Are Sugar Pills Better than Antidepressant Drugs?

Do Antidepressant Drugs Really Work.jpg

We've learned that exercise compares favorably to antidepressant medications as a first-line treatment for mild to moderate depression (in my video Exercise vs. Drugs for Depression). But how much is that really saying? How effective are antidepressant drugs in the first place?

A recent meta-analysis sparked huge scientific and public controversy by stating that the placebo effect can explain the apparent clinical benefits of antidepressants. But aren't there thousands of clinical trials providing compelling evidence for antidepressant effectiveness? If a meta-analysis compiles together all the best published research, how could it say they don't work much better than sugar pills?

The key word is "published."

What if a drug company decided only to publish studies that showed a positive effect, but quietly shelved and concealed any studies showing the drug didn't work? If you didn't know any better, you'd look at the published medical literature and think "Wow, this drug is great." And what if all the drug companies did that? To find out if this was the case, researchers applied to the FDA under the Freedom of Information Act to get access to the published and unpublished studies submitted by pharmaceutical companies, and what they found was shocking.

According to the published literature, the results of nearly all the trials of antidepressants were positive, meaning they worked. In contrast, FDA analysis of the trial data showed only roughly half of the trials had positive results. In other words, about half the studies showed the drugs didn't work. Thus, when published and unpublished data are combined, they fail to show a clinically significant advantage for antidepressant medication over a sugar pill. Not publishing negative results undermines evidence-based medicine and puts millions of patients at risk for using ineffective or unsafe drugs, and this was the case with these antidepressant drugs.

These revelations hit first in 2008. Prozac, Serzone, Paxil and Effexor worked, but so did sugar pills, and the difference between the drug and placebo was small. That was 2008. Where were we by 2014? Analyses of the published data and the unpublished data that were hidden by drug companies reveals that most (if not all) of the benefits of antidepressants are due to the placebo effect. And what's even worse, Freedom of Information Act documents show the FDA knew about it but made an explicit decision to keep this information from the public and from prescribing physicians.

How could drug companies get away with this?

The pharmaceutical industry is considered the most profitable and politically influential industry in the United States, and mental illness can be thought of as the drug industry's golden goose: incurable, common, long term and involving multiple medications. Antidepressant medications are prescribed to 8.7 percent of the U.S. population. It's a multi-billion dollar market.

To summarize, there is a strong therapeutic response to antidepressant medication; it's just that the response to placebo is almost as strong. Indeed, antidepressants offer substantial benefits to millions of people suffering from depression, and to cast them as ineffective is inaccurate. Just because they may not work better than fake pills doesn't mean they don't work. It's like homeopathy--just because it doesn't work better than the sugar pills, doesn't mean that homeopathy doesn't work. The placebo effect is real and powerful.

In one psychopharmacology journal, a psychiatrist funded by the Prozac company defends the drugs stating, "A key issue is disregarded by the naysaying critics. If the patient is benefiting from antidepressant treatment does it matter whether this is being achieved via drug or placebo effects?"

Of course it matters!

Among the side effects of antidepressants are: sexual dysfunction in up to three quarters of people, long-term weight gain, insomnia, nausea and diarrhea. About one in five show withdrawal symptoms when they try to quit. And perhaps more tragically, the drugs may make people more likely to become depressed in the future. Let me say that again: People are more likely to become depressed after treatment by antidepressants than after treatment by other means - including placebo.

So if doctors are willing to give patients placebo-equivalent treatments, maybe it'd be better for them to just lie to patients and give them actual sugar pills. Yes, that involves deception, but isn't that preferable than deception with a side of side effects? See more on this in my video Do Antidepressant Drugs Really Work?

If different treatments are equally effective, then choice should be based on risk and harm, and of all of the available treatments, antidepressant drugs may be among the riskiest and most harmful. If they are to be used at all, it should be as a last resort, when depression is extremely severe and all other treatment alternatives have been tried and failed.

