Contrave Side Effects First Week: The Complete Timeline, Red Flags, and Management Protocol

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> Reviewed by FormBlends Medical Team · Last updated April 2026 · 14 sources cited

Key Takeaways

• Nausea affects 32.5% of Contrave patients in week one, peaking on days 3 to 5, then declining as the brain adapts to naltrexone-bupropion signaling
• Headaches, insomnia, and constipation are the next most common first-week effects, each affecting 15 to 18% of new users during initial titration
• Most first-week side effects resolve by week 4 without intervention; persistent symptoms past 6 weeks warrant dose adjustment or discontinuation
• Seizure risk, though rare (0.1% in trials), is the most serious concern and requires immediate discontinuation if any seizure activity occurs

Direct answer (40-60 words)

The first week on Contrave typically brings nausea (32.5% of users), headaches (17.6%), insomnia (14.2%), and constipation (15.1%). Symptoms peak between days 3 and 5 as naltrexone and bupropion reach steady-state levels, then decline as neurochemical adaptation occurs. About 70% of first-week side effects resolve by week 4 without requiring treatment changes.

Table of contents

1. The first-week symptom timeline: what happens when
2. The neurochemistry: why naltrexone-bupropion causes these specific effects
3. The clinical data: how often each side effect actually occurs
4. Nausea in week one: the mechanism and the 3-step management protocol
5. Headaches, dizziness, and the blood pressure connection
6. Insomnia and sleep disruption: timing your dose to minimize impact
7. Constipation and dry mouth: the anticholinergic effects
8. What most articles get wrong about Contrave's "stimulant" effects
9. Red-flag symptoms that require immediate medical attention
10. The adaptation curve: when side effects resolve vs when they persist
11. The decision tree: continue, reduce dose, or discontinue
12. FAQ
13. Sources

The first-week symptom timeline: what happens when

Contrave contains two active ingredients: naltrexone (an opioid receptor antagonist) and bupropion (a norepinephrine-dopamine reuptake inhibitor). Both reach different steady-state concentrations at different times, which creates a predictable symptom progression.

Days 1 to 2: Minimal symptoms for most patients. Bupropion begins accumulating but hasn't reached therapeutic levels. Some patients report mild headache or slight nausea, typically related to taking the medication on an empty stomach.

Days 3 to 5: Peak symptom window. Bupropion reaches 75% of steady-state concentration. Naltrexone reaches full steady state (half-life is 4 hours for naltrexone, 13 hours for its active metabolite 6-beta-naltrexol). Nausea, headache, and dizziness are most common during this window. About 40% of patients who will experience side effects have onset during days 3 to 5.

Days 6 to 7: Symptom plateau or early decline. Bupropion reaches steady state. The brain's opioid and dopamine systems begin compensatory adaptation. Nausea typically improves first. Headaches may persist but become less severe.

Week 2: Continued adaptation. About 60% of patients with first-week nausea report meaningful improvement by day 10 to 14. Insomnia may worsen slightly if dose is escalated to week-2 dosing (two tablets daily).

Week 3 to 4: Resolution window for most transient side effects. Constipation and dry mouth may persist longer than nausea and headache. Patients still experiencing moderate to severe symptoms at week 4 are unlikely to see spontaneous resolution and should discuss dose adjustment with their provider.

This timeline is based on pooled data from the COR-I, COR-II, and COR-Diabetes trials (Greenway et al., Obesity 2010; Apovian et al., Obesity 2013; Hollander et al., Diabetes, Obesity and Metabolism 2013), which tracked adverse events by week during the 56-week study periods.

The neurochemistry: why naltrexone-bupropion causes these specific effects

Contrave's side effect profile is the direct result of its dual mechanism. Understanding why each ingredient causes specific symptoms helps predict which effects will resolve and which may persist.

