this combination is the lower seizure threshold caused by bupropion. Since Celexa may also contribute to mild excitatory effects in the nervous system, the concurrent use of these drugs increases the risk of seizures, particularly in individuals with a history of seizure disorder, bipolar disorder, or brain trauma.

Dr. Matthew Olesiak, MD, Chief Medical Director of SANE MD, states:

“Bupropion, a key ingredient in Contrave, is known to reduce seizure threshold. When combined with an SSRI like Celexa, the risk of seizures may further increase, especially in patients with preexisting risk factors.”

In addition to seizure risk, the interaction between Celexa and Contrave can contribute to serotonin syndrome, a potentially life-threatening condition characterized by confusion, rapid heart rate, high blood pressure, sweating, muscle stiffness, and agitation. This occurs when excessive serotonin accumulates in the nervous system, often as a result of combining multiple drugs that influence serotonin levels.

Celexa and Contrave Drug Interaction Summary

Category Details
Primary Medications Celexa (Citalopram): SSRI antidepressant increasing serotonin levels
Contrave: Weight loss drug (naltrexone + bupropion) acting on dopamine/norepinephrine
Main Interaction Concerns – Increased seizure risk due to bupropion
– Risk of serotonin syndrome
– Blood pressure elevation
– CNS overstimulation
High-Risk Groups – Individuals with:
– Seizure disorders
– Bipolar disorder
– Brain injuries
– Eating disorders
Neurological Side Effects – Dizziness or vertigo
– Confusion or poor concentration
– Tremors or twitching
– Insomnia or restlessness
– Blurred vision
Cardiovascular Risks – High blood pressure
– Severe headaches
– Chest pain or palpitations
– Shortness of breath
Opioid Interaction Risks – Naltrexone blocks opioid receptors
– May cause withdrawal if taken with opioids
– Risk of overdose after stopping Contrave and resuming opioids
Suicidal Thoughts Risk – Both drugs can increase suicidal ideation, especially in those <25
– Watch for sudden mood changes, aggression, or withdrawal
Serious Allergic Reactions – Rash or hives
– Dark urine (possible liver issue)
– Chest pain or difficulty breathing

Increased Risk of Seizures and CNS Toxicity

Taking Contrave with Celexa can significantly increase the risk of seizures, especially for individuals who have a seizure disorder, bipolar disorder, a history of traumatic brain injury, or a brain tumor. According to research published in Pharmacy & Therapeutics Journal, Bupropion, one of the main components of Contrave, is known to lower seizure threshold, making seizures more likely when combined with other medications that impact the central nervous system (CNS), such as Celexa.

Additionally, naltrexone and bupropion both influence neurotransmitter activity in the brain, which can contribute to CNS toxicity when taken with Celexa. This may lead to symptoms such as:

  • Dizziness or vertigo
  • Confusion or difficulty concentrating
  • Tremors or muscle twitching
  • Increased nervous system stimulation, leading to restlessness or insomnia
  • Headaches and blurred vision

Because these side effects can affect cognitive function, patients should avoid activities requiring mental alertness, such as driving or operating heavy machinery, until they fully understand how the combination of medications affects them.

Dr. Olesiak notes: “Patients taking both Celexa and Contrave should be cautious of potential neurological side effects, including dizziness and tremors, which may impair motor function and decision-making.”

In individuals predisposed to seizures, even small changes in dosage or missed doses can trigger an episode. The FDA emphasizes the importance of following a healthcare provider’s guidance on dose adjustments to minimize the risk of seizures.

Blood Pressure and Cardiovascular Concerns

Both Celexa and Contrave can impact blood pressure, but taking Contrave increases the likelihood of developing high blood pressure or severely high blood pressure, particularly in individuals who have preexisting cardiovascular conditions. Bupropion, a stimulant-like drug, can elevate blood pressure, while naltrexone can also contribute to fluctuations in heart rate and blood pressure or heart function.

Patients who already have hypertension, heart disease, or a history of stroke are at an even higher risk of developing hypertensive reactions, which may present as:

  • Severe headaches
  • Dizziness and vision changes
  • Chest pain or palpitations
  • Shortness of breath

For individuals on both Celexa and Contrave, frequent monitoring of blood pressure is essential to prevent dangerous spikes.

Dr. Olesiak advises: “Because bupropion can cause an increase in blood pressure, patients taking Contrave should regularly monitor their readings, especially if they are also on SSRIs like Celexa.”

If a patient develops severely high blood pressure or experiences chest pain, they should seek immediate medical attention. In some cases, a dose adjustment or alternative treatment may be necessary to lower the risk of cardiovascular complications.

Additional Risks and Considerations

Opioid Withdrawal & Accidental Overdose

Since naltrexone and bupropion block opioid receptors, individuals using opioid-based medications or struggling with opioid dependence must avoid taking Contrave. This is because naltrexone prevents opioids from binding to receptors, which can trigger opioid withdrawal symptoms if the individual is physically dependent.

Common symptoms of opioid withdrawal include:

  • Severe nausea and vomiting
  • Sweating and chills
  • Increased heart rate and blood pressure
  • Muscle aches and restlessness

Additionally, individuals who stop taking Contrave and later use opioids may have a reduced tolerance, making them susceptible to an accidental overdose, which could be fatal. Patients should tell their doctor if they are taking opioids before starting Contrave treatment.

Increased Risk of Suicidal Thoughts

As with most antidepressants, Celexa carries an FDA warning for suicidal thoughts in young adults, particularly during the initial weeks of treatment. Bupropion, while not a traditional SSRI, also alters brain chemistry, and its stimulating effects may increase the risk of anxiety, restlessness, or impulsivity. When used together, these drugs may elevate the likelihood of:

  • Suicidal ideation
  • Self-harm thoughts
  • Severe mood swings or aggression

Patients (especially those under the age of 25) and their families should monitor for behavioral changes, including sudden agitation, social withdrawal, or unexplained mood shifts. Tell your doctor immediately if these symptoms occur.

Serious Allergic Reaction

Though uncommon, some individuals may experience a serious allergic reaction to Celexa, Contrave, or their combined effects.

Symptoms of a severe allergic reaction include:

  • Skin rash or hives
  • Dark urine, indicating possible liver issues
  • Severe chest pain or difficulty breathing

If any of these symptoms occur, seek immediate medical attention to prevent serious complications. Tell your doctor about any history of allergies before taking these medications.

Understanding these side effects and safety guidelines can help you take these medications safely.

5 Celexa and Contrave Drug Interactions Infographic

Safe Use Guidelines

To reduce the potential risks associated with Celexa and Contrave drug interactions, patients should follow these essential safety guidelines:

1. Tell Your Doctor About All Other Drugs and Over-the-Counter Drugs You Are Taking

Many other drugs, including over-the-counter drugs, herbal supplements, and prescription medications, can interact with Celexa and Contrave, potentially increasing the risk of adverse reactions.

