Side Effects of Contrave: A Symptom-by-Symptom Guide With Management Strategies

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> Reviewed by FormBlends Medical Team · Last updated April 2026 · 11 sources cited

Key Takeaways

• The most common Contrave side effects are nausea (32%), constipation (19%), headache (18%), vomiting (11%), and dizziness (10%), based on the COR-1 trial.
• Serious side effects include suicidal ideation (boxed warning), seizures, increased blood pressure, and liver injury. They are rare but require monitoring.
• Most GI side effects are worst during the 4-week titration phase and improve once patients reach maintenance dose.
• Contrave should not be combined with other opioids, MAO inhibitors, or alcohol abuse, and is contraindicated in uncontrolled hypertension and seizure disorders.
• About 1 in 4 patients in trials discontinued Contrave due to side effects, mostly nausea and headache.

Direct answer (40-60 words)

The most common Contrave side effects are nausea, constipation, headache, vomiting, dizziness, insomnia, and dry mouth. Most appear during the 4-week titration phase and improve at maintenance dose. Serious but rare risks include suicidal thoughts (boxed warning), seizures, and elevated blood pressure. About 1 in 4 patients in trials stopped due to side effects.

Table of contents

1. The 30-second answer
2. What is Contrave and why does the side-effect profile look this way?
3. Common side effects: incidence, timing, and what they feel like
4. The titration schedule and why side effects peak in week 2 to 3
5. Serious side effects: what to monitor for
6. Suicidal ideation, mood changes, and the boxed warning
7. Seizure risk: who is at higher risk
8. Blood pressure and heart rate: monitoring practicalities
9. Drug interactions that worsen side effects
10. Symptom-by-symptom management strategies
11. When to call your provider, when to stop the drug
12. FAQ
13. Sources
14. Footer disclaimers

What is Contrave and why does the side-effect profile look this way?

Contrave is a fixed-dose combination tablet of two older medications: naltrexone and bupropion.

• Naltrexone is an opioid receptor antagonist used for opioid use disorder and alcohol dependence.
• Bupropion is a norepinephrine and dopamine reuptake inhibitor used as an antidepressant and for smoking cessation.

The combination targets two areas of the brain involved in appetite regulation: the hypothalamus (hunger signaling) and the mesolimbic reward system (food cravings). Together, they reduce appetite and food cravings in many patients (Greenway et al., Lancet 2010).

The side-effect profile reflects both ingredients. Bupropion contributes most of the headaches, insomnia, dry mouth, and seizure risk. Naltrexone contributes most of the nausea, vomiting, and constipation. The serotonergic and dopaminergic effects of bupropion are also why mood changes are part of the safety conversation.

Each Contrave tablet contains 8 mg of naltrexone and 90 mg of bupropion (extended-release). Maintenance dose is two tablets twice daily, totaling 32 mg naltrexone and 360 mg bupropion per day.

Common side effects: incidence, timing, and what they feel like

Data below are from the COR-1, COR-II, and COR-BMOD phase 3 trials, which together enrolled over 4,500 patients (Apovian et al., Obesity 2013).

Side effect	Contrave incidence	Placebo incidence	Typical timing
Nausea	32%	7%	Worst in week 1 to 3, settles by week 8
Constipation	19%	7%	Builds over weeks 2 to 6, may persist
Headache	18%	11%	First 1 to 2 weeks
Vomiting	11%	3%	Same window as nausea
Dizziness	10%	3%	First 2 weeks
Insomnia	9%	3%	Builds over weeks 1 to 4
Dry mouth	8%	2%	Throughout treatment
Diarrhea	7%	5%	Variable

Most of these are dose-dependent. Patients who have GI symptoms at the 1-tablet morning dose often have worse symptoms at the full 4-tablet daily dose. The titration schedule is designed to slowly build tolerance.

