In September 2014, the FDA recently approved a new weight loss drug Contrave. This drug is considered the third pharmaceutical treatment for obesity in the United States. Although it probably seems odd to mention a weight loss drug on a mental health website, the fact is that this new drug is a formulation of two older drugs – one of which happens to be an antidepressant.
It was developed by Orexigen Therapeutics and the potential revenue to be generated from this drug is thought to exceed annual earnings of $600 million. Based on clinical trials, participants were found to lose significantly more weight on Contrave combined with exercise and a healthy diet compared with individuals taking a placebo, exercise, and a healthy diet. Initially the drug was rejected by the FDA in 2011 due to uncertainty of long-term cardiovascular effects.
What is Contrave? (Bupropion / Naltrexone)
Contrave is a drug that was created as a combined formulation that consists of Bupropion (Wellbutrin) and Naltrexone. Bupropion is an atypical antidepressant medication that has been around for years. It is commonly used when traditional serotonin-targeted treatments are ineffective. Naltrexone is a drug that is used often to help with managing dependence on alcohol and/or opioids.
The amount of Bupropion in this drug is regarded as being significant enough to produce an antidepressant effect. Therefore most individuals could be treating both depression and addressing obesity with one formulation.
- Function: NDRI – This drug functions primarily as an “NDRI” or norepinephrine-dopamine reuptake inhibitor. In other words, it inhibits the reuptake of the neurotransmitters norepinephrine and dopamine (to a lesser extent).
- Effect: Stimulating – Bupropion tends to have a stimulating effect compared to most antidepressant medications. Those who take it usually notice that it increases their energy levels and they feel more stimulated. Additionally it is known to function as a smoking cessation aid, and those who take it tend to notice that it decreases appetite and speeds up metabolism.
- Dosage: In Contrave, the recommended starting dose consists of two tablets, each containing 90 mg Bupropion; resulting in 180 mg each administration. Since two tablets are to be taken 2x per day, a total of 4 tablets get ingested within a 24 hour period, result in 360 mg Bupropion which theoretically could yield an antidepressant effect. Most people on Wellbutrin (Bupropion) for depression take 100 mg, 150 mg, 300 mg, or 450 mg per day.
The amount of Naltrexone in this drug is comparable to the amount prescribed for substance dependence. Therefore most individuals could be treating substance dependence along with obesity in one formulation.
- Function: Opioid receptor antagonist – This drug works primarily as an opioid receptor antagonist at the “Kappa” and “Mu” receptors. To a lesser degree, it has also been shown to effect the “Delta” receptor. In layman’s terms, the drug blocks opioid receptors which act to block the pleasurable effects of opioids.
- Effect: Alteration of reward pathways – The effect of Naltrexone is less understood than that of Bupropion, but some speculate that as an opioid receptor antagonist, it alters functioning in the risk-reward centers of the brain. The antagonism of opioids is thought to decrease cravings for various foods.
- Dosage: In Contrave, the dosage of Naltrexone is 8 mg per tablet, but since 4 tablets are taken per day, it results in a starting dose of 32 mg Naltrexone. In comparison to the dosage taken for alcohol and opioid dependence, the amount in Contrave is slightly less. Most people start out at 25 mg Naltrexone for alcohol and opioid dependence and increase their dose to 50 mg for maintenance.
Contrave (Bupropion / Naltrexone)
Although the approval by the FDA is for weight loss, one could make the argument that this combination may also be effective in treating depression, opioid dependence, and alcohol dependence. The dosage in the drug compared to the dosages for depression and substance dependence are relatively similar and could even be more effective when combined than standalone options.
- Effect: Synergistic – It is believed that Bupropion works in synergy with Naltrexone to enhance weight loss. Both drugs have shown promise as individual treatments for weight loss, but the combination of the two tend to yield significantly better results.
- Function: The stimulation that a person receives from the Bupropion is thought to help them with energy levels and decrease appetite. Additionally Bupropion is believed to speed up the metabolism, and is often referred to as the best antidepressant for weight loss. Naltrexone is believed to help address the psychological cravings associated with food, particularly sweets. The synergistic effect is a result of changes in hypothalamus activity, which signals to the rest of the brain to decrease hunger and food cravings.
