Diet Pills that “Help” Depression—with Confusion, Hostility, and Heart Problems

So-called weight-loss drugs are huge business, but they’re going from bad to worse. The newest include antidepressant ingredients—and most users won’t even know they’re there—with more really awful side effects.

On February 1, the FDA declined to approve the weight-loss drug Contrave for the time being, expressing concern about Contrave’s cardiovascular effects when used long-term in a population of overweight and obese subjects. Officials told the manufacturer it must conduct a study “of sufficient size and duration” to demonstrate that the risk of heart attacks, strokes, and other major cardiovascular events does not undermine the drug’s risk-benefit profile. In other words, this was not a rejection of the drug, merely a request for more information.
A few months ago, an FDA advisory panel had voted to recommend approval of Contrave, which is made by Orexigen. Contrave was thought to have the best shot at approval, compared with two other experimental weight-loss drugs from other manufacturers, Lorqess and Qnexa. Lorqess was rejected last September because one of its ingredients increased the risk of breast tumors in lab animals. And Qnexa was rejected twice, once in October over heart risk concerns, and again this past January because one of its ingredients is associated with cleft lips in the children of women who take it. (Glaxo’s Alli—also known as Orlistat—is still being widely marketed, despite the risk that you might not be able to sit through a business meeting without messing yourself. How lovely. Well, that and the possiblity of liver damage.)
Following the FDA’s decision, market analysts say the likelihood of Orexigen pursuing the study are “less than 50%.” Within a week, Orexigen laid off about 40% of its workforce to save cash and focus resources on Contrave. Last month, Orexigen’s CFO resigned “for personal reasons.”
The really insidious thing about Contrave is that it is a combination of two existing drugs: naltrexone, used to treat alcohol and drug addiction, and sustained-release bupropion, an antidepressant known by the brand name Wellbutrin. Bupropion is also sold as Zyban, to help people quit smoking.
Neurotransmitters are chemical messengers that are used to communicate between brain cells. Most antidepressants are SSRIs—selective serotonin reuptake inhibitors—which work by changing the levels of one or more of these naturally occurring brain chemicals. SSRIs block the reabsorption (reuptake) of the neurotransmitter serotonin in the brain. Changing the balance of serotonin seems to help brain cells send and receive chemical messages, which in turn boosts mood. SSRIs are called selective because they seem to primarily affect serotonin, not other neurotransmitters.
Buproprion, by contrast, is a norepinephrine–dopamine reuptake inhibitor, not an SSRI. In other words, it works along different chemical pathways. As this article shows (but spins as a positive), because of the different pharmacological composition—whoopee!—you can use Contrave alongside SSRIs! Two antidepressant drugs must be better than one, right?
Wrong. Wellbutrin’s side effects include agitation, headaches, nausea, tremors, insomnia, blurred vision, high blood pressure, a rapid heart rate, confusion, hostility, hearing changes, irregular heart rhythms—and seizures. In fact, the high incidence of seizures caused the drug’s withdrawal from the market initially, until it was realized that for most people, the effects were dose-dependent. Even so, these effects are far from uncommon; they affect at least 5% of patients, with some affecting as many as 31%. Some people break out in hives from head to toe, but this isn’t considered serious enough to cause concern by the manufacturer!
Weight-loss drugs already use a similar approach. The popular FDA-approved diet pill Merdia acts like an antidepressant by blocking the reuptake of norepinephrine, serotonin, and dopamine in brain synapses.
If Contrave were to win final approval, patients who simply want to lose weight may be given antidepressants—despite their terrible side effects—without necessarily realizing it.
The use of the SSRI antidepressants (the other class of antidepressants) for weight loss is becoming popular as well. Doctors often prescribe the off-label use of “Phen-Pro” for weight loss. “Phen-Pro” is the combination of phentermine (an appetite suppressant of the amphetamine and phenethylamine class) and a low dose of one of the following antidepressants: Prozac, Zoloft, Celexa, Lexapro, trazadone, or Effexor. The second medicine is necessary because phentermine used alone stops working after a few weeks. Though the combination has not been FDA approved, each of these drugs individually has been.
Unfortunately, SSRIs are extremely addictive, and withdrawal from them can cause physical pain and nausea, not to mention a relapse in depression so severe as to drive the patient to suicide.
The FDA now requires a black box label on all antidepressant medications warning of increased risks of suicidal thinking and behavior in young people during the initial months of treatmentBut as our next article details, the black box warning covers only part of the danger to users and the people around them.

