Common side effects
In clinical trials (COR-I and COR-II), Contrave was studied in over 4,500 patients. Most side effects are mild to moderate, occur during the first few weeks of dose escalation, and diminish as the body adjusts to the medication. The 4-week titration schedule is specifically designed to reduce the intensity of these early effects.
The most frequently reported side effects in clinical trials include:
- Nausea (33% of patients) — the most common side effect, usually mild and peaking during the first two weeks of titration. Taking Contrave with food can help.
- Constipation (19%) — manageable with increased hydration and dietary fiber intake.
- Headache (18%) — typically resolves within the first two weeks without intervention.
- Vomiting (10%) — less common than nausea and follows the same timing pattern.
- Dizziness (10%) — usually mild; patients should avoid sudden position changes.
- Insomnia (9%) — taking the second daily dose earlier in the day can help.
- Dry mouth (8%) — staying hydrated throughout the day is the best remedy.
- Diarrhea (7%) — usually transient and resolves without treatment.
| Side Effect | Frequency | Typical Onset | Typical Duration |
|---|---|---|---|
| Nausea | 33% | Week 1–2 | 2–4 weeks |
| Constipation | 19% | Week 1–3 | Often ongoing; manageable |
| Headache | 18% | Week 1 | 1–2 weeks |
| Vomiting | 10% | Week 1–2 | 2–4 weeks |
| Dizziness | 10% | Week 1–2 | 1–3 weeks |
| Insomnia | 9% | Week 1–2 | Variable; dose-timing helps |
| Dry mouth | 8% | Week 1–2 | Often ongoing; mild |
| Diarrhea | 7% | Week 1–3 | 1–2 weeks |
Frequency data from COR-I and COR-II clinical trials. Placebo-subtracted rates were lower. Individual experiences vary.
Most patients who tolerate the first four weeks of titration report that ongoing side effects are minimal. The nausea, in particular, tends to be the most bothersome early effect — but for most people it resolves as the body adapts to the medication.
The black box warning
Contrave carries an FDA black box warning — the most serious type of drug safety warning — for suicidal thoughts and behaviors. This is due to its bupropion component, which is also approved as an antidepressant (marketed as Wellbutrin).
Important context for understanding this warning:
- This is a class-wide warning. All medications containing antidepressants are required to carry this warning, regardless of the condition they are prescribed for. It is not specific to Contrave’s use for weight loss.
- The risk is primarily in younger patients. Clinical data show elevated risk in children, adolescents, and young adults under 25. In adults over 25, antidepressants were not associated with increased suicidality and may actually reduce risk in patients over 65.
- Bupropion is a norepinephrine-dopamine reuptake inhibitor (NDRI), not an SSRI. Its mechanism is distinct from most other antidepressants, but the class warning still applies.
The black box warning is serious and should not be dismissed — but it is a class-wide regulatory requirement for all antidepressant-containing medications, not a finding specific to Contrave in weight loss patients.
What your clinician will do
At PEAK, every patient is screened for depression and mood disorders before starting Contrave. During titration and ongoing treatment, clinicians monitor for signs of mood changes, including:
- New or worsening depression or anxiety
- Agitation, restlessness, or irritability
- Panic attacks
- Insomnia or unusual changes in behavior
- Suicidal thoughts or self-harm ideation
If you or someone close to you notices any of these changes, contact your clinician immediately. Contrave can be safely discontinued under medical supervision.
Serious side effects and contraindications
While most patients tolerate Contrave well, there are less common but clinically significant risks that both patients and prescribers should be aware of.
Seizures
Bupropion lowers the seizure threshold. The risk is dose-dependent and estimated at approximately 0.1% at the recommended Contrave dose. Patients should never exceed the prescribed dose. Contrave is contraindicated in patients with seizure disorders or any history of seizures. Risk factors that further lower the seizure threshold include alcohol withdrawal, benzodiazepine withdrawal, and eating disorders (due to electrolyte imbalances).
Elevated blood pressure
Some patients experience increases in blood pressure, particularly in the first three months of treatment. Blood pressure should be measured before starting Contrave and monitored regularly. Contrave should not be started in patients with uncontrolled hypertension.
Hepatotoxicity
Rare cases of liver injury have been reported with naltrexone use. Liver function should be monitored, and patients should report symptoms such as dark urine, yellowing of the skin, or persistent abdominal pain.
Allergic reactions
Hypersensitivity reactions are rare but possible. Symptoms may include rash, hives, swelling, or difficulty breathing. Seek emergency care immediately if these occur.
Angle-closure glaucoma
Bupropion can cause pupil dilation, which may trigger angle-closure glaucoma in susceptible individuals. Patients with narrow angles should be evaluated before starting treatment.
