Contrave Side Effects: A Symptom-by-Symptom Breakdown With Real Trial Frequencies

Key Takeaways

• Contrave is naltrexone 8 mg + bupropion 90 mg, an oral combination pill FDA-approved in September 2014 for chronic weight management.
• The most common side effects from the phase 3 COR (Contrave Obesity Research) trials are nausea (32%), constipation (19%), headache (18%), vomiting (11%), and dizziness (10%).
• Contrave carries a boxed warning for suicidal thoughts and behaviors (from the bupropion component) and a separate seizure warning that contraindicates it in anyone with a history of seizures or eating disorders.
• About 1 in 4 patients in COR-I discontinued for adverse events, mostly nausea and dizziness during the 4-week titration.
• Most GI side effects peak in the first 4 weeks, fade by week 8 to 12, and are reduced by taking pills with food and avoiding high-fat meals.

Direct answer (40-60 words, snippet-optimized)

The most common Contrave side effects are nausea (32.5%), constipation (19.2%), headache (17.6%), vomiting (10.7%), and dizziness (9.9%), per the COR-I trial. Most are mild, peak during the 4-week titration, and improve. Contrave also carries a black box warning for suicidality, plus a separate seizure risk that makes it contraindicated in patients with seizure history, bulimia, or anorexia.

Table of contents

1. The 30-second answer
2. The full Contrave side effect list with trial frequencies
3. GI side effects: nausea, constipation, vomiting, dry mouth
4. Neurologic side effects: headache, dizziness, insomnia
5. Cardiovascular side effects: blood pressure and heart rate
6. The black box warning: suicidality
7. The seizure risk and absolute contraindications
8. Drug interactions that matter
9. Side effects that mean call a provider today
10. Side effects that mean go to the ER
11. How long do Contrave side effects last
12. How Contrave side effects compare to other weight-loss drugs
13. Managing side effects without quitting
14. FAQ
15. Sources
16. Footer disclaimers

The full Contrave side effect list with trial frequencies

Contrave is a fixed-dose combination of naltrexone hydrochloride and bupropion hydrochloride, sold by Currax Pharmaceuticals. Each pill contains 8 mg naltrexone and 90 mg bupropion in an extended-release matrix. The target maintenance dose is 2 pills twice daily (32 mg naltrexone + 360 mg bupropion total).

The side effect profile below comes from the four phase 3 COR trials (COR-I, COR-II, COR-BMOD, and COR-Diabetes), pooled in the Contrave FDA prescribing information and published in Greenway et al., Lancet, 2010 and Apovian et al., Obesity, 2013.

Side effect	Contrave 32/360 mg	Placebo
Nausea	32.5%	6.7%
Constipation	19.2%	7.2%
Headache	17.6%	10.4%
Vomiting	10.7%	2.9%
Dizziness	9.9%	3.4%
Insomnia	9.2%	5.9%
Dry mouth	8.1%	2.3%
Diarrhea	7.1%	5.2%
Anxiety	4.2%	2.8%
Hot flush	4.2%	1.2%
Tremor	4.0%	1.2%
Increased blood pressure	3.6%	0.5%
Tinnitus	3.0%	0.6%

A few patterns worth flagging. Nausea is the dominant complaint and is roughly 5 times more common than placebo. The rate is high because Contrave is started at low dose (1 pill in week 1) and titrated weekly to the full 4-pill dose by week 4. About 24% of patients in COR-I dropped out for adverse events vs 12% on placebo.

Insomnia and dizziness reflect the bupropion component, which is also the active ingredient in Wellbutrin. Constipation reflects the naltrexone component, which slows GI transit. Most side effects fall into one of those two buckets.

GI side effects: nausea, constipation, vomiting, dry mouth

Roughly 1 in 3 patients on Contrave reports nausea. Most of that signal is in the first 4 weeks during titration, and it tracks closely with the bupropion dose increase rather than the naltrexone dose.

Nausea typically peaks in week 2 to 3, when patients move from 2 pills daily to 3 pills daily. Severity is usually mild to moderate. About 6.3% of patients in COR-I discontinued for nausea specifically. The mechanism is dual: bupropion can directly stimulate the chemoreceptor trigger zone, and naltrexone's opioid receptor blockade can disturb gut motility.

