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 treatment. But 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.
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