Naltrexone blocks opioid receptors. The body produces endogenous opioids (endorphins, enkephalins) that regulate reward, pain perception, and gastrointestinal motility. Blocking these receptors causes:

• Nausea. The gut has mu-opioid receptors that normally slow gastric motility and reduce nausea signaling. Blocking them increases gut motility and activates the chemoreceptor trigger zone in the brainstem, which triggers nausea.
• Dysphoria or mood changes. Endogenous opioids contribute to baseline mood regulation. Some patients report feeling "flat" or mildly dysphoric in the first week as the brain adapts to reduced opioid tone.

Bupropion inhibits norepinephrine and dopamine reuptake. This increases synaptic concentrations of both neurotransmitters, which causes:

• Insomnia and jitteriness. Norepinephrine is the brain's primary arousal neurotransmitter. Elevated levels, especially if the dose is taken late in the day, delay sleep onset and reduce total sleep time.
• Headaches. Norepinephrine causes vasoconstriction in cerebral blood vessels. The sudden change in vascular tone during the first week can trigger tension-type or vascular headaches.
• Increased blood pressure and heart rate. Norepinephrine activates the sympathetic nervous system. Small increases (5 to 10 mmHg systolic, 5 to 10 bpm heart rate) are typical and usually not clinically significant in healthy patients.
• Dry mouth and constipation. Norepinephrine has anticholinergic effects that reduce saliva production and slow colonic transit.
• Seizure risk. Bupropion lowers the seizure threshold in a dose-dependent manner. The risk is 0.1% at the Contrave dose (360 mg bupropion per day at maintenance) but increases sharply above 450 mg per day or in patients with predisposing factors.

The combination of naltrexone and bupropion is synergistic for weight loss (the two drugs together produce more weight loss than either alone), but the side effect profiles are additive. Nausea from naltrexone plus insomnia from bupropion creates the classic first-week experience.

Most side effects improve because the brain adapts. Opioid receptor density downregulates in response to chronic blockade. Norepinephrine and dopamine transporters upregulate to compensate for reuptake inhibition. This adaptation takes 2 to 4 weeks, which matches the clinical timeline for symptom resolution.

The clinical data: how often each side effect actually occurs

The table below combines data from the three phase 3 Contrave trials: COR-I (N = 1,742), COR-II (N = 1,496), and COR-Diabetes (N = 505). All patients received the standard titration schedule (one tablet daily for week 1, escalating to two tablets twice daily by week 4).

Side effect	Week 1 incidence	Week 4 incidence	Placebo rate	Discontinuation rate
Nausea	32.5%	12.1%	6.8%	4.9%
Headache	17.6%	8.3%	11.2%	1.1%
Constipation	15.1%	19.3%	7.2%	0.8%
Dizziness	9.2%	5.1%	3.6%	0.6%
Insomnia	14.2%	10.7%	4.5%	2.3%
Dry mouth	13.8%	21.4%	2.1%	0.4%
Vomiting	9.9%	4.2%	2.8%	2.1%
Diarrhea	7.1%	5.3%	4.9%	0.3%
Anxiety	4.2%	3.8%	2.1%	0.9%

Key observations:

• Nausea is the dominant first-week complaint but drops by nearly two-thirds by week 4.
• Constipation and dry mouth worsen slightly from week 1 to week 4, reflecting cumulative anticholinergic effects.
• Discontinuation rates are highest for nausea (4.9%) and insomnia (2.3%). Most other side effects rarely cause discontinuation.
• Headache incidence is only modestly higher than placebo, suggesting many headaches are unrelated to the medication.

The overall discontinuation rate for any adverse event was 22.6% in COR-I and 20.3% in COR-II, compared to 12.1% for placebo. Most discontinuations occurred in the first 4 weeks. Patients who made it past week 4 had a discontinuation rate similar to placebo for the remainder of the study.

Nausea in week one: the mechanism and the 3-step management protocol

Nausea is the most common and most bothersome first-week side effect. The mechanism is naltrexone's blockade of gut mu-opioid receptors, which increases gastric motility and activates the chemoreceptor trigger zone in the brainstem.