Antidepressants may not work better than placebo for mild and moderate depression, but for very severe depression, the drugs do beat out sugar pills. But that's just a small fraction of the people taking these drugs. That means that the vast majority of depressed patients--as many as nine out of ten--are being prescribed medications that have negligible benefits to them.

Too many doctors quickly decide upon a depression diagnosis without necessarily listening to what the patient has to say and end up putting them on antidepressants without considering alternatives. And fortunately, there are effective alternatives. Physical exercise, for example can have lasting effects, and if that turns out to also be a placebo effect, it is at least a placebo with an enviable list of side effects. Whereas side effects of antidepressants include things like sexual dysfunction and insomnia, side effects of exercise include enhanced libido, better sleep, decreased body fat, improved muscle tone and a longer life.


There are other ways meta-analyses can be misleading. See The Saturated Fat Studies: Buttering Up the Public and The Saturated Fat Studies: Set Up to Fail.

More on the ethical challenges facing doctors and whether or not to prescribe sugar pills in The Lie That Heals: Should Doctors Give Placebos?

I've used the Freedom of Information Act myself to get access to behind the scenes industry shenanigans. See, for example, what I found out about the egg industry in Who Says Eggs Aren't Healthy or Safe? and Eggs and Cholesterol: Patently False and Misleading Claims.

This isn't the only case of the medical profession overselling the benefits of drugs. See How Smoking in 1956 is Like Eating in 2016, The Actual Benefit of Diet vs. Drugs and Why Prevention is Worth a Ton of Cure (though if you're worried about your mood they might make you even more depressed!)

In health,

Michael Greger, M.D.

PS: If you haven't yet, you can subscribe to my free videos here and watch my live, year-in-review presentations:

Image Credit: GraphicStock. This image has been modified.

Original Link

Are Sugar Pills Better than Antidepressant Drugs?

Do Antidepressant Drugs Really Work.jpg

We've learned that exercise compares favorably to antidepressant medications as a first-line treatment for mild to moderate depression (in my video Exercise vs. Drugs for Depression). But how much is that really saying? How effective are antidepressant drugs in the first place?

A recent meta-analysis sparked huge scientific and public controversy by stating that the placebo effect can explain the apparent clinical benefits of antidepressants. But aren't there thousands of clinical trials providing compelling evidence for antidepressant effectiveness? If a meta-analysis compiles together all the best published research, how could it say they don't work much better than sugar pills?

The key word is "published."

What if a drug company decided only to publish studies that showed a positive effect, but quietly shelved and concealed any studies showing the drug didn't work? If you didn't know any better, you'd look at the published medical literature and think "Wow, this drug is great." And what if all the drug companies did that? To find out if this was the case, researchers applied to the FDA under the Freedom of Information Act to get access to the published and unpublished studies submitted by pharmaceutical companies, and what they found was shocking.

According to the published literature, the results of nearly all the trials of antidepressants were positive, meaning they worked. In contrast, FDA analysis of the trial data showed only roughly half of the trials had positive results. In other words, about half the studies showed the drugs didn't work. Thus, when published and unpublished data are combined, they fail to show a clinically significant advantage for antidepressant medication over a sugar pill. Not publishing negative results undermines evidence-based medicine and puts millions of patients at risk for using ineffective or unsafe drugs, and this was the case with these antidepressant drugs.

These revelations hit first in 2008. Prozac, Serzone, Paxil and Effexor worked, but so did sugar pills, and the difference between the drug and placebo was small. That was 2008. Where were we by 2014? Analyses of the published data and the unpublished data that were hidden by drug companies reveals that most (if not all) of the benefits of antidepressants are due to the placebo effect. And what's even worse, Freedom of Information Act documents show the FDA knew about it but made an explicit decision to keep this information from the public and from prescribing physicians.

How could drug companies get away with this?

The pharmaceutical industry is considered the most profitable and politically influential industry in the United States, and mental illness can be thought of as the drug industry's golden goose: incurable, common, long term and involving multiple medications. Antidepressant medications are prescribed to 8.7 percent of the U.S. population. It's a multi-billion dollar market.