- Results: When combined with proactive efforts to lose weight such as eating healthy and getting adequate exercise, treatment with Contrave was found to help people lose a significant amount of weight compared to a placebo. Specifically, in clinical studies, the average weight loss on this medication was between 5 lbs. and 22 lbs. over a 6-month term.
Why not just get Wellbutrin and Naltrexone prescriptions?
To help people save money, I speculate that people will simply get prescriptions for Wellbutrin and Naltrexone to be taken together rather than pay a significant amount of money out-of-pocket. Obviously those with good health insurance will likely not have to pay much, but individuals without insurance that want access to a treatment may need a doctor to simply prescribe both of these medications to be taken together.
Is there really a difference between the two taken separately (together) vs. the two in one formulation? Only research could give us the answer, but most would probably guess that there isn’t going to be much difference. Perhaps the release of the drug, the interaction, or absorption of the drug could be difference. If you are thinking about going this route to save money, be sure to talk to consult your doctor.
Both have been used as off-label obesity treatments for years. The ethics behind prescribing these drugs for obesity is questionable, which is why most doctors have not prescribed these drugs in the past. However, since the combination has been established as an FDA approved combination, some doctors may start practicing poly-pharmacology with varying dosages of these drugs.
Contrave for depression: Could it be used as an antidepressant?
There are well-established links between obesity and development of serious mood disorders such as depression. It seems as though the more obese someone becomes, the more depressed they are likely to become as well. Additionally, the link is reciprocal in that the more depressed someone becomes, the more likely they are to gain weight and develop obesity.
In theory, this may be a useful drug to essentially address multiple problems with one pill. At certain doses a person may notice an antidepressant effect along with weight loss. For many obese, depressed individuals, it isn’t clear whether the obesity lead to the depression or vice-versa. In any regard, this is a medication that should help most people at least address their obesity, with an outside chance that it could help depressive symptoms.
Treating obesity can improve depression and vice-versa
For many individuals, treating obesity can be extremely helpful in reducing their depression. Waking up every day, looking in the mirror, and seeing an overweight body can be extremely depressing. Let’s face reality, society places a big emphasis on having a good physical appearance. In general, the more “fit” and better looking a person is, the more likely they are to find a prospective mate for a relationship – and thus increase their chances of happiness in certain regards.
Those with a better self-image are also more likely to be happy with the way they look, thus improving mood naturally. For others, losing weight can serve to increase confidence and make them feel as though they “fit in” with others. Although not all cases of obesity are caused by genetic factors, most experts would agree that genetics play an important role in most cases – regardless of exercise and dietary habits.
If you have a history of obesity and depression, this drug may be something to consider. It will obviously be a unique fit for those with obesity and comorbid depression and vice-versa. Researchers have been studying how depression and obesity could interact with a recent finding that a specific part of the brain can influence exercise motivation and that same part, called the habenula can lead to depression and negative thinking. This establishes links between exercise motivation and depression, which are both linked to obesity.
The goal of many pharmaceutical researchers will be to come up with medications that treat depression and obesity and/or address comorbid genetic factors.
Final thoughts on Contrave for obesity and weight loss
Although this is a unique formulation, do not expect this drug to help you lose a lot of weight without effort. Most people will still have to put forth some effort to keep their weight off. Additionally, I wouldn’t expect it to work for a long-term. It may work great for awhile, but eventually your body will build up a tolerance to the effects of the drug.
It should be speculated that when a person withdraws from the drug, they will return to the same situation that lead them to use the drug in the first place. Although it will be changing physiological activity, it’s only a matter of time before your physiology resets itself to homeostasis and your normal weight returns. There is a huge genetic component that contributes to obesity, which can be very frustrating.
Since this is a new formulation, long-term effects of ingesting Bupropion and Naltrexone are not well documented. It can be hypothesized that the combination should be relatively safe since these two drugs have been approved for usage in the United States since the 1980s. In any regard, this drug may be very beneficial for individuals in need of something to help them keep their weight down.
As better treatments for obesity emerge, this drug will eventually be outdated. In the future, scientists will have a better understanding of the genetic components that contribute to obesity and metabolic slowing. When they come up with strategies to specifically target genetics (e.g. gene therapy), appropriate modifications and cures can be made. In the meantime, everyone will continue to hop on the latest weight loss drug tends like Contrave for some much-needed help with obesity.