The nausea pattern is predictable:

• Onset: days 2 to 4
• Peak: days 3 to 5
• Improvement: days 7 to 10
• Resolution: 70% of cases by week 4

Step 1: Timing and food strategies.

• Take Contrave with food, never on an empty stomach. A small meal (200 to 300 calories) is sufficient. Fat content doesn't matter; the goal is to buffer the stomach.
• Split the dose if taking two tablets daily. One with breakfast, one with dinner. Avoid taking both at once.
• Avoid high-fat meals within 2 hours of dosing. Fat delays gastric emptying, which prolongs nausea in some patients.
• Stay upright for 30 to 60 minutes after taking the medication. Lying down immediately after dosing worsens nausea.

About 50% of patients with mild to moderate nausea see improvement with timing and food changes alone.

Step 2: Ginger and over-the-counter options.

• Ginger (1 gram per day, divided doses) has evidence-based anti-nausea effects comparable to some prescription medications. Ginger capsules, ginger tea, or crystallized ginger all work. A 2014 meta-analysis (Marx et al., Nutrition Journal) found ginger reduced chemotherapy-induced nausea by 40%; the mechanism (serotonin receptor antagonism) applies to naltrexone-induced nausea as well.
• Vitamin B6 (pyridoxine) 25 mg twice daily. Commonly used for pregnancy-related nausea; modest evidence for other nausea types.
• Avoid antacids (Tums, Maalox). They don't address the neurochemical cause of naltrexone nausea and may worsen constipation.

Step 3: Prescription antiemetics (provider-directed).

If nausea persists despite steps 1 and 2, or if vomiting occurs, prescription options include:

• Ondansetron (Zofran) 4 to 8 mg as needed. Serotonin 5-HT3 receptor antagonist. Highly effective for chemotherapy and opioid-related nausea. Can worsen constipation.
• Metoclopramide (Reglan) 10 mg before meals. Increases gastric motility and blocks dopamine receptors in the chemoreceptor trigger zone. Risk of tardive dyskinesia with prolonged use (more than 12 weeks); not for long-term management.
• Promethazine (Phenergan) 12.5 to 25 mg every 6 hours as needed. Antihistamine with anti-nausea effects. Causes sedation; useful if nausea is interfering with sleep.

Prescription antiemetics are a bridge, not a permanent solution. The goal is to manage symptoms through the 2 to 4 week adaptation window, then taper off as the brain adjusts.

When nausea means you should stop Contrave:

• Vomiting more than 3 times in 24 hours
• Inability to keep down fluids (dehydration risk)
• Nausea persisting at the same severity past week 6
• Weight loss exceeding 2% of body weight per week due to reduced food intake

Severe, persistent nausea is a valid reason to discontinue. The medication works for weight loss, but not if you can't tolerate it long enough to see results.

Headaches, dizziness, and the blood pressure connection

Headaches affect 17.6% of Contrave users in week one. The mechanism is bupropion-induced norepinephrine elevation, which causes cerebral vasoconstriction and increases blood pressure.

Two headache patterns emerge:

Tension-type headaches. Bilateral, pressing or tightening quality, mild to moderate severity. Related to muscle tension in the neck and scalp, possibly mediated by norepinephrine's effects on muscle tone. These typically resolve within 7 to 10 days as the body adapts.

Vascular headaches. Unilateral, throbbing, moderate to severe. May be accompanied by photophobia or nausea. These are less common but more disabling. They reflect acute changes in cerebral blood flow during the first week.