And with all this, the FDA is still trying to ban nutritional supplements geared toward weight loss. Don’t let them! If you haven’t already done so, please see our Action Alert.


  1. Sure they are trying to ban nutritional supplements because the organic community knows the FDA is killing people! It does not take a rocket scientist to know this espescially when you see the latest drug commercial and listen to the side effects not to mention the diet drinks that are inundated with the known carcinogen Aspartame and this has been proven to cause brain cancer and then you have the popular chemical dye Red 40 that they allow in anything from a snack cake to yogurt when it is banned in the UK! Please do not get me started about Splenda and Sweet and Low when I have heard out of the very mouth of a surgeon that Sweet and Low causes Alzheimers disease and then Splenda has not had enough studies done on it and I have also been told by an R..N. that splenda breaks down into chlorine in the stomach after ingestion! All allowed by the FDA!

    1. The real clincher is how they are testing these drugs. Read Public Law 105-85 and 86 for starters. Aerial spray a population and then just check the clinics for medical reports.” May cause death” … they got a head count! Time for the real “change”. Make the punishment fir the crime.

    1. Ibuprofen causes more cases of aplastic anemia than wellbutrin. Stop taking ibuprofen too!!! This is the most ludicrous thing I have read in a very long time. Hundreds of drugs have a greater chance of causing aplastic anemia then Wellbutrin.

  2. I found SSRIs effective but for me they had the side effect of inattention and forgetfulness. Buproprion offered the benefits without the harm. I had NONE of the side effects that you list. In any sufficiently large test population some symptoms will occur with enough frequency to merit reporting when they are not due to the drug at all.
    I used Buproprion at a time when I had no other health issues. Since then, due to age, genetics and sleep apnea, I am hypertensive and would not risk exacerbating that with Buproprion. Once I am fully controlled, I would consider Buproprion again.
    In contrast, obese people almost always have cardiovascular issues secondary to their obesity. Practically any intervention including diet, exercise or surgery would be at least a temporary stressor and would trigger some deaths in a test population. An outbreak of influenza would do the same.
    Bariatric specialists are realists. Most of their patients WILL die from their condition. Few will be cured but many will gain years of life from losing only a few percent of body weight and keeping it off. They know that each drug will have marginal benefit to a fraction of patients and that sets a low bar for drug approval. Why assume that dietary supplements would be more successful under the same test conditions?
    Any pharmaceutical company with deep enough pockets could turn a nutritional supplement into a prescription drug if it were safe and effective. Do you think that they are stupid?
    I do not use weight-loss supplements and propose that a weight loss supplement which has any physiological effect would pose the same risk to a similarly morbid population. The presumption that only pharmaceuticals have side-effects is laughable.
    Antidepressants and nutritional supplements both raise the same issues. They help some and hurt others. Physicians are realistic about their degree of doubt and their risk of harm. In contrast, many supplement users and vendors present a religious belief that a natural product could never cause any harm and that their specific product would benefit anyone.

    1. Mr Cruder:
      You say, “Any pharmaceutical company with deep enough pockets could turn a nutritional supplement into a prescription drug if it were safe and effective. Do you think that they are stupid?”
      According to the NIMH, “Scientists are also researching omega-3 fatty acids (most commonly found in fish oil) to measure their usefulness for long-term treatment of bipolar disorder.” Glaxo has also poured millions into marketing LOVAZA, aka omega-3-acid esters, which was approved by the FDA for the treatment of high triglycerides. My friends in Canada, including one who used to work for GSK there, says that LOVAZA will indeed be marketed in the future for depression et al. As a precursor for that inevitable day, the drug companies are leaning hard on Health Canada (the FDA of that country) to tighten regulation on natural supplements like Fish Oils. Some 33,000 products have already been pulled from the market in the Great White North, paving the way for copycat synthetic versions of these dietary supplements in favor of “approved” pharmaceutical versions.
      So, no, sir, Pharma is anything BUT stupid. After paying our billions to consumers harmed by many of their mental health drugs, they are looking to lessen their liability.
      I am thrilled that you have felt positive change as a result of your use of these drugs, but all we want is FULL Access to all of the science and adverse event reporting so that consumers can truly make an informed choice.
      Kevin P. Miller