To summarize, there is a strong therapeutic response to antidepressant medication; it's just that the response to placebo is almost as strong. Indeed, antidepressants offer substantial benefits to millions of people suffering from depression, and to cast them as ineffective is inaccurate. Just because they may not work better than fake pills doesn't mean they don't work. It's like homeopathy--just because it doesn't work better than the sugar pills, doesn't mean that homeopathy doesn't work. The placebo effect is real and powerful.

In one psychopharmacology journal, a psychiatrist funded by the Prozac company defends the drugs stating, "A key issue is disregarded by the naysaying critics. If the patient is benefiting from antidepressant treatment does it matter whether this is being achieved via drug or placebo effects?"

Of course it matters!

Among the side effects of antidepressants are: sexual dysfunction in up to three quarters of people, long-term weight gain, insomnia, nausea and diarrhea. About one in five show withdrawal symptoms when they try to quit. And perhaps more tragically, the drugs may make people more likely to become depressed in the future. Let me say that again: People are more likely to become depressed after treatment by antidepressants than after treatment by other means - including placebo.

So if doctors are willing to give patients placebo-equivalent treatments, maybe it'd be better for them to just lie to patients and give them actual sugar pills. Yes, that involves deception, but isn't that preferable than deception with a side of side effects? See more on this in my video Do Antidepressant Drugs Really Work?

If different treatments are equally effective, then choice should be based on risk and harm, and of all of the available treatments, antidepressant drugs may be among the riskiest and most harmful. If they are to be used at all, it should be as a last resort, when depression is extremely severe and all other treatment alternatives have been tried and failed.

Antidepressants may not work better than placebo for mild and moderate depression, but for very severe depression, the drugs do beat out sugar pills. But that's just a small fraction of the people taking these drugs. That means that the vast majority of depressed patients--as many as nine out of ten--are being prescribed medications that have negligible benefits to them.

Too many doctors quickly decide upon a depression diagnosis without necessarily listening to what the patient has to say and end up putting them on antidepressants without considering alternatives. And fortunately, there are effective alternatives. Physical exercise, for example can have lasting effects, and if that turns out to also be a placebo effect, it is at least a placebo with an enviable list of side effects. Whereas side effects of antidepressants include things like sexual dysfunction and insomnia, side effects of exercise include enhanced libido, better sleep, decreased body fat, improved muscle tone and a longer life.


There are other ways meta-analyses can be misleading. See The Saturated Fat Studies: Buttering Up the Public and The Saturated Fat Studies: Set Up to Fail.

More on the ethical challenges facing doctors and whether or not to prescribe sugar pills in The Lie That Heals: Should Doctors Give Placebos?

I've used the Freedom of Information Act myself to get access to behind the scenes industry shenanigans. See, for example, what I found out about the egg industry in Who Says Eggs Aren't Healthy or Safe? and Eggs and Cholesterol: Patently False and Misleading Claims.

This isn't the only case of the medical profession overselling the benefits of drugs. See How Smoking in 1956 is Like Eating in 2016, The Actual Benefit of Diet vs. Drugs and Why Prevention is Worth a Ton of Cure (though if you're worried about your mood they might make you even more depressed!)

In health,

Michael Greger, M.D.

PS: If you haven't yet, you can subscribe to my free videos here and watch my live, year-in-review presentations:

Image Credit: GraphicStock. This image has been modified.

Original Link

Why are Chickens Fed Prozac?

NF-Jan28 Illegal Drugs in Chicken Feathers.jpeg

Between 1940 and 1971, the synthetic estrogen DES was prescribed to several million pregnant women with the promise that it would "help prevent miscarriages." Problems were first highlighted in 1953 when it became clear that DES was not only ineffective but potentially harmful. However, a powerful and emotive advertising campaign ensured that its use continued until 1971, when it was found to cause cancer of the vagina in the daughters of the mothers who took it. DES was also used to stunt the growth of girls who were predicted to grow "abnormally tall." As one pediatric textbook put it in 1968, "excessive tallness in girls can be a handicap ... it provides difficulty in the purchase of smart clothes; the victim is ineligible for certain sought-after professional positions such as air line hostess; and poses problems in selecting suitable dancing partners."