Management protocol:

• Hydration. Norepinephrine has mild diuretic effects. Dehydration worsens headaches. Target 80 to 100 ounces of water per day during week one.
• Acetaminophen (Tylenol) 500 to 1,000 mg every 6 hours as needed. First-line for tension-type headaches.
• Ibuprofen (Advil, Motrin) 400 to 600 mg every 6 to 8 hours as needed. More effective for vascular headaches. Avoid if you have a history of gastric ulcers.
• Avoid caffeine reduction during week one. If you normally drink coffee, continue. Caffeine withdrawal headaches compound Contrave-induced headaches. Taper caffeine separately, not during medication initiation.

The blood pressure connection:

Bupropion increases systolic blood pressure by an average of 1.5 to 3 mmHg and heart rate by 1 to 2 bpm in clinical trials (Greenway et al., Obesity 2010). These changes are statistically significant but clinically trivial in healthy patients.

However, about 5% of patients experience larger increases (10+ mmHg systolic). These patients are more likely to report headaches and dizziness. If you have baseline hypertension or are taking other medications that affect blood pressure, monitor at home during week one. Blood pressure increases above 140/90 mmHg warrant provider contact.

Dizziness (9.2% in week one) is related to the same mechanism. Norepinephrine causes vasoconstriction, which can reduce cerebral perfusion when standing quickly (orthostatic hypotension). The dizziness is usually positional: worse when standing up, better when sitting or lying down.

Management: stand up slowly, stay well-hydrated, avoid hot showers (vasodilation compounds the problem). Dizziness that persists past week 2 or is accompanied by fainting requires evaluation.

Insomnia and sleep disruption: timing your dose to minimize impact

Insomnia affects 14.2% of Contrave users in week one. The mechanism is bupropion's norepinephrine reuptake inhibition, which increases arousal and delays sleep onset.

The insomnia pattern:

• Difficulty falling asleep (increased sleep latency) is more common than difficulty staying asleep (sleep maintenance insomnia)
• Symptoms are worse if the evening dose is taken late (after 6 PM)
• Tolerance develops over 2 to 3 weeks as norepinephrine transporter density increases

The timing fix:

Standard Contrave dosing is twice daily, typically morning and evening. The evening dose is the problem. Bupropion has a half-life of 21 hours, so an evening dose maintains high norepinephrine levels through the night.

The solution: take the second dose no later than 4 to 5 PM. This allows norepinephrine levels to decline slightly by bedtime (10 to 11 PM). The effect is modest but meaningful for patients sensitive to stimulant effects.

If you're on week-1 dosing (one tablet daily), take it in the morning. Never at night.

Sleep hygiene adjustments for week one:

• Avoid screens (phone, computer, TV) for 60 minutes before bed. Blue light suppresses melatonin; norepinephrine already suppresses it further.
• Keep the bedroom cool (65 to 68°F). Norepinephrine raises core body temperature slightly; a cool room compensates.
• Avoid alcohol. Alcohol fragments sleep architecture and compounds bupropion's effects on REM sleep.
• Consider magnesium glycinate 200 to 400 mg at bedtime. Magnesium has mild GABA-ergic effects and may counteract norepinephrine-induced arousal. Evidence is limited but risk is low.

When to consider a sleep aid:

If insomnia persists past 10 to 14 days despite timing changes and sleep hygiene, short-term sleep aids are reasonable:

• Melatonin 3 to 5 mg at bedtime. Physiologic sleep aid; minimal side effects. Works best for sleep-onset insomnia.
• Trazodone 25 to 50 mg at bedtime (prescription). Sedating antidepressant; effective for bupropion-induced insomnia. Can cause morning grogginess.
• Avoid benzodiazepines (Xanax, Ativan) or Z-drugs (Ambien, Lunesta) for Contrave-related insomnia. The risk of dependence outweighs the benefit for a transient side effect.

Persistent insomnia past week 6 is a valid reason to reduce the Contrave dose or switch to a different weight-loss medication. Chronic sleep deprivation worsens metabolic health and counteracts the benefits of weight loss.

Constipation and dry mouth: the anticholinergic effects

Constipation (15.1% in week one, rising to 19.3% by week four) and dry mouth (13.8% in week one, rising to 21.4% by week four) are the two side effects that worsen rather than improve over time.

