Contrave vs. Phentermine: Which Weight Loss Pill Delivers Better Results?

Obesity and overweight are significant health concerns affecting a large percentage of the adult population. According to the Centers for Disease Control and Prevention (CDC), nearly three-quarters of adults aged 20 and older are overweight, including those with obesity, and 42% of adults are classified as obese. Initial treatment recommendations include lifestyle interventions, such as healthy nutrition, increased physical activity, and behavioral modifications, but weight loss is usually modest, and most people regain weight over time. Since most people do not achieve the desired weight loss with lifestyle modification, medications and surgical interventions are often considered.

Weight loss drugs, also commonly known as anti-obesity drugs, are medications intended to assist in weight loss. There are a few ways they can do this, including increasing metabolism, preventing fat absorption, and suppressing appetite.

Among the various options available, Contrave and phentermine are two FDA-approved prescription medications frequently discussed. This article provides a detailed comparison of Contrave and phentermine, covering their mechanisms of action, efficacy, safety, cost, and other critical factors to help individuals make informed decisions about their weight loss journey.

Understanding the Medications

Contrave

Contrave is a prescription-only weight loss medication with two primary active ingredients: naltrexone and bupropion. It is available as a brand name only, and you cannot buy Contrave over the counter.

Naltrexone: An opioid antagonist that reduces cravings for food. Naltrexone is an FDA-approved drug used to treat opioid use disorder and alcohol use disorder. Naltrexone works to help individuals with addiction by preventing these pleasurable feelings associated with alcohol and opioid use. Over time, drugs, alcohol, and even food can hijack the brain’s reward center creating an unhealthy addiction cycle. Naltrexone can also help you lose weight.
Bupropion: Helps restore the brain’s balance of dopamine and norepinephrine, neurotransmitters that are involved in reward, stress, and memory. It is the active ingredient in common antidepressants like Wellbutrin and Aplenzin.

It is thought that the two ingredients in Contrave work on two separate areas of the brain that regulate food intake. When combined, bupropion and naltrexone may work together to not only reduce hunger cravings, but also reduce stress associated with food cravings and urges and improve mental awareness which all can have positive effects on weight loss. This could explain why Contrave is such an effective weight loss medication when used with diet and exercise.

Contrave is indicated for chronic weight management in adults with a body mass index (BMI) of 30 kg/m2 or more (obese)-or 27 kg/m2 or more (overweight) with at least one other weight-related risk factor, such as high blood pressure, Type 2 diabetes, or high cholesterol.

Phentermine

Phentermine is a generic prescription drug used for weight loss. You cannot buy phentermine over the counter. Phentermine brand names include Adipex, Adipex-P, Atti-Plex, Fastin, Ionamin, and Lomaira. It is classified as an anorectic drug and is a stimulant that acts similarly to amphetamine.

Phentermine is thought to work by various mechanisms, including actions on the central nervous system (CNS), metabolic effects, and possibly as an appetite suppressant. It is primarily an anorexiant drug that focuses entirely on decreasing appetite.

Phentermine stimulates the nervous system to increase heart rate and blood pressure. It increases the level of some neurotransmitters in the brain, including dopamine and norepinephrine.

Phentermine is indicated as a short-term (several weeks) weight loss treatment. Adult patients with a BMI of 30 kg/m2 or more-or 27 kg/m2 or more with at least one other weight-related risk factor/comorbidity may be a candidate for a phentermine prescription.

Read also: Safe Diet Pills

How They Work

Contrave: Decreases the desire to eat and increases the feeling of fullness. Naltrexone and bupropion work together to help patients reduce cravings and increase feelings of fullness.
Phentermine: Simply suppresses appetite. It is primarily an anorexiant drug that focuses entirely on decreasing appetite.

Dosage and Administration

Contrave: Is available as an extended-release tablet. The Contrave dosage is slowly increased, from one tablet in the morning, over a period of four weeks to its maintenance dosage of two tablets twice daily. Contrave should be taken in the morning and evening, but not with a high-fat meal. The dosage is increased weekly over 4 weeks to 2 tablets by mouth twice a day, in the morning and evening (but not with a high-fat meal).
Phentermine: Should be taken in the morning as directed by your doctor. It should be taken either before breakfast, or one to two hours after breakfast, to help control appetite. Your doctor will prescribe the lowest possible dose that is effective. Some patients will be prescribed a smaller dose several times daily. Taking phentermine at night should always be avoided, because the medication can cause insomnia. The typical dosage is 15 to 37.5 mg by mouth every morning.

Efficacy

RCT evidence demonstrates that semaglutide, liraglutide, phentermine/topiramate, and bupropion/naltrexone all reduce body weight compared with placebo when added to standard lifestyle modification.

Contrave: In studies, over 56 weeks, the average weight loss in people taking Contrave was about 17 pounds. In one study, the Contrave group lost an average of 5.4 percent of their body weight compared to the placebo group, who lost 1.3 percent. Additionally, 42 percent of Contrave patients lost more than 10 percent of their body weight. After starting Contrave, you can expect to lose 5 percent of your body weight when paired with diet and regular exercise after 12 weeks of treatment. In clinical trials for Contrave, between 36% and 57% of people (depending on which study) lost 5% or more of body weight, and 15% to 35% of people lost 10% or more.
Phentermine: A 2010 study in the journal Diabetes, Obesity, and Metabolism found that 96 percent of adults with obesity who took phentermine for 12-weeks lost at least 5 percent of their body weight. Within that same group, 62 percent lost more than 10 percent body weight. A 2021 study found 80 percent of adults who took phentermine for six-months lost at least 5 percent of their body weight.