What helps:

• Always take pills with food, never on an empty stomach
• Avoid high-fat meals during the titration weeks
• Slow the titration if symptoms are bad (your provider can hold you at 2 or 3 pills longer)
• Ginger tea, ginger chews, or ginger capsules 250 to 500 mg
• Cold or room-temperature foods (warm food smells trigger nausea more)
• Stay hydrated with small frequent sips rather than large glasses

Constipation affects about 1 in 5 patients. Naltrexone is an opioid receptor antagonist, which sounds like it should speed the gut up. In practice, low-dose naltrexone has mixed effects on motility and many patients slow down. Add to that reduced food intake (less bulk going in) and the result is firm, infrequent stools.

What helps:

• Drink at least 64 oz of water daily
• Add psyllium 5 to 10 g daily (Metamucil)
• Magnesium citrate 200 to 400 mg at bedtime
• Walking after meals
• Stool softeners (docusate 100 mg twice daily) for short-term relief

Vomiting is less common but more disruptive. About 11% report at least one episode. Persistent vomiting beyond 24 hours is a flag for dehydration or, less commonly, a hypersensitivity reaction. Don't push fluids forcefully. Sip cold water or oral rehydration solution and call a provider if vomiting continues past a day.

Dry mouth affects about 8% of patients and reflects the bupropion component's anticholinergic activity. Sugar-free gum, frequent sips of water, and over-the-counter saliva substitutes (Biotene) help. Dry mouth increases dental cavity risk if it's chronic, so brushing and flossing matters more than usual.

The GI cluster usually resolves within 8 to 12 weeks at the maintenance dose. Patients who push through the first 4 weeks rarely have lasting problems.

Neurologic side effects: headache, dizziness, insomnia

About 1 in 6 patients reports headache, mostly in the first 2 weeks. Bupropion has a known headache signal in its own right, and the dose escalation amplifies it.

Headache is usually tension-type, frontal or generalized, and responds to standard over-the-counter analgesics. Acetaminophen 500 mg is the safest choice because it doesn't interact with bupropion. NSAIDs are also fine. If headaches are severe or include visual changes, call a provider, as severe headache can occasionally signal a hypertensive episode.

Dizziness affects about 10% of patients and is most often described as lightheadedness on standing rather than true vertigo. The mechanism is partly orthostatic (bupropion-related blood pressure shifts) and partly central. Stand up slowly, hydrate, and avoid driving until you know how Contrave affects you.

Insomnia affects about 9% of patients and is a classic bupropion effect. Bupropion is mildly stimulating, similar to a low-grade caffeine effect. Taking the second daily dose before 5 PM is the simplest fix. Don't take Contrave at bedtime.

Other neurologic effects from the trials:

• Tremor (4%): usually a fine hand tremor, mild
• Anxiety (4%): especially during the first 2 weeks
• Disturbance in attention (4%): trouble focusing, usually transient
• Tinnitus (3%): ringing or buzzing in ears, mostly transient

If neurologic symptoms are severe or include confusion, slurred speech, or visual changes, that's a same-day call to a provider, not a wait-and-see.

Cardiovascular side effects: blood pressure and heart rate

Bupropion and naltrexone both nudge blood pressure and heart rate upward. The effect is modest but real.

In the COR trials:

• Systolic blood pressure rose by about 1 mmHg vs a 1 to 2 mmHg drop on placebo (placebo patients lost weight too)
• Diastolic blood pressure was similar
• Resting heart rate rose by about 1 beat per minute on average
• About 3.6% of patients had a clinically meaningful BP increase requiring intervention

The labeling recommends measuring blood pressure and heart rate before starting Contrave and monitoring during treatment. Patients with uncontrolled hypertension should not start until BP is controlled. The drug is contraindicated in patients with severe uncontrolled hypertension.

A separate cardiovascular outcomes trial (LIGHT) was halted early in 2015 after interim data review. The trial had been designed to confirm cardiovascular safety. The premature termination meant the drug didn't get a definitive cardiovascular outcomes claim, though the FDA did not pull the approval.

If you have a history of heart attack, stroke, or significant arrhythmia, talk with a cardiologist before starting Contrave. The drug is not strictly contraindicated, but the risk-benefit calculation tightens.