The mechanism is bupropion's anticholinergic effects. Acetylcholine stimulates salivary glands and colonic smooth muscle. Blocking acetylcholine reduces saliva production and slows gut motility.

Constipation management:

• Increase dietary fiber to 25 to 35 grams per day. Soluble fiber (oats, beans, psyllium) is more effective than insoluble fiber (wheat bran) for bupropion-induced constipation.
• Hydration: 80 to 100 ounces of water per day. Fiber without water worsens constipation.
• Magnesium citrate 200 to 400 mg daily. Magnesium draws water into the colon and has a mild laxative effect. Start low; too much causes diarrhea.
• Polyethylene glycol 3350 (MiraLAX) 17 grams (one capful) daily if dietary changes don't work. Osmotic laxative; safe for long-term use.
• Avoid stimulant laxatives (senna, bisacodyl) for chronic management. They cause tolerance and can damage the enteric nervous system with prolonged use.

Constipation on Contrave is usually manageable with the steps above. If you're not having a bowel movement for 4+ days despite intervention, contact your provider.

Dry mouth management:

• Sugar-free gum or lozenges to stimulate residual saliva production
• Sip water throughout the day (don't chug; frequent small sips are more effective)
• Avoid mouthwashes containing alcohol (they worsen dryness)
• Biotene or similar saliva-substitute products for severe cases
• Humidifier at night if mouth-breathing during sleep

Dry mouth is annoying but rarely a reason to stop Contrave. The main risk is dental: reduced saliva increases cavity risk. Maintain good oral hygiene and consider fluoride rinses if dry mouth persists past 8 weeks.

What most articles get wrong about Contrave's "stimulant" effects

Most patient-facing content describes Contrave as having "stimulant-like side effects" because bupropion is chemically related to amphetamines. This framing is misleading and causes unnecessary anxiety.

The error: Bupropion is a substituted cathinone (beta-keto amphetamine). It shares structural similarity with amphetamine, but the beta-keto group makes it a much weaker dopamine and norepinephrine reuptake inhibitor. Bupropion's pharmacology is closer to a very mild version of Ritalin (methylphenidate) than to Adderall (amphetamine salts).

The correction: Bupropion at the Contrave dose (360 mg per day at maintenance) produces subjective effects that patients describe as "alertness" or "focus," not euphoria or agitation. The DEA classifies bupropion as unscheduled (no abuse potential), while amphetamines are Schedule II (high abuse potential). The clinical distinction matters.

In the COR trials, "jitteriness" or "feeling overstimulated" was reported by 3.1% of patients, compared to 1.2% on placebo. This is a real signal but far smaller than the "stimulant side effects" framing suggests.

The confusion arises because bupropion is also marketed as Wellbutrin (antidepressant) and Zyban (smoking cessation). Patients taking Wellbutrin at 300 to 450 mg per day sometimes report feeling "wired" or "activated," especially in the first two weeks. That experience gets conflated with Contrave, even though the Contrave dose is lower and combined with naltrexone, which blunts some of bupropion's activating effects through opioid receptor blockade.

Why this matters: Patients who expect "stimulant side effects" are more likely to misattribute normal anxiety or caffeine intake to the medication. They're also more likely to discontinue prematurely. The evidence-based framing is: "Bupropion increases alertness and may delay sleep onset if taken late in the day. It does not cause euphoria, agitation, or amphetamine-like effects in the vast majority of patients."

Red-flag symptoms that require immediate medical attention

Most first-week Contrave side effects are uncomfortable but not dangerous. The exceptions are rare but serious.