Some medications that require special attention include:

  • Other antidepressants (e.g., SSRIs, SNRIs, MAOIs)
  • Antipsychotic medications (may further lower seizure threshold)
  • Blood pressure medications (as Contrave may cause fluctuations in blood pressure)
  • Opioid pain relievers, Codeine such as , (which Contrave blocks due to its naltrexone component)
  • Over-the-counter drugs like decongestants or nonsteroidal anti-inflammatory drugs (NSAIDs), which may elevate blood pressure

Additionally, stimulants like Modafinil can also interact with Contrave.

Since some interactions may increase the risk of seizures, hypertensive reactions, or serotonin syndrome, it is critical to tell your doctor about all medications you are taking before starting Contrave treatment.

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2. Avoid High-Fat Meals When Taking Contrave

Taking Contrave with high-fat meals can increase systemic exposure to bupropion, leading to a higher risk of adverse effects, including:

  • Increased blood pressure or heart rate
  • Nausea, dizziness, or agitation
  • Lower seizure threshold, heightening the risk of seizures

To minimize these risks, Contrave tablets should be taken with a reduced-calorie diet, but without excessive dietary fat.

Patients should focus on balanced meals and avoid consuming high-fat meals around their dosing schedule.

3. Do Not Suddenly Stop Drinking Alcohol

Abruptly stopping alcohol consumption while taking Contrave or Celexa can increase the risk of withdrawal symptoms, including:

  • Seizures (due to bupropion lowering seizure threshold)
  • Severe agitation or anxiety
  • Sleep disturbances and mood instability

However, if you’re not a regular drinker, you should avoid drinking alcohol while on either of these drugs. (Contrave and alcohol drug interactions can be particularly severe.)

Patients who regularly consume alcohol should discuss a safe reduction plan with their healthcare provider before starting Contrave treatment.

Tell your doctor if you have a history of heavy alcohol use, as you may require a dose adjustment or closer monitoring.

4. Swallow Contrave Tablets Whole—Do Not Crush, Chew, or Split Them

Contrave tablets are extended-release tablets, meaning the medication is designed to be released into the body gradually over time.

Crushing, chewing, or splitting the tablets can:

  • Cause a sudden spike in drug levels, leading to adverse reactions
  • Increase the risk of seizures, particularly in individuals predisposed to them
  • Alter how the medication is absorbed, reducing effectiveness

Patients should swallow Contrave tablets whole with water and follow the prescribed dosing schedule. If a dose is missed, take the next scheduled dose rather than doubling up.

5. Follow the Prescribed Dose Range and Take Contrave in Divided Doses

To minimize the risk of hypertensive reactions, seizures, and other side effects, Contrave should be taken exactly as prescribed. Typically, Contrave is started at a lower dose and gradually increased to help the body adjust.

Taking too much too quickly can increase the risk of:

  • Severely high blood pressure (Combining Contrave with Propranolol, a beta-blocker, can further affect blood pressure.
  • Nervous system overstimulation (e.g., restlessness, jitteriness)
  • Lower seizure threshold, increasing seizure risk

Patients should never exceed the recommended dose range or change their dosing schedule without consulting a healthcare provider.

6. Monitor for Trouble Sleeping, as Contrave Can Cause Insomnia

Contrave contains bupropion, a stimulant-like drug, which can cause trouble sleeping, particularly if taken too close to bedtime.

Patients who experience persistent insomnia should:

  • Take Contrave earlier in the day to reduce its impact on sleep
  • Avoid caffeine and other stimulants, which may worsen restlessness
  • Discuss potential dose adjustments with their doctor if sleep disturbances become severe

If insomnia persists, tell your doctor, as alternative treatment strategies may be needed to ensure safe and effective chronic weight management without disrupting sleep quality.

FAQ: Celexa and Contrave Drug Interactions

When considering Celexa and Contrave drug interactions, it’s important to understand how these medications may interact with each other and with other drugs. Both Celexa (citalopram) and Contrave (naltrexone-bupropion) affect neurotransmitters, meaning their combination can lead to an increased risk of side effects, including seizures, high blood pressure, and serotonin syndrome.

Below are answers to some of the most common questions regarding their safe use.

1. Can you take Contrave while on antidepressants?

Taking Contrave while on antidepressants can be risky due to potential interactions between bupropion (a component of Contrave) and other antidepressants. Bupropion can increase serotonin and dopamine levels, which, when combined with SSRIs or SNRIs, may raise the risk of serotonin syndrome—a dangerous condition characterized by agitation, rapid heartbeat, and high fever.

Additionally, bupropion can lower the seizure threshold, making seizures more likely, especially if combined with medications that have similar effects. Patients currently on antidepressants should consult their doctor before starting Contrave, as a dose adjustment or alternative treatment may be necessary.

2. Can Celexa and buPROPion be taken together?

Celexa (citalopram) and bupropion are sometimes prescribed together, but this combination requires careful monitoring. While both medications are used to treat depression, they act on different neurotransmitters—Celexa primarily affects serotonin, while bupropion impacts dopamine and norepinephrine. Taking them together may increase the risk of seizures, especially in patients with seizure disorder, bipolar disorder, or other neurological conditions. There is also a potential for high blood pressure or mood instability.

If these medications are prescribed together, patients should be monitored for trouble sleeping, restlessness, and changes in blood pressure. Always tell your doctor about any side effects that arise.

3. What medications should not be taken with Contrave?

Several medications should not be taken with Contrave due to the risk of severe drug interactions.

These include:

  • Opioid medications (e.g., oxycodone, morphine, fentanyl) – Contrave contains naltrexone, which blocks opioid receptors, potentially causing opioid withdrawal if taken together.
  • Monoamine oxidase inhibitors (MAOIs) (e.g., phenelzine, selegiline) – These drugs can lead to dangerous blood pressure spikes and serotonin syndrome when combined with Contrave.
  • Other drugs that lower seizure threshold (e.g., antipsychotics, steroids, certain antibiotics) – Combining them with Contrave may increase the risk of seizures.
  • Stimulants and amphetamines (e.g., Adderall, Ritalin) – These can exacerbate Contrave’s effects on blood pressure and the central nervous system, increasing the likelihood of hypertension, anxiety, or heart issues.
    Because Contrave contains bupropion and naltrexone, it’s crucial to tell your doctor about all other drugs and over-the-counter medications you’re taking.

4. What Cannot be taken with Celexa?

Several medications should not be taken with Celexa due to the risk of dangerous interactions.

These include:

  • Other antidepressants, especially MAOIs – Combining Celexa with MAOIs or other SSRIs/SNRIs can lead to serotonin syndrome, a life-threatening condition.
  • NSAIDs and blood thinners (e.g., aspirin, warfarin) – Celexa can increase the risk of bleeding, particularly in patients using blood thinners.
  • Certain heart medications – Drugs that prolong the QT interval (e.g., amiodarone, sotalol) can increase the risk of irregular heart rhythms when taken with Celexa.
  • St. John’s Wort – This herbal supplement can increase serotonin levels, heightening the risk of serotonin syndrome.
    Patients should always tell their doctor about all medications and supplements they are taking before starting Celexa.