What they feel like in practice:

• Nausea on Contrave is more constant and waves rather than the post-meal spike pattern seen with GLP-1 medications. Patients describe it as "low-grade queasy all day."
• Headache tends to be tension-type (across the forehead or temples) and responds to ibuprofen or acetaminophen. Migraine sufferers sometimes report more frequent migraines during the first weeks.
• Insomnia is mostly sleep-onset (difficulty falling asleep) rather than middle-of-night waking. Avoiding the second daily dose after 4 PM helps.
• Dry mouth is dose-dependent and improves with water sipping, sugar-free gum, and limiting caffeine.
• Constipation is the side effect most likely to persist long-term and the one most likely to cause patients to quit if not managed.

The titration schedule and why side effects peak in week 2 to 3

Contrave is titrated over 4 weeks to manage side effects. The standard schedule:

Week	Morning dose	Evening dose	Total daily naltrexone/bupropion
1	1 tablet	0	8 mg / 90 mg
2	1 tablet	1 tablet	16 mg / 180 mg
3	2 tablets	1 tablet	24 mg / 270 mg
4+	2 tablets	2 tablets	32 mg / 360 mg

Side effects typically peak in week 2 to 3 because that is when the dose is rising fastest and the body has not yet adapted. Many patients report:

• Week 1: mild nausea, slight headache, sleep slightly disturbed.
• Week 2: nausea and headache more noticeable, dry mouth appearing.
• Week 3: peak symptoms, occasional vomiting, persistent low energy.
• Week 4 to 8: symptoms gradually settle, energy returns.
• Week 8 to 12: stable side-effect profile, mostly mild.

If side effects are severe at any titration step, it is reasonable to slow down. Holding at the current dose for 2 weeks before escalating is a common adjustment. Some patients never reach the full 4-tablet dose and stay on 3 tablets daily for tolerability, which still produces meaningful weight effect.

If symptoms have not settled by week 6 to 8, the medication may not be a good fit. About 25% of patients in trials discontinued before reaching maintenance dose, mostly because of nausea and headache that did not improve.

Serious side effects: what to monitor for

Beyond the common discomforts, Contrave has several serious risks. Most are rare, but each one is worth knowing about.

Suicidal ideation and mood changes (boxed warning). Bupropion carries a class-wide boxed warning for suicidal thoughts and behavior, especially in young adults, when started or when dose is increased. Patients should be monitored for new or worsening depression, suicidal ideation, agitation, hostility, or unusual changes in behavior.

Seizures. Bupropion lowers the seizure threshold. The Contrave label estimates seizure risk at about 0.06% in the trials, lower than the rates seen with high-dose immediate-release bupropion. Risk is higher in patients with eating disorders (active anorexia or bulimia), alcohol use disorder, abrupt withdrawal from alcohol or benzodiazepines, severe head injury, brain tumor, or use of other seizure-threshold-lowering drugs.

Increased blood pressure and heart rate. Trial data showed average increases of 1 to 2 mmHg in systolic blood pressure and 1 to 2 bpm in heart rate. Some patients had clinically significant rises requiring intervention. The drug is contraindicated in uncontrolled hypertension.

Liver injury. Rare cases of significant liver enzyme elevations and a few cases of severe hepatotoxicity have been reported. Patients should be told to report yellowing of the skin or eyes, dark urine, severe fatigue, right-upper-quadrant pain, or unexplained nausea persisting beyond the titration phase.

Glaucoma exacerbation. Bupropion can cause angle-closure glaucoma in patients with shallow angles. Eye pain with redness and visual changes is a red flag.

Hypoglycemia. In diabetic patients, weight loss from Contrave can lower blood glucose. Dose adjustment of insulin or sulfonylureas may be needed.

Allergic reactions and serum sickness-like reactions. Rash, urticaria, joint pain, and fever in the first weeks should prompt a provider call.

These serious effects are why Contrave requires baseline blood pressure monitoring, screening for seizure risk factors, screening for active eating disorders, and a discussion of mood history before prescribing.

Suicidal ideation, mood changes, and the boxed warning

The boxed warning on Contrave's label flags an increased risk of suicidal thoughts and behaviors during initial treatment with bupropion-containing medications, especially in patients under age 24. The warning is based on FDA meta-analysis of antidepressant trials in young adults (FDA, 2007).