What most people don't know is that the greatest usage of DES was by the livestock industry, used to improve "feed conversion" in cattle and chickens. Within a year of approval, DES was fed to millions of farm animals. Although it was shown to be a human carcinogen in 1971, DES used in meat production was not completely banned until 1979. (Now, the meat industry just uses different synthetic estrogen implants.) Even decades after DES was banned, we're still seeing its effects--an elevation of birth defects even down to the third generation.

Arsenic is another human carcinogen that was fed to chickens. This time by the billions. The arsenic not only ends up in the meat (as I've talked about previously in Arsenic in Chicken and How Many Cancers Caused by Arsenic Laced Chicken?), but also in the feathers, which are fed back to the animals. Because a third of the bird is inedible, the industry takes billions of pounds of heads, bones, guts, and feathers and uses them as fertilizer and animal feed. This feather meal is fed back to chickens, pigs, cows, sheep, and fish. Straight feathers are not particularly nutritious; so guts, heads, and feet may be added for a little extra protein, and manure added for minerals. The problem is that feather meal used as animal feed could contribute to additional arsenic exposure in persons who consume meat. This gave researchers at John Hopkins University and Arizona State an idea. By testing feather meal, they might be able to find out what else chickens are fed. In their study, "Feather Meal: A Previously Unrecognized Route for Reentry into the Food Supply of Multiple Pharmaceuticals and Personal Care Products," (highlighted in my video, Illegal Drugs in Chicken Feathers) they found that all feather samples tested positive for antibiotic type drugs (between two and ten different kinds in each sample), including fluoroquinolones, which have been banned for years. Either the poultry industry is illegally still using the stuff, or it's being used in other animals fed to the chicken. Regardless, when feather meal is fed back to chickens, they are getting exposed to this drug that is against the law to feed to chickens, creating a cycle of re-exposure to banned drugs.

Then it just gets weirder. The feathers contained a half dozen other drugs: Prozac, an antihistamine, a fungicide, a sex hormone, and caffeine. Why doesn't the poultry industry just say no? Evidently, the antihistamines are to combat the respiratory problems from packing so many tens of thousands into the confinement sheds, and the caffeine helps keeps the chickens stay awake so they eat more and grow faster.

The drugs fed to chickens are one reason used to explain why poultry has been tied to increased cancer risk. See Chicken Dioxins, Viruses, or Antibiotics?.

The most concerning drugs currently in the U.S. poultry supply are the antibiotics, though. See, for example:

Ironically, not only may antibiotics in chicken contribute to antibiotic resistant infections, but to the infections in the first place. Check out my video Avoiding Chicken to Avoid Bladder Infections.

Then as if adding potentially harmful chemicals to the chickens themselves wasn't bad enough, more are added in the processing plant: Phosphate Additives in Chicken.

In health,
Michael Greger, M.D.

PS: If you haven't yet, you can subscribe to my free videos here and watch my live year-in-review presentations Uprooting the Leading Causes of Death, More Than an Apple a Day, From Table to Able, and Food as Medicine.

Image Credit: U.S. Department of Agriculture / Flickr

Original Link

Can We Fight the Blues With Greens?

 

 

 

 

 

 

 

 

NF-Mar27 Can We Fight Blues with Greens?.jpg

Why does frequent consumption of vegetables appear to cut one’s odds of depression by more than half? And "frequent" was defined as eating vegetables not 3 or more times a day, but just 3 or more times a week.