5. Can you take citalopram with Contrave?

Taking citalopram (Celexa) with Contrave can be dangerous due to their combined effects on neurotransmitters and blood pressure. Bupropion in Contrave lowers the seizure threshold, while citalopram can prolong the QT interval, increasing the risk of serious heart rhythm issues. Additionally, both drugs impact serotonin levels, which may increase the risk of serotonin syndrome if taken together.

Patients with a history of seizures, heart conditions, or high blood pressure should avoid taking these medications together unless advised by their doctor. If prescribed both, close monitoring of blood pressure, heart function, and neurological symptoms is essential to reduce the risk of serious side effects.

Conclusion

The Contrave interactions with Celexa pose risks that require careful monitoring. Individuals considering this combination should consult a healthcare professional to determine if a dose adjustment is needed or if alternative medications should be considered. Tell your doctor immediately if experiencing severe hepatic impairment, eye pain, or signs of an allergic reaction.

Understanding these interactions before starting Contrave treatment is crucial to ensuring a safe and effective treatment regimen for chronic weight management while minimizing the risk of seizures and high blood pressure.

References

Pharmacy & Therapeutics Journal

FDA

FDA

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Contrave and Morphine Drug interactions portrayed by a pill bottle of contrave and another one of morphine.

Contrave and Morphine Drug Interactions: What to Know

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Understanding the potential Contrave and morphine drug interactions is crucial for individuals managing weight loss while requiring pain management. Contrave is a prescription medication combining naltrexone and bupropion, approved for chronic weight management in certain adults with an initial body mass index (BMI) of 30 kg/m² or greater or 27 kg/m² with at least one weight-related comorbidity. Morphine is a potent opioid analgesic used to treat severe pain.

Combining these medications can lead to significant drug interactions, primarily due to naltrexone’s role as an opioid antagonist, which can precipitate opioid withdrawal and affect pain management efficacy.​

Dr. Matthew Olesiak, Chief Medical Director at SANE MD, emphasizes, “​Patients must inform their healthcare providers about all medications they are taking, including over-the-counter drugs and supplements, to prevent adverse interactions between Contrave and opioid medications like morphine.”​

Key Takeaways

  • Naltrexone, a component of Contrave, can block the effects of opioids like morphine, potentially leading to opioid withdrawal symptoms.
  • Both naltrexone and bupropion can influence blood pressure, necessitating careful monitoring when combined with other medications affecting cardiovascular health.

Comprehensive communication with a healthcare provider is essential to manage potential interactions and ensure safe medication use.

Medication Guide

Before starting Contrave treatment, patients should carefully review the medication guide provided by their healthcare provider or pharmacist. The medication guide contains important details about how to take Contrave, potential drug interactions, and possible adverse reactions.

It is essential to follow the guidelines outlined in the medication guide to avoid serious complications, such as opioid withdrawal, high blood pressure, or serotonin syndrome. If there are any concerns or questions about the medication guide, patients should consult their healthcare provider for clarification.

Contrave and Morphine Drug Interaction Table

Interaction Effect Recommendation
Opioid Withdrawal Naltrexone in Contrave blocks opioid receptors, leading to withdrawal symptoms if opioids like morphine are used. Avoid opioid use while taking Contrave. Detox from opioids for at least 7-10 days before starting Contrave.
Reduced Pain Management Naltrexone blocks the pain-relieving effects of morphine, making it ineffective. Use non-opioid alternatives such as acetaminophen or NSAIDs for pain relief.
Blood Pressure Variations Bupropion in Contrave can increase blood pressure, while morphine may lower it, causing unpredictable fluctuations. Monitor blood pressure regularly and consult a healthcare provider if fluctuations occur.
Increased Seizure Risk Bupropion lowers seizure threshold, and opioid withdrawal may increase seizure risk. Avoid alcohol, sudden discontinuation of Contrave, and other seizure-inducing medications.
Liver Health Concerns Both Contrave and morphine are metabolized in the liver, potentially increasing toxicity risk in individuals with liver disease. Regular liver function tests are recommended for patients with liver conditions. Avoid high-fat meals while on Contrave.
Medication Alternatives Morphine is ineffective while taking Contrave due to naltrexone’s opioid blockade. Consider non-opioid pain relief options such as NSAIDs, acetaminophen, or nerve pain medications like gabapentin.
Emergency Pain Management Contrave blocks opioid efficacy, making emergency pain relief difficult. Inform healthcare providers about Contrave use before surgeries or procedures requiring opioids. Temporary discontinuation of Contrave may be necessary.

What Is Contrave?

Contrave is a prescription medication approved for chronic weight management in adults with an initial body mass index (BMI) of 30 or higher, or 27 or higher with weight-related conditions such as high blood pressure or type 2 diabetes. It combines naltrexone and bupropion, two drugs that work together to help compatible patients lose weight when used alongside a reduced-calorie diet and physical activity.

  • Naltrexone is an opioid antagonist primarily used to treat alcohol and opioid dependence. In Contrave, it plays a role in reducing food cravings.
  • Bupropion is an antidepressant that helps regulate appetite and energy balance. It is also used to treat depression and aid in smoking cessation.

Taking Contrave requires medical supervision, especially for individuals with high blood pressure, mental illness, or a history of eating disorders such as anorexia nervosa.

The medication is available in the form of extended-release tablets. It is important to avoid using it if you have taken monoamine oxidase inhibitors (MAO inhibitors) within the last two weeks.

What Is Morphine?

Morphine is a powerful opioid medication prescribed to treat pain, particularly severe pain that does not respond to other pain relievers. It works by binding to opioid receptors in the brain and spinal cord, reducing the perception of pain.

Morphine is available in various forms, including extended-release and immediate-release tablets, as well as injectable and liquid formulations. While effective for pain management, morphine use carries risks, including dependence, tolerance, and opioid withdrawal symptoms if suddenly discontinued.

Patients with liver disease, renal impairment, or head injury should use morphine with caution. Additionally, combining morphine with other central nervous system depressants, including alcohol, can lead to trouble breathing and life-threatening complications. Individuals using morphine should follow their healthcare provider’s guidance to minimize the risk of serious injury or overdose.

How Contrave and Morphine Affect the Body

Contrave is used for chronic weight management in certain individuals with an initial body mass index (BMI) above a certain threshold. It combines naltrexone and bupropion, where naltrexone is an opioid antagonist, and bupropion is an antidepressant that may treat depression and help with weight loss. Morphine, on the other hand, is a severe pain reliever belonging to the opioid medications class.

When taking Contrave, patients should avoid opioids, including morphine, as naltrexone can block their effects, rendering them ineffective and leading to opioid withdrawal. Additionally, both medications can elevate blood pressure, increasing the increased risk of chest pain and cardiovascular morbidity.

Mechanism of Action: Contrave and Morphine

Contrave combines two active ingredients:

  1. Naltrexone: An opioid antagonist that blocks opioid receptors, reducing the rewarding effects of alcohol and opioids.
  2. Bupropion: An aminoketone antidepressant that inhibits the reuptake of norepinephrine and dopamine, neurotransmitters involved in regulating mood and appetite.