In practice:

• Most patients on Contrave do not experience worsening mood. Some report improved mood as a side benefit of bupropion's antidepressant action.
• Patients with active or recent depression should have baseline mental health stability before starting.
• Family members and patients should be told to watch for new or worsening depression, anxiety, agitation, panic, irritability, hostility, or thoughts of self-harm in the first weeks.
• Any of these warrant a same-day call to the prescriber or, in severe cases, urgent psychiatric evaluation.

Patients with a history of suicidal ideation or recent suicide attempt should generally not start Contrave without psychiatric coordination. The drug is not absolutely contraindicated, but the boxed warning is real and the risk-benefit calculation needs careful attention.

If you experience new suicidal thoughts at any point on Contrave, stop the medication and seek same-day care. The 988 Suicide and Crisis Lifeline is available 24/7 in the U.S. for immediate support.

Seizure risk: who is at higher risk

Seizure incidence in the Contrave phase 3 trials was 0.06% (4 patients across the development program). The rate is lower than older immediate-release bupropion at high doses (around 0.4%) because Contrave uses a sustained-release bupropion formulation that avoids high peak levels.

Patients at higher risk:

• Active or recent eating disorder. Bulimia or anorexia nervosa, current or within the past year, is a contraindication.
• Active alcohol use disorder. Heavy drinking lowers seizure threshold and the abrupt cessation that sometimes accompanies starting weight-loss medication is itself a seizure risk.
• Abrupt withdrawal from benzodiazepines or barbiturates. Tapering should happen before starting Contrave.
• History of seizure disorder. Generally a contraindication.
• Severe head injury. Discuss with prescriber.
• CNS tumors. Discuss with prescriber.
• Concurrent use of other drugs that lower seizure threshold. Tramadol, theophylline, systemic steroids, antipsychotics, other antidepressants in some combinations.

Patients without these risk factors have a very low absolute seizure rate. The drug remains a reasonable option for many, but the screening conversation matters.

Blood pressure and heart rate: monitoring practicalities

Bupropion increases sympathetic tone modestly. Clinical trial data shows:

• Average systolic blood pressure increase: 1 to 2 mmHg
• Average heart rate increase: 1 to 2 bpm
• Larger increases (5 mmHg or more) in approximately 5% of patients

The drug is contraindicated in uncontrolled hypertension. Baseline blood pressure should be controlled before starting, and follow-up readings should occur at:

• Week 4 (after reaching full maintenance dose)
• Month 3
• Every 3 to 6 months thereafter

If systolic blood pressure rises above 140 or diastolic above 90, or if existing hypertension worsens, the medication should be reassessed. Many patients tolerate Contrave on stable antihypertensive therapy.

A practical home approach:

• Buy a validated automatic blood pressure cuff (around $40).
• Check blood pressure twice weekly during titration, then weekly during the first 3 months.
• Bring readings to provider visits.

If you have a heart condition or take blood pressure medication, your prescriber may want more frequent monitoring or in-office cardiology checks.

Drug interactions that worsen side effects

Several common medications interact significantly with Contrave.

Strict contraindications:

• Other bupropion-containing products (Wellbutrin, Zyban, Aplenzin). Combining doubles bupropion exposure and seizure risk.
• MAO inhibitors (phenelzine, tranylcypromine, selegiline, isocarboxazid, linezolid). Severe hypertensive crisis risk.
• Chronic opioid use. Naltrexone in Contrave will precipitate opioid withdrawal in patients on regular opioids.
• Tramadol and methadone. Increased seizure risk plus opioid interaction.

Significant cautions:

• Antidepressants (SSRIs, SNRIs, tricyclics, MAOIs). Generally avoided in combination because of overlapping serotonergic and seizure-threshold effects. Talk to prescriber.
• Antipsychotics. Lower seizure threshold; combination requires careful evaluation.
• Levodopa, amantadine. May increase CNS side effects.
• Drugs metabolized by CYP2D6 (some antidepressants, antiarrhythmics, beta blockers). Bupropion inhibits CYP2D6, raising levels of co-administered drugs.
• Alcohol. Avoid heavy drinking. Mild to moderate use should be discussed with the prescriber.

Procedural note: patients on Contrave who need surgery should tell their anesthesiologist. The naltrexone component will block opioid pain medications, requiring alternative pain management strategies.