The black box warning: suicidality

Contrave carries a boxed warning, the strongest the FDA can require, for suicidal thoughts and behaviors. The warning exists because bupropion is also approved as an antidepressant (Wellbutrin) and shares the class-wide antidepressant boxed warning for suicidality in patients up to age 24.

The warning specifically addresses:

• Increased risk of suicidal thoughts and behaviors in children, adolescents, and young adults (under 25)
• The need to monitor for clinical worsening, suicidality, and unusual behavior changes during treatment
• Family members and caregivers should be alerted to the need to watch for these signs

The COR trials enrolled adults 18 and older and excluded patients with current depression or active suicidal ideation. Real-world post-marketing data (FAERS through 2024) has logged suicidality reports, but the rate is consistent with the broader bupropion class.

In practical terms: Contrave is not a good choice if you have active depression, untreated bipolar disorder, or any history of suicidal ideation. Bupropion alone (without naltrexone) is sometimes used as an antidepressant in stable patients, but adding the naltrexone, the dose escalation, and the weight-loss target adds complexity.

If you start Contrave and notice mood worsening, new anxiety, agitation, panic, irritability, hostility, impulsivity, mania, or suicidal thoughts, contact your provider the same day. Do not stop the drug abruptly without guidance, but do get evaluated.

The seizure risk and absolute contraindications

Bupropion lowers the seizure threshold in a dose-dependent way. At the standard Contrave maintenance dose (360 mg bupropion daily), the seizure rate is approximately 0.1%, which sounds low but is high enough to make the FDA list strict contraindications.

Contrave is absolutely contraindicated in patients with:

• Seizure disorder, current or past
• Bulimia or anorexia nervosa, current or past (seizure risk is markedly elevated in these populations)
• Chronic opioid use, including methadone or buprenorphine maintenance
• Acute opioid withdrawal
• Pregnancy
• Use of MAO inhibitors within the past 14 days
• Uncontrolled hypertension
• Known hypersensitivity to bupropion or naltrexone

Caution (not absolute contraindication) in patients with:

• Renal impairment (dose reduction needed)
• Hepatic impairment (dose reduction needed)
• History of head trauma
• Conditions that lower seizure threshold (alcohol withdrawal, stimulant abuse)
• Bipolar disorder (mania risk)

The naltrexone component blocks opioid receptors. If you take a prescription opioid for pain after starting Contrave, the opioid will be partially or fully blocked and you may not get adequate analgesia. Worse, if you take a high opioid dose to overcome the blockade and the naltrexone wears off, you can get a delayed full opioid effect including respiratory depression. Tell every prescriber and emergency responder that you're on Contrave.

Drug interactions that matter

The drug interaction list for Contrave is long. The high-yield interactions:

Avoid completely:

• MAO inhibitors (phenelzine, tranylcypromine, selegiline). 14-day washout required.
• Linezolid and IV methylene blue (also MAOIs)
• All opioid-containing medications, including codeine cough syrup, tramadol, and many over-the-counter cold medications
• Other bupropion-containing products (Wellbutrin, Aplenzin, Forfivo) to avoid double-dosing

Monitor closely with:

• SSRIs and SNRIs (additive serotonin effects)
• Tricyclic antidepressants (additive seizure risk)
• Antipsychotics (additive seizure risk)
• Theophylline (lowered seizure threshold)
• Systemic corticosteroids (lowered seizure threshold)
• Tramadol (markedly increases seizure risk)

CYP2D6 substrates: Bupropion inhibits CYP2D6, which means it can raise levels of drugs metabolized by that enzyme. Important examples:

• Beta-blockers (metoprolol, propranolol)
• Some antiarrhythmics (flecainide, propafenone)
• Tamoxifen (bupropion can blunt its anticancer effect by reducing conversion to active metabolite)
• Many antidepressants (paroxetine, fluoxetine, venlafaxine)

If you're on tamoxifen for breast cancer, Contrave is a poor choice. Talk with your oncologist before starting.