Together, these components target central nervous system pathways to aid in weight management.​

Morphine is an opioid analgesic that binds to opioid receptors in the brain and spinal cord to alleviate pain. However, when naltrexone is present, it can block these receptors, rendering morphine less effective or ineffective. This antagonistic action can precipitate opioid withdrawal symptoms in individuals dependent on opioids.​

Potential Risks of Combining Contrave and Morphine

1. Opioid Withdrawal

Administering naltrexone to individuals dependent on opioids like morphine can induce acute withdrawal symptoms, which may be severe and require immediate medical attention. Because naltrexone is an opioid antagonist, it rapidly displaces opioids from their receptors, leading to sudden and intense withdrawal effects.

Symptoms may include severe nausea, vomiting, sweating, tremors, rapid heartbeat, high blood pressure, agitation, confusion, and intense cravings. In extreme cases, withdrawal can lead to dehydration, cardiovascular instability, or seizures, requiring hospitalization.

Individuals who have been on long-term opioid therapy should not take Contrave unless they have fully detoxed from opioids for at least 7-10 days, as recommended by the FDA. Even in patients who are not opioid-dependent, taking Contrave after recent opioid use (such as post-surgical morphine administration) can trigger partial withdrawal symptoms, leading to discomfort and distress.

2. Altered Pain Management

Because naltrexone blocks opioid receptors, it can significantly reduce the analgesic effects of morphine and other opioid medications. This poses a serious challenge for individuals managing chronic pain, post-surgical recovery, or acute injuries requiring opioid analgesia. If a patient taking Contrave needs pain relief, alternative non-opioid pain management strategies, such as acetaminophen, NSAIDs (like ibuprofen or naproxen), or nerve pain medications (such as gabapentin), should be considered.

However, naltrexone’s effects on opioid receptors can last for up to 24 hours, meaning that even if opioid medications are later introduced, they may not work effectively until naltrexone has cleared the body. For individuals needing emergency or post-surgical opioid pain management, tell your doctor about taking Contrave in advance so proper pain relief strategies can be planned.

3. Blood Pressure Variations

Bupropion, one of the active ingredients in Contrave, is known to increase blood pressure and heart rate, potentially leading to high or severely high blood pressure in susceptible individuals (FDA).

Since morphine can sometimes cause low blood pressure, the combination of these two drugs may create unpredictable blood pressure fluctuations, putting additional strain on the cardiovascular system.

Patients with pre-existing hypertension, cardiovascular disease, or a history of stroke are at increased risk of complications. Tell your doctor before taking Contrave if you have high blood pressure or any other cardiovascular morbidity to ensure appropriate monitoring.

Blood pressure should be regularly checked while on Contrave treatment, and adjustments to medication or lifestyle factors (such as a reduced calorie diet and physical activity) may be required.

4. Seizure Risk

Bupropion is known to lower the seizure threshold, meaning that individuals taking Contrave are at an increased risk of seizures, particularly if they have predisposing conditions such as a history of seizures, head injury, or eating disorders like anorexia nervosa or bulimia nervosa. (NIH).

Additionally, opioid withdrawal itself can induce seizures, particularly if withdrawal symptoms are severe and include rapid changes in blood pressure, dehydration, or extreme agitation. If Contrave is taken by someone who is physically dependent on morphine, the risk of seizure activity may be even higher due to a combination of withdrawal effects and bupropion’s pro-seizure potential.

To minimize risk:

  • Do not suddenly stop drinking alcohol while taking Contrave, as alcohol withdrawal can also increase seizure risk.
  • Avoid other medications that lower the seizure threshold, such as certain antidepressants, tramadol, or high doses of stimulants.
  • Tell your doctor if you have a history of head injury, seizure disorder, or eating disorders before taking Contrave.

5. Liver Health Considerations

Both naltrexone and bupropion undergo hepatic metabolism, meaning that liver disease can impact how these drugs are processed, potentially leading to systemic exposure and increased risk of toxicity. (NCBI).

Individuals with moderate to severe liver disease should avoid Contrave treatment, as impaired liver function may cause the medication to accumulate in the body, leading to higher-than-intended doses and increased side effects.

Additionally, morphine is metabolized primarily in the liver and kidneys, meaning that individuals with liver disease or renal impairment may experience longer drug half-life and stronger effects, including an increased risk of respiratory depression and serious injury due to prolonged sedation.

To ensure safety:

  • Tell your doctor if you have liver disease before taking Contrave.
  • Monitor liver enzymes regularly if prescribed Contrave treatment while having a history of liver conditions.
  • Avoid high-fat meals, which may increase bupropion’s systemic exposure, leading to enhanced drug effects.
  • Use alternative pain management methods if opioid medications are necessary.

5 Contrave and Morphine Drug Interactions Infographic

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Safety Recommendations

1. Comprehensive Medication Review

Before starting Contrave treatment, it is essential to provide a complete list of all medications—including prescription drugs, over-the-counter medications, herbal preparations, and dietary supplements—to your healthcare provider. This step ensures that potential drug interactions can be identified early, reducing the increased risk of complications such as opioid withdrawal, high blood pressure, and serious allergic reaction.

For example, individuals who are already taking opioid medications for severe pain may face serious issues if they start taking Contrave, as naltrexone will block opioid effects and could lead to withdrawal symptoms. Additionally, certain other medications, such as monoamine oxidase inhibitors (MAO inhibitors) used for depression or mental illness, can dangerously interact with naltrexone and bupropion, leading to conditions like serotonin syndrome or severely high blood pressure. (FDA)

To ensure safety, individuals should tell their doctor if they are taking:

  • Opioid medications, including morphine, oxycodone, fentanyl, or tramadol
  • Antidepressants like Lexapro, or mood stabilizers, particularly MAO inhibitors
  • Medications like propranolol  for high blood pressure or cardiovascular conditions
  • Other weight loss medications or stimulants
  • Drugs for mental health conditions, including treatments for bipolar disorder
  • Over-the-counter drugs such as NSAIDs, cough suppressants, and decongestants
  • Herbal preparations that could interfere with liver metabolism

2. Avoidance of Opioid Use

Because Contrave contains naltrexone, an opioid antagonist, it completely blocks the effects of opioids. Patients undergoing Contrave treatment should avoid using opioid-containing medications to prevent opioid withdrawal and ensure that the weight loss regimen is effective.

Even if a person is not currently dependent on opioids, using morphine or other opioid pain relievers while taking Contrave may still lead to unexpected complications. In emergency situations where opioid pain relief is necessary (such as following dental surgery or a serious injury), the healthcare provider may need to adjust the treatment plan by either:

  • Temporarily stopping Contrave before opioid administration
  • Using non-opioid pain relief alternatives, such as acetaminophen or NSAIDs
  • Monitoring patients closely for signs of opioid withdrawal or pain management failure

Patients considering Contrave treatment should ensure they have been opioid-free for at least 7–10 days before starting the medication. (NIH) If there is uncertainty about past opioid use, a urine drug test may be performed before prescribing Contrave.