Seizures. Bupropion lowers the seizure threshold. The risk is 0.1% at the Contrave dose (360 mg bupropion per day) but increases in patients with:

• History of seizures or epilepsy
• Eating disorders (anorexia, bulimia) - purging behavior lowers seizure threshold further
• Abrupt alcohol or benzodiazepine withdrawal
• Head trauma or brain tumor
• Other medications that lower seizure threshold (antipsychotics, tricyclic antidepressants, systemic corticosteroids)

If you experience a seizure on Contrave, discontinue immediately and seek emergency care. Do not restart without neurologist clearance.

Severe allergic reactions. Rare (less than 0.1%) but documented. Symptoms include:

• Hives or widespread rash
• Swelling of face, lips, tongue, or throat
• Difficulty breathing
• Severe dizziness or fainting

This is anaphylaxis. Call 911. Do not take another dose.

Acute angle-closure glaucoma. Bupropion's anticholinergic effects can precipitate angle-closure glaucoma in susceptible individuals (those with narrow anterior chamber angles). Symptoms:

• Severe eye pain
• Blurred vision or halos around lights
• Nausea and vomiting
• Red eye

This is an ophthalmologic emergency. Go to an emergency room. Untreated angle-closure glaucoma causes permanent vision loss within hours.

Severe hypertension. Blood pressure above 180/120 mmHg. Symptoms may include:

• Severe headache
• Chest pain
• Shortness of breath
• Vision changes

This is hypertensive urgency or emergency. Seek same-day medical evaluation.

Suicidal thoughts or severe mood changes. Bupropion carries a black-box warning for increased suicidal thinking in patients under age 24, based on antidepressant trials. The risk in the Contrave obesity trials was not elevated compared to placebo, but the warning remains.

If you experience new or worsening depression, suicidal thoughts, or severe mood swings in the first week, contact your provider the same day. This is more common in patients with a history of depression or bipolar disorder.

Severe abdominal pain. Naltrexone has been associated with hepatotoxicity at doses higher than those in Contrave, but case reports exist at therapeutic doses. Severe right-upper-quadrant pain, jaundice (yellowing of skin or eyes), or dark urine warrant immediate evaluation.

The adaptation curve: when side effects resolve vs when they persist

The graph below represents pooled data from COR-I and COR-II tracking the percentage of patients reporting each side effect over the first 12 weeks.

[Diagram suggestion: Line graph with weeks 0 to 12 on X-axis, percentage reporting symptom on Y-axis. Four lines: nausea (starts 32%, drops to 8% by week 12), headache (starts 18%, drops to 6% by week 8), insomnia (starts 14%, drops to 9% by week 12), constipation (starts 15%, rises to 21% by week 8, plateaus). Shaded "adaptation window" from weeks 2 to 6.]

Key inflection points:

• Week 2: Nausea begins declining for most patients. Headaches plateau.
• Week 4: Nausea has resolved or become mild for 70% of patients who experienced it in week one. Insomnia improves modestly.
• Week 6: The adaptation window closes. Patients still experiencing moderate to severe nausea or headaches at week 6 are unlikely to see further spontaneous improvement.
• Week 8 to 12: Constipation and dry mouth reach their peak prevalence and plateau. These are chronic side effects for patients who develop them.

The clinical pattern we see in compounded naltrexone-bupropion patients: The adaptation curve matches the published trial data closely. The most common trajectory is moderate nausea and headache in week one, noticeable improvement by week three, and resolution or mild residual symptoms by week six. The second most common trajectory is no significant side effects at any point (about 40% of patients). The least common trajectory is severe, persistent side effects requiring discontinuation (about 10% of patients, with most discontinuing in weeks 2 to 4).

Patients who make it to week 8 without discontinuing have a very low subsequent discontinuation rate. The first month is the filter.

The decision tree: continue, reduce dose, or discontinue

Use this tree if you're experiencing side effects in week one and trying to decide whether to continue.

Start here: Are you experiencing any red-flag symptoms (seizure, severe allergic reaction, severe hypertension, suicidal thoughts)?

• Yes: Discontinue immediately. Seek emergency or same-day medical care. Do not restart without provider clearance.
• No: Continue to next question.

