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was the case, researchers applied to the FDA under the Freedom of Information Act to get access to the published and unpublished studies submitted by pharmaceutical companies, and what they found was shocking.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 Thus, when published and unpublished data are combined, they fail to show a clinically significant advantage for antidepressant medication over a sugar pill.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 Analyses of the published data and the unpublished data that were hidden by drug companies reveals that most (if not all) of the benefits of antidepressants are due to the placebo effect.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

Using Diet to Treat Asthma and Eczema

NF-Jul9 Treating Asthma and Eczema with Plant Based Diets.jpg

I previously discussed the power of fruits and vegetables to help prevent and treat asthma and allergies. If adding a few more servings of fruits and vegetables may help asthma, what about a diet centered around plants? Twenty patients with allergic eczema were placed on a vegetarian diet. At the end of two months, their disease scores, which covered both subjective and objective signs and symptoms, were cut in half, similar to what we might see using one of our most powerful drugs. The drug works much quicker, within about two weeks, but since drugs can often include dangerous side effects the dietary option is more attractive. This was no ordinary vegetarian diet, however. This was an in-patient study using an extremely calorically-restricted diet--the subjects were practically half fasting. Therefore, we don't know which component was responsible for the therapeutic effect.

What about using a more conventional plant-based diet against a different allergic disease, asthma? In Sweden, there was an active health movement that claimed that a vegan diet could improve or cure asthma. This was a bold claim, so in order to test this, a group of orthopedic surgeons at Linköping University Hospital followed a series of patients who were treated with a vegan regimen for one year. (This study is highlighted in my video, Treating Asthma and Eczema with Plant-Based Diets.) Participants had to be willing to go completely plant-based, and they had to have physician-verified asthma of at least a year's duration that wasn't getting better or was getting worse despite the best medical therapies available.

The researchers found quite a sick group to follow. The thirty-five patients had long-established, hospital-verified bronchial asthma for an average duration of a dozen years. Of the 35 patients, 20 had been admitted to the hospital for acute asthmatic attacks during the last two years. Of these, one patient had received acute infusion therapy (emergency IV drugs) a total of 23 times during this period and another patient claimed he had been to the hospital 100 times during his disease and on every occasion had evidently required such treatments. One patient even had a cardiac arrest during an asthma attack and had been brought back to life on a ventilator. These were some pretty serious cases.

The patients were on up to eight different asthma medicines when they started, with an average of four and a half drugs, and were still not getting better. Twenty of the 35 were constantly using cortisone, which is a powerful steroid used in serious cases. These were all fairly advanced cases of the disease, more severe than the vegan practitioners were used to.

Eleven couldn't stick to the diet for a year, but of the 24 that did, 71% reported improvement at four months and 92% at one year. These were folks that had not improved at all over the previous year. Concurrently with this improvement, the patients greatly reduced their consumption of medicine. Four had completely given up their medication altogether, and only two weren't able to at least drop their dose. They went from an average of 4.5 drugs down to 1.2, and some were able to get off cortisone.

Some subjects said that their improvement was so considerable they felt like "they had a new life." One nurse had difficulty at work because most of her co-workers were smokers, but after the plant-based regimen she could withstand the secondhand smoke without getting an attack and could tolerate other asthma triggers. Others reported the same thing. Whereas previously they could only live in a clean environment and felt more or less isolated in their homes, they could now go out without getting asthmatic attacks.

The researchers didn't find only subjective improvements. They also found a significant improvement in a number of clinical variables, most importantly in measures of lung function, vital capacity, forced expiratory volume, and physical working capacity, as well as significant drops in sed rate (a marker of inflammation) and IgE (allergy associated antibodies).

The study started out with 35 patients who had suffered from serious asthma for an average of 12 years, all receiving long-term medication, with 20 using cortisone, who were "subjected to vegan food for a year," and, in almost all cases, medication was withdrawn or reduced, and asthma symptoms were significantly reduced.

Despite the improved lung function tests and lab values, the placebo effect can't be discounted since there was no blinded control group. However, the nice thing about a healthy diet is that there are only good side effects. The subjects' cholesterol significantly improved, their blood pressures got better, and they lost 18 pounds. From a medical standpoint, I say why not give it a try?