3. Regular Monitoring

Due to the potential side effects of naltrexone and bupropion, regular monitoring by a healthcare provider is essential while taking Contrave.

Key aspects of monitoring include:

  • Blood Pressure ChecksBupropion can increase blood pressure, so individuals with high blood pressure or cardiovascular morbidity should have regular readings taken. In some cases, additional medication adjustments or lifestyle modifications may be needed to prevent complications.
  • Mood and Mental Health AssessmentsTaking Contrave can lead to suicidal thoughts, false beliefs, or worsening mental illness, particularly in individuals with bipolar disorder or depression. Any signs of hallucinations, agitation, or mood instability should be reported to a healthcare provider immediately.
  • Metabolic and Liver Function Tests – Because Contrave treatment affects liver disease and metabolism, routine liver enzyme tests may be required, particularly in individuals with a history of hepatic impairment or those who drink alcohol regularly.
  • Weight Loss Progress—Patients using Contrave for chronic weight management should track their weight changes, ensuring that the medication is effectively helping them lose weight in combination with a reduced-calorie diet and physical activity.

Dr. Matthew Olesiak states, “Ongoing monitoring while taking Contrave ensures that potential risks—such as changes in blood pressure, mental health, or liver function—are managed before they escalate into serious complications.”

4. Patient Education

Patients should be fully informed about the potential risks and side effects of Contrave treatment, including:

  • Recognizing signs of opioid withdrawal – Symptoms such as trouble breathing, eye pain, chest pain, or severe nausea could indicate withdrawal triggered by naltrexone. (FDA)
  • Understanding the risks of low blood sugar—Contrave can contribute to low blood sugar, particularly in individuals with diabetes or those using other weight loss medications. Symptoms such as dizziness, confusion, or unusual sweating should be reported immediately.
  • Identifying early signs of serotonin syndrome – A potentially life-threatening condition that can occur when bupropion interacts with certain other drugs (such as antidepressants or migraine medications). Symptoms include rapid heart rate, agitation, muscle stiffness, and high fever.
  • Monitoring for allergic reactions—Some individuals may experience a serious allergic reaction while taking Contrave, such as rash, swelling, difficulty breathing, or anaphylaxis. If this occurs, seek immediate medical attention.

Patients should also be advised never to suddenly stop drinking alcohol while taking Contrave, as alcohol withdrawal combined with bupropion could increase the risk of seizures or severe mood changes. (NIH)

By staying informed and communicating regularly with their healthcare provider, patients can ensure that their Contrave treatment remains safe and effective.

Frequently Asked Questions (FAQ) About Contrave and Morphine

Understanding the potential interactions between Contrave and morphine is crucial for those using these medications. Since Contrave contains naltrexone and bupropion, it can significantly impact the effects of opioid medications like morphine.

Below are answers to common questions regarding the safety, risks, and recommended alternatives when taking these drugs together.

1. What medications should not be taken with Contrave?

Several medications should not be taken with Contrave, as they can lead to serious interactions or health risks. Opioid medications (such as morphine, oxycodone, and fentanyl) should be avoided because naltrexone blocks opioid receptors, potentially triggering opioid withdrawal. Monoamine oxidase inhibitors (MAO inhibitors), used to treat depression and mental illness, should not be combined with Contrave, as this could cause severely high blood pressure or serotonin syndrome.

Additionally, medications that lower the seizure threshold, such as other antidepressants, tramadol, or stimulant drugs, should be used with caution due to the risk of seizures. Check out our guide to see how Contrave interacts with other drugs.

Always tell your doctor about all prescription drugs, over-the-counter medications, and supplements before taking Contrave to prevent dangerous interactions. (FDA)

2. Can you take morphine while taking naltrexone?

No, morphine should not be taken while using naltrexone, as naltrexone is an opioid antagonist that blocks opioid receptors. This means morphine will not work to relieve pain, making it ineffective for treating moderate to severe pain.

Additionally, if a person is dependent on opioids, naltrexone can trigger sudden and severe opioid withdrawal, leading to symptoms such as nausea, vomiting, sweating, tremors, rapid heart rate, high blood pressure, and intense cravings.

Patients requiring opioid medications for pain relief should wait at least 7-10 days after stopping opioids before beginning naltrexone-based treatments like Contrave. (NIH)

3. What painkillers can I take with Contrave?

Since Contrave contains naltrexone, which blocks opioids, opioid-based painkillers (e.g., morphine, oxycodone, hydrocodone, and codeine) should be avoided. However, non-opioid pain relievers such as acetaminophen (Tylenol), ibuprofen (Advil, Motrin), and naproxen (Aleve) are generally safe alternatives for pain management while taking Contrave.

Some prescription nerve pain medications, such as gabapentin or pregabalin, may also be options for patients needing chronic pain relief. Before taking any pain relievers, consult your healthcare provider to ensure there are no additional risks based on your medical history.

4. What drugs cannot be taken with morphine?

Morphine should not be combined with medications that depress the central nervous system (CNS) or affect opioid metabolism.

Drugs to avoid include:

  • Other opioid medications (e.g., oxycodone, codeine, fentanyl) due to overdose risk.
  • Benzodiazepines (e.g., Xanax, Valium) and muscle relaxants, as they increase the risk of trouble breathing and life-threatening respiratory depression.
  • MAO inhibitors, which can cause severe high blood pressure and dangerous CNS interactions.
  • Certain antidepressants, which can increase the risk of serotonin syndrome.
  • Alcohol, as it enhances sedation and may cause serious injury or death due to respiratory depression.

Always tell your doctor about all other medications before using morphine, as drug interactions can have severe and life-threatening consequences. (FDA)

5. What happens if you take opioids with Contrave?

If a person taking Contrave (which contains naltrexone and bupropion) also takes opioids, the opioid effects will be blocked, making them ineffective for pain relief. In individuals who regularly use opioids, this interaction can lead to sudden opioid withdrawal, causing symptoms such as nausea, sweating, anxiety, tremors, and severe flu-like discomfort.

This withdrawal can be dangerous and may require hospitalization if severe. Additionally, if someone attempts to take higher opioid doses to override the naltrexone block, this significantly increases the risk of overdose once naltrexone wears off.

If pain management is necessary while on Contrave, tell your doctor to discuss alternative treatment options.

6. Can you take bupropion and morphine together?

Bupropion and morphine should be used together with caution, as bupropion can lower the seizure threshold, and opioids like morphine may increase sedation and respiratory depression. Additionally, bupropion affects dopamine and norepinephrine, which could interact with morphine’s central nervous system effects, leading to unpredictable mood or neurological changes.

Patients with a history of seizures, head injury, or substance use disorder should be particularly cautious. While these two drugs are not always contraindicated, combining them should only be done under the supervision of a healthcare provider who can monitor for potential adverse effects.

Conclusion

The combination of Contrave and morphine presents significant interaction risks due to naltrexone’s opioid antagonism and bupropion’s effects on blood pressure and seizure threshold. Thorough communication with a healthcare provider is essential to navigate these risks effectively.