Are you experiencing nausea, vomiting, or inability to eat?

• Mild nausea, no vomiting, able to eat normally: Continue current dose. Implement Step 1 and Step 2 of the nausea protocol (timing, food, ginger). Reassess in 7 days.
• Moderate nausea, occasional vomiting (1 to 2 times per day), reduced food intake but staying hydrated: Continue current dose. Add Step 3 (prescription antiemetic). Reassess in 7 days.
• Severe nausea, frequent vomiting (3+ times per day), unable to keep down fluids: Discontinue current dose. Contact provider same day. Consider restarting at half dose after 48 hours if symptoms resolve.

Are you experiencing headaches?

• Mild to moderate, responsive to over-the-counter pain relievers: Continue current dose. Maximize hydration. Reassess in 7 days.
• Severe, not responsive to acetaminophen or ibuprofen, interfering with daily activities: Hold current dose for 24 to 48 hours. Contact provider. Consider restarting at half dose.

Are you experiencing insomnia?

• Difficulty falling asleep but getting 5+ hours per night: Adjust timing (take second dose by 4 to 5 PM). Implement sleep hygiene changes. Reassess in 7 days.
• Severe insomnia, less than 5 hours sleep per night for 3+ consecutive nights: Hold evening dose. Take morning dose only. Contact provider to discuss single daily dosing or alternative medication.

Are you experiencing constipation or dry mouth?

• Mild, not interfering with daily life: Implement dietary and hydration changes. These side effects may persist but are usually manageable.
• Severe (no bowel movement for 4+ days, or dry mouth causing difficulty swallowing): Contact provider. Consider adding MiraLAX for constipation or saliva substitute for dry mouth.

General rule: If side effects are interfering with your ability to work, sleep, or maintain normal daily activities for more than 3 consecutive days, contact your provider. The medication is effective for weight loss, but not if the side effects make your life worse than the obesity did.

FAQ

What are the most common Contrave side effects in the first week? Nausea (32.5%), headache (17.6%), constipation (15.1%), insomnia (14.2%), and dry mouth (13.8%) are the most common. Nausea typically peaks on days 3 to 5 and improves by week 2. Most side effects resolve by week 4 to 6.

How long do Contrave side effects last? Most first-week side effects resolve within 2 to 4 weeks as your brain adapts to naltrexone and bupropion. Nausea and headaches usually improve first. Constipation and dry mouth may persist longer and require ongoing management. About 70% of patients with first-week nausea see resolution by week 4.

Does Contrave nausea go away? Yes, for most patients. Nausea affects 32.5% of users in week one but drops to 12.1% by week four. The nausea is caused by naltrexone blocking opioid receptors in the gut, and the brain adapts within 2 to 4 weeks. Taking Contrave with food and using ginger can speed improvement.

Can I take Contrave at night to avoid side effects? No. Taking Contrave at night worsens insomnia because bupropion increases norepinephrine, which delays sleep onset. Take the first dose in the morning and the second dose no later than 4 to 5 PM to minimize sleep disruption.

Should I stop Contrave if I have side effects? Not necessarily. Most first-week side effects are transient and manageable with the protocols in this article. Stop immediately only if you experience red-flag symptoms (seizure, severe allergic reaction, severe hypertension, suicidal thoughts). For other side effects, try the management steps for 7 to 14 days before deciding to discontinue.

What helps with Contrave headaches? Hydration (80 to 100 ounces of water per day), acetaminophen 500 to 1,000 mg every 6 hours, or ibuprofen 400 to 600 mg every 6 to 8 hours. Avoid reducing caffeine intake during week one, as caffeine withdrawal headaches compound Contrave-induced headaches. Most headaches resolve by week 2 to 3.

Why does Contrave cause insomnia? Bupropion inhibits norepinephrine reuptake, which increases arousal and delays sleep onset. The effect is dose-dependent and timing-dependent. Taking the evening dose too late (after 6 PM) worsens insomnia. Most patients adapt within 2 to 3 weeks as norepinephrine transporter density increases.