Side effects that mean call a provider today

Schedule a same-day or next-day call for any of:

• Persistent nausea or vomiting beyond 24 hours
• Inability to keep liquids down for 12 hours
• New or worsening depression, anxiety, panic, or agitation
• Suicidal thoughts of any kind
• Severe headache, especially with vision changes
• Blood pressure readings consistently above 140/90 if previously normal
• Heart rate consistently above 100 at rest
• Yellowing of skin or eyes (possible liver toxicity)
• Severe rash or hives

These symptoms aren't necessarily emergencies, but they shouldn't wait a week.

Side effects that mean go to the ER

Call 911 or go to the nearest emergency department for:

• A seizure of any duration
• Sudden severe chest pain, especially with shortness of breath
• Signs of stroke (sudden weakness on one side, slurred speech, facial droop)
• Severe allergic reaction (swelling of face, lips, tongue; difficulty breathing)
• Suicidal intent or plan
• Loss of consciousness
• Severe abdominal pain
• Signs of severe hypertension (sudden severe headache, blurred vision, confusion)

Don't drive yourself if you have severe symptoms. The ER is the right call when symptoms could indicate a life-threatening complication.

How long do Contrave side effects last

Most side effects follow the titration arc. Symptoms peak during the 4-week titration, plateau in week 5 to 8, and improve significantly by week 12 at the maintenance dose.

Time point	What to expect
Week 1 (1 pill morning)	Mild nausea, possible headache, sleep changes
Week 2 (1 pill morning + 1 evening)	Nausea more prominent, dry mouth, dizziness
Week 3 (2 morning + 1 evening)	Peak GI symptoms for many patients
Week 4 (2 morning + 2 evening)	Maintenance dose reached; symptoms still active
Week 5 to 8	Adaptation phase; symptoms taper for most
Week 8 to 12	Mild residual symptoms or none for ~70% of patients
Beyond 12 weeks	Most patients tolerate the medication without active management

If symptoms haven't materially improved by week 12 at the maintenance dose, that's the point to have a conversation about dose reduction or stopping.

How Contrave side effects compare to other weight-loss drugs

Across published trials, the obesity drug class shares some side effects (GI issues, headache) but Contrave's profile is distinct from injectable GLP-1 medications.

Medication	Nausea rate	Discontinuation for AE	Average weight loss at 1 year
Contrave (naltrexone/bupropion) 32/360 mg	32.5%	24%	5 to 9%
Phentermine/topiramate (Qsymia) 15/92 mg	15.7%	19%	9 to 11%
Orlistat (Xenical) 120 mg TID	5% (GI fat-related)	8%	3 to 4%
Semaglutide (Wegovy) 2.4 mg	44%	7%	14 to 15%
Tirzepatide (Zepbound) 15 mg	28%	4 to 7%	20 to 22%

Contrave has higher nausea rates than the GLP-1 drugs in absolute terms because the dose escalation hits hard and the bupropion component contributes its own GI signal. The discontinuation rate is also notably higher.

For a patient who can't or won't inject, Contrave is a reasonable oral option. For most patients seeking maximum weight loss, the injectable GLP-1 class outperforms.

Managing side effects without quitting

About 24% of Contrave patients in COR-I discontinued for adverse events. The other 76% stayed on, and most managed symptoms with a few practical changes.

During week 1 to 4 (titration phase):

• Take pills with food, every time
• Cap fat at 30% of daily calories
• Drink 2 to 3 liters of fluid daily
• Take the morning dose with breakfast and the evening dose with dinner (not bedtime)
• Have ginger candy or a Sea-Band wristband on hand
• Slow the titration with provider permission if symptoms are bad

During week 5 to 12 (adaptation phase):

• Reintroduce moderate-fat foods slowly
• Add fiber gradually if constipation is the main issue
• Monitor blood pressure weekly at home
• Track sleep quality; insomnia can worsen mood

Long-term:

• Periodic blood pressure and heart rate checks
• Monitor for mood changes, especially in the first 6 months
• Keep an updated medication list and tell every prescriber you're on Contrave
• Reassess weight loss at 12 weeks; if you haven't lost 5% of body weight, the label says to stop

FAQ

What are the most common side effects of Contrave? Nausea (32.5%), constipation (19.2%), headache (17.6%), vomiting (10.7%), and dizziness (9.9%) are the top five from the COR trials. Most are mild, peak during the 4-week titration, and improve by week 8 to 12 at the maintenance dose.