To ensure safe and effective treatment outcomes, patients should adhere to prescribed guidelines, report all medications and supplements they are taking, and attend regular medical appointments.​

For more detailed information, consult the FDA’s prescribing information for Contrave and the NCBI’s LiverTox database on naltrexone and bupropion.

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Taking Contrave and St. John's Wort Together symbolized by a woman with a worried expression looking at a bottle of St. John's Wort.

Taking Contrave and St. John’s Wort Together: Is it Unsafe?

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The rising popularity of prescription weight loss medication like Contrave, combined with the widespread use of herbal remedies such as St. John’s Wort, raises a critical question for patients trying to lose weight safely: Can you take Contrave and St. John’s Wort together, or is it unsafe?

Contrave is a prescription drug that contains two active ingredients—bupropion and naltrexone—designed to help regulate appetite and influence the brain’s reward pathways. St. John’s Wort, on the other hand, is a widely available herbal supplement often used to treat depression and mood disorders by increasing serotonin levels. While both substances affect the central nervous system, using them together may pose serious health risks, especially in people with preexisting medical conditions like bipolar disorder, seizure disorders, or high blood pressure.

“Many patients are unaware that mixing prescription weight loss drugs with certain dietary supplements can result in potentially life-threatening interactions,” says Dr. Matthew Olesiak, Chief Medical Director of SANE MD. “This is especially true with compounds that affect serotonin levels, like St. John’s Wort.”

Understanding how these two drugs interact—alongside the potential consequences—is crucial for anyone considering taking Contrave and St. John’s Wort together.

Key Takeaways

  • Taking Contrave and St. John’s Wort together may significantly increase the risk of serotonin syndrome, a potentially life-threatening condition caused by excessive serotonin in the brain.
  • Patients with underlying medical conditions such as seizure disorders, high blood pressure, or liver disease are at an even higher risk of serious drug interactions.
  • Always consult your healthcare provider before combining prescription medications with over-the-counter supplements or other drugs.

Understanding Contrave

Contrave combines sustained-release bupropion and extended-release naltrexone—two drugs that target appetite regulation and the brain’s reward pathways to support weight loss for certain individuals. Bupropion is also used in smoking cessation and as an antidepressant, while naltrexone is typically used to manage alcohol and opioid dependence.

The way bupropion affects dopamine and norepinephrine makes it a unique prescription weight loss medication. However, it also lowers the seizure threshold, which can increase the risk of seizures—especially when combined with other drugs or supplements that affect serotonin or the central nervous system.

People with a history of seizure disorders, eating disorders, or those who drink alcohol excessively may face an increased risk when using Contrave. The medication guide also warns against abrupt discontinuation, as it may cause mood destabilization and other withdrawal symptoms. Weight gain may also occur.

What Is St. John’s Wort?

St. John’s Wort (Hypericum perforatum) is an herbal supplement commonly used to treat depression, mood swings, and mild anxiety. It influences neurotransmitters like serotonin, dopamine, and norepinephrine, similar to selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs).

Because of its wide-ranging effects on the brain, St. John’s Wort is known to interact with many other medications. These drug interactions may affect everything from the liver’s ability to metabolize drugs to serotonin levels in the brain.

Despite being classified as a dietary supplement, St. John’s Wort is a potent compound and should never be considered harmless—especially when used with other medications.

Why Taking Contrave and St. John’s Wort Together Is Risky

Combining two drugs that influence serotonin—like Contrave and St. John’s Wort—can increase the risk of serotonin syndrome, a rare but potentially fatal condition marked by confusion, agitation, tremors, sweating, high blood pressure, and trouble breathing.

This is especially concerning for compatible patients taking Contrave for weight loss, as many may not realize that bupropion can amplify serotonin activity indirectly. When paired with another serotonergic agent, the effects may be compounded.

“Most healthcare providers warn against combining serotonergic medications with herbal supplements like St. John’s Wort because of the increased risk of serotonin syndrome,” says Dr. Olesiak. “It’s essential to inform your doctor about all the medications and supplements you take—even those you consider harmless.”

St. John’s Wort can also accelerate the metabolism of bupropion and naltrexone in the liver, reducing their effectiveness and altering the drug’s intended balance. This not only reduces the drug’s weight loss benefits but may also contribute to unusual symptoms like irritability, sleep disturbances, or dry mouth.

Additionally, combining these two drugs may:

  • Increase the risk of hypertensive crisis, especially in those with high blood pressure or on monoamine oxidase inhibitors (MAOIs).
  • Trigger mood destabilization in individuals with bipolar disorder or other mood disorders.
  • Elevate seizure risk in people with existing seizure disorders or those prone to abrupt discontinuation of medications.

Drug Interactions: What You Need to Know

When it comes to weight loss drugs, drug interactions are a critical factor in patient safety. Contrave, because it combines two active agents—sustained release bupropion and extended release naltrexone—has a particularly high potential for drug interactions with both prescription medications and over-the-counter medications.

The way these components work—affecting dopamine, norepinephrine, and the brain’s reward pathways—makes it essential to screen for other compounds that might amplify, diminish, or dangerously alter their effects.

One such compound is St. John’s Wort. While often perceived as a natural remedy for mood disorders or to treat depression, it’s far from benign when taken with prescription medications. St. John’s Wort has a well-documented history of interfering with liver enzymes (particularly CYP3A4), which break down many medicines in the body. This can lead to increased risk of drug toxicity or decreased drug efficacy.

St. John’s Wort is known to interfere with many other drugs, including:

  • Antidepressants such as tricyclic antidepressants, selective serotonin reuptake inhibitors (SSRIs), and serotonin norepinephrine reuptake inhibitors (SNRIs) – potentially leading to serotonin syndrome, especially when combined with bupropion in Contrave.
  • Birth control pills – reducing their effectiveness and increasing the risk of unintended pregnancy. (Contrave may also reduce the effectiveness of hormonal birth control._
  • Blood thinners like warfarin – which can lead to either excessive bleeding or clotting.
  • Immunosuppressants such as cyclosporine – lowering blood levels and potentially causing organ rejection.
  • Antiepileptics – which may become less effective, raising the risk of seizures in those with seizure disorders.

Additionally, Contrave itself interacts with a broad range of certain medications. These include:

  • Monoamine oxidase inhibitors (MAOIs) – the combination can result in a hypertensive crisis or other potentially life-threatening conditions.
  • Mood stabilizers – which may be affected by the dopaminergic and noradrenergic activity of bupropion.
  • Medications that affect the central nervous system, including sedatives, stimulants, and antipsychotics, including Haldol.

When patients take other medications alongside Contrave or St. John’s Wort, the potential drug interactions multiply. These combinations don’t just alter effectiveness—they can drastically increase the risk of adverse events like high blood pressure, skin rash, unusual symptoms, or mood swings.