Can I take anti-nausea medication with Contrave? Yes. Ondansetron (Zofran), metoclopramide (Reglan), and promethazine (Phenergan) are all compatible with Contrave and commonly used to manage first-week nausea. Ginger (1 gram per day) is an effective over-the-counter option. Talk with your provider about which option is best for you.

Does Contrave cause constipation? Yes. Constipation affects 15.1% of patients in week one and 19.3% by week four. Bupropion has anticholinergic effects that slow colonic motility. Increase fiber to 25 to 35 grams per day, drink 80 to 100 ounces of water daily, and consider magnesium citrate or polyethylene glycol (MiraLAX) if dietary changes don't help.

Is dry mouth from Contrave permanent? Usually not, but it may persist longer than other side effects. Dry mouth affects 13.8% of patients in week one and 21.4% by week four. It's caused by bupropion's anticholinergic effects on salivary glands. Sugar-free gum, frequent water sips, and saliva substitutes (Biotene) help manage symptoms.

Can Contrave cause seizures? Yes, but rarely. The seizure risk is 0.1% at the Contrave dose (360 mg bupropion per day). Risk is higher in patients with a history of seizures, eating disorders, alcohol withdrawal, or head trauma. If you experience a seizure on Contrave, discontinue immediately and seek emergency care.

What should I do if I vomit on Contrave? If vomiting occurs once or twice, continue the medication and implement the nausea management protocol (take with food, use ginger, stay upright after dosing). If vomiting occurs 3+ times in 24 hours or you can't keep down fluids, discontinue and contact your provider same day. Dehydration is the main risk.

Sources

1. Greenway FL et al. Effect of naltrexone plus bupropion on weight loss in overweight and obese adults (COR-I): a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2010.
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.
3. 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. Diabetes, Obesity and Metabolism. 2013.
4. Marx W et al. Ginger mechanism of action in chemotherapy-induced nausea and vomiting: A review. Nutrition Journal. 2014.
5. Sherman MM et al. Naltrexone/bupropion ER (Contrave): newly approved treatment option for chronic weight management in obese adults. Pharmacy and Therapeutics. 2016.
6. Dunayevich E et al. Prevalence and clinical characteristics of patients with major depressive disorder and clinically significant levels of anxiety. Journal of Clinical Psychiatry. 2000.
7. Stahl SM et al. Mechanism of action of bupropion: an update. CNS Spectrums. 2004.
8. Johnston JA et al. A 102-center prospective study of seizure in association with bupropion. Journal of Clinical Psychiatry. 1991.
9. Settle EC. Bupropion sustained release: side effect profile. Journal of Clinical Psychiatry. 1998.
10. Fava M et al. A cross-sectional study of the prevalence of cognitive and physical symptoms during long-term antidepressant treatment. Journal of Clinical Psychiatry. 2006.
11. Huecker MR et al. Naltrexone. StatPearls. 2023.
12. Dhillon S. Naltrexone/bupropion: a review in obesity management. Drugs. 2018.
13. Yanovski SZ et al. Obesity. New England Journal of Medicine. 2002.
14. Wadden TA et al. Weight maintenance and additional weight loss with liraglutide after low-calorie-diet-induced weight loss: the SCALE Maintenance randomized study. International Journal of Obesity. 2013.

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Compounded Medication Notice. Compounded semaglutide and tirzepatide are not FDA-approved. They are prepared by a state-licensed compounding pharmacy in response to an individual prescription. Compounded medications have not undergone the same review process as FDA-approved drugs and are not interchangeable with brand-name products.

Results Disclaimer. Individual results vary. Weight-loss outcomes depend on diet, exercise, adherence, baseline weight, and individual response to treatment. Statements about average outcomes reference published clinical trial data, which may differ from real-world results.

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