- Uncontrolled hypertension
- Seizure disorders or history of seizures
- Anorexia nervosa or bulimia nervosa (current or past)
- Chronic opioid or opiate agonist use (naltrexone blocks opioid receptors)
- Abrupt discontinuation of alcohol, benzodiazepines, or antiepileptic drugs
- Use of MAO inhibitors within 14 days
- Known allergy to naltrexone, bupropion, or any inactive ingredients
- Pregnancy (Contrave is not approved for use during pregnancy)
Your clinician will review your full medical history, current medications, and risk factors before prescribing Contrave. These contraindications are not barriers to treatment in general — they may simply mean a different weight loss medication is more appropriate for you.
For a detailed cost and coverage breakdown, see our guide to Contrave cost and insurance. You can also compare Contrave directly with phentermine to see which non-GLP-1 option fits your situation.
How dose titration minimizes side effects
Contrave uses a structured 4-week dose escalation schedule. This gradual increase is specifically designed to reduce the severity of nausea and other gastrointestinal side effects that occur when the body first encounters the medication.
| Week | Morning Dose | Evening Dose | Daily Total |
|---|---|---|---|
| Week 1 | 1 tablet | None | 1 tablet |
| Week 2 | 1 tablet | 1 tablet | 2 tablets |
| Week 3 | 2 tablets | 1 tablet | 3 tablets |
| Week 4+ | 2 tablets | 2 tablets | 4 tablets (full dose) |
Each tablet contains naltrexone 8mg / bupropion 90mg. Full dose = naltrexone 32mg / bupropion 360mg daily.
Skipping the titration or escalating too quickly significantly increases the likelihood and severity of nausea and other side effects. At PEAK, we strongly advise patients to follow the schedule exactly as prescribed.
Taking Contrave with food further reduces nausea. We recommend taking each dose with a meal. Tablets should be swallowed whole — do not cut, crush, or chew them, as this can release the medication too quickly and increase side effects.
The titration schedule is not optional. In clinical trials, patients who followed the 4-week dose escalation had significantly fewer discontinuations due to nausea than those who started at higher doses. If you’re struggling with side effects during titration, talk to your clinician before adjusting the schedule on your own.
How PEAK monitors for side effects
At PEAK, prescribing Contrave is only the beginning. We provide structured monitoring throughout treatment to catch side effects early, manage them effectively, and ensure patient safety.
Pre-treatment screening
Before your first prescription, your clinician conducts a thorough evaluation including depression and mood disorder screening, seizure history review, baseline blood pressure measurement, current medication review (to identify interactions), and assessment of contraindications including eating disorder history and opioid use.
Titration check-ins (Weeks 1–4)
During the 4-week dose escalation, patients receive check-ins to assess nausea, sleep quality, mood, and overall tolerability. If side effects are significant, your clinician may slow the titration or adjust the timing of doses.
Ongoing monthly follow-ups
After reaching full dose, patients are seen regularly to track:
- Weight loss progress and metabolic markers
- Side effect presence and severity
- Mood and psychological wellbeing
- Blood pressure
- Liver function (as indicated)
When to contact your clinician immediately
Reach out right away if you experience any of the following:
- Suicidal thoughts or significant mood changes
- Seizure activity
- Severe allergic reaction (rash, swelling, difficulty breathing)
- Signs of liver injury (dark urine, yellowing skin, abdominal pain)
- Chest pain or rapid heartbeat
- Any side effect that feels severe or is not improving
PEAK has a clear protocol for dose adjustment and discontinuation. If Contrave is not the right fit, we work with you to transition to an alternative medication rather than simply stopping treatment.
Tips for managing common side effects
Most Contrave side effects are manageable with simple strategies. Here are practical tips based on the most common complaints during treatment:
Nausea
Take each dose with food. This is the single most effective strategy for reducing nausea. Avoid taking Contrave on an empty stomach. If nausea persists, smaller meals throughout the day may help.
Insomnia
Take your evening dose earlier. Because bupropion is a mild stimulant, taking the second dose too close to bedtime can interfere with sleep. Try taking it with dinner rather than before bed.
Constipation
Increase fiber and water intake. Add whole grains, fruits, and vegetables to your diet. Aim for at least 8 glasses of water per day. Over-the-counter fiber supplements can also help.
Dry mouth
Stay hydrated throughout the day. Sip water regularly. Sugar-free gum or lozenges can also stimulate saliva production.
Dizziness
Rise slowly from sitting or lying positions. This is especially important during the first few weeks. Avoid driving or operating heavy machinery if dizziness is significant.
Headache
Stay hydrated and maintain regular meals. Most headaches resolve within the first two weeks. Over-the-counter pain relievers are generally safe, but check with your clinician.
Keep a symptom journal during titration. Write down what you experience, when it happens, and how severe it is. This gives your clinician valuable data to fine-tune your treatment plan at each check-in.
Most patients who tolerate the first 4 weeks of titration have minimal ongoing side effects. The early weeks are the hardest — and the titration schedule is designed to get you through them with the least discomfort. If you’re considering stopping because of side effects, talk to your clinician first. There are often adjustments that can help.