Duration of Use

Contrave: Is indicated for long-term use.
Phentermine: Is indicated for short-term use. Phentermine is usually taken for a few weeks until tolerance develops.

Cost and Availability

Contrave: Is sometimes covered by insurance plans but is generally not covered by Medicare prescription plans. A typical prescription for Contrave without insurance coverage should be no more than $199 if you pay out-of-pocket with a Contrave savings card from the manufacturer. Although generic naltrexone and generic bupropion are available, generic Contrave, which contains both naltrexone and bupropion, is not yet available. Neither naltrexone nor bupropion should be used alone as a Contrave generic.
Phentermine: Insurance and Medicare prescription plans do not usually cover phentermine. Phentermine without insurance costs about $40 for 30, 37.5 mg tablets. Generic phentermine is cheaper than brand-name Contrave.

Side Effects and Risks

Contrave and phentermine have some similar side effects, such as stomach problems, headache, and difficulty sleeping.

Common Side Effects of Contrave

Nausea
Constipation
Headache
Vomiting
Dizziness
Insomnia
Dry mouth

Common Side Effects of Phentermine

Increased heart rate
Increased blood pressure
Insomnia
Dry mouth
Constipation
Nervousness

Serious Risks and Warnings

Contrave: Has a black box warning. This is the strongest warning required by the FDA. The warning states that although Contrave contains bupropion, an antidepressant, Contrave is not approved to treat depression or other psychiatric disorders. Antidepressants may cause an increased risk of suicidal thoughts and behavior in children, adolescents, and young adults up to age 24. People taking Contrave for weight loss should be monitored for the development of psychiatric side effects including depression, mania, psychosis, hallucinations, paranoia, delusions, homicidal ideation, hostility, aggression, anxiety, panic, and agitation-in addition to suicidal thoughts and behaviors mentioned above. If symptoms occur, stop Contrave and contact your healthcare provider. Contrave may increase heart rate and can cause liver problems and angle-closure glaucoma. If you have taken opioids in the past, you may be more sensitive to lower doses of opioids and there is a risk of accidental overdose if you take opioids again. This is due to the naltrexone ingredient in Contrave. Taking large doses of opioids can cause serious injury, coma, or death.
Phentermine: Can cause pulmonary hypertension. Phentermine stimulates the central nervous system. For most people, phentermine increases energy so it’s used with caution on patients with anxiety. It is also not safe to use in many patients with heart disease and diseases of rapid heart rate.

Contraindications

Contrave: One of the primary contraindications for Contrave includes eating disorders such as anorexia or bulimia. These require an entirely different approach to solve. Qsymia and Contrave are contraindicated during pregnancy and lactation.
Phentermine: Because phentermine increases heart rate and blood pressure, you shouldn’t take it if you have a pre-existing heart condition.

Drug Interactions

With either drug, weight loss can result in low blood sugar. Blood glucose levels should be monitored. Contrave and phentermine can raise blood pressure.

Special Considerations

Pregnancy: Weight loss can cause harm to an unborn baby. Contrave or phentermine should be stopped when a pregnancy is detected. Contact your doctor if you are pregnant or think you may be pregnant. Qsymia and Contrave are contraindicated during pregnancy and lactation.
Alcohol: You should not mix Contrave or phentermine with alcohol. Taking Contrave with alcohol can increase the risk of psychiatric events. Excess use of alcohol or stopping alcohol abruptly can also increase the risk of seizures if you are taking Contrave.
Tolerance: Tolerance may occur in several weeks with phentermine.

Abuse Potential

Phentermine is a short-term treatment for weight loss, classified as a Schedule IV controlled substance with the potential for abuse and dependence. Phentermine is considered a controlled-substance, because it has a risk of abuse and dependency. People who have previously struggled with substance abuse disorder said that they were put-off by the stimulant effects of this medication.

Contrave has a low potential for abuse relative to those in schedule 3. It has a currently accepted medical use in treatment in the United States.

Making the Right Choice

Choosing between Contrave and phentermine depends on individual needs, health status, and weight loss goals.

Choose Phentermine if: You’re looking for a short-term option for relatively quick results. However, it’s worth considering that it has more contraindications and potential side effects.
Choose Contrave if: You prefer long-term treatment for sustained weight loss. Instead of working at a neurotransmitter level, it implements antidepressant and smoking cessation qualities. Contrave may be a better choice in a patient with a history of substance use disorder.

There are no studies directly comparing phentermine vs. Contrave. Drug selection is based on a variety of factors, such as other medical conditions, anticipated side effects and drug interactions, and insurance coverage. For example, a patient who does not have insurance coverage may be better suited for phentermine, which is relatively inexpensive.

Alternative Weight Loss Medications

Other common weight-loss drugs include Alli (orlistat), Xenical (orlistat), and Qsymia (phentermine/topiramate). Injectable drugs, which are used for Type 2 diabetes and/or weight loss, include Ozempic (semaglutide), Saxenda (liraglutide), Victoza (liraglutide), and new drug Wegovy (semaglutide). Plenity is a new weight loss pill as of Fall 2020 and is only available via prescription from doctors. The Plenity weight loss pill is made from cellulose and citric acid. The patient ingests 3 tablets and 16 oz of water before lunch and dinner. Plenity tablets swell 100 times their original size, taking more space in the stomach and gives the user a feeling of fullness (satiety). Since Plenity isn’t absorbed by the body, side effects are less common than other weight loss medications.

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