  3. It is a shame that people do not want to take responsibility for their actions and expect pills wwith serious and some times dangeous sside effects. I am sending this info to my congressman Rahall and senator Rockfeller may be they can help. I am on the local prescription drug abuse prevention. I will definitely share this with my committee members
    Tara Sharma

  4. Please keep it up !
    We wish you all the best …
    Faiza and Mumtaz
    8th March 2011

  5. Instead of using weight loss tablets why not have a Meal Replacement drink? You can get them here in Australia and they have all the vitamins in them and a higher dose of protein, which you usually get through your meat and certain vegetables.
    If you stick to that and don’t eat a huge meal as well, it works better than any tablet with all the consequences of the additives.

  6. Nice article – it’s a perfect example of spin. While some of the points in your article are well-taken, e.g., bupropion can indeed cause hostility in some people it is very helpful when taken by many people. And your wording of the issue with seizures leads directly to the possibility that 31% of people suffered seizures on the medication when in reality the increase in seizures compared to placebo was 3% vs. 1% in individuals with bulimia. To the best of my knowledge, there is no evidence to suggest that the risk of seizures in non-bulimic individuals who are on reasonable doses of bupropion is higher than in the general population. The withdrawal syndrome from SSRIs/SNRI’s is relatively benign when individuals are warned ahead of time what to look for and the antidepressant is tapered slowly. For the record, I am not impressed by Contrave as a weight loss drug for several reasons including my dislike for fixed dose combination drugs (a la Symbyax) and no evidence to suggest that either bupropion or naltrexone alone are associated with significant weight loss. The key to weight loss in decreased calorie intake and increase exercise. Period. But your article is unnecessarily alarmist & conceivably could deter individuals from much-needed treatment.

  7. We can fight all these drugs but I think, like the drugs attack only symptoms of problems and not causes, we’re only fighting symptoms of the cause as well. The truth is, we will always be fighting one messed up drug after another. We need to be fighting the FDA and pushing for a serious reform in the government agency which controls our drugs and food, not the drugs and food themselves. However, I used Wellbutrin and I support shutting down this new drug.

  8. This is typical of how the chemical drugs industry operates. The health of all is far down their list, if there at all. Money is the goal, let’s say the god.

  9. Aren’t most diet pills (and diet supplements) useless? The key to long-term weight-loss is completely changing your diet for good. Actually diet supplements give the supplement industry a bad name. If your truly concerned about your health than change your diet first.
    And we all know the psychiatry industry is the biggest quackery in conventional medicine.

  10. Recently, I read a book called the ME Diet. ME stands for metabolic effect. The authors claim is that the type of wieght you loose is much more important then the amount. You want to loose fat tissue and not muscle tissue. If you loose muscle as you loose weight then you will lower your metabolic rate and soon you gain back whatever you have lost. On the other hand if you loose fat tissue and gain muscle then your metabolic rate go higher and you will be healthier and able to stay at the right weight for you.
    On their diet you can have all the fiber carbs ie most fruits and veggies you want but limited starch carbs ie bread, pasta etc. and lots of healthy protein and some healthy fat ie olive oil. The exercise they most recommend is weight training because it builds muscle. So everyone has a choice – a healthy informed lifestyle which takes determination and commitment or take drugs with short term benefits and long term dire consequences.

  11. Almost all of these comment are missing the nutrition link. Teach people about real nutrition not the kind that RDs practice and teach people about herbs and other supplements. None of these drugs will be needed.

  12. Not to mention the whole theory about neurotransmitters (e.g., serotonin) is still hypothetical, that’s why they say in ads “Paxil [for example] is *thought* to help regulate…etc. etc.”
    A popular antidepressant in France (tianeptine) is an SSRE btw (selective serotonin reuptake *enhancer*–iow it has the opposite mechanism of action from SSRIs, how is that possible you might ask)

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