A 2012 study was found that eliminating animal products improved mood within two weeks. The researchers blamed arachidonic acid, found primarily in chicken and eggs, which might adversely impact mental health via a cascade of brain inflammation. More on this inflammatory omega-6 fatty acid in:

But better moods on plant-based diets could also be from the good stuff in plants—a class of phytonutrients that cross the blood brain barrier into our heads. A recent review in the journal, Nutritional Neuroscience, suggests that eating lots of fruits and vegetables “may present a noninvasive natural and inexpensive therapeutic means to support a healthy brain.” But how?

To understand the latest research, we need to understand the underlying biology of depression—the so-called monoamine theory of depression. It's the idea that depression may arise out of a chemical imbalance in the brain. In my video Fighting the Blues with Greens? I run through an oversimplified version.

One of the ways the billions of nerves in our brain communicate with one another is through chemical signals called neurotransmitters. Two nerve cells don’t actually touch—there’s a physical gap between them. To bridge that gap, when one nerve wants to tap the other on the shoulder it releases chemicals into that gap, including three monoamines: serotonin, dopamine and norepinephrine. These neurotransmitters then float over to the other nerve to get its attention. The first nerve then sucks them back in to be reused the next time it wants to talk. It’s also constantly manufacturing more monoamines, and an enzyme, monoamine oxidase, is constantly chewing them up to maintain just the right amount.

The way cocaine works is by acting as a monoamine re-uptake inhibitor. It blocks the first nerve from sucking back up these three chemicals and so there’s a constant tapping on the shoulder—constant signaling—to the next cell. Amphetamines work in the same way but also increase the release of monoamines. Ecstasy works like speed, but just causes comparatively more serotonin release.

After awhile, the next nerve may say “enough already!” and down-regulate its receptors to turn down the volume. It puts in earplugs. So we need more and more of the drug to get the same effect, and then when we’re not on the drug we may feel crappy because normal volume transmission just isn’t getting through.

Antidepressants are thought to work along similar mechanisms. People who are depressed appear to have elevated levels of monoamine oxidase in their brain. That’s the enzyme that breaks down those neurotransmitters. In the video mentioned previously, I show the levels of monoamine oxidase in the brains of depressed individuals versus healthy individuals. If the levels of our neurotransmitter-eating enzyme is elevated, then our levels of neurotransmitters drops, and we become depressed (or so the theory goes).

So a number of different classes of drugs have been developed. The tricyclic antidepressants, named because they have three rings like a tricycle, appear to block norepinephrine and dopamine re-uptake, and so even though our enzymes may be eating these up at an accelerated rate, what gets released sticks around longer. Then there were the SSRIs (the selective serotonin reuptake inhibitors) like Prozac. Now we know what that means—they just block the re-uptake of serotonin. Then there are drugs that just block the re-uptake of norepinephrine, or block dopamine re-uptake, or a combination. But if the problem is too high levels of monoamine oxidase, why not just block the enzyme? Make a monoamine oxidase inhibitor. They did, but monoamine oxidase inhibitors are considered drugs of last resort because of serious side effects—not the least of which is the dreaded “cheese effect,” where eating certain foods while on the drug can have potentially fatal consequences. If only there was a way to dampen the activity of this enzyme without the whole bleed-into-our-brain-and-die thing.

Now we can finally talk about the latest theory as to why fruits and vegetables may improve our mood. There are inhibitors of the depression-associated enzyme in various plants. There are phytonutrients in spices, such as clove, oregano, cinnamon, and nutmeg, that inhibit monoamine oxidase, but people don’t eat enough spices to get enough into the brain. A certain dark green leafy has a lot, but its name is tobacco, which may actually be one of the reasons cigarettes make smokers feel so good. OK, but what if we don’t want brain bleeds or lung cancer? Well, there is a phytonutrient found in apples, berries, grapes, kale, onions, and green tea that may indeed affect our brain biology enough to improve our mood, which may help explain why those eating plant-based diets tend to have superior mental health.

For other natural treatments for mental illness, check out:

-Michael Greger, M.D.

If you haven’t yet, you can subscribe to my free videos here and watch my live year-in-review presentations Uprooting the Leading Causes of Death and More Than an Apple a Day.

Image credit: liz west / Flickr

Original Link