If you missed the first three videos of this 4-part series here are the links:

More on eczema and diet can be found in my videos:

There are a number of other conditions plant-based diets have been found to be effective in treating:

-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, and From Table to Able.

Image Credit: KristyFaith / Flickr

Original Link

Slowing Cognitive Decline with Berries

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A plant-based diet is thought to have played a significant role in human evolution and the consumption of whole plant foods and even just extracts have repeatedly been associated with a decreased risk of aging related diseases. And by healthy aging I'm not talking preventing wrinkles, what about protecting our brain? "Two of the most dreaded consequences of dementia with aging are problems moving around and difficulty remembering things. Dementia robs older adults of their independence, control, and identity."

Fruits and vegetables help reduce the risk of other chronic diseases, so might they work for brain diseases as well?

There has been a proliferation of recent interest in plant polyphenols as agents in the treatment of dementia. There are 4,000 different kinds of polyphenols found ubiquitously in foods of plant origin, but berries are packed with them, possessing powerful antioxidant and anti-inflammatory properties. There's a subset of polyphenols called anthocyanidins, which are found in blue and purple pigmented fruits and berries. These polyphenols are uniquely and specifically capable of "both crossing the blood-brain barrier and localizing in brain regions involved in learning and memory." And that's precisely where we need them.

The brain takes up less than 2% of body weight but may burn up to 50% of the body's fuel, creating a potential firestorm of free radicals. Maybe these brain-seeking phytonutrients in berries could fight oxidation and inflammation, and even increase blood flow? This raised a thought-provoking idea. Maybe a "nutritional intervention with blueberries may be effective in forestalling or even reversing the neurological changes associated with aging?" It would be a decade before the first human trial was conducted, but it worked! "Blueberry supplementation improves memory in older adults," suggesting that "consistent supplementation with blueberries may offer an approach to forestall or mitigate brain degeneration with age."

What other blue or purple foods can we try? Concord grape juice was also tested and had a similar benefit, suggesting that supplementation with purple grape juice may enhance cognitive function for older adults with early memory decline. Why use juice and not whole concord grapes? Because then you couldn't design a placebo that looked and tasted exactly the same to rule out the very real and powerful placebo effect. And also because the study was funded by the Welch's grape juice company.

This effect was confirmed in a follow-up study, showing for the first time an increase in neural activation in parts of the brain associated with memory using functional MRI scans. But this brain scan study was tiny: just four people in each group. And same problem in the blueberry study: it had only nine people in it.

Why haven't large population-based studies been done? Because we haven't had good databases on where these phytonutrients are found. We know how much vitamin C is in a blueberry, but not how much anthocyanidin--until now. The Harvard Nurses' Health Study, highlighted in my video, How to Slow Brain Aging by Two Years, followed the cognitive function of more than 16,000 women for years, and found that "long-term consumption of berries was related to significantly slower rates of cognitive decline, even after careful consideration of confounding socioeconomic status" (that is, even after taking into account the fact that rich people eat more berries). The Harvard Nurses' Health Study was the first population-based evidence that greater intakes of blueberries and strawberries were highly associated with slower rates of cognitive decline, and not just by a little bit. "The magnitude of associations were equivalent to the cognitive differences that one might observe in women up to two and a half years apart in age." In other words, women with higher intake of berries appeared to have delayed cognitive aging by as much as two and a half years.

Why shouldn't we just take some anthocyanidin supplement? Because there hasn't been a single study that found any kind of cognitive benefit by just giving single phytonutrients. In fact, the opposite is true. "Whole blueberries appear to be more effective than individual components, showing that the whole is greater than the sum of its parts." These findings have potentially substantial public health implications, as increasing berry intake represents a fairly simple dietary modification to test in older adults for maintaining our brain function.

What other ways could we improve our memory and cognitive function?

What other near-miraculous properties of berries are there?

I add them to my morning smoothie: A Better Breakfast.

-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, and From Table to Able.

Image Credit: Angelo Desantis / Flickr

Original Link