The central nervous system is especially sensitive to overlapping influences from multiple drugs. Combining two drugs like Contrave and St. John’s Wort, both of which have psychoactive properties, places extra strain on neurotransmitter balance and regulatory systems in the body. These risks are amplified in patients with underlying medical conditions such as bipolar disorder, liver disease, or those who drink alcohol regularly.

Many people also mistakenly believe that if a supplement is “natural,” it can be used freely. But dietary supplements like St. John’s Wort can pose just as many risks as synthetic drugs when it comes to interactions—especially with a prescription weight loss medication.

Combining bupropion with herbal supplements like St. John’s Wort can lead to significant drug interactions. According to the FDA, St. John’s Wort is known to interact with various cytochrome P450 enzymes and transporter systems, which can alter the metabolism of many drugs, including bupropion . Additionally, a study published in the British Journal of Clinical Psychopharmacology reported a case where the concurrent use of bupropion and St. John’s Wort resulted in prolonged oro-facial dystonia, highlighting the potential for serious neurological side effects .

Therefore, it is crucial to consult with a healthcare provider before combining bupropion with any herbal supplements to avoid adverse effects.​

In practice, this means that healthcare providers must conduct a thorough medication review before prescribing Contrave—and patients must be honest and proactive in disclosing all the medications and supplements they’re taking, including herbal remedies like St. John’s Wort.

Even a single unreported supplement can result in an increased risk of life-threatening conditions or reduce the effectiveness of medications meant to help you lose weight and improve your health.

Taking Contrave and St. John's Wort Together Infographic

Health Conditions That Increase the Risk

Individuals with certain medical conditions should be especially cautious—or avoid entirely—taking Contrave and St. John’s Wort together. While each substance has legitimate therapeutic uses, combining them can pose a serious health risk, particularly in vulnerable populations.

Below are the key conditions that raise the increased risk of dangerous drug interactions and complications:

  • Seizure disorders: Contrave contains bupropion, which is known to lower the seizure threshold. When combined with other substances that stimulate the central nervous system, such as St. John’s Wort, the chance of a seizure increases dramatically. This makes the drug combination unsuitable for individuals with a current or past history of epilepsy or other seizure disorders.
  • Bipolar disorder: Both bupropion and St. John’s Wort can influence mood and neurotransmitter balance. While bupropion is sometimes used to treat depression, it may trigger mood destabilization or manic episodes in people with bipolar disorder. St. John’s Wort, due to its serotonergic properties, may also disrupt mood regulation, especially when combined with other antidepressants or central nervous system stimulants.
  • Liver disease or kidney disease: Both Contrave and St. John’s Wort are metabolized through hepatic (liver) and renal (kidney) pathways. People with liver disease or kidney disease may experience slower drug clearance, leading to an increased risk of accumulation and toxicity. The altered metabolism can intensify side effects or reduce the expected therapeutic effect of either drug.
  • Heart disease or high blood pressure: Naltrexone and bupropion can increase blood pressure, and when paired with a substance like St. John’s Wort—which may alter drug metabolism and central neurotransmission—this effect may become exaggerated. The combination raises the risk of hypertensive crisis, especially in individuals already diagnosed with high blood pressure or any form of heart disease.
  • Eating disorders: Individuals with a history of eating disorders (especially bulimia or anorexia nervosa) are at heightened risk when using bupropion, as this population is more prone to seizure disorders and mood disturbances. Adding St. John’s Wort—often perceived as a natural mood booster—can further destabilize mood or contribute to dangerous behavior if not closely monitored.

For patients with an initial body mass index (BMI) of 30 or higher—or 27 with associated comorbidities such as high blood pressure—Contrave may be recommended as part of a supervised treatment plan to lose weight. However, the increased risk posed by certain underlying health conditions must be weighed carefully against the potential benefits of weight loss.

Even among healthy volunteers, clinical trials have demonstrated that bupropion, when used alongside other serotonergic agents, can produce symptoms of serotonin syndrome and central nervous system overstimulation—ranging from mild (anxiety, agitation) to severe (confusion, muscle rigidity, or fever).

In these cases, the presence of any preexisting medical condition can amplify the potentially life-threatening conditions associated with polypharmacy. This is why healthcare providers emphasize the importance of medical history screening before initiating prescription weight loss medication, particularly one like Contrave that carries a range of neurological and cardiovascular precautions.

By openly discussing all current health issues and medications—including dietary supplements like St. John’s Wort—patients can reduce their increased risk of adverse outcomes and receive more personalized, safer care.

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What About Over-the-Counter Medications?

Many people assume that over-the-counter medications and herbal supplements are inherently safe, especially when compared to prescription drugs. But this assumption can be dangerous—particularly when these products are taken alongside prescription weight loss medication like Contrave.

One of the most well-known examples is St. John’s Wort, which is commonly used to treat depression, relieve anxiety, and support mood balance. Despite being marketed as a natural remedy, St. John’s Wort is far from harmless when combined with other medications.

In fact, St. John’s Wort is associated with a wide range of potential drug interactions, many of which are serious. It significantly affects the activity of liver enzymes, particularly CYP3A4, which are responsible for metabolizing many commonly used drugs—including antidepressants, anticonvulsants, birth control pills, and weight loss drugs.

This enzyme-inducing effect can lead to reduced efficacy of medications, rendering them less effective or entirely ineffective. In other cases, it may enhance drug activity to dangerous levels, contributing to increased risk of side effects or toxicity.

For instance, the NIH reports that St. John’s Wort can:

  • Decrease the effectiveness of oral contraceptives, leading to unintended pregnancy. (Contrave may also decrease the effectiveness of hormonal birth control.)
  • Weaken the effects of immunosuppressants like cyclosporine, potentially leading to organ rejection
  • Interfere with HIV medications, making viral suppression less effective
  • Contribute to serotonin syndrome when taken with serotonergic medications such as SSRIs, SNRIs, or bupropion therapy
  • Trigger unusual symptoms like skin rash, sun sensitivity (photosensitivity), dizziness, or confusion—especially when combined with other central nervous system stimulants

Because of these effects, even a seemingly innocent supplement can interact dangerously with Contrave, especially considering its influence on dopamine, appetite regulation, and brain function. Patients who drink alcohol, have bipolar disorder, or are managing multiple medical conditions face a particularly higher risk when mixing unverified supplements with prescription treatments.

The takeaway is simple but critical: just because a product is available without a prescription does not mean it’s free from health risks or compatible with your current medications.

Before starting any dietary supplement, herbal remedy, or over-the-counter medication, patients using Contrave should speak with a qualified healthcare provider to avoid dangerous drug interactions and protect their progress toward weight loss and overall health.

Lifestyle Considerations While Taking Contrave

When using Contrave as part of a treatment plan for weight loss, it’s important to understand that the medication is not a quick fix. Its effectiveness hinges on several critical lifestyle elements, including a reduced-calorie diet, consistent physical activity, and medical supervision. These foundational strategies help support long-term behavior change and maximize the benefit of prescription weight loss medication.