If you take other prescription medications, review the full list with your prescriber before starting Contrave. Many combinations are workable; some require alternative weight-loss approaches.

Symptom-by-symptom management strategies

Nausea.

• Take tablets with food, not on an empty stomach.
• Stay hydrated; aim for 80 oz fluid daily.
• Ginger candy, peppermint, or low-dose ondansetron (provider-dispensed) help.
• If severe, hold at current dose for 2 weeks before escalating.

Constipation.

• Aim for 25 to 35 g fiber daily (vegetables, fruit, whole grains, beans).
• 2 to 3 liters of fluid per day.
• Magnesium citrate 400 mg at bedtime is gentle and effective.
• If insufficient, polyethylene glycol (Miralax) one cap daily.
• Prunes, pears, and kiwi are well-tolerated natural laxatives.

Headache.

• Acetaminophen 500 to 1000 mg or ibuprofen 200 to 400 mg as needed.
• Hydration matters; many Contrave headaches are partially dehydration-driven.
• If migraines worsen, talk to your prescriber. Some triptans interact with bupropion.

Insomnia.

• Take the second daily dose no later than mid-afternoon.
• Reduce caffeine after noon.
• Consistent bedtime; no screens for 30 minutes before sleep.
• Magnesium glycinate 200 to 400 mg at bedtime can help.
• If insomnia persists past week 8, talk with your prescriber about timing or dose.

Dizziness.

• Stand up slowly from sitting or lying.
• Stay hydrated; check blood pressure if dizziness is frequent.
• Avoid alcohol and benzodiazepines, which compound dizziness.

Dry mouth.

• Sip water frequently; avoid sugary drinks.
• Sugar-free gum or lozenges.
• Use a humidifier at night.
• Avoid antihistamine medications, which worsen dry mouth.

Vomiting.

• Sip clear fluids first, then bland foods (toast, rice, banana).
• If vomiting persists more than 24 hours or you cannot keep fluids down, call provider.
• Severe vomiting on Contrave may warrant a slower titration or discontinuation.

When to call your provider, when to stop the drug

Call 911 or go to the emergency room:

• Active suicidal thoughts with intent or plan
• New seizure (loss of consciousness, convulsions, post-event confusion)
• Severe chest pain or shortness of breath
• Severe headache with vision changes (could indicate hypertensive emergency)
• Anaphylaxis (swelling of face/lips, difficulty breathing)

Stop the medication and call your provider same day:

• Yellowing of skin or eyes (jaundice)
• Severe abdominal pain
• Dark urine or pale stools (signs of liver injury)
• New or worsening depression with intrusive thoughts
• New severe agitation or panic attacks
• Eye pain with redness and vision changes (possible angle-closure glaucoma)

Within 24 to 48 hours:

• Persistent vomiting beyond 24 hours
• Constipation not responding to OTC management for 7+ days
• New or worsening headaches that do not respond to usual measures
• Blood pressure consistently above 140/90 on home monitoring
• New rash that is spreading or accompanied by fever

Routine next visit:

• Mild persistent nausea after week 8
• Mild dry mouth
• Slight insomnia that is manageable
• Minor headaches responsive to OTC pain relievers

The general rule: any new mental health change is urgent. Any sign of liver, allergic, or cardiovascular concern is urgent. Most other side effects can wait for a routine visit unless they are severe or persistent.

FAQ

What are the most common side effects of Contrave? Nausea (32%), constipation (19%), headache (18%), vomiting (11%), and dizziness (10%) are the top five from the COR phase 3 trials. Insomnia, dry mouth, and diarrhea round out the common list. Most are worst during the 4-week titration and improve at maintenance dose.

How long do Contrave side effects last? Most common side effects peak in week 2 to 3 and improve substantially by week 8. Constipation can persist longer. If side effects have not settled by week 8 to 12, the medication may not be a good fit.

Is Contrave safe long-term? Long-term safety data extends to 4 to 6 years for naltrexone-bupropion specifically. Both individual ingredients have decades of separate use. Major long-term concerns are the cumulative cardiovascular effect of small blood pressure increases and the rare but real risk of liver injury.