Why does Contrave cause nausea? Both ingredients contribute. Bupropion can directly stimulate the brain's nausea center, and naltrexone affects gut motility. The 4-week dose escalation amplifies both effects. Symptoms typically improve as the body adapts over 8 to 12 weeks.

Does Contrave cause weight loss? Yes, modestly. In COR-I, patients on Contrave lost 6.1% of body weight at 56 weeks vs 1.3% on placebo. Average loss is 5 to 9% of body weight at one year for patients who continue treatment.

Is Contrave safe long term? Long-term safety data extend to about 56 weeks from the COR program. The cardiovascular outcomes trial (LIGHT) was halted early. There are no long-term randomized data beyond about a year. Patients on Contrave should have periodic blood pressure, mood, and weight checks.

Does Contrave cause depression? Contrave can either improve or worsen mood depending on the patient. Bupropion is also used as an antidepressant. The boxed warning addresses a small but real signal for new or worsening suicidal thoughts, especially in patients under 25. Active depression or recent suicidal ideation is a contraindication.

Can Contrave cause seizures? Yes, at a rate of approximately 0.1% at the standard dose. The risk is markedly higher in patients with seizure history, eating disorders, or use of other drugs that lower seizure threshold. These groups cannot take Contrave.

Does Contrave affect blood pressure? Contrave can raise blood pressure modestly (about 1 mmHg systolic on average) and heart rate (about 1 bpm). Patients should have blood pressure measured before starting and monitored periodically. Uncontrolled hypertension is a contraindication.

Can I drink alcohol on Contrave? Use caution. Alcohol can lower seizure threshold and worsen GI side effects. Heavy or binge drinking should be avoided entirely. If you stop drinking abruptly after heavy use, alcohol withdrawal also lowers seizure threshold, which compounds the bupropion risk.

What happens if I take an opioid pain medication on Contrave? The naltrexone component blocks opioid receptors. Standard doses of opioids will be partially or fully blocked, so you may not get adequate pain relief. Larger doses to overcome the blockade are dangerous because the blockade can wear off and produce delayed full opioid effect. Tell every prescriber you're on Contrave.

What's the worst side effect of Contrave? Seizure is the most serious risk. Suicidal thoughts and behaviors are the most clinically watched. Severe hypertensive episodes, allergic reactions, and serotonin syndrome (when combined with MAOIs) are rare but life-threatening.

Will Contrave side effects go away? For about 76% of patients, GI and neurologic side effects resolve or become tolerable within 8 to 12 weeks. About 24% in trials discontinued for side effects. Persistent severe symptoms beyond 12 weeks warrant a conversation about stopping.

Does Contrave interact with antidepressants? Yes, several. SSRIs and SNRIs raise serotonin syndrome risk modestly. Tricyclics raise seizure risk. MAOIs are absolutely contraindicated within 14 days. Tell your psychiatrist before starting and don't combine without close supervision.

Sources

1. Greenway FL, et al. Effect of naltrexone plus bupropion on weight loss in overweight and obese adults (COR-I). Lancet. 2010;376:595-605.
2. 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.
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. Contrave Prescribing Information. Currax Pharmaceuticals, current revision.
6. Nissen SE, et al. Effect of naltrexone-bupropion on major adverse cardiovascular events in overweight and obese patients with cardiovascular risk factors (LIGHT trial interim results). JAMA. 2016;315:990-1004.
7. FDA Drug Safety Communication: Suicidal thoughts in young adults taking antidepressants, 2007 (class warning applicable to bupropion).
8. American Association of Clinical Endocrinology Obesity Pharmacotherapy Guidelines. Endocrine Practice. 2022.
9. Khera R, et al. Association of pharmacological treatments for obesity with weight loss and adverse events: a systematic review and meta-analysis. JAMA. 2016;315:2424-2434.
10. FDA Adverse Event Reporting System (FAERS) public dashboard, naltrexone-bupropion entries through 2024.
11. American Diabetes Association. Standards of Medical Care in Diabetes 2025. Diabetes Care. 2025;48(Suppl 1).
12. Yanovski SZ, Yanovski JA. Long-term drug treatment for obesity: a systematic and clinical review. JAMA. 2014;311:74-86.
13. National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), Prescription Medications to Treat Overweight & Obesity, 2024.

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