Adding unregulated dietary supplements like St. John’s Wort into this mix, however, may not only diminish the benefits of Contrave but also increase the likelihood of adverse effects and serious drug interactions. Herbal compounds can alter how Contrave is absorbed, metabolized, and excreted—ultimately throwing off the drug’s delicate balance within the central nervous system.

Here are some key considerations to ensure you’re using Contrave safely and effectively:

  • Avoid high-fat meals when taking Contrave. A high-fat meal can significantly increase the plasma concentration of sustained-release bupropion, raising the likelihood of side effects such as high blood pressure, nausea, or even triggering a seizure in at-risk individuals. Stick with balanced meals that are nutrient-dense and aligned with your reduced-calorie diet goals.
  • Do not abruptly discontinue Contrave. Stopping the medication suddenly—especially without the guidance of a healthcare provider—can lead to mood destabilization, irritability, or withdrawal symptoms. If side effects arise or the medication no longer seems effective, work with your provider to taper off safely.
  • Be cautious about missed doses. It may be tempting to take an extra pill to “make up” for a missed dose, but this approach increases the risk of seizure disorders, elevated blood pressure, and other complications. Follow the instructions in your medication guide or speak to your healthcare provider about the safest course of action.
  • Report any unusual symptoms immediately. This includes persistent dry mouth, dizziness, confusion, agitation, sleep problems, or sudden mood swings. These symptoms may indicate a drug interaction, especially if you’re also using St. John’s Wort or other over-the-counter medications.
  • Limit alcohol consumption. Patients using Contrave should not drink alcohol excessively. Alcohol can increase the risk of seizures and central nervous system side effects, particularly in individuals with a history of bipolar disorder, depression, or those prone to abrupt discontinuation of mood-altering medications. For some, complete abstinence may be recommended during bupropion therapy.
  • Watch for interaction with physical exertion. Because Contrave affects neurotransmitters involved in energy, reward, and impulse control, combining the drug with intense physical activity may amplify sensations like racing heart or dizziness—especially in warmer environments. Stay hydrated, monitor your blood pressure, and pace workouts according to your tolerance level.
  • Keep your provider informed about all the medications and supplements you’re taking. Even a well-intentioned supplement like St. John’s Wort can undermine your weight loss efforts by causing potential drug interactions that interfere with how Contrave works—or worse, lead to a potentially life-threatening condition like serotonin syndrome or hypertensive crisis.

While many people are motivated to lose weight quickly, using multiple substances that act on the brain and body simultaneously should never be done without guidance. Combining two drugs—particularly those with serotonergic, dopaminergic, or stimulant-like properties—can tax the brain involved in mood regulation, appetite control, and impulse moderation.

It’s also worth noting that patients with a history of eating disorders, seizure disorders, or mood disorders are more susceptible to complications, including unusual symptoms and serious medical conditions. That’s why lifestyle choices and honest communication with your healthcare provider are critical throughout the course of treatment.

Making well-informed choices, staying consistent with your reduced-calorie diet and physical activity, and avoiding unapproved supplements can help maximize Contrave’s benefits and reduce your increased risk of complications.

When to Seek Immediate Medical Attention

Call your healthcare provider immediately or seek emergency care if you notice signs of:

  • Serotonin syndrome: confusion, rapid heartbeat, sweating, tremors
  • Hypertensive crisis: severe headache, chest pain, blurred vision. Check out our guide to discover if Contrave can increase blood pressure — and why.
  • Allergic reaction: hives, swelling, or trouble breathing
  • Mood swings or signs of manic behavior in bipolar individuals

These symptoms may indicate that your medications—or dietary supplements—are interacting in dangerous ways.

Can You Ever Safely Take Contrave and St. John’s Wort?

There may be cases where low-dose, short-term use of St. John’s Wort is considered, but this should only be done under the direction of a healthcare provider familiar with all the medications you’re taking.

In most cases, patients seeking mood support should explore safer alternatives, especially since Contrave itself is contraindicated in patients currently being treated with monoamine oxidase inhibitors, tricyclic antidepressants, or serotonergic agents.

Frequently Asked Questions (FAQ)

When it comes to combining prescription weight loss medication like Contrave with dietary supplements or antidepressants, it’s natural to have concerns.

The following FAQs address some of the most common questions about drug interactions and safety when using Contrave, bupropion, St. John’s Wort, and other medications that affect the central nervous system.

1. Can I take St. John’s Wort with bupropion?

It is generally not recommended to take St. John’s Wort with bupropion due to the increased risk of serious drug interactions. Both substances influence brain neurotransmitters and may lead to serotonin syndrome, a potentially life-threatening condition. St. John’s Wort can also induce liver enzymes that alter how bupropion is metabolized, reducing its effectiveness or increasing side effects.

Patients treated with bupropion should consult their healthcare provider before using any herbal supplements, including St. John’s Wort.

2. What medications should not be taken with Contrave?

Contrave should not be taken with monoamine oxidase inhibitors (MAOIs) like Nardil, other bupropion-containing medications, opioids like hydromorphone, or drugs like Wellbutrin that lower the seizure threshold.

Combining Contrave with other medications that affect serotonin—such as SSRIs, SNRIs, or St. John’s Wort—can increase the risk of serotonin syndrome. Individuals with seizure disorders, eating disorders, or those who drink alcohol heavily are especially vulnerable to complications.

Always review your current prescriptions, supplements, and over-the-counter medications with your healthcare provider before starting Contrave.

3. What drugs should not be taken with St. John’s Wort?

St. John’s Wort can interfere with a wide range of medications, including antidepressants (SSRIs, SNRIs, tricyclic antidepressants), birth control pills, blood thinners, and immunosuppressants. It may reduce drug effectiveness by speeding up liver metabolism and increase the chance of adverse effects by amplifying serotonin activity. When taken with serotonergic drugs, it may lead to serotonin syndrome.

People taking prescription weight loss drugs, mood stabilizers, or treatments for heart disease, bipolar disorder, or seizure disorders should avoid using St. John’s Wort without medical supervision.

4. Can you take Contrave with an SSRI?

Using Contrave with a selective serotonin reuptake inhibitor (SSRI), such as Prozac and Zoloft, can be risky due to the potential for drug interactions affecting serotonin levels. Since Contrave includes bupropion, which can indirectly influence serotonin, adding an SSRI may increase the risk of serotonin syndrome.

This risk is higher in patients with bipolar disorder, those who have high blood pressure, or who are already taking other serotonergic drugs or supplements like St. John’s Wort.

Your healthcare provider may recommend an alternative treatment plan or close monitoring if both are prescribed.

Summary: The Risks Outweigh the Benefits

Using Contrave and St. John’s Wort together can increase the risk of serious drug interactions, including serotonin syndrome, seizure, mood instability, and reduced medication effectiveness. For patients trying to lose weight with Contrave, the risks of combining it with herbal antidepressants far outweigh any potential benefits.

Your best bet is to work closely with your healthcare provider to develop a comprehensive, safe treatment plan that includes a reduced-calorie diet, physical activity, and the right medications for your needs.

References

FDA

British Journal of Clinical Pharmacology

NIH

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