Can Contrave cause depression? Bupropion is itself an antidepressant, so for most patients Contrave is mood-neutral or mood-improving. The boxed warning highlights a small risk of new or worsening depression and suicidal thoughts, especially in patients under 24, in the first weeks of treatment. Monitor closely and report any concerning changes.

Why does Contrave cause nausea? The naltrexone component is the main driver of nausea. Naltrexone-induced nausea is a well-known effect that occurs in opioid use disorder treatment too. Taking Contrave with food and slow titration are the main mitigations.

Does Contrave raise blood pressure? Slightly. Average increases are 1 to 2 mmHg systolic. About 5% of patients have larger increases. Baseline blood pressure should be controlled before starting, and follow-up monitoring at week 4, month 3, and every 3 to 6 months thereafter is standard.

Can Contrave cause seizures? Yes, rarely. Phase 3 trial seizure rate was 0.06%. Risk is higher in patients with eating disorders, alcohol use disorder, abrupt benzodiazepine withdrawal, head injury history, or concurrent seizure-threshold-lowering medications.

What can I take for Contrave-induced constipation? Increase fiber to 25 to 35 g daily, drink 2 to 3 liters of fluid, and use magnesium citrate 400 mg at bedtime or polyethylene glycol (Miralax) one cap daily. Constipation that does not respond to these within a week warrants a provider call.

Can I drink alcohol on Contrave? Mild to moderate alcohol use is generally allowable but should be discussed with your prescriber. Heavy drinking is contraindicated because alcohol lowers seizure threshold and can compound side effects. Abruptly stopping heavy alcohol use after starting Contrave is itself a seizure risk.

Can I take Contrave with antidepressants? Generally not without careful prescriber coordination. Other bupropion-containing products are contraindicated. SSRIs, SNRIs, tricyclics, and MAOIs all have potential interactions. If you take an antidepressant, your prescriber will weigh combination versus alternative weight-loss options.

What should I do if I miss a dose of Contrave? Skip the missed dose and take the next dose at the regular time. Do not double up. Missing one or two doses does not cause significant problems. Missing several days can require restarting the titration to avoid GI symptoms returning at full force.

Does Contrave interact with opioid pain medications? Yes, significantly. The naltrexone component blocks opioid receptors. Standard opioid pain medications (oxycodone, hydrocodone, morphine) will not work normally on Contrave. Patients needing surgery should inform their anesthesiologist; alternative pain strategies are needed.

Sources

1. Apovian CM, et al. A randomized, phase 3 trial of naltrexone SR/bupropion SR on weight and obesity-related risk factors (COR-II). Obesity. 2013;21:935-943.
2. Greenway FL, et al. Effect of naltrexone plus bupropion on weight loss in overweight and obese adults (COR-I). Lancet. 2010;376:595-605.
3. Wadden TA, et al. Weight loss with naltrexone SR/bupropion SR combination therapy as an adjunct to behavior modification (COR-BMOD). Obesity. 2011;19:110-120.
4. Hollander P, et al. Effects of naltrexone sustained-release/bupropion sustained-release combination therapy on body weight and glycemic parameters in overweight and obese patients with type 2 diabetes (COR-Diabetes). Diabetes Care. 2013;36:4022-4029.
5. FDA prescribing information for Contrave (naltrexone HCl/bupropion HCl extended-release tablets). U.S. Food and Drug Administration. Updated 2023.
6. FDA. Antidepressant use in children, adolescents, and adults. FDA Public Health Advisory. 2007.
7. American Diabetes Association. Standards of Medical Care in Diabetes. Diabetes Care. 2024;47(Suppl 1).
8. Yanovski SZ, Yanovski JA. Long-term drug treatment for obesity: a systematic and clinical review. JAMA. 2014;311:74-86.
9. Halford JCG, et al. Pharmacological management of appetite expression in obesity. Nat Rev Endocrinol. 2010;6:255-269.
10. Apovian CM. Naltrexone/bupropion for the treatment of obesity and obesity with type 2 diabetes. Future Cardiol. 2016;12:129-138.
11. National Institute of Mental Health. Suicide prevention resource. NIH. 2024.

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