Common Side Effects of Contrave
Many individuals starting Contrave experience temporary and mild-to-moderate side effects, especially during the initial four-week dosage escalation period. As the body adjusts to the medication, these issues often subside. The most commonly reported adverse reactions from clinical studies include:
- Nausea
- Constipation
- Headache
- Vomiting
- Dizziness
- Insomnia (trouble sleeping)
- Dry mouth
- Diarrhea
- Fatigue
- Increases in blood pressure and heart rate
For many, gastrointestinal problems like nausea and constipation are the most bothersome, but they can often be managed with careful dietary adjustments and hydration.
Serious Warnings and Adverse Effects
Beyond the more common and manageable side effects, Contrave carries several serious warnings, including an FDA-mandated boxed warning for psychiatric risks. A boxed warning is the most serious type of warning issued by the FDA for medications with potentially dangerous effects.
Psychiatric Risks
Contrave contains bupropion, an ingredient also used in some antidepressants. This component can increase the risk of suicidal thoughts and behavior, especially in younger adults. It is crucial for patients and their caregivers to monitor for any sudden changes in mood, thoughts, or behavior, including:
- Worsening depression or anxiety
- Feeling agitated, irritable, or restless
- Panic attacks
- Aggression or violence
- Acting on dangerous impulses
- Thoughts about suicide or dying
Bupropion can also trigger manic or hypomanic episodes in individuals with a history of bipolar disorder or those with risk factors for it.
Seizure Risk
Contrave can cause seizures, with the risk increasing with higher doses or with certain medical conditions. To minimize this risk, patients should adhere strictly to their prescribed dosage and avoid taking the medication with high-fat meals. Certain patient groups are at a higher risk and should not take Contrave, including those with a history of seizure disorders, eating disorders (anorexia or bulimia), or those undergoing abrupt withdrawal from alcohol, benzodiazepines, or anti-seizure medications.
Cardiovascular Concerns
Increases in blood pressure and heart rate have been observed in patients taking Contrave. While the clinical significance is not fully understood for all patients, those with pre-existing heart conditions or uncontrolled hypertension should be monitored closely. Contrave is not recommended for individuals with uncontrolled high blood pressure.
Liver Damage
Cases of liver damage and hepatitis have been associated with naltrexone, a component of Contrave. Symptoms can include dark urine, yellowing of the eyes or skin (jaundice), and unusual fatigue. Patients with pre-existing liver problems should be cautious, and those with severe impairment should not use the medication.
Opioid Interaction Dangers
Naltrexone blocks the effects of opioids. Taking Contrave concurrently with opioid medications can cause precipitated withdrawal in individuals who are opioid dependent. Trying to overcome this blockade with high doses of opioids is extremely dangerous and can lead to a fatal overdose. Patients must be opioid-free for 7 to 10 days before starting Contrave.
Angle-Closure Glaucoma
Contrave can cause pupillary dilation, which may trigger an angle-closure attack in individuals with narrow angles in their eyes. This is a medical emergency that can lead to vision loss if untreated.
Contraindications and Drug Interactions
In addition to the specific side effects, Contrave has several contraindications and drug interactions that must be considered before treatment begins. These include:
Contraindications:
- Use of other bupropion-containing products (e.g., Wellbutrin, Aplenzin)
- Concurrent or recent use of monoamine oxidase inhibitors (MAOIs)
- Bulimia or anorexia nervosa
- Chronic opioid use
- Uncontrolled hypertension
- History of seizures
Drug Interactions:
- Opioid analgesics: Naltrexone blocks their effect, posing an overdose risk.
- CYP2D6 substrates: Can increase levels of certain antidepressants and antipsychotics.
- CYP2B6 inhibitors and inducers: Can alter bupropion exposure.
- Drugs lowering the seizure threshold: Increases risk of seizure.
- Dopaminergic drugs (e.g., levodopa): Increased risk of CNS toxicity.
Comparison of Contrave Downsides with Other Weight-Loss Medications
| Feature | Contrave | GLP-1 Agonists (e.g., Wegovy, Zepbound) | Phentermine | Orlistat |
|---|---|---|---|---|
| Mechanism | Naltrexone (opioid antagonist) and bupropion (antidepressant) targeting appetite and reward centers. | Mimics hormone (GLP-1) to reduce appetite and slow gastric emptying. | Sympathomimetic amine, acts as a stimulant to suppress appetite. | Lipase inhibitor, blocks fat absorption. |
| Common Side Effects | Nausea, constipation, headache, vomiting, dizziness, insomnia. | Nausea, vomiting, diarrhea, indigestion, constipation. | Increased heart rate, blood pressure, insomnia, nervousness. | Oily stools, flatulence, fecal urgency. |
| Serious Side Effects | Seizures, liver damage, psychiatric issues (boxed warning), angle-closure glaucoma. | Pancreatitis, gallbladder problems, thyroid C-cell tumors (boxed warning for thyroid cancer on some). | Heart valve disease, pulmonary hypertension, addiction potential. | Severe liver injury. |
| Administration | Oral tablet, typically twice daily. | Weekly or daily injection. | Oral tablet, once daily. | Oral capsule, three times daily. |
| Drug Interactions | Numerous, especially with opioids, MAOIs, and drugs metabolized by CYP2D6. | Fewer, but caution with other medications. | Potential for CNS stimulants and MAOIs. | Minimal systemic absorption, fewer drug interactions. |
| Efficacy | Generally modest weight loss (5-10%). | Potentially greater weight loss (15%+). | Effective for short-term use. | Moderate, depends on diet compliance. |
The Importance of Lifestyle Adjustments
It's important to recognize that Contrave is not a magic solution for weight loss. It is intended to be used as a supplement to a reduced-calorie diet and increased physical activity. In fact, if a patient does not lose at least 5% of their body weight after 12 weeks at the maximum dose, it is unlikely they will achieve or sustain meaningful weight loss with continued treatment. Without committing to fundamental changes in diet and exercise habits, any weight lost while on the medication is likely to be regained if treatment is stopped.
Conclusion: Evaluating the Downsides of Contrave
While Contrave offers a non-stimulant option for weight management, its use comes with significant drawbacks. Common side effects like nausea and constipation are manageable for many but can be persistent. More serious risks, particularly the FDA boxed warning for suicidal thoughts, seizure risk, and cardiovascular effects, necessitate careful medical screening and monitoring. Additionally, the drug's effectiveness is contingent upon concurrent lifestyle changes, meaning it is not a standalone solution. The potential for serious drug interactions and specific contraindications related to psychiatric history, opioid use, and other conditions further highlight that Contrave is not appropriate for everyone. Any individual considering Contrave should have a thorough discussion with a healthcare provider about their full medical history and the potential risks versus benefits before starting treatment.
For official and comprehensive prescribing information, refer to the U.S. Food and Drug Administration